isotretinoin and Skin-Neoplasms

In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.

Topics: Acne Vulgaris; Dermatology; Humans; Isotretinoin; Retinoids; Skin Neoplasms; United States

Solid organ transplant recipients (SOTRs) are at an increased risk of epithelial malignancies, mainly squamous cell carcinoma, and its precursor lesions such as actinic keratoses, warts, and porokeratosis, which may respond to retinoid therapy.. To review the published evidence on the efficacy and safety of topical and systemic retinoids for the treatment and prophylaxis of malignant and premalignant conditions that mostly afflict SOTRs.. Systematic review of the literature to summarize the level of evidence and grade of recommendation for retinoid therapy with emphasis in the SOTR population.. Acitretin has the highest strength of recommendation (Grade A) for prophylaxis of nonmelanoma skin cancer (NMSC) and treatment and prophylaxis of actinic keratoses in SOTR. In nonimmunosuppressed patients, acitretin and isotretinoin have a Grade B recommendation for treatment of recalcitrant warts. Topical retinoids have not shown efficacy in preventing NMSC in immunocompetent patients.. Retinoids constitute a highly efficacious alternative for the management of the most common conditions that affect SOTRs. Acitretin has the most robust evidence for chemoprophylaxis in SOTRs. Knowledge about the specific indications and expected side effects of topical and systemic retinoids may help optimize their therapeutic potential.

Topics: Acitretin; Administration, Cutaneous; Administration, Oral; Carcinoma, Squamous Cell; Dermatologic Agents; Dermatology; Evidence-Based Medicine; Graft Rejection; Humans; Immunosuppressive Agents; Isotretinoin; Keratosis, Actinic; Organ Transplantation; Skin Neoplasms; Transplant Recipients; Treatment Outcome; Warts

Topics: Administration, Topical; Aged; Biopsy, Needle; Diagnosis, Differential; Female; Follow-Up Studies; Forehead; Humans; Immunohistochemistry; Isotretinoin; Neoplasms, Adnexal and Skin Appendage; Rare Diseases; Skin Neoplasms; Syringoma; Treatment Outcome

In this chapter, we will discuss the most common alopecias due to drugs and other skin and systemic disorders. The following hair disorders will be analyzed: telogen effluvium (acute and chronic); anagen effluvium; folliculotropic mycosis fungoides; and folliculitis due to bacteria, fungi, parasites, human immunodeficiency virus disease, lupus erythematosus, and sarcoidosis. We will cover topics including the epidemiology, etiology, clinical picture, and diagnosis of and current treatments for each disease.

Topics: Alopecia; Anticonvulsants; Antidepressive Agents; Antineoplastic Agents; Dermatologic Agents; Dermatomycoses; Diet; Folliculitis; Herpes Zoster; HIV Infections; Humans; Isotretinoin; Lamotrigine; Lithium Compounds; Lupus Erythematosus, Systemic; Malnutrition; Mycosis Fungoides; Paroxetine; Sarcoidosis; Seasons; Skin Neoplasms; Starvation; Stress, Psychological; Syphilis; Triazines; Valproic Acid

Based on the review of the medical publications, this article summarizes the main advances in the field of pediatric dermatology which occurred during the last year. The main results concern psoriasis, atopic dermatitis, acne and hemangiomas. A particular attention was given to genodermatoses.

Topics: Attention; Child; Depression; Dermatologic Agents; Dermatology; Etanercept; Eye Diseases; Humans; Immunoglobulin G; Immunosuppressive Agents; Isotretinoin; Mutation; Propranolol; Proto-Oncogene Proteins c-akt; Receptors, Tumor Necrosis Factor; Severity of Illness Index; Skin Diseases; Skin Neoplasms; Vasodilator Agents; Vitamin D

A 23-year-old man with a typical trichilemmal cyst nevus is reported. This recently described disorder is sufficiently characteristic to differentiate it from sebaceous nevus, nevus comedonicus, porokeratotic eccrine nevus, nevus corniculatus, follicular basaloid hamartoma, Munro's nevus and Gardner's syndrome.

Topics: Dermatologic Agents; Epidermal Cyst; Facial Neoplasms; Humans; Isotretinoin; Male; Nevus; Skin Neoplasms; Sweat Gland Neoplasms; Treatment Outcome; Young Adult

The incidence of non-melanoma skin cancer is increasing worldwide. Systemic retinoids are useful for the chemoprophylaxis of non-melanoma skin cancers. Retinoids have pleiotropic effects, but their exact cancer chemopreventive mechanism is still not clear.. The aim of this study was to review published literature evaluating the use of oral retinoids in the chemoprevention of non-melanoma skin cancers.. The study reviewed all relevant papers found through a search of the electronic databases MEDLINE (from 1966 to January 2008) and Embase (from 1974 to January 2008).. General and specific indications for retinoid chemoprophylaxis are defined. The pharmacokinetics and dose regimens of the two most commonly used oral retinoids (isotretinoin and acitretin) in the chemoprevention of non-melanoma skin cancers are presented. The use of oral retinoids is associated with adverse effects, which are discussed in detail. The future of retinoid cancer chemoprevention depends on the development and research of novel retinoids with improved bioavailability and minimized toxicity.

Topics: Acitretin; Administration, Oral; Chemoprevention; Dermatologic Agents; Dose-Response Relationship, Drug; Humans; Isotretinoin; Patient Selection; Retinoids; Skin Neoplasms

Topics: Darier Disease; Dose-Response Relationship, Drug; Humans; Ichthyosis; Isotretinoin; Keratoderma, Palmoplantar; Pityriasis; Skin Neoplasms

Systemic isotretinoin has been used to treat severe acne vulgaris for 20 years. However, isotretinoin also represents a potentially useful choice of drugs in many dermatologic diseases other than acne vulgaris. Diseases such as psoriasis, pityriasis rubra pilaris, condylomata acuminata, skin cancers, rosacea, hidradenitis suppurativa, granuloma annulare, lupus erythematosus and lichen planus have been shown to respond to the immunomodulatory, anti-inflammatory and antitumor activities of the drug. Isotretinoin also helps prevent skin cancers such as basal cell carcinoma or squamous cell carcinoma. A combination of systemic isotretinoin and interferon-alpha-2a may provide a more potent effect than isotretinoin alone in the prevention and treatment of skin cancers.Systemic isotretinoin may be considered as an alternative drug in some dermatologic diseases unresponsive to conventional treatment modalities. However, randomized clinical trials aimed at determining the role of systemic isotretinoin therapy in dermatologic diseases other than acne vulgaris are required.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Condylomata Acuminata; Dermatologic Agents; Drug Therapy, Combination; Granuloma Annulare; Hidradenitis Suppurativa; Humans; Isotretinoin; Keratolytic Agents; Lichen Planus; Lupus Erythematosus, Systemic; Pityriasis Rubra Pilaris; Psoriasis; Rosacea; Sebaceous Glands; Skin Diseases; Skin Neoplasms

There has been a significant increase in the number of cases of skin cancer diagnosed in the US in the past few years. Thus, it seems appropriate to review the available compounds that might be used in the chemoprevention of these lesions. This review focuses on the retinoids and details their results in clinical trials for treatment and prevention of skin cancer. Side effects of the various retinoid derivatives are also discussed. It is concluded that isotretinoin (13-cis-retinoic acid) is the most effective retinoid for the prevention of non-melanoma skin cancers in high-risk patients in clinical trials. Current basic research is focused on developing receptor-selective retinoids which would have a higher therapeutic index for the treatment and chemoprevention of skin cancer.

Topics: Benchmarking; Humans; Isotretinoin; Retinoids; Skin Neoplasms; Tretinoin

Systemic retinoids represent a growing armamentarium in the treatment of a wide range of skin disorders and malignancies. Although these drugs can have substantial toxicities, their wise use can result in safe and efficacious therapy that can alter dramatically the lives of individuals with severe skin disorders.

Topics: Acne Vulgaris; Anticarcinogenic Agents; Humans; Isotretinoin; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms

Isotretinoin (13-cis-retinoic acid) is a retinoid that has been used over the past 2 decades to treat a wide variety of dermatologic conditions, some with great success. Although it is beneficial in many skin conditions, the side effects and toxicities of oral retinoids require careful monitoring by experienced physicians. The clinical applications of oral retinoids continue to expand both within and beyond the field of dermatology.

Topics: Acne Vulgaris; Administration, Oral; Adult; Aged; Aging; Dermatologic Agents; Humans; Isotretinoin; Middle Aged; Psoriasis; Skin Diseases; Skin Neoplasms

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.

Topics: Anti-Inflammatory Agents; Combined Modality Therapy; Female; Humans; Interferon-alpha; Isotretinoin; Keratolytic Agents; Methylprednisolone; Middle Aged; Mycosis Fungoides; Phototherapy; Sarcoidosis; Skin Neoplasms; Syndrome

Three patients developed erosive pustular dermatosis of the scalp (EPDS). Two of them, both males, had previously undergone surgical excision for squamous cell carcinoma and basal cell carcinoma, and a female experienced avulsive trauma of the scalp. The erosive lesions and crusts were located at the site of a skin graft; microbiological cultures were negative for bacterial and fungal growth. Histological examination ruled out pustular bullous disorders. Topical therapy with corticosteroids and antibiotics resulted in clinical remission in only 2 cases. The third case showed a tendency to recur despite numerous therapeutic attempts with oral dapsone and isotretinoin. We conclude that surgical trauma is a possible cause of EPDS. Our patients seem to be the first reported cases of EPDS in skin grafts following plastic surgical procedures.

Topics: Administration, Cutaneous; Administration, Oral; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Bacteria; Betamethasone; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dapsone; Female; Fungi; Gentamicins; Humans; Isotretinoin; Keratolytic Agents; Male; Middle Aged; Recurrence; Remission Induction; Scalp; Scalp Dermatoses; Skin Diseases, Vesiculobullous; Skin Neoplasms; Skin Transplantation

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Antineoplastic Agents; Bowen's Disease; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Interferon-alpha; Interferons; Isotretinoin; Keratolytic Agents; Male; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Retinoids; Skin Neoplasms

Topics: Humans; Immunotherapy; In Vitro Techniques; Isotretinoin; Mutation; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum

Various combinations of retinoids, metabolic and synthetic derivatives of vitamin A, and interferons (IFNs) have demonstrated synergistic antiproliferative, differentiating, and antiangiogenic activity in some human hematologic and solid-tumor systems. This synergistic antitumor activity may be due to enhanced gene expression. In several cell systems, the actions of IFNs are enhanced by differentiation of cells with retinoic acid (RA). Combined RA-IFN effects have been correlated with the induction of higher levels of IFN-stimulated genes than the levels induced by either agent alone. Natural and synthetic retinoids have been found to augment the antiproliferative activity of IFNs in several squamous cell carcinoma (SCC) and breast tumor cell lines. Results of recent clinical trials indicate substantial activity of 13-cis-RA (13cRA) combined with IFN against advanced SCC of the skin and cervix, and possibly against other solid tumors. Two phase II trials have confirmed activity against locally advanced SCC of the cervix. Successful integration of this regimen with radiotherapy appears to be the most probable means of optimizing clinical outcome. Further studies are needed to determine the mechanistic details of the RA-IFN interaction.

Topics: 2',5'-Oligoadenylate Synthetase; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Drug Synergism; Enzyme Induction; Female; Humans; Interferon-alpha; Isotretinoin; Mice; Protein Kinases; Skin Neoplasms; Tumor Cells, Cultured; Uterine Cervical Neoplasms

Preclinical data indicate that the combination of retinoids and interferons have synergistic antiproliferative and differentiating effects in some hematologic and solid tumor models. These observations have led to clinical trials in which 13-cis-retinoic acid (13cRA) 1 mg/kg/day was combined with interferon alpha-2a (IFN alpha) 3 or 6 x 10(6) U/day. The first two such trials produced exciting results: 50% response rate in patients with previously untreated stages IB-IVA cervix cancer and 68% in patients with advanced squamous cell skin cancer. These data led to a number of additional trials of the combination, but the high response rates seen in the initial cervix and skin trials have not been duplicated in the other squamous tumors tested (head and neck, lung, pretreated cervix). In addition, trials in two non-squamous histologies were negative (lung and melanoma). However, the regimen was not always studied in an optimal population of previously untreated patients and the negative results in pretreated cervix patients point to the relevance of this consideration. Nevertheless, the observation that the combination of 13cRA and IFN alpha (both of which bind to specific receptors and change gene expression) is able to induce regression in advanced tumors, must be regarded as highly important. Key questions to be addressed include an understanding of the biologic mechanism of specific tumor sensitivity (why some squamous tumors and not others?), and mechanisms of resistance in sensitive tumor types (e.g. cervix). Such data may lead to trials targeted to tumor types with defined biologic features having a high likelihood of clinical benefit. In the meantime, studies integrating this combination with other active treatment modalities such as radiation is warranted in cervix and skin carcinomas.

Topics: Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Neoplasms; Recombinant Proteins; Skin Neoplasms; Uterine Cervical Neoplasms

Primary care physicians should be familiar with the effects and appropriate uses of retinoids. Topical tretinoin (Retin-A) can reverse photoaging of the skin, although some transient, undesirable side effects usually occur. In patients with acne vulgaris, topical tretinoin and systemic isotretinoin (Accutane) are the only agents that act upon the apparent underlying causes. Recurrence is unlikely after successful results are achieved. Chronic hypervitaminosis A presents insidiously, and physicians must maintain a high index of suspicion. Complete history taking should always include questions about the patient's use of vitamin supplements.

Topics: Acne Vulgaris; Administration, Topical; Animals; Drug Eruptions; Drug Therapy, Combination; Humans; Hypervitaminosis A; Isotretinoin; Medical History Taking; Physical Examination; Skin Aging; Skin Neoplasms; Tretinoin

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Ear, External; Fluorouracil; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms

Topics: Animals; Etretinate; Humans; Isotretinoin; Keratosis; Mycosis Fungoides; Retinoids; Skin Neoplasms; Vitamin A

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Animals; Female; Humans; Infant, Newborn; Isotretinoin; Kinetics; Precancerous Conditions; Pregnancy; Skin Neoplasms; Tretinoin

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively non-toxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.

Topics: Acne Vulgaris; Bone Diseases; Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Isomerism; Isotretinoin; Keratosis; Kinetics; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Triglycerides; Vitamin A

The retinoids are synthetic derivatives of vitamin A. Isotretinoin (13-cis-retinoic acid) is now being widely used in the United States for severe acne and etretinate is available in Europe and other countries for psoriasis. These drugs are also effective for a number of other skin diseases. This is an attempt to review basic knowledge of retinoids with which the practicing dermatologist should be familiar, to review the current status of studies, and to speculate on the present and future roles of these drugs in dermatology.

Topics: Acne Vulgaris; Etretinate; Humans; Inflammation; Isotretinoin; Keratins; Psoriasis; Retinoids; Sebum; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases; Tretinoin; Vitamin A

Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Darier's disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to 'traditional' therapy.

Topics: Acne Vulgaris; Animals; Anti-Inflammatory Agents; Carcinogens; Cell Differentiation; Cell Division; Humans; Immunity; Isotretinoin; Kinetics; Mutagens; Psoriasis; Rosacea; Sebaceous Glands; Skin; Skin Absorption; Skin Diseases; Skin Neoplasms; Teratogens; Tissue Distribution; Tretinoin

Topics: Breast Neoplasms; Etretinate; Humans; Isomerism; Isotretinoin; Skin Diseases; Skin Neoplasms; Tretinoin

Sun exposure may lead to actinic keratoses (AKs), field cancerization, and skin cancer. Effective treatment of AKs and field cancerization is important. Oral and topical retinoids can be used for this purpose. To compare clinical, histological, and immunohistochemical effects of oral and topical retinoid for AKs and field cancerization on face and upper limbs of immunocompetent patients, as well as the impact on quality of life, safety, and tolerability.. This study compared 10 mg/day oral isotretinoin (ISO) to 0.05% tretinoin cream (TRE) every other night, associated with sunscreen (SPF 60). Patients of both genders, aged 50-75 years, underwent cryotherapy with liquid nitrogen for AKs at baseline and after 120 days when they were randomized into two groups, TRE (n = 31) and ISO (n = 30), for 6 months. Outcome measures were: number of AKs, histological (thickness of stratum corneum and epithelium) and immunohistochemical parameters (p53, Bcl-2 and Bax), dermatology life quality index (DLQI), and adverse events.. Both treatments reduced the number of AKs (around 28%), the thickness of stratum corneum, and expression of p53 and Bax. By contrast, the epithelium thickness and Bcl-2 expression increased. There was no difference in the outcomes between TRE and ISO. Both treatments improved quality of life and were well tolerated with minimal side effects.. Retinoids are effective and safe for field cancerization. Classical treatments for field cancerization (imiquimod and ingenol mebutate) are used for a short period; retinoids may be a good choice to intercalate with them and can be used continuously.

Topics: Administration, Cutaneous; Administration, Oral; Aged; Antineoplastic Agents; bcl-2-Associated X Protein; Facial Dermatoses; Female; Humans; Immunohistochemistry; Isotretinoin; Keratosis, Actinic; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Quality of Life; Skin Cream; Skin Neoplasms; Tretinoin; Tumor Suppressor Protein p53; Upper Extremity

Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin vs. placebo on recurrence of nonmelanoma skin cancer in high-risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose-response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, whereas only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC, hazard ratios (HRs) for the first quartile were as follows: HR = 2.92, 95% confidence interval (CI) = 1.67-5.10 crude; HR = 1.95, 95% CI = 1.00-3.80 adjusted. For isotretinoin and SCC, HRs for the first quartile were as follows: HR = 2.38, 95% CI = 1.35-4.19 crude; HR = 1.69, 95% CI = 0.87-3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose.

Topics: Aged; Antineoplastic Agents; Arizona; California; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isotretinoin; Male; Middle Aged; Neoplasm Recurrence, Local; Patient Dropouts; Proportional Hazards Models; Skin Neoplasms; Vitamin A

To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC.. Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation.. At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities.. Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Prognosis; Prospective Studies; Recombinant Proteins; Skin Neoplasms; Survival Rate

Patients with recessive dystrophic epidermolysis bullosa (RDEB) are at high risk of developing squamous cell carcinoma on or after midadolescence, and most patients die of metastatic squamous cell carcinoma within 5 years of diagnosis of their first squamous cell carcinoma.. We sought to determine whether isotretinoin can be safely administered to patients with RDEB as a possible chemopreventive agent.. A total of 20 patients with RDEB aged 15 years or older were treated daily for 8 months with isotretinoin (with a targeted dosage of 0.5 mg/kg/d).. No unusual adverse reactions were noted in this patient population. Several patients experienced reduced blistering at lower doses and increased mechanical fragility at maintenance dosage.. Isotretinoin, at least up to a dosage of 0.5 mg/kg/d, may be safely used in patients with RDEB. Although increased fragility may occur, patients tolerated this drug well and were receptive to its long-term use for possible chemoprevention of cancer. Whether such an effect will occur is yet to be proven.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Dermatologic Agents; Epidermolysis Bullosa Dystrophica; Female; Humans; Isotretinoin; Male; Middle Aged; Risk Factors; Skin Neoplasms

The purpose of this study was to test interferon alfa (IFNalpha), 13-cis-retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin.. Patients with advanced skin SCC received IFNalpha (5 x 10(6) IU/m(2), subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m(2), intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1-m7 and SRB12-p9).. Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines.. The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFNalpha, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non-cross-resistant biologic effects in vitro, which may account for the combination's clinical activity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cisplatin; Fatigue; Female; Fever; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon-alpha; Isotretinoin; Male; Middle Aged; Neutropenia; Skin Neoplasms; Survival Analysis; Treatment Outcome; Tumor Cells, Cultured

To analyze whether an abnormal retinal function in patients with a cutaneous malignant melanoma was due to paraneoplastic retinopathy or due to isotretinoin or interferon-alpha.. We studied 15 patients with malignant melanoma in stage IIa and IIb who are all participants in a randomized, multicentered, double-blind placebo-controlled clinical trial comparing interferon-alpha/isotretinoin versus interferon-alpha/placebo performed by the Department of Dermatology, University of Graz. Our assessment included a full ophthalmic history and examination, electrophysiological testing (ERG, EOG), dark adaption, color vision and visual field testing.. The most prevalent ocular symptom patients complained about was ocular dryness (8 patients). Electrophysiological as well as psychophysical testings showed no abnormalities in 12 patients. In 1 patient the therapy was stopped because of electrophysiological and psychophysiological pathology. This patient suffered from severe reduction of night vision and visual disturbances. Another patient had had night blindness since childhood which remained stable.. We postulate that in 1 of 15 patients, visual complaints are caused with a high probability by melanoma-associated retinopathy although, in the literature, isotretinoin is described to show similar effects on retinal function.

Topics: Aged; Antineoplastic Agents; Color Perception; Double-Blind Method; Drug Therapy, Combination; Electroretinography; Female; Humans; Interferon-alpha; Isotretinoin; Male; Melanoma; Night Blindness; Paraneoplastic Syndromes; Prognosis; Retinal Diseases; Skin Neoplasms; Visual Acuity; Visual Fields

The objective of this study was to examine the effect of retinol and isotretinoin on the incidence of nonmelanoma skin cancer in high-risk subjects. A total of 525 participants with a history of at least four basal cell carcinomas (BCCs) and/or cutaneous squamous cell carcinomas (SCCs) were entered into a randomized, double-blind, placebo-controlled trial, performed in free-standing study clinics. Participants were randomly assigned to receive oral retinol (25,000 units), isotretinoin (5-10 mg), or placebo supplementation daily for 3 years. The time to first new occurrence of BCC or cutaneous SCC was used as the outcome measure. During the study period, 319 BCCs and 125 cutaneous SCCs were diagnosed clinically and pathologically. There were no differences between those who received retinol, isotretinoin, or the placebo, with regard to the time to first occurrence or to the total number of tumors noted. No beneficial effects were noted with regard to the prevention of nonmelanoma skin cancer with either retinol or isotretinoin.

Topics: Adult; Aged; Blood Chemical Analysis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Double-Blind Method; Female; Humans; Isotretinoin; Keratolytic Agents; Liver Function Tests; Male; Middle Aged; Proportional Hazards Models; Skin Neoplasms; Vitamin A

Twenty-five patients with metastatic malignant melanoma were treated with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and recombinant interferon alfa-2a (INF-alpha) subcutaneously at 3 million units daily for 16-48 weeks. Therapy was well tolerated; fatigue and hyperlipidemia were the most frequent dose-limiting toxicity and necessitated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4-36%). Responses occurred primarily in patients with limited tumor burden and disease confined to the skin and lymph nodes. Significant elevations in peripheral blood 2'-5'-oligoadenylate synthetase activity and natural killer activity were observed with therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens of two responding lesions showed extensive necrosis of tumor. One specimen showed large aggregates of melanophages in association with tumor. The combination of isotretinoin and IFN-alpha is an active, easily administered regimen with acceptable toxicity for metastatic malignant melanoma.

Topics: 2',5'-Oligoadenylate Synthetase; Adult; Aged; Antineoplastic Agents; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Killer Cells, Natural; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Necrosis; Neoplasm Metastasis; Neoplasm Staging; Recombinant Proteins; Skin Neoplasms

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Precancerous Conditions; Skin Neoplasms

This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.

Topics: Aged; Carcinoma, Basal Cell; CD4-CD8 Ratio; Cell Count; Environmental Exposure; Humans; Isotretinoin; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms; Sunlight; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Time Factors

We conducted a prospective roentgenographic survey of patients participating in a randomized, placebo-controlled, multicenter clinical trial that evaluated the effectiveness of chronic, very-low-dose (approximately 0.14 mg/kg per day for 3 years) isotretinoin in preventing the subsequent occurrences of new basal cell carcinoma in patients with previous basal cell carcinoma. To assess potential skeletal changes, a sample of 269 patients from among a total of 981 enrollees were randomly selected for comparative roentgenographic review. Baseline and 36-month roentgenograms of the cervical and thoracic spine of each patient were read side by side by a radiologist, masked to treatment group, who noted both the presence and extent of abnormalities at each vertebral level at baseline and the progression of existing or occurrence of new abnormalities at previously unaffected levels at 36 months.. In comparison with the placebo group, significantly more patients in the isotretinoin group exhibited progression of existing hyperostotic abnormalities (40% vs 18%; P less than .001) and new hyperostotic involvement at previously unaffected vertebral levels (8% vs 1%; P = .015).. Our findings indicate that chronic, very-low-dose isotretinoin can induce hyperostotic axial skeletal changes similar to those reported in patients taking higher doses.

Topics: Adult; Aged; Carcinoma, Basal Cell; Cervical Vertebrae; Female; Humans; Hyperostosis, Diffuse Idiopathic Skeletal; Isotretinoin; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Radiography; Skin Neoplasms; Thoracic Vertebrae

Retinoids (vitamin A derivatives) and interferon-alpha (IFN-alpha) are potent regulators of malignant cell differentiation and proliferation, and both have immunomodulatory and antiangiogenesis activity. A large body of preclinical and clinical data supports the use of combination therapy with 13-cis-retinoic acid (13-cRA) and IFN-alpha in patients with squamous cell carcinoma of the skin. This carcinoma is an extremely common and frequently severely disfiguring cancer, for which about 10% of patients remain uncured following standard local therapy.. Our purpose was to test whether a 20% or greater complete response rate could be achieved using a combination of these two agents in patients with advanced squamous cell carcinoma of the skin in whom local therapy had failed or was unfeasible or who had regional and/or distant metastases.. Thirty-two patients with heavily pretreated, advanced inoperable cutaneous squamous cell carcinoma of the skin were given a combination of oral 13-cRA (1 mg/kg per day) and subcutaneous recombinant human IFN alpha-2a (3 million units per day) for at least 2 months, unless disease progressed earlier, in a phase II trial.. Nineteen (68%) of the 28 assessable patients responded, seven (25%) of whom had complete responses. Response rates were 93% (13 of 14) in patients with advanced local disease (six complete responses), 67% (four of six) in patients with regional disease (no complete responses), and 25% (two of eight) in patients with distant metastases (one complete response). The relationship between decreased response rate and increased extent of disease was highly statistically significant (P less than .005, chi-square test). The median response duration was greater than 5 months. No life-threatening toxic effects occurred in assessable patients treated with this combination, although dose reductions were required in 18 patients. The major limiting side effect in this elderly patient population (median age, 67 years) was cumulative fatigue.. These results indicate that combined systemic therapy with 13-cRA and IFN alpha-2a is highly effective in patients with advanced squamous cell carcinoma of the skin.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Evaluation; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Male; Middle Aged; Recombinant Proteins; Remission Induction; Skin Neoplasms

High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity.. To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers.. Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects.. After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001).. This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects.. The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials.

Topics: Aged; Anticarcinogenic Agents; Carcinoma, Basal Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms

In a pilot study the therapeutic effect and side effect profile of low-dose interferon alfa-2b in combination with a retinoid for the treatment of cutaneous T cell lymphoma were evaluated. Seven patients (four women, three men) with histologically confirmed cutaneous T cell lymphoma were included. Four patients had received therapy previously. The treatment schedule consisted of 2 million U of interferon alfa-2b administered subcutaneously three times per week and oral 13-cis-retinoic acid, 1 mg/kg/day, with subsequent dose reduction in case of response. The combination therapy produced two complete and two partial remissions. Responses were maintained by continuous therapy for up to 15 months even after dose reduction of both agents by 50%. Side effects were negligible and did not result in discontinuation of treatment in any patient.

Topics: Administration, Oral; Adult; Aged; Drug Therapy, Combination; Female; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Isotretinoin; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Skin Neoplasms

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare and chronic skin disorder, which may trouble the patient considerably. The condition is generally believed to be resistant to therapy, although some authors have reported success with several treatments. including dithranol and etretinate. The present case, a classical presentation of ILVEN, again illustrates the refractoriness to various treatments, including an experimental treatment with topical 13-cis-retinoic acid. A review of the literature on therapeutic possibilities of ILVEN is presented. Based on our own observations and literature data, it is attractive to hypothesize that a positive result with treatments such as dithranol and retinoids should be interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.

Topics: Adolescent; Anthralin; Female; Humans; Inflammation; Isotretinoin; Nevus; Skin Neoplasms

The Isotretinoin-Basal Cell Carcinoma Prevention Trial (ISO-BCC Study) is a double-masked, randomized, placebo controlled, multicenter clinical trial. It is the first intramural cancer chemoprevention trial sponsored by the Division of Cancer Prevention and Control of the National Cancer Institute. This trial was designed to evaluate the effectiveness of chronic administration of low dosage levels (10 mg) of a synthetic retinoid, isotretinoin, in reducing the incidence of basal cell carcinoma in a high-risk population and to determine the incidence and severity of side effects associated with this long-term treatment. Between 1984 and 1987, eight clinical centers enrolled 981 participants between the ages of 40 and 75, who had two or more biopsy proven basal cell carcinomas in the 5 years before trial entry. This article describes the trial design, recruitment results, and baseline characteristics of the participant population in the ISO-BCC Study.

Topics: Adult; Aged; Carcinoma, Basal Cell; Double-Blind Method; Epidemiologic Methods; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Mass Screening; Middle Aged; Research Design; Risk Factors; Skin Neoplasms

To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas. Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug. Before, during, and after treatment, biopsies of all suspicious lesions were performed, and skin cancers were surgically removed. The patients had a total of 121 tumors (mean, 24; range, 8 to 43) in the two-year interval before treatment. During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019). After the drug was discontinued, the tumor frequency increased a mean of 8.5-fold (range, 2- to 19-fold) over the frequency during treatment (P = 0.007). Although all patients experienced mucocutaneous toxic effects, and triglyceride, liver-function, or skeletal abnormalities developed in some, high-dose oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Clinical Trials as Topic; Female; Humans; Isotretinoin; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Thirty-nine patients with mycosis fungoides in various stages or Sézary syndrome were treated with isotretinoin and 29 with etretinate as single drug therapy. Complete remission within 2 months was obtained with isotretinoin in 8 cases (21%) and partial remission in another 15 cases (38%). Etretinate induced complete remission in 5 cases (21%) and partial remission in 11 (46%). Only 1 case with Sézary syndrome went into partial remission. The first sign of remission occurred in 2 to 4 weeks. During continued treatment remissions could not always be maintained. Isotretinoin and etretinate were considered to be of equal potency in the treatment of mycosis fungoides.

Topics: Drug Eruptions; Etretinate; Humans; Isotretinoin; Lymphatic Metastasis; Mycosis Fungoides; Remission Induction; Sezary Syndrome; Skin Neoplasms; Tretinoin

In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.

Topics: Carcinoma, Basal Cell; Clinical Trials as Topic; Etretinate; Humans; Isotretinoin; Keratosis; Photosensitivity Disorders; Skin Neoplasms; Tretinoin; Urinary Bladder Neoplasms

Topics: Clinical Trials as Topic; Humans; Isotretinoin; Skin Neoplasms; Tretinoin; Vitamin A

Epitheliotropic lymphoma is an uncommon cutaneous malignancy of T lymphocytes. Limited information is available regarding the treatment and outcome of dogs with this disease.. To evaluate the treatment outcome and toxicity profile of isotretinoin in dogs with epitheliotropic lymphoma.. Twelve dogs with a diagnosis of epitheliotropic lymphoma were included.. A medical database was searched for dogs diagnosed with epitheliotropic lymphoma and treated with isotretinoin between 2010 and 2021. Diagnosis, treatment details and tumour response were recorded for 12 dogs.. All lesions resolved in four of 12 (33%) treated dogs. Lesions visibly improved in a further three dogs, giving a response rate of 58%. Two dogs' lesions remained unchanged and three progressed despite therapy. Adverse effects occurred in three dogs (25%), all of which were rapidly resolving or not affecting quality of life.. Isotretinoin treatment was a well-tolerated and effective treatment for canine epitheliotropic lymphoma.. Contexte - Le lymphome épithéliotrope est une tumeur maligne cutanée peu fréquente des lymphocytes T. Peu d’informations sont disponibles concernant le traitement et les résultats des chiens atteints de cette maladie. Objectifs - Évaluer les résultats du traitement et le profil de toxicité de l'isotrétinoïne chez les chiens atteints de lymphome épithéliotrope. Animaux - Douze chiens avec un diagnostic de lymphome épithéliotrope ont été inclus. Matériels et méthodes - Une base de données médicale a été recherchée pour les chiens diagnostiqués avec un lymphome épithéliotrope et traités à l'isotrétinoïne entre 2010 et 2021. Le diagnostic, les détails du traitement et la réponse tumorale ont été enregistrés pour 12 chiens. Résultats - Toutes les lésions ont disparu chez quatre des 12 (33 %) chiens traités. Les lésions se sont visiblement améliorées chez trois autres chiens, donnant un taux de réponse de 58 %. Les lésions de deux chiens sont restées stables et trois ont progressé malgré la thérapie. Des effets indésirables sont survenus chez trois chiens (25 %), qui se résolvaient tous rapidement ou n'affectaient pas la qualité de vie. Conclusion - Le traitement à l'isotrétinoïne a été un traitement bien toléré et efficace du lymphome épithéliotrope canin.. Introducción - El linfoma epiteliotrópico es una neoplasia maligna cutánea poco frecuente de linfocitos T. Se dispone de información limitada sobre el tratamiento y el resultado del mismo en perros con esta enfermedad. Objetivos- evaluar el resultado del tratamiento y el perfil de toxicidad de la isotretinoína en perros con linfoma epiteliotrópico. Animales- se incluyeron 12 perros con diagnóstico de linfoma epiteliotrópico. Materiales y métodos- se buscó en una base de datos médica perros diagnosticados con linfoma epiteliotrópico y tratados con isotretinoína entre 2010 y 2021. Se reciplaron datos del diagnóstico, los detalles del tratamiento y la respuesta del tumor en 12 perros. Resultados- todas las lesiones se resolvieron en cuatro de 12 (33 %) perros tratados. Las lesiones mejoraron visiblemente en otros tres perros, con una tasa de respuesta del 58%. Las lesiones de dos perros permanecieron estables y tres progresaron a pesar de la terapia. Efectos adversos fueron reportados en tres perros (25%), todos los cuales se resolvieron rápidamente o no afectaron a la calidad de vida. Conclusión- el tratamiento con isotretinoína fue bien tolerado y eficaz para el linfoma epiteliotrópico canino.. Hintergrund - Das epitheliotrope Lymphom ist eine seltene kutane Malignität von T Lymphozyten. Es gibt nur wenig Information in Bezug auf die Behandlung und den Ausgang dieser Erkrankung bei Hunden. Ziele - Eine Evaluierung des Behandlungserfolges und der Toxizitätsprofile von Isotretinoin bei Hunden mit epitheliotropem Lymphom. Tiere - Zwölf Hunde mit der Diagnose eines epitheliotropen Lymphoms wurden inkludiert. Materialien und Methoden - Eine medizinische Datenbank wurde auf Hunde, die zwischen 2010 und 2021 mit einem epitheliotropen Lymphom diagnostiziert und mit Isotretinoin behandelt worden waren, durchsucht. Die Diagnose, die Behandlungsdetails und die Tumorantwort wurden bei 12 Hunden festgehalten. Ergebnisse - Alle Läsionen verschwanden bei vier von 12 (33%) behandelten Hunden. Bei drei weiteren Hunden verbesserten sich die Läsionen sichtlich, was eine Antwortrate von 58% ergab. Bei zwei Hunden blieben die Veränderungen stabil und bei drei Hunden schritten sie trotz Behandlung voran. Nebenwirkungen traten bei drei Hunden (25%) auf, von denen alle rasch wieder verschwanden und die Lebensqualität nicht weiter beeinflussten. Schlussfolgerung - Isotretinoin war eine gut tolerierte und wirksame Behandlung bei Hunden mit epitheliotropem Lymphom.. 背景 - 上皮向性リンパ腫は、Tリンパ球皮膚悪性腫瘍でまれな疾患である。本疾患の治療および転帰に関する情報は限られている。 目的 - 本研究の目的は、上皮向性リンパ腫の犬におけるイソトレチノインの治療成績および毒性プロファイルを評価することであった。 供試動物 - 上皮向性リンパ腫と診断された犬 12 頭を対象とした。 材料と方法 - 2010年から2021年の間に上皮向性リンパ腫と診断され、イソトレチノインで治療された犬を医療データベースで検索した。12 頭の犬について、診断、治療の詳細、腫瘍の反応を記録した。 結果 - 治療を受けた 12 頭中 4 頭 (33%) ですべての病変が消失した。さらに3頭の犬で病変が目に見えて改善し、奏効率は58%であった。2 頭は病変が安定し、3 頭は治療にもかかわらず進行した。副作用は3頭 (25%) に発現したが、いずれも速やかに消失し、QOLに影響を与えることはなかった。 結論 - イソトレチノイン治療は、犬の上皮性リンパ腫に対して忍容性が高く、有効な治療法であった。.. 背景-趋上皮性淋巴瘤是一种不常见的T淋巴细胞皮肤恶性肿瘤。关于该疾病犬的治疗和结局的可用信息有限。 目的-评价异维A酸在趋上皮性淋巴瘤犬中的治疗结局和毒性特征。 纳入动物-12只诊断为趋上皮性淋巴瘤的犬。 材料和方法-检索了2010年至2021年间诊断为趋上皮性淋巴瘤,并接受异维A酸治疗的犬的医学数据库。记录了12只犬的诊断、治疗详情和肿瘤反应。 结果-4/12(33%)只治疗犬的所有病变均消退。另外3只犬的病变明显改善, 缓解率为58%。尽管接受了治疗, 但2只犬的病变保持稳定, 3只继续发展。3只犬(25%)出现不良反应, 均迅速消退或不影响生活质量。 结论-异维A酸治疗犬趋上皮性淋巴瘤是一种耐受性良好且有效的治疗方法。.. Contexto - O linfoma epiteliotrópico é uma neoplasia cutânea de linfócitos T incomum. As informações disponíveis sobre o tratamento e evolução de cães com essa doença são limitadas. Objetivos - Avaliar a resposta ao tratamento e o perfil de toxicidade da isotretinoína em cães com linfoma epiteliotrópico. Animais - Doze cães com linfoma epiteliotrópico foram incluídos. Materiais e métodos - Pesquisou-se em um banco de dados médico os cães diagnosticados com linfoma epiteliotrópico e tratados com isotretinoína entre 2010 e 2021. Diagnóstico, detalhes do tratamento e resposta tumoral foram registrados para 12 cães. Resultados - Todas as lesões se resolveram em quatro de 12 (33%) cães. As lesões melhoraram visivelmente em outros três cães, gerando uma taxa de resposta de 58%. As lesões de dois cães permaneceram estáveis e três progrediram apesar da terapia. Ocorreram efeitos adversos em três cães (25%), mas todos apresentaram resolução rápida ou não tiveram alteração na qualidade de vida. Conclusão - O tratamento com isotretinoína foi bem tolerado e eficaz para o linfoma epiteliotrópico canino.

Topics: Animals; Dog Diseases; Dogs; Isotretinoin; Lymphoma; Quality of Life; Skin Neoplasms

The treatment of Cutaneous T-cell lymphoma (CTCL) met huge challenges because of the heterogeneity and the scarcity of targeted drugs. ECPIRM derived from isotretinoin exhibited strong anti-proliferation effects in Hut78 and MJ cells rather than Myla cells. However, there was no data regarding the potential target of ECPIRM for its selective activity.. To investigate the potential target of ECPIRM for its selective anti-proliferation activity.. We evaluated the cell viability of CTCL cells after ECPIRM treatment, and detected the effects of ECPIRM on the biomarker genes of CTCL. Subsequently, the mRNA and protein level of Interleukin-2-inducible T-cell kinase (ITK) was determined. Then the induction of apoptosis triggered by ITK inhibitor BMS-509744 and ITK siRNAs were detected, and the docking of ECPIRM interacted with ITK and the effects of ECPIRM on ITK-mediated signaling pathway were analyzed. Finally, we evaluated the anti-growth activity of ECPIRM in Hut78-xenografted nude mice, and the relative expression of cleaved caspase-3, ITK, p-ERK and p-Akt were determined.. ITK was highly expressed in Hut78 and MJ cells rather than Myla cells, and targeted inhibition of ITK triggered cell apoptosis. ECPIRM efficiently bound the hydrophobic active pocket of ITK, and significantly inhibited ITK-mediated signaling pathway. In addition, ECPIRM suppressed tumor growth in Hut78-xenografted model, and upregulated the expression of cleaved caspase 3 and inhibited the expression of ITK, p-ERK and p-Akt in tumor tissues, which was consistent with in vitro study.. ECPIRM might provide a novel strategy for CTCL by inhibiting ITK-mediated signaling pathway.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Female; Humans; Isotretinoin; Lymphoma, T-Cell, Cutaneous; Mice; Protein-Tyrosine Kinases; Signal Transduction; Skin Neoplasms; Xenograft Model Antitumor Assays

Topics: Acne Conglobata; Acne Vulgaris; Animals; Cysts; Dermatologic Agents; History, 20th Century; Humans; Isotretinoin; Mice; Models, Animal; Papilloma; Placebo Effect; Skin Neoplasms; Vitamin A

Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54-67% and complete response (CR) rates 7-27%. Data on RAR-agonist monotherapy are limited.. To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF.. Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files.. Thirty-five patients (26 males) of median age 50 years (range 8-83) with early-stage MF (IA 9, IB 26) underwent 37 treatment events: 25 acitretin and 12 isotretinoin at a median dosages of 0.3 mg/kg (range 0.2-0.9) and 0.2 mg/kg (range 0.1-0.7), respectively. Median time to maximal response was 6 months for both (range 1-10 for acitretin, 3-16 for isotretinoin); median treatment duration was 10 months (range 3-46) for acitretin, and 9 months (range 3-55) for isotretinoin. OR was 64% for acitretin and 80% for isotretinoin, and CR, 4% and 8%, respectively. Side-effect profiles were as previously reported for retinoids.. Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.

Topics: Acitretin; Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatologic Agents; Female; Humans; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Retinoid X Receptors; Retrospective Studies; Skin Neoplasms; Young Adult

A case of multiple xanthogranulomas located bilaterally on arms, armpits, legs, trunk, abdomen, scalp, neck and plantar surfaces in a 25-year-old man is reported. The patient was evaluated by polarised light dermoscopy and reflectance confocal microscopy (RCM) that showed peculiar aspects. In particular, dermoscopy showed a homogeneous orange-yellowish hue that is related to the histopathological presence of foamy histiocytes and Touton giant cells; the last typically appeared at RCM as peculiar giant cells surrounded by highly refractive ring due to the cytoplasm rich of lipids. Laboratory investigations, including routine haematological examination, liver and renal function tests, serum lipid and sugar levels were normal. The patient started isotretinoin 20 mg once daily. After 6 months, some lesions flattened, leading to yellowish or hyperpigmented macules, but new lesions raised up.

Topics: Adult; Dermatologic Agents; Dermoscopy; Diagnosis, Differential; Humans; Isotretinoin; Male; Microscopy, Confocal; Skin Neoplasms; Xanthomatosis

Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells.. The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM.. The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis.. ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling.. ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.

Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Isotretinoin; Janus Kinase 1; Janus Kinase 3; Lymphoma, T-Cell, Cutaneous; Molecular Structure; Signal Transduction; Skin Neoplasms; STAT3 Transcription Factor; STAT5 Transcription Factor; Structure-Activity Relationship

Epidermodysplasia verruciformis (also known as Lewandowsky-Lutz dysplasia) is an extremely rare autosomal recessive genodermatosis, in which the skin is unusually sensitive to human papilloma viruses (HPV). It is associated with a high risk of developing non-melanocytic skin tumors. Treatment with keratolytic retinoids is currently considered to be the most effective therapy. Retinoids have a broad spectrum of activity and inhibit the growth of squamous cell carcinoma and other malignant tumors. We report the case of an 81-year-old woman who had been receiving prophylactic treatment with oral isotretinoin at a daily dose of 1.0-0.33 mg/kg bodyweight for about 18 years because of her epidermodysplasia verruciformis (HPV types 9 & 57 detected). We observed a reduction of the incidence of squamous cell carcinomas of the skin and presume a causal relationship between the treatment with this retinoid and the reduction of squamous cell carcinomas of the skin in this patient.

Topics: Administration, Oral; Aged, 80 and over; Carcinoma, Squamous Cell; Dermatologic Agents; Epidermodysplasia Verruciformis; Female; Humans; Isotretinoin; Skin Neoplasms

Vemurafenib, a kinase inhibitor that targets tumors with the BRAF V600E mutation, is a promising option for unresectable or metastatic melanoma. Cutaneous side-effects have been reported including alopecia, photosensitivity, squamous cell carcinoma, keratoacanthomas, keratosis pilaris-like eruption, and palmoplantar hyperkeratosis. Acneiform eruptions have been reported in 3%-6% of the patients treated with BRAF inhibitors,and 5 cases are described in the literature. Although they responded well to topical therapies, oral antibiotics, or observation, one case required oral etretinate and the withdrawal of vemurafenib because the adverse event reached grade 3. We report one case of a severe acneiform eruption associated with vemurafenib with a good response to isotretinoin allowing continuation of the BRAF inhibitor.

Topics: Acneiform Eruptions; Adult; Antineoplastic Agents; Dermatologic Agents; Drug Eruptions; Female; Humans; Isotretinoin; Melanoma; Severity of Illness Index; Skin Neoplasms; Vemurafenib

Lymphangioma circumscriptum (LC) is a superficial form of lymphatic malformation that can be difficult to treat. Therapeutic approaches to LC such as laser therapy, sclerotherapy, and surgical excision give varying results. This is the first description of a case of LC successfully treated with oral isotretinoin. Further studies are needed to confirm whether this is a reproducible treatment option.

Topics: Administration, Oral; Adolescent; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunohistochemistry; Isotretinoin; Keratolytic Agents; Lymphangioma; Skin Neoplasms; Thigh; Treatment Outcome

Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Humans; Isotretinoin; MAP Kinase Signaling System; Phosphorylation; Receptors, Retinoic Acid; Skin Neoplasms; Transcription Factor AP-1

The chemoprevention refers to the use of various types of chemical agents for preventing carcinogenic progression. Systemic retinoids are the most studied chemopreventive agents due to their capacity to regulate cell proliferation and their demonstrated efficacy in several clinical studies.. The aim of the authors was to give precise indications regarding the use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer (NMSC).. The authors reviewed the literature found through a search to MEDLINE (from 2001 to December 2011).. Both acitretin and isotretinoin are effective for the prevention of NMSC. Isotretinoin is preferred in xeroderma pigmentosum and nevoid basal cell carcinoma syndrome, whereas acitretin is more used in transplant recipients, psoriasis and severe sun damage.. Despite numerous studies of the literature concerning retinoids in chemoprevention of NMSC, precise details of the type of retinoid to use, dosage and the duration of this preventive treatment and how to manage side effects in the case of long-lasting treatment are still not uniform and comparable. Moreover, neither guidelines nor approval by Food and Drug Administration exist to regulate the use of retinoids in chemoprevention.

Topics: Acitretin; Basal Cell Nevus Syndrome; Dermatologic Agents; Humans; Isotretinoin; Off-Label Use; Organ Transplantation; Psoriasis; Risk Factors; Skin Neoplasms; Sunlight; Xeroderma Pigmentosum

Retinoid therapy is used for chemo-prevention in immuno-suppressed patients at high risk of developing skin cancer. The retinoid signalling molecule, tripartite motif protein 16 (TRIM16), is a regulator of keratinocyte differentiation and a tumour suppressor in retinoid-sensitive neuroblastoma. We sought to determine the role of TRIM16 in skin squamous cell carcinoma (SCC) pathogenesis. We have shown that TRIM16 expression was markedly reduced during the histological progression from normal skin to actinic keratosis and SCC. SCC cell lines exhibited lower cytoplasmic and nuclear TRIM16 expression compared with primary human keratinocyte (PHK) cells due to reduced TRIM16 protein stability. Overexpressed TRIM16 translocated to the nucleus, inducing growth arrest and cell differentiation. In SCC cells, TRIM16 bound to and down regulated nuclear E2F1, this is required for cell replication. Retinoid treatment increased nuclear TRIM16 expression in retinoid-sensitive PHK cells, but not in retinoid-resistant SCC cells. Overexpression of TRIM16 reduced SCC cell migration, which required the C-terminal RET finger protein (RFP)-like domain of TRIM16. The mesenchymal intermediate filament protein, vimentin, was directly bound and down-regulated by TRIM16 and was required for TRIM16-reduced cell migration. Taken together, our data suggest that loss of TRIM16 expression plays an important role in the development of cutaneous SCC and is a determinant of retinoid sensitivity.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Dermatologic Agents; DNA-Binding Proteins; Down-Regulation; Humans; Immunohistochemistry; In Vitro Techniques; Isotretinoin; Protein Binding; Skin Neoplasms; Transcription Factors; Tripartite Motif Proteins; Tumor Cells, Cultured; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Vimentin

Folliculosebaceous cystic hamartoma (FSCH) is a relatively recently described malformation with follicular and sebaceous components and a particular type of stroma with adipocytes. We conducted an anatomo-clinical study in order to clarify the clinical and histological characteristics of FSCH.. We included all cases of FSCH diagnosed between 1985 and February 2011 at our dermatopathology laboratory. Clinical information was obtained from medical records and requests for histological examination.. We studied 25 cases of FSCH in 25 patients of mean age 51 years. The sex ratio was 1.3. The mean disease duration was 9 years. Lesions were described mainly as flesh-colored, occasionally pedunculated nodules and were found primarily on the face (60%). The diagnosis of FSCH had never been mentioned by the clinician. Histological examination revealed in all cases one or more follicular cystic structures surrounded by sebaceous glands in a stroma containing adipocytes. A number of variants were identified, such as the presence of a mucinous stroma, a neuroid component with protein S 100 expression, and rudimentary hair follicles in adjacent dermis. One case involved a proliferating cyst while another was on the scalp in the area of pre-existing radiodermatitis. Only one relapse was noted, 5 years after the initial excision.. FSCH is a benign, underdiagnosed lesion, localized on the face, particularly on the nose. It is dome-shaped or pedunculated and grows slowly. Differential diagnoses include nevus lipomatosus superficialis and "sebaceous" trichofolliculoma. FSCH can be readily identified by the presence of adipocytes and a fibrous stroma. One case was unique in its appearance of a large pedunculated nodule with a proliferating cyst. Prior to the invidualization of this entity, such cases were interpreted as nevus lipomatosus superficialis or "sebaceous" trichofolliculoma, although their histological appearance was inconsistent with such a diagnosis.

Topics: Acitretin; Adipocytes; Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Diagnosis, Differential; Epidermal Cyst; Facial Dermatoses; Female; Follicular Cyst; Hair Follicle; Hamartoma; Humans; Isotretinoin; Lasers, Gas; Male; Middle Aged; Neoplasms, Basal Cell; Radiodermatitis; Retrospective Studies; Skin Diseases; Skin Neoplasms; Stromal Cells; Young Adult

Topics: Aged; Aged, 80 and over; Graft Occlusion, Vascular; Humans; International Normalized Ratio; Isotretinoin; Male; Skin Neoplasms

Topics: Dermatologic Agents; Humans; Inflammatory Bowel Diseases; Isotretinoin; Psoriasis; Skin Diseases; Skin Neoplasms

Multiple cutaneous osteomas are a rare complication of chronic inflammatory acne that often goes unrecognized. We report a case concerning a 35-year-old woman.. A 35-year-old woman had been treated for acne since the age of 22 years, as part of which she received two courses of oral isotretinoin. We noted the secondary appearance of several microcysts on the face for which the excision was very difficult. Curiously, these small formations did not contain keratin but were very callous. Histological examination revealed foci of osseous metaplasia, probably of postinflammatory origin. Treatment consisted solely of excision of the lesions.. Osteoma cutis comprises two distinct groups (primary and secondary). In our case, there were multiple cutaneous osteomas of the face resulting from chronic acne. The differential diagnosis was idiopathic miliary osteomatosis of the face, but this was ruled out by the young age of the patient, the improvement of the acneiform lesions under isotretinoin (confirming the initial diagnosis of acne) and the subsequent appearance of microcysts. Although there are as yet no codified treatments, excision appears to yield good results.

Topics: Acne Vulgaris; Adult; Anti-Bacterial Agents; Dermatologic Agents; Durapatite; Female; Fenofibrate; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Isotretinoin; Minocycline; Neoplasms, Multiple Primary; Osteoma; Skin Neoplasms

Retinoids and the histone deacetylase inhibitor valproic acid have shown anticancer properties, but the photocarcinogenic or photoprotective effect is unclear. Therefore, we investigated whether a topical formulation of valproic acid is photocarcinogenic or photoprotective in hairless female C3.Cg/TifBomTac immunocompetent mice exposed to simulated solar radiation (SSR) and whether valproic acid changes the effect of the retinoids: tazarotene and isotretinoin. The products were applied on the dorsal skin of 400 mice (five times weekly) followed by SSR (three times weekly) 3-4 h after the application. This was performed during 12 months or until death. Tumors appeared sooner in groups treated with tazarotene and isotretinoin compared with that of the group treated with valproic acid and the control group. The present study shows that valproic acid alone is not photocarcinogenic or photoprotective in hairless mice. When valproic acid is combined with tazarotene or isotretinoin, it does not change their photocarcinogenicity significantly.

Topics: Administration, Cutaneous; Animals; Carcinogens; Dermatologic Agents; Dose-Response Relationship, Radiation; Female; Isotretinoin; Kaplan-Meier Estimate; Mice; Mice, Hairless; Nicotinic Acids; Photochemical Processes; Skin; Skin Neoplasms; Ultraviolet Rays; Valproic Acid

To determine the chemotherapeutic effect of retinoids on albino mouse skin.. Eighty albino mice were selected for this study and were divided into four groups (A-D, 20 mice in each group). 7,12-Dimethylbenz(a)anthracene (DMBA) and tetradecanoylphorbal-13-acetate (TPA) were given for 15 weeks to produce tumors. Retinoids were given topically and orally after the development of tumors for the following 15 weeks.. Of the 80 mice, 69 (86.25%) developed different types of lesion and 11 (13.75%) remained lesion free. Of the 69 mice that developed lesions, 50 (62.50%) developed benign lesions and 19 (23.75%) developed malignant lesions. In all groups of mice, treatment with retinoids was effective against all benign lesions and the early stages of carcinogenesis of the skin. The chemotherapeutic effect against malignant tumors was not satisfactory.. This study demonstrates that retinoids are effective as chemopreventive agents in premalignant lesions of the skin, but have a very weak chemotherapeutic role in malignant neoplasms. If retinoids are given at an early stage, they can cause regression of premalignant lesions of the skin. They are best administered both orally and parenterally. These agents should be recommended as they reduce the potential effects of carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Diterpenes; Isotretinoin; Mice; Precancerous Conditions; Retinyl Esters; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vitamin A

A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.

Topics: Animals; Dog Diseases; Dogs; Fatal Outcome; Isotretinoin; Male; Mycosis Fungoides; Prednisolone; Skin Neoplasms

Topics: Antineoplastic Agents; Humans; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Skin Neoplasms

An 18-month-old cross-breed dog developed multiple skin nodules, which over 8 months had increased in size and number. Biopsy samples were submitted for histopathological examination and revealed multiple benign pilomatrixomas. The dog was treated with 1 mg kg(-1) isotretinoin daily, which led to a stabilization of the size and number of the lesions. Attempts to lower the dosage to an every other day regimen led to an increase in the nodules' size and number. Monthly complete blood count and chemistry tests and Schirmer tear tests were performed to monitor any adverse effects of the retinoid treatment. No adverse effects were noted. To the authors' knowledge, this is the first report of multiple pilomatrixomas arising in a young dog and successfully controlled with oral retinoids.

Topics: Animals; Dermatologic Agents; Diagnosis, Differential; Dog Diseases; Dogs; Drug Administration Schedule; Hair Diseases; Isotretinoin; Male; Pilomatrixoma; Skin Neoplasms

The present paper assesses the chemopreventive potential of retinoic acid on benzoyl peroxide (BPO)-induced cutaneous tumor promotion response and oxidative stress in murine skin. In this study, we have shown the activities of cutaneous antioxidant enzymes and phase II metabolizing enzymes and the glutathione content were decreased while epidermal ornithine decarboxylase (ODC) activity and DNA synthesis were induced in benzoyl peroxide treated animals. Topical application of retinoic acid resulted in significant inhibition of benzoyl peroxide-induced epidermal ornithine decarboxylase activity and DNA synthesis. Application of retinoic acid at three different doses prior to the application of benzoyl peroxide recovered the depleted level of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, thus resulting in significant inhibition of oxidative stress in dose dependent manner. Enhanced susceptibility of cutaneous microsomal lipid peroxidation and xanthine oxidase activity were significantly reduced (P > 0.05). The antimutagenic effect of retinoic acid was tested against benzoyl peroxide mediated mutagenicity in Salmonella typhimurium strain TA-98 and TA-100 using 3-methyl cholanthrene-induced murine skin (S9 fraction) as the metabolic activation system. Indeed, with the addition of various concentrations of retinoic acid there was significant reduction in the number of revertants per plate in concentration dependent manner. In summary, our data indicates that retinoic acid may exhibit cancer chemopreventive activity in skin tumorigenesis model.

Topics: Administration, Topical; Animals; Benzoyl Peroxide; Biomarkers, Tumor; Cell Division; Disease Models, Animal; Glutathione Peroxidase; Glutathione Reductase; Isotretinoin; Male; Mice; Oxidative Stress; Sensitivity and Specificity; Skin; Skin Neoplasms

Confluent and reticulated papillomatosis is an uncommon dermatosis of unknown etiology which is often difficult to diagnose. Lesions appear on the mid-trunk and affect mostly young females. We report a 15-year-old girl with typical clinical and histologic features of this rare disorder in whom the lesions rapidly improved after minocycline therapy. Topical treatment with isotretinoin and erythromycin was ineffective.

Topics: Administration, Oral; Administration, Topical; Adolescent; Biopsy; Cyproterone Acetate; Diagnosis, Differential; Erythromycin; Female; Humans; Isotretinoin; Minocycline; Papilloma; Recurrence; Skin; Skin Neoplasms

Annular elastolytic giant cell granuloma is a rare disease characterized by annular configurated lesions with typical histopathologic findings. We report a case of annular elastolytic giant cell granuloma in a 50-year-old male patient. Treatment modalities for this disease are limited and mostly unsatisfactory, although isotretinoin was found to be effective in a single case. However, systemic isotretinoin treatment of 12 weeks' duration was of no benefit in the presented case.

Topics: Administration, Oral; Diagnosis, Differential; Granuloma, Giant Cell; Humans; Isotretinoin; Keratolytic Agents; Male; Middle Aged; Neck; Skin Neoplasms; Treatment Failure

Topics: Child; Female; Humans; Isotretinoin; Nevus; Skin Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase III as Topic; Decision Making; Evidence-Based Medicine; Humans; Interferon-alpha; Isotretinoin; Practice Guidelines as Topic; Research Design; Skin Neoplasms

Retinoids have been shown to inhibit the growth of squamous cell carcinoma and other malignancies. They have also been shown to alter gap junctional intercellular communication (GJIC) and the expression of connexins, the protein subunits of gap junctions. We report in this study that the alteration of GJIC by retinoids may be directly related to inhibitory effects on cell growth.. SCC-13 cells were treated with all-trans retinoic acid (tRA) and 13-cis retinoic acid (cRA) at 10(-7) and 10(-6) M concentrations in culture. No treatment and ethanol vehicle controls were included for each experiment. Serial cell counts of parallel cultures were performed to determine cell growth. The parachute technique was performed in combination with fluorescence activated cell sorting (FACS) analysis to determine GJIC. Northern and Western blot analysis were performed to assess connexin mRNA and protein expression.. The growth rate was inhibited for cells treated with tRA (10(-6) M) (P < 0.05) and cRA (10(-6) M) (P = 0.068) vs. vehicle control. GJIC was significantly inhibited with both tRA (10(-7) and 10(-6) M) (P < 0.001) and cRA (10(-7) and 10(-6) M) (P < 0.001) at 24, 48, and 96 h as determined by FACS analysis. To correlate GJIC with cell growth, we studied the effect of glycyrrhetinic acid, a known inhibitor of GJIC. Glycyrrhetinic acid also significantly inhibited cell growth (P < 0.05) vs. control. Connexin 26 and connexin 43 mRNA and protein expression were not significantly altered after retinoid treatment.. Retinoic acids inhibit both cell growth and GJIC in SCC-13 cells. Retinoids may inhibit cell growth through alteration of GJIC in SCC-13 cells.

Topics: Blotting, Northern; Blotting, Western; Carcinoma, Squamous Cell; Cell Communication; Cell Division; Connexin 26; Connexin 43; Connexins; Flow Cytometry; Gap Junctions; Glycyrrhizic Acid; Isotretinoin; Logistic Models; Retinoids; RNA, Messenger; Skin Neoplasms; Tretinoin; Tumor Cells, Cultured

Topics: Administration, Topical; Antineoplastic Agents; Carcinoma, Squamous Cell; Humans; Isotretinoin; Organ Transplantation; Skin Neoplasms; Tretinoin

We report the case of a 7-year old boy with xeroderma pigmentosum and a large squamous cell carcinoma of the cheek. He received a combination of isotretinoin (1 mg/kg/day) and chemotherapy for a period of 3 months and showed complete remission of the tumor. Treatment modalities of malignancies in xeroderma pigmentosum are reviewed and discussed in relation to the literature. The advantages of our protocol were emphasized because of the rapid improvement in a short time with minimal side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Child; Cisplatin; Fluorouracil; Humans; Isotretinoin; Keratolytic Agents; Male; Skin Neoplasms; Treatment Outcome; Xeroderma Pigmentosum

We recently synthesized several conformationally constrained retinoic acid (RA) analogues [8-(2'-cyclohexen-1'-ylidene)-3, 7-dimethyl-2,4,6-octatrienoic acids with different alkyl substituents at 2' (R1) and 3' (R2) positions on the cyclohexene ring] (Muccio et al. J. Med. Chem. 1996, 39, 3625) as cancer chemopreventive agents. UAB8 (R1 = Et; R2 = iPr), which contains sufficient steric bulk at the terminal end of the polyene chain to mimic the trimethylcyclohexenyl ring of RA, displayed biological properties similar to those of RA. To explore the efficacy of this retinoid in acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML), we evaluated UAB8 isomers in in vitro assays which measure the capacity of retinoids to inhibit aberrant myeloid colony growth from blood or bone marrow cells obtained from human JMML patients and in assays measuring the potential of retinoids to differentiate NB4 cells (an APL cell line). Both (all-E)- and (13Z)-UAB8 were 2-fold more active than RA in the NB4 cell differentiation assay; however, only (all-E)-UAB8 had comparable activity to the natural retinoids in the JMML cell assays. These results were compared to the biological effectiveness of a new retinoid, UAB30 [8-(3', 4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4, 6-octatrienoic acid], which had different nuclear receptor binding and transactivational properties than UAB8. Relative to (all-E)-RA and (all-E)-UAB8, (all-E)-UAB30 bound well to RARalpha but did not activate transcription-mediated RARalpha homodimers, even though it was effective in RARbeta- and RARgamma-mediated transactivational assays. In APL assays, this retinoid had much reduced activity and was only moderately effective in JMML assays and in cancer chemoprevention assays.

Topics: Animals; Antineoplastic Agents; Cell Line; Chickens; Child; Fatty Acids, Unsaturated; HL-60 Cells; Humans; In Vitro Techniques; Leukemia, Myelomonocytic, Chronic; Leukemia, Promyelocytic, Acute; Mice; Molecular Conformation; Naphthalenes; Papilloma; Radioligand Assay; Receptors, Retinoic Acid; Skin; Skin Neoplasms; Stereoisomerism; Transcription, Genetic; Tretinoin; Tumor Stem Cell Assay

Patients with xeroderma pigmentosum (XP) frequently develop sunlight-induced skin cancer. Infrequently, internal neoplasms may also occur. A 21-year-old patient with XP, who had many skin cancers, developed a rare internal tumour - a grade II diffuse fibrillary spinal cord astrocytoma - during a break in a therapeutic trial of isotretinoin for skin cancer prevention. Treatment of neoplasms in XP patients presents special difficulties because of their defect in DNA repair.. The study objective was to raise awareness of the cancer surveillance process in XP patients and the concerns involved in choice of therapy.. Since the spinal cord tumour was inoperable, the patient was treated with x-radiation, continued on isotretinoin treatment and was followed closely for tumour response.. Despite sensitivity to sunlight, the patient had a normal acute response to the x-ray treatment without excessive skin reaction. Serial examinations by magnetic resonance imaging (MRI) starting 8 months after x-ray treatment was initiated, showed a marked gadolinium enhancement followed by regression. This clearing was first seen at 2 years after biopsy and persisted to at least 9 years after treatment.. In contrast to the exaggerated sensitivity to UV radiation, XP patients may tolerate therapeutic doses of x-radiation. Isotretinoin treatment may have contributed to the good response of this spinal cord astrocytoma.

Topics: Adult; Astrocytoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Isotretinoin; Keratolytic Agents; Male; Skin Neoplasms; Spinal Cord Neoplasms; Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.

Topics: Adolescent; Adult; Cells, Cultured; Child; Drug Administration Schedule; Female; Humans; Interleukin-2; Isotretinoin; Keratolytic Agents; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Male; Middle Aged; Skin Neoplasms; Tumor Necrosis Factor-alpha; Xeroderma Pigmentosum

Topics: Administration, Oral; Basal Cell Nevus Syndrome; Female; Humans; Isotretinoin; Keratolytic Agents; Middle Aged; Organ Transplantation; Postoperative Complications; Practice Guidelines as Topic; Retinoids; Risk Factors; Skin Neoplasms; Xeroderma Pigmentosum

Topics: Animals; Antineoplastic Agents; Apoptosis; Clinical Trials, Phase III as Topic; Humans; Isotretinoin; Keratolytic Agents; Neoplasms; Neoplasms, Experimental; Receptors, Retinoic Acid; Retinoids; Skin; Skin Neoplasms; Tretinoin

Topics: Administration, Oral; Angiolymphoid Hyperplasia with Eosinophilia; Female; Humans; Isotretinoin; Keratolytic Agents; Middle Aged; Neoplasms, Vascular Tissue; Skin Neoplasms

Keratoacanthoma is a common cutaneous neoplasm, although the persistent form is less common and often more difficult to manage. Multiple treatment approaches have been attempted with variable efficacy. Establishing the diagnosis and selecting a treatment plan for persistent keratoacanthoma is often challenging.. Our purpose is to describe the difficulty one may encounter in the diagnosis and treatment of persistent keratoacanthoma. Hopefully, review of this clinical conundrum may facilitate the management of the reader's future patients.. We describe a case of persistent keratoacanthoma where the diagnosis was initially elusive and the management challenging. Our thought process during each stage of diagnosis and management is described in the form of "issues" with references to the appropriate literature.. After several diagnostic and therapeutic interventions, successful treatment was achieved with administration of oral isotretinoin. Long-term remission continued as the dosage was tapered.. Persistent keratoacanthoma may be challenging to diagnose and manage, presenting a clinical conundrum. Careful review of the clinicopathologic presentation and an understanding of the various treatment options may result in a successful outcome.

Topics: Administration, Oral; Chemotherapy, Adjuvant; Combined Modality Therapy; Dermatologic Surgical Procedures; Humans; Isotretinoin; Keratoacanthoma; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Skin; Skin Neoplasms; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bowen's Disease; Carcinoma, Squamous Cell; Female; Humans; Interferon-alpha; Isotretinoin; Neoplasms, Multiple Primary; Skin Neoplasms

We recently demonstrated that conformationally defined 6-s-trans-retinoic acid (RA) analogs were effective in the prevention of skin papillomas (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) and selective agonists for nuclear receptor binding and activation (Alam et al. J. Med. Chem. 1995, 38, 2302-2310). In order to probe important structure-activity relationships, we evaluated a homologous series of four 6-s-trans-retinoids that are 8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different substituents at 2' (R2) and 3' (R1) positions on the cyclohexene ring. UAB1 (R1 = R2 = H), UAB4 (R1 = R2 = Me), UAB7 (R1 = Me, R2 = iPr), and UAB8 (R1 = Et, R2 = iPr) contain alkyl R groups that mimic, to different extents, portions of the trimethylcyclohexenyl ring of RA. Both 9Z- and all-E-isomers of these retinoids were evaluated in binding assays for cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), a nuclear retinoic acid receptor (RAR alpha), and a nuclear retinoid X receptor (RXR alpha). The all-E-isomers of UAB retinoids bound tightly to CRABPs and RAR alpha, the binding affinity of the all-E-isomer increased systematically from UAB1 to UAB8, and binding for the latter was comparable to that of all-E-RA. In contrast to RA, the (9Z)-UAB retinoids were at least 200-fold less active than the all-E-isomers in binding to RAR alpha. The (9Z)-UAB isomers exhibited increasingly stronger binding to RXR alpha, and (9Z)-UAB8 was nearly as effective as (9Z)-RA in binding affinity. The retinoids were also evaluated in gene expression assays mediated by RAR alpha and RXR alpha homodimers or RAR alpha/RXR alpha heterodimers. Consistent with the binding affinities, the (all-E)-UAB retinoids activated gene transciption mediated by RAR alpha homodimers or RAR alpha/RXR alpha heterodimers, while the (9Z)-UAB isomers activated only the RXR alpha homodimer-mediated transcription. The all-E- and 9Z-isomers of the UAB retinoids were further evaluated for their capacity to prevent the induction of mouse skin papillomas. When compared to RA, only the (all-E)-UAB retinoids containing bulky R1 and R2 groups were effective in this chemoprevention assay. (9Z)-RA displayed equal capacity as RA to prevent papillomas, while the 9Z-isomers of the UAB retinoids were much less effective. Taken together, these studies demonstrate that the cyclohexenyl ring substituents of 6-s-trans-UAB retinoids are important for their biological activities and that the ch

Topics: Animals; Anticarcinogenic Agents; Cell Nucleus; Mice; Models, Molecular; Molecular Conformation; Molecular Structure; Papilloma; Receptors, Retinoic Acid; Retinoid X Receptors; Retinoids; Skin Neoplasms; Stereoisomerism; Structure-Activity Relationship; Thermodynamics; Transcription Factors; Transcription, Genetic

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Basal Cell Nevus Syndrome; Female; Humans; Interferon-alpha; Isotretinoin; Skin Neoplasms; Treatment Failure

Topics: Humans; Isotretinoin; Kidney Transplantation; Skin Neoplasms

Cutaneous T-cell lymphoma (CTCL) may respond to many therapies, but long-term disease-free survival is uncommon. Patients with advanced disease have a median survival of approximately 3 years.. Our purpose was to combine known effective agents sequentially to determine whether we could achieve remission in more patients or for longer duration.. Patients with mycosis fungoides (n = 23) or Sézary syndrome (n = 5) were treated with 4 months of recombinant interferon alfa together with isotretinoin, followed by total skin electron beam therapy alone (for stage I to II disease) or preceded by chemotherapy (for stage III to IV disease). Maintenance therapy consisted of interferon for 1 year and topical nitrogen mustard for 2 years.. Twenty-eight patients were treated. The overall response rate (complete and partial remissions) was 82%. Although the median duration of remission was 5 months in patients with stage III to IV disease, two patients remain in complete remission at 39 + and 46 + months. In patients with stage I to II disease the median duration of remission has not been reached at a median follow-up of 18 months. Five patients, all with stage III to IV disease, have died. Overall, the regimen was well tolerated with one treatment-related death from neutropenic sepsis.. Combined modality therapy may be effective for the treatment of CTCL with similar response rates to other current therapies.

Topics: Administration, Cutaneous; Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Cause of Death; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Interferon Type I; Isotretinoin; Keratolytic Agents; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Radiotherapy Dosage; Radiotherapy, High-Energy; Recombinant Proteins; Remission Induction; Sezary Syndrome; Skin Neoplasms; Survival Rate

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Dermatologic Agents; Emollients; Female; Humans; Isotretinoin; Keratolytic Agents; Lactic Acid; Papilloma; Remission Induction; Skin Neoplasms

An 8-year-old spayed female ferret was examined for diffuse generalized alopecia, erythema, erosions, crusts, and ulcerated plaques that were nonresponsive to long-term administration of corticosteroids. Cutaneous epitheliotropic lymphoma was diagnosed on the basis of histologic examination of skin biopsy specimens. Neoplastic cells were determined to be of T-lymphocytic origin by results of immunohistochemical staining with a rabbit anti-CD3 monoclonal antibody. Additional laboratory abnormalities detected included anemia, azotemia, isosthenuria, pyuria, and bacteriuria. Treatment included isotretinoin and amoxicillin trihydrate plus clavulanate potassium administered orally, and oatmeal-based shampoos. Isotretinoin was tolerated well and cutaneous lesions resolved after 60 days of treatment, but pretreatment azotemia worsened and the ferret was euthanatized. Necropsy revealed cutaneous epitheliotropic lymphoma, pyelonephritis, and interstitial nephritis. Renal disease most likely was caused by immunosuppression secondary to chronic treatment with corticosteroids and aging. Isotretinoin, although not curative, may be useful for the palliative treatment of cutaneous epitheliotropic lymphoma in ferrets.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Clavulanic Acid; Clavulanic Acids; Combined Modality Therapy; Dietary Proteins; Female; Ferrets; Isotretinoin; Keratolytic Agents; Lymphoma; Penicillins; Skin Neoplasms

It is well known that patients with heritable cutaneous diseases may have excess tumors during their lifetime. This relationship has been shown for such diverse conditions as xeroderma pigmentosum, Bloom syndrome, basal cell nevus syndrome, and psoriasis. However, multiple cutaneous tumors have not been previously described in people with lamellar ichthyosis. This article describes the cases of two such patients, possible treatment, and a previously undescribed ichthyosis syndrome.

Topics: Adolescent; Adult; Biopsy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Etretinate; Humans; Ichthyosis; Isotretinoin; Male; Neoplasms, Second Primary; Scalp; Skin Neoplasms

Topics: Acitretin; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Female; Humans; Isotretinoin; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Remission Induction; Skin Neoplasms

Topics: Aged; Calcitriol; Female; Humans; Isotretinoin; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Skin Neoplasms

Various retinoids and interferons exert anti-tumor effects both in experimental studies and in clinical trials. Recent reports indicate that they have a synergistic antineoplastic activity. Our study aimed to determine whether these synergistic anti-tumor effects are related to inhibition of tumor-cell-induced angiogenesis. A further aim was to compare the anti-angiogenic activity of various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic acid receptor RXR, given alone and in combination with interferon alpha-2a (IFN alpha-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse was used. Angiogenesis was induced by intradermal injection of HPV16- or HPV18 DNA-harboring tumor-cell lines. All-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as IFN alpha-2a applied to mice intraperitoneally for 5 consecutive days before induction of angiogenesis resulted in significant inhibition of angiogenesis. Combination of retinoids with IFN alpha-2a led to a synergistic inhibition of angiogenesis, as compared to the effects of the drugs given alone. Similar results were obtained when tumor cells were preincubated in vitro with the compounds, before injection into untreated mice. Our findings on synergistic anti-angiogenic effects of retinoids and IFN alpha-2a could explain, at least partially, the anti-tumor efficacy of combined therapy with these agents, and provide support for the role of angiogenesis in tumor growth.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Drug Synergism; HeLa Cells; Humans; Interferon alpha-2; Interferon-alpha; Isomerism; Isotretinoin; Keratinocytes; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic; Papillomaviridae; Recombinant Proteins; Retinoids; Skin Neoplasms; Tretinoin; Tumor Cells, Cultured; Tumor Virus Infections

Topics: Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Head and Neck Neoplasms; Humans; Interferon-alpha; Isotretinoin; Male; Neoplasms; Papillomaviridae; Papillomavirus Infections; Skin Neoplasms; Tumor Virus Infections; Uterine Cervical Neoplasms

The virus-associated T cell leukaemias/lymphomas are characterized by a poor prognosis primarily because of the rapid emergence of drug resistance which may lead to failure of subsequent chemotherapy. We report here a case of Epstein-Barr virus-associated T cell lymphoma which relapsed soon after chemotherapy and radiotherapy. The neoplastic cells of the relapsed tumour expressed high levels of multi-drug resistance gene (mdr1)-related P-glycoprotein and glutathione-S-transferase-pi, both of which were absent in the pre-chemotherapy tumour tissues. Empirical treatment with oral 13-cis-retinoic acid (RA) was then given with subsequent complete disappearance of the tumour. The therapeutic effect of RA appears to act through an apoptotic process. In accordance with our previous report of a successful salvage of a refractory Ki-1 large cell lymphoma. RA appears to be a potentially useful drug for some specific type T-cell lymphomas.

Topics: Aged; Apoptosis; Blotting, Southern; Drug Resistance, Multiple; Female; Herpesvirus 4, Human; Humans; Isotretinoin; Lymphoma, T-Cell, Cutaneous; Phenotype; Skin Neoplasms; Tumor Virus Infections

Topics: Aged; Carcinoma, Squamous Cell; Drug Therapy, Combination; Facial Neoplasms; Humans; Interferon-alpha; Isotretinoin; Male; Remission Induction; Skin Neoplasms; Treatment Outcome

Topics: Carcinoma, Basal Cell; Humans; Isotretinoin; Skin Neoplasms

The purpose of this study was to evaluate the synthetic retinoids isotretinoin and etretinate to treat dogs with intracutaneous cornifying epitheliomas (ICE), other benign skin neoplasias, and cutaneous lymphoma. Twenty-four dogs were used. All tumors were diagnosed by histologic examination. Ten dogs with multiple (at least 5) benign skin tumors (7 with ICE, 1 each with inverted papillomas, sebaceous adenomas and epidermal cysts) were treated with isotretinoin (n = 7) and/or etretinate (n = 5). Twelve dogs with cutaneous lymphoma were treated with isotretinoin, and 2 dogs with cutaneous lymphoma were initially treated with etretinate. Successful treatment with isotretinoin was achieved in 1 dog with ICE, 1 with inverted papillomas, and 1 with epidermal cysts. Partial improvement with isotretinoin was seen in 2 dogs with ICE. Successful treatment was achieved with etretinate in 4 dogs with ICE (Norwegian Elkhound was the predominant breed with ICE). Remission was achieved in 6 of the 14 dogs with cutaneous lymphoma. Adverse effects developed in 7 of the 24 dogs, so treatment was stopped in 2 dogs.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Dog Diseases; Dogs; Etretinate; Isotretinoin; Lymphoma; Skin Neoplasms

Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Xeroderma Pigmentosum

Topics: Adult; Aged; Carcinoma, Basal Cell; Female; Humans; Hyperostosis; Isotretinoin; Male; Middle Aged; Prospective Studies; Radiography; Skin Neoplasms

Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage.

Topics: Adult; Aged; Cells, Cultured; Chromatids; DNA Damage; Female; Humans; Isotretinoin; Lymphocytes; Male; Middle Aged; Skin Neoplasms; X-Rays; Xeroderma Pigmentosum

Topics: Adult; Gynecomastia; Humans; Isotretinoin; Lymphoma, B-Cell; Male; Scalp; Skin Neoplasms; Skin Transplantation

Topics: Carcinoma, Basal Cell; Clinical Trials as Topic; Double-Blind Method; Humans; Isotretinoin; Multicenter Studies as Topic; Skin Neoplasms

Topics: Anticarcinogenic Agents; beta Carotene; Carcinoma, Basal Cell; Carotenoids; Humans; Isotretinoin; Skin Neoplasms

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Evaluation; Humans; Interferon-alpha; Isotretinoin; Middle Aged; Skin Neoplasms

Topics: beta Carotene; Carotenoids; Diet; Humans; Isotretinoin; Skin Neoplasms

Topics: Adult; Humans; Isotretinoin; Male; Neoplasms, Multiple Primary; Papilloma; Skin Neoplasms

Controlled localized radiofrequency heating and systemic isotretinoin were used serially as therapy in a hairless dog that developed multiple cutaneous squamous cell carcinomas in chronically sun-damaged skin. During the course of therapy, four superficial tumors regressed completely, both clinically and histologically. Two larger, deeper tumors showed clinical signs of regression but histologic clearing did not occur. Both treatment modalities are known to have antitumor effects independently and may exert their effects in an additive fashion. However, it is also possible that heat-induced injury to tumor cells could lead to retinoid-mediated enhancement of an immunologic response to tumor antigens or some other process that might lead to regression.

Topics: Animals; Carcinoma, Squamous Cell; Combined Modality Therapy; Dog Diseases; Dogs; Hot Temperature; Isotretinoin; Male; Neoplasms, Multiple Primary; Radio Waves; Skin Neoplasms

13-cis retinoic acid has been shown to be a stereospecific suicide inhibitor of thioredoxin reductase purified from human melanoma tissue. All trans retinoic acid does not inhibit this enzyme. The covalent addition of 13-cis retinoic acid to the thiolate active site of thioredoxin reductase produces a thioether enzyme-inhibitor complex. This has been established by a kinetic analysis and by active site labeling with 3H-13 cis retinoic acid. A mechanism involving Michael addition of the thiolate group in the active site of thioredoxin reductase to the 13-cis double bond of enzyme-bound inhibitor has been proposed. This reaction may be important in the human epidermis because thioredoxin reductase has been shown to be a major antioxidant catalyst in human keratinocytes, melanocytes, melanoma cells, and in human skin as well as in melanoma tissues.

Topics: Cells, Cultured; Cytosol; Epidermis; Humans; Isotretinoin; Kinetics; Melanoma; NADH, NADPH Oxidoreductases; Skin Neoplasms; Stereoisomerism; Thioredoxin-Disulfide Reductase

Topics: Adult; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Diseases in Twins; Humans; Isotretinoin; Male; Skin Neoplasms; Twins; Twins, Monozygotic

We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed.

Topics: Administration, Oral; Adolescent; Adult; Aged; Biopsy; Dysplastic Nevus Syndrome; Female; Humans; Isotretinoin; Male; Melanoma; Middle Aged; Risk Factors; Skin Neoplasms

Twelve patients with multiple basal cell carcinomas resulting from varying causes were treated with high-dose oral isotretinoin (mean daily dosage: 3.1 mg/kg/day) for a mean of 8 months. Of the 270 tumors monitored in these patients, only 8% underwent complete clinical and histologic regression. All patients developed moderate to severe acute toxicities, leading five patients to withdraw from the study. Retinoid skeletal toxicity was identified in two patients who were examined after long-term therapy. Lower doses of isotretinoin (0.25 to 1.5 mg/kg/day) were ineffective for chemotherapy but demonstrated a chemopreventive effect in a subset of three patients who received these lower doses for 3 to 8 years. Two of these three patients have been observed after discontinuation of therapy. In one patient with a history of arsenic exposure, only one new tumor has appeared in a 27-month posttreatment observation period; in the other patient with the nevoid basal cell carcinoma syndrome, 29 new tumors have appeared within a 13-month period. This suggests that the need for long-term maintenance therapy with isotretinoin for chemoprevention of basal cell carcinoma may depend on the underlying cause of the skin cancers.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Basal Cell; Female; Humans; Isomerism; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Remission Induction; Skin Neoplasms; Tretinoin

Thirty patients, 13 female and 17 male, have been followed from 3 months to 22 years (mean, 81 months; median, 63 months) and special studies have been performed on a proportion of these in order to try to predict malignant evolution. Age at onset was from 20 to 70 years (mean, 43 years; median, 42 years). Duration of disease was from 1 to 30 years (mean, 119 months; median 161 months). Seven patients also had parapsoriasis en plaque or plaque-stage mycosis fungoides at the time of diagnosis and one patient had erythroderma. None of the 22 uncomplicated lymphomatoid papulosis patients developed malignant cutaneous lymphoma during the period of observation, while the remaining 8 patients who had concurrent parapsoriasis en plaque, mycosis fungoides, or erythroderma did not deteriorate further. Single-cell deoxyribonucleic acid (DNA) measurements on the dermal infiltrate were done in 13 patients and were abnormal in 7 patients. Two of these had greatly abnormal DNA histograms and at the same time an abnormal clinical presentation with multiple nodules and tumors. The remaining five patients had DNA histograms that indicated a potential for malignancy. Monoclonal antibody studies were performed on skin biopsy specimens of 10 patients. The dermal infiltrate was dominated by T-helper lymphocytes and some Hodgkin and Reed-Sternberg cells could be detected by the antibodies Ki-1, Ki-24, and Ki-27. Human T-lymphotropic virus type I (HTLV-I) antibodies were found in 3 of 18 patients examined. Treatment with psoralens plus ultraviolet A (PUVA) was effective (partial or complete remission) in six patients but they relapsed at cessation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Viral; Deltaretrovirus; Deltaretrovirus Antibodies; DNA; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Methotrexate; Middle Aged; Precancerous Conditions; PUVA Therapy; Skin Diseases; Skin Neoplasms; Tretinoin

Retinoids, including isotretinoin, have demonstrated antiproliferative and antineoplastic activity in laboratory and clinical trials. In a phase II trial, 25 patients with extensive mycosis fungoides were evaluated for response to isotretinoin. There was a 44% (11 patients) objective clinical response rate with three clinical complete responses without concomitant evidence of pathologic clearing of the disease. An additional 24% (six patients) showed a minor degree of clinical improvement. The median time to response was two months (range, 0.5 to eight months) and the median response duration was eight months or longer (range, one to 25 months). Chronic toxic reactions consisted primarily of drying of the skin and mucous membranes and resulted in dose reduction in the majority of patients. It is concluded that isotretinoin produces significant clinical benefit to some patients with mycosis fungoides.

Topics: Adult; Aged; Aged, 80 and over; Drug Eruptions; Drug Evaluation; Female; Humans; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Tretinoin; Triglycerides

The present study was designed to determine the effects of dietary 13-cis-retinoic acid and retinyl palmitate on mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Female CD-1 mice were initiated with 150 nmol of 7,12-dimethylbenz(a)anthracene and promoted twice weekly with 8 nmol of TPA. Diets supplemented with retinyl palmitate to yield 60,000 or 200,000 IU or 700,000 for 5 wk followed by 350,000 IU per kg of diet (700,000/350,000) fed to mice during tumor promotion resulted in 9%, 37%, and 65% inhibition of the papilloma yield, respectively, at 21 wk of promotion. Although topical applications of 13-cis-retinoic acid have been almost as effective as retinoic acid in preventing the appearance of mouse skin tumors, dietary 13-cis-retinoic acid at 200,000 or 700,000 IU per kg of diet resulted in no reduction in papilloma yield but did result in a dose-dependent decrease in the tumor burden (weight of tumors per mouse). Therefore, dietary retinyl palmitate yielded a dose-dependent inhibition of the number and weight of tumors promoted by TPA, whereas dietary 13-cis-retinoic acid resulted in a decrease in weight but not in number of tumors promoted by TPA.

Topics: Administration, Cutaneous; Animals; Cell Transformation, Neoplastic; Diet; Diterpenes; Dose-Response Relationship, Drug; Female; Isotretinoin; Mice; Papilloma; Retinyl Esters; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors; Tretinoin; Vitamin A

To determine the efficacy of oral isotretinoin in refractory advanced squamous cell carcinoma of the skin.. Case series trial.. Tertiary care center at a university hospital.. A consecutive collection of four patients with advanced squamous cell carcinoma of the skin who failed to respond to standard surgical or radiation therapy.. Isotretinoin in gelatin capsules was given at a total daily dose of 1 mg/kg body weight in two divided doses for at least 4 weeks.. Bidimensional tumor measurements at monthly intervals showed striking responses to isotretinoin in all four patients. Response durations ranged from 2 to more than 23 months. The drug produced reversible moderate mucocutaneous side effects and asymptomatic laboratory abnormalities.. Impressive responses to isotretinoin occurred in our four patients and in six of ten other reported patients. Retinoic acid's mechanisms of action in cutaneous squamous cell carcinoma is not precisely known, but may involve the modulation of epidermal growth factor receptors and certain protein kinases. These in-vitro findings and the clinical data suggest that retinoids may be an effective and well-tolerated therapy for refractory advanced squamous cell carcinoma of the skin. The absence of any other effective systemic therapy indicates the need for continuing trials with retinoids in this disease.

Topics: Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Humans; Isotretinoin; Male; Middle Aged; Neoplasm Recurrence, Local; Skin Neoplasms; Tretinoin

A group of 50 patients with basal cell carcinoma of the face was treated by 13-cis-retinoic acid. The treatment resulted in diminution of the tumors. Complete regression was observed in 4 cases. Histological examination revealed necrosis of cancer cells and mononuclear infiltration into the treated tumors. In the group with weak clinical and histological reaction to the treatment all basal cell carcinomas were of adenoid type. A better effect was observed in the group with lower serum retinol level. This treatment method seems to be supplementary to surgery in prevention of the tumor recurrence.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Tretinoin; Vitamin A

Two patients with multiple basal cell carcinomas, due either to the nevoid basal cell carcinoma syndrome (NBCCS) or arsenical insecticide exposure, were treated with oral isotretinoin for 7 or 8 years, respectively. Gradually decreasing dosage levels were employed. During the initial courses of therapy, high doses (2.0-3.0 mg/kg/day) were intended as chemotherapy. In these patients only 6 of 40 (15%) lesions underwent complete clinical regression. In subsequent courses aimed at chemoprevention, the dose was progressively reduced from 1.5 to 0.25 mg/kg/day. During therapy, no new lesions were observed in the patient with the arsenical exposure. The NBCCS patient developed 1 new lesion during therapy at 1.0 mg/kg/day, 1 new lesion at 0.5 mg/kg/day and 5 new lesions at 0.25 mg/kg/day. Treatment was discontinued and the patient with the arsenic exposure developed his first new tumor 17 months afterwards; in contrast, the NBCCS patient developed 29 tumors within 13 months. These findings suggest that long-term therapy with isotretinoin is needed for the continuation of the cancer chemopreventive effect. However, the need for continuous rather than intermittent maintenance therapy, and the determination of the optimal dose for this purpose may depend on the etiology of the multiple carcinomas and on the tolerability of the lowest effective dose by the individual patient. With these encouraging data, it now appears appropriate to expand this pilot study and perform larger trials to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.

Topics: Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Humans; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Prognosis; Skin Neoplasms; Tretinoin

Oral retinoids are effective in the treatment of patients with a variety of malignant and nonmalignant skin disorders, including mycosis fungoides. We treated six patients with cutaneous T-cell lymphomas with isotretinoin 1 to 2 mg/kg/d. All patients experienced symptomatic relief (fading of skin lesions and disappearance of pruritus) within two to eight weeks of starting the drug therapy; pretreatment and posttreatment biopsy specimens were unchanged. Adverse effects were minor and primarily consisted of drying of the mucous membranes. We conclude that isotretinoin is a well-tolerated, easily administered drug that provides good palliation of symptoms and signs associated with cutaneous T-cell lymphoma in patients who are unable or unwilling to comply with standard therapy.

Topics: Aged; Female; Humans; Isotretinoin; Lymphoma, Non-Hodgkin; Male; Middle Aged; Skin Neoplasms; T-Lymphocytes; Tretinoin; Xerostomia

Sixteen patients - 12 with cutaneous T cell lymphoma (CTCL), 1 with Sézary syndrome, 1 with actinic reticuloid, and 2 with parapsoriasis variegata - were treated with either a new, potent arotinoid alone or with combined etretinate (Tigason) and PUVA therapy (Re-PUVA). 92% of all patients showed a minor up to a distinct response of their skin lesions within 12.6 +/- 7.4 weeks. More than 50% of the skin lesions cleared in 67% of the patients. After discontinuation of the retinoid therapy, relapses occurred in all cases within 3-10 weeks. There was no difference between the therapeutic efficacy of arotinoid alone and the Re-PUVA regimen, but the latter was less toxic.

Topics: Antineoplastic Agents; Benzoates; Combined Modality Therapy; Humans; Isotretinoin; Lymphoma; PUVA Therapy; Retinoids; Skin Neoplasms; T-Lymphocytes; Tretinoin

The effects of retinol, all-trans-retinoic acid, isotretinoin and etretinate on the activity of basement membrane collagen degrading enzyme was studied in melanoma cells. The results indicated that retinoids at concentrations of up to 10(-6) M did not significantly affect type IV collagenolytic activity in these cells in vitro. Since type IV collagenolytic enzyme may be involved in the metastatic potential of tumour cells, it appears that retinoids do not affect the metastatic potential of melanoma cells by affecting type IV collagenolytic activity.

Topics: Cells, Cultured; Etretinate; Humans; Isotretinoin; Melanoma; Microbial Collagenase; Neoplasm Metastasis; Retinoids; Skin Neoplasms; Tretinoin; Vitamin A

The effect of the time and duration of retinoid treatment on the inhibition of Stage II tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied in CD-1 mice. All mice were initiated with 400 nmol of benzo(a)pyrene and received Stage I tumor promotion (3.2 nmol of TPA twice weekly for 2 wk). Animals were then randomized into groups which received 13-cis-retinoic acid during early, middle, or late Stage II promotion. 13-cis-Retinoic acid pretreatments starting on Day 1, Wk 8, or Wk 23 of Stage II promotion resulted in 47, 28, or 19% inhibition, respectively, of TPA-induced tumor formation. One-half of the mice receiving 13-cis-retinoic acid at Day 1 or Wk 8 were removed from the retinoid treatments at Wk 23, the time of cessation of TPA promotion. The inhibition of tumor formation remained constant during the 15-wk observation period after cessation of retinoid treatment, suggesting that retinoid inhibition of mouse skin tumor promotion is stable in the absence of further promotion and preceded the step of irreversible conversion of promoter dependence to promoter independence.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Topical; Animals; DNA; Female; Isotretinoin; Mice; Mice, Inbred Strains; Skin Neoplasms; Tetradecanoylphorbol Acetate; Time Factors; Tretinoin

The effects of dietary supplementation of 13-cis-retinoic acid (13-cis-RA) and alpha-difluoromethylornithine (DFMO) in the drinking water on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation was determined. Administration of 13-cis-RA in the diet and DFMO in the drinking water was started 1 week and 2 days before the first TPA application to the dimethylbenz[a]anthracene-initiated skin of either female CD-1 or SENCAR mice, respectively. Dietary 13-cis-RA failed to inhibit both the tumor yield and the incidence; papillomas per mouse at 0, 5, 50, 100 and 200 mg/kg diet 13-cis-RA doses were 25, 30, 22, 28 and 25 respectively at 18 weeks of promotion treatment and at all doses 100% of the mice bore papillomas. However, dietary 13-cis-RA dramatically reduced the size of skin tumor promoted with TPA. 13-Cis-RA at doses of 5, 50, 100 and 200 mg/kg diet inhibited skin papillomas (greater than 4 mm diameter) per mouse by 28, 55, 76 and 93%, respectively. Retinoid treatment did not affect body weight gains and the survival was more than 80% in all groups. In accord with our previous findings, DFMO when given in drinking water, was a very effective inhibitor of mouse skin tumor promotion by TPA; DFMO at 0.25% concentration inhibited the number of papillomas by 50%. Inhibition of skin tumor promotion by combined treatments with dietary 13-cis-RA (100 mg/kg) and DFMO (0.25%) in the drinking water was possibly additive. The retinoid and DFMO preclude TPA-increased ornithine decarboxylase (ODC) activity and the accumulation of putrescine by differential effects on ODC, an enzyme associated with skin tumor promotion by TPA.

Topics: Animals; Diet; Eflornithine; Female; Isotretinoin; Mice; Mice, Inbred Strains; Ornithine; Ornithine Decarboxylase; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tretinoin

A 56-year-old man with a 7-year history of well-documented mycosis fungoides is reported. Because the patient was a treatment failure with topical nitrogen mustard due to severe allergic contact dermatitis, and because of recent reports of the efficacy of retinoid compounds, he was treated with a 6-month course of isotretinoin with total clearing of his skin lesions. Previous case reports and possible mechanisms of action are reviewed.

Topics: Humans; Immunity; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Nitrogen Mustard Compounds; Skin Neoplasms; Tretinoin

A dermatitis occurring during the treatment of mycosis fungoides with A vitamin analogues (13-cis-retinoic acid and etretinate) and mimicking a progression of the disease is described. It is considered to be a skin reaction due to the treatment. Its benign nature is revealed by histology showing a lymphocytic infiltrate without any atypical sign.

Topics: Aged; Diagnosis, Differential; Drug Eruptions; Etretinate; Humans; Isotretinoin; Middle Aged; Mycosis Fungoides; Skin; Skin Neoplasms; Tretinoin

A florid case of osteoma cutis was observed following isotretinoin treatment of severe cystic acne in which a few scattered osteomata of the skin were observed prior to the treatment with isotretinoin.

Topics: Acne Vulgaris; Adult; Facial Neoplasms; Female; Humans; Isomerism; Isotretinoin; Osteoma; Skin Neoplasms; Time Factors; Tretinoin

Topics: Adult; Female; Humans; Isotretinoin; Skin Neoplasms; Tretinoin

Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.

Topics: Adult; Cells, Cultured; Enzyme Induction; Female; Humans; Indomethacin; Isotretinoin; Male; Ornithine Decarboxylase Inhibitors; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tretinoin

Twenty patients with mycosis fungoides and four with Sézary's syndrome were treated with 13-cis-retinoic acid as single therapy in an initial dose of 1 to 2 mg per kg body weight in most cases. Complete remission in mycosis fungoides was obtained in six cases (33%) and partial remission in another ten cases (50%). No convincing response was observed in three cases, and progression of limited nodular lesions occurred in one case. In cases responding to treatment the first sign of remission was observed within two to four weeks. Our short-term experience is that the drug is effective in early as well as advanced stages of mycosis fungoides. Patients with Sézary's syndrome, however, did not respond to the same extent.

Topics: Adult; Aged; Female; Humans; Isomerism; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Time Factors; Tretinoin

Treatment with 13-cis-retinoic acid during 12 weeks of a patient with multiple trichoepitheliomas and acne cystica et comedonica did not affect the number of trichoepitheliomas. The cystic lesions, most of them trichoepitheliomas with only a few non-inflammatory cystic acne lesions, were not affected by this treatment.

Topics: Acne Vulgaris; Adult; Face; Humans; Isotretinoin; Male; Neck; Skin Neoplasms; Tretinoin

Tumor initiation in CD-1 mice by benzo[a]pyrene (BaP) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was unaffected by topical pretreatment with 13-cis-retinoic acid (13-cis-RA). Likewise, anthralin-induced tumor promotion in SENCAR mice was unaffected by pretreatment with 13-cis-RA. These results suggest that the action of retinoids in preventing either tumor initiation or promotion is very carcinogen or cocarcinogen specific.

Topics: Animals; Anthralin; Benzo(a)pyrene; Benzopyrenes; Female; Isotretinoin; Methylnitronitrosoguanidine; Mice; Papilloma; Skin Neoplasms; Time Factors; Tretinoin

Two retinoids (13-cis-retinoic acid and retinyl palmitate ) have been shown to exert a good preventive effect in chemically induced papillomas and carcinomas of the skin in female Swiss mice; this effect was investigated over a period of 23 weeks. The tumors were induced by repeated topical application of 3-methylcholanthrene (0.3% MCA, dissolved in acetone; 14 applications). Retinyl palmitate (RP; 6 mg in 0.1 ml acetone/mouse; 10 applications) and 13-cis-retinoic acid (RA; 3 mg in 0.1 ml acetone/mouse; 10 applications) were also administered topically for the 3rd to 9th week from the start of the experiment. This investigation gave evidence for the fact that both the retinoids did not only inhibit the development of skin papillomas but had also a marked effect on skin carcinomas.

Topics: Animals; Diterpenes; Isotretinoin; Methylcholanthrene; Mice; Papilloma; Retinyl Esters; Skin Neoplasms; Tretinoin; Vitamin A

An 83-year-old woman with multiple squamous cell carcinomas and keratoacanthomas of the legs was treated with orally administered isotretinoin (13 cis-retinoic acid). Complete regression of the tumors was noted during the initial six-month treatment period. In the subsequent 36 months, four new cutaneous tumors were excised. There have been no recurrences of lesions that regressed while the patient was receiving retinoid therapy.

Topics: Administration, Oral; Aged; Carcinoma, Squamous Cell; Female; Humans; Isotretinoin; Keratoacanthoma; Leg; Skin Diseases; Skin Neoplasms; Tretinoin

Patients with basal cell carcinoma were treated locally with 13-cis-retinoic acid. Disappearance of the tumors was observed in two of fifteen patients. Thirteen patients whose tumors diminished after the treatment were finally managed surgically. Biopsy specimens were examined histopathologically and by autoradiography. Treated tumors showed reduction of labeling indices as compared with the nontreated group.

Topics: Adult; Aged; Carcinoma, Basal Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Tretinoin

Four patients with refractory cutaneous T-cell lymphoma (mycosis fungoides) were treated with 13-cis-retinoic acid. Near complete clearing of extensive tumours and plaques was seen in one patient, who remains in partial remission with continued improvement after fifteen months. Two patients showed improvement in pruritus and 50% reduction in plaques by four and six weeks, respectively. The fourth patient had improvement in pruritus and clearing of plaques, but dryness and scaling necessitated reduction and eventually withdrawal of the treatment.

Topics: Adult; Aged; Female; Humans; Isotretinoin; Male; Middle Aged; Mycosis Fungoides; Skin Neoplasms; Time Factors; Tretinoin

Topics: Humans; Isotretinoin; Lymphoma; Skin Neoplasms; T-Lymphocytes; Tretinoin

The naturally occurring retinoids (vitamin A alcohol = retinol and all-trans-retinoic acid) have been largely replaced by synthetic retinoids in recent years as systemic drugs for use in dermatology. At the present time, two synthetic retinoids are commercially available: etretinate (Tigason) and isotretinoin (Accutane). These compounds-which have a more favourable therapeutic index than the naturally occurring retinoids-ushered in a new era of dermatological therapy by their potent antikeratinizing, antiseborrhoeic (only isotretinoin) and antineoplastic action. The broadest indications for the use of these retinoids are psoriasis (etretinate) and cystic acne (isotretinoin), whereas the most dramatic effects are encountered in a number of severe ichthyosiform disorders. Another important, although at present not clearly defined role of the retinoids is in the prophylaxis of skin tumours.

Topics: Acne Vulgaris; Etretinate; Humans; Ichthyosis; Isotretinoin; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Benzoates; Cell Differentiation; Cell Division; Guinea Pigs; Humans; Hyperplasia; In Vitro Techniques; Isotretinoin; Neoplasms, Experimental; Rabbits; Retinoids; Skin; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Acne Vulgaris; Humans; Isotretinoin; Keratins; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

Three patients with multiple basal cell carcinomas, due either to excessive sunlight exposure, the nevoid basal cell carcinoma syndrome, or arsenical insecticide exposure, were treated with oral isotretinoin for 2 1/2 to 4 years. Although higher doses were used initially, approximately 1.5 mg/kg/day was used for long-term therapy in all three patients. Therapeutic effects on existing tumors varied between each patient, and only nine of sixty-five lesions underwent complete clinical regression. No tumors enlarged in two patients; a few tumors enlarged slightly in the third patient, particularly during the later courses of therapy when isotretinoin was given at lower dosage. No new lesions have been observed in any of these three patients. With these encouraging preliminary data, it now may be appropriate to perform larger trials for longer periods of time to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.

Topics: Aged; Carcinoma, Basal Cell; Humans; Isomerism; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Skin Neoplasms; Tretinoin

Investigation of retinoids for anticancer activity in humans, either in the chemopreventive or treatment mode, has been little studied. We summarize here our ongoing investigations in four different areas: (1) secondary prevention of cervical dysplasia with topical application of all-trans-retinoic acid; (2) adjuvant treatment of resected high-risk stage I and II malignant melanoma with bacille Calmette Guérin (BCG) plus or minus oral vitamin A; (3) topical vitamin A acid therapy for cutaneous metastatic melanoma; an (4) oral isotretinoin as an anticancer agent.

Topics: Diterpenes; Female; Humans; Isomerism; Isotretinoin; Melanoma; Neoplasms; Palmitates; Retinyl Esters; Skin Neoplasms; Tretinoin; Uterine Cervical Dysplasia; Vitamin A

Analogues of retinoic acid that have their major modifications in the 5,6 double bond and 4-methylene group regions of the beta-cyclogeranylidene ring have been synthesized as potential agents for the treatment and prevention of epithelial cancer. These modifications were intended to reduce retinoid toxicity by lowering the effective treatment dose because the major metabolic deactivation pathway would be inhibited. Ethyl (E)-3,7-dimethyl-9-(exo-2-bicyclo[2.2.1]-heptyl)-2,4,6,8-nonatetraenoate (7), ethyl (E)-3,7-dimethyl-9-(2,2,6-trimethylbicyclo[4.1.0]hept-1-yl)-2,4,6,8-nonatetraen oate (18), (E)-1-(4-carbethoxyphenyl)-2-methyl-4-(2,2,6-trimethylbicyclo[4.1.0]hept-1-yl)- 1,3-butadiene (28), (E)-retinoic acid-4,4,18,18,18-d5 (39), and ethyl (E)-3,7-dimethyl-9-(3,3-ethano-2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoate (47) displayed moderate to excellent activity in an assay for the inhibition of tumor promoter-induced mouse epidermal ornithine decarboxylase.

Topics: Animals; Antineoplastic Agents; Mice; Neoplasms, Experimental; Ornithine Decarboxylase; Skin Neoplasms; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; Tretinoin

Topics: Animals; Etretinate; Female; Folic Acid; Humans; Isomerism; Isotretinoin; Neoplasms; Neoplasms, Experimental; Skin Neoplasms; Tretinoin; Uterine Cervical Neoplasms; Vitamin A; Vitamin E

Topics: Administration, Oral; Adult; Foot Dermatoses; Foot Diseases; Humans; Isotretinoin; Keratoacanthoma; Male; Neoplasms, Multiple Primary; Skin Neoplasms; Tretinoin