chondroitin-sulfates and Carcinoma--Squamous-Cell

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.

Topics: Amino Acid Motifs; Animals; Antigens, Neoplasm; Carbohydrate Epimerases; Carcinoma, Squamous Cell; Cell Movement; Chondroitin Sulfates; Dermatan Sulfate; DNA-Binding Proteins; Ehlers-Danlos Syndrome; Extracellular Matrix; Eye Abnormalities; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Iduronic Acid; Joint Instability; Molecular Conformation; Neoplasm Proteins; Skin Abnormalities; Stem Cells; Sulfotransferases; Thumb

Despite extensive use of Integra in burn reconstruction, little has been published regarding its utility in complex hand wounds from nonburn trauma or cancer resection. This study aimed to review outcomes following Integra use for hand reconstruction following cancer resection or nonburn trauma with exposed bone, joints, and/or tendons.. Retrospective review was performed of patients undergoing hand reconstruction with Integra for exposed bones, joints, or tendons over a 6-year period at a single institution.. Fourteen patients underwent hand reconstruction using Integra, 8 following cancer resection and 6 following acute nonburn trauma. The mean defect size was 19 cm. Integra is an effective method to treat complex hand wounds with exposed bone, joints, and/or tendons. This technique can be used in the office, lessens the need for local or free flap coverage, and provides an excellent aesthetic outcome. Integra should be considered a viable option in hand reconstruction algorithm.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Female; Hand; Hand Injuries; Humans; Male; Melanoma; Middle Aged; Negative-Pressure Wound Therapy; Patient Satisfaction; Retrospective Studies; Skin Neoplasms; Surgical Flaps

Small intraoral defects are usually reconstructed using skin autografts. However, the goal of this research was to describe an alternative to classic techniques using artificial dermis (Integra) in the reconstruction of these types of injuries.. Four patients with small intraoral lesions in different locations underwent resection. The created defects were covered with a bilayer of Integra; then, a chlorhexidine stent cure (Laboratorios Salvat, Barcelona, Spain) was applied. The patients were followed up daily during the first week to detect any signs of infection, dehiscence, or loss of the lamina. Thereafter, they were followed up once a week for 1 month.. None of the patients presented with infections or loss of the dermis. When the silicon sheet was detached, granulation tissue was detected, with complete re-epithelialization of the lesion in the postoperative weeks 3 to 4.. The use of the Integra allowed for the rapid reconstruction of slight intraoral defects while preventing the morbidity associated with classic techniques. In this study, no complications were observed.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Chondroitin Sulfates; Collagen; Female; Gingival Neoplasms; Humans; Male; Oral Surgical Procedures; Plastic Surgery Procedures; Tongue Neoplasms

High-risk human papillomavirus (HPV) infection, mainly with HPV16 type, has been increasingly considered as an important etiologic factor in head and neck cancers. Detection of HPV16 is therefore crucial for these types of cancer, but clinical tests are not performed routinely in public health systems owing to the high cost and limitations of the existing tests. In this article, we report on a potentially low-cost genosensor capable of detecting low concentrations of HPV16 in buffer samples and distinguishing, with high accuracy, head and neck cancer cell lines according to their HPV16 status. The genosensor consisted of a microfluidic device that had an active layer of a HPV16 capture DNA probe (cpHPV16) deposited onto a layer-by-layer film of chitosan and chondroitin sulfate. Impedance spectroscopy was the principle of detection utilized, leading to a limit of detection of 10.5 pM for complementary ssDNA HPV16 oligos (ssHPV16). The genosensor was also able to distinguish among HPV16

Topics: Adenine; Carcinoma, Squamous Cell; Cell Line, Tumor; Chitosan; Chondroitin Sulfates; DNA, Single-Stranded; Electric Impedance; Head and Neck Neoplasms; Human papillomavirus 16; Humans; Limit of Detection; Microfluidic Analytical Techniques; Nanostructures; Papillomavirus Infections; Thymine

In this report, we used liquid chromatography-mass spectrometry and Western blotting to analyze the content and structure of glycosaminoglycans, glycolipids and selected proteins to compare differences between patient-matched normal and cancerous lung tissues obtained from lung cancer patients. The cancer tissue samples contained over twice as much chondroitin sulfate (CS)/dermatan sulfate (DS) as did the normal tissue samples, while the amount of heparan sulfate (HS) and hyaluronan (HA) in normal and cancer tissues were not significantly different. In HS, several minor disaccharide components, including NS6S, NS2S and 2S were significantly lower in cancer tissues, while the levels of major disaccharides, TriS, NS and 0S disaccharides were not significantly different in normal and cancer tissues. In regards to CS/DS, the level of 4S disaccharide (the major component of CS-type A and DS) decreased and the level of 6S disaccharide (the major component of CS- type C) increased in cancer tissues. We also compared the content and structure of GAGs in lung tissues from smoking and non-smoking patients. Analysis of the glycolipids showed all lipids present in these lung tissues, with the exception of sphingomyelin were higher in cancer tissues than in normal tissues. Western analysis showed that syndecan 1 and 2 proteoglycans displayed much higher expression in cancer tissue/biopsy samples. This investigation begins to provide an understanding of patho-physiological roles on glycosaminoglycans and glycolipids and might be useful in identifying potential biomarkers in lung cancer.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chondroitin Sulfates; Chromatography, Liquid; Dermatan Sulfate; Disaccharides; Female; Glypicans; Heparitin Sulfate; Humans; Hyaluronic Acid; Lung Neoplasms; Male; Middle Aged; Retrospective Studies; Smoking; Syndecan-1; Tandem Mass Spectrometry

Dermal regeneration templates may be used in the reconstruction of large defects after the excision of cutaneous malignancies. We describe the successful use of Integra

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Dermatologic Surgical Procedures; Head and Neck Neoplasms; Humans; Male; Melanoma; Neoplasms, Multiple Primary; Plastic Surgery Procedures; Regeneration; Scalp; Skin Neoplasms; Skin Physiological Phenomena

Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly upregulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, was downregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and deregulated actin cytoskeleton dynamics and focal adhesion formation. Our findings show that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, downregulation of IdoA by DS-epi1 inhibitors may represent a new anticancer therapy.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma, Squamous Cell; Cell Movement; Chondroitin Sulfates; Dermatan Sulfate; DNA-Binding Proteins; Esophageal Neoplasms; Female; Flow Cytometry; Gene Knockdown Techniques; Humans; Iduronic Acid; Immunohistochemistry; Male; Mass Spectrometry; Middle Aged; Neoplasm Proteins

In 23 cases of carcinoma of the head and neck, the combined use of Somatostatin and/or its analogue Octreotide, prolactin inhibitors, Melatonin, Retinoids, Vitamin E, Vitamin D3, Vitamin C, Calcium, chondroitin-sulphate, and minimal oral doses of cyclophosphamide (50-100 mg/day) led to a decided increase in survival with respect to the median values reported in the literature for the same tumours and stages, together with an evident improvement in the quality of life, partial or complete objective responses and, in some cases, complete and stable cure with functional recovery. The rationale and the mechanisms of molecular biology of the treatment are discussed, showing that the treatment has a differentiating, apoptotic, antiproliferative, antiangiogenic and antimetastatic effect, and, unlike chemo- and/or radiotherapy, preserves and enhances the trophism and functionality of organs, tissues and immunitary and antitumoral homeostasis. This result, achieved without toxicity, demonstrates the efficacy of this biological multitherapy (Prof. Luigi Di Bella's method or DBM) and is in agreement with the positive results already published on the use of the DBM in various neoplastic diseases. We believe it is of use to report these cases to invite greater interest in the possibilities opened up by this biological multitherapy.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antioxidants; Calcium; Carcinoma, Medullary; Carcinoma, Squamous Cell; Chondroitin Sulfates; Cyclophosphamide; Drug Therapy, Combination; Esophageal Neoplasms; Head and Neck Neoplasms; Humans; Melatonin; Octreotide; Retinoids; Retrospective Studies; Sarcoma; Vitamins

Integra dermal regeneration template - a two-stage, tissue-engineered, artificial skin - was introduced in the UK in May 1996. There were no restrictions on clinical application and a series of applications in reconstructive surgery were undertaken. One case involved a Caucasian lady with a nose tip basal cell carcinoma (BCC) who had a single-stage reconstruction. The 6-year follow-up was remarkable as it showed a scarless repair.. We undertook a clinical evaluation to explore the outcome of one-stage Integra reconstruction in a selected series of Chinese patients.. Ten patients (five male and five female; age range: 54-86 years) with complicated or atypical cutaneous lesions involving the head and neck were treated in an outpatient setting.. Pathology revealed eight BCCs, one squamous cell carcinoma (SCC) and one seborrhoeic keratosis. Healing took place either by wound contraction alone or in conjunction with re-epithelialisation. All wounds were fully healed within 6 weeks. Follow-up ranged from 18 to 30 months, and there has been no recurrence of the malignant lesions.. In selected cases, one-stage reconstruction using Integra can reduce operating time with no delay for frozen section, flap raising or graft harvesting. More immediate postoperative care is needed, but the long-term aesthetic results are uniformly acceptable.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Female; Head and Neck Neoplasms; Humans; Keratosis, Seborrheic; Male; Middle Aged; Nose Diseases; Skin Neoplasms; Wounds and Injuries

Scalp reconstruction after wide tumor excision is particularly challenging. Free tissue transfers, local flaps, or skin grafts can be used but present some disadvantages especially with old patients with local advanced cancers, systemic diseases and in patients with a prior history of recurring scalp skin cancers in which the risk of burying a recurring tumor with a flap is likely. The Authors expose their early experience with Integra dermal regeneration template for scalp reconstruction after scalp tumor excision.. Eight patients with primary or secondary scalp tumor underwent a first surgical procedure under local anaesthesia for tumor removal and Integra positioning followed by a second operation performed three weeks later to reconstruct the defect by removing the superficial silicon layer of Integra and by covering the defect with a split thickness skin graft. The average surface area of the defect was 143.27 cm(2). The average operating time was 30.4 minutes for the first operation and 45.6 minutes for the second operation. In six cases Integra was grafted as a classic full-thickness skin graft. In the remaining two cases the Integra template was meshed. The artificial derma was attached to the edge of the wound by either sutures or staples.. There was a full graft take on all cases. The mean follow-up was 24 months. In two cases we were able to detect early tumor recurrence two months after the operation. Satisfactory cosmetic and functional results were obtained in all patients.. In the scalp defect reconstructions after tumor excision, Integra allows to obtain a thicker and more durable coverage than skin graft on the skull, allowing to detect a tumor recurrence earlier than a flap reconstruction with no risk of burying an eventual underlying residual tumor. These operations are performed under local anaesthesia and are therefore suitable for elderly patients.

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Humans; Melanoma; Plastic Surgery Procedures; Sarcoma; Scalp; Skin Neoplasms; Skin, Artificial; Wounds and Injuries

Integra® has already established its role in acute burn injuries and scar management. It can also be used to cover non-vascularised wounds such as exposed bone resulting from trauma or tumour resection. The aim of this series was to review all cases that underwent Integra® reconstruction following cancer excision. In particular we were interested in the use of Integra for day-case and local anaesthetic procedures in cases where excision was required down to bone or tendon.. All patients who had Integra reconstruction over a three-year period were prospectively followed. A total of 14 cases were identified for inclusion into the series. In each case patient factors such peripheral vascular disease, age and patient choice meant that traditional methods of reconstruction were not possible. As a result a staged Integra® reconstruction was performed.. The 14 cases comprised 11 (78%) males and 3 (22%) females with the majority being diagnosed with Squamous cell carcinomas, 3 (40%) or Malignant Melanomas, 3 (20%). The most common operative sites were digital (5) and scalp (6) in 72% of the cases. The average graft take was 87%. There were 4 early, 4 delayed and 3 late complications in a total of 8 patients mostly resulting in a delay in healing. In 6/14 patients (43%) there were no complications.. Tumour excision and wide local excision may leave patients with defects requiring complex reconstructive surgery. The options available are often compounded by various patient factors. In complex cases we have found the use of Integra® to be a safe and viable alternative to traditional methods of wound closure.

Topics: Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Female; Fingers; Head and Neck Neoplasms; Humans; Male; Melanoma; Plastic Surgery Procedures; Retrospective Studies; Scalp; Skin Neoplasms; Skin, Artificial

Topics: Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Humans; Male; Middle Aged; Penile Neoplasms; Penis; Plastic Surgery Procedures; Skin, Artificial; Urologic Surgical Procedures, Male

Topics: Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Epidermolysis Bullosa Dystrophica; Humans; Male; Skin Neoplasms; Skin Transplantation; Skin, Artificial; Transplantation, Autologous

Among tissue-engineered skins, two bilayered cellular constructs and one cryopreserved dermal substitute have been approved for the treatment of epidermolysis bullosa. Nevertheless, the application of artificial skin technology to surgical treatment of squamous cell carcinomas in a patient with epidermolysis bullosa has never been reported.. To reconstruct the large defect remaining after squamous cell carcinoma excision in a patient with dominantly inherited dystrophic epidermolysis bullosa.. To apply a 10 x 15 cm Integra sheet (Integral Life-sciences Corporation, Plainsboro, NJ, USA) (an acellular collagen matrix coated with a thin polysiloxane elastomer) to the excised area and 3 weeks later to cover the Integra sheet with an ultrathin meshed skin graft.. The graft take was complete, and the donor site totally regenerated, except for three small bullae at 7 weeks postoperatively.. Integra offers the advantage of filling huge defects with its dermal layer of collagen fibers and provides an optimal graft bed. This first step makes it possible to use very thin grafts 3 weeks later.

Topics: Adult; Biocompatible Materials; Carcinoma, Squamous Cell; Chondroitin Sulfates; Collagen; Comorbidity; Epidermolysis Bullosa; Humans; Skin Neoplasms; Skin, Artificial

Chondroitin 6-sulphate is a glycosaminoglycan component of both cell membrane and basement membrane proteoglycans. In vitro it can inhibit tenascin, a molecule critical for epithelial cell migration during development and in wound healing. The immunohistochemical expression of chondroitin-6-sulphate and tenascin has been examined in 143 laryngeal biopsies from 38 patients, with particular attention to changes occurring with squamous cell carcinoma invasion. All tissues were formalin-fixed and paraffin-embedded. An avidin-biotin complex immunoperoxidase technique was used. Immunostaining for chondroitin-6-sulphate was seen in the basement membrane and/or cell membranes of basal and suprabasal cells of the laryngeal epithelium. Immunostaining of cell or basement membrane was seen at least focally in 67 of 71 (94 per cent) biopsies with no atypia, in 39 of 45 (87 per cent) biopsies with mild/moderate atypia, and in 16 of 16 (100 per cent) biopsies with severe dysplasia or carcinoma in situ (CIS); but in only 2 of 18 biopsies with invasion, although in neither of these was chondroitin-6-sulphate immunostaining seen at the actual site of invasion. Tenascin immunostaining was seen along the basement membrane in all biopsies. Those with CIS or invasion showed, in addition, strong tenascin staining of the adjacent stroma. The loss of chondroitin-6-sulphate immunostaining concurrent with squamous cell carcinoma invasion in the larynx suggests that loss of a chondroitin-6-sulphate-containing proteoglycan, or a change in proteoglycan side-chain composition, is a critical step in laryngeal epithelial tumour invasion.

Topics: Biomarkers; Carcinoma in Situ; Carcinoma, Squamous Cell; Chondroitin Sulfates; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Neoplasm Invasiveness; Tenascin

Topics: Antibodies, Monoclonal; Basement Membrane; Carcinoma, Squamous Cell; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Collagen; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunohistochemistry; Keratosis; Laminin; Proteoglycans; Skin Neoplasms

Twenty seven bladder tumors, three ureteral tumors and one renal pelvic tumor were studied by means of light microscopic histochemical methods for demonstration and identification of acid mucopolysaccharides. Alcian blue (pH 1.0), alcian blue (pH 2.5), periodic acid-Schiff (PAS) and aldehyde-fuchusin stainings were performed. These stainings showed that all tumor specimens contained acid mucopolysaccharides. For identifying individual acid mucopolysaccharides, enzyme digestion procedures were performed prior to staining with alcian blue. (streptomyces hyaluronidase, testicular hyaluronidase, chondroitinase ABC, chondroitinase AC, keratanase, heparinase, heparitinase.) According to these experiments, high-grade, and high-stage tumors contained large amounts of sulfated mucopolysaccharides. Squamous cell carcinomas of the bladder contained especially large amounts of chondroitin sulfate AC.

Topics: Aged; Alcian Blue; Carcinoma, Squamous Cell; Chondroitin Sulfates; Female; Glycosaminoglycans; Histocytochemistry; Humans; Kidney Neoplasms; Male; Middle Aged; Ureteral Neoplasms; Urinary Bladder Neoplasms

The glycosaminoglycans of four normal human bladders and fourteen bladder cancers were characterized and quantitated (after proteolytic extraction) by specific enzyme digestion, cellulose acetate electrophoresis and densitometry. Hyaluronic acid, heparan sulfate, dermatan sulfate and chondroitin sulfate were identified in both normal and cancerous bladders. Hyaluronic acid and dermatan sulfate were the major glycosaminoglycans of the normal epithelium/submucosa while heparan sulfate and dermatan sulfate were predominant in normal bladder muscle. Bladder cancer glycosaminoglycan content was influenced by the stage and grade of the neoplasm. Hyaluronic acid and dermatan sulfate tended to decrease and chondroitin sulfate to increase in infiltrating cancers, whereas a decrease in the percentage of heparan sulfate correlated closely with higher grade tumors. The bladder cancer glycosaminoglycan profile may be indicative of the tumor's invasive potential.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Child; Chondroitin Sulfates; Densitometry; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Urinary Bladder; Urinary Bladder Neoplasms

The quantitative changes of glycosaminoglycans in tumor tissue of human lung cancers (2 squamous cell carcinomas, 4 adenocarcinomas and 5 small cell carcinomas) were studied. The total amount of glycosaminoglycans in human lung cancer tissues increased 1.4 to 4 times in comparison with that in normal lung tissues. The increase in tissue content of glycosaminoglycans was accompanied by an increase in the chondroitin sulfate level in every histologic type of lung cancer, as well as by a marked increase in hyaluronic acid level in squamous cell carcinomas, and a moderate increase in its level in small cell carcinomas. The concentrations of dermatan sulfate and heparan sulfate in lung cancer tissues did not show any significant changes compared with those in normal lung tissues. The increase in total amount and changes in the composition of glycosaminoglycans in human lung cancer tissue were closely related to the histologic type of the tumor.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chondroitin Sulfates; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Lung Neoplasms

The glycosaminoglycans were prepared by exhaustive Pronase digestion and alkaline treatment of squamous cell carcinoma and adenocarcinoma tissues of human lung, and of tissues taken at a site distant from the tumor as a control. The glycosaminoglycan classes were characterized by chemical enzymic, and electrophoretic methods. The presence of oversulfated chondroitin-and/or dermatan-sulfates which have not up till now been found in lung tissues was also demonstrated in carcinoma and control tissues, their contents being higher in the carcinoma tissues. The levels of whole glycosaminoglycans were markedly increased in carcinoma tissue. The classes of glycosaminoglycans which increased in lung carcinoma tissue were predominatly chondroitin-4-and/or-6-sulfates and hyauronic acid.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Chondroitin Sulfates; Glycopeptides; Glycosaminoglycans; Heparitin Sulfate; Hexosamines; Humans; Hyaluronic Acid; Lung; Lung Neoplasms; Sulfates