chlorophyll-a and Carcinoma--Squamous-Cell

There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery.. To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma.. Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma.. Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection.. Adverse events and highest laser light dose.. Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2.. The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study.. clinicaltrials.gov Identifier: NCT00470496.

Topics: Aged; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Chlorophyll; Female; Head and Neck Neoplasms; Humans; Intraoperative Care; Lasers; Male; Photochemotherapy; Treatment Outcome

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction.. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction.. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses.. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chlorophyll; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Photochemotherapy; Photosensitizing Agents; STAT3 Transcription Factor; Tissue Distribution; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antigens, Surface; Antineoplastic Agents; Antioxidants; Antiviral Agents; Aporphines; Atherosclerosis; Benzoyl Peroxide; beta Catenin; Biofilms; Biomarkers; Brain; Cannabis; Carcinoma, Squamous Cell; Case-Control Studies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child; China; Chlorides; Chlorophyll; Cholesterol, LDL; Coinfection; Corylus; Cross-Sectional Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Developmental Disabilities; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Electroencephalography; Environmental Exposure; Enzyme Inhibitors; Epilepsy, Generalized; Ethnicity; Female; Fertilization in Vitro; Fluorescent Dyes; Follow-Up Studies; Forecasting; Glutamate Carboxypeptidase II; Glycine; Half-Life; Head and Neck Neoplasms; Health Communication; Heart Ventricles; Hepacivirus; Hepatitis C; Heterosexuality; HIV Infections; Humans; Hypercholesterolemia; Immunoassay; Inhalation Exposure; Isocitrate Dehydrogenase; Laryngeal Neoplasms; Ligands; Light; Lipopolysaccharide Receptors; Liver Cirrhosis; Lung; Lung Neoplasms; Magnetic Resonance Imaging, Cine; Male; Maternal Age; Mechanical Phenomena; Mice; Mice, Nude; Mice, SCID; Microglia; MicroRNAs; Microscopy, Fluorescence; Microsomes, Liver; Middle Aged; Minority Groups; Mitochondrial Membrane Transport Proteins; Models, Biological; Molecular Structure; Molecular Weight; Monte Carlo Method; Muscle Hypotonia; Mutagenesis, Site-Directed; Mutation, Missense; Natriuretic Peptide, Brain; Neoplasms; Nickel; Nitric Oxide; Optical Imaging; Oxides; Particle Size; Particulate Matter; PCSK9 Inhibitors; Peptide Fragments; Phenotype; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Piper; Placenta Growth Factor; Plant Extracts; Plant Leaves; Plant Stems; Platinum; Point-of-Care Testing; Population Surveillance; Postpartum Period; Pregnancy; Pregnancy, Twin; Prevalence; Prospective Studies; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyridines; Pyridones; Racial Groups; Rats; Respiratory Physiological Phenomena; Retrospective Studies; Risk Factors; RNA, Long Noncoding; Semiconductors; Sexual and Gender Minorities; Sexual Behavior; Social Media; Sodium; Solubility; Stereoisomerism; Stochastic Processes; Structure-Activity Relationship; Substance-Related Disorders; Sustained Virologic Response; Sweat; Temperature; Time Factors; Tissue Distribution; Titanium; Transplantation, Heterologous; Tumor Cells, Cultured; Tungsten; Tyramine; United States; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Veterans; Xenograft Model Antitumor Assays; Young Adult

There is an urgent need to develop efficient combination drug delivery approaches to address the low efficiency of clinical cancer monotherapy. However, how to achieve high-efficient synchronous co-delivery and synergistic therapy remains a big challenge. Herein, we report a self-facilitated nanoassembly of a heterotypic chemo-photodynamic dimer for multimodal cancer therapy. A reactive oxygen species (ROS)-responsive dimer of paclitaxel (PTX) and pyropheophorbide a (PPa) is rationally designed and synthesized. The "Two-in-One" dimer serves as both carrier material and cargo, could self-assemble into nanoparticles in water with ultrahigh co-loading capacity and self-facilitated ROS-responsive drug release. The endogenous ROS overproduced in tumor cells together with PPa-generated ROS under laser irradiation synergistically facilitate on-demand drug release from the nano-assembly. The disintegration of nanoassembly triggered by ROS effectively addresses the dilemma of aggregation-caused quenching (ACQ) effect of photosensitizer (PPa). Both in vitro and in vivo results suggest that PTX-initiated chemotherapy in combination with PPa-mediated PDT exhibits synergistic antitumor activity. Our findings provide a strategy for the rational design of nanocarrier for high-efficient synergetic cancer therapy.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyll; Combined Modality Therapy; Dimerization; Drug Delivery Systems; Drug Liberation; Female; Fluorescent Dyes; Humans; Mice, Inbred BALB C; Nanocapsules; Neoplasms, Experimental; Optical Imaging; Paclitaxel; Photochemotherapy; Photosensitizing Agents; Rats, Sprague-Dawley; Reactive Oxygen Species

Carica papaya leaf decoction, an Australian Aboriginal remedy, has been used widely for its healing capabilities against cancer, with numerous anecdotal reports. In this study we investigated its in vitro cytotoxicity on human squamous cell carcinoma cells followed by metabolomic profiling of Carica papaya leaf decoction and leaf juice/brewed leaf juice to determine the effects imparted by the long heating process typical of the Aboriginal remedy preparation. MTT assay results showed that in comparison with the decoction, the leaf juice not only exhibited a stronger cytotoxic effect on SCC25 cancer cells, but also produced a significant cancer-selective effect as shown by tests on non-cancerous human keratinocyte HaCaT cells. Furthermore, evidence from testing brewed leaf juice on these two cell lines suggested that the brewing process markedly reduced the selective effect of Carica papaya leaf on SCC25 cancer cells. To tentatively identify the compounds that contribute to the distinct selective anticancer activity of leaf juice, an untargeted metabolomic approach employing Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry followed by multivariate data analysis was applied. Some 90 and 104 peaks in positive and negative mode respectively were selected as discriminatory features from the chemical profile of leaf juice and >1500 putative compound IDs were obtained via database searching. Direct comparison of chromatographic and tandem mass spectral data to available reference compounds confirmed one feature as a match with its proposed authentic standard, namely pheophorbide A. However, despite pheophorbide A exhibiting cytotoxic activity on SCC25 cancer cells, it did not prove to be the compound contributing principally to the selective activity of leaf juice. With promising results suggesting stronger and more selective anticancer effects when compared to the Aboriginal remedy, Carica papaya leaf juice warrants further study to explore its activity on other cancer cell lines, as well as investigation to confirm the identity of compounds contributing to its selective effect, particularly those compounds altered by the long heating process applied during the traditional Aboriginal remedy preparation.

Topics: Carcinoma, Squamous Cell; Carica; Cell Death; Cell Line, Tumor; Cell Survival; Chlorophyll; Chromatography, Liquid; Humans; Keratinocytes; Mass Spectrometry; Metabolomics; Multivariate Analysis; Native Hawaiian or Other Pacific Islander; Plant Extracts; Plant Leaves; Reference Standards

Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyll; Core Binding Factor Alpha 3 Subunit; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Mouth Neoplasms; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Signal Transduction; Wnt Proteins

We have previously shown that the (124)I-analog of methyl 3-(1'-m-iodobenzyloxy) ethyl-3-devinyl-pyropheophorbide-a derived as racemic mixture from chlorophyll-a can be used for PET (positron emission tomography)-imaging in animal tumor models. On the other hand, as a non-radioactive analog, it showed excellent fluorescence and photodynamic therapy (PDT) efficacy. Thus, a single agent in a mixture of radioactive ((124)I-) and non-radioactive ((127)I) material can be used for both dual-imaging and PDT of cancer. Before advancing to Phase I human clinical trials, we evaluated the activity of the individual isomers as well as the impact of a chiral center at position-3(1) in directing in vitro/in vivo cellular uptake, intracellular localization, epithelial tumor cell-specific retention, fluorescence/PET imaging, and photosensitizing ability. The results indicate that both isomers (racemates), either as methyl ester or carboxylic acid, were equally effective. However, the methyl ester analogs, due to subcellular deposition into vesicular structures, were preferentially retained. All derivatives containing carboxylic acid at the position-17(2) were noted to be substrate for the ABCG2 (a member of the ATP binding cassette transporters) protein explaining their low retention in lung tumor cells expressing this transporter. The compounds in which the chirality at position-3 has been substituted by a non-chiral functionality showed reduced cellular uptake, retention and lower PDT efficacy in mice bearing murine Colon26 tumors.

Topics: Animals; Biological Transport; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyll; Chlorophyll A; Colonic Neoplasms; Epithelial Cells; Fibroblasts; Humans; Iodine Radioisotopes; Lung Neoplasms; Mice; Mice, Inbred BALB C; Molecular Imaging; Neoplasm Transplantation; Organ Specificity; Photochemotherapy; Photosensitizing Agents; Spirulina; Stereoisomerism; Tumor Burden

To investigate the effect and potential mechanisms about apoptosis induction and migration suppression of photodynamic therapy with a new photosensitizer, 9-hydroxypheophorbide-α (9-HPbD), and diode laser on HN-3 human laryngeal squamous cancer cells.. The attached HN-3 cancer cells were photosesitized with 0.29 μg/ml and 0.59 μg/ml 9-HPbD for 6 h and irradiated by 664 nm diode laser for 15 min at an energy density of 2.0 J/cm for activating 9-HPbD. Wound healing assay and photographing was respectively performed immediately after laser irradiation. Photographing focusing on the same location was repeated 12 h, 24 h and 36 h after PDT and cells migration distance counted respectively. H2DCFDA staining was used to assess accumulation of reactive oxygen series (ROS) 1 h after PDT. MTT assay, Hoechst33342/PI double staining, western blotting were respectively performed to assess cellular viability, apoptosis and the expression of Enos, p-c-Jun, EGFR.. Phototoxicity and apoptosis on HN-3 cells induced by 9-HPbD-PDT was exhibited in a dose-related manner. Neither 9-HPbD alone nor laser alone was cytotoxic to HN-3 cells. Generation of ROS was initiated immediately after PDT. The apoptotic cells, marked with condensed/fragmented blue or pink nuclei, and up-regulated expression of eNOS, p-c-Jun were subsequently induced 24 h after PDT. Coupled with a down-regulated expression of EGFR, a photosensitizer dose-ralated cell migration suppression was initiated by PDT. After pretreatment of GSH or ascorbic acid, a kind of antioxidant, the efficacy of PDT-induced apoptosis and migration suppression was partially inhibited.. Activation of p-c-Jun, eNOS and down-regulated expression of EGFR may respectively involve in the apoptosis induction and cell migration suppression after 9-HPbD-PDT. Generation of ROS may play an important role in the course of apoptosis induction and migration suppression of HN-3 cells initiated by 9-HPbD-PDT.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Survival; Chlorophyll; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Lasers; Photochemotherapy; Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck

Quantification of fluorescence in vivo is complicated by the influence of tissue optical properties on the collected fluorescence signal. When tissue optical properties in the measurement volume are quantified, one can obtain the intrinsic fluorescence, which equals the product of fluorophore absorption coefficient and quantum yield. We applied this method to in vivo single-fiber fluorescence spectroscopy measurements on mouse tongue, skin, liver, and oral squamous cell carcinoma, where we detected intrinsic fluorescence spectra of the photosensitizers chlorin e6 and Bremachlorin at t=[3,4.5,6,24,48]  h incubation time. We observed a tissue-dependent maximum of 35% variation in the total correction factor over the visible wavelength range. Significant differences in spectral shape over time between sensitizers were observed. Although the wavelength position of the fluorescence intensity maximum for ce6 shifted to the red, Bremachlorin showed a blue shift. Furthermore, the Bremachlorin peak appeared to be broader than the ce6 fluorescence peak. Intrinsic fluorescence intensity, which can be related to photosensitizer concentration, was decreasing for all time points but showed significantly more Bremachlorin present compared to ce6 at long incubation times. Results from this study can be used to define an optimal treatment protocol for Bremachlorin-based photodynamic therapy.

Topics: Animals; Carcinoma, Squamous Cell; Chlorophyll; Chlorophyllides; Female; Fluorescence; Green Fluorescent Proteins; Liver; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Mouth Neoplasms; Normal Distribution; Optics and Photonics; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin; Spectrometry, Fluorescence; Spectrophotometry; Tongue

Pheophorbide a (Pa) is a chlorine-based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll-a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells.. Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B-II and the formation of autophagosome and acidic vesicular organelles (AVOs).. Pa-PDT inhibited the proliferation of OSCC cells in a dose-dependent manner. Pa-PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa-PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa-PDT-mediated cytotoxicity through an increase in necrosis.. These results suggest that synthesized Pa-PDT exerts anti-tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa-PDT induces autophagy, and autophagy inhibition enhances Pa-PDT-mediated necrosis in OSCC cells.

Topics: Apoptosis; Autophagy; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Humans; MAP Kinase Signaling System; Microtubule-Associated Proteins; Mouth Neoplasms; Necrosis; Phagosomes; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species

Photodynamic therapy (PDT) with several photosensitizers is a promising modality for the treatment of cancer. In this study, the therapeutic effect of PDT using the synthetic photosensitizer pheophorbide a (Pa-PDT) was examined in AT-84 murine oral squamous cell carcinoma (OSCC) cells. The MTT assay revealed that Pa-PDT induced cell growth inhibition in a dose- and time-dependent manner. Pa-PDT treatment significantly induced intracellular ROS generation, which is critical for cell death induced by Pa-PDT. Cell cycle analysis showed the increased sub-G1 proportion of cells in Pa-PDT-treated cells. Induction of apoptotic cell death was confirmed by DAPI staining and the reduction of mitochondrial membrane potential (ΔΨm) on Pa-PDT-treated cells. The changes in apoptosis-related molecules were next examined using western blotting. Cytochrome c release and cleavage of caspase-3 and PAPR were observed in AT-84 cells, whereas Bcl-2 protein levels were decreased. To determine the therapeutic effect of Pa-PDT in vivo, a murine OSCC animal model was used. Treatment of mice with Pa-PDT significantly inhibited tumor growth, especially PDT with Pa intravenous administration (i.v. Pa-PDT), and increased proliferative cell nuclear antigen (PCNA) levels and TUNEL-stained apoptotic cells compared to vehicle-treated controls. The data demonstrate that the in vitro effects of Pa-PDT on the inhibition of tumor cell proliferation and induction of apoptosis correlate to the anticancer activity of Pa-PDT in vivo. Our findings suggest the therapeutic potential of Pa-PDT in OSCC.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Caspase 3; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Cytochromes c; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C3H; Mitochondria; Mouth Neoplasms; Photochemotherapy; Photosensitizing Agents; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species

Skin phototoxicity is one of the main side effects of photodynamic therapy (PDT). To overcome this problem, some new photosensitizers have been developed with longer absorbance wavelengths and shorter half-life in the body. In this study, we investigated the mechanism of PDT mediated by a new chlorophyll derivative photosensitizer, 9-hydroxypheophorbide alpha (9-HPbD), on AMC-HN-3 cancer cells. Phototoxicity and apoptosis on AMC-HN-3 cells induced by 9-HPbD was exhibited in a time- and dose-dependent manner. Mitochondria and endoplasmic reticulum (ER) were observed as preferential sites of 9-HPbD accumulation. Photoactivation of 9-HPbD-loaded AMC-HN-3 cells led to a rapid generation of reactive oxygen species (ROS) at 30 min, followed by a loss of mitochondrial membrane potential (MMP) at 2 h, translocation of apoptosis-inducing factor (AIF) at 2 h, and the release of cytochrome c at 3 h following PDT. Caspase-12, an important caspase involved in ER-induced apoptosis, and C/EBP homologous protein (CHOP), an ER stress inducible transcription factor, were also upregulated after PDT (3-12 h and 6-12 h, respectively). Subsequently, activation of caspase-9 at 6 h, caspase-3 and PARP at 12 h also occurred in PDT-treated AMC-HN-3 cells. The above observations demonstrate that both mitochondria and ER serve not only as the sites of sensitizer binding, but also the subcellular targets of 9-HPbD-PDT, effective activation of which is responsible for 9-HPbD PDT-induced apoptosis in AMC-HN-3 cells.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyll; Drug Screening Assays, Antitumor; Endoplasmic Reticulum; Enzyme Activation; Head and Neck Neoplasms; Humans; Lasers; Lipid Peroxidation; Mitochondria; Neoplasm Proteins; Oxidative Stress; Photochemotherapy; Protein Transport; Radiation-Sensitizing Agents; Reactive Oxygen Species

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

Topics: Animals; Carcinoma, Squamous Cell; Chlorophyll; Combined Modality Therapy; Disease Models, Animal; Female; Gallium; Male; Mice; Mice, Inbred C3H; Photochemotherapy; Photosensitizing Agents; Porphyrins; Random Allocation; Skin Neoplasms; Survival Analysis; Ultrasonic Therapy

Photodynamic therapy has been shown to be an effective treatment modality for surface-oriented neoplasms of the skin, respiratory, gastrointestinal, and urogenital systems. The purpose of this study was to assess the safety and efficacy of photodynamic therapy using a new photosensitizer in the treatment of squamous cell carcinomas of the feline facial skin.. Cats with naturally occurring squamous cell carcinomas of the facial skin were entered into the study. Tumors were staged using a modification of the World Health Organization (WHO) system for classification of feline tumors of epidermal origin. Photodynamic therapy was delivered to the tumors using an argon-pumped dye laser 24 hours after the administration of the photosensitizer pyropheophorbide-alpha-hexyl-ether (HPPH-23). Following treatment, tumors were evaluated for complete response rates and local control durations.. Fifteen tumors were staged T1a (< 1.5 cm diameter, noninvasive), 18 T1b (< 1.5 cm, invasive), and 28 T2B (> 1.5 cm, invasive). Complete response rates as well as local control durations were significantly (P < 0.05) related to stage. Complete response was achieved in 100% of T1a tumors, 56% of T1b tumors, and 18% of T2b tumors. One-year local control rates were 100% for T1a tumors and 53% for T1b tumors; overall 1-year local control rate for all treated tumors was 62%. Clinical, hematological, and biochemical evidence of toxicity was not seen in any cat following drug administration. However, morbidity was observed following treatment of large, invasive tumors of the nasal plane.. Photodynamic therapy with the photosensitizer HPPH-23 was safe and effective in treating early stage squamous cell carcinomas of the feline nasal plane and facial skin. However, toxicity was encountered following treatment of large neoplasms.

Topics: Animals; Carcinoma, Squamous Cell; Cats; Chlorophyll; Edema; Inflammation; Opportunistic Infections; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms

Topics: Carcinoma, Squamous Cell; Chlorophyll; Chlorophyll A; Contrast Media; Copper; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Lymphography; Uterine Cervical Neoplasms

Topics: Carcinoma, Squamous Cell; Chlorophyll; Contrast Media; Ethiodized Oil; Female; Humans; Inguinal Canal; Iodized Oil; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Lymphatic System; Lymphography; Melanoma; Methods; Pelvis; Vulvar Neoplasms