phytochlorin and Carcinoma--Squamous-Cell

The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and head and neck squamous cell carcinoma (HNSCC).. From 1985 to 2015, PubMed/Medline, Google Scholar, EMBASE, and ISI Web of Knowledge were searched using different combinations of the following key words: PDT, oral precancer, leukoplakia, erythroplakia, erythroleukoplakia, verrucous hyperplasia, oral submucous fibrosis, and HNSCC. Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded.. Twenty-six studies were included in the present study. The number of patients ranged from 2 to 147, with a mean age of 50-67 years. The reported numbers of PMDS and HNSCC ranged between 5 and 225. Photosensitizers used were aminolevulinic acid, meta-tetrahydroxyphenylchlorin, Foscan, hematoporphyrin derivatives, Photofrin, Photosan, and chlorine-e6. Laser wavelength, power density, irradiation duration were 585-652 nm, 50-500 mW/cm. PDT is effective in the management of PMDS and HNSCC.

Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Chlorophyllides; Databases, Factual; Dihematoporphyrin Ether; Erythroplasia; Head and Neck Neoplasms; Hematoporphyrins; Humans; Hyperplasia; Indoles; Laser Therapy; Lasers; Leukoplakia; Leukoplakia, Oral; Mesoporphyrins; Oral Submucous Fibrosis; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome

Hypoxia is an important pathological hallmark of the tumor microenvironment, associated with metabolic alterations, cell proliferation, aggressiveness, metastasis, and therapy resistance in cancers. Hypoxia impedes the outcome of photodynamic therapy (PDT), which is largely dependent on molecular oxygen to generate cytotoxic

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyllides; Head and Neck Neoplasms; Hypoxia; Mice; Mouth Neoplasms; Nanomedicine; Nanoparticles; Oxygen; Photochemotherapy; Photosensitizing Agents; Platinum; Porphyrins; Squamous Cell Carcinoma of Head and Neck

Although most cutaneous squamous cell carcinoma (cSCC) cases are generally nonlethal and manageable with surgical excision, there ares till significant hazards for patients who are ineligible for surgical resection. We sought to find a suitable and effective treatment for cSCC.. We modified chlorin e6 by adding a hydrogen chain with a six-carbon ring to the benzene ring and named this new photosensitizer as STBF. We first investigated the fluorescence characteristics, cellular uptake of STBF and subcellular localization. Next, cell viability was detected by CCK-8 assay and the TUNEL staining was performed. Akt/mTOR-related proteins were examined by western blot.. STBF-photodynamic therapy (PDT) inhibits cSCC cells viability in a light dose dependent manner. The antitumor mechanism of STBF-PDT might be due to the suppression of the Akt/mTOR signaling pathway. Further animal investigation determined that STBF-PDT led to a marked reduction in tumor growth.. Our results suggest that STBF-PDT exerts significant therapeutic effects in cSCC. Thus, STBF-PDT is expected to be a promising method for the treatment of cSCC and the photosensitizer STBF may be destined for a wider range of applications in photodynamic therapy.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Photochemotherapy; Photosensitizing Agents; Porphyrins; Proto-Oncogene Proteins c-akt; Signal Transduction; Skin Neoplasms; TOR Serine-Threonine Kinases

The activity of chlorin e6 (Ce6) in photodynamic therapy of cancers is significantly reduced by its propensity to form aggregates. It was postulated that disaggregation of Ce6 could be achieved with the use of hydroxypropyl-beta-cyclodextrin (HP-β-CD) through solubility enhancement.. An initial phase solubility study of Ce6 was conducted with various concentrations of HP-β-CD at three different pH conditions, i.e. pH 3, pH 5 and pH 7. Solubility-induced disaggregation of Ce6 was illustrated by fluorescence spectroscopy and singlet oxygen generation studies. Interaction between Ce6 and HP-β-CD was further demonstrated by solid-state characterization techniques. Inclusion complex formulations were tested for improved efficacy on squamous cancer cell lines.. Increase in Ce6 solubility was observed, especially at pH 7, indicating the formation of inclusion complex between Ce6 and HP-β-CD. This resulted in disaggregation of Ce6 aggregates illustrated by fluorescence spectroscopy. The mode of binding was predominated by H-bonding supported by temperature-dependent binding studies and molecular simulation work. The inclusion complex demonstrated improved photodynamic efficacy through enhanced singlet oxygen generation and phototoxicity on human oral squamous carcinoma cells.. pH-dependent complexation between Ce6- and HP-β-CD-induced disaggregation of Ce6 aggregates and the resultant formulations facilitated improved PDT efficacy on tested cancer cell lines.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Calorimetry, Differential Scanning; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Chlorophyllides; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Compounding; Head and Neck Neoplasms; Humans; Hydrogen-Ion Concentration; Models, Molecular; Mouth Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Powder Diffraction; Singlet Oxygen; Solubility; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; Squamous Cell Carcinoma of Head and Neck; Thermodynamics; Time Factors

Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab.

Topics: Animals; Antibodies, Monoclonal, Humanized; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Chlorophyllides; Combined Modality Therapy; Drug Synergism; ErbB Receptors; Head and Neck Neoplasms; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents; Random Allocation; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays

After years of setbacks, therapeutic cancer vaccines have become an alternative treatment option. Among the diversity of targeted tumour associated antigens (TAA), cancer-testis antigens (CTAs) are promising targets for cancer immunotherapy because they are highly immunogenic; meanwhile, they are expressed in human tumours of different histological origin but not in adult somatic tissues. Epigenetic modifications, such as DNA methylation, regulate CTAs expression both in normal and cancer cells. 5-Aza-2'-deoxycytidine (5-AZA-CdR), a DNA hypomethylating drug, induces the expression of CTAs in neoplastic cells. In these studies, we used 5-AZA-CdR-mediated up-regulation of CTAs and chlorin e6-mediated photodynamic effect in the production of a whole-tumour-cell vaccine against murine squamous cell carcinoma SCCVII in C3H/HeN mice. The results show that 5-AZA-CdR can be used to elevate levels of diverse CTAs in SCCVII cells. The 5-AZA-CdR-based vaccine, combined with the systemic administration of 5-AZA-CdR, delayed tumour growth. However, the treatment had no effect on survival in mice, most likely because of the toxicity of systemic treatment with 5-AZA-CdR. The photodynamic effect diminished therapeutic potential of 5-AZA-CdR-based vaccine. Chemo-immunotherapy with 5-AZA-CdR and therapeutic cancer vaccines may be an alternative approach to cancer therapy. However, further studies are needed to optimize treatment and vaccine preparation protocols.

Topics: Animals; Antigens, Neoplasm; Antimetabolites, Antineoplastic; Azacitidine; Cancer Vaccines; Carcinoma, Squamous Cell; Cell Line, Tumor; Chlorophyllides; Decitabine; DNA Methylation; Enzyme-Linked Immunosorbent Assay; Kaplan-Meier Estimate; Male; Mice; Mice, Inbred C3H; Photochemotherapy; Photosensitizing Agents; Porphyrins; Transplantation, Homologous

The effect of photodynamic therapy (PDT) is dependent on the localization of photosensitizer in the treatment volume at the time of illumination. Investigation of photosensitizer pharmacokinetics in and around the treatment volume aids in determining the optimal drug light interval for PDT.. In this paper we have investigated the distribution of the photosensitizers chlorin e6 and Bremachlorin in the oral squamous cell carcinoma cell-line OSC19-Luc-Gfp in a tongue tumor, tumor boundary, invasive tumor boundary, and normal tongue tissue by the use of confocal microscopy of frozen sections. Tongues were harvested at t = [3, 4.5, 6, 24, 48] hours after injection.. Both photosensitizers showed a decreasing fluorescence with increasing incubation time, and at all time points higher fluorescence was measured in tumor boundary than in tumor itself. For short incubation times, a higher fluorescence intensity was observed in the invasive tumor border and normal tissue compared to tumor tissue. Bremachlorin showed a small increase in tumor to normal ratio at 24 and 48 hours incubation time. Ce6 was undetectable at 48 hours. We did not find a correlation between photosensitizer localization and the presence of vasculature.. The modest tumor/tumor boundary to normal selectivity of between 1.2 and 2.5 exhibited by Bremachlorin 24 and 48 hours after administration may allow selective targeting of tongue tumors. Further studies investigating the relationship between Bremachlorin concentration and therapeutic efficacy PDT with long incubation times are warranted.

Topics: Animals; Carcinoma, Squamous Cell; Chlorophyllides; Drug Combinations; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Photochemotherapy; Photosensitizing Agents; Porphyrins; Random Allocation; Tongue Neoplasms

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

Recent investigations have established that tumour cells treated in vitro by photodynamic therapy (PDT) can be used for generating potent vaccines against cancers of the same origin. In the present study, cancer vaccines were prepared by treating mouse SCCVII squamous cell carcinoma cells with photosensitiser chlorin e6-based PDT and used against poorly immunogenic SCCVII tumours growing in syngeneic immunocompetent mice. The vaccine potency increased when cells were post-incubated in culture after PDT treatment for 16 h before they were injected into tumour-bearing mice. Interfering with surface expression of phosphatidylserine (annexin V treatment) and apoptosis (caspase inhibitor treatment) demonstrated that this post-incubation effect is affiliated with the expression of changes associated with vaccine cell death. The cured mice acquired resistance to re-challenge with the same tumour, while the engagement of cytotoxic T lymphocytes was demonstrated by detection of high numbers of degranulating CD8+ cells in vaccinated tumours. The vaccines prepared from ex vivo PDT-treated SCCVII tumour tissue were also highly effective, implying that surgically removed tumour tissue can be directly used for PDT vaccines. This opens attractive prospects for employing PDT vaccines tailored for individual patients targeting specific antigens of the patient's tumour.

Topics: Animals; Cancer Vaccines; Carcinoma, Squamous Cell; Cell Death; Cell Proliferation; Chlorophyllides; Cytotoxicity, Immunologic; Disease Models, Animal; Female; Injections, Subcutaneous; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Porphyrins; Time Factors

Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resection, or as a feedback mechanism to assess response to treatment. In oral precancer, the epidermal growth factor receptor (EGFR) is overexpressed and could be used as a marker for early detection or as a target for therapy. The goal of this study was to test an anti-EGFR MAb (C225) coupled to either the near-infrared fluorescent dye N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid for detection or a photochemically active dye (chlorin(e6)) for therapy of early premalignancy in the hamster cheek pouch carcinogenesis model. Fluorescence levels in the carcinogen-treated tissue correlated with the histological stage of the lesions when the C225-N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid conjugate was used but did not do so with the irrelevant conjugates. Discrete areas of clinically normal mucosa with high fluorescence (hot spots) were subsequently shown by histology to contain dysplastic areas. The best contrast between normal and carcinogen-treated cheek pouches was found at 4-8 days after injection. To test the potential of immunophotodiagnosis as a feedback modality for therapeutic intervention, experiments were conducted with the same MAb conjugated to chlorin(e6) followed by illumination to reduce expression of the EGFR by a photodynamic effect. Subsequent immunophotodiagnosis showed that this treatment led to a significant reduction in fluorescence in the carcinogen-treated cheek pouch compared with nonilluminated areas. This difference between illuminated and dark areas was not seen in the normal cheek pouch. Taken together, the results demonstrate the potential for development of immunophotodiagnosis as a diagnostic tool and as a method of monitoring response to therapy and that the EGFR may be an appropriate target in head and neck cancer.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Chlorophyllides; Cricetinae; ErbB Receptors; Fluorescent Dyes; Humans; Immunoconjugates; Immunotherapy; Male; Mesocricetus; Mouth Neoplasms; Phototherapy; Pilot Projects; Porphyrins; Precancerous Conditions; Radiation-Sensitizing Agents; Tumor Cells, Cultured