phytochlorin and Head-and-Neck-Neoplasms

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 Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded..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

Chemotherapy in head and neck squamous cell carcinoma (HNSCC) has many systemic side effects, as well as hypoxia-induced chemoresistance. To reduce side effects and enhance chemosensitivity are urgently needed.. We synthesized a drug delivery system (named CECMa NPs) based on cisplatin (CDDP) and metformin (chemotherapeutic sensitizer), of which chlorin e6 (Ce6) and polyethylene glycol diamine (PEG) were synthesized as the shell, an anti-LDLR antibody (which can target to hypoxic tumor cells) was modified on the surface to achieve tumor targeting.. The NPs possessed a great synergistic effect of chemotherapy and phototherapy. After laser stimulation, both CDDP and metformin can be released in situ to achieve anti-tumor effects. Meanwhile, PDT and PTT triggered by a laser have anticancer effects. Furthermore, compared with free cisplatin, CECMa exhibits less systemic toxicity with laser irradiation in the xenograft mouse tumor model.. CECMa effectively destroyed the tumors via hypoxia targeting multimodal therapy both in vitro and in vivo, thereby providing a novel strategy for targeting head and neck squamous cell carcinoma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Chlorophyllides; Cisplatin; Combined Modality Therapy; Drug Delivery Systems; Head and Neck Neoplasms; Humans; Male; Metformin; Mice, Inbred BALB C; Multifunctional Nanoparticles; Photochemotherapy; Phototherapy; Polyethylene Glycols; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Tumor Hypoxia; Xenograft Model Antitumor Assays

Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT).. We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT.. We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues.. First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction.. Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chlorophyllides; DNA Damage; DNA-Activated Protein Kinase; Down-Regulation; Drug Therapy, Combination; ErbB Receptors; Head and Neck Neoplasms; Humans; Mice; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Piperidines; Porphyrins; Quinazolines; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2

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

Tumor response to photodynamic therapy (PDT) is dependent on treatment parameters used. In particular, the light fluence rate may be an important determinant of the treatment outcome. In this clinical case report, we describe the response of angiosarcoma to PDT carried out using different fluence rates and drug and light doses. A patient with recurrent multifocal angiosarcoma of the head and neck was recruited for PDT. A new generation chlorin-based photosensitizer, Fotolon, was administered at a dose of 2.0 to 5.7 mg/kg. The lesions were irradiated with 665 nm laser light for a light dose of 65 to 200 J/cm2 delivered at a fluence rate of 80 or 150 mW/cm2. High dose PDT carried out at a high fluence rate resulted in local control of the disease for up to a year; however, the disease recurred and PDT had to be repeated. PDT of new lesions carried out at a lower fluence rate resulted in tumor eradication. More significantly, it also resulted in spontaneous remission of neighboring and distant untreated lesions. Repeat PDT carried out on a recurrent lesion at a lower fluence rate resulted in eradication of both treated and untreated lesions despite the lower total light dose delivered. Immunohistochemical examination of biopsy samples implies that PDT could have activated a cell-mediated immune response against untreated lesions. Subsequent histopathological examination of the lesion sites showed negative for disease. Our clinical observations show that lower fluence rate PDT results in better outcome and also indicate that the fluence rate, rather than the total light dose, is a more crucial determinant of the treatment outcome. Specifically, lower fluence rate PDT appears to activate the body's immune response against untreated lesions.

Topics: Chlorophyllides; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Immunity, Cellular; Lasers; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins; Povidone; Protoporphyrins; Skin Neoplasms