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The Journal of Surgical Research Jul 2021Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy... (Comparative Study)
Comparative Study
BACKGROUND
Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration-approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice.
METHODS
Human non-small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT.
RESULTS
Porfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point.
CONCLUSIONS
PS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Dihematoporphyrin Ether; Humans; Injections, Intravenous; Lung; Lung Neoplasms; Mice; Photochemotherapy; Photosensitizing Agents; Pneumonectomy; Xenograft Model Antitumor Assays
PubMed: 33713956
DOI: 10.1016/j.jss.2020.12.067 -
Gan To Kagaku Ryoho. Cancer &... Aug 1995Porfimer sodium (Photofrin II) is a photosensitizer which distributes selectively to tumor tissues, and causes tumor cell death by combination with light irradiation.... (Review)
Review
Porfimer sodium (Photofrin II) is a photosensitizer which distributes selectively to tumor tissues, and causes tumor cell death by combination with light irradiation. Photodynamic therapy (PDT) by combination of porfimer sodium and laser was developed as a new cancer therapy. Tumor selectivity of porfimer sodium are based on the following reasons; 1) high affinity for lipoprotein, especially, low density lipoprotein (LDL), 2) elevation of LDL receptor activity in cancer tissue, and 3) lack or imcompleteness of lymphatic system in cancer tissue. Porfimer sodium is activated by laser irradiation at 630 nm, which can reacts with tissue oxygen to produce highly reactive excited siglet oxygen (1O2). This highly reactive molecule is subsequently capable of killing tumor cells through oxidation of cellular component like mitochondrial enzymes. In addition, this highly reactive intermediate causes destruction of the tumor capillaries, which accelerates tumor cell death. The growth suppression or lethal damage to tumor cells by PDT of porfimer sodium and excimer dye laser were observed in experimental tumor models. In human clinical trials, the rates of complete response (CR) for roentgenographically occult lung cancer, stage I lung cancer, superficial esophageal cancer, superficial gastric cancer and carcinoma in situ or dysplasia of the cervix were 84.8%, 50.0%, 90.0%, 87.5% and 94.4%, respectively. The major side effects were cutaneous symptoms e.g. photosensitivity, pigmentation, increasing GOT, GPT but these symptoms were not severe. PDT using porfimer sodium and excimer dye laser must be clinically useful for the treatment of inoperable early cancer or conservation of organ functions.
Topics: Animals; Dihematoporphyrin Ether; Female; Humans; Lung Neoplasms; Male; Photochemotherapy; Rabbits; Rats; Stomach Neoplasms; Tumor Cells, Cultured; Uterine Cervical Dysplasia
PubMed: 7661580
DOI: No ID Found -
Photodiagnosis and Photodynamic Therapy Mar 2020Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated...
BACKGROUND
Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma.
METHODS
Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6-180 months).
RESULTS
The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %-72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01).
CONCLUSIONS
Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Dihematoporphyrin Ether; Female; Humans; Male; Middle Aged; Photochemotherapy; Squamous Cell Carcinoma of Head and Neck; Survival Rate
PubMed: 31866532
DOI: 10.1016/j.pdpdt.2019.101627 -
Journal of Biomedical Optics Nov 2019The goal of our study was to determine the susceptibility of different pancreatic cell lines to clinically applicable photodynamic therapy (PDT). The efficacy of PDT of...
The goal of our study was to determine the susceptibility of different pancreatic cell lines to clinically applicable photodynamic therapy (PDT). The efficacy of PDT of two different commercially available photosensitizers, verteporfin and sodium porfimer, was compared using a panel of four different pancreatic cancer cell lines, PANC-1, BxPC-3, CAPAN-2, and MIA PaCa-2, and an immortalized non-neoplastic pancreatic ductal epithelium cell line, HPNE. The minimum effective concentrations and dose-dependent curves of verteporfin and sodium porfimer on PANC-1 were determined. Since pancreatic cancer is known to have significant stromal components, the effect of PDT on stromal cells was also assessed. To mimic tumor-stroma interaction, a co-culture of primary human fibroblasts or human pancreatic stellate cell (HPSCs) line with PANC-1 was used to test verteporfin-PDT-mediated cell death of PANC-1. Two cytokines (TNF-α and IL-1β) were used for stimulation of primary fibroblasts (derived from human esophageal biopsies) or HPSCs. The increased expression of smooth muscle actin (α-SMA) confirmed the activation of fibroblasts or HPSC upon treatment with TNF-α and IL-1β. Cell death assays showed that both sodium porfimer- and verteporfin-mediated PDT-induced cell death in a dose-dependent manner. However, verteporfin-PDT treatment had a greater efficiency with 60 × lower concentration than sodium porfimer-PDT in the PANC-1 incubated with stimulated fibroblasts or HPSC. Moreover, activation of stromal cells did not affect the treatment of the pancreatic cancer cell lines, suggesting that the effects of PDT are independent of the inflammatory microenvironment found in this two-dimensional culture model of cancers.
Topics: Biopsy; Cell Death; Cell Line, Tumor; Coculture Techniques; Dihematoporphyrin Ether; Drug Screening Assays, Antitumor; Fibroblasts; Humans; Microscopy, Fluorescence; Pancreas; Pancreatic Neoplasms; Photochemotherapy; Stromal Cells; Tumor Microenvironment; Verteporfin
PubMed: 31741351
DOI: 10.1117/1.JBO.24.11.118001 -
Gastrointestinal Endoscopy Clinics of... Jan 2011Photodynamic therapy (PDT) is a photochemical process that uses a photosensitizer drug activated by laser light to produce mucosal ablation. Porfimer sodium PDT has... (Review)
Review
Photodynamic therapy (PDT) is a photochemical process that uses a photosensitizer drug activated by laser light to produce mucosal ablation. Porfimer sodium PDT has proved long-term efficacy and durability in the treatment of Barrett's esophagus and high-grade dysplasia and early esophageal adenocarcinoma. Its use has been limited by serious side effects including prolonged cutaneous photosensitivity and stricture formation. Other photosensitizers with a better safety profile have been used mostly in Europe with limited experience. The future of PDT lies on a better understanding of dosimetry, tissue properties, and host genetic factors.
Topics: Adenocarcinoma; Aminolevulinic Acid; Barrett Esophagus; Dihematoporphyrin Ether; Esophageal Neoplasms; Humans; Mesoporphyrins; Photochemotherapy; Photosensitizing Agents; Precancerous Conditions
PubMed: 21112498
DOI: 10.1016/j.giec.2010.09.002 -
Cancer Nov 1993Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound porfimer...
BACKGROUND
Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm fluorescence of the porphyrin by subtracting nonspecific 612 nm excitation from 630 nm excitation. The technique was applied in the developmental stages of the 9,10 dimethyl-1,2-benzanthracene (DMBA)-induced hamster buccal cheek pouch carcinoma model to (1) quantitate and characterize porfimer sodium fluorescence and uptake as it relates to lesion progression and biochemical changes and (2) determine whether porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli.
METHODS
Groups of Syrian Golden hamsters had their cheek pouch buccal mucosa exposed to a 0.5% DMBA in acetone three times per week for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinomas), or other specified durations. The rate of malignant transformation was either promoted (by either carbon dioxide laser incision or continued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2] or bombesin antagonist RC-3095 [D-Tpi-Gln-Trp-Ala-Val-Gly-His-Leu psi (CH2NH)Leu-NH2]). Groups of DMBA-exposed hamsters were subsequently injected with 1.0 mg/kg of porfimer sodium during the various stages of tumor development. Twenty-four hours after injection, fluorescence levels were measured by in vivo fluorescence photometry. Samples of tumors, dysplastic mucosal tissue, and normal-appearing oral mucosa were biopsied and used for either tissue extraction assays, histopathologic examination, or tyrosine kinase activity assay as an index of rate of transformation.
RESULTS
Results demonstrated that porfimer sodium is retained in DMBA-treated tissue. Fluorescence is completely accounted for by porfimer sodium uptake. The duration of exposure to carcinogen is proportional to porfimer sodium fluorescence. This relationship establishes that premalignant lesions can be distinguished from normal tissue by porfimer sodium uptake and fluorescence. The changes in increased tyrosine kinase activity paralleled the increase in porfimer sodium fluorescence. Alterations in the rate of tissue transformation produced equivalent alterations in porfimer sodium-induced fluorescence.
CONCLUSIONS
These results suggest that porfimer sodium uptake and fluorescence can be used in a prognostic manner to diagnose and determine the course of transformation of individual lesions.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Bombesin; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cheek; Cricetinae; Dihematoporphyrin Ether; Disease Models, Animal; Fluorescence; Mesocricetus; Mouth Neoplasms; Peptide Fragments; Photometry; Protein-Tyrosine Kinases; Somatostatin
PubMed: 8106141
DOI: 10.1002/1097-0142(19931115)72:10<3068::aid-cncr2820721032>3.0.co;2-j -
Gastrointestinal Endoscopy Oct 2005
Topics: Adenocarcinoma; Barrett Esophagus; Dihematoporphyrin Ether; Esophageal Neoplasms; Esophagoscopy; Humans; Photochemotherapy; Photosensitizing Agents; Precancerous Conditions; Treatment Outcome
PubMed: 16185960
DOI: 10.1016/j.gie.2005.07.017 -
Cancer Biology & Therapy Jan 2013Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome...
Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome tumor relapse have been proposed, such as the use of chemotherapeutic drugs or radiation in small, frequent fractionated doses without an extended break period between treatment intervals. Yet, tumors usually acquire resistance and eventually escape the therapy. Several mechanisms have been proposed to explain the resistance of tumors to therapy, one of which involves the cancer stem cell or tumor-initiating cell (TIC) concept. TICs are believed to resist many conventional therapies, in part due to their slow proliferation and self-renewal capacities. Therefore, emerging efforts to eradicate TICs are being undertaken. Here we show that treatment with Photofrin II, among the most frequently used photosensitizers, sensitized a TIC-enriched U-87MG human glioblastoma cell to radiation, and improve treatment outcome when used in combination with radiotherapy. A U-87MG tumor cell population enriched with radiation-resistant TICs becomes radio-sensitive, and an inhibition of cell proliferation and an increase in apoptosis are found in the presence of Photofrin II. Furthermore, U-87MG tumors implanted in mice treated with Photofrin II and radiation exhibit a significant reduction in angiogenesis and vasculogenesis, and an increased percentage of apoptotic TICs when compared with tumors grown in mice treated with radiation alone. Collectively, our results offer a new possible explanation for the therapeutic effects of radiosensitizing agents, and suggest that combinatorial treatment modalities can effectively prolong treatment outcome of glioblastoma tumors by inhibiting tumor growth mediated by TICs.
Topics: Animals; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemoradiotherapy; Dihematoporphyrin Ether; Glioblastoma; Humans; Mice; Mice, Nude; Neoplastic Stem Cells; Neovascularization, Pathologic; Photosensitizing Agents; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 23114641
DOI: 10.4161/cbt.22630 -
Lasers in Medical Science Dec 2006We studied pulse energy density dependence of two distinctive clinical photosensitizers, Porfimer sodium and Talaporfin sodium, in terms of oxygen consumption,...
We studied pulse energy density dependence of two distinctive clinical photosensitizers, Porfimer sodium and Talaporfin sodium, in terms of oxygen consumption, photodegradation in these photosensitizer solutions, and rat prostate cancer cell line photocytotoxicity. The transient transmittances during the pulsed irradiation to these photosensitizer solutions were measured with the pulse energy densities ranging from 0.31 to 31 mJ/cm2. We revealed that Talaporfin sodium was easier to produce absorption saturation than Porfimer sodium. The significant suppression of Talaporfin sodium mediated oxygen consumption, photodegradation, and photocytotoxicity which were observed with pulse energy densities increasing from 0.5 to 10 mJ/cm2. This result could be mainly attributed to absorption saturation. On the other hand, Porfimer sodium did not display significant absorption saturation with the pulse energy densities ranging from 0.31 to 31 mJ/cm2. The photodegradation mechanism for Porfimer sodium changed at high pulse energy density. This phenomenon might accelerate the photodegradation and cause the photocytotoxicity suppression.
Topics: Animals; Cells, Cultured; Dihematoporphyrin Ether; Laser Therapy; Male; Oxygen Consumption; Photochemotherapy; Photosensitizing Agents; Porphyrins; Prostate; Prostatic Neoplasms; Rats
PubMed: 17024319
DOI: 10.1007/s10103-006-0403-0 -
Lasers in Surgery and Medicine Jun 2006Porfimer sodium photodynamic therapy (ps-PDT) for Barrett's esophagus is a powerful endoscopic treatment that can eliminate high-grade dysplasia (HGD) and Barrett's...
Porfimer sodium photodynamic therapy (ps-PDT) for Barrett's esophagus is a powerful endoscopic treatment that can eliminate high-grade dysplasia (HGD) and Barrett's mucosa and reduce the risk of development of cancer in these patients. Ps-PDT typically results in destruction of Barrett's esophagus in the majority of the treated area. However, residual small island of Barrett's mucosa may persist after PDT. Therefore, adjuvant thermal ablation should be available during follow-up endoscopies for ablation of residual islands of Barrett's mucosa. PDT should be applied concurrent with effective proton pump inhibitor therapy. This article provides a practical guide for application of porfimer sodium balloon PDT for management of Barrett's esophagus with HGD. Recommendations are provided for patient selection and screening, delivery of PDT to include light dosimetry, methodology for follow-up endoscopies, as well as discussing the potential side effects and complications.
Topics: Anti-Ulcer Agents; Barrett Esophagus; Catheter Ablation; Dihematoporphyrin Ether; Esophageal Neoplasms; Esophageal Stenosis; Humans; Mucous Membrane; Omeprazole; Patient Selection; Photochemotherapy; Photosensitizing Agents; Precancerous Conditions; Randomized Controlled Trials as Topic
PubMed: 16788927
DOI: 10.1002/lsm.20367