talaporfin and Bile-Duct-Neoplasms

The efficacy of adjuvant photodynamic therapy (PDT) using the new photosensitizer, talaporfin sodium (TPS), was assessed in 7 patients with bile duct carcinoma (BDC). The 664-nm semiconductor laser (100 J/cm(2)) was applied through endoscopy to the tumor lesion within 6 h after injection of TPS. Cases included three non-resectable and 4 resected BDC with remnant cancer cells at the bile duct stump. Radiated lesions exhibited mild inflammatory responses. Locally advanced tumor occluding bile duct was relieved by PDT and patency was maintained for 16 months. Two patients developed mild photodermatitis but no severe morbidity. One patient died of other disease, and two patients died of liver metastasis within 6 months, but local recurrence was not observed. Three patients maintained cancer-free survival for 6-13 months. One patient survived with good status for 24 months. Adjuvant TPS-PDT is a safe and useful treatment for local control of BDC. Compared to the conventional PDT, the patient's quality of life is remarkably improved.

Topics: Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma; Female; Humans; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins

Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study's objective was to evaluate the increased cytocidal effect by apoptotic PDT using a novel photosensitizer, glucose-conjugated chlorin, by irradiation of light-emitting diode laser (G-PDT) in comparison with conventional PDT using talaporfin sodium (T-PDT).. The cytocidal effect of G-PDT was compared to that of T-PDT as a control. Tumor viability was determined by an in vitro MTS assay. The percentage of apoptosis-positive cells was examined by triple stain flow cytometry (annexin V, ethidium homodimer III and Hoechst 33342) in the BDC cell line (NOZ cell) in vitro. The change in transplanted tumor volume in vivo (4-week-old male BALB/c mice) was examined 7 days after PDT.. Cell death was induced in a light dose-dependent manner by PDT. The laser power was set at 5 Jules/cm(2) to obtain half maximal inhibitory concentration (IC50) in T-PDT and G-PDT and the concentration of photosensitivity for G-PDT (2.02 μg/ml) was lower than that for T-PDT (4.14 μg/ml). Both T-PDT and G-PDT showed increased induction rates in comparison to the light only or G-chlorin only. Furthermore, the rate of apoptosis in the G-PDT (92.6%) was increased in comparison to that in the T-PDT (38.9%). The increased rates of tumor volume during the 7 days in both the G-PDT and T-PDT groups were significantly lower than that in the non-PDT group (p<0.01). At day 7, the increased rates of tumor volume in the G-PDT group were significantly lower than that in the T-PDT group (p<0.05).. The new G-PDT treatment showed a high prevalence of apoptosis and inhibition of tumor growth in treatment of BDC cells.

Topics: Animals; Apoptosis; Bile Duct Neoplasms; Cell Line, Tumor; Cell Survival; Cholangiocarcinoma; Flow Cytometry; Glucose; Humans; In Situ Nick-End Labeling; Lasers; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Porphyrins; Prevalence

We herein report the case of a 72-year-old man who underwent photodynamic therapy (PDT) with talaporfin sodium for recurrent cholangiocarcinoma after surgical resection. Endoscopic retrograde cholangiography (ERC) showed severe stenosis with an irregular surface measuring approximately 1 cm in length from the anastomotic site, and a recurrent nodular lesion was observed at the anastomotic site of the right anterior intrahepatic bile duct on gastrointestinal endoscopy. ERC after PDT revealed a dramatic improvement in the bile duct stenosis, and the nodular lesion had disappeared. No adverse events from the PDT were detected. PDT using talaporfin sodium may be a safe alternative treatment for cholangiocarcinoma.

Topics: Aged; Antineoplastic Agents; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Male; Neoplasm Recurrence, Local; Neoplasm, Residual; Photochemotherapy; Photosensitizing Agents; Porphyrins; Treatment Outcome

Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments.. The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen-labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice).. Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis-diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group (P<0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability (P<0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups (P<0.05). The proliferating cell nuclear antigen-labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups (P<0.05).. A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bile Duct Neoplasms; Biomarkers, Tumor; Cell Line, Tumor; Cell Survival; Cisplatin; Deoxycytidine; Drug Synergism; Fluorouracil; Gemcitabine; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred BALB C; Organoplatinum Compounds; Oxaliplatin; Photochemotherapy; Photosensitizing Agents; Porphyrins; Proliferating Cell Nuclear Antigen; Treatment Outcome; Vascular Endothelial Growth Factor A

The aim of this study was to compare the effects of laserphyrin-PDT (L-PDT) on biliary cancer with those of the conventional photosensitizer, photofrin-PDT (P-PDT).. An animal tumor model was established by inoculation of NOZ cells in 4-week-old male BALB/c mice. The laser light wavelength was set at 630 nm for P-PDT and 660 nm for L-PDT, at a frequency of 10 Hz. Each group received a total energy flux of 60 J/cm(2). The proportion of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling)-positive cells, expression of VEGF (vascular endothelial growth factor) and the PCNA (proliferating cell nuclear antigen)-labeling index (LI) were assessed after PDT.. L-PDT had significantly more potent apoptotic effects at 48 and 72 h after light exposure compared with P-PDT (P < 0.001). The mean PCNA-LI was significantly lower in the L-PDT group than the P-PDT group and the index was significantly lower at several time points after PDT (6, 12, 24, 48 and 72 h after laser light exposure) in the L-PDT than P-PDT (P < 0.001 vs. control). The cell proliferative activity was significantly decreased at 12 and 24 h after P-PDT compared with the control (P < 0.001). VEGF expression was significantly higher at 3 h after L-PDT compared with the control (P < 0.05), whereas it was significantly higher at many time points after P-PDT (3, 6, 48 and 72 h; P < 0.05 vs. control).. L-PDT is a better approach for biliary cancer than the conventional P-PDT, based on its potent apoptotic and cytostatic effects.

Topics: Animals; Apoptosis; Bile Duct Neoplasms; Carcinoma; Dihematoporphyrin Ether; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Treatment Outcome