talaporfin and Carcinoma

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) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin has not been clarified. Thus, we investigated the uptake, transportation, and elimination mechanisms of talaporfin in carcinoma and sarcoma. The results showed that talaporfin co-localized in early endosomes and lysosomes. Talaporfin uptake was via clathrin- and caveolae-dependent endocytosis and a high amount of intracellular ATP was essential. Inhibition of lysosomal enzymes maintained intracellular talaporfin levels. Inhibition of K-Ras signaling reduced talaporfin uptake in carcinoma and sarcoma cell lines. Talaporfin was taken up by clathrin- and caveolae-dependent endocytosis, translocated from early endosomes to lysosomes, and finally degraded by lysosomes. We also demonstrated that ATP is essential for the uptake of talaporfin and that activation of K-Ras is involved as a regulatory mechanism. These results provide new insights into the metabolism of talaporfin in cancer cells for the enhancement of PDT for carcinoma and sarcoma.

Topics: Carcinoma; Cell Line, Tumor; Humans; Photosensitizing Agents; Porphyrins; Sarcoma

Radiation is the treatment of choice for canine nasal tumours but, in almost all cases, there is local recurrence associated with poor prognosis. This report describes the effect of endoscopic photodynamic therapy using talaporfin sodium for canine intranasal carcinoma recurring after radiation therapy. Rhinoscopic photodynamic therapy was administered after radiation therapy in three dogs with recurrent intranasal carcinoma. Two to 24 illuminations of a 665-nm diode laser were performed two hours after intravenous bolus injection of 5·0 mg/kg of talaporfin sodium. Photodynamic therapy induced almost complete remission and prolonged survival time in all cases suggesting that it might be a useful treatment for intranasal carcinomas that recur after radiation.

Topics: Animals; Carcinoma; Dogs; Endoscopy; Lasers, Semiconductor; Neoplasm Recurrence, Local; Nose Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Radiotherapy

Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980's. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step.

Topics: Carcinoma; Dihematoporphyrin Ether; Endoscopy, Gastrointestinal; Gastrointestinal Neoplasms; Humans; Japan; Lasers; Photochemotherapy; Photosensitizing Agents; Porphyrins

We evaluated an alternative procedure for sentinel lymph node biopsy (SLNB) for breast cancer after approval of the study by the Ethics Committee of Tokyo Medical University Hospital in 2004. We examined the efficacy and safety of SLNB using the photosensitizer talaporfin sodium (Laserphyrin®, Meiji Seika Pharma, Tokoyo, Japan), compared with current methods.. The study included 21 breast cancer patients (Japanese women; median age, 54 years; range, 35-75). All patients received a breast cancer operation combined with SLNB between June 2004 and May 2005. Three milliliters of talaporfin solution was locally injected into the subareolar region just before the operation. We attempted to identify a sentinel lymph node (SLN) that exhibited fluorescence and was consistent with a radioisotope (RI) localization technique. Our purpose was to verify the accuracy and validity of the talaporfin fluorescence imaging method after 8 years of application.. There was no consistent correlation between fluorescence and pathological SLN metastasis, although all four cases of pathological SLN metastasis revealed positive fluorescence. In some cases in which we could not identify SLNs by the RI technique, we could identify SLNs using talaporfin. The method using talaporfin did not adversely affect the patients after the operation, even the chronic renal failure patient. After 8 years, all patients are alive, and none had lymph node recurrence. Side effects were not observed.. SLNB using the photosensitizer talaporfin sodium in breast cancer patients is considered to be useful as complementary to other current methods. We could evaluate the accuracy and validity of this method 8 years after all of the procedures were performed. In the future, a large-scale clinical study with statistical analyses should be conducted.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Female; Follow-Up Studies; Humans; Middle Aged; Optical Imaging; Photosensitizing Agents; Porphyrins; Sentinel Lymph Node Biopsy

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