Search PubMed⌕ Search

Biomedical subjects

T Okunaka

Publications and source records attributed to T Okunaka.

29 records · Page 2Linked to original sources
PubMed1992

Correlation between photodynamic efficacy of differing porphyrins and membrane partitioning behavior.

The ability of a photosensitizer to partition into membrane is determined by its structure and physical properties. Partitioning behavior can be quantitated as the partition coefficient (Kp) for a particular drug. This property may be an important determinant of cytocidal efficacy in photodynamic therapy. The Kp of five photoactive drugs--13,17-ditetraammonium protoporphyrin (PH1008), photofrin II (PII), hematoporphyrin (Hp), benzoporphyrin derivative monoacid (BPD-MA), coproporphyrin (Cp), and uroporphyrin (Up)--was determined using a simple liposome system composed of sonicated egg phosphatidylcholine single bilayer vesicles. The cytocidal efficacy of each drug was compared by determining the concentration of drug resulting in 50% maximal lysis (C50) obtained by measuring the hemoglobin absorbance at 414 nm released from lysed human red blood cells. The percentage lysis at 1 microM final drug concentration was also determined. An argon-dye laser was used to administer light of 630-nm wavelength for a total exposure of 5 J/cm2. Porphyrins with a greater tendency to partition into phosphocholine bilayer membranes demonstrated a greater lytic efficacy in the rbc system utilized. The comparison of physical properties with lytic ability may be useful in understanding the mechanism by which PDT exerts its effects and in predicting the clinical efficacy of different drugs.

Cell Membrane↗
PubMed1992

Primary lung cancer producing alpha-fetoprotein.

Reports of alpha-fetoprotein-producing lung tumors are rare. Only 24 such patients with these tumors have been previously studied. We report the case of a patient with a large cell carcinoma of the lung and a serum alpha-fetoprotein level of 9,300 ng/mL, with no evidence of hepatic or other systemic abnormalities. Serum levels of alpha-fetoprotein returned to normal postoperatively.

Biomarkers, Tumor↗
PubMed1992

A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells.

Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.

Humans↗
PubMed1992

A comparison between argon-dye and excimer-dye laser for photodynamic effect in transplanted mouse tumor.

Photodynamic therapy (PDT) utilizing a hematoporphyrin derivative (HpD) as a sensitizer has become a viable option for the local treatment of neoplastic disease. The argon-dye laser system is commonly used as a light source in this treatment modality. The excimer-dye laser, on the other hand, delivers high-energy red light in a pulsatile fashion. In this investigation, we treated BALB/c mice bearing mouse kidney sarcoma cell tumors with PDT using HpD at the dose of 5 mg/kg body weight as a photosensitizer and either a standard argon-dye laser or the pulsatile excimer-dye laser as the light source. At equal light energy doses (50 J/cm2), necrotic changes at depths averaging 4 mm from the tumor surface were obtained with the argon-dye laser (200 mW power output) while tumor necrosis at depths exceeding 15 mm from the tumor surface was obtained using the excimer-dye laser (6 mJ/pulse, 5 Hz). To determine the best conditions for photoirradiation with the excimer-dye laser, tumor-bearing mice were treated with different total light doses (10, 30 and 50 J/cm2), dose rates (1, 3 and 6 mJ/cm2), and frequencies (5, 15 and 50 Hz) of light exposure. Our results indicate that the optimal effects obtained with the excimer-dye laser are related to the total light dose used and the dose rate, but not to the frequency of light exposure.

Animals↗
PubMed1991

Photodynamic therapy for multiple primary bronchogenic carcinoma.

In recent years, multiple primary lung cancers have been reported with greater frequency, partly as a result of technologic advances in the detection of lung cancer and therapeutic achievements in its management. Photodynamic therapy (PDT) is a relatively new therapy used with increasing frequency in the treatment of a wide variety of malignancies, including central lung cancers. In PDT, the differential retention of an injected photosensitizer by malignant tissue is exploited by treatment with a low-power laser beam delivered endoscopically. Since 1980, 145 patients with central lung cancers, including 35 cases of endoscopically evaluated early-stage lesions were treated with PDT at Tokyo Medical College. Thirteen of these 145 patients had multiple primary bronchogenic carcinomas, five cases of which were synchronous with the rest, metachronous. Three of 13 patients with multiple tumors had early-stage lesions and were treated with endoscopic PDT alone. In the other ten cases, PDT was used to treat accessible early-stage foci although operative excision was required for advanced lesions. Mean survival after PDT, alone or in combination with surgery, was 38 months (range, 14 to 87 months), and seven patients remain alive to date. It was concluded that PDT is useful in extending the therapeutic options for, and improving the prognosis of patients with, multiple primary bronchogenic carcinomas.

Adenocarcinoma↗
PubMed1990

Photodynamic therapy of esophageal carcinoma.

Photodynamic therapy (PDT) utilizing either hematoporphyrin derivative or Photofrin II is proving to be an effective modality in the treatment of early superficial (ES) or advanced invasive (AI) carcinoma of the esophagus. An argon-pumped dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel of a gastroscope after intravenous injection of photosensitizer. Between 1982 and 1989, 20 patients (ES = 6; AI = 14) were treated in this manner. Complete remission was obtained in 4 of 6 ES cases, and the mean survival after PDT alone or in combination with other therapy was 27 months. Five patients remain alive to date. In the AI group, significant remissions were obtained in 6 cases while partial remissions were observed in another 8. The mean dysphagia grade improved from 4.0 to 2.8. We conclude that PDT is efficacious in the treatment of ES esophageal cancer, where complete remission may be achieved, and as palliative therapy in advanced cases to alleviate dysphagia.

Aged↗
PubMed1987

[Qualitative improvement of the surgical treatment of cancer using laser equipment--surgical technic after photodynamic therapy].

Nineteen patients with lung cancer were treated by combined preoperative photodynamic therapy (PDT) and surgery. Preoperative photodynamic therapy was performed for the purpose of either reducing the extent of resection or increasing operability. Clinically, nine patients had stage I disease, one had stage II, eight had stage III and one had stage IV. There were two cases of tracheal superficial invasion from primary lesions, three cases of intrabronchial polypoid tumor or superficial invasion of the carina by primary lesions, eleven cases of polypoid tumor or superficial invasion of the main bronchus, and three cases of double primary lesions. Argon dye laser was used in this study. Preoperative PDT was performed 48 to 72 hours after intravenous injection of hematoporphyrin derivative (HpD). Therapeutic conditions were 60 to 600 joules/cm2 for the superficial invasive areas and an additional 200 to 800 m W for 8 to 15 minutes for polypoid lesions. Surgical resection was performed 1 to 9 weeks after PDT. The initial purpose of PDT was achieved in 15 of the 19 patients treated. In five of six originally inoperable cases, conversion to an operable status was achieved. Thirteen patients were originally candidates for pneumonectomy, and it became possible to reduce the extent of resection to lobectomy in ten of them. This study suggests that PDT may have an important role in combination with surgery and other modalities in advanced lung cancers.

Adenocarcinoma↗