Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

[Preliminary investigation of intestinal microflora in patients with hepatic cirrhosis].

OBJECTIVE: To examine the differential levels of fecal Bifidobacterium, Bacteroides, Eubacterium rectale-Clostridium, Escherichia coli, Enterococcus, and Clostridium difficile between patients with hepatic cirrhosis and healthy controls. Fecal samples were collected from 29 patients with hepatic cirrhosis treated in the Department of Digestive Diseases at Zunyi Hospital between March and December of 2010. METHODS: Fecal samples were collected from 13 healthy college students for use as controls. All samples were assessed by pH measurement, bacterial culture for turbidity, fluorescence in situ hybridization, and laser scanning confocal microscopy. The t-test and rank correlation test were used to determine statistical significance of intergroup differences in each tested parameter. RESULTS: The feces of patients with hepatic cirrhosis had higher pH than that of healthy controls (6.79+/-0.64 vs. 6.18+/-0.74, P less than 0.05). The bacterial turbidity was not significantly different between the feces of hepatic cirrhosis patients and healthy controls (1.15+/-0.59 vs. 1.39+/-1.01, P more than 0.05). The numbers of Bifidobacterium, Bacteroides, Eubacterium rectale-Clostridium, Escherichia coli, Enterococcus, and Clostridium difficile in feces of patients with hepatic cirrhosis were significantly lower than those of the controls (all P less than 0.01). No significant correlation was found between the number or ratio of bacteria species and the severity of hepatic cirrhosis (Child-Pugh scores; P more than 0.05). CONCLUSION: The total quantity of intestinal bacteria in patients with hepatic cirrhosis is not significantly different from that in healthy patients. However, the profile of intestinal bacteria is different, which may explain the increased pH of fecal samples from patients with hepatic cirrhosis, but the differential profile is not correlated to cirrhosis pathogenesis.

Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma.

Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma.

[Efficacy and safety of different dosages of intravesical epirubicin instillation for prevention of primary superficial bladder carcinoma from recurrence].

OBJECTIVE: To investigate the efficiency and safety of different regimens by intravesical instillation of epirubicin, a derivative of adriamycin, for the prevention of primary superficial bladder carcinoma from recurrence. METHODS: Ninety patients supplemented with intravesical epirubicin instillation after operation were randomly divided into three groups: Group A--80 mg in one dose; Group B--repeated epirubicin 40 mg q wk x 4-8 sessions followed by q month to the end of the second year; or Group C--50 mg q month to the same duration. All patients were followed up for two years by observing the recurrence rates and side effects. RESULTS: The recurrence rate of groups A, B and C at one year was 16.7%, 13.3% and 16.7%, respectively, without any significant difference observed. However, it was 50.0%, 36.7% and 36.7% at two years, at which time the recurrence rate of group A was significantly higher than those of groups B and C. The side effects rate was 23.3%, 40.0% and 33.3% for groups A, B and C, respectively. The more instillations the patients had, the more severe side effects were. CONCLUSION: Early postoperative single high dose intravesical instillation of epirubicin combined with repeated lower doses of the same drug every month may be an efficient and safe regimen to prevent the primary superficial bladder carcinoma from recurrence.

Preparation of photosensitizer-loaded PLLA nanofibers and its anti-tumor effect for photodynamic therapy in vitro.

Photodynamic therapy (PDT) is a promising new treatment for cancer that has been recently accepted clinically. PDT is based on the administration of tumor-localizing photosensitizers (PSs), followed by exposing the neoplastic area to the light absorbed by the PS. In this article, a novel anticancer nanofiber membrane containing purpurin-18 (0.1%) was successfully prepared. The thickness of membrane was 0.028 mm, and the average fiber diameter was around 357 nm by scanning electron microscope (SEM). It was indicated that purpurin-18 possessed excellent compatibility with PLLA from FTIR spectrum. The physical properties of fiber membrane were also characterized by Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). Cell morphology and the interaction between cells and nanofibers were studied by SEM. The results showed that both SMMC 7721 and ECA109 cells can adhere and spread on the surface of the polymer nanofiber, and both cells can interact and integrate well with the surrounding fibers. The efficacy of PDT was determined by MTT assays. The results showed that the cells were killed immediately after PDT and purpurin-18 had no different efficacy to different cancer cell lines. In summary, the PS-loaded PLLA nanofibers were prepared successfully, and the SMMC 7721 and ECA109 cells could be inhibited and killed through photodynamic therapy.