Antitumor activity evaluation of meso-tetra (pyrrolidine substituted) pentylporphin-mediated photodynamic therapy in vitro and in vivo.

Photodynamic therapy is a minimally invasive and promising new method in cancer treatment and has attracted considerable attention in recent years. An ideal photosensitizer is a crucial element to photodynamic therapy. In the present paper, a novel porphyrin derivative, 5, 10, 15, 20-tetrakis (5-(pyrrolidin-1-yl) pentyl) porphin (TPPP) was synthesized. Its spectroscopic and physicochemical properties, therapeutic efficacy as a photosensitizer in photodynamic therapy for human bladder cancer in vitro and in vivo were investigated. TPPP had strong absorption at 648nm (ε=1.75×10(4)M(-1)cm(-1)), and two fluorescence emission peaks at 652nm and 718nm. PDT with TPPP showed low dark toxicity and high phototoxicity to human bladder cancer T24 cells in vitro. In bearing T24 tumor nude mice, the growth of tumor was significantly inhibited by combining use of 5mg/kg TPPP with 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation at 3h following injection of TPPP. The antitumor effect was also confirmed with histopathological assay. The histopathological study results revealed that PDT using TPPP and 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation induced tumor cells shrunken and necrotic. These results indicate that TPPP is useful as a new photosensitizer in PDT for cancer, and deserves further investigation.

Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo.

This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1-hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC-939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT).

Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion.

BACKGROUND: Microvascular invasion (MiVI) is a major risk factor of survival outcomes after curative resection for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the impact of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on HCC patients with MiVI. METHODS: From January 2004 to June 2013, HCC patients with histologically confirmed MiVI and well-tolerated liver function who underwent PA-TACE after R0 hepatectomy (RH) or RH alone were studied retrospectively. In the PA-TACE group, PA-TACE was given 4 weeks after RH. Uni- and multivariate analyses were used to identify the prognostic significance of PA-TACE. RESULTS: Of the 322 HCC patients with MiVI included in the analysis, 185 entered into the RH group and 137 entered into the PA-TACE group. The baseline characteristics of the two groups were similar except for alanine aminotransferase (ALT) level (p = 0.037). The 1-, 2-, 3-, and 5-year recurrence-free survival (RFS) rates were respectively 69.3, 55.5, 46.7, and 35.0 % for the PA-TACE group and 47.0, 36.2, 34.1, and 30.3 % for the RH group (log-rank, χ(2) = 6.309; p = 0.012). The 1-, 2-, 3-, and 5-year overall survival (OS) rates were respectively 94.2, 78.8, 71.5, and 54.0 % for the PA-TACE group and 78.9, 62.2, 54.1, and 43.2 % for the RH group (log-rank, χ(2) = 7.537; p = 0.006). Multivariate Cox proportional hazards regression analysis showed PA-TACE to be an independent risk factor of postoperative RFS and OS. CONCLUSIONS: This study showed that PA-TACE may be beneficial for HCC patients with MiVI.

Mitochondrial ultrastructure & release of proteins during liver regeneration.

BACKGROUND & OBJECTIVES: It has been reported that some proteins are released from mitochondria during liver regeneration after partial hepatectomy (PH), but the relationship between proteins release and mitochondrial permeability transition (MPT) remains unclear. We undertook this study to demonstrate the changes of mitochondrial ultrastructure and proteins release during liver regeneration and to determine the relationship between proteins release and MPT in liver regeneration in rats. METHODS: After PH and administration of cyclosporin-A (CsA, a specific inhibitor of MPT), ultrastructural morphology of mitochondria in the remnant liver were determined by electron microscopy. Catalytic activity of mitochondrial and cytosolic proteins including aspartate aminotransferase (AST) and glutamic acid dehydrogenase (GDH) was measured. RESULTS: The liver mitochondria at 24 and 72 h were quite variable in morphology and ultrastructure. The enzyme activities of AST and GDH in cytosol released from mitochondrial matrix changed significantly at 24 and 72 h. CsA can inhibit the permeability of mitochondria partly at the same time. INTERPRETATION & CONCLUSIONS: The changes of mitochondria in ultrastructure reflected the feature of MPT, and the changes of enzymes activities released from mitochondrial matrix were consistent with those of mitochondrial ultrastructure. CsA can inhibit these changes to some extent. There was a close relationship of MPT with mitochondrial ultrastructure and proteins release during liver regeneration.

Surgical excision of giant primary carcinoma in the medial liver lobe.

OBJECTIVE: To assess the techniques for surgical excision of giant primary carcinoma in the medial liver lobe. METHODS: Operative managements, complications and their causes during and after resection of giant carcinoma in the medial liver lobe were analyzed retrospectively in 166 cases treated from October 1996 through December 2001. RESULTS: Of the 166 patients, 123 (74.1 %) underwent tumor resection and 43 (25.9 %) regular lobectomy, including left trilobectomy (8, 4.8 %), medial lobectomy (21, 12.7 %), right anterior lobectomy (11, 6.6 %), and hemihepatectomy (3, 1.8 %). All patients were subjected to surgery with intermittent interruption of the first porta hepatis under normothermia. The total interruption time was 7-68 minutes and average time was 24.5 minutes. The maximum single interruption time was 41 minutes. Intraoperative blood loss was 50-4000 ml, averaging 726 ml. The maximum blood transfusion was 5200 ml, averaging was 811 ml, and transfusion was not needed in 54 patients. Postoperative complications occurred in 9 patients (5.4%), of whom, 2 (1.2%) died of liver failure and acute respiratory distress syndrome respectively. CONCLUSIONS: An adequate reserve of liver function is a prerequisite for a smooth recovery after operation. Careful intraoperative management is crucial to decrease postoperative complications.