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Masakazu Hasegawa

Publications and source records attributed to Masakazu Hasegawa.

8 recordsLinked to original sources
PubMed2006

Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas.

Gastrointestinal neuroendocrine carcinomas (NECs) are extremely aggressive and poorly prognostic. We showed previously that human achaete-scute homologue gene 1 (hASH1), a basic helix-loop-helix transcription factor regulated by Notch, was aberrantly expressed in NECs. To date, no effective therapeutic strategies for NECs have been investigated. Notch, Wnt and Hedgehog (Hh) signalings are important for stem cell self-renewal and carcinogenesis in the gastrointestinal epithelium. In this study, we showed that Hh signaling was clearly upregulated in NECs in Gli1-dependent manner. Specific therapeutic effects of cyclopamine on NECs were also demonstrated. RT-PCR showed that among eight frozen samples (three NECs, one carcinoid tumor, three adenocarcinomas and one normal mucosa), the band intensities of Gli1 were the strongest in NECs, moderately strong in a carcinoid tumor, very weak in adenocarcinomas and undetectable in a normal mucosa. In real-time RT-PCR, the expression levels of Gli1 in NECs were 108.4, 28.6 and 16.3 times higher than that in an adenocarcinoma. In immunohistochemistry using 25 paraffin-embedded tissues, all twelve NECs and three of six carcinoid tumors showed positive stainings for Gli1, whereas six of seven adenocarcinomas were negative. In vitro, RT-PCR showed that NEC cell lines expressed Gli1 mRNA significantly. Administration of cyclopamine suppressed cell proliferation and invasion, and induced apoptosis in NECs. In cyclopamine-treated NECs, downregulation of Gli1, Ptch1, Snail and hASH1, and upregulation of E-cadherin were demonstrated at mRNA levels. Such effects were not observed in a Gli1-negative colonic adenocarcinoma cell line or in control alkaloid-treated NECs. Hh signaling may play a crucial role in the pathophysiology of NECs. Blockade of Hh pathway using cyclopamine or its synthetic derivatives might open an effective therapeutic strategy to NECs, not only by suppressing tumor viability but also by altering tumor cell nature.

Adenocarcinoma↗
PubMed2006

[Altered fractionation].

For improving radiotherapy treatment results, altered fractionation (AF) is one of the most important biological factors to modify the conventional fractionation schedule. AF is classified into two categories. One is decreasing in dose-per-fraction and increasing in total dose, so-called hyperfractionation (HF), which expands the difference in radio-sensitivity between tumor and normal tissue. On the other hand, shortening of overall treatment time, so-called accelerated hyperfractionation (AHF), prevents accelerated repopulation of tumor cells during radiotherapy. AF is rarely recognized as a standard therapy despite many reports about its efficacy against various cancers, totally. This is often used for head and neck cancer. However, the problem is that they usually improve local-control, but do not always improve survival. Although AHF is recognized as one of a standard treatment for small cell lung cancer, it is still objectionable and disputable. Besides these, efficacy of AF against non-small cell lung cancer, bladder cancer and malignant glioma, has been reported. However, AF is not considered as a standard treatment. Accompanied with spread out of stereotactic irradiation, dose-fractionation-time relationship becomes to be more important subject, especially hypofractionation, to clarify the new aspect of AF.

Dose Fractionation, Radiation↗
PubMed2003

Intraluminal low-dose-rate 192Ir brachytherapy combined with external beam radiotherapy and biliary stenting for unresectable extrahepatic bile duct carcinoma.

PURPOSE: To evaluate the results of combined-modality therapy, including external beam radiotherapy, intraluminal (192)Ir, and biliary stenting for extrahepatic bile duct carcinoma. MATERIALS AND METHODS: Between 1988 and 1998, 93 patients with unresectable extrahepatic bile duct carcinoma underwent definitive radiotherapy. The dose of external beam radiotherapy was 50 Gy in 25 fractions. Low-dose-rate (192)Ir was delivered at a dose of 27-50 Gy (mean 39.2) at 0.5 cm from the source. An expandable metallic endoprosthesis was used to establish an internal bile passage. RESULTS: The median survival was 12 months, with a 1-, 3-, and 5-year actuarial survival rate of 50%, 10%, and 4%, respectively. Tumor length, hepatic invasion, and distant metastasis significantly affected survival. Ninety-six percent of patients could successfully remove external drainage catheters. The actuarial biliary patency rate for these patients at 1, 3, and 5 years was 52%, 29%, and 18%, respectively. Tumor length, tumor diameter and T stage were significantly associated with the patency rate. Mild-to-severe gastroduodenal complications were observed in 32 patients and were significantly associated with the active length of (192)Ir and linear source activity. Eight patients had treatment-related biliary fistula. CONCLUSIONS: Our combined-modality therapy provided reasonable local control and improved the quality of life of patients with extrahepatic bile duct carcinoma. Because none of the treatment characteristics had any impact on survival or biliary patency, lower dose levels and/or a localized target volume are recommended to minimize morbidity.

Adult↗
PubMed2003

Evaluation of a forced-air-ventilated micro-isolation system for protection of mice against Pasteurella pneumotropica.

Studies to date have established that the physical environment inside cages can be controlled adequately by setting the intra-cage ventilation at 60 air changes per hour in a forced-air-ventilated micro-isolation system (FVMIS). In this study, the capability of FVMIS to prevent inter-cage transmission of microorganisms was evaluated using Pasteurella pneumotropica as a reference microorganism. One FVMIS rack and a conventional rack were used, and cages with mice positive for P. pneumotropica and those with P. pneumotropica-free mice were housed on both racks. The mice were examined for P. pneumotropica contamination every 4 weeks after initiating the experiment for 12 weeks using a polymerase chain reaction method. Some P. pneumotropica-free mice housed in open air cages in the conventional rack became positive for P. pneumotropica (four of 28 animals after 4 weeks; eight of 28 animals after 12 weeks), but all P. pneumotropica-free mice housed in the FVMIS cages remained negative for the bacterium throughout the experiment. The results demonstrate that FVMIS can prevent inter-cage transmission of P. pneumotropica when proper cage handling practice is under taken.

Animals↗
PubMed2002

Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H(+)-ATPase-like protein.

ShIF is a bone marrow stroma cell-derived factor originally identified to support proliferation of bone marrow cells in vitro. This protein shares high sequence homology to the yeast vacuolar H(+)-ATPase subunit, Vph1p, and the 116 kDa proton pump of the rat and bovine synaptic vesicle, Vpp1. We examined the function of ShIF in the proliferation of human umbilical vein endothelial cells (HUVEC). ShIF inhibited HUVEC proliferation in a dose-dependent manner. Recombinant ShIF added at 10 and 20 ng/ml inhibited HUVEC proliferation by 21.6 and 44.3%, respectively and increasing the concentration of ShIF to 100 ng/ml inhibited proliferation by as much as 55.5%. When HUVEC cells were cultured at various concentrations of ShIF in the presence of anti-ShIF antibody, the inhibitory effects of ShIF to HUVEC proliferation were abrogated by 89-91% indicating that the activity of ShIF to HUVEC was specific. HUVEC cultured in the presence of ShIF and bafilomycin, a specific inhibitor of ATPase, resulted to a 90% growth inhibition. Thus, ShIF may act as an antagonist to the ATPase complex by disrupting the production of cellular ATP thereby decreasing the ability of HUVEC to proliferate.

Animals↗
PubMed2002

Genetic approach and phenotype-based complementation screening for identification of stroma cell-derived proteins involved in cell proliferation.

The functional capacities of stromal cell lines to support stem cell activity are heterogeneous and the mechanism of how they support bone marrow cultures remains unclear. Recently, we reported a strategy of functional analysis in which a genetic approach is combined with phenotype-based complementation screening to search for a novel secreted growth factor from mouse bone marrow stroma called ShIF that supported proliferation of bone marrow cells. To investigate the role of stromal cells in hemopoiesis, we extended this strategy to search for stroma-derived proteins that induce cell proliferation by establishing stroma-dependent Ba/F3 mutants of three stroma cell lines from two mouse tissues. Seven stroma-dependent Ba/F3 mutants were used as responder cells to identify cDNAs from stroma cell lines whose products supported proliferation not only to the mutant cells but also to hemopoietic progenitor cells in vitro.

Animals↗
PubMed2002

[Percutaneous transhepatic central venous port implantation via the middle hepatic vein: a case report].

Percutaneous transhepatic central venous access with a subcutaneous infusion port was performed in a 34-year-old woman with extensive third-degree burns whose peripheral vessels were not available because of infection or dermatoplastic sites. This procedure could be done in the same way as the usual PTCD maneuver without serious complications. The infusion system functioned well, and the patient's alimentation could be carried out.

Adult↗