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Genetic Polymorphisms of Hepatic ABC-Transporter in Patients with Hepatocellular Carcinoma

Journal of Cancer Therapy 2010年第3期1卷 114-123页

作者： Minoru Fukuda Yasutsugu Kawahara takeshi hirota Setsuko Akizuki Shigeto Shigeto Hisato Nakajima Ichiro Ieiri Akihiro Ohnishi 不详

We examined whether genetic polymorphisms of efflux transporters in hepatocytes are associated with susceptibility to develop hepatocellular carcinoma (HCC). Genetic polymorphisms of drug transporters expressed in hepatocytes were analyzed using DNA samples from hepatitis C virus (HCV)-seropositive cirrhotic patients with HCC (n = 58), and allele and haplotype frequencies were compared with those in healthy subjects (n = 61). To search for single nucleotide polymorphisms (SNPs) in HCC susceptibility genes, 34 SNPs in 6 efflux transporters [MDR1 (ABCB1), ABCC1, ABCC2, ABCC3, ABCG2 and ABCB11] were determined. No significant association was observed for any single SNP;however, some haplotypes in ABCC1 and ABCB11 were associated with HCC. Furthermore, three combinations of SNPs (3435C > T in ABCB1 and 825T > C in ABCC1), (3435C > T in ABCB1 and -15281_-15278CTCT > delete in ABCB11), and (825T > C in ABCC1 and -15281_-15278CTCT > delete in ABCB11) were significantly associated with HCC. The present study suggests that genetic variations of ABC transporters such as ABCB1, ABCB11, and ABCC1 are associated with susceptibility to develop HCC, implying that aberrant hepatic clearance of toxic substances may increase the risk of hepatocarcinogenesis. Further studies of how these polymor-phisms are associated with phenotypic differences are warranted.

关键词： Genetic Polymorphism Drug Transporter Hepatitis C Virus Hepatocellular Carcinoma

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Histopathological Evidence for Irradiation Angiopathy in Head and Neck Cancer

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International Journal of Otolaryngology and Head & Neck Surgery 2015年第2期4卷 108-114页

作者： Nobuhiro Uwa Hiroyuki Hao Yoshitane Tsukamoto Tomonori Terada Kosuke Sagawa takeshi Mohri Takashi Daimon Hiroshi Doi Yohei Sotsuka Guillaume van Eys Marie-Luce Bochaton-Piallat Seiichi hirota Masafumi Sakagami Department of Otolaryngology Hyogo College of Medicine Nishinomiya Japan Department of Surgical Pathology Hyogo College of Medicine Nishinomiya Japan Department of Biostatistics Hyogo College of Medicine Nishinomiya Japan Department of Radiology Hyogo College of Medicine Nishinomiya Japan Department of Plastic Surgery Hyogo College of Medicine Nishinomiya Japan Department of Genetics and Cell Biology University of Maastricht Maastricht The Netherlands Department of Pathology and Immunology University of Geneva-CMU Geneva Switzerland

Objective: To evaluate the incidence of cervical angiopathy caused by radiation therapy for head and neck cancer. Methods: Segments of 57 cervical arteries were obtained during surgery for head and neck malignant tumors and divided into two groups (irradiated group and non-irradiated group) based on the treatment prior to vascular resection. In order to evaluate vascular injury after radiation therapy, we examined the degree of medial atrophy, medial fibrosis, smooth muscle cell (SMC) differentiation in the media and intima, intimal hyperplasia and endothelial cell (EC) injury. Sections of arterial segments were stained with hematoxylin-eosin, Elastica van Gieson and Masson’s trichrome, and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, S100A4 and CD31 in the resected vessels was conducted. Results: The median interval between the completion of radiation therapy and vascular resection was nine months. No significant differences were observed between the two groups in terms of medial atrophy, medial fibrosis and intimal hyperplasia. The ratio of the smoothelin-positive area per α-SMA-positive area in the media and the S100A4-positive proportion in the intima, indicating the degree of differentiation of the medial SMC and dedifferentiation of the intimal SMC, respectively, showed no significant differences, despite the tendency toward a lower smoothelin-positive area per α-SMA-positive area in the media of the irradiated arteries. The EC coverage revealed on CD31 immunohistochemistry was significantly decreased, with mural thrombus adhesion, in the irradiated group. Conclusions: The ECs of small arteries are damaged by irradiation. Although we did not confirm the statistical significance of medial SMC dedifferentiation, a decreased expression of smoothelin tended to be observed in the media of the irradiated arteries. Our findings provide histopathological evidence of irradiation angiopathy in head and neck cancer and may help to improve the surgi

关键词： Angiopathy Endothlial Cell Pathology Radiation Head and Neck

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