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81.
Ayumi Denda Wakashi Kitayama Hideki Kishida Nao Murata Masahiro Tsutsumi Toshifumi Tsujiuchi Dai Nakae Yoichi Konishi 《Cancer science》2002,93(2):125-132
Development of hepatocellular carcinomas in rats caused by a choline-deficient, L-amino acid defined (CDAA) diet, usually associated with fatty liver, fibrosis, cirrhosis and oxidative DNA damage, has been recognized as a useful model of hepatocarcinogenesis caused by endogenous factors. In the present study, in order to further explore involved factors and genes, we established an equivalent model in spontaneous liver tumor-resistant C57BL/6J mice. Six-week-old males and females were continuously fed the CDAA diet and histological liver lesions and oxidative DNA damage due to 8-hydroxydeoxyguanosine (8-OHdG) were examined after 22, 65 and 84 weeks. In male mice, fatty change and fibrosis were evident at 22 weeks, and preneoplastic foci of altered hepatocytes were seen at an incidence of 8/8 (100%) and a multiplicity of 6.6±4.0 per mouse at 65 weeks. Hepatocellular adenomas and carcinomas developed at incidences of 16/24 (66.7%) and 5/ 24 (20.8%), and multiplicities of 1.421±1.32 and 0.29±0.62, respectively, at 84 weeks. The female mice exhibited resistance to development of these lesions. The CDAA diet also increased 8-OHdG levels in male but not female mice. These results indicate that a CDAA diet causes hepatocellular preneoplastic foci, adenomas and carcinomas associated with fibrosis and oxidative DNA damage in mice, as in rats, providing a hepatocarcinogenesis model caused by endogenous factors in mice. 相似文献
82.
Proteasome inhibition circumvents solid tumor resistance to topoisomerase II-directed drugs 总被引:10,自引:0,他引:10
Physiological cell conditions, such as glucose deprivation and hypoxia, play a role in developing drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase IIalpha (topo IIalpha), rendering cells resistant to topo II-targeted drugs, such as etoposide and doxorubicin. We show here that inhibition of proteasome attenuated drug resistance by inhibiting topo IIalpha depletion induced by glucose starvation and hypoxia. topo IIalpha restoration was seen only at the protein levels, indicating that the topo IIalpha protein depletion occurred through a proteasome-mediated degradation mechanism. The stress-induced etoposide resistance was effectively prevented in vitro by the proteasome inhibitor lactacystin in both intrinsically resistant and sensitive tumor cells (colon cancer HT-29 and ovarian cancer A2780 cells, respectively). Furthermore, lactacystin effectively enhanced the antitumor activity of etoposide in the refractory HT-29 xenograft. These results indicate that lactacystin could serve as a new therapeutic agent to circumvent resistance to topo II-targeted chemotherapy in solid tumors. 相似文献
83.
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85.
Yamamichi N Yamamichi-Nishina M Mizutani T Watanabe H Minoguchi S Kobayashi N Kimura S Ito T Yahagi N Ichinose M Omata M Iba H 《Oncogene》2005,24(35):5471-5481
86.
87.
Evaluation of TS-1 based treatment and expression of thymidylate synthase and dihydropyrimidine dehydrogenase on oral squamous cell carcinoma 总被引:1,自引:0,他引:1
Seventeen oral squamous cell carcinoma (SCC) patients underwent chemotherapy with TS-1 (8 males and 9 females, mean age; 75.1 years, range; 47-102 years). TS-1 permitted five cases of oral chemotherapy on an outpatient basis and 8 cases in elder patients over 80-years of age. Excepting five patients who underwent TS-1 therapy as post-operative adjuvant chemotherapy, the therapeutic efficacy of TS-1 in 12 patients with or without irradiation, surgery or chemotherapy resulted in 3 cases of complete response (CR), 6 cases of partial response (PR), 3 cases of stable disease (SD), with no progressive disease (PD) cases (overall response rate; 75%). SCC samples obtained from biopsy were immunohistochemically stained with anti-TS and DPD polyclonal antibody. Although the statistical significance was not clear, the expression of TS and DPD for CR cases was lower than that for SD cases. TS-1 therapy improved quality of life (QOL) especially in elder patients with oral SCC, and our immunohistochemical results suggested the predictive possibilities of TS and DPD expression in response to TS-1. 相似文献
88.
The source of patellofemoral pain is a common orthopaedic complaint that often is difficult to determine because of the lack of correlation between symptoms and specific clinical measurements. Excessive joint contact stresses resulting from patellofemoral malalignment and pathologic femoral shape often are associated with this pain. These measures are likely sensitive to the limb position (orientation and position relative to the imaging system with which they are quantified). Because of this sensitivity, the measures have large variations and do not show correlations with subjective symptoms. The purpose of this study was to determine if varying limb position resulted in significant changes in standard clinical measures of patellofemoral alignment and femoral shape. This dependence was investigated by simulating alterations in limb position through resectioning of three-dimensional magnetic resonance image sets (20 healthy knees) to create axial images with altered orientation (eight images) or location (four images) relative to a fixed reference. By quantifying the variability of the clinical measures across all images, it was determined that simulated alterations in limb position produced greater variability in femoral shape and patellofemoral alignment measures than the variability seen across control subjects. This indicated that a standardized method for establishing limb position relative to the imager is warranted. 相似文献
89.
Shimooka N Utsunomiya R Kubo S Hasegawa H Tominaga S Yoshimine T 《No shinkei geka. Neurological surgery》2005,33(6):595-598
A 59-year-old man presented with generalized convulsion. MR imaging demonstrated a homogeneously enhanced dural lesion infiltrating the parenchyma in the right parietal region. He had no history of sinusitis and the lesion a resembled malignant tumors, so surgical treatment was performed. The histopathological studies showed pachymeningitis extending to the cerebral parenchyma, so the diagnosis of pachymeningoencephalitis was made. After the operation, the patient had no neurological deficits and anticonvulsant therapy was continued. We report the third case of idiopathic local pachymenigoencephalitis that we could range extensively in the world. The clinical features and pathogenesis are discussed. 相似文献
90.
Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes 总被引:4,自引:0,他引:4
Kadoi Y Saito S Fujita N Goto F 《The Journal of thoracic and cardiovascular surgery》2005,129(3):576-583
OBJECTIVES: The mechanisms of postoperative cognitive dysfunction in patients with diabetes after coronary artery bypass grafting are not fully understood. We sought to determine which type 2 diabetes-related factors contributed to postoperative cognitive dysfunction at 7 days and 6 months after coronary artery bypass grafting. METHODS: One hundred eighty patients with type 2 diabetes who were scheduled for elective coronary artery bypass grafting were studied. As a control group, 100 patients without diabetes mellitus matched for age, sex, and educational level were examined. Hemodynamic parameters (arterial and jugular venous blood gas values) were measured during cardiopulmonary bypass. All patients underwent a battery of neurologic and neuropsychologic tests the day before surgery, 7 days after surgery, and 6 months after surgery. RESULTS: Age (odds ratio 1.5, 95% confidence interval 1.3-1.8, P = .03), presence of hypertension (odds ratio 1.8, 95% confidence interval 1.3-2.0, P = .01), jugular venous oxygen saturation less than 50% time (odds ratio 1.5, 95% confidence interval 1.1-2.0, P = .045), presence of ascending aorta atherosclerosis (odds ratio 1.5, 95% confidence interval 1.1-2.6, P = .01), diabetic retinopathy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .01), and insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .05), were associated with cognitive impairment at 7 days. Insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.8, P = .01), diabetic retinopathy (odds ratio 1.3, 95% confidence interval 1.2-2.9, P < .01), and hemoglobin A 1c (odds ratio 1.9, 95% confidence interval 1.3-3.1, P = .047) were associated with cognitive impairment at 6 postoperative months. CONCLUSIONS: Insulin therapy, diabetic retinopathy, and hemoglobin A 1c were factors in cognitive impairment at 7 days and 6 months after coronary artery bypass grafting in patients with type 2 diabetes. 相似文献