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21.
Inhibition of infiltration and angiogenesis by thrombospondin-1 in papillary thyroid carcinoma. 总被引:9,自引:0,他引:9
Katsuhiro Tanaka Hiroshi Sonoo Junichi Kurebayashi Tsunehisa Nomura Sumiko Ohkubo Yutaka Yamamoto Shigeru Yamamoto 《Clinical cancer research》2002,8(5):1125-1131
PURPOSE: Angiogenesis is essential for tumor growth and is controlled by the balance between angiogenic and antiangiogenic factors. We studied the expression of angiogenic factors and antiangiogenic factors in papillary thyroid carcinoma. EXPERIMENTAL DESIGN: We investigated immunohistochemically the expression patterns and levels of antiangiogenic factor and its receptor, thrombospondin-1 (TSP-1) and CD36, and four angiogenic factors, vascular endothelial growth factor (VEGF), VEGF-C, angiopoietin-2 (Ang-2), and Tie-2, in the primary tumors of 75 papillary thyroid carcinoma patients. We also examined the microvessel count (MVC), using CD31 staining. RESULTS: VEGF expression strongly correlated with other angiogenic factors. The cytoplasm of cancer cells stained positive for all factors. Tie-2 and TSP-1 receptor also appeared in endothelia of microvessels. TSP-1 inversely correlated with the degree of invasion of the primary tumor to other adjacent organs and with MVC. A higher MVC correlated with poorer survival. To clarify the balance between angiogenic and antiangiogenic factors in the same tumor, we calculated the ratio of each angiogenic factor against TSP-1 as the antiangiogenic factor. The ratios VEGF/TSP-1, VEGF-C/TSP-1, and Ang-2/TSP-1 significantly correlated with a higher MVC. Furthermore, the ratios VEGF/TSP-1 and Ang-2/TSP-1 significantly correlated with the degree of infiltration. CONCLUSIONS: To the best of our knowledge, this is the first report demonstrating that the balance between angiogenic and antiangiogenic factors correlates with distinct invasion to other organs and neovascularization of papillary thyroid carcinoma. 相似文献
22.
Kiyoshi Takagi Takuya Moriya Masafumi Kurosumi Kimako Oka Yasuhiro Miki Akiko Ebata Takashi Toshima Shoji Tsunekawa Hiroyuki Takei Hisashi Hirakawa Takanori Ishida Shin-ichi Hayashi Junichi Kurebayashi Hironobu Sasano Takashi Suzuki 《Hormones & cancer》2013,4(1):1-11
It is speculated that estrogens play important roles in the male breast carcinoma (MBC) as well as the female breast carcinoma (FBC). However, estrogen concentrations or molecular features of estrogen actions have not been reported in MBC, and biological significance of estrogens remains largely unclear in MBC. Therefore, we examined intratumoral estrogen concentrations, estrogen receptor (ER) α/ERβ status, and expression profiles of estrogen-induced genes in MBC tissues, and compared these with FBC. 17β-Estradiol concentration in MBC (n?=?4) was significantly (14-fold) higher than that in non-neoplastic male breast (n?=?3) and tended to be higher than that in FBC (n?=?7). Results of microarray analysis clearly demonstrated that expression profiles of the two gene lists, which were previously reported as estrogen-induced genes in MCF-7 breast carcinoma cell line, were markedly different between MBC and FBC. In the immunohistochemistry, MBC tissues were frequently positive for aromatase (63 %) and 17β-hydroxysteroid dehydrogenase type 1 (67 %), but not for steroid sulfatase (6.7 %). A great majority (77 %) of MBC showed positive for both ERα and ERβ, and its frequency was significantly higher than FBC cases. These results suggest that estradiol is locally produced in MBC tissue by aromatase. Different expression profiles of the estrogen-induced genes may associate with different estrogen functions in MBC from FBC, which may be partly due to their ERα/ERβ status. 相似文献
23.
Shiiki S Sonoo H Seki M Nomura T Hironou M Ookubo S Udagawa K Yamamoto Y Nakashima K Ikeda M Tanaka K Kurebayashi J 《Gan to kagaku ryoho. Cancer & chemotherapy》2006,33(10):1431-1435
We investigated 29 patients with advanced and recurrent breast cancers who underwent capecitabine therapy in the department. Patients'backgrounds: 41-89 years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six percent of patients were positive for ER and/or PgR. Multiorgan metastases occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases; skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who received chemotherapy was 93%, and the rate of those who received endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5 cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression (TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was 2-23 months (median length, 12 months). OS was significantly longer in patients who had therapeutic effects than in patients with no such effects. TTP was significantly longer in patients who had therapeutic effects and in those who had longer SD than in patients with no such effects. OS was significantly longer in patients who had TTP of 6 months or longer. Clinical benefit (presence vs. absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP. Capecitabine is expected to prolong the length of survival in patients who are able to continue treatment for 6 months or longer. 相似文献
24.
Fukushima K Takahashi T Takaguchi M Ueyama H Ito S Kurebayashi Y Kawanishi T McKimm-Breschkin JL Takimoto T Minami A Suzuki T 《Biological & pharmaceutical bulletin》2011,34(7):996-1000
Human parainfluenza virus type 1 (hPIV1) generally does not show visible plaques in common cell lines, including Lewis lung carcinoma-monkey kidney (LLC-MK(2)) cells, by plaque formation assays for human parainfluenza virus type 3 (hPIV3) and Sendai virus. In several conditions of the plaque formation assay, complete elimination of serum proteins in the overlay medium was necessary for visualization of hPIV1-induced plaque formation in LLC-MK(2) cells. We developed a plaque formation assay for hPIV1 isolation and titration in LLC-MK(2) cells using an initial overlay medium of bovine serum albumin-free Eagle's minimum essential medium containing agarose and acetylated trypsin for 4-6 d followed by a second overlay staining medium containing agarose and neutral red. The assay allowed both laboratory and clinical hPIV1 strains to form large plaques. The plaque reduction assay was also performed with rabbit anti-hPIV1 antibody as a general evaluation model of viral inhibitors to decrease both the plaque number and size. The results indicate that the plaque formation assay is useful for hPIV1 isolation, titration, evaluation of antiviral reagents and epidemiologic research. 相似文献
25.
Yutaka Kurebayashi Hanako Tsujikawa Katsutoshi Sugimoto Daisuke Yunaiyama Yoichi Araki Kazuhiro Saito Hiroshi Takahashi Tatsuya Kakegawa Takuya Wada Yusuke Tomita Masakazu Abe Yu Yoshimasu Hirohito Takeuchi Taiki Hirata Kentaro Sakamaki Kazuhiro Kakimi Toshitaka Nagao Takao Itoi Michiie Sakamoto 《Hepatology research》2023,53(10):1008-1020
26.
Goya K Kitamura T Inaba M Otsuki M Yamamoto H Kurebayashi S Sumitani S Saito H Kouhara H Kasayama S Kawase I 《Metabolism: clinical and experimental》2003,52(10):1302-1306
Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients. 相似文献
27.
Kurebayashi J 《Current opinion in obstetrics & gynecology》2008,20(1):51-54
PURPOSE OF REVIEW: Current topics on adjuvant therapy for premenopausal patients with breast cancer are reviewed. RECENT FINDINGS: The Early Breast Cancer Trialists' Collaborative Group overview showed that women under 50 received a remarkable benefit from postoperative chemotherapy and endocrine therapy. The impact of chemotherapy-induced amenorrhea on patient outcome remains to be defined. The addition of luteinizing-hormone-releasing hormone agonists to tamoxifen, chemotherapy or both significantly reduced both recurrence and death in premenopausal patients with endocrine-responsive breast cancer. Exploratory trials are investigating the use of more complete estrogen suppression with luteinizing-hormone-releasing hormone agonists with aromatase inhibitors. There is no consensus on how long these agonists should be used in the adjuvant setting. Chemotherapy-induced ovarian failure is frequently associated with infertility. The suppression of ovarian function using luteinizing-hormone-releasing hormone agonists during chemotherapy seems promising for preserving ovarian function. Chemotherapy-induced ovarian failure and prolonged luteinizing-hormone-releasing hormone agonist therapy cause premature menopausal symptoms. To minimize the menopausal symptoms, intervention strategies should be investigated. SUMMARY: There are a number of unresolved issues in terms of the optimal use of chemotherapy and endocrine therapy in premenopausal patients with breast cancer. Well-designed and well-organized randomized clinical trials are essential to resolve these issues. 相似文献
28.
K Fukuoka M Hirokawa M Shimizu Y Sadahira T Manabe J Kurebayashi H Sonoo 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》1999,107(8):762-766
We report a case of adenoid cystic carcinoma (ACC) of the breast with a prominent basaloid feature. The patient was a 62-year-old Japanese woman with a right breast mass, measuring 1.5 cm in diameter. Histologically, the tumor was composed of basal cell-like tumor cells, and it was originally diagnosed as invasive ductal carcinoma. The presence of PAS-positive basement membrane material around the tumor cell nests may be a diagnostic clue to ACC. The prognosis of ACC of the breast is considered to be favorable. However, basaloid type ACC may represent a poor prognosis, since our case revealed an aggressive behavior in spite of its small size. 相似文献
29.
Mark Duquette Peter M. Sadow Amjad Husain Jennifer N. Sims Zeus A. Antonello Andrew H. Fischer Chen Song Elena Castellanos-Rizaldos G. Mike Makrigiorgos Junichi Kurebayashi Vania Nose Paul Van Hummelen Roderick T. Bronson Michelle Vinco Thomas J. Giordano Dora Dias-Santagata Pier Paolo Pandolfi Carmelo Nucera 《Oncotarget》2015,6(40):42445-42467
BRAFV600E mutation exerts an essential oncogenic function in many tumors, including papillary thyroid carcinoma (PTC). Although BRAFV600E inhibitors are available, lack of response has been frequently observed. To study the mechanism underlying intrinsic resistance to the mutant BRAFV600E selective inhibitor vemurafenib, we established short-term primary cell cultures of human metastatic/recurrent BRAFV600E-PTC, intrathyroidal BRAFV600E-PTC, and normal thyroid (NT). We also generated an early intervention model of human BRAFV600E-PTC orthotopic mouse. We find that metastatic BRAFV600E-PTC cells elicit paracrine-signaling which trigger migration of pericytes, blood endothelial cells and lymphatic endothelial cells as compared to BRAFWT-PTC cells, and show a higher rate of invasion. We further show that vemurafenib therapy significantly suppresses these aberrant functions in non-metastatic BRAFV600E-PTC cells but lesser in metastatic BRAFV600E-PTC cells as compared to vehicle treatment. These results concur with similar folds of down-regulation of tumor microenvironment–associated pro-metastatic molecules, with no effects in BRAFWT-PTC and NT cells. Our early intervention preclinical trial shows that vemurafenib delays tumor growth in the orthotopic BRAFWT/V600E-PTC mice. Importantly, we identify high copy number gain of MCL1 (chromosome 1q) and loss of CDKN2A (P16, chromosome 9p) in metastatic BRAFV600E-PTC cells which are associated with resistance to vemurafenib treatment. Critically, we demonstrate that combined vemurafenib therapy with BCL2/MCL1 inhibitor increases metastatic BRAFV600E-PTC cell death and ameliorates response to vemurafenib treatment as compared to single agent treatment. In conclusion, short-term PTC and NT cultures offer a predictive model for evaluating therapeutic response in patients with PTC. Our PTC pre-clinical model suggests that combined targeted therapy might be an important therapeutic strategy for metastatic and refractory BRAFV600E-positive PTC. 相似文献
30.