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A49T, V89L and TA repeat polymorphisms of steroid 5α-reductase type II and breast cancer risk in Japanese women
Chunxia Yang, Nobuyuki Hamajima, Hiroji Iwata, Toshiko Saito, Keitaro Matsuo, Kaoru Hirose, Manami Inoue, Toshiro Takezaki, Kazuo Tajima
Breast Cancer Research , 2002, DOI: 10.1186/bcr445
Abstract: The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods.The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36–1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13–2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24–0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found.This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.Breast cancer is a hormone-related cancer, as are cancers of the endometrium, ovary, and prostate [1]. Although the molecular mechanisms involved in initiation and progression are poorly understood, there is evidence that extracellular levels of androgens are associated with the development of breast cancer [2,3]. Nested case–control studies have shown that increased circulating levels of testosterone elevate the risk of breast cancer [4-6]. Experimental studies suggest, however, that androgens exert a potent antiproliferative effect on the growth of several hormone-sensitive human breast cancer cells under both basal and estrogen-induced incubation conditions in vitro[7], as well as in vivo, using ZR-75-1 human breast cancer cells in nude mice [8]. Androgens have been used for the treatment of breast cancer [9,10].Steroid 5α-reductase converts testosterone to the metabolically more active dihydrotestosterone, whic
Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients
Tatsuya Toyama, Zhenhuan Zhang, Mariko Nishio, Maho Hamaguchi, Naoto Kondo, Hirotaka Iwase, Hiroji Iwata, Satoru Takahashi, Hiroko Yamashita, Yoshitaka Fujii
Breast Cancer Research , 2007, DOI: 10.1186/bcr1682
Abstract: The genotypes of TP53 codon 72 and MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients (median follow-up, 61.7 months). The effects of several variables on survival were tested by Cox's proportional hazards regression analysis.We showed that the Pro/Pro genotype of TP53 codon 72 was associated with poorer disease-free survival (DFS) than other genotypes by Kaplan-Meier analysis (P = 0.049) and multivariate Cox's proportional hazards regression analysis (P = 0.047, risk ratio of recurrence = 1.67), whereas MDM2 SNP309 status was not associated with DFS. The association of the Pro/Pro TP53 genotype with poorer DFS was especially significant in patients who received adjuvant chemotherapy (P = 0.009). In contrast, among the patients who had received adjuvant hormonal therapy or no adjuvant systemic therapy, TP53 codon 72 genotype was not associated with DFS.The Pro/Pro genotype of TP53 codon 72 appears to be an independent prognostic marker in breast cancer patients.The TP53 tumor suppressor pathway is well-known to be crucial for maintaining genomic integrity and preventing cells from undergoing oncogenic transformation [1,2]. MDM2 plays a key role in regulating the TP53 pathway by binding directly to the p53 protein, inhibiting its activity and mediating degradation via the ubiquitination system [3]. p53 also positively regulates MDM2 expression, thereby creating a negative feedback loop [3]. Overexpression of MDM2 is observed both in epithelial cells of transgenic mice with induced mammary carcinomas [4] and in multiple human tumors, including breast cancer [5-7].The TP53 codon 72 Arg>Pro (CGC to CCC) polymorphism of exon 4 [8] (National Center for Biotechnology Information single-nucleotide polymorphism (SNP) identification number rs1042522) has been suggested to play a role in several different cancer types. These two variant protein forms may behave differently, as the Arg/Arg genotype has been reported to induce apoptosis more effectively t
Possible association of β2- and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer
Xin-En Huang, Nobuyuki Hamajima, Toshiko Saito, Keitaro Matsuo, Mitsuhiro Mizutani, Hiroji Iwata, Takuji Iwase, Shigeto Miura, Tsutomu Mizuno, Shinkan Tokudome, Kazuo Tajima
Breast Cancer Research , 2001, DOI: 10.1186/bcr304
Abstract: A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment.Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99).A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association.The incidence of breast cancer has increased greatly in Japan over the past 2 decades [1], and it has been estimated that breast cancer would become the most common malignant disease in Japanese females by the year 2000 [2]. One of the main risk factors for breast cancer in menopausal women is obesity [3,4]. The increased amount of adipose tissue after menopause is considered to elevate estradiol production, which in turn increases the risk for breast cancer. Thus, genetic traits that are related to obesity may influence the risk of postmenopausal breast cancer in an indirect manner.It is now known that the adrenergic system plays a key role in regulating energy balance through both thermogenesis and lipid mobilization from brown or white adipose tissues [5,6], and that human fat cells are equipped with adrenergic receptors (adrenoceptors) β1, β2 (ADRB2) and β3 (ADRB3). The degree of affi
Zero Sound Propagation in Femto-Scale Quantum Liquids  [PDF]
Yoritaka Iwata
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.36064
Abstract: Charge equilibration has been recognized as a dominant process at the early stage of low-energy heavy-ion reactions. The production of exotic nuclei is suppressed under the appearance of charge equilibration, in which the proton-neutron ratios of the final reaction products are inevitably averaged. Therefore charge equilibration plays one of the most crucial roles in the synthesis of chemical elements. Focusing on how and when the charge equilibration takes place, zero sound propagation in femto-scale quantum liquids is explained.
Alternative Infinitesimal Generator of Invertible Evolution Families  [PDF]
Yoritaka Iwata
Journal of Applied Mathematics and Physics (JAMP) , 2017, DOI: 10.4236/jamp.2017.54071
A logarithm representation of evolution operators is defined. Generators of invertible evolution families are characterized by the logarithm representation. In this article, using the logarithm representation, a concept of evolution operators without satisfying the semigroup property is introduced. In conclusion the existence of alternative infinitesimal generator is clarified.
Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2 homodimers in a clinic-based cohort of patients with metastatic breast cancer
Masakazu Toi, Jeff Sperinde, Weidong Huang, Shigehira Saji, John Winslow, Xueguang Jin, Yuping Tan, Shinji Ohno, Seigo Nakamura, Hiroji Iwata, Norikazu Masuda, Kenjiro Aogi, Satoshi Morita, Christos Petropoulos, Michael Bates
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-56
Abstract: HERmark, a proximity-based assay designed to detect and quantitate protein expression and dimerization in formalin-fixed paraffin-embedded (FFPE) tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples from patients with MBC. Assay results were correlated with OS using univariate Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses.Initial analyses revealed a parabolic relationship between continuous measures of HER2 expression and risk of death, suggesting that the assumption of linearity for the HER2 expression measurements may be inappropriate in subsequent multivariate analyses. Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2-expressing group.These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.Over-expression of HER2 has been linked to both adverse prognosis and improved responsiveness to treatment with trastuzumab (Herceptin, Genentech) in a sub-population of metastatic breast cancers [1-5]. Trastuzumab offers significant disease-free and overall survival advantages in both the metastatic and adjuvant settings in patients with HER2 over-expressing tumors [6-11]. Currently, the selection of patients with breast cancer for treatment with trastuzumab is based on the measurement of HER2 receptor protein expression by immunohistochemistry (IHC), or by the presence of HER2 gene amplification as detected by FISH. Despite the success of trastuzumab, recent data from NCCTG 9831, NSABP B-31, and CALGB 150002 have called into question the accuracy of the current methods used to identify those patients who are most likely to benefit from treatment with trastuzumab [12-14]. New approaches to the accurate quantitation of HE
Development of a New Rapid Isolation Device for Circulating Tumor Cells (CTCs) Using 3D Palladium Filter and Its Application for Genetic Analysis
Akiko Yusa, Makoto Toneri, Taisuke Masuda, Seiji Ito, Shuhei Yamamoto, Mina Okochi, Naoto Kondo, Hiroji Iwata, Yasushi Yatabe, Yoshiyuki Ichinosawa, Seichin Kinuta, Eisaku Kondo, Hiroyuki Honda, Fumihito Arai, Hayao Nakanishi
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088821
Abstract: Circulating tumor cells (CTCs) in the blood of patients with epithelial malignancies provide a promising and minimally invasive source for early detection of metastasis, monitoring of therapeutic effects and basic research addressing the mechanism of metastasis. In this study, we developed a new filtration-based, sensitive CTC isolation device. This device consists of a 3-dimensional (3D) palladium (Pd) filter with an 8 μm-sized pore in the lower layer and a 30 μm-sized pocket in the upper layer to trap CTCs on a filter micro-fabricated by precise lithography plus electroforming process. This is a simple pump-less device driven by gravity flow and can enrich CTCs from whole blood within 20 min. After on-device staining of CTCs for 30 min, the filter cassette was removed from the device, fixed in a cassette holder and set up on the upright fluorescence microscope. Enumeration and isolation of CTCs for subsequent genetic analysis from the beginning were completed within 1.5 hr and 2 hr, respectively. Cell spike experiments demonstrated that the recovery rate of tumor cells from blood by this Pd filter device was more than 85%. Single living tumor cells were efficiently isolated from these spiked tumor cells by a micromanipulator, and KRAS mutation, HER2 gene amplification and overexpression, for example, were successfully detected from such isolated single tumor cells. Sequential analysis of blood from mice bearing metastasis revealed that CTC increased with progression of metastasis. Furthermore, a significant increase in the number of CTCs from the blood of patients with metastatic breast cancer was observed compared with patients without metastasis and healthy volunteers. These results suggest that this new 3D Pd filter-based device would be a useful tool for the rapid, cost effective and sensitive detection, enumeration, isolation and genetic analysis of CTCs from peripheral blood in both preclinical and clinical settings.
La conférence nationale souveraine et la démocratisation au Togo: du point de vue de la société civile
Takuo Iwata
Africa Development , 2000,
Abstract: The aim of this article is to analyse the process of democratic transition instituted by the Sovereign National Conference (SNC) in Togo, from the standpoint of the notion of civil society. In Togo, despite the itarian regime instituted by General Eyadema has remained in power since 1967, the Togolese had lived a period of hope when there had a beginning of democratic transition initiated by the SNC. The SNC is the result of the maturity of citizens associations, which had opened positive perspectives for the future of politics in this country. This conference has been of great importance in the political history of Africa. This study proposes to analyse the democratisation process in Togo from the standpoint of the SNC. But it also aims at thinking of the democratisation of other African countries, especially those who have organised a SNC, and studying the relationship between African policy and the notion of civil society. (Africa Development: 2000 XXV (3&4): 135-160)
Genecialist manifesto: overcoming the “class struggle” in medicine
Iwata K
International Journal of General Medicine , 2013,
Abstract: Kentaro Iwata Division of Infectious Diseases, Kobe University Hospital, Kobe, Hyogo, Japan Abstract: Generalists and specialists are often considered two completely distinct species, which culminates in the establishment of a concept of dichotomy. However, these dichotomy can at times fuel tension and even erupt into open conflict. In order to resolve this issue, the author herein proposes the concept of a “genecialist.” The genecialist refers to a hybrid comprising elements inherent to both generalists and specialists. This potentially overcomes the multitude of issues associated with both generalists and specialists in the practical aspects of medicine. The coalescence of these two contrarieties may hold the key to improving the future of health care. Mediating and integrating both categories into one consolidated entity carries the potential to stem the tide of class warfare between generalists and specialists. Keywords: genecialist, aufheben, generalist, specialist, asymmetry
Spin-orbit force contribution to dissipative dynamics
Iwata Yoritaka
EPJ Web of Conferences , 2012, DOI: 10.1051/epjconf/20122107001
Abstract: UA procedure of obtaining nucleus-nucleus potentials from time-dependent density functional calculations is presented. The role of the spin-orbit force in heavy-ion collision dynamics is studied with respect to the nucleus-nucleus potential. Consequently a novel dissipation mechanism, which should not be classified into the wall-window type dissipation, is proposed.
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