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51.
Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis 总被引:4,自引:0,他引:4
Nomura M Watari J Yokota K Saitoh Y Obara T Kohgo Y 《Virchows Archiv : an international journal of pathology》2000,437(1):17-24
Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether
cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI),
apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised
of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas
with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic
cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry
for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas.
PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat
elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and
2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with
LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and
in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar
among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis
not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.
Received: 1 July 1999 / Accepted: 17 January 2000 相似文献
52.
Jun Nakura Lin Ye Koichi Kihara Hidehisa Yamagata Kouzin Kamino Yusuke Nakamura Tetsuro Miki Toshio Ogihara 《Journal of human genetics》1995,40(3):281-282
Two polymorphic dinucleotide (CA) repeat clones were isolated from cosmids, cCI8-1121 and cCI8-1199, mapped to chromosome 8p11.2-p12. 相似文献
53.
Hiroyoshi Suzuki Miburu Emi Akira Komiya Yoshiyuki Fujiwara Ryuichi Yatani Yusuke Nakamura Jun Shimazaki 《Genes, chromosomes & cancer》1995,13(3):168-174
Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p2 1.3 flanked by markers cMSR-32 and C18- 105 1. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer. © 1995 Wiley-Liss, Inc. 相似文献
54.
Masafumi Ito Atsuko Nakagawa Atsuo Nakayama Yutaka Uno Izumi Takahashi Junpei Asai 《Pathology international》1990,40(2):149-152
Malignant salivary gland tumors in children are very rare. This report describes the autopsy of a child with parotid gland cancer. The patient, a 10 month old girl, was admitted to the Nagoya First Red Cross Hospital with facial nerve palsy. lncisional biopsy of a post-auricular tumor was performed, and undifferentiated carcinoma was diagnosed. The patient died 6 months later of respiratory failure due to pulmonary lymphangitis carcinomatosis. Light and electron microscopic and immunohistochemical examinations of the tumor tissue were performed. The tumor cells were arranged in a medullary, sheet-like manner. Keratinization or mucus lakes were not observed. PAS-alcian blue staining demonstrated intracytoplasmic mucus as granules, and also small intercellular droplets of mucus that might otherwise have been unnoticed. Ultrastructurally, some of the tumor cells had tonofilament-like keratin filaments, and also small hollow spaces bounded by microvilli and containing secretory particles. These were stained by antisera against CEA and keratin. These findings are suggestive of differentiation to mucoepider-moid carcinoma. We also review and discuss malignant salivary tumors of epithelial origin in children. Acta Pathol Jpn 40: 149–152, 1990. 相似文献
55.
Immunohistochemical detection of hepatocellular carcinoma in the setting of ongoing necrosis after radiofrequency ablation. 总被引:3,自引:0,他引:3
Tomoo Itoh Yasuko Orba Hidehiro Takei Yusuke Ishida Makoto Saitoh Hideaki Nakamura Takashi Meguro Shoichi Horita Miri Fujita Kazuo Nagashima 《Modern pathology》2002,15(2):110-115
After radiofrequency ablation (RFA), hepatocellular carcinoma undergoes complete necrosis and an ongoing necrosis that is irreversible and characterized histologically by disrupted cell outlines, homogenous cytoplasmic eosinophilia, and preserved nuclear staining, with the cells appearing quite distinct from viable cancer cells. Antibody to detect single-stranded DNA (ssDNA) specifically labeled nuclei in the setting of ongoing necrosis, but not viable tumor cells, whereas human mitochondrial antibody labeled the cytoplasm of viable cells but not cells of ongoing necrosis. The results demonstrate that RFA causes denaturation of both DNA and proteins and that the immunohistochemistry of ssDNA and mitochondrial protein is useful in detection of ongoing necrosis after RFA and provides pathological information on the validity of this procedure. 相似文献
56.
Makito Hirano Hirohide Asai Takao Kiriyama Yoshiko Furiya Takaaki Iwamoto Tomohisa Nishiwaki Aya Yamamoto Toshio Mori Satoshi Ueno 《Neuroscience letters》2007
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is caused by mutations in the gene encoding aprataxin (APTX). Although several in vitro findings proposed that impaired enzymatic activities of APTX are responsible for EAOH/AOA1, potential instability of mutant proteins has also been suggested as the pathogenesis based on in vivo finding that mutant proteins are almost undetectable in EAOH/AOA1 tissues or cells. The present study aimed to experimentally prove instability of mutant proteins in neuronal cells, the cell type preferentially affected by this disease. Results of pulse-chase experiments demonstrated that all of the disease-associated mutants had extremely shorter half-lives than the WT. We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells. 相似文献
57.
Mutsuo Furihata Tamotsu Takeuchi Jun Iwata Hiroshi Sonobe Yuji Ohtsuki Akihiko Wakatsuki Nobuyuki Morioka Yusuke Sagara 《Pathology international》1998,48(12):967-973
Primary ovarian angiosarcoma is extremely rare. Only 16 cases have histologicaliy been reported to date In the Ilterature. A case of angiosarcoma arising In the right ovary of a 46-year-old female is presented. Grossly, the resected right ovary was completely replaced by a solid tumor mass, which revealed multiple necrotic and/or hemorrhagic foci. This case revealed the typical histological features of angiosarcoma with sinusoldal and solid patterns of anaplastic tumor cells. Immunohlstochemically, tumor cells were strongly and diffusely positive for CD31 and CD34, in particular, along the cytoplasmic membrane of the tumor cells. Ultrastructurally, tumor cells possessed the intermediate junctions between tumor cells, discontinuous basal laminae attached to the irregularly shaped blood vessels and occasional cytoplasmic pinocytotlc vesicles. These findings confirmed the case as being one of angiosarcoma of the ovary. The patient died 9 months after surgery as a result of developed multlfocal brain metastases. A total of 17 cases reported as primary ovarian anglosarcoma, including this presented case, are clinicopathologically reviewed. 相似文献
58.
59.
Yamazaki K McGovern D Ragoussis J Paolucci M Butler H Jewell D Cardon L Takazoe M Tanaka T Ichimori T Saito S Sekine A Iida A Takahashi A Tsunoda T Lathrop M Nakamura Y 《Human molecular genetics》2005,14(22):3499-3506
The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations. 相似文献
60.
Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839) 总被引:7,自引:0,他引:7
Kakiuchi S Daigo Y Ishikawa N Furukawa C Tsunoda T Yano S Nakagawa K Tsuruo T Kohno N Fukuoka M Sone S Nakamura Y 《Human molecular genetics》2004,13(24):3029-3043
Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and quality-of-life of a subset of patients with advanced non-small cell lung cancer (NSCLC). However, a large portion of the patients showed no effect to this agent. To establish a method to predict the response of NSCLC patients to gefitinib, we used a genome-wide cDNA microarray to analyze 33 biopsy samples of advanced NSCLC from patients who had been treated with an identical protocol of second to seventh line gefitinib monotherapy. We identified 51 genes whose expression differed significantly between seven responders and 10 non-responders to the drug. We selected the 12 genes that showed the most significant differences to establish a numerical scoring system (GRS, gefitinib response score), for predicting response to gefitinib treatment. The GRS system clearly separated the two groups without any overlap, and accurately predicted responses to the drug in 16 additional NSCLC cases. The system was further validated by the semi-quantitative RT-PCR, immunohistochemistry and ELISA for serological test. Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro. Our results suggested that sensitivity of a given NSCLC to gefitinib can be predicted according to expression levels of a defined set of genes that may biologically affect drug sensitivity and survival of lung cancer cells. Our scoring system might eventually lead to achievement of personalized therapy for NSCLC patients. 相似文献