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Taro Shuin

Publications and source records attributed to Taro Shuin.

At least 19 recordsLinked to original sources
PubMed2026

Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.

Bladder cancer is the ninth most common cancer worldwide, caused by genetic and environmental risk factors. Here, we report the findings of a multi-population meta-analysis of genome-wide association studies, including 32,470 individuals with and 1,753,462 without bladder cancer. We identify 70 independent risk loci, of which 43 are novel. Using a 70-marker polygenic risk score (HR = 1.63 per standard deviation), we increase the area under the curve from 0.71 (baseline risk model) to 0.75. Integrative analyses reveal the enrichment of the associated variants within accessible chromatin regions, and of the prioritized genes within pathways for xenobiotic metabolism and smoking behavior. Specifically, we show that the 15q25.1 variant rs71581744-ACCCC/A co-localizes with tissue-specific CHRNA3 expression, modulates mRNA stability, and associates with risk of muscle-invasive bladder cancer among current smokers. Together, these findings substantially expand the known genetic architecture of bladder cancer risk and highlight the germline regulation of smoking behavior as a mechanism driving bladder cancer susceptibility.

Humans↗
PubMed2007

Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapy.

To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This scoring system had clearly distinguished the responder group from the non-responder group. To further validate the clinical significance of the system, we applied it to 22 additional cases of bladder cancer patients and found that the scoring system correctly predicted clinical response for 19 of the 22 test cases. The group of patients with positive predictive scores had significantly longer survival than that with negative scores. When we compared our results with a previous report describing the prognosis of the patients with cystectomy alone, the results imply that patients with positive scores are likely to benefit from M-VAC neoadjuvant chemotherapy, but that the chemotherapy would shorten the lives of patients with negative scores. We are confident that our prediction system to M-VAC therapy should provide opportunities for achieving better prognosis and improving the quality of life of patients. Taken together, our data suggest that the goal of 'personalized medicine', prescribing the appropriate treatment regimen for each patient, may be achievable by selecting specific sets of genes for their predictive values according to the approach shown here.

Aged↗
PubMed2006

Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression.

PURPOSE: The aim of this study is to identify novel molecular targets for development of novel treatment or diagnostic markers of prostate cancer through genome-wide cDNA microarray analysis of prostate cancer cells purified by laser microdissection. EXPERIMENTAL DESIGN AND RESULTS: Here, we identified molecule interacting with CasL-2 prostate cancer variants (MICAL2-PV), novel splicing variants of MICAL2, showing overexpression in prostate cancer cells. Immunohistochemical analysis using an antibody generated specific to MICAL2-PV revealed that MICAL2-PV was expressed in the cytoplasm of cancer cells with various staining patterns and intensities, whereas it was not or hardly detectable in adjacent normal prostate epithelium or prostatic intraepithelial neoplasia. Interestingly, immunohistochemical analysis of 105 prostate cancer specimens on the tissue microarray indicated that MICAL2-PV expression status was strongly correlated with Gleason scores (P < 0.0001) or tumor classification (P < 0.0001). Furthermore, the expression levels of MICAL2-PVs were also concordant to those of c-Met, a marker of tumor progression, with statistical significance (P = 0.0018). To investigate its potential of molecular therapeutic target for prostate cancers, we knocked down endogenous MICAL2-PVs in prostate cancer cells by small interfering RNA, which resulted in the significant reduction of prostate cancer cell viability. CONCLUSIONS: Our findings suggest that MICAL2-PV is likely to be involved in cancer progression of prostate cancer and could be a candidate as a novel molecular marker and/or target for treatment of prostate cancers with high Gleason score.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment.

von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that is associated with various tumors and cysts in the central nervous system (CNS) and other visceral organs. Inactivation of the VHL tumor suppressor protein with loss of function of the VHL protein, and Elongin B, C complex results in a dysfunction of the ubquitination of hypoxia-inducible factor, which is an important step in the development of highly vascular tumors. The most frequent tumors are hemangioblastoma in the CNS and retina, pheochromocytoma in the adrenal gland, renal cell carcinoma and pancreatic neuroendocrine tumors. In this review, we summarize the recent literatures on the pathogenesis, clinical characteristics, diagnosis and treatment of VHL disease. Progress in molecular diagnosis and molecular targeting therapy is expected to improve the diagnosis and treatment of this disease. Medical, psychological and societal supports for patients with VHL disease and their families and supportive communication among the VHL families are also very important. They have proved to be of benefit for patients with this disease to overcome various social and psychological problems in the US and Europe. Since some drugs targeting the vascular endothelial growth factors or its receptor are undergoing clinical trials, a better prognosis of the tumor in VHL disease can be expected.

Adrenal Gland Neoplasms↗
PubMed2006

Clinical characteristics of pancreatic neuroendocrine tumors in Japanese patients with von Hippel-Lindau disease.

OBJECTIVE: The aim of this study was to elucidate the clinical characteristics of pancreatic neuroendocrine tumors (NET) in Japanese patients with von Hippel-Lindau (VHL) disease. METHODS: We sent a questionnaire to all members of the Japan Pancreas Society in 2002 asking for the number of patients with VHL and complications of NET and/or cystic lesion in the pancreas. Furthermore, we sent a second questionnaire to obtain detailed information about the clinical characteristics of pancreatic NET. RESULTS: A total of 58 patients with VHL were reported. Among these, 34 (59%) patients had pancreatic lesions, including 10 with pancreatic NET, 23 with a cystic lesion, and one with both. The mean age at identification of pancreatic NET was 34.6 years (range, 22-64 years). The mean diameter of the tumors was 4.3 cm (range, 1-12.5 cm). Distant metastases were found in 2 (20%) cases. During the follow-up period (3.3 years; range, 0-8 years), 7 patients are alive, and 2 patients died of hemangioblastomas. CONCLUSIONS: Pancreatic NET in the VHL disease showed a relatively lower incidence of metastasis compared with sporadic non-functioning pancreatic NET, yielding a favorable prognosis. Because they present no hormonal syndrome, periodic screening examinations are warranted to identify pancreatic NET at an early stage.

Adult↗
PubMed2006

[Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer].

PURPOSE: To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method. MATERIALS AND METHODS: Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy. RESULTS: Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect. CONCLUSION: Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.

Administration, Intravesical↗
PubMed2006

[Conservative therapy by percutaneous radiofrequency ablation of renal cell carcinomas--therapeutic experiments of four patients with seven renal tumors--].

We report 7 renal cell carcinomas in 4 patients treated by percutaneous image-guided radiofrequency ablation (RFA). The mean age of the patients was 59 years (male: 2, female: 2). All 4 were imperative cases. Two patients (5 tumor) had hereditary multiple renal cell carcinomas with von Hippel-Lindau (VHL) disease. The other two patients had sporadic renal cell carcinomas. RFA was performed guided by computed tomography under conscious sedation with local anesthetics. The mean size of the treated tumors was 4.5 (1.8-8.1) cm. Impedance-regulated RF energy from a generator at 94 (45-130) watts was applied at 11 (8-14) min intervals. The average procedure time was 91 (45-165) minutes. The maximum tissue temperature reached 82 (56-91) degrees C immediately after ablation. Three of the 7 lesions (42.9 %) were locally well controlled during the mean follow-up period of 6.3 (4-9) months. The two patients with VHL disease developed visceral metastasis after There were no major complications. Minor complications encountered included flank pain, nausea, perinephritic hematoma and fever. Although percutaneous image-guided RFA showed limited success in large or central renal tumors, the therapy against small exophytic renal tumors would be well tolerable and successful.

Aged↗
PubMed2006

Genome-wide gene expression profiles of clear cell renal cell carcinoma: identification of molecular targets for treatment of renal cell carcinoma.

In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes. We identified 257 genes that were commonly up-regulated and 721 genes that were down-regulated in RCCs. None of top 24 up-regulated genes that showed most significant differences in informative RCC-cases were included in previous reports describing expression profiles of RCC using RNAs isolated from bulk tissues. These findings suggest that it is important to purify as much as possible the populations of cancerous and normal epithelial cells obtained from surgical specimens. Among the significantly-transactivated genes, we focused on Semaphorin 5B (SEMA5B) and knocked-down its expression in RCC cells by small-interfering RNA (siRNA). Effective down-regulation of its expression levels in RCC cells significantly attenuated RCC cell viability. In conclusion, our data should be helpful for a better understanding of the tumorigenesis of RCC and should contribute to the development of diagnostic tumor markers and molecular-targeting therapy for patients with RCC.

Adult↗
PubMed2005

Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer.

Genes encoding the serine proteinase inhibitor B family (SERPINBs) are mainly clustered on human chromosome 18 (18q21). Several serpins are known to affect malignant phenotypes of tumor cells, so aberrant genetic variants in this molecular family are candidates for conferring susceptibility for risk of cancer. We investigated whether eight selected non-synonymous variations within SERPINB loci at 18q21 might be associated with risk of prostate cancer in Japanese men. A case-control study involving 292 prostate-cancer patients and 384 controls revealed significant differences in regard to distribution of four missense variations in genes encoding plasminogen activator inhibitor 2 (PAI2) and SERPINB10. The most significant association was detected for the N120D polymorphism in the PAI2 gene (P = 5.0 x 10(-5)); men carrying the 120-N allele (120-N/N and 120-N/D genotypes) carried a 2.4-fold increased risk of prostate cancer (95% confidence interval 1.45-4.07). Associations were also detected for three other missense polymorphisms in those two genes. Strong linkage disequilibrium in the region encompassing PAI2 and SERPINB10 extended to about 50 kbp. The results suggested that missense variations in one or both of these genes confer important risks for prostate cancer, and may be themselves tumorigenic. Although confirmative replication studies on larger cohorts are awaited, clinical examination of these variations may become useful for identifying individuals at high risk for prostate cancer.

Alleles↗
PubMed2005

Effect of combination therapy with a novel bisphosphonate, minodronate (YM529), and docetaxel on a model of bone metastasis by human transitional cell carcinoma.

PURPOSE: Transitional cell carcinoma (TCC) of the urinary tract is a chemosensitive tumor. Most deaths from TCC of the urinary tract are caused by metastasis, which is resistant to conventional chemotherapy. Frequent sites of metastases from TCC of the urinary tract are regional lymph nodes, liver, lung, and bone. Of these distant metastases, bone metastasis is consistently resistant to cisplatin-based conventional chemotherapy. Therefore, in this study, we investigated whether or not a newly developed minodronate, YM529, could prevent osteolytic bone metastasis of human TCC and also enhance the effect of docetaxel in a bone tumor model of athymic nude mice. EXPERIMENTAL DESIGN: In the present study, we evaluated the effect of in vitro treatment with minodronate and/or docetaxel on the proliferation by cell count, the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and the biological activity of osteoclast by pit formation assay in human bladder cancer cell line, UMUC-14, and mouse osteoclast cells. In vivo, we examined the effect of minodronate in a bone tumor model of athymic nude mice, in which the percutaneous intraosseal injection in the tibia of UMUC-14, leads to osteolytic bone tumor, as a bone metastasis model. To examine whether or not minodronate could inhibit tumorigenicity and enhance the effect of the chemotherapeutic agent, docetaxel, we gave minodronate i.p. and/or docetaxel i.p. to nude mice 3 days after an intraosseal tumor implantation. Moreover, proliferation and the induction of apoptosis of cancer cells and osteoclasts in bone tumors were determined by immunohistochemistry and the TUNEL assay. RESULTS: In vitro: In vitro treatment with docetaxel inhibited proliferation and resorption pit-forming activity and induced apoptosis of mouse osteoclast cells and UMUC-14 cells. In vitro treatment with minodronate inhibited proliferation and activity and induced apoptosis of mouse osteoclast cells but not UMUC-14 cells. The treatment with minodronate enhanced the inhibition of proliferation and activity by docetaxel in osteoclasts. In vivo: In vivo combination therapy with docetaxel and minodronate significantly reduced the tumor incidence compared with the control (P < 0.05) and also growth of intraossal TCC in athymic nude mice compared with the control (P < 0.001), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). Drug-induced body weight loss was not significantly different in any treatment group. Therapy with minodronate significantly enhanced inhibition of proliferation by docetaxel in osteoclasts of bone tumors compared with the control (P < 0.01), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). CONCLUSIONS: These studies indicate that combination therapy with minodronate and docetaxel may be beneficial in patients with bone metastasis of human TCC in the urinary tract.

Acid Phosphatase↗
PubMed2005

PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET.

Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Ibeta/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Ibeta expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Ibeta pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.

Cell Growth Processes↗
PubMed2005

Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.

To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.

Animals↗
PubMed2005

Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling.

PURPOSE: Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), can improve the resectability of larger neoplasms for some patients and offer a better prognosis. However, some suffer severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting response to the M-VAC therapy. EXPERIMENTAL DESIGN: We analyzed gene expression profiles of biopsy materials from 27 invasive bladder cancers using a cDNA microarray consisting of 27,648 genes, after populations of cancer cells had been purified by laser microbeam microdissection. RESULTS: We identified dozens of genes that were expressed differently between nine "responder" and nine "nonresponder" tumors; from that list we selected the 14 "predictive" genes that showed the most significant differences and devised a numerical prediction scoring system that clearly separated the responder group from the nonresponder group. This system accurately predicted the drug responses of 8 of 9 test cases that were reserved from the original 27 cases. Because real-time reverse transcription-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative reverse transcription-PCR-based prediction system that could be feasible for routine clinical use. CONCLUSIONS: Our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

Aged↗
PubMed2005

Hypoxia-inducible factor-1alpha is involved in the attenuation of experimentally induced rat glomerulonephritis.

BACKGROUND/AIM: Among various kidney disease models, there are few rat glomerulonephritis (GN) models that develop in a short time, and with mainly glomerular lesions. Hypoxia-inducible factor (HIF)-1alpha is a transcriptional factor that induces genes supporting cell survival, but the involvement of HIF-1alpha in attenuating the progression of GN remains to be elucidated. We developed a new model of rat GN by coadministration of angiotensin II (AII) with Habu snake venom (HV) and investigated whether HIF-1alpha is involved in renal protection. METHODS: Male Wistar rats were unilaterally nephrectomized on day 1, and divided into 4 groups on day 0; N group (no treatment), HV group, A group (AII), and H+A group (HV and AII). To preinduce HIF-1alpha, cobalt chloride (CoCl2) was injected twice before injections of HV and AII in 11 rats. RESULTS: GN was detected only in the H+A group; observed first on day 2 and aggravated thereafter. HIF-1alpha was expressed in the glomeruli and renal tubules in the A and H+A groups. In the H+A group, GN was remarkably reduced by CoCl2 pretreatment (44.9 to 12.2%, p < 0.01). CONCLUSION: Both HV and AII were critical for the development of GN, and HIF-1alpha remarkably attenuated the progression of GN.

Angiotensin II↗
PubMed2005

Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.

BACKGROUND: To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors. METHODS: They evaluated intratumoral microvessel density (MVD) by immunohistochemical staining, assessed the expression of angiogenesis-related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 metastatic tumor specimens were resected from 24 patients. RESULTS: The pathologic stage (P=0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P=0.000025) and the ratio of matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P <0.05). Relative to the primary tumors, the metastatic tumors also had high MVD, overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P <0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P=0.049 and P=0.001, respectively). Furthermore, the M/E ratio in metastatic tumor specimens resected from the lung and lymph node was an independent prognostic factor for metastasis (P=0.01823 and P=0.03950, respectively). CONCLUSIONS: The current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC.

Aged↗
PubMed2005

Hemangioblastomatosis of the central nervous system without von Hippel-Lindau disease: a case report.

We report a very rare case of hemangioblastomatosis in a patient without von Hippel-Lindau disease (VHL). A 50-year-old woman had a history of surgical procedures for total removal of a cerebellar hemangioblastoma (HB). Twenty-one years after the last operation, she developed communicating hydrocephalus; computed tomographic (CT) scans of the brain showed no recurrence of HB in the posterior fossa. Subsequently, she underwent placement of a ventriculo-peritoneal shunt. One year later, she was readmitted because of progressive numbness and pain in the left lower limb. Magnetic resonance imaging (MRI) showed multiple Gd-enhancing tumors around the brain stem, in the cerebellum, and in the cervical and thoracolumbar regions of the spine. She underwent surgical removal of the tumors in the cerebellum and spinal cord. Although the extirpated tissues were histopathologically verified HB with less than 1% MIB-1 labeling index, surgery was followed by external beam radiation therapy with doses of 40 Gy to the whole brain, 10 Gy to the posterior fossa and 30 Gy to the whole spine. However, she subsequently developed quadriparesis and became bedridden.

Central Nervous System Neoplasms↗
PubMed2005

Genetic changes in localized prostate cancer of Japanese patients shown by comparative genomic hybridization.

To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.

Adenocarcinoma↗