Hiroshi Yano

Nagasaki University Hospital, Nagasaki, Nagasaki, Japan

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Publications (25)49.98 Total impact

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    ABSTRACT: Even after needle biopsy, the preoperative differential diagnoses of intracystic tumors of the breast are challenging because of their nonspecific radiological characteristics and subtle cytological and histological appearance. The aim of this study is to investigate a novel diagnostic method, targeting genomic instability (GIN) in intracystic tumors of the breast, using tumor DNA from samples obtained by fine-needle aspiration biopsy (FNAB). Thirteen consecutive intracystic tumors of the breast, including five cancers and eight benign tumors, were studied. Three FNAB passages per tumor were used for array comparative genomic hybridization (aCGH) analysis to quantify GIN in each tumor. Tumor DNA from the main tumor, taken from formalin-fixed, paraffin-embedded (FFPE) blocks corresponding to FNAB samples, was also analyzed to compare cytogenetic profiles between these sample types. After three FNAB passages, an average of 7.09 μg (0.24-25.0 μg) of DNA was obtained. The quality of the DNA and the aCGH data was excellent, as judged by the mean derivative log ratio spread (DLRSpread) of 0.22 (0.15-0.29). The cytogenetic profiles of paired FNAB and main tumor FFPE samples were highly similar, with an average concordance rate of 97.7 % (81.2-100 %). aCGH analysis from FNAB samples showed significantly more GIN in cancers than in benign tumors, with mean frequencies of aberrant chromosomal regions of 17.5 and 0.34 %, respectively (Wilcoxon's rank sum test, P = 0.0016). Our novel diagnostic method, which targets GIN, can clearly distinguish cancers from benign tumors of breast intracystic lesions with minimal invasion, thereby avoiding the need for surgical excisional biopsy.
    Breast Cancer 01/2014; · 1.33 Impact Factor
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    ABSTRACT: We developed an easy, quick, and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting. (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric, and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity, and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity, and accuracy of the SDB method were 100%, 98.0%, and 98.3%, respectively. (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy, and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy, and mean required time of the SDB method were 93.3%, 96.9%, 96.6%, and 43.3 minutes, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2013; · 6.20 Impact Factor
  • The Breast Journal 06/2011; 17(4):427-30. · 1.83 Impact Factor
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    ABSTRACT: While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases.
    PLoS ONE 01/2011; 6(4):e19354. · 3.73 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the clinical outcomes of chest wall reconstruction using a new, expanded polytetrafluoroethylene prosthesis, 'DualMesh'. Between December 2005 and March 2010, chest wall reconstruction using 2-mm DualMesh was performed in 11 patients. The indication for resection was primary lung cancer in six patients, malignant mesothelioma in one patient, recurrent lung cancer in one patient, recurrent invasive thymoma in one patient, postirradiated osteomyelitis in one patient, and chondro-hamartoma in one patient. The mean observation period was 23 months, and four cases were observed for more than three years. There were no operative deaths and no wound infections. There were two postoperative complications: prolonged air leakage occurred in a patient with pulmonary emphysema who underwent right lower lobectomy, and slight paradoxical respiration occurred in the patient who underwent resection of the entire sternal body for osteomyelitis. Follow-up chest computed tomography was performed routinely. No dehiscence occurred in any cases. Chest wall reconstruction using DualMesh demonstrated acceptable durability and biocompatibility, even after long-term follow-up. DualMesh has the potential to become an ideal prosthesis for the bony chest wall as an alternative to conventional polytetrafluoroethylene or polypropylene grafts.
    Interactive Cardiovascular and Thoracic Surgery 11/2010; 11(5):581-4. · 1.11 Impact Factor
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    ABSTRACT: We assessed the usefulness and limitations of utilizing apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI) for the differential diagnosis of benign and malignant non-mass-like breast lesions. We retrospectively reviewed 27 such lesions (16 malignant, 11 benign) detected on magnetic resonance (MR) imaging and analyzed the enhancing patterns of dynamic contrast-enhanced DCE-MRI (distribution and internal enhancement), kinetic curve patterns, and ADC values. All images were obtained with a 1.5-tesla MR unit, with patients supine. On DCE-MRI, malignant lesions tended to show either segmental or branching-ductal distribution, and when lesions with these patterns were considered malignant, sensitivity was 68.8%; specificity, 63.6%; positive predictive value (PPV), 73.3%; negative predictive value (NPV), 58.3%; and accuracy, 66.7%. Kinetic curve analysis did not reliably differentiate benign and malignant non-mass-like lesions. There was no significant difference between the mean ADC value of the malignant lesions, 0.968 × 10(-3) mm(2)/s at b=1000 s/mm(2), and that of benign lesions, 1.207 × 10(-3) mm(2)/s (P=0.109). Receiver operating characteristic (ROC) analysis revealed the most effective threshold of ADC value for differentiating tumors as 1.1 × 10(-3) mm(2)/s; values lower than this were observed more often in malignant than benign lesions (P=0.054). Us of this threshold yielded sensitivity of 68.8%; specificity, 72.7%; PPV, 78.6%; NPV, 61.5%; and accuracy, 70.4%. Combining the ADC value criteria with the analysis of DCE-MRI pattern increased sensitivity to 93.8%, negative predictive value (NPV) to 85.7%, and accuracy to 77.8% but decreased specificity to 54.5%. Use of ADC values does not adequately improve DCE-MRI performance for differential diagnosis of non-mass-like breast lesions, but adding the ADC value criteria to the DCE-MRI pattern analysis improves sensitivity, NPV, and accuracy.
    Magnetic Resonance in Medical Sciences 01/2010; 9(4):217-25. · 0.75 Impact Factor
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    ABSTRACT: Lung cancer commonly occurs in individuals who are 60 years of age or older. Lung cancer in patients younger than 40 years of age is rare and is often advanced when discovered. However, the biological features of lung cancer in young adults have not yet been fully elucidated. This study was conducted to determine the role of p53 expression and neoangiogenesis in lung adenocarcinomas of young patients. Lung adenocarcinomas, which were surgically resected from 20 patients younger than 40 years of age between 1977 and 1996, were compared with lung adenocarcinomas selected with random sampling from 45 patients older than 60 years of age. The expression of p53, vascular endothelial growth factor (VEGF), CD34, a marker for vascular endothelial cells, and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically in both young and elderly patient groups. Lung adenocarcinomas with p53-positive staining showed higher expression of VEGF protein than p53-negative tumors in both the young and the elderly groups. However, the intratumoral microvessel count was significantly higher in the p53-positive young group than in the elderly group. The percentage of VEGF-positive cells correlated significantly with intratumoral microvessel counts in the young group. The survival rate tended to be poorer in patients with a high VEGF labeling index and p53-positive staining than in other young patients. Lung adenocarcinoma occurring in young patients tends to have a poorer prognosis, and angiogenesis of lung adenocarcinoma in young patients is more closely correlated with p53 expression than in elderly patients.
    The Tohoku Journal of Experimental Medicine 03/2009; 217(2):101-7. · 1.37 Impact Factor
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    ABSTRACT: Mouse mammary tumor virus (MMTV) is the causative agent of breast tumors in mice. Recently, DNA sequences homologous or closely related to MMTV env gene have been specifically detected in breast cancer tissue from significant numbers of American, Australian, and Tunisian women, suggesting a viral etiology for at least a part of human breast cancer. However, the viral sequences have not been detected from any of breast cancer samples in several subsequent studies. Thus, whether MMTV-related retrovirus is a causative agent of human breast cancer remains controversial. To demonstrate if MMTV-related retrovirus is involved in Japanese cases of breast cancer, breast tissue specimens from 46 breast cancer patients and 3 patients with benign mammary tumors were investigated. Extensive analysis using PCR and Southern blot hybridization, however, could not detect the MMTV env gene-like sequence in any of the samples tested as well as in MCF7 cells that has previously been described as a positive control. Thus, MMTV itself or MMTV-related retrovirus is not associated with breast carcinogenesis in Japanese women, and it is unclear whether this conclusion is merely a reflection of regional differences in its epidemics.
    Journal of Medical Virology 09/2008; 80(8):1447-51. · 2.37 Impact Factor
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    ABSTRACT: The activating point mutation of the BRAF gene, BRAF(T1799A), is the most common and specific genetic alteration in adult papillary thyroid carcinoma (PTC) and a possible marker of malignant potential of PTC. We have applied the PCR-RFLP method using fine-needle aspiration biopsy samples not only to our clinical practice but also to the international medical assistance effort around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy-seven cases (100 nodules) from Japan and 131 cases (137 nodules) from Kazakhstan were examined. There were 14 Japanese and 76 Kazakhstani cases of cytological malignant tumors from the examined samples. We detected 12 (85.7% of PTC) and 19 (25% of PTC) cases with BRAF(T1799A) among the Japanese and Kazakhstani cases, respectively. Of these cases, we found mutations in one cytologically "suspicious" case and even in two pathologically "benign" cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those three, were confirmed as PTC by careful pathological examination, including immunohistochemical analysis. In summary, our PCR-RFLP method for BRAF(T1799A) detection using FNAB samples is useful not only for preoperative diagnosis of PTC but also as a complementary diagnostic tool for accurate pathological diagnosis, even after surgery.
    Endocrine Journal 07/2007; 54(3):399-405. · 2.23 Impact Factor
  • Endocrine Journal - ENDOCR J. 01/2007; 54(3):399-405.
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    ABSTRACT: To predict the risk of liver dysfunction associated complications after hepatectomy, we evaluated perioperative parameters in patients after hepatectomy. We examined 185 consecutive patients who underwent hepatectomy for liver tumors. Background liver was normal liver in 73 patients, chronic viral hepatitis in 49, cirrhosis in 46 and icteric liver in 17. Postoperative complications associated liver dysfunction (long-term ascites, intraabdominal infection and hepatic failure) occurred in 70 (38%) patients. Univariate analysis identified 9 significant parameters associated with postoperative complications (resected volume > or = 50%, intraoperative bleeding volume > or = 1500 mL, liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy of < 0.85, alanine aminotransferase > or = 80 IU/L, total cholesterol < 150 mg/dL, prothrombin activity [PT] < 80%, Liver Damage grade B, histopathological activity index [HAI] of > or = 8 and hyaluronic acid [HA] of > or = 150 ng/mL). Multivariate logistic regression analysis identified resected volume, intraoperative bleeding, PT and HA levels as four significant independent predictors of post-hepatectomy complication with odds ratios of 7.0, 4.4, 7.5, and 5.4, respectively. Preoperative assessment and correction of abnormal PT and HA, careful evaluation of resected volume and attempt to reduce intraoperative bleeding are important to avoid postoperative hepatic complications.
    Hepato-gastroenterology 01/2007; 54(75):839-43. · 0.77 Impact Factor
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    ABSTRACT: Mammographic density reflects comprehensive changes in the mammary gland. The condition of the tumour microenvironment is a possible factor affecting tumour progression, as well as a tumour risk factor. This study aimed to determine whether mammographic density correlates with tumour clinicopathological features and prognosis in breast cancer patients. The analysis involved 163 Japanese women who underwent surgery for breast cancer between 1999 and 2003 in the Nagasaki University Hospital, Japan. Mammographic density was classified according to the breast imaging reporting and data system (BI-RADS) categories 1-4. Age, tumour size, axillary lymph node involvement, steroid receptor (SR) status, histological grade and Nottingham prognostic index (NPI) were analysed by density category and tested for statistically significant differences across categories. A significant difference (P<0.05) by breast-density category was found only for age. SR-negative tumours had significantly worse NPI scores than SR-positive tumours in breast-density categories 2 (P=0.03) and 4 (P<0.001). A high distant-metastasis frequency was observed in category 4 SR negatives (44%) versus category 4 SR positives (4.3%). These findings reveal that although the BI-RADS breast-density category alone is not associated with prognosis in breast cancer, patients who are both category 4 and SR negative have an extremely poor prognosis.
    International Journal of Oncology 05/2005; 26(5):1307-12. · 2.66 Impact Factor
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    ABSTRACT: Breast cancer has emerged as the most frequent malignant neoplasm among Japanese women in recent years, raising awareness in society of the issue of breast cancer, including good screening and therapies. In fact, the establishment of breast cancer screening program with mammography in the United States and Western Europe has contributed to improve the diagnosis of breast cancer at early stage, and proper management, including various options of evidence-based treatment has not only reduced mortality but also enhanced patients' quality of life. However, the mortality rate due to breast cancer in Japan has continued to increase, and the number of patients is also increasing rapidly. It is therefore very urgent to develop a good system of breast care in all medical facilities as well as the provision of a national scheme in Japan. In this report, we review the situations of breast surgery at Nagasaki University Hospital from 1975 to 2004 and current management practices for breast disease, and evaluate the possibility of establishing a better system for breast care at our hospital, which could then act as a core medical institute in Nagasaki
    01/2005;
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    ABSTRACT: Argyrophilic nucleolar organizer regions (AgNORs) and MIB-1 as proliferating activities have been applied separately to assess the malignant potential of cancer cells. We conducted staining of AgNORs and MIB-1 in 42 surgically-resected invasive breast carcinomas. Paraffin-embedded sections were used for double staining and the mean AgNOR counts in 100 MIB-1-positive and -negative cells were calculated. The mean AgNOR count in MIB-1-positive cells was significantly higher than in MIB-1-negative ones. AgNOR counts in MIB-1-positive tumors were significantly higher in tumors > or =2 cm and those with positive nodes. Multivariate analysis identified the AgNOR count in MIB-1-positive tumors as the only independent factor related to node metastasis. Survival of patients with lower counts of AgNORs in MIB-1-positive tumors was significantly better compared to those with higher counts. Double staining of MIB-1 and AgNORs is useful for predicting lymph node metastasis and prognosis of patients with breast carcinoma.
    Anticancer research 01/2005; 25(6B):3957-62. · 1.71 Impact Factor
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    ABSTRACT: To investigate numerical aberrations of chromosome 17 and the p53 locus in early stages of hepatocellular carcinoma (HCC), 12 fresh-frozen specimens of small HCCs (less than 30 mm in size) were examined by dual-color fluorescence in situ hybridization. We used a chromosome 17 alpha-satellite DNA probe and a p53 locus-specific DNA probe. We also performed immunohistochemical analysis for p53 protein in the same cases. Gain of chromosome 17 was the most frequently observed anomaly, present in 58% of cases, and deletion of the p53 locus was observed in 50% of cases. The combination of chromosome 17 gain and p53 locus deletion was observed in 33.3% of cases. However, overexpression of p53 protein was not observed in any specimens. Our results suggest that gain of chromosome 17 and deletion of the p53 locus could represent early genetic events, prior to overexpression of p53 protein due to mutation, in early stage HCC.
    Anticancer research 01/2004; 24(1):111-5. · 1.71 Impact Factor
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    ABSTRACT: The relationship between patient prognosis and various tumor biological factors has been reported previously, and prognostic factors of tumor biology may improve predictions of prognosis after hepatectomy for hepatocellular carcinoma (HCC) and may contribute to a new staging classification. This study was designed to provide an immunohistochemical analysis of tumor biological factors in patients who underwent hepatectomy for HCC. Factors analyzed included p53 overexpression, microvessel counts, proliferating cell nuclear antigen, and expression of nm23. We examined 81 HCCs from patients with chronic liver diseases. In patients who underwent chemoembolization before surgery, or those a who had confluent multinodular tumor, p53 expression tended to be higher than in patients without chemoembolization (33% vs 11%) or those with a simple nodular tumor (28% vs 10%), but the difference was not statistically significant ( P = 0.051 and P = 0.092, respectively). A lower tumor microvessel count and negative nm23 expression were significantly associated with poor disease-free survival by univariate analysis ( P < 0.01 and P < 0.05, respectively). A lower tumor microvessel count was found to be a significant prognostic factor for disease-free and overall survivals (risk ratios, 2.44 and 3.13, respectively; P < 0.05), in addition to tumor size, vascular invasion, and longterm ascites, by Cox's multivariate analysis. Tumor microvessel count appears to be a useful prognostic marker for predicting HCC recurrence and patient survival.
    Journal of Gastroenterology 01/2004; 39(2):148-54. · 3.79 Impact Factor
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    ABSTRACT: The present study was undertaken to evaluate p53 gene mutation as a prognostic factor in patients with colorectal cancer. Nonisotopic RNase cleavage assay (NIRCA), recently used for detecting gene mutations, was employed to detect p53 gene mutations in this study. In 15 samples of colorectal tumors, NIRCA was confirmed to be simple, accurate, and thus useful for clinical use, compared with polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP). In another group of 79 cases of colorectal cancer analyzed for p53 gene mutation by using NIRCA, mutations were detected in 58 of 79 (73.4%) cases. Multivariate Cox proportional-hazards analysis showed that p53 gene mutation was a significant prognostic factor in patients with colorectal cancer. Our results showed that NIRCA is a simple and sensitive method, and thus useful for genetic screening of colorectal cancer. Furthermore, our results showed that p53 gene mutation is an independent predictor of poor prognosis in colorectal cancers.
    Digestive Diseases and Sciences 11/2003; 48(10):1984-9. · 2.26 Impact Factor
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    ABSTRACT: Thymidylate synthase (TS) is the target enzyme of 5-fluoropyrimidines. The TS gene promoter enhancer region (TSER) possesses tandem, repeated, regulatory sequences that are polymorphic in humans. This polymorphism has been reported to influence TS expression in vitro and in vivo. In this study, we assessed whether or not the TSER genotype is an efficacious marker for tumor sensitivity to 5-fluorouracil (5-FU)-based oral adjuvant chemotherapy for colorectal cancer. One hundred and thirty-five Japanese patients who received curative resection and 5-FU-based oral adjuvant chemotherapy were studied. TSER genotypes of the tumors were analyzed by PCR. The numbers of repeated sequences of representative bands were determined by direct sequence. The genotypes of two-/two-repeats (TSER 2/2), two-/three-repeats (TSER 2/3), three-/three-repeats (TSER 3/3), and three-/five-repeats (TSER 3/5) were found in 11 (8.1%), 32 (23.7%), 85 (63.0%), and 7 (5.2%) tumors, respectively. Patients were classified into two groups: TSER 2/2 or 2/3 group; and the TSER 3/3 group. The relationship between the TSER genotype group and disease-free intervals was analyzed by univariate and multivariate analyses. Five-year disease-free survivals of the TSER 2/2 or 2/3 group and the TSER 3/3 group were 77% and 75%, respectively (P = 0.89). Multivariate analysis revealed that stage was the only independent prognostic factor and that the TSER genotype did not have a prognostic significance (hazard ratio for TSER 3/3, 0.91; P = 0.84). In conclusion, TSER genotype is not an efficacious marker for tumor sensitivity to 5-FU-based oral adjuvant chemotherapy for Japanese colorectal cancer patients after curative resection.
    Clinical Cancer Research 10/2003; 9(10 Pt 1):3700-4. · 7.84 Impact Factor
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    ABSTRACT: The chromosomal aberrations underlying the development of resistance to fluoropyrimidines have not yet been identified. To characterise the genomic changes that induce the development of resistance to fluoropyrimidines, we used comparative genomic hybridisation (CGH) to analyse and compare the parent DLD-1 human colorectal cancer cell line and two cell lines, DLD-1/5-FU and DLD-1/FdUrd, which were resistant to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), respectively. Both resistant cell lines showed a genetic aberration derived from the parental cell line DLD-1. Losses of 3p and 3q were also detected as additional genetic changes in the two resistant cell lines. Both resistant cell lines showed decreased orotate phosphoribosyltransferase (OPRT) activity, which is associated with the activity of the uridine monophosphate (UMP) synthase gene (3q13). These results suggested that the loss of 3q might be a genetic change responsible for the decreased OPRT activity and fluoropyrimidine cytotoxic response in cancer cells. Amplification of 18p11.2-p11.3 containing the thymidine synthase (TS) gene (18p11.32) was observed only in the DLD-1/FdUrd-resistant cell line, which overexpresses TS. These findings suggested that 18p amplification represents a genetic change associated with the overexpression of the TS protein. Our results indicate that chromosomal aberrations identified by CGH could explain, at least in part, acquired fluoropyrimidine resistance.
    European Journal of Cancer 06/2003; 39(7):975-80. · 5.06 Impact Factor
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    ABSTRACT: The genetic aberrations associated with development and progression of gastric carcinomas (GCs) are poorly understood. The aim of this study was to identify chromosomal aberrations associated with the development and/or progression of intestinal-type GC. Comparative genomic hybridization (CGH) analysis was applied to 36 intestinal-type GCs. We compared chromosomal aberrations detected by CGH analysis with clinicopathological parameters. Frequent gains of DNA copy number were found on 8q, 13q, 20q, 3q, 6q and losses were found on 17p, 18q in intestinal-type GCs. No significant differences were observed in the chromosomal aberrations between tumor stage, tumor location, peritoneal dissemination, liver metastasis or other distant metastasis. However, the frequencies of 20q12-13 gain and 18q21-22 loss were significantly higher in tumors with lymph node metastasis than in those without metastasis. Gains of 20q and losses of 18q may contribute to lymph node metastasis and the malignant phenotype in intestinal-type GCs.
    Anticancer research 01/2003; 23(4):3353-7. · 1.71 Impact Factor