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Gastric Cancer Specimens (gastric + cancer_specimen)
Selected AbstractsImproving the quality of processing gastric cancer specimens: The pathologist's perspective,JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Alyson L. Mahar BSc Abstract Background and Objectives Research into surgeon and pathologist knowledge of guidelines for lymph node (LN) assessment in gastric cancer demonstrated a knowledge deficit. To understand factors affecting optimal assessment we surveyed pathologists to identify external barriers. Methods Pathologists were identified using two Ontario physician databases and surveyed online or by mail, with a 40% response rate. Results The majority (56%) of pathologists stated assessing an additional five LNs would not be a burden. Most (80%) pathologists disagreed with pay for performance for achieving quality standards. Qualitative analysis determined the majority of pathologists believed achieving quality standards was inherent to their profession and should not require incentives. Poor surgical specimen was identified as a barrier and underscores the importance of aiming quality improvement initiatives at the multidisciplinary team. Conclusion In addition to education, tailoring an intervention to address all barriers, including laboratory constraints may be an effective means of improving gastric cancer care. J. Surg. Oncol. 2010; 101:195,199. © 2010 Wiley-Liss, Inc. [source] Overexpression of cathepsin,B in gastric cancer identified by proteome analysisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2005Matthias P. A. Ebert Abstract We aimed to validate an analytical approach based on proteomics on gastric cancer specimens for the identification of new putative diagnostic or prognostic markers. Primary screening was performed on gastrectomy specimens obtained from ten consecutive patients with gastric cancer. Gastric epithelial cells were obtained with an epithelial cell enrichment technique, homogenized and then separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The differential protein expression pattern was verified stepwise by Western blotting and immunohistochemistry on samples from 28 and 46,cancer patients, respectively. The putative clinical applicability and prognostic use were tested by an enzyme-linked immunoabsorbent assay on serum samples obtained from 149,cancer patients. One hundred-ninety-one differentially expressed protein spots were found by 2-D PAGE and identified by mass spectrometry, including cathepsin,B, which was over-expressed in six (60%) patients. Western blotting confirmed that the active form of cathepsin,B is over-expressed, while immunohistochemistry showed strong cytoplasmic staining in cancer tissues of 45 (98%) patients. The serum level of cathepsin,B was increased in patients with gastric cancer compared to healthy controls (P,=,0.0026) and correlated with T-category and the presence of distant metastases (P,<,0.05). Serum levels above 129,pmol·L,1 were associated with a reduced survival rate (P,=,0.0297). Proteome analysis is a valuable tool for the identification of prognostic markers in gastric cancer: Increased cathepsin,B serum levels are associated with advanced tumor stages and progressive disease, which enables the classification of some gastric cancer patients into a subgroup that should undergo aggressive therapy. [source] Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinomaAPMIS, Issue 8 2009JEEYUN LEE Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim DH, Kim K-M, Park CK. Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 2009; 117: 598,606. There are no known reliable biomarkers which can predict poor clinical outcome following curative resection of gastric adenocarcinoma. Given the importance of signal transducer and activator of transcription 3 (STAT3) activation in carcinogenesis, we attempted to determine whether STAT3 activation is prognostic of survival in curatively resected gastric cancer patients. We analyzed 311 surgically resected gastric cancer specimens for STAT3 activation and its downstream molecules such as matrix metalloproteinase (MMP)-9, MMP-10, cyclin D1, survivin, vascular endothelial growth factor (VEGF)-C, and VEGFR-3 using immunohistochemical studies and assessed their correlation with clinical outcome. Using immunohistochemistry, 303 specimens were interpretable for pSTAT3tyr705 expression. The pSTAT3 was detected in 79 (26.1%) of 303 gastric cancers. Of the downstream molecules tested, STAT3 activation was significantly associated with MMP-9 and MMP-10 expressions. On univariate analyses, 5-year disease-free survival (DFS) and overall survival (OS) for the tumors with STAT3 activation were considerably poorer than for those without STAT3 activation with statistical significance (5-year DFS 58.2% vs 68.3%; pSTAT3(,) vs pSTAT3(+); p = 0.0223; 5-year OS 59.5% vs 70.5%; pSTAT3(,) vs pSTAT3(+); p = 0.0128). On multivariate analyses, STAT3 activation was independently associated with inferior DFS (p = 0.049, hazard ratio [HR] = 1.445, 95% CI, 1.025, 2.120) along with AJCC stage IIIA or IIIB (p = 0.004, HR = 1.708, 95% CI, 1.178, 2.475). The STAT3 activation was also strongly correlated with inferior OS (p = 0.042, HR = 1.506, 95% CI, 1.025, 2.213). Based on our data, pSTAT3tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer. The clinical impact of a STAT3-targeted agent should be investigated in gastric cancer patients. [source] DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosaeCANCER SCIENCE, Issue 7 2010Masaki Yamashita Interferon regulatory factors (IRFs) are transcription factors known to play key roles in innate and adaptive immune responses, cell growth, apoptosis, and development. Their function in tumorigenesis of gastric cancer remains to be determined, however. In the present study, therefore, we examined epigenetic inactivation of IRF1,9 in a panel of gastric cancer cell lines. We found that expression of IRF4, IRF5, and IRF8 was frequently suppressed in gastric cancer cell lines; that methylation of the three genes correlated with their silencing; and that treating the cells with the demethylating agent 5-aza-2,-deoxycytidine (DAC) restored their expression. Expression of IRF5 in cancer cells was enhanced by the combination of DAC treatment and adenoviral vector-mediated expression of p53, p63, or p73. Interferon-,-induced expression of IRF8 was also enhanced by DAC. Moreover, treating gastric cancer cells with DAC enhanced the suppressive effects of interferon-,, interferon-,, and interferon-, on cell growth. Among a cohort of 455 gastric cancer and noncancerous gastric tissue samples, methylation of IRF4 was frequently observed in both gastric cancer specimens and noncancerous specimens of gastric mucosa from patients with multiple gastric cancers, which suggests IRF4 methylation could be a useful molecular marker for diagnosing recurrence of gastric cancers. Our findings indicate that epigenetic IRF inactivation plays a key role in tumorigenesis of gastric cancer, and that inhibition of DNA methylation may restore the antitumor activity of interferons through up-regulation of IRFs. (Cancer Sci 2010) [source] A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinomaCANCER SCIENCE, Issue 11 2006Junichi Sakamoto In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m2). Patients with locally advanced (UICC-TNM [International Union Against Cancer,tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of 131I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of 131I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting. (Cancer Sci 2006; 97: 1248,1254) [source] | ||||||||||