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[PMID]: 29099112
[Au] Autor:Sevilla-Lizcano DB; Frias-Soria CL; Ortiz-Hidalgo C
[Ad] Address:Departamento de Patología Quirúrgica y Molecular, Centro Médico ABC.
[Ti] Title:Enfermedad de Castleman. Análisis histopatológico e inmunohistoquímico de 39 casos.
[So] Source:Gac Med Mex;153(5):550-558, 2017.
[Is] ISSN:0016-3813
[Cp] Country of publication:Mexico
[La] Language:eng
[Ab] Abstract:Introduction: Castleman disease (CD) is a rare lymphoproliferative that comprises two distinct clinical subtypes (unicentric and multicentric) and has two basic histopathology patterns that are hyaline-vascular (HV) and plasma-cell (PC) type. Some cases of multicentric PC disease are associated with HHV-8 infection. Objective: To present the histopathologic and immunohistochemical characteristics of 39 cases of CD. Methods: A review of cases with the diagnosis CD from the files of the Department of Pathology of the ABC Medical Centre in Mexico City was performed. Thirty-nine cases of CD were identified, and a detailed paraffin immunophenotypic study of 9 of them was completed using desmin, cytokeratin OSCAR (CO) and Epidermal growth factor receptor (EGFR), to evaluate the dendritic cell population. Results and Conclusions: Of the 39 cases of CD, 24 were HV and 15 CP. All HV cases were unicentric and only one case of CP was multicentric. The most frequent localization in both subtypes was in lymph nodes; 21/24 cases in HV and 15 cases of CP. All cases were immunostained with CD20 that was expressed in the germinal centers (CGs), CD3 in the paracortical zone, and CD21 in follicular dendritic cells (CDF) within CGs, with expansion towards the area of the hyperplastic mantle zone (only in the HV variant). One case of CD CP was positive for HHV-8. Of the nine cases (6 HV and 3 PC cases) that were detailed with IHC, we found EGFR expression in FDC in all but one of the 9 cases studied and desmin was positive in fibroblastic reticulum cells (FRC) in all, but one of the cases of CD. CO was positive FRC in 3 of 6 cases of HV type and all (3) of the PC type. Clinical, histopathological and HIV and HHV-8 status markers, allow for the classification of CD into groups with markedly different outcomes and disease associations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:In-Data-Review
[do] DOI:10.24875/GMM.17003021

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[PMID]: 29098421
[Au] Autor:Tranoulis A; Thomakos N; Sotiropoulou M; Rodolakis A
[Ad] Address:Department of Gynaecological Oncology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece. tasostranoulis@yahoo.com.
[Ti] Title:What is the accuracy of frozen section in the diagnosis of mucinous ovarian tumours? A 9-year review of performance in a Greek tertiary referral centre.
[So] Source:Arch Gynecol Obstet;, 2017 Nov 02.
[Is] ISSN:1432-0711
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: This retrospective study aimed to evaluate the diagnostic accuracy of the intra-operative frozen sections (FS) of mucinous ovarian tumours (mOT). METHODS: Between 2007 and 2015, a total of 105 mucinous ovarian samples were collected during laparotomy. The intra-operative FS accuracy was evaluated and potential factors correlated with increased inaccuracy assessed using both univariate and multivariate analysis. RESULTS: The overall FS accuracy was 82.6%, while diagnostic discrepancy observed in 18/105 cases, including under-diagnosis in 14 and over-diagnosis in four cases. Amongst six cases diagnosed as benign with FS, five were upgraded to low malignant potential and one to malignant in the final formalin fixed, paraffin embedded section (FFPES). Amongst the 37 low malignant potential (LMP) cases, two were finally diagnosed as benign and eight as malignant. Amongst malignant tumours the diagnostic agreement occurred in 21/23 cases, while solely two cases were over-diagnosed. The false FS interpretation resulted in inadequate surgical management in 8/105 (7.6%) cases. Misdiagnosis had a statistically significant association with tumour size greater than 13 cm. The ratio of tumour size per number of frozen sections (TSFSR) less than 8 found to be an independent predictor of inaccuracy [OR 2.46, 95% confidence interval (CI) 1.74-3.46, P < 0.001]. CONCLUSIONS: The accuracy rate of FS in our study was 82.6%. Frozen section had low accuracy amongst LMP tumours adversely influencing the adequate surgical management. This discordance seems to reflect adverse predictors such as the LMP heterogeneity, maximal tumour diameter and low TSFSR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:Publisher
[do] DOI:10.1007/s00404-017-4582-7

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[PMID]: 29098284
[Au] Autor:Qian ZR; Rubinson DA; Nowak JA; Morales-Oyarvide V; Dunne RF; Kozak MM; Welch MW; Brais LK; Da Silva A; Li T; Li W; Masuda A; Yang J; Shi Y; Gu M; Masugi Y; Bui J; Zellers CL; Yuan C; Babic A; Khalaf N; Aguirre A; Ng K; Miksad RA; Bullock AJ; Chang DT; Tseng JF; Clancy TE; Linehan DC; Findeis-Hosey JJ; Doyle LA; Thorner AR; Ducar M; Wollison B; Laing A; Hahn WC; Meyerson M; Fuchs CS; Ogino S; Hornick JL; Hezel AF; Koong AC; Wolpin BM
[Ad] Address:Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
[Ti] Title:Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma.
[So] Source:JAMA Oncol;, 2017 Nov 02.
[Is] ISSN:2374-2445
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Importance: Although patients with resected pancreatic adenocarcinoma are at high risk for disease recurrence, few biomarkers are available to inform patient outcomes. Objective: To evaluate the alterations of the 4 main driver genes in pancreatic adenocarcinoma and patient outcomes after cancer resection. Design, Setting, and Participants: This study analyzed protein expression and DNA alterations for the KRAS, CDKN2A, SMAD4, and TP53 genes by immunohistochemistry and next-generation sequencing in formalin-fixed, paraffin-embedded tumors in 356 patients with resected pancreatic adenocarcinoma who were treated at the Dana-Farber/Brigham and Women's Cancer Center (October 26, 2002, to May 21, 2012), University of Rochester Medical Center (March 1, 2006, to November 1, 2013), or Stanford Cancer Institute (September 26, 1995, to May 22, 2013). Associations of driver gene alterations with disease-free survival (DFS) and overall survival (OS) were evaluated using Cox proportional hazards regression with estimation of hazard ratios (HRs) and 95% CIs and adjustment for age, sex, tumor characteristics, institution, and perioperative treatment. Data were collected September 9, 2012, to June 28, 2016, and analyzed December 17, 2016, to March 14, 2017. Main Outcomes and Measures: The DFS and OS among patients with resected pancreatic adenocarcinoma. Results: Of the 356 patients studied, 191 (53.7%) were men and 165 (46.3%) were women, with a median (interquartile range [IQR]) age of 67 (59.0-73.5) years. Patients with KRAS mutant tumors had worse DFS (median [IQR], 12.3 [6.7 -27.2] months) and OS (20.3 [11.3-38.3] months) compared with patients with KRAS wild-type tumors (DFS, 16.2 [8.9-30.5] months; OS, 38.6 [16.6-63.1] months) and had 5-year OS of 13.0% vs 30.2%. Particularly poor outcomes were identified in patients with KRAS G12D-mutant tumors, who had a median (IQR) OS of 15.3 (9.8-32.7) months. Patients whose tumors lacked CDKN2A expression had worse DFS (median, 11.5 [IQR, 6.2-24.5] months) and OS (19.7 [10.9-37.1] months) compared with patients who had intact CDKN2A (DFS, 14.8 [8.2-30.5] months; OS, 24.6 [14.1-44.6] months). The molecular status of SMAD4 was not associated with DFS or OS, whereas TP53 status was associated only with shorter DFS (HR, 1.33; 95% CI, 1.02-1.75; P = .04). Patients had worse DFS and OS if they had a greater number of altered driver genes. Compared with patients with 0 to 2 altered genes, those with 4 altered genes had worse DFS (HR, 1.79 [95% CI, 1.24-2.59; P = .002]) and OS (HR, 1.38 [95% CI, 0.98-1.94; P = .06]). Five-year OS was 18.4% for patients with 0 to 2 gene alterations, 14.1% for those with 3 alterations, and 8.2% for those with 4 alterations. Conclusions and Relevance: Patient outcomes are associated with alterations of the 4 main driver genes in resected pancreatic adenocarcinoma.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:Publisher
[do] DOI:10.1001/jamaoncol.2017.3420

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[PMID]: 29097624
[Au] Autor:Andeen NK; Yang HY; Dai DF; MacCoss MJ; Smith KD
[Ad] Address:Departments of Pathology and.
[Ti] Title:DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN.
[So] Source:J Am Soc Nephrol;, 2017 Nov 02.
[Is] ISSN:1533-3450
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12-24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:Publisher

  5 / 51496 MEDLINE  
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[PMID]: 29097500
[Au] Autor:Bosch M; Akhter A; Chen BE; Mansoor A; Lebrun D; Good D; Crump M; Shepherd L; Scott DW; Stewart DA; Canadian Cancer Trials Group
[Ad] Address:University of Saskatchewan, Saskatoon, Canada.
[Ti] Title:A bio-clinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma.
[So] Source:Haematologica;, 2017 Nov 02.
[Is] ISSN:1592-8721
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2. In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent digital gene expression profiling to evaluate BCL2, MYC, P53, and STAT3 expression, and to determine Cell-of-Origin using the Lymph2Cx assay. No method of determining Cell-of Origin predicted event-free or overall survival. Factors independently associated with survival outcomes in multivariate analysis included primary refractory disease, elevated serum LDH at relapse, and MYC or BCL2 protein or gene expression. A bio-clinical score using these 4 factors predicted outcome with 3-year event-free survival for cases with 0-1 vs 2-4 factors of 55% vs 16% (p<0.0001) respectively, for assessing MYC and BCL2 by immunohistochemistry, and 46% vs 5% (p<0.0001) assessing MYC and BCL2 mRNA by digital gene expression, and 42% vs 21% (p=0.079) assessing MYC and BCL2 by fluorescent in-situ hybridization. This proposed bio-clinical model should be further studied and validated in other datasets, but may discriminate relapsed/refractory DLBCL patients who could benefit from conventional salvage therapy from others who require novel approaches. The LY12 study was registered at ClinicalTrials.gov: NCT00078949.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:Publisher

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[PMID]: 29093617
[Au] Autor:Olmedillas-López S; Lévano-Linares DC; Alexandre CLA; Vega-Clemente L; Sánchez EL; Villagrasa A; Ruíz-Tovar J; García-Arranz M; García-Olmo D
[Ad] Address:Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital, Madrid 28040, Spain. susana.olmedillas@fjd.es.
[Ti] Title:Detection of G12D in colorectal cancer stool by droplet digital PCR.
[So] Source:World J Gastroenterol;23(39):7087-7097, 2017 Oct 21.
[Is] ISSN:2219-2840
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:AIM: To assess G12D mutation detection by droplet digital PCR (ddPCR) in stool-derived DNA from colorectal cancer (CRC) patients. METHODS: In this study, tumor tissue and stool samples were collected from 70 patients with stage I-IV CRC diagnosed by preoperative biopsy. mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffin-embedded (FFPE) tumor tissues. The G12D mutation was then analyzed by ddPCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type (WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by ddPCR was performed for these patients as well. RESULTS: Among the total 70 patients included, mutations were detected by pyrosequencing in 32 (45.71%), whereas 38 (54.29%) had WT tumors. The frequency of mutations was higher in left-sided tumors (11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was G12D (14.29%, = 10), which was more frequent in early-stage tumors (I-IIA, = 7). In agreement with pyrosequencing results, the G12D mutation was detected by ddPCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The G12D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point mutation. CONCLUSION: ddPCR is a reliable and sensitive method to analyze G12D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171102
[Lr] Last revision date:171102
[St] Status:In-Process
[do] DOI:10.3748/wjg.v23.i39.7087

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Baracat, Edmund Chada
Simöes, Manuel de Jesus
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[PMID]: 29092637
[Au] Autor:Carbonel AAF; Lima PDA; Lim JJ; Fuchs LFP; Paiotti APR; Sasso GRDS; Simões RS; Soares Junior JM; Baracat EC; Simões MJ
[Ad] Address:a Department of Gynecology , Paulista School of Medicine/Federal University of São Paulo - EPM/UNIFESP , São Paulo , Brazil.
[Ti] Title:The effects of soybean isoflavones and 17ß-estradiol in uterus and mammary glands of diabetic rat models.
[So] Source:Gynecol Endocrinol;:1-6, 2017 Nov 02.
[Is] ISSN:1473-0766
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10 mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171102
[Lr] Last revision date:171102
[St] Status:Publisher
[do] DOI:10.1080/09513590.2017.1393510

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[PMID]: 29089751
[Au] Autor:He S; Xie L; Lu J; Sun S
[Ad] Address:Department of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
[Ti] Title:Characteristics and potential role of M2 macrophages in COPD.
[So] Source:Int J Chron Obstruct Pulmon Dis;12:3029-3039, 2017.
[Is] ISSN:1178-2005
[Cp] Country of publication:New Zealand
[La] Language:eng
[Ab] Abstract:BACKGROUND: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role. MATERIALS AND METHODS: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E) staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS) of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-ßRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR). The expression levels of TGF-ß/Smad pathway-related makers (TGF-ßRII, p-Smad2, p-Smad3, Smad7 and TGF-ß) in alveolar M2 macrophages were detected by two consecutive paraffin section IHS. RESULTS: The COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased ( <0.05). The level of CD206 cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-ßRII, Smad2, Smad3 and Smad7 are all enhanced ( <0.05) in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-ß/Smad pathway-related markers are all increased in alveolar M2 macrophages of the model group. CONCLUSION: This study found an increased deposition of alveolar M2 macrophages in the mouse COPD model and an increased expression level of TGF-ß/Smad pathway in M2 macrophages, both in vitro and in vivo, induced by CSE and/or CS exposure, indicating that M2 macrophages might contribute to COPD through changing of phenotype and TGF-ß/Smad pathway.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171103
[Lr] Last revision date:171103
[St] Status:In-Process
[do] DOI:10.2147/COPD.S147144

  9 / 51496 MEDLINE  
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[PMID]: 29084507
[Au] Autor:Liu J; Peng Y; Lai J; Gao W; Song A; Zhang G
[Ad] Address:Department of Cardiology, Jiangmen Central Hospital, No.23, Haibang Street, Jiangmen, Guangdong, 529030, China.
[Ti] Title:Fluid upstream shear stress of rabbit aortic stenosis inhibits neointimal hyperplasia by promoting endothelization after balloon injury.
[So] Source:BMC Cardiovasc Disord;17(1):273, 2017 Oct 30.
[Is] ISSN:1471-2261
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Atherosclerosis is associated with disturbed blood flow characterized by low and oscillatory shear stress (SS), however, few study directly links SS to neointimal hyperplasia in animal model. This study was focused on the effects of changed SS upon the neointimal hyperplasia which responded to balloon injury in a novel rabbit model with partially-constricted abdominal aorta. METHODS: We established a rabbit model subjected to partial abdominal aortic constriction with a cylinder-shaped cannula as a model of disturbed flow, which was similar to the hemodynamic features of stenosis caused by atherosclerosis plaque. Further, balloon injury was performed to investigate the relationship between SS and neointimal hyperplasia. Four weeks later, the abdominal aorta was assessed with digital subtraction angiography (DSA) and intravascular ultrasound (IVUS). The vascular sections were embedded in paraffin blocks for morphometric analysis to evaluate neointimal hyperplasia, and anti-CD31 immunohistochemical staining was for endothelialization ratio. RESULTS: In upstream the stenosis, the changed SS leads to neointimal hyperplasia compared with normal SS (11,729 ± 1205 vs 8418 ± 737, P = 0.023). However, the upstream SS of the stenosis can promote vascular re-endothelialization after balloon injury compared with normal SS, verified by endothelialization ratio (0.36 ± 0.03 vs 0.32 ± 0.03, P = 0.017), thereby attenuate neointimal hyperplasia (64,851 ± 3995 vs 68,335 ± 3867, P = 0.018). CONCLUSION: The upstream SS of stenosis, not downstream SS, inhibits the neointimal hyperplasia after balloon injury by promoting vascular re-endothelializtion.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1710
[Cu] Class update date: 171102
[Lr] Last revision date:171102
[St] Status:In-Process
[do] DOI:10.1186/s12872-017-0690-3

  10 / 51496 MEDLINE  
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[PMID]: 29072128
[Au] Autor:Arita H; Nagata M; Yoshida R; Matsuoka Y; Hirosue A; Kawahara K; Sakata J; Nakashima H; Kojima T; Toya R; Murakami R; Hiraki A; Shinohara M; Nakayama H
[Ad] Address:1 Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
[Ti] Title:FBXW7 expression affects the response to chemoradiotherapy and overall survival among patients with oral squamous cell carcinoma: A single-center retrospective study.
[So] Source:Tumour Biol;39(10):1010428317731771, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.
[Mh] MeSH terms primary: Biomarkers, Tumor/genetics
Carcinoma, Squamous Cell/genetics
Cell Cycle Proteins/genetics
F-Box Proteins/genetics
Mouth Neoplasms/genetics
Ubiquitin-Protein Ligases/genetics
[Mh] MeSH terms secundary: Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/biosynthesis
Carcinoma, Squamous Cell/drug therapy
Carcinoma, Squamous Cell/pathology
Carcinoma, Squamous Cell/surgery
Cell Cycle Proteins/biosynthesis
Cell Proliferation/drug effects
Drug Resistance, Neoplasm/genetics
F-Box Proteins/biosynthesis
Female
Fluorouracil/administration & dosage
Gene Expression Regulation, Neoplastic/drug effects
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mouth Neoplasms/drug therapy
Mouth Neoplasms/pathology
Mouth Neoplasms/surgery
Prognosis
Retrospective Studies
Ubiquitin-Protein Ligases/biosynthesis
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Biomarkers, Tumor); 0 (Cell Cycle Proteins); 0 (F-Box Proteins); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 6.3.2.19 (FBXW7 protein, human); U3P01618RT (Fluorouracil)
[Em] Entry month:1711
[Cu] Class update date: 171102
[Lr] Last revision date:171102
[Js] Journal subset:IM
[Da] Date of entry for processing:171026
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317731771


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