The Expression of FAT1 is Associated with Overall Survival in Children with Medulloblastoma

2016 ◽  
Vol 103 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Jianzhong Yu ◽  
Hao Li

Purpose The FAT1 gene is involved in some cancers; however, its role in medulloblastoma is less clear. This study investigated the effects of FAT1 expression on the prognosis of medulloblastoma patients. Methods Whole exome sequencing was undertaken in 40 medulloblastoma patient samples. FAT1 mRNA and protein expression levels in normal and brain tumor tissues were determined by fluorescence quantitative PCR and immunohistochemistry, respectively. The association of FAT1 expression with overall survival (OS) was examined by Kaplan-Meier curve analysis with a log-rank test. Following lentiviral-mediated FAT1 knockdown using shRNA in Daoy cells, proliferation, Wnt signaling, and β-catenin protein expression were determined. Results Eight FAT1 missense mutations were detected in 7 patients. FAT1 mRNA expression in tumors was significantly lower than in adjacent normal tissue ( p = 0.043). The OS of patients with high FAT1 protein expression was significantly longer than that of patients with low FAT1 protein expression (median survival time: 24.3 vs 4.8 months, respectively; p = 0.002). shFAT1 cells had significantly higher proliferation rates than shControl cells ( p≤0.028). Furthermore, the mRNA expression of LEF1, β-catenin, and cyclin D1 was significantly upregulated in shFAT1-Daoy cells ( p≤0.018). Conclusions Low FAT1 expression was associated with poor prognosis in children with medulloblastoma. Furthermore, FAT1 may act on Wnt signaling pathway to exert its antitumor effect.

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hefei Wang ◽  
Yu Ren ◽  
Xiao Hu ◽  
Min Ma ◽  
Xiao Wang ◽  
...  

The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the β-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet β-cells from adipose-derived stem cells (ADSCs). After induction, ADSCs expressed markers of β-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation. Compared with pancreatic adult stem cells (PASCs), the quantities of insulin, GLUT2, and Irs2 mRNA decreased, whereas Gcg, Gck, and Irs1 mRNA increased. Over time, during differentiation, insulin mRNA and protein expression increased, Gcg and Gck mRNA expression increased, Irs1 mRNA expression decreased and then increased, and Irs2 mRNA increased and then decreased (all P<0.05). The expression of Dvl-2, LRP5, and GSK3β mRNA as well as the Dvl-2, GSK3β, and p-GSK3β proteins also increased (P<0.05). Expression of TCF7L2 (6–10 d) and β-catenin mRNA as well as the β-catenin protein increased but not significantly (P>0.05). Our results indicate that the Wnt signaling is activated during ADSC differentiation into islet β-cells, but there was no obvious enrichment of nonphosphorylated β-catenin protein.


2017 ◽  
Vol 42 (2) ◽  
pp. 743-752 ◽  
Author(s):  
Ren-Jun Peng ◽  
Bing Jiang ◽  
Xi-Ping Ding ◽  
He Huang ◽  
Yi-Wei Liao ◽  
...  

Aim: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. Methods: The rat model of SCI was established using Allen’s method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of β-catenin, Wnt3a, GSK-3β and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. Results: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the β-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3β and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.


2021 ◽  
pp. 000313482199506
Author(s):  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Won-Suk Lee ◽  
Jeong-Heum Baek

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.


2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p&lt;0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p&lt;0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p&lt;0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p&lt;0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p&lt;0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p&lt;0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p&lt;0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p&lt;0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p&lt;0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p&lt;0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.


2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.


2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Nathalie Taquet ◽  
Serge Dumont ◽  
Jean-Luc Vonesch ◽  
Didier Hentsch ◽  
Jean-Marie Reimund ◽  
...  

Crohn's disease (CD) is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417±71 times in CD peripheral blood mononuclear cells (PBMCs). Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10±3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.


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