scholarly journals Rho GTPase-Activating Protein 35 rs1052667 Polymorphism and Osteosarcoma Risk and Prognosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jinmin Zhao ◽  
Hua Xu ◽  
Maolin He ◽  
Zhe Wang ◽  
Yang Wu

The Rho GTPase-activating protein 35 (ARHGAP35), an important Rho family GTPase-activating protein, may be associated with tumorigenesis of some tumors. Here, we investigated the relationship between an important polymorphic variant at 3′-UTR of this gene (rs1052667) and osteosarcoma risk and prognosis. This hospital-based case-control study, including 247 osteosarcoma patients and 428 age-, sex-, and race-matched healthy controls, was conducted in Guangxi population. Genotypes were tested using TaqMan PCR technique. We found a significant difference in the frequency of rs1052667 genotypes between cases and controls. Compared with the homozygote of rs1052667 C alleles (rs1052667-CC), the genotypes with rs1052667 T alleles (namely, rs1052667-CT or -TT) increased osteosarcoma risk (odds ratios: 2.41 and 7.35, resp.). Moreover, rs1052667 polymorphism was correlated with such pathological features of osteosarcoma as tumor size, tumor grade, and tumor metastasis. Additionally, this polymorphism also modified the overall survival and recurrence-free survival of osteosarcoma cases. Like tumor grade, ARHGAP35 rs1052667 polymorphism was an independent prognostic factor influencing the survival of osteosarcoma. These results suggest that ARHGAP35 rs1052667 polymorphism may be associated with osteosarcoma risk and prognosis.

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii36-ii36
Author(s):  
Dai Kamamoto ◽  
Hikaru Sasaki ◽  
Ryota Sasao ◽  
Takumi Fujiyama ◽  
Kazunari Yoshida

Abstract The optimal treatment for grade II/III meningioma is operation with or without radiation therapy. However, their natural course is sometimes aggressive with high recurrent rate. There is no effective treatment other than operation and radiation therapy, therefore, a new therapeutic strategy for grade II/III meningioma is urgently required.PD-1 and PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. In Japan, anti-PD-1 antibody and anti-CTLA-4 antibody are approved for unresectable melanoma or advanced / recurrent non-small cell lung cancer and their high effectiveness has been reported. We investigated the expression of PD-L1 (clone:28-8) in 51 cases of grade II/III meningioma by immunohistochemistry and analyzed the relationship between the expression with overall survival, progression free survival and initial WHO grade. For now, we have evaluated 25 cases of PD-L1 immunohistochemistry and PD-L1 showed positivity in 15 cases. There is no correlation observed between PD-L1 expression and patients’ prognosis. Although it does not reach a significant difference, the WHO grade at the time of initial operation tends to be high in those with high PD-L1 staining rate.Similar studies that were previously reported did not use antibodies targeting clone 28-8, which was used as a companion diagnosis for nivolumab administration, but “Correlation between PD-L1 expression and WHO grade”, or “PD-L1 expression is an independent prognostic factor” have been reported. In our investigation, which was using antibodies for companion diagnosis, PD-L1 was positive in more than half of Grade II / III meningiomas and it also related to WHO grade. These results suggest the possibility that tumor immune evasion mechanisms are also working in meningiomas. At the conference, we will report it with the specific data from all cases with a literature review.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4612-4612
Author(s):  
P. M. Pierorazio ◽  
S. M. Lambert ◽  
T. R. McCann ◽  
A. E. Katz ◽  
C. A. Olsson ◽  
...  

4612 Background: The presence of high-grade prostatic intraepithelial neoplasia (HGPIN) has been associated with future development of prostate cancer. High-grade intraepithelial neoplasia in other malignancies is associated with adverse outcome. This study examines the relationship between the presence of HGPIN in prostatectomy specimens, biochemical disease free survival (bDFS) and other cancer specific outcomes following radical retropubic prostatectomy (RRP). Methods: The Columbia University Urologic Oncology Database was reviewed and 2,522 were identified who had undergone radical prostatectomy from 1988 to 2005; 2,133 patients with or without HGPIN were included. Two-sample proportion analysis of means with 95% confidence intervals and ANOVA techniques were used to evaluate the relationship between HGPIN and pathologic stage, Gleason sum, perineural invasion, multifocality, extracapsular extension (ECE), margin status, and nodal status. Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model controlling for preoperative PSA, Gleason sum and pathologic stage were used to assess differences in bDFS. Results: 1,885 of 2,133 (88.4%) patients demonstrated HGPIN. There was no significant difference in the distribution of pathologic stage or Gleason sum between the patients with and without HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs. 57.5%; p = 0.003), multifocality (63.0 vs. 38.4%; p = 0.000) and ECE (56.4% vs. 48.4%; p = 0.059). There was no statistically significant difference observed in nodal status or margin status between the two groups. Patients without HGPIN had an increased bDFS demonstrated by a predicted disease free survival of 73.6% versus 67.0% at 9 years (p = 0.045) with a median follow-up of 50 months. In the multivariate Cox hazard model HGPIN, PSA, Gleason sum and pathologic stage were validated as independent predictors of failure (p < 0.001). The risk of failure was 1.9 × greater in the HGPIN-positive group than the HGPIN-negative group (p=0.006). Conclusions: The presence of HGPIN in the radical prostatectomy specimen denotes a significantly higher rate of tumor multifocality, perineural invasion, ECE, and ultimately biochemical recurrence. No significant financial relationships to disclose.


2002 ◽  
Vol 22 (24) ◽  
pp. 8721-8734 ◽  
Author(s):  
Takeshi Nakamura ◽  
Misako Komiya ◽  
Kiyoaki Sone ◽  
Eiji Hirose ◽  
Noriko Gotoh ◽  
...  

ABSTRACT Neurotrophins are key regulators of the fate and shape of neuronal cells and act as guidance cues for growth cones by remodeling the actin cytoskeleton. Actin dynamics is controlled by Rho GTPases. We identified a novel Rho GTPase-activating protein (Grit) for Rho/Rac/Cdc42 small GTPases. Grit was abundant in neuronal cells and directly interacted with TrkA, a high-affinity receptor for nerve growth factor (NGF). Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases. Overexpression of the TrkA-binding region of Grit inhibited NGF-induced neurite elongation. Further, we found some tendency for neurite promotion in full-length Grit-overexpressing PC12 cells upon NGF stimulation. These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases.


2020 ◽  
Vol 6 (2) ◽  
pp. 34-38
Author(s):  
Mohammad Moniruzzaman ◽  
Ashesh Kumar Chowdhury ◽  
ASM Areef Ahsan ◽  
Md Zakiur Rahman ◽  
Saimun Nahar Rumana ◽  
...  

Background: Rapid diagnosis is essential for effective therapy among the patients with sepsis. Objectives: The purpose of the present study was to determine the relationship of serum levels of IL-6, IL-8 in patients with various stages of sepsis. Methodology: This case control study was conducted in the Department of Immunology at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka from January 2015 to December 2015 for a period of one (01) year. All patients had been selected from the ICU of BIRDEM General Hospital with known clinicopathological parameters of sepsis. Serum levels of IL-6 and IL-8 were assessed using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: In this study, a total of 80 subjects was enrolled of which 60 patients were with at least 2 SIRS criteria and 20 healthy age matched controls without SIRS. Significant difference was found in IL-6 and IL-8 values in the patients with bacteriological culture positive and negative group (p<0.05). AUC for IL-6 was 0.710 (95% CI 0.580-0.840), sensitivity 54.16%, specificity 59.09%, PPV 74.28% and NPV 52% with cutoff value >177pg/ml. Conclusion: Elevated levels of serum IL-6 and IL-8 is found in the patients with sepsis Bangladesh Journal of Infectious Diseases 2019;6(2):34-38


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mansour Karajibani ◽  
Farzaneh Montazerifar ◽  
Razieh Hosseini ◽  
Fatemeh Suni ◽  
Ali Reza Dashipour ◽  
...  

Background: Malnutrition causes nutritional, metabolism, and biochemical disorders and finally leads to mortality. Several studies have highlighted that serum liver enzymes are increased in patients with malnutrition. Objectives: This study aimed to evaluate the relationship between malnutrition and liver enzymes in hospitalized children in Zahedan. Methods: This case-control study was conducted among 145 hospitalized children under six years old, including 74 cases and 71 controls. The case group was diagnosed with malnutrition according to weight for age indices (Z-Score < -2SD), and controls were determined based on the following indices (Z-Score > -2SD) of classification of WHO 2006 growth standards. Serum was isolated after taking blood from the samples. Then liver enzymes, including AST, ALP, and ALT, were measured by spectrophotometric method. Results: A total of 145 subjects were enrolled that consisted of 74 cases and 71 controls. No significant difference was observed in serum liver markers, including AST, ALT, and ALP between the two groups, However, the level of AST, ALT, and ALP was higher than the standard level. There was a significant correlation between AST with ALT (r = 0.74, P < 0.001), and ALP (r = 0.27, P = 0.03). Conclusions: The findings indicated that there was no significant alteration in enzyme markers in the two groups. However, AST and ALT levels increased, and ALP levels decreased compared with the control. Different degrees of malnutrition, including mild, moderate, and severe, can probably change the levels of hepatic enzymes in under-nourished children. Alteration of these liver enzymes could be due to the metabolic modification, which can be the result of protein deficiency.


Sarcoma ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Thomas Cash ◽  
Hong Yin ◽  
Courtney McCracken ◽  
Zhi Geng ◽  
Steven G. DuBois ◽  
...  

Background. Ezrin is a membrane-cytoskeleton linker protein that has been associated with metastasis and poor outcomes in osteosarcoma and high-grade soft tissue sarcomas. The prognostic value of ezrin expression in Ewing sarcoma is unknown.Methods. The relationship between ezrin expression and outcome was analyzed in a cohort of 53 newly diagnosed Ewing sarcoma patients treated between 2000 and 2011. The intensity and proportion of cells with ezrin immunoreactivity were assessed in diagnostic tumor tissue using a semiquantitative scoring system to yield intensity and positivity scores for each tumor.Results. Ezrin expression was detected in 72% (38/53) of tumor samples. The proportion of patients with metastatic disease was equal in the positive and negative ezrin expression groups. There was no significant difference in the 5-year event-free survival (EFS) between patients with positive versus negative ezrin expression. Patients whose tumor sample showed high ezrin intensity had significantly better 5-year EFS when compared to patients with low/no ezrin intensity (78% versus 55%;P=0.03).Conclusions. Ezrin expression can be detected in the majority of Ewing sarcoma tumor samples. Intense ezrin expression may be correlated with a favorable outcome; however further investigation with a larger cohort is needed to validate this finding.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 682-682
Author(s):  
Aalok Kumar ◽  
Renata D'Alpino Peixoto ◽  
Hagen F. Kennecke ◽  
Caroline Speers ◽  
Winson Y. Cheung

682 Background: The utility of neoadjuvant radiation (XRT) for the treatment of stages II-III rectal cancer has been demonstrated previously. However, the optimal amount and duration XRT in this setting remains unknown. Using a population-based cohort of stage II and II rectal cancer (RC) patients treated with curative intent including XRT, our aims were to 1) examine the patterns in XRT use and 2) explore the relationship between XRT course and survival. Methods: We analyzed patients diagnosed with clinical stage II-III RC from 2006 to 2010 and treated with long course 45-50.4 Gray (LC) or short course 25 Gray (SC) XRT at any 1 of 5 regional cancer centers in British Columbia. Logistic regression models were constructed to determine the factors associated with the course of XRT given, LC vs. SC. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between XRT course and disease-free (DFS), overall survival (OS), local recurrence free survival (LRFS) and distant recurrence free survival (DRFS). Results: 427 patients were identified: median age 65 years (range 31 to 94), 67% men, 87% T3/4 tumors, and 74% with N1 or N2 disease. Among them, 240 (56%) received SC and 187 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to receive LC (OR for LC 5.08, 95% CI, 2.51-11.22, p<0.0001 and 8.35, 95% CI, 3.35-22.39, p<0.0001, respectively), while older age patients were less likely to receive LC (OR 0.95, 95% CI, 0.94-0.98, p<0.0001). On univariate analysis, there was no significant difference seen in DFS, OS, LRFS, and DRFS between LC and SC. Similarly, in multivariate analyses comparing LC vs. SC, the course of XRT was not associated with differences in DFS (HR 1.06, 95% CI, 0.68-1.64, p=0.80), OS (HR 0.91, 95% CI, 0.61-1.37, p=0.66), LRFS (HR 0.79, 95% CI, 0.39-1.57, p=0.50) and DRFS (HR 0.99, 95% CI, 0.60-1.61, p=0.95). Additional baseline clinical and tumor characteristics did not influence outcomes (all p>0.05). Conclusions: Appropriate pre-operative selection of SC vs. LC neoadjuvant XRT for early stage RC based on patient and tumor characteristics was not associated with differences in survival outcomes.


2019 ◽  
Vol 47 (10) ◽  
pp. 4904-4910
Author(s):  
Aziz Ari ◽  
Cihad Tatar ◽  
Enver Yarikkaya

Objective Helicobacter pylori commonly occurs in the stomach, but localizations outside the stomach and related diseases have also been investigated. However, the relationship between H. pylori and gallstones remains controversial. We aimed to investigate the relationships between H. pylori in the stomach and the gallbladder and gallstones. Methods This prospective case-control study included patients who underwent cholecystectomy because of gallstones, pancreatic head cancer, or hepatic resection. The patients were separated into two groups according to the detection of H. pylori in gallbladder samples using Giemsa staining. Stomach H. pylori status was based on previous gastroscopy. Results The study enrolled 60 patients, comprising 27 patients with gallstones and 33 without. There was no significant difference in the incidence of gallstones between patients with or without H. pylori in the stomach or gallbladder. Furthermore, the presence of H. pylori in the stomach was measured in 14 patients and was significantly correlated with H. pylori in the gallbladder. Conclusion The current study showed no relationship between the occurrence of gallstones and the presence of H. pylori in either the gallbladder or the stomach. In contrast to previous reports, this suggests that H. pylori does not play a role in the development of gallstones.


2019 ◽  
Vol 47 (10) ◽  
pp. 4753-4763
Author(s):  
Jin Shu ◽  
Xuelian Hui ◽  
Xin Zheng ◽  
Juan Zhao ◽  
Zhaochen Xu ◽  
...  

Objective Breast cancer (BC) is a common malignancy among women worldwide. Fibroblast growth factor receptor 2 (FGFR2) rs2981582 is reported to play a vital role in BC development. However, the relationship between them remains unclear. Methods Ninety-five patients and 140 healthy controls were enrolled in the study. Plasma DNA was genotyped by the MassARRAY method. A meta-analysis was conducted to clarify the effect of FGFR2 polymorphism on BC risk. Results Our case-control study results revealed a significant difference in CC, TC, and TT genotypes between patients and controls. Logistic regression analysis showed that TT and TC genotype and the dominant mode were significantly correlated with BC development [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.050–2.27; OR = 1.81, 95% CI: 1.24–2.73; OR = 2.15, 95% CI: 1.25–5.31, respectively], even after adjusting for age, body weight, drinking, smoking, and estrogen receptor status. A meta-analysis of 15 studies showed significant differences among the dominant, recessive, heterozygote, and homozygote models between patients and controls. Conclusions Our results showed an association of FGFR2 rs2981582 polymorphism with BC in an Asian population. However, a more comprehensive study of the relationship between the polymorphism and BC is still needed.


Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 450-453
Author(s):  
Aydan Eroğlu ◽  
Yonca Eğin ◽  
Nejat Akar

AbstractTamoxifen is widely used in the treatment of breast cancer and associated with an increased risk of thromboembolism (TE). An elevated homocysteine is one of the risk factors for TE. The aim of the study was to assess the effect of tamoxifen on serum homocysteine levels in breast cancer patients. We performed a case-control study in 20 female subjects to evaluate the relationship between homocysteine levels, and 5,10-methylenetetrahyrofolate reductase (MTHFR) C677T and dihydrofolate reductase (DHFR) 19-bp intron-1 deletion polymorphisms in breast cancer patients and in control subjects. It was observed that homocysteine levels were decreased during tamoxifen therapy, but this finding was not statistically significant. There was also no statistically significant difference in homocysteine levels between the two groups (p> 0.05). MTHFR C677T and DHFR 19-bp deletion polymorphisms were not associated with serum homocysteine value in either group.


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