scholarly journals P14.122 Integrin α5 is a poor prognostic factor in patients with glioblastoma treated by the Stupp protocol

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii97
Author(s):  
N Etienne-Selloum ◽  
J Prades ◽  
D Bello Roufai ◽  
F El Azumi ◽  
M Boone ◽  
...  
Keyword(s):  
Protein Expression ◽  
Survival Data ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Expression Level ◽  
Rank Test ◽  
Protein Expression Level ◽  
Poor Prognostic Factor ◽  
Integrin Α5 ◽  
Stupp Protocol

Abstract BACKGROUND Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness through preclinical studies and genomic analysis of several cohorts of patients. However, protein expression data are still missing to confirm this hypothesis. Our aim was to investigate the prognostic value of integrin α5 protein expression level in GBM. MATERIAL AND METHODS We retrospectively determined the protein expression level of integrin α5 using immunochemistry in tumors from patients treated in 6 French centers. Paraffin sections of GBM were labeled by immunofluorescence and analyzed by confocal microscopy. The corresponding clinical and survival data have been identified and analyzed. The primary end-point was overall survival (OS). RESULTS Out of 297 patients newly diagnosed with GBM between 2006 and 2013, 152 met the inclusion criteria (scheduled for initial treatment with the Stupp protocol, age > 18 years) and 95 tumor samples were suitable for immunohistochemical analysis. The median age is 58 years, (64 men, 34 women). Most of patients received macroscopic (43%) or partial (36%) surgery. In univariate analysis using the Log Rank test, high integrin α5 expression level was associated with poor prognosis (PFS: hazard ratio (HR) = 1,696, p=0,0355; OS: HR=1,598, p = 0,0508). Corresponding median OS were 15,6 versus 19,2 months. Similarly, OS was significantly reduced with age (> 60 years), lower resection degree, higher RPA (recursive partitioning analysis) score and non-methylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter. In the subgroup of patients who received the full initial protocol (temozolomide treatment together with radiotherapy and later as adjuvant treatment; n=58) mean OS was strongly reduced when integrin α5 expression level was high (15,6 versus 22,8 months, p=0,0162) suggesting an impact of integrin signaling on temozolomide response in GBM. CONCLUSION Our study validates for the first time that the high protein level expression of α5 integrin is associated with poor prognosis in GBM. It also confirms its potential as a therapeutic target and its likely role in resistance to temozolomide as previously shown in preclinical study.

scholarly journals Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma

2021 ◽  
Vol 14 (9) ◽  
pp. 882
Author(s):  
Nelly Etienne-Selloum ◽  
Julien Prades ◽  
Diana Bello-Roufai ◽  
Mathieu Boone ◽  
Henri Sevestre ◽  
...  
Keyword(s):  
Protein Expression ◽  
Expression Level ◽  
Prognostic Impact ◽  
Integrin Subunit ◽  
Line Treatment ◽  
Protein Expression Level ◽  
First Line ◽  
Integrin Α5 ◽  
Stupp Protocol ◽  
First Line Treatment

Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness and treatment resistance through preclinical studies and genomic analysis in patients. However, further protein expression data are still required to confirm this hypothesis. In the present study, we investigated by immunofluorescence the expression of integrin α5 and its prognostic impact in a glioblastoma series of patients scheduled to undergo the Stupp protocol as first-line treatment for GBM. The integrin α5 protein expression level was estimated in each tumor by the mean fluorescence intensity (MFI) and allowed us to identify two subpopulations showing either a high or low expression level. The distribution of patients in both subpopulations was not significantly different according to age, gender, recursive partitioning analysis (RPA) prognostic score, molecular markers or surgical and medical treatment. A high integrin α5 protein expression level was associated with a high risk of recurrence (HR = 1.696, 95% CI 1.031–2.792, p = 0.0377) and reduced overall survival (OS), even more significant in patients who completed the Stupp protocol (median OS: 15.6 vs. 22.8 months; HR = 2.324; 95% CI 1.168–4.621, p = 0.0162). In multivariate analysis, a high integrin α5 protein expression level was confirmed as an independent prognostic factor in the subpopulation of patients who completed the temozolomide-based first-line treatment for predicting OS over age, extent of surgery, RPA score and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 0.029). In summary, for the first time, our study validates that a high integrin α5 protein expression level is associated with poor prognosis in GBM and confirms its potential as a therapeutic target implicated in the Stupp protocol resistance.

scholarly journals Comprehensive Analysis of ESRRA in Endometrial Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Operating Characteristics ◽  
Protein Expression Level ◽  
Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

scholarly journals Evaluation of Patched-1 Protein Expression Level in Low Risk and High Risk Basal Cell Carcinoma Subtypes

2019 ◽  
Vol 20 (9) ◽  
pp. 2851-2857 ◽  
Author(s):  
Rowida Almomani ◽  
Mariam Khanfar ◽  
Khaldon Bodoor ◽  
Firas Al-Qarqaz ◽  
Mohammad Alqudah ◽  
...  
Keyword(s):  
High Risk ◽  
Basal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Low Risk ◽  
Expression Level ◽  
Protein Expression Level ◽  
Patched 1

scholarly journals Piceatannol Ameliorates Hepatic Oxidative Damage and Mitochondrial Dysfunction of Weaned Piglets Challenged with Diquat

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1239
Author(s):  
Peilu Jia ◽  
Shuli Ji ◽  
Hao Zhang ◽  
Yanan Chen ◽  
Tian Wang
Keyword(s):  
Oxidative Damage ◽  
Protein Expression ◽  
Complex I ◽  
Sirtuin 1 ◽  
Expression Level ◽  
Control Group ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Protein Expression Level ◽  
Atp Production

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis.

Interleukin-6 stimulates α-MG uptake in renal proximal tubule cells: involvement of STAT3, PI3K/Akt, MAPKs, and NF-κB

2007 ◽  
Vol 293 (4) ◽  
pp. F1036-F1046 ◽  
Author(s):  
Yu Jin Lee ◽  
Jung Sun Heo ◽  
Han Na Suh ◽  
Min Young Lee ◽  
Ho Jae Han
Keyword(s):  
Protein Expression ◽  
Proximal Tubule ◽  
Signaling Pathways ◽  
Interleukin 6 ◽  
Renal Proximal Tubule ◽  
Expression Level ◽  
Protein Expression Level ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells

Recent studies have shown that interleukin 6 (IL-6) acts on the cellular proliferation-activating transduction signals during cellular regeneration. Therefore, this study examined the effect of IL-6 on the activation of Na+/glucose cotransporters (SGLTs) and its related signaling pathways in primary cultured renal proximal tubule cells (PTCs). IL-6 increased the level of α-methyl-d-[14C]glucopyranoside (α-MG) uptake in time- and dose-dependent manners. IL-6 also increased SGLT1 plus SGLT2 mRNA and protein expression level. The IL-6 receptors (IL-6Rα and gp130) were expressed in PTCs. In addition, genistein and herbimycin A completely blocked the IL-6-induced increases in α-MG uptake and the protein expression level of SGLTs. On the other hand, IL-6 increased the level of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-sensitive cellular reactive oxygen species (ROS), and IL-6-induced increases in α-MG uptake and the protein expression level of SGLTs were blocked by ascorbic acid or taurine (antioxidants). IL-6 also increased the phosphorylation of signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) in a time-dependent manner. A pretreatment with STAT3 inhibitor LY 294002, an Akt inhibitor, or MAPK inhibitors significantly blocked the IL-6-induced increase in α-MG uptake. In addition, IL-6 increased the level of nuclear factor-κB (NF-κB) phosphorylation. A pretreatment with SN50 or BAY 11-7082 also blocked the IL-6-induced increase in α-MG uptake. In conclusion, IL-6 increases the SGLT activity through ROS, and its action in renal PTCs is associated with the STAT3, PI3K/Akt, MAPKs, and NF-κB signaling pathways.

Mechanism of Anti-Hepatic Fibrosis of TGF-β1/Smad Signaling Pathway Affected by Chymase Inhibitors

2020 ◽  
Vol 10 (6) ◽  
pp. 782-788
Author(s):  
Xue-Ji Han ◽  
Ning Chen ◽  
Ming-Shi Yin
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Model Group ◽  
Protein Expression Level ◽  
Smad Signaling Pathway ◽  
Chymase Inhibitor ◽  
Liver Tissues

Objective: This study aims to investigate the pathological mechanism of chymase inhibitors (Chy-I) on liver tissue in rats with hepatic fibrosis. Methods: Rats in the model group and chymase inhibitor group were established by using carbon tetrachloride. Rats in the chymase inhibitor group intragastrically received Chy-I (10 mg/kg/d) during the modeling. The pathological changes of rat liver tissues induced by chymase inhibitors were investigated, and the mRNA and protein expression of TGF-β1, Smad3 and Smad7 were observed in rat liver tissues. Results: When compared to the model group, The results presented that the liver tissue pathology of rats had been significantly improved in the Chy-I group. When compared to the normal group, the mRNA expression level and protein expression level of TGF-β1 and Smad3 in liver tissues had significantly increased, but the mRNA expression level and protein expression level of Smad7 significantly decreased (p < 0 05). When compared to the model group, the mRNA expression level and protein expression level of TGF-β1 and Smad3 was significantly downregulated, but the mRNA expression level and protein expression level of Smad7 was significantly upregulated in the Chy-I group. Conclusion:Chy-I plays an active role in blocking hepatic fibrosis in rats by affecting the TGF-β1/Smad signaling pathway in liver tissues through multiple sites.

Factors influencing survival in inflammatory breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 136-136
Author(s):  
Julie A. Cupp ◽  
Diane Liu ◽  
Yu Shen ◽  
Naoto T. Ueno ◽  
Ricardo H. Alvarez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Poor Prognosis ◽  
Cox Model ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Rapid Progression ◽  
Progression Of Disease ◽  
Delay In Treatment

136 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer associated with poor prognosis, characterized by rapidly growing mass, skin changes, and regional adenopathy. The objective of this study was to determine if delay in treatment influenced survival in IBC patients. Methods: A prospective IBC database identified 93 women with stage III IBC who received care at MD Anderson from 2007 - 2012 and were retrospectively reviewed. All patients received neoadjuvant chemotherapy followed by surgery, unless progression of disease was noted, and postmastectomy radiation. Impact of time from onset of symptoms to chemotherapy or to surgery on overall survival (OS) and progression free survival (PFS) were evaluated after adjusting for the baseline covariates in the Cox model. Results: A majority of patients were white (77.4%) with an average age of 54 years. Average days from onset of symptoms to first chemo is 95 (range 16 – 387) and to surgery is 283 (range 184 – 585). Four patients had progression while on chemo. There were 14 deaths with median follow up of 2.6 years from diagnosis. In univariate analysis, delay in treatment, > 90 days from onset of symptoms to chemo, did not affect OS or PFS. Obtaining negative margins was statistically significant for OS and PFS measured from first chemo (p=0.005 and p=0.007). Positive HER-2 status was associated with longer PFS time from chemo (p=0.02, log-rank test) and from surgery (p=0.009). Positive progesterone receptor (PR) was found to be statistically significantly associated with longer OS time from chemo (p=0.01) and from surgery (p=0.03). Clinical and imaging response to chemo were associated with better OS (p=0.007 and p=0.005) and pathologic response was marginally associated with improved OS and PFS (p=0.07 and p=0.06), both measured from surgery. In multivariate Cox model, adjusting for PR or HER2, days from onset of symptoms to chemo or surgery did not have significant impact on OS or PFS. Conclusions: While traditionally delay diagnosis and treatment is considered one of the factors associated with poor prognosis, our study suggests otherwise. However, due to such rapid progression of disease, early diagnosis is still important in the overall management of patients diagnosed with IBC.

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