scholarly journals V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as a prognostic biomarker of poor outcomes in esophageal cancer patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aihemaijiang Kuerbanjiang ◽  
Maimaitiyiming Maimaituerxun ◽  
Yanjun Zhang ◽  
Yiliang Li ◽  
Gang Cui ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Analysis ◽  
Small Interfering Rna ◽  
Poor Prognosis ◽  
Scratch Test ◽  
Control Group ◽  
Viral Oncogene ◽  
Interfering Rna ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

Abstract Background Esophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes. Methods We used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan–Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models. Results The results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice. Conclusion BRAF overexpression may serve as an effective predictive factor for poor prognosis.

scholarly journals Treatment of NRAS-mutated advanced or metastatic melanoma: rationale, current trials and evidence to date

2017 ◽  
Vol 9 (7) ◽  
pp. 481-492 ◽  
Author(s):  
Amélie Boespflug ◽  
Julie Caramel ◽  
Stephane Dalle ◽  
Luc Thomas
Keyword(s):  
Metastatic Melanoma ◽  
Cytotoxic Chemotherapy ◽  
Disease Course ◽  
Line Treatment ◽  
First Line ◽  
Viral Oncogene ◽  
Melanoma Patients ◽  
Murine Sarcoma ◽  
Review Current ◽  
Viral Oncogene Homolog

The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15–25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment. We will review current preclinical and clinical developments in NRAS-mutated melanoma, and analyze ongoing clinical trials that are evaluating the benefit of different targeted and immune-based therapies, either tested as single agents or in combination, in NRAS-mutant melanoma.

scholarly journals Inhibition of PTEN Gene Expression by Small Interfering RNA on PI3K/Akt/FoxO3a Signaling Pathway in Human Nasopharyngeal Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382091795
Author(s):  
Liang Zhong Yao ◽  
Yan Li Zhu ◽  
Jun Jie Liu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Small Interfering Rna ◽  
Quantitative Polymerase Chain Reaction ◽  
Pten Gene ◽  
Control Group ◽  
Expression Levels ◽  
Human Nasopharyngeal Carcinoma ◽  
Interfering Rna

The objective of this article is to study the effect of inhibiting phosphatase and tensin homolog deleted chromatosome 10 gene on phosphoinositide 3-kinase/protein kinase B ( Akt)/Forkhead homeobox O3a signaling pathway in human nasopharyngeal carcinoma HK-1 cells. Nasopharyngeal carcinoma HK-1 cell lines were divided into PTEN gene interference group (siPTEN), nonspecific small interfering RNA group (siNC), empty vector group (Vector), and no transfection control group (Normal). The mRNA and protein expression levels of PTEN, PI3K, p-Akt, and FoxO3a were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot. Immunofluorescence was used to detect the subcellular localization of PTEN, PI3K, p-Akt, and FoxO3a in HK-1 cells. The proliferation of HK-1 cells was detected by MTT assay, and the apoptosis of HK-1 cells was detected by flow cytometry. Compared with the siNC group, the expression levels of PTEN, FoxO3a messenger RNA, and protein in the siPTEN group were significantly decreased ( P < .05), while the expression levels of PI3K, p-Akt messenger RNA, and protein were significantly increased ( P < .05). The growth rate of HK-1 cells in the siPTEN group was significantly higher than the siNC group ( P < .05), while the apoptosis rate was significantly lower than that of the siNC group ( P < .05). Small interfering RNA can inhibit the expression of PTEN in HK-1 cells, and PTEN can participate in the development of NPC by affecting PI3K/Akt/FoxO3a signaling pathway.

scholarly journals V-raf murine sarcoma viral oncogene homolog B (BRAF) mutations in hairy cell leukaemia

2015 ◽  
Vol 58 (1) ◽  
pp. 62
Author(s):  
Neeraj Arora ◽  
Sheila Nair ◽  
Rekha Pai ◽  
Sukesh Nair ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Hairy Cell Leukaemia ◽  
Cell Leukaemia ◽  
Hairy Cell ◽  
Braf Mutations ◽  
Viral Oncogene ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

CD24 Gene Polymorphism - A Novel Prognostic Factor in Esophageal Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e49-e54 ◽  
Author(s):  
Eran Sadot ◽  
Sarah Kraus ◽  
Michael Stein ◽  
Ilana Naboishchikov ◽  
Ohad Toledano ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Statistical Significance ◽  
Rflp Analysis ◽  
Tumor Stage ◽  
Control Group ◽  
Coding Region ◽  
Regional Lymph Nodes ◽  
Significant Difference

Background The CD24 gene has been correlated with poor prognosis of various malignancies. The significance of CD24 in esophageal cancer remains unknown. Our aim was to evaluate the association between CD24 genetic polymorphism and esophageal cancer. Materials and Methods Between June 2011 and May 2012 patients with esophageal cancer and healthy controls were prospectively enrolled and clinicopathological data were collected. Genomic DNA was extracted and restriction fragment length polymorphism (RFLP) analysis was performed to determine CD24 polymorphism at the coding region of CD24, which results in a substitution of the amino acid Ala by Val. Statistical significance was determined by unpaired t-test, χ2-test, and Fisher's exact test. Results A total of 102 patients were included, of whom 51 had esophageal cancer and the rest comprised a healthy control group. The incidence of the polymorphism variant (Val/Val) among the healthy subjects and the esophageal cancer cohort was 6% in both groups. The incidence of N3 (metastasis in 7 or more regional lymph nodes) was markedly higher in those esophageal cancer patients who carried the polymorphism variant compared with those who did not carry it (66% and 2%, respectively, p=0.007). No significant difference was found between the groups with regard to age, gender, histology type, tumor location, tumor stage, and other histological characteristics of the tumor. Conclusions This CD24 polymorphism may serve as a novel prognostic marker identifying esophageal cancer patients with poor prognosis. Further studies are warranted to evaluate CD24 function and to validate its predictive potential with regard to esophageal cancer.

scholarly journals Ring Finger Protein 149 Is an E3 Ubiquitin Ligase Active on Wild-type v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

2012 ◽  
Vol 287 (28) ◽  
pp. 24017-24025 ◽  
Author(s):  
Seung-Woo Hong ◽  
Dong-Hoon Jin ◽  
Jae-Sik Shin ◽  
Jai-Hee Moon ◽  
Young-Soon Na ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Wild Type ◽  
Viral Oncogene ◽  
Finger Protein ◽  
Type V ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

scholarly journals Atypical BRAF and NRAS Mutations in Mucosal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1133 ◽  
Author(s):  
Nicolas Dumaz ◽  
Fanélie Jouenne ◽  
Julie Delyon ◽  
Samia Mourah ◽  
Armand Bensussan ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Mucosal Melanoma ◽  
Mitogen Activated Protein Kinase ◽  
Nras Mutation ◽  
Viral Oncogene ◽  
Mitogen Activated Protein ◽  
Murine Sarcoma ◽  
Worse Prognosis ◽  
Viral Oncogene Homolog

Primary mucosal melanomas represent a minority of melanomas, but have a significantly worse prognosis than cutaneous melanomas. A better characterization of the molecular pathogenesis of this melanoma subtype could help us understand the risk factors associated with the development of mucosal melanomas and highlight therapeutic targets. Because the Mitogen-Activated Protein Kinase (MAPK) pathway plays such a significant role in melanoma development, we explore v-raf murine sarcoma viral oncogene homolog B (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations in mucosal melanoma and compare them to the mutation profiles in cutaneous melanoma and other tumors with BRAF and NRAS mutations. We show that in addition to being less frequent, BRAF and NRAS mutations are different in mucosal melanoma compared to cutaneous melanomas. Strikingly, the BRAF and NRAS mutation profiles in mucosal melanoma are closer to those found in cancers such as lung cancer, suggesting that mutations in mucosal melanoma could be linked to some genotoxic agents that remain to be identified. We also show that the atypical BRAF and NRAS mutations found in mucosal melanomas have particular effects on protein activities, which could be essential for the transformation of mucosal melanocytes.

lncRNA deleted in lymphocytic leukaemia 1 (DLEU1) promotes the migration and invasion of human embryonic trophoblast cells

Zygote ◽  
2020 ◽  
Vol 28 (5) ◽  
pp. 397-402
Author(s):  
Zhongxiang Li ◽  
Mingbin Hou
Keyword(s):  
Small Interfering Rna ◽  
Lymphocytic Leukaemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Regulatory Protein ◽  
Migration And Invasion ◽  
Control Group ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Interfering Rna ◽  
Human Trophoblast Cells

SummaryTo investigate the roles of lncRNA deleted in lymphocytic leukaemia 1 (DLEU1) on migration and invasion of human trophoblast cells. Human chorionic trophoblast cell line HTR8/SVneo was cultured and transfected using lncRNA DLEU1 small interfering RNA. Real-time quantitative polymerase chain reaction was used to detect lncRNA DLEU1 expression. The activity of migration regulatory protein CDC42 was detected by western blot. The downstream miRNA targets of lncRNA and mRNAs targeted by corresponding miRNAs were respectively predicted using bioinformatics analyses. Compared with the control group, the expression of lncRNA DLEU1 in the small interfering RNA group was significantly decreased (P < 0.05). There was no significant change in cell proliferation capacity for transfected cells (lncRNA DLEU1 siRNA-1, P = 0.537; lncRNA DLEU1 siRNA-2, P = 0.384), but cell migration (lncRNA DLEU1 siRNA-1, P = 0.025; lncRNA DLEU1 siRNA-2, P = 0.019) and invasion (lncRNA DLEU1 siRNA-1, P = 0.0327; lncRNA DLEU1 siRNA-2, P = 0.021) was significantly reduced. CDC42 activity in the lncRNA DLEU1 knockdown group decreased and the phosphorylation of cofilin increased. Therefore, downregulation of lncRNA DLEU1 suppressed the migration and invasion of human trophoblast cells.

scholarly journals Necessity of Microdissecting Different Tumor Components in Pulmonary Tumor Pyrosequencing

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Dahui Qin ◽  
Zhong Zheng ◽  
Shanxiang Shen ◽  
Prudence Smith ◽  
Farah K. Khalil
Keyword(s):  
Gene Mutations ◽  
Molecular Testing ◽  
Tissue Sampling ◽  
Wild Type ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Pulmonary Tumor ◽  
New Challenges ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

Microdissection is a useful method in tissue sampling prior to molecular testing. Tumor heterogeneity imposes new challenges for tissue sampling. Different microdissecting methods have been employed in face of such challenge. We improved our microdissection method by separately microdissecting the morphologically different tumor components. This improvement helped the pyrosequencing data analysis of two specimens. One specimen consisted of both adenocarcinoma and neuroendocrine components. When both tumor components were sequenced together for KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutations, the resulting pyrogram indicated that it was not a wild type, suggesting that it contained KRAS mutation. However, the pyrogram did not match any KRAS mutations and a conclusion could not be reached. After microdissecting and testing the adenocarcinoma and neuroendocrine components separately, it was found that the adenocarcinoma was positive for KRAS G12C mutation and the neuroendocrine component was positive for KRAS G12D mutation. The second specimen consisted of two morphologically different tumor nodules. When microdissected and sequenced separately, one nodule was positive for BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E and the other nodule was wild type at the BRAF codon 600. These examples demonstrate that it is necessary to microdissect morphologically different tumor components for pyrosequencing.

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