BRAF and KRAS mutations in penile cancer and their correlation with clinical features.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 221-221 ◽  
Author(s):  
C. M. Valverde ◽  
J. Hernandez-Losa ◽  
C. Ferrandiz-Pulido ◽  
R. Morales ◽  
C. Suarez ◽  
...  
Keyword(s):  
Penile Cancer ◽  
Developed Countries ◽  
Advanced Stage ◽  
Clinicopathologic Features ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Histologic Subtype ◽  
Small Series ◽  
Kras Status

221 Background: Penile cancer is a rare disease in developed countries. While surgery may be curative for patients with localized disease, for metastatic patients systemic chemotherapy may offer palliation with usually short-lived responses. Thus, new options in this setting are needed. Retrospective series have reported EGFR overexpression in more than 90% of the cases and also interesting results of EGFR directed therapies in these patients have been comunicated. The role of KRAS status or other molecular markers as prognostic or predictive factors remains unclear. The aim of this study was to determine the prevalence of BRAF and KRAS somatic mutations in penile cancer and their correlation with clinicopathologic features. Methods: We analyzed 28 samples collected from de archives of the Pathology Department at our institution from 1996 to 2009. The DNAs were extracted from FFPE blocks by Biorobot EZ1 following the manufacturer protocol of the EZ1-DNA Tissue kit (Qiagen). KRAS and BRAF mutations were amplified with specific primers, and sequenced by Sanger with Bigdye terminator v3.1 Cycle Sequencing Kit. Medical records were reviewed for clinical data. Results: No BRAF mutations were found, but we identified somatic missense mutations in the KRAS gene (all activating G12D mutations) in 6/27 samples (22%, one not evaluable). Median age at diagnosis (73 vs. 71), grade and histologic subtype did not differ between wt and mutated (mt) patients. There was a trend toward a more advanced stage at diagnosis in mt versus wt : 33 versus 47% stage I, 16 versus 9% stage II and 50 versus 38% stage III respectively. 2/6 mt patients died (due to other causes) as did 5/21 wt patients (3 of them because of disease progression). Conclusions: BRAF mutations seem not involved in the EGFR pathway in penile carcinomas. The prevalence of KRAS mutations was unexpectedly high in our series and mt patients tended to be diagnosed at a more advanced stage. Unfortunately, no correlation was found with other clinicopathologic features, including overall survival in our small series. These results suggest a role of KRAS mutation in the development of these carcinomas and support the importance to determine KRAS status in patients to be treated with anti-EGFR based therapies. No significant financial relationships to disclose.

scholarly journals Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tiago F. Andreis ◽  
Bruno S. Correa ◽  
Fernanda S. Vianna ◽  
Fernanda De-Paris ◽  
Marina Siebert ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Predictive Biomarkers ◽  
Egfr Mutations ◽  
Southern Brazil ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Histologic Subtype ◽  
Molecular Alterations ◽  
Common Histologic Subtype ◽  
L1 Protein

PURPOSE Adenocarcinoma is the most common histologic subtype of non–small-cell lung cancer, representing 40% of all diagnoses. Several biomarkers are currently used to determine patient eligibility for targeted treatments, including analysis of molecular alterations in EGFR and ALK, as well as programmed death-ligand 1 (PD-L1) protein expression. Epidemiologic data reporting the frequency of these biomarkers in Brazilian patients with lung adenocarcinoma (LUAD) are limited, and existing studies predominantly included patients from the southeast region of the country. MATERIALS AND METHODS The goal of this study was to investigate the frequency of somatic mutations in the EGFR, KRAS, NRAS, and BRAF genes, ALK, and PD-L1 expression in a series of Brazilian patients diagnosed with LUAD predominantly recruited from centers in southern Brazil. Molecular analysis of the EGFR, KRAS, NRAS, and BRAF genes was performed by next-generation sequencing using DNA extracted from tumor tissue. Immunohistochemistry was used to detect ALK and PD-L1 expression. RESULTS Analysis of 619 tumors identified KRAS mutations in 189 (30.2%), EGFR mutations in 120 (19.16%), and BRAF mutations in 19 (3%). Immunohistochemistry demonstrated ALK and PD-L1 expression in 4% and 35.1% of patients, respectively. CONCLUSION To our knowledge, this is the first study investigating the molecular epidemiology of patients with LUAD from southern Brazil and the largest assessing the frequency of multiple predictive biomarkers for this tumor in the country. The study also reveals a distinct mutation profile compared with data originating from other regions of Brazil.

NRAS mutations in patients with advanced cancers treated with target-based therapies in early-phase clinical trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3106-3106 ◽  
Author(s):  
Vinu Madhusudanannair ◽  
Filip Janku ◽  
Gerald Steven Falchook ◽  
David S. Hong ◽  
Jennifer J. Wheler ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Mapk Signaling ◽  
Tumor Shrinkage ◽  
Breast Cancers ◽  
Wild Type ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Clinical Center ◽  
Early Phase Clinical Trials

3106 Background: NRAS mutations in cancers increase MAPK signaling. It is plausible that NRAS mutations may be associated with sensitivity to drugs targeting the MAPK pathway. Methods: Tumors from 689 patients with advanced cancers referred to the Clinical Center for Targeted Therapy (phase I program) were screened in a CLIA-certified laboratory for NRAS mutations and if feasible, for PIK3CA, KRAS, BRAF mutations and PTEN aberrations. Whenever possible, patients with NRAS mutations were treated with agents targeting the RAF-MEK pathway. Results: Of the 689 patients, 58 (8%) had NRAS mutations. NRAS mutations were most prevalent in melanoma (26/170, 25%), thyroid (5/26, 19%), endometrial (2/27, 7%), non-small cell lung (1/31, 3%), ovarian (1/60, 2%) and colorectal cancers (1/74, 1%). NRAS mutations were not seen in any of the tested head and neck squamous cell cancers (n = 44); sarcomas (n = 41) and breast cancers (n = 25). None (0/62, 0%) of the patients tested for KRAS had simultaneous NRAS and KRAS mutations, and only 2/42 (5%) tested for BRAF had simultaneous NRAS and BRAF mutations. Of 58 patients with NRAS mutations, 14 (24%) were enrolled in trials that included MEK axis inhibitors. Of these 14 patients, 13 had melanoma and 1 had ovarian cancer and 4/14 (29%) demonstrated tumor shrinkage >10% from baseline. In comparison, only 22/187 (12%) patients with wild-type/unknown NRAS, KRAS and BRAF treated on the same trials demonstrated tumor shrinkage >10% (p=0.086). Conclusions: NRAS mutations are diagnosed in variety of advanced cancers. Patients with NRAS mutations demonstrated a trend to better antitumor activity with MEK axis inhibitors compared to patients without NRAS, KRAS or BRAF mutations. Further studies are warranted to delineate the role of NRAS mutations in patients treated with MEK axis inhibitors.

Stage and histology influence the relationship between MDM2 promoter polymorphism and esophageal cancer and overall survival (OS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21047-21047
Author(s):  
H. J. Mackay ◽  
P. Bradbury ◽  
K. Asomaning ◽  
W. Zhou ◽  
M. Kulke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Early Stage ◽  
Disease Stage ◽  
Advanced Stage ◽  
Mdm2 Snp309 ◽  
Prognostic Role ◽  
Histologic Subtype ◽  
The Relationship

21047 Background: A single nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to affect OS of advanced stage gastric adenocarcinoma (AD) and early stage squamous (SQ) cell carcinoma of the lung. The aim of this study was to evaluate the role of this polymorphism in the prognosis of esophageal cancer, another aerodigestive cancer. Methods: 150 early stage (E) and 118 locally advanced stage (LA) esophageal cancers were genotyped for MDM2 SNP309 using Taqman. The primary endpoint was overall survival (OS). Results: E disease: n=23 stage I; n=127 stage II. LA disease: n=93, Stage III; n=25, Stage IVA. AD comprised 215 (81%), while SQ comprised 45 (17%) of cases; 8 (3%) had poorly differentiated tumors. Median follow-up = 32 months. Median OS were 36 and 21 months for E and LA disease, respectively. Both histology and disease stage affected the relationship between SNP309 and esophageal cancer OS (see Table ). The wildtype T/T genotype conferred a worse OS in E patients (log-rank, p=0.03), especially those with AD (log-rank, p=0.003). In Cox proportional hazards interaction analyses, after adjusting for age, gender, stage and PS, there were statistically significant interactions between MDM2 SNP309 and disease stage (interaction p=0.004) and between MDM2 SNP309 and histologic subtype (AD vs. SQ)(interaction p=0.02). Thus, the direction of SNP309 association from our AD and E esophageal cancer patients are opposite to those of our SQ and LA esophageal cancer patients. However, our SQ and LA results are similar to the SQ lung cancer and advanced stage gastric cancers previously reported. This suggests that biologic mechanisms underpinning the prognostic role of SNP309 are dependent on extent of disease and histologic subtype. Conclusion: Histology and disease stage interact with the prognostic role of MDM2 SNP309 polymorphism in esophageal cancer OS. [Table: see text] No significant financial relationships to disclose.

BRAF and KRAS mutations in liver-resected metastatic colorectal cancer (mCRC) patients (pts).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 476-476
Author(s):  
Francesca Bergamo ◽  
Marta Schirripa ◽  
Fotios Loupakis ◽  
Chiara Cremolini ◽  
Mariaelena Casagrande ◽  
...  
Keyword(s):  
Liver Resection ◽  
High Risk ◽  
Braf Mutation ◽  
Prognostic Role ◽  
Kras Mutations ◽  
Curative Intent ◽  
Mutational Status ◽  
Kras Status ◽  
The Impact

476 Background: Up today there are no molecular markers to identify mCRC pts candidate to curative liver surgery at high risk of relapse. There are conflicting results about the prognostic role of KRAS mutation in mCRC pts, while BRAF mutation is a well-known negative prognostic factor characterizing a subgroup of mCRCs with a distinct metastatic spread. We analyzed the impact of BRAF and KRAS mutations on relapse free-survival (RFS) and overall survival (OS) in pts undergoing liver resection with curative intent. Methods: Medical records of pts referred to 3 Italian institutions between 1995 and 2012 were reviewed. 3024 mCRC pts were identified. 401 pts (13.3%) underwent liver resection with curative intent and had adequate follow-up. Mutational status was assessable on 360 samples from primary tumors (n=63), metastases (mts) (n=59) or both (n=238). Primary objective was to evaluate the impact of BRAF mutation on RFS in mCRC pts candidate to liver resection. Secondary objectives were to evaluate the prognostic role of BRAF status on OS, and of KRAS status on RFS and OS in this population. Results: BRAF and KRAS were mutated in 11 (3%) and 116 (32%) out of 360 cases respectively. In 238 cases in which paired samples from primary and metastases were available, no discordance was found in BRAF status while 18 cases (7.6%) showed a discrepancy in KRAS status and were thus excluded from analysis. Pts with BRAF mutation had significantly shorter median RFS compared to pts with BRAF wt tumor (5.7 mos vs 11.7 mos, HR=4.25; 95%CI: 1.52-11.88, p=0.005). OS was significantly reduced in pts with BRAF mutated tumors vs wt (HR=5.39; 95%CI: 1.59-18.27, p=0.007). Mutated KRAS was not prognostic for RFS (HR=1.14; 95%CI: 0.87-1.49, p=0.34), while demonstrated a weak prognostic impact on OS (HR=1.52; 95%CI: 1.05-2.21, p=0.03). In this cohort high-risk Fong score were significantly associated with shorter RFS (p<0.0001) and OS (p<0.0001). Conclusions: BRAF mutation is associated with higher probability of relapse and worse outcome in liver resected mCRC. KRAS mutation was not associated with RFS after liver resection. BRAF mutational status may become a new prognostic marker when planning liver resection in mCRC pts.

Incidence and prognostic impact of KRAS and BRAF mutations in patients undergoing liver surgery for colorectal metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3616-3616 ◽  
Author(s):  
Georgios Karagkounis ◽  
Michael S. Torbenson ◽  
Hubert D Daniel ◽  
Nilofer Saba Azad ◽  
Luis A. Diaz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Surgical Therapy ◽  
Molecular Biomarkers ◽  
Braf V600e ◽  
Colorectal Metastases ◽  
Prognostic Impact ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Risk Of Recurrence ◽  
Kras Status

3616 Background: Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer metastases, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the prevalence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). Methods: KRAS and BRAF analysis was performed on 202 patients undergoing curative intent surgical therapy of CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS: codon 12/13, BRAF: V600E). The frequency of mutations was ascertained and their impact on outcome determined relative to other clinicopathologic factors. Results: KRAS gene mutations were detected in 58/202 patients (29%) undergoing surgery for CRLM, comparable to that reported in non-surgical patient series. In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. KRAS mutations were associated with worse long-term survival (HR=2.13, CI=1.25-3.65), as well as risk of recurrence (HR=1.89, CI=1.12-3.19). ). In addition, KRAS mutation was also associated with risk of recurrence following surgical therapy (HR=1.89, CI=1.12-3.19).While other clinicopathologic features, including tumor number, CEA and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited the ability to determine its prognostic impact. Conclusions: While KRAS mutations were found in approximately one third of patients, BRAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and disease-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.

How to Assure Stable Development in Unstable Financial Environment?

2007 ◽  
pp. 4-26 ◽  
Author(s):  
M. Ershov
Keyword(s):  
Stock Market ◽  
Developed Countries ◽  
Market Liquidity ◽  
Market Mechanisms ◽  
Russian Economy ◽  
The Developed Countries ◽  
Russian Stock Market ◽  
Stable Development ◽  
Financial Environment

Growing involvement of Russian economy in international economic sphere increases the role of external risks. Financial problems which the developed countries are encountered with today result in volatility of Russian stock market, liquidity problems for banks, unstable prices. These factors in total may put longer-term prospects of economic growth in jeopardy. Monetary, foreign exchange and stock market mechanisms become the centerpiece of economic policy approaches which should provide for stable development in the shaky environment.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Physical capital stock, technological upgrading and modernisation in Hungary

2005 ◽  
Vol 55 (2) ◽  
pp. 201-221 ◽  
Author(s):  
Andrea Szalavetz
Keyword(s):  
Capital Accumulation ◽  
Physical Capital ◽  
Developed Countries ◽  
Point Of View ◽  
Technology Generation ◽  
Development Policies ◽  
Specific Factors ◽  
Physical Capital Accumulation

This paper discusses the relation between the quality and quantity indicators of physical capital and modernisation. While international academic literature emphasises the role of intangible factors enabling technology generation and absorption rather than that of physical capital accumulation, this paper argues that the quantity and quality of physical capital are important modernisation factors, particularly in the case of small, undercapitalised countries that recently integrated into the world economy. The paper shows that in Hungary, as opposed to developed countries, the technological upgrading of capital assets was not necessarily accompanied by the upgrading of human capital i.e. the thesis of capital skill complementarity did not apply to the first decade of transformation and capital accumulation in Hungary. Finally, the paper shows that there are large differences between the average technological levels of individual industries. The dualism of the Hungarian economy, which is also manifest in terms of differences in the size of individual industries' technological gaps, is a disadvantage from the point of view of competitiveness. The increasing differences in the size of the technological gaps can be explained not only with industry-specific factors, but also with the weakness of technology and regional development policies, as well as with institutional deficiencies.

Nutrition in inflammatory bowel disease

2009 ◽  
Vol 150 (18) ◽  
pp. 839-845 ◽  
Author(s):  
János Banai
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fast Food ◽  
Optimal Growth ◽  
Developed Countries ◽  
Aetiological Factor ◽  
Artificial Nutrition ◽  
Food Preservatives ◽  
Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

Role of The Halal Industry in Recovering the National Economy in Covid-19 Pandemic

2020 ◽  
Vol 8 (2) ◽  
pp. 202-214
Author(s):  
Cucu Susilawati
Keyword(s):  
National Economy ◽  
Banking Sector ◽  
Developed Countries ◽  
Online News ◽  
Financial Industry ◽  
National Economic ◽  
Halal Food ◽  
Vigorous Growth ◽  
Business Sectors

The outbreak of the Covid-19 pandemic in Indonesia is attacking not only public health but also the economy. The presence of Covid-19 has many important impacts on developed countries. There are at least four industries most impacted by this pandemic, including households, MSMEs, companies and the financial industry. However, the halal industry is believed to be more resilient to the Covid-19 pandemic. This durability is because of the principles attributed to the halal sector, namely the importance of fairness, balance and openness. The author’s goal is therefore to carry out more in-depth research on the role of the halal industry in supporting the national economy, which is under pressure because of the COVID-19 pandemic. This type of study is a literature review with a material analysis approach that explores the conditions of the halal industry in Indonesia in depth. The material received is as books, published information, and online news. The findings of this study reveal that there are three halal business sectors that are believed to be more vulnerable to the Covid-19 pandemic in order to facilitate national economic recovery. Halal finance, halal food and halal fashion industries are among them. Halal finance from both the banking sector and the Islamic stock market has proved to be more robust than the mainstream financial sector. Besides guaranteed halal food, its wellbeing is also guaranteed, and halal fashion is now on the rise as Muslim fashion is increasingly innovative and global. We believe the three of them to have experienced vigorous growth, and also to continue to draw customers. And also after the Covid-19 pandemic, these three sectors could survive. Thus the halal industry also contributes to Indonesian economy.

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