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Yixing Jiang Heath Mackley Hua Cheng Jaffer A. Ajani 《Current colorectal cancer reports》2010,6(4):206-211
Ras and Raf proteins are two major players in the MAP kinase pathway. They are crucial downstream regulators of multiple receptor tyrosine kinase-mediated cell growth, transformation, and maintenance of the malignant phenotype in human cancers. Mutations have been identified in K-Ras and B-Raf in patients with colorectal cancer. Clinical studies in colorectal cancers demonstrate that the therapeutic efficacy of cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor, depends on the presence of wild-type K-Ras. However, mutations in B-Raf do not predict cetuximab resistance. These observations have led to the use of K-Ras as a predictive biomarker, allowing clinicians to direct the therapy of cancer patients based on their K-Ras mutational status. 相似文献
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Han-chun Chen Hui-juan Chen Md. Asaduzzaman Khan Zhou-zhou Rao Xin-xing Wan Bo Tan Dian-zheng Zhang 《Tumour biology》2011,32(2):367-373
This case–control study investigated the mutations in p53 and k-ras genes of 123 gastric carcinoma patients and 129 normal individuals from Hunan, China. By isolating genomic DNA from peripheral blood and employing polymerase chain reaction–single strand conformation polymorphism and DNA sequencing, the mutations of p53 exons-5, 6, 7, and 8 and k-ras were detected. The overall mutation frequency of p53 was 29.3%, and mutation was found in all four exons studied. The point mutations were predominant and among them, G:C→A:T was the highest (41.7%), followed by A:T→G:C (25%), G:C→C:G (11.1%), G:C→T:A (8.3%), and A:T→T:A (2.8%). The frameshift mutation was 11.1%. Mutations were detected in codons-131, 132, 133, 135, 149, 151, 162, 167, 173, 174, and 175 of exon 5, codons-193, 197, 213, and 215 of exon 6, codons-245, 246, 248, 249, and 270 of exon 7, and codons-271, 272, 273, and 282 of exon 8 of p53. The overall frequency of mutation in k-ras was 9.8%, mostly in codon-12 (91.7%) and in codon-13 (8.3%). There was no significant relationship between p53 and k-ras gene mutation in gastric carcinoma patients. Also, the relationships between p53 mutation and age, sex, smoking or drinking, and tumor metastasis were not significant. However, the patients with high/high-middle differentiated gastric carcinoma had a higher association with of p53 mutations. This study identified some novel p53 mutations in gastric cancer and showed mutation pattern and frequency of p53 and k-ras in the population of the central southern region of China. 相似文献
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Yun Jeong Kim Soo Jung Lee Jong Gwang Kim Sang Kyun Sohn Yee Soo Chae Joon Ho Moon Byung Woog Kang Jin Young Park Jun Seok Park Gyu Seog Choi 《Medical oncology (Northwood, London, England)》2011,28(4):1075-1079
Endothelial nitric oxide synthase (eNOS)–derived nitric oxide (NO) is involved in numerous physiologic and pathophysiologic process including tumor angiogenesis and apoptosis. Accordingly, the present study analyzed polymorphisms of eNOS gene and their impact on the prognosis for patients with colorectal cancer. Four hundred and forty-four consecutive patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 2 polymorphisms of eNOS gene (eNOS T786C and eNOS G894T) determined using a real-time PCR genotyping assay. The 2 eNOS gene polymorphisms were successfully amplified, and the frequencies of each genotype are as follows [T786C: TT (82.2%), TC (16.9%), CC (0.9%); G894T: GG (82.0%), GT (17.3%), TT (0.7%)]. Multivariate survival analysis including stage, age, site of disease, and CEA level showed that these polymorphisms were not associated with survival. For the clinicopathologic parameters, CEA level and TNM stage were significant prognostic factors in a Cox model for survival. The eNOS gene polymorphisms investigated in this study were not found to be an independent prognostic marker for Korean patients with surgically resected colorectal cancer. However, further studies are warranted to clarify the role of the eNOS gene polymorphisms as a prognostic biomarker for colorectal patients with cancer. 相似文献
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Lara Bethke Emily Webb Gabrielle Sellick Matthew Rudd Stephen Penegar Laura Withey Mobshra Qureshi Richard Houlston 《BMC cancer》2007,7(1):123
Background
Cytochrome P 450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones. 相似文献8.
BRCA1 and BRCA2 genes have a high allelic heterogeneity. The knowledge of the most prevalent mutations and their geographical distribution can be useful in designing efficient mutational screening. In the present work we reviewed the frequency of BRCA1 and BRCA2 recurrent mutations in seven geographic areas of Spain to evaluate the effects of their heterogeneous prevalence in genetic testing. We observed that prevalence of recurrent mutations vary according to the geographical origin of the studied families, and accounted for a variable number of positive families depending on the series. Therefore, more upcoming data of larger Spanish population cohorts collected from different areas in the country will allow to design a wider comprehensive panel of recurrent mutations that may be applicable worldwide to families with Hispanic origin. 相似文献
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Paola Matarrese Barbara Ascione Laura Ciarlo Rosa Vona Carlo Leonetti Marco Scarsella Anna M Mileo Caterina Catricalà Marco G Paggi Walter Malorni 《Molecular cancer》2010,9(1):207
Background
Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness. 相似文献11.
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<Emphasis Type="Italic">CYP2D6</Emphasis> Polymorphisms and Tamoxifen Metabolism: Clinical Relevance
The selective estrogen receptor modulator tamoxifen has been used for more than three decades to treat metastatic and early-stage
receptor-positive breast cancer and, more recently, to prevent the disease. Biotransformation of tamoxifen to the potent antiestrogen
endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. Genetic variants in the CYP2D6 gene may result in CYP2D6 enzymes with reduced or null activity. Strong and intermediate inhibitors of CYP2D6, which may
be used to treat hot flashes or psychiatric conditions in breast cancer patients, can also negatively impact enzyme function.
Prospective data are lacking, but the balance of current evidence strongly suggests that, compared with women with two wild-type
alleles, the presence of two null alleles, and possibly one null allele, predicts reduced tamoxifen metabolism and an inferior
outcome in postmenopausal women with early breast cancer who receive adjuvant treatment with the drug. Unfortunately, studies
to date have been largely retrospective and the interpretation of their results is limited by examination of archival tissue
samples and the inclusion of heterogeneous populations. Although we do not currently recommend routine CYP2D6 testing for women who do not have alternative standard therapies, the use of concomitant strong or intermediate inhibitors
of CYP2D6 should be avoided if feasible. This review summarizes the literature to date with a focus on clinically relevant
recent studies that examined the association between CYP2D6 polymorphisms and tamoxifen-associated outcomes. 相似文献
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Susmita Ghosh Amlan Ghosh Guru P Maiti Nupur Mukherjee Sankhadeep Dutta Anup Roy Susanta Roychoudhury Chinmay K Panda 《Molecular cancer》2010,9(1):58
Introduction
To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC), alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines. 相似文献15.
Judith M. E. Walsh René Salazar Celia Kaplan Lamkieu Nguyen Jimmy Hwang Rena J. Pasick 《Journal of cancer education》2010,25(1):36-42
Colorectal cancer (CRC) screening rates are low among Latinos. To identify factors associated with CRC screening, we conducted a telephone survey of Latino primary care patients aged 50–79 years. Among 1,013 participants, 38% were up-to-date (UTD) with fecal occult blood test (FOBT); 66% were UTD with any CRC screening (FOBT, sigmoidoscopy, or colonoscopy). Individuals less than 65, females, those less acculturated, and patients of female physicians were more likely to be UTD with FOBT. CRC screening among Latinos is low. Younger patients, women, and patients of female physicians receive more screening. 相似文献
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