Francisco Rodríguez-Moranta

Bio: Francisco Rodríguez-Moranta is an academic researcher from Bellvitge University Hospital. The author has contributed to research in topics: Colorectal cancer & Inflammatory bowel disease. The author has an hindex of 27, co-authored 94 publications receiving 3227 citations. Previous affiliations of Francisco Rodríguez-Moranta include University of Barcelona.

Correction: Corrigendum: Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study

Abstract: Scientific Reports 7: Article number: 43263; published online: 24 February 2017; updated: 17 May 2017 The original version of this Article contained a typographical error in the spelling of the author Pablo Fernandez-Navarro, which was incorrectly given as Pablo Fernandez Navarro. This has now been corrected in both the PDF and HTML versions of the Article.

Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer

Abstract: ContextThe selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability.ObjectiveTo establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers.Design, Setting, and PatientsA prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.InterventionsMicrosatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing.Main Outcome MeasuresEffectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations.ResultsTwo hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001).ConclusionThe revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.

Colorectal cancer: from prevention to personalized medicine.

Abstract: Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass.

Postoperative Surveillance in Patients With Colorectal Cancer Who Have Undergone Curative Resection: A Prospective, Multicenter, Randomized, Controlled Trial

Abstract: Purpose Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability. Patients and Methods Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added. Results A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. Af...

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Patterns of Somatic Mutation in Human Cancer Genomes

Abstract: AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore PL02-05 All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Defective Mismatch Repair As a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon Cancer

Abstract: Purpose Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. Methods MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with ...