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Objective: To investigate the molecular deficiency in MMR genes associated to Lynch syndrome., Material and Methods: Immunohistochemical and microsatellite instability (MSI) analysis were performed in 5 families with suspected Lynch syndrome according to the clinical criteria, Amsterdam and/or Bethesda that had been treated at the Hospital Nacional Almanzor Aguinaga Asenjo (Lambayeque-Peru) during 2007-2010., Results: The absence of expression of MLH1/PMS2 and high MSI (MSI-H) were observed in a male patient aged 60 with adenocarcinoma grade I. In addition, the point mutational analysis was performed in BRAF (V600E) to rule that it is a sporadic case of colorectal cancer. The absence of mutation in BRAF together with the molecular analysis suggests the suspicion as a Lynch syndrome., Conclusions: It is the first molecular study reported in the Peruvian population and demonstrates the importance of molecular analysis in families with suspected hereditary colorectal cancer in order to provide possibilities of surveillance and monitoring that have been shown to reduce morbidity and mortality of colorectal cancer in the Peruvian population.

Introduction: Excessive consume of hypercaloric and high in saturated fat food causes an atherogenic dyslipidemia. In this study we analyzed the effects of PPARβ/δ activator GW501516 on the hypertriglyceridemia induced by a high-fat diet., Methods: Male mice were randomized in three groups: control (standard chow), high fat diet (HFD, 35% fat by weight, 58% Kcal from fat) and high fat diet plus GW501516 (3mg/Kg/day). Treatment duration was three weeks., Results: HFD-induced hypertriglyceridemia was accompanied by a reduction in hepatic levels of phospho-AMPK and in PGC-1α and Lipin1 mRNA levels. All these effects were reversed by GW501516 treatment. The lack of changes in phospho-AMPK levels after GW501516 treatment in HFD-fed animals could be the result of an increase in the AMP/ATP ratio. GW501516 treatment also increased Lipin1 protein levels in the nucleus, led to the amplification of the PGC-1α-PPARα pathway and increased PPARα DNA-binding activity, as well as the expression of PPARα-target genes involved in fatty acid oxidation. GW501516 also increased β-hydroxibutirate plasmatic levels, a hepatic β-oxidation end product. Finally, GW501516 increased the hepatic levels of the PPARα endogenous ligand 16:0/18:1-PC and the expression of the VLDL receptor., Conclusion: These data indicate that the hypotriglyceridemic effect of GW501516 in mice subjected to HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-Lipin1-PPARα pathway., (Copyright © 2012 Elsevier España, S.L. and SEA. All rights reserved.)

Introduction: Huntington's disease is an autosomal dominant hereditary disorder. This neurodegenerative illness is characterized by mutation of the huntingtin protein gene, causing the formation of intracellular protein aggregates., Development: Intensive research efforts have been made to investigate the molecular mechanism involved. For this reason, the development of animal and cellular models of Huntington's disease has offered alternative approaches to study of this disease. The alteration of succinate dehydrogenase activity has been linked to Huntington's disease. 3-nitropropionic acid is an inhibitor of this enzyme, prompting oxidative stress and death neuronal, mimic some aspects of Huntington's disease as anatomical, physiological and chemical changes., Conclusion: This model is a useful tool to study the mechanisms involved in this disease and to evaluate new therapeutic strategies.

Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene.

Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.

Object: The aim of this study was to investigate prognosis value of p53 oncosuppresor gene and labeling index by MIB-1 and PCNA monoclonal antibodies in malignant gliomas., Methods and Results: We operated 60 patient with malignant glioma between July 1994 and August 1998. Forty-five cases had the histopathological diagnosis of Glioblastoma Multiforme and fifteen cases of anaplastic astrocytoma or olygoastrocytoma. Initially we compare MIB-1/PCNA labeling index in eighteen cases. Patients < 40 years old, short period of symptoms preoperatively, only one cerebral lobe localization, total surgical exeresis, Karnofsky index > 70 postoperatively, low labeling index (MIB < 8.6%), forward radiotherapy treatment and surgical re-operation, were identified like favourable outcome factors in the uninvariable analysis. However to the multivariable analysis, only had outcome significance: patients < 40 years old, low labeling index, Karnofsky index > 70 postoperatively and surgical reoperation., Conclusions: On the basis of the results of current analysis, moreover classical factors associated with better outcome, low labeling index to Glioblastoma Multiforme have been noted in patients with longer survival, and must be included to conventional histopathological studies.

The p53 tumor suppressor gene is believed to play an important role in the progression of malignant tumors through mutation and overexpression. The p53 protein and Ki-67 immmunochemistry were performed on an early gallbladder carcinoma with atypical epithelium. Overexpression of the protein was found in adenocarcinoma area with diffusely distributed positive cells (p53 index: 76 +/- 24%) and in atypical epithelial areas with foci of diffusely distributed positive cells (p53 Index: 30 +/- 14%), while the Ki-67 index was 6 +/- 4% in the adenocarcinoma areas and 6 +/- 2% in the atypical epithelial areas in each p53 measured corresponding areas. This suggest that p53 protein overexpression occurs in early carcinoma and/or atypical epithelium at least in some cases and that it is an early event in the development of gallbladder adenocarcinomas and also that the atypical epithelium may belong to carcinoma.