SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene

<p>Abstract</p> <p>Background</p> <p>The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the <it>SMAD4 </it>gene mutations with <it>KRAS </it>mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of <it>SMAD4 </it>gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and <it>KRAS </it>mutant genotype.</p> <p>Methods</p> <p>We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of <it>SMAD4 </it>and exon 1 of <it>KRAS </it>by PCR-SSCP and/or PCR-Direct sequencing.</p> <p>Results</p> <p>The overall mutation rate of mutation cluster region (MCR) region of <it>SMAD4 </it>gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the <it>SMAD4 </it>gene mutants were found to have mutations in <it>KRAS </it>gene as well. The association between the <it>KRAS </it>mutant genotype with <it>SMAD4 </it>mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the <it>SMAD4 </it>gene (P =< 0.05).</p> <p>Conclusion</p> <p>Our study suggests that <it>SMAD4 </it>gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the <it>KRAS </it>mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.</p

Relationships, love and sexuality: what the Filipino teens think and feel

<p>Abstract</p> <p>Background</p> <p>In order to achieve a change among teens' sexual behavior, an important step is to improve our knowledge about their opinions concerning relationships, love and sexuality.</p> <p>Methods</p> <p>A questionnaire including topics on relationships, love and sexuality was distributed to a target population of 4,000 Filipino students from third year high school to third year college. Participants were obtained through multi-stage sampling of clusters of universities and schools. This paper concentrates on teens aged 13 to 18.</p> <p>Results</p> <p>Students reported that they obtained information about love and sexuality mainly from friends. However, they valued parents' opinion more than friends'. They revealed few conversations with their parents on these topics. A majority of them would like to have more information, mainly about emotion-related topics. Almost half of respondents were not aware that condoms are not 100% effective in preventing STIs or pregnancies. More girls, compared to boys, were sensitive and opposed to several types of sexism. After adjusting for sex, age and institution, the belief of 100% condom effectiveness and the approval of pornography and sexism were associated with being sexually experienced.</p> <p>Conclusion</p> <p>There is room for further encouraging parents to talk more with their children about sexuality, specially aspects related to feelings and emotions in order to help them make better sexual choices. Indeed, teens wish to better communicate with their parents on these issues. Condoms are regarded as safer than what they really are by almost half of the participants of this study, and such incorrect knowledge seems to be associated with sexual initiation.</p

Genomic instability--the engine of tumorigenesis?

Human cancers harbour numerous mutations and it has been proposed that these result from some form of inherent genomic instability. Some cancers have proven genomic instability or features that are indicative of this. Inherited cancer syndromes exist that are caused by deficient DNA repair or chromosomal integrity. By contrast, theoretical analysis and experimental data from sporadic colorectal tumours provide little general evidence of genomic instability in early lesions. These apparently conflicting data raise the question of whether or not genomic instability is necessary for driving tumour growth, and whether or not it is the usual initiating event in tumorigenesis