K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival

PLA(2) signaling is involved in calpain-mediated degradation of synaptic dihydropyrimidinase-like 3 protein in response to NMDA excitotoxicity

Dihydropyrimidinase-like 3 (DPYSL3) is believed to play a role in neuronal differentiation, axonal outgrowth and neuronal regeneration, as well as cytoskeleton organization. Recently we have shown that glutamate excitotoxicity and oxidative stress result in calpain-dependent cleavage of DPYSL3, and that NOS plays a role in this process [R. Kowara, Q. Chen, M. Milliken, B. Chakravarthy, Calpain-mediated truncation of dihydropyrimidinase-like 3 protein (DPYSL3) in response to NMDA and H2O2 toxicity, J. Neurochem. 95 (2005) 466-474; R. Kowara, K.L. Moraleja, B. Chakravarthy, Involvement of nitric oxide synthase and ROS-mediated activation of L-type voltage-gated Ca(2+) channels in NMDA-induced DPYSL3 degradation, Brain Res. 1119 (2006) 40-49]. The present study investigates the involvement of PLA(2) signaling in NMDA-induced DPYSL3 degradation. Exposure of rat primary cortical neurons (PCN) to PLA(2) and COX-2 inhibitors significantly prevented NMDA-induced DPYSL3 degradation. Since the metabolic product of PLA(2) signaling, PGE(2), which augments toxic effect of NMDA, is known to stimulate cAMP, the effect of adenyl cyclase activator (forskolin plus IBMX) and inhibitor (MDL12,300) on NMDA-induced DPYSL3 degradation was tested. Our data indicate that the activation of adenyl cyclase contributes to NMDA-induced DPYSL3 degradation. Furthermore, cAMP-dependent protein kinase (PKA) inhibitor PKI (14-22) provided additional evidence of PKA involvement in NMDA-induced DPYSL3 degradation. In summary, the obtained data show the contribution of PLA(2) signaling to NMDA-induced calpain activation and subsequent degradation of synaptic protein DPYSL3NRC publication: Ye

Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer.

Searching for ways to improve the characterization of breast cancer we examined the relationship between the status of the FHIT gene transcript and amplification of c-myc and the c-erbB2 oncogene. Abnormal FHIT transcript was detected in 32 of 79 cancers examined. The presence of Fhit protein estimated by Western blots was evident only in cancers exhibiting a normal-sized FHIT transcript. This indicates that abnormal FHIT transcripts observed in our study did not encode any Fhit protein or the amount of such protein was very low. There was no association between the presence of aberrant FHIT gene transcript with age, tumor size, estrogen and progesterone receptor status, local metastases and histological grading. However, the abnormalities in FHIT gene transcripts were observed with different frequency depending on the histopathological type of the tumor. The aberrant FHIT transcript was detected in 60% of lobular cancers and only in 28% of ductal cancers. Analyzing the occurrence of c-myc and c-erbB2 amplification and the presence of aberrant FHIT gene transcripts we found that the aberrant FHIT transcript more frequently occurred in tissues with c-myc amplification. There was a significant (P <0.05) correlation between the occurrence of the aberrant FHIT gene transcript with accompanying c-myc amplification and positive lymph node status. However, in order to evaluate the predictive value of these findings in breast cancer, an extended clinical follow up will be necessary

K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma.

The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival

Increased plasma levels of hsa-miR-21-5p in patients with reduced left ventricle ejection fraction admitted urgently due to acute coronary syndrome

Myocardial ischemia that occurs during acute coronary syndrome (ACS) induces a cascade of pathophysiological processes which might lead to left ventricle dysfunction reflected by decreased left ventricular ejection fraction (LVEF) in echocardiographic examination. The enzymes regulating extracellular matrix (ECM) like matrix metalloproteinase 9 (MMP-9) also take part in this process. The MMP-9 activity is under control of a microRNA particle miR-21, which down-regulates its inhibitors. The study has shown, that in ACS population (n = 26) patients with LVEF &lt; 50% presented increased miR-21 relative expression levels comparing to patients with LVEF ≥50% (3,33 vs 1,64; p = 0,015). Moreover, a significant negative correlation between LVEF and miR-21 in this group of patients has also been presented