Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Mutations in the KRAS and BRAF genes have been confirmed as negative predictors of the response to EGFR-targeted therapies.In this study we evaluated KRAS and BRAF status in 159 colorectal cancer samples obtained from the University of Tirana.We evaluated KRAS mutations in codons 12, 13, 61, 146 and in codon 600 of BRAF by direct sequencing. 90 patients were male (57%) and 69 female (43%); the patients' ages ranged from 17 to 85 (median 61.7). 24 patient were stage I, 36 stage II, 84 stage III and 15 stage IV.Out of the 159 cases, 28 (17,6%) showed KRAS mutation (13 G12D, 4 G12C, 4 G12V, 3 G12A, 2 G13 D, 1 G12S and 1 A146T), and 10 (6,3%) showed BRAF mutation (all V600E). No significant correlations between KRAS and BRAF mutations and various clinicopathological parameters was found.This is the first report of KRAS and BRAF status in Albanian patients with colorectal carcinoma (CRC) and though the relatively small sample size might not provide enough statistics power.The results of KRAS and BRAF mutation analysis could be used in the selection of patients for anti-EGFR therapy.The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_187.
BackgroundExploring the literature stream of the knowledge perspective as well as that of start-ups andincubation, and subsequently bringing the two together.AimTo construct propositions regarding ...
MicroRNA (miRNA) expression is dysregulated in many human malignancies, and a growing number of studies are focused on their potential use as tumor biomarkers. To identify a miRNA signature for papillary thyroid carcinomas (PTC), we investigated miRNA expression profiles in two independent cohorts of PTCs, which included major histological subtypes [classical-type (PTC‑CT), follicular-variant (PTC‑FV), and tall-cell variant (PTC‑TCV)] and cases with low or intermediate risk of recurrence. Using TaqMan® Array Human MicroRNA A+B Cards v3.0, we first performed microRNA profiling of normal and neoplastic thyroid tissues from 29 PTC patients. Promising candidates were then investigated in a second, independent cohort of 76 PTCs using Custom TaqMan® Array MicroRNA Cards. We identified a molecular signature of 11 miRNAs that were significantly upregulated (miR‑146b-5p, miR‑146b-3p, miR‑221-3p, miR‑222‑5p, miR‑222‑3p) or downregulated (miR‑1179, miR‑486‑5p, miR‑204-5p, miR‑7-2-3p, miR‑144-5p, miR‑140-3p) in PTC tissues vs. normal thyroid tissue. Upregulation of miR‑146b-5p and miR‑222‑3p was also significantly associated with an increased risk of recurrence. Higher than normal expression of miR‑146b-5p and miR‑146b-3p characterized PTC‑CT and PTC‑TCV but not PTC‑FV, whereas miR‑21-5p was significantly upregulated only in PTC‑TCV. When PTC‑FV were subclassified as encapsulated (PTC‑EFV) or infiltrative (PTC‑IFV), miR‑204-5p was downregulated in all histological subtypes except PTC‑EFV, which displayed expression levels similar to those of normal thyroid tissues. These findings provide new insights into the molecular classification of PTC, showing that different miRNA expression profiles are associated with different histological types of PTC and different risks of recurrence.
Abstract Thrombocytopenia is a common side effect of chemotherapy, responsible for increased risk of bleeding and delay of treatment schedules in cancer patients. It is currently unknown how chemotherapeutic agents affect platelet production and whether the platelet precursors megakaryocytes represent a direct target of cytotoxic drugs. We investigated the effects of chemotherapeutic agents on primary megakaryocytes by using a culture system that recapitulates in vitro human megakaryopoiesis and found that cytotoxic drugs predominantly destroyed megakaryocytic progenitors at early stages of differentiation. Immature megakaryocytes could be protected from chemotherapeutic agents by the cytokine stem cell factor (SCF), which binds the c-kit receptor expressed on hematopoietic stem and progenitor cells. In chemotherapy-treated megakaryocytes, SCF activated Akt, neutralized the mitochondrial apoptotic machinery, and inhibited caspase activity. Interfering with Akt activation abrogated the antiapoptotic effects of SCF, whereas exogenous expression of constitutively active Akt inhibited drug-induced apoptosis of primary megakaryocytes, indicating the Akt pathway as primarily responsible for SCF-mediated protection of megakaryocyte progenitors. These results indicate apoptosis of megakaryocyte progenitors as a major cause of chemotherapy-induced thrombocytopenia and suggest that SCF may be used to prevent platelet loss in cancer patients with c-kit–negative tumors. [Cancer Res 2007;67(10):4767–4773]
