MicroRNAs in Colorectal Cancer Drug Resistance: Shooters become Targets

Copyright: © 2013 Fanale D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. MicroRNAs (MiRNAs) are involved in the regulation of several biological processes such as development, differentiation, metabolism, apoptosis and proliferation. Recently, it has been shown that deregulated expression of miRNAs are present in different human cancers, suggesting a potential role in carcinogenesis [1,2]. Recent evidence suggests that miRNAs may represent potential new therapeutic approaches in patients with dru…

COMPARISON OF CLINICAL AND LABORATORY DATA, INCLUDING JAK-2 46/1 HAPLOTYPE, BETWEEN PATIENTS WITH IDIOPATHIC ERYTHROCYTOSIS AND POLYCYTHEMIA VERA.

Splenomegaly Impacts Prognosis in Essential Thrombocythemia and Polycythemia Vera: A Single Center Study

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

Clinical history of thrombosis before diagnosis of overt myeloproliferative neoplasms in triple negative patients

Thromboses are the most important preventable risk factors for morbidity and mortality in myeloproliferative neoplasms (MPN). We here performed a retrospective cross sectional study of patients with a diagnosis of Philadelphia negative MPN and a prior history of thrombosis, analyzed from electronic charts. Among a cohort of 260 patients with MPNs (78PV, 102ET, 80 MF), forty four were found triple negative for JAK-2, calreticulin and MPL gene mutations. Sixty-nine (26.54%) patients (29F, 40M) had a personal past clinical history of arterial or venous thrombosis. Among patients with thrombosis, 13(18.8%) cases (11ET, 2MF) were triple negative (median age:60 years). Most events, in particular …

JAK2 ALLELE BURDEN IN PATIENTS WITH PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

E26The effects of LIPUS on ctDNA release in the medium of NSCLC cell lines

Low Intensity Pulsed Ultrasound (LIPUS) application has been shown to have an encouraging effect in inducing a transient pore formation through cellular membranes. This permeability condition has been demonstrated to be useful in enhancing gene and drug delivery. Nowadays, in the management of NSCLC patients, the use of liquid biopsy has entered the clinical practice. One of the main limits in the analysis of circulating tumor DNA is the low concentration rate of nucleic acids in body fluids. Ultrasound stimulation (US) has been recently demonstrated to be effective for the release of specific circulating tumor biomarkers in many mouse models. We demonstrated the role of US in inducing the …

The role of microRNAs in driving EGFR-TKI resistance in NSCLC cell lines

Background: the inhibition of EGFR kinase activity by tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, can result in improved response and prolonged progression-free survival (PFS) in NSCLC patients harboring sensitizing exon 19del and exon 21 L858R mutations. Unfortunately, almost all patients will develop resistance to EGFR-TKI, in particular T790M is the most frequent mutation. Nowadays, new methods are urgently needed for a rapid, cost-effective and non-invasive identification of biomarkers as a valuable tool for obtaining the genetic follow-up data during the course of the disease. Circulating microRNAs might represent a new precious biomarker for patients’ moni…

The prognostic role of KRAS and BRAF in patients undergoing surgical resection of colorectal cancer liver metastasis: a systematic review and meta-analysis

Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of liver metastasis (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and Methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected by sear…

Sexually transmitted infections among men who have sex with men living in Western Sicily (south Italy)

Efficacy of ruxolitinib retreatment in a patient with high-risk myelofibrosis using the international prognostic scoring system

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm in which clonal proliferation of hematopoietic stem cells and bone marrow fibrosis coexist.1 Patients may eventually die due to leukemic progression, which occurs in up to 20% of cases, or because of cardiovascular comorbidities or cytopenia, which causes susceptibility to infections and bleeding.2 Myelofibrosis diagnosis relies upon the evaluation of several clinical and laboratory criteria suggested by the World Health Organization (WHO) in 2016.3 The major mutations leading to myelofibrosis usually occur in the JAK2, CALR, and MPL genes. However, in almost 10% of the cases, none of the above-mentioned mutations can be detected …

VUS variants in BRCA genes of hereditary breast/ovarian cancer

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines th…

CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL

Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to promoting the thrombotic event due to the interaction between platelets, leukocytes, and endothelium alterations. Moreover, a significant role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study, we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET .

The Essential Thrombocythemia, Thrombotic Risk Stratification, and Cardiovascular Risk Factors

Essential thrombocythemia is a rare hematological malignancy with good overall survival, but moderate to high risk of developing arterial or venous thrombosis lifelong. Different thrombotic risk scores for patients with essential thrombocythemia have been proposed, but only one of them (the IPSET-t scoring system) takes into account the classical cardiovascular risk factors as one of the scoring items. Currently, in clinical practice, the presence of cardiovascular risk factors in patients with diagnosis of ET rarely determines the decision to initiate cytoreductive therapies. In our study, we compared different risk models to estimate the thrombotic risk of 233 ET patients and the role of …

Abstract 448: Molecular analysis of BRAF gene and PTEN gene expression in metastatic colorectal cancer patients: Feasibility study

Abstract Introduction There are numerous causes triggering CRC. 25-80% of CRC shown a deregulation in Epidermal Growth Factor Receptor (EGFR) pathway. Two signaling pathways downstream of the EGFR are dysregulated in CRC the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3-kinase (PI3K) pathway. Activating mutations in KRAS and BRAF (MAPK pathway) and PIK3CA affect prognosis and/or response to anti-EGFR MoAb. PTEN is a downstream effector of EGFR pathway and is involved in PI3K pathway. Loss of PTEN protein expression can occur through epigenetic silencing and mutation or allelic loss. Immunohistochemistry (IHC) is the most effective way to assay for loss of PTEN expressio…

Cardiovascular Risk in Polycythemia Vera: Thrombotic Risk and Survival: Can Cytoreductive Therapy Be Useful in Patients with Low-Risk Polycythemia Vera with Cardiovascular Risk Factors?

<b><i>Background/Aims:</i></b> Cardiovascular risk factors are not considered in the current scores for evaluation of the thrombotic risk in myeloproliferative neoplasms, and in polycythemia vera (PV) in particular. Cytoreduction is currently not indicated in low-risk patients with PV, despite the absence or presence of cardiovascular risk factors. Our purpose is to highlight how cardiovascular risk factors in patients with PV increase the thrombotic risk both in low- and high-risk patients. <b><i>Methods:</i></b> We collected and analyzed data from 165 consecutive patients with a diagnosis of PV followed at our institution and compared the fr…

A headlight on liquid biopsies: a challenging tool for breast cancer management

Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g., PI3K/Akt/mTOR, PTEN, TP53). To date, diagnosis and metastasis monitoring is mainly carried out through tissue biopsy and/or re-biopsy, a very invasive procedure limited only to certain locations and not always feasible in clinical practice. In order to improve disease monitoring over time and to avoid painful procedure such as tissue biopsy, liquid biopsy may represent a new precious tool. Indeed, it represents a bas…

Management of Ponatinib in Patients with Chronic Myeloid Leukemia with Cardiovascular Risk Factors

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hype…