Dissecting Clonal Hematopoiesis in Tissues of Classical Hodgkin Lymphoma Patients.

Clonal hematopoiesis predisposes to hematological malignancies. However, clonal hematopoiesis is understudied in classical Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes.

miR-199a-3p Modulates MTOR and PAK4 Pathways and Inhibits Tumor Growth in a Hepatocellular Carcinoma Transgenic Mouse Model.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Prognosis is poor, and therapeutic options are limited. MicroRNAs (miRNAs) have emerged as potential therapeutic molecules against cancer.

Cardiovascular disease-related miRNAs expression: potential role as biomarkers and effects of training exercise.

Cardiovascular diseases (CVDs) are one of the most important causes of mortality worldwide, therefore the need of effective preventive strategies is imperative. Aging is associated with significant changes in both cardiovascular structure and function that lower the threshold for clinical signs and symptoms, making older people more susceptible to CVDs morbidity and mortality. microRNAs (miRNAs) modulate gene expression at post-transcriptional level and increasing evidence has shown that miRNAs are involved in cardiovascular physiology and in the pathogenesis of CVDs.

Influence of physical exercise on microRNAs in skeletal muscle regeneration, aging and diseases.

Skeletal muscle is a dynamic tissue with remarkable plasticity and its growth and regeneration are highly organized, with the activation of specific transcription factors, proliferative pathways and cytokines. The decline of skeletal muscle tissue with age, is one of the most important causes of functional loss of independence in older adults. Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living.

Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments.

A decreased physical fitness has been reported in patients and survivors of acute lymphoblastic leukemia (ALL). This is influenced by the negative effects of the disease and by the treatments of childhood cancer. In the past, children were advised to recover in bed, and to take as much relax as possible.

Impact of physical exercise in cancer survivors during and after antineoplastic treatments.

Cancer patients experience symptoms and adverse effects of treatments that may last even after the end of treatments. Exercise is a safe, non-pharmacological and cost-effective therapy that can provide several health benefits in cancer patient and survivors, reducing cancer symptoms and cancer treatment side effects. The purpose of this review is to describe how the physical exercise is capable to reduce cancer symptoms and cancer treatment side effects.

Roles and clinical implications of microRNAs in acute lymphoblastic leukemia.

MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate the expression of target genes by binding to messenger RNAs. miRNAs play a role in various biological processes, including proliferation, apoptosis, and tumorigenesis. Dysregulation of miRNAs is implicated in invasion and metastasis in several human cancer types, and leukemia is not an exception.

PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.

B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival.

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia.

Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved.

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474.

The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common lethal human malignancies worldwide and its advanced status is frequently resistant to conventional chemotherapeutic agents and radiation. We evaluated the cytotoxic effect of the orally bioavailable dual PI3K/mTOR inhibitor, NVP-BGT226, on a panel of HCC cell lines, since hyperactivated PI3K/Akt/mTOR signaling pathway could represent a biomolecular target for Small Inhibitor Molecules in this neoplasia. We analyzed the drug activity in both normoxia and hypoxia conditions, the latter playing often a relevant role in the induction of chemoresistance and angiogenesis.

Triple Akt inhibition as a new therapeutic strategy in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder in which chemotherapy resistance and refractory relapses occur, with a poorer prognostic outcome.Constitutively active PI3K/Akt/mTOR pathway is a common feature of T-ALL upregulating cell proliferation, survival and drug resistance. This pathway is currently under clinical trials with small molecules inhibitors (SMI).