Association of Gene Polymorphisms and Its Regulatory miRNAs with Methotrexate Toxicity in Children with Acute Lymphoblastic Leukemia.

Methotrexate (MTX) is an anti-folate chemotherapeutic agent that is considered to be a gold standard in Acute Lymphoblastic Leukemia (ALL) therapy. Nevertheless, toxicities induced mainly due to high doses of MTX are still a challenge for clinical practice. MTX pharmacogenetics implicate various genes as predictors of MTX toxicity, especially those that participate in MTX intake like ().

Association of microRNA Polymorphisms with Toxicities Induced by Methotrexate in Children with Acute Lymphoblastic Leukemia.

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses.

Association of , , and Gene Polymorphisms with Sporadic Congenital Heart Disease in Greek Patients.

Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the gene polymorphism (-94ins/ delATTG), rs28362491, gene polymorphism rs2277923, gene polymorphism rs11785481 and gene polymorphism .

Cervical, anal and oral HPV detection and HPV type concordance among women referred for colposcopy.

Background: Infection with human papillomaviruses (HPVs) can cause benign and malignant tumours in the anogenital tract and the oropharynx both in men and women. The aim of the presented study was to investigate cervical, anal, and oral HPV-detection rates among women referred to colposcopy for abnormal Cervical Cancer (CaCx) screening results and assess the concordance of HPV-types among these anatomical sites.

Methods: Women referred to colposcopy at a single centre due to abnormal cytology, conducted for CaCx screening, were subjected to cervical Liquid-based Cytology (LBC) smear testing, anal and oral sampling.

The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma.

The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity.

NK Cell-Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines.

Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F-IgG) could direct innate immune cells with Fc receptors to folate receptor-expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry.

The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2.

MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.

Metastatic melanoma is the most aggressive form of this cancer. It is important to understand factors that increase or decrease metastatic activity in order to more effectively research and implement treatments for melanoma. Increased cell invasion through the extracellular matrix is required for metastasis and is enhanced by matrix metalloproteinases (MMPs).

miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions.

Background: Expression of microRNAs (miRs) has been shown to be altered in many solid tumours and is being explored in melanoma. The malignant potential of some melanocytic lesions is difficult to predict. We hypothesised that characterisation of miR expression in borderline melanocytic proliferations would lead to the identification of a molecular profile that could be used with known prognostic factors to differentiate lesions with high malignant potential.

Enhanced anti-tumor activity of interferon-alpha in SOCS1-deficient mice is mediated by CD4⁺ and CD8⁺ T cells.

Interferon-alpha (IFN-α) is an immunomodulatory cytokine that is used clinically for the treatment of melanoma in the adjuvant setting. The cellular actions of IFN-α are regulated by the suppressors of cytokine signaling (SOCS) family of proteins. We hypothesized that the anti-tumor activity of exogenous IFN-α would be enhanced in SOCS1-deficient mice.

Use of a nanoporous biodegradable miniature device to regulate cytokine release for cancer treatment.

The clinical management of locally recurrent or unresectable malignant melanoma continues to pose a significant challenge. These lesions are typically painful and currently available treatments, such as repeated intratumoral injections of interferon-alpha (IFN-α), are costly and inconvenient. Nanotechnology offers promise as a novel means of drug delivery.

IFN-alpha-induced signal transduction, gene expression, and antitumor activity of immune effector cells are negatively regulated by suppressor of cytokine signaling proteins.

Proteins belonging to the suppressors of cytokine signaling (SOCS) family have been shown to regulate cytokine signal transduction in various cell types but their role in modulating the response of immune cells to IFN-alpha has not been fully explored. We hypothesized that SOCS proteins would inhibit the antitumor activity of IFN-alpha-stimulated immune cells. Transcripts for SOCS1, SOCS2, SOCS3, and cytokine-inducible Src homology 2-containing protein were identified in total human PBMC (PBMCs, NK cells, and T cells) within 1-2 h of stimulation with IFN-alpha (10(3)-10(5) U/ml).