Identification of the Biosynthetic Gene Cluster of Thermoactinoamides and Discovery of New Congeners by Integrated Genome Mining and MS-Based Molecular Networking.

The putative non-ribosomal peptide synthetase (NRPS) gene cluster encoding the biosynthesis of the bioactive cyclohexapeptide thermoactinoamide A () was identified in DSM 43016. Based on an prediction, the biosynthetic operon was shown to contain two trimodular NRPSs, designated as ThdA and ThdB, respectively. Chemical analysis of a bacterial crude extract showed the presence of thermoactinoamide A (), thereby supporting this biosynthetic hypothesis.

Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway.

ABCC6, belonging to sub-family C of ATP-binding cassette transporter, is an ATP-dependent transporter mainly present in the basolateral plasma membrane of hepatic and kidney cells. Although the substrates transported are still uncertain, ABCC6 has been shown to promote ATP release. The extracellular ATP and its derivatives di- and mono-nucleotides and adenosine by acting on specific receptors activate the so-called purinergic pathway, which in turn controls relevant cellular functions such as cell immunity, inflammation, and cancer.

ZSCAN4 mouse embryonic stem cells have an oxidative and flexible metabolic profile.

Cultured mouse embryonic stem cells are a heterogeneous population with diverse differentiation potential. In particular, the subpopulation marked by Zscan4 expression has high stem cell potency and shares with 2 cell stage preimplantation embryos both genetic and epigenetic mechanisms that orchestrate zygotic genome activation. Although embryonic de novo genome activation is known to rely on metabolites, a more extensive metabolic characterization is missing.

MSI and EBV Positive Gastric Cancer's Subgroups and Their Link With Novel Immunotherapy.

Gastric cancers have been historically classified based on histomorphologic features. The Cancer Genome Atlas network reported the comprehensive identification of genetic alterations associated with gastric cancer, identifying four distinct subtypes- Epstein-Barr virus (EBV)-positive, microsatellite-unstable/instability (MSI), genomically stable and chromosomal instability. In particular, EBV-positive and MSI gastric cancers seem responsive to novel immunotherapies drugs.

Monoclonal antibodies in newly diagnosed and smoldering multiple myeloma: an updated review of current clinical evidence.

: Monoclonal antibodies (MoAbs) are rapidly changing the therapeutic scenario of multiple myeloma. Most of the available data, however, come from studies performed in patients with relapsed or refractory disease.: Here, the most recent results from clinical trials that have investigated (or are investigating) efficacy and safety of MoAbs as front-line treatments in both transplant-eligible and not-eligible patients with newly diagnosed multiple myeloma, as well as in smoldering myeloma, are reviewed.

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses.

: In the last few years, monoclonal antibodies have rapidly modified the therapeutic strategies for treating patients with multiple myeloma.: In this review, the most recent literature data regarding indications for which monoclonal antibodies are currently or will be shortly approved as salvage therapies in relapsed/refractory myeloma are discussed. In particular, updated results until March 22, 2020 of antibodies directed against CD38 (daratumumab and isatuximab), SLAMF7 (elotuzumab), BCMA (GSK2857916/belantamab mafodotin), and PD-1/PD-1 L axis (nivolumab and pembrolizumab) will be analyzed in detail.

Superiority of Droplet Digital PCR Over Real-Time Quantitative PCR for Allele Mutational Burden Assessment in Myeloproliferative Neoplasms: A Retrospective Study.

mutational status is an essential diagnostic index in myeloproliferative neoplasms (MPNs). Although widely used for detection of mutation in peripheral blood (PB), sensitive real-time quantitative PCR (qPCR) presents some methodological limitations. Recently, emerging alternative technologies, like digital droplet PCR (ddPCR), have been reported to overcome some of qPCR's technical drawbacks.

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies.

Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance.

Bevacizumab in Combination With Either FOLFOX-4 or XELOX-2 in First-line Treatment of Patients With Metastatic Colorectal Cancer: A Multicenter Randomized Phase II Trial of the Gruppo Oncologico dell'Italia Meridionale (GOIM 2802).

Introduction: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC.

Nandrolone induces a stem cell-like phenotype in human hepatocarcinoma-derived cell line inhibiting mitochondrial respiratory activity.

Nandrolone is a testosterone analogue with anabolic properties commonly abused worldwide, recently utilized also as therapeutic agent in chronic diseases, cancer included. Here we investigated the impact of nandrolone on the metabolic phenotype in HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes I and III and enhanced mitochondrial reactive oxygen species (ROS) production.

Association between neutropenia and response to ramucirumab and paclitaxel in patients with metastatic gastric cancer.

The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer. This is a retrospective study of patients treated with ramucirumab plus paclitaxel. Fifty-three patients were evaluated.

Retinoic Acid Induces Embryonic Stem Cells (ESCs) Transition to 2 Cell-Like State Through a Coordinated Expression of and .

Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) of the blastocyst. In serum/LIF culture condition, they show variable expression of pluripotency genes that mark cell fluctuation between pluripotency and differentiation metastate. The ESCs subpopulation marked by zygotic genome activation gene (ZGA) signature, including , retains a wider differentiation potency than epiblast-derived ESCs.

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study.

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab.

Neoadjuvant treatment by ECT in cutaneous malignant neoplastic lesions.

Electrochemotherapy (ECT) is a local treatment and its use has been standardised for cutaneous nodules of any histological origin. In this study, we use ECT as a neoadjuvant therapy to reduce the size of neoplastic lesions to obtain an ideal cleavage plane where vital or very important vascular and/or nervous structures are separated from the tumour, thus allowing a radical surgical excision, which is otherwise unfeasible. In their retrospective study, the authors identified 41 patients who were treated at our institution with neoadjuvant intent.

Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: A retrospective multicentre study.

Background: Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials.

A joint molecular networking study of a sponge and a cyanobacterial bloom revealed new antiproliferative chlorinated polyketides.

The bloom-forming cyanobacteria sp. have been recently shown to produce some of the chlorinated peptides/polyketides previously isolated from the marine sponge . A comparative analysis of extracts from and sp.

Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications.

An extensive body of literature describes anticancer property of dichloroacetate (DCA), but its effective clinical administration in cancer therapy is still limited to clinical trials. The occurrence of side effects such as neurotoxicity as well as the suspicion of DCA carcinogenicity still restricts the clinical use of DCA. However, in the last years, the number of reports supporting DCA employment against cancer increased also because of the great interest in targeting metabolism of tumour cells.

In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products.

Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of the substituent groups in the quinone moiety. Aiming to broaden the knowledge of the underlying mechanism of the antiproliferative effect of these prenylated compounds, herein we report the synthesis of two quinones and and of their corresponding dioxothiazine fused quinones and inspired to the marine natural product aplidinone A (), a geranylquinone featuring the 1,1-dioxo-1,4-thiazine ring isolated from the ascidian .

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial.

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial.

Methods: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy.

Hepatocellular carcinoma in older adults: A comprehensive review by Young International Society of Geriatric Oncology.

Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults.

Fast Detection of Two Smenamide Family Members Using Molecular Networking.

Caribbean sponges of the genus are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed in the metabolome of two new members of the smenamide family, namely smenamide F () and G (). The structure of smenamide F () and G () was determined by spectroscopic analysis (NMR, MS, ECD).

Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

Background: Erythropoiesis-stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower "standard doses" (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking.