The molecular conversations of sarcomas: exosomal non-coding RNAs in tumor's biology and their translational prospects.

Exosomes mediate cell-to-cell crosstalk involving a variety of biomolecules through an intricate signaling network. In recent years, the pivotal role of exosomes and their non-coding RNAs cargo in the development and progression of several cancer types clearly emerged. In particular, tumor bulk and its microenvironment co-evolve through cellular communications where these nanosized extracellular vesicles are among the most relevant actors.

Challenges in the diagnosis and management of tumor-induced osteomalacia: A case report.

The present case report is aimed to highlight the difficulty and the reason for the delayed diagnosis of phosphaturic mesenchymal tumors, emphasizing the need of standardized protocols for diagnosis, surgery and follow-up in high-volume hospitals. The clinical signs and symptoms, diagnostic and therapeutic procedures, immunohistological features were analyzed. Delayed diagnosis of phosphaturic mesenchymal tumor was primarily due to non-specific clinical symptoms such as fatigue, muscular and bone pain, and multiple fractures.

The Conundrum of Cancer-Associated Thrombosis: Lesson Learned from Two Intriguing Cases and Literature Review.

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines.

Radiation-induced sarcomas: A single referral cancer center experience and literature review.

Background And Objective: The oncogenic effect of ionizing radiation is widely known. Sarcomas developing after radiation therapy (RT), termed "iatrogenic disease of success", represent a growing problem, since the advancements in cancer management and screening programs have increased the number of long-term cancer survivors. Although many patients have been treated with radiation therapy, only few data are available on radiation-induced sarcomas (RIS).

CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy.

Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence.

Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results.

Patients And Methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study.

Results: Older patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.

Gastrointestinal stromal tumours and other primary gastrointestinal neoplasms. A single-center experience.

Background: In our surgical daily activity, we report the observation of rare tumour as Gastrointestinal Stromal Tumours (GIST). We report the incidence and behaviour of new cases of GIST operated in our Center during the last decade, from 2008 to 2018 and here we also describe the concomitant observation of a second gastroenteric tumor.

Method: We have examined all the case files and histological examinations of patients with CD 117-positive GISTs treated in our Institute from 2008 to 2018.

Spontaneous Membrane Nanodomain Formation in the Absence or Presence of the Neurotransmitter Serotonin.

Detailed knowledge on the formation of biomembrane domains, their structure, composition, and physical characteristics is scarce. Despite its frequently discussed importance in signaling, e.g.

Serotonin Alters the Phase Equilibrium of a Ternary Mixture of Phospholipids and Cholesterol.

Unsaturated and saturated phospholipids tend to laterally segregate, especially in the presence of cholesterol. Small molecules such as neurotransmitters, toxins, drugs etc. possibly modulate this lateral segregation.

Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry.

Store-operated calcium entry (SOCE) through STIM-gated ORAI channels governs vital cellular functions. In this context, SOCE controls cellular redox signaling and is itself regulated by redox modifications. However, the molecular mechanisms underlying this calcium-redox interplay and the functional outcomes are not fully understood.

New synthesized polyoxygenated diarylheptanoids suppress lipopolysaccharide-induced neuroinflammation.

In neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, neuroinflammation induced by the microglial activation plays a crucial role. In effort to develop effective anti-neuroinflammatory compounds, different new linear polyoxygenated diarylheptanoids were synthesized. In LPS-triggered BV-2 microglial cells their ability to reduce the concentration of IL-6 and TNF-α pro-inflammatory cytokines was evaluated.

Predictive Impact of Mucinous Tumors on the Clinical Outcome in Patients with Poorly Differentiated, Stage II Colon Cancer: A TOSCA Subgroup Analysis.

Background: Although American Society of Clinical Oncology and European Society for Medical Oncology guidelines have identified the negative prognostic factors that clinicians have to consider when treating their patients with stage II colon cancer (CC), the role of histological subtype is controversial.

Subjects, Materials, And Methods: The randomized, multicenter, phase III TOSCA trial compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. The objective of this substudy was to evaluate the influence of histological subtypes on the impact of the treatment duration of adjuvant chemotherapy in terms of relapse-free survival (RFS) and overall survival (OS) in 85 mucinous adenocarcinoma (MUC) and 389 nonmucinous adenocarcinoma (NMUC) patients with high-risk stage II, grade 3 CC.

Chasing the Full Free Energy Landscape of Neuroreceptor/Ligand Unbinding by Metadynamics Simulations.

Predicting the complete free energy landscape associated with protein-ligand unbinding may greatly help designing drugs with highly optimized pharmacokinetics. Here we investigate the unbinding of the iperoxo agonist to its target human neuroreceptor M, embedded in a neuronal membrane. By feeding out-of-equilibrium molecular simulations data in a classification analysis, we identify the few essential reaction coordinates of the process.

Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study.

The RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21.

Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid.

Myricanol 1, a constituent of Myrica species, has been reported to lower the levels of the microtubule-associated protein tau (MAPT), whose accumulation plays an important role in some neurodegenerative diseases, such as Alzheimer's disease (AD). Herein we described a new synthetic route to prepare myricanol in 9 steps and 4.9% overall yield starting from commercially available 2,3-dimethoxyphenol and methyl 3-(4-benzyloxyphenyl)propanoate.

Phase II Study of Preoperative Treatment with External Radiotherapy Plus Panitumumab in Low-Risk, Locally Advanced Rectal Cancer (RaP Study/STAR-03).

Background: Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment.

Materials And Methods: Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, wild-type status, and negative circumferential radial margin.

Reducing Mutant Huntingtin Protein Expression in Living Cells by a Newly Identified RNA CAG Binder.

Expanded CAG trinucleotide repeats in Huntington's disease (HD) are causative for neurotoxicity. The mutant CAG repeat RNA encodes neurotoxic polyglutamine proteins and can lead to a toxic gain of function by aberrantly recruiting RNA-binding proteins. One of these is the MID1 protein, which induces aberrant Huntingtin (HTT) protein translation upon binding.

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme.

Background: TAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking.

Patients And Methods: We treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme.

Designing the Sniper: Improving Targeted Human Cytolytic Fusion Proteins for Anti-Cancer Therapy via Molecular Simulation.

Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv) specifically binding to e.

TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma.

TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors.

Clinical Usefulness of a Mobile Application for the Appropriate Selection of the Antiarrhythmic Device in Heart Failure.

Background: Appropriate selection of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device can be challenging in patients with left ventricular (LV) dysfunction. In this setting, limited information exists about the role of medical applications in helping physicians to choose the most useful device.

Methods: We developed a medical application that provides guidelines-based algorithms for helping doctors in decision process using the Apache Cordova application programming interface.

Molecular view of ligands specificity for CAG repeats in anti-Huntington therapy.

Huntington's disease is a fatal and devastating neurodegenerative genetic disorder for which there is currently no cure. It is characterized by Huntingtin protein's mRNA transcripts with 36 or more CAG repeats. Inhibiting the formation of pathological complexes between these expanded transcripts and target proteins may be a valuable strategy against the disease.

Role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity: two cases and review of the literature.

Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor.