Oncogenic PIK3CA corrupts growth factor signaling specificity.

Technical limitations have prevented understanding of how growth factor signals are encoded in distinct activity patterns of the phosphoinositide 3-kinase (PI3K)/AKT pathway, and how this is altered by oncogenic pathway mutations. We introduce a kinetic, single-cell framework for precise calculations of PI3K-specific information transfer for different growth factors. This features live-cell imaging of PI3K/AKT activity reporters and multiplexed CyTOF measurements of PI3K/AKT and RAS/ERK signaling markers over time.

Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients.

In preclinical experiments, cyclic fasting-mimicking diets (FMDs) showed broad anticancer effects in combination with chemotherapy. Among different tumor types, triple-negative breast cancer (TNBC) is exquisitely sensitive to FMD. However, the antitumor activity and efficacy of cyclic FMD in TNBC patients remain unclear.

Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial.

Objective: The Metformin and Dietary Restriction to Prevent Age-Related Morbid Events in People With Metabolic Syndrome (MeMeMe) trial tested whether 1,700 mg/day metformin (MET) with or without a Mediterranean diet (MedDiet) intervention could reduce the cumulative incidence of major noncommunicable diseases in people with metabolic syndrome.

Research Design And Methods: A total of 1,442 participants were randomly assigned to one of four interventions: 1) MET (1,700 mg/day) plus MedDiet intervention (MET+MedDiet); 2) placebo plus MedDiet intervention; 3) MET (1,700 mg/day) alone; and 4) placebo alone. Participants were followed up for 3 years on average.

Erosion of the temporal bone by vestibular schwannoma: morphometrics and predictive modeling.

Purpose: To perform a comprehensive morphometric analysis of vestibular schwannomas (VS) using multimodal imaging, focusing on the relationship between tumor characteristics and internal acoustic canal (IAC) changes.

Methods: We analyzed a cohort of patients undergoing radiosurgery for VS, utilizing high-definition MRI and bone CT for detailed anatomical assessment. Image co-registration and fusion techniques were employed to examine VS and IAC dimensions.

Evaluation of a novel blood collection set for venipuncture in oncology patients with difficult venous access: Impact on sample quality, phlebotomist satisfaction and patient pain perception.

Purpose: Difficult venous access (DVA), characterized by non-visible and non-palpable veins, is common in oncology patients. The objectives of this study were to compare the performances of two blood collection sets in an oncology phlebotomy setting: BD Vacutainer® UltraTouch™ Push Button (UT-PBBCS) and BD Vacutainer® Safety-Lok™ Blood Collection Set (SLBCS). The two sets were evaluated to assess whether use of a smaller gauge (G) needle (down-gauging) may reduce patient pain and improve peripheral venous access experience during phlebotomy in oncology patients.

Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.

Background: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut.

Routine perioperative blood tests predict survival of resectable lung cancer.

There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed.

A small-molecule PI3Kα activator for cardioprotection and neuroregeneration.

Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling.

Deviation of DBS Recording Microelectrodes during Insertion Assessed by Intraoperative CT.

Introduction: Intraoperative microelectrodes recording with the Ben Gun microdrive system are often used during DBS surgery. An accurate location of these microelectrodes will directly influence the interest of this recording. We have studied the imprecision of implantation of these microelectrodes.

Preoperative Neutrophil-to-Lymphocyte Ratio and a New Inflammatory Biomarkers Prognostic Index for Primary Retroperitoneal Sarcomas: Retrospective Monocentric Study.

Purpose: Inflammatory biomarkers and neutrophil-to-lymphocyte ratio (NLR) are associated with prognosis in several tumors. Data on sarcomas are limited, and insufficient on retroperitoneal sarcoma (RPS).

Experimental Design: Patients with primary RPS operated between 2002 and 2016 were included.

Evaluation of Simplified Diet Scores Related to -Reactive Protein in Heavy Smokers Undergoing Lung Cancer Screening.

The aim of this study was to assess the relationship between adherence to a healthy diet, such as the Mediterranean diet (MedDiet), and -reactive protein (CRP) in Italian heavy smokers undergoing an LDCT screening program (bioMILD trial), using scores calculated by simple questionnaires. Simple formats of food frequency questionnaires were administered to a sample of 2438 volunteers, and the adherence to a healthy diet was measured by the validated 14-point MEDAS and by two adaptations proposed by us: 17-item revised-MEDAS and 18-item revised-MEDAS. The OR of CRP ≥ 2 mg/L for 1-point increase in 14-point MEDAS score was 0.

Circulating Fatty Acid Profile as a Biomarker for Immunotherapy in Advanced Non-Small Cell Lung Cancer.

Introduction: Lipid metabolism impacts immune cell differentiation, activation, and functions, modulating inflammatory mediators, energy homeostasis, and cell membrane composition. Despite preclinical evidence, data in humans lack concerning tumors and immunotherapy (IO). We aimed at investigating the correlations between circulating lipids and the outcome of non-small cell lung cancer (NSCLC) patients treated with IO.

Efficacy of mRNA anti-SARS-CoV-2 vaccination and dynamics of humoral immune response in patients with solid tumors: results from the institutional registry of an Italian tertiary cancer center.

Background: Systemic immunosuppression characterizing cancer patients represents a concern regarding the efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and real-world evidence is needed to define the efficacy and the dynamics of humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines.

Methods: We conducted an observational study that included patients with solid tumors who were candidates for mRNA anti-SARS-CoV-2 vaccination at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. The primary objective was to monitor the immunologic response to the mRNA anti-SARS-CoV-2 vaccination in terms of anti-spike antibody levels.

Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover.

Focal adhesions are multifunctional organelles that couple cell-matrix adhesion to cytoskeletal force transmission and signaling and to steer cell migration and collective cell behavior. Whereas proteomic changes at focal adhesions are well understood, little is known about signaling lipids in focal adhesion dynamics. Through the characterization of cells from mice with a kinase-inactivating point mutation in the class II PI3K-C2β, we find that generation of the phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P) membrane lipid promotes focal adhesion disassembly in response to changing environmental conditions.

COVID-19 Vaccination in Health Care Workers in Italy: A Literature Review and a Report from a Comprehensive Cancer Center.

The coronavirus disease 2019 pandemic still represents a global public health emergency, despite the availability of different types of vaccines that reduced the number of severe cases, the hospitalization rate and mortality. The Italian Vaccine Distribution Plan identified healthcare workers (HCWs) as the top-priority category to receive access to a vaccine and different studies on HCWs have been implemented to clarify the duration and kinetics of antibody response. The aim of this paper is to perform a literature review across a total of 44 studies of the serologic response to COVID-19 vaccines in HCWs in Italy and to report the results obtained in a prospective longitudinal study implemented at the Fondazione IRCCS Istituto Nazionale Tumori (INT) of Milan on 1565 HCWs.

Application of morphological characteristics of radiofrequency lesions to individual parameters of thermal rhizolysis for trigeminal neuralgia.

Background: Thermic rhizolysis is a reliable therapy for pharmaco-resistant trigeminal neuralgia (TN). Temperature, duration of electrocautery and needle location can influence the efficacy and complications of the therapy.

Methods: We performed experimental thermocautery on egg white with increasing parameters of time (30-120 s) and temperature (60-95°C); we analysed the shape, size and volume of the thermic lesions produced.

Management of Dietary Habits and Diarrhea in Fap Individuals: A Mediterranean Low-Inflammatory Dietary Intervention.

Background: A total colectomy and a frequent life-long endoscopic surveillance are guaranteed to patients with Familial Adenomatous Polyposis (FAP) to reduce their risk of duodenal and rectal stump cancers. However, after surgery, individuals with FAP suffer from an increased number of diarrheal discharges that force them to dietary restrictions. A non-randomized pilot study was conducted to assess whether a three-month low-inflammatory Mediterranean dietary intervention reduces gastro-intestinal markers of inflammation in FAP individuals.

T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies.

Patients affected by lymphoid malignancies (LM) are frequently immune-compromised, suffering increased mortality from COVID-19. This prospective study evaluated serological and T-cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B- and T-cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex.

Preventive Anti-inflammatory Diet to Reduce Gastrointestinal Inflammation in Familial Adenomatous Polyposis Patients: A Prospective Pilot Study.

Familial adenomatous polyposis (FAP) is an autosomal-dominant hereditary condition associated with germline mutations in the adenomatous polyposis coli gene. Patient management involves prophylactic surgery and intensive life-long endoscopic surveillance. Diet is a major concern for patients with FAP, who are generally free of symptoms before surgery but tend to have issues related to bowel function postoperatively.

COVID-19 Pandemic: Huge Stress Test for Health System Could Be a Great Opportunity to Update the Workflow in a Modern Surgical Pathology.

Background: On December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. This disease, characterized by the rapid human-to-human transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly in more than 200 countries. Northern Italy's regions have been hit hard in terms of deaths.

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial.

Women carriers of / mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance.

Effects of cabozantinib on bone turnover markers in real-world metastatic renal cell carcinoma.

Background: Cabozantinib strongly inhibits osteoclast differentiation and bone resorption in vitro. We aimed to evaluate its effect on bone turnover markers (BTMs) in metastatic renal cell carcinoma.

Methods: This is a monocentric prospective study on patients with mRCC treated with cabozantinib between October 2016 and July 2018.

κ and λ urine free light chains: a new method for quantification.

Background: Immunofixation electrophoresis of urinary proteins, coupled with densitometric analysis, is the gold standard method for determining urinary monoclonal free light chains (FLCs), i.e. Bence Jones protein.