Reverse signaling by semaphorin 4C elicits SMAD1/5- and ID1/3-dependent invasive reprogramming in cancer cells.

Semaphorins are a family of molecular signals that guide cell migration and are implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act as both ligands ("forward" mode) and signaling receptors ("reverse" mode); however, reverse semaphorin signaling in cancer is relatively less understood. Here, we identified a previously unknown function of transmembrane semaphorin 4C (Sema4C), acting in reverse mode, to elicit nonconventional TGF-β/BMP receptor activation and selective SMAD1/5 phosphorylation.

Multi-site evaluation of the Razor stereotactic diode for CyberKnife small field relative dosimetry.

Purpose: The aims of this study were: (i) to validate in a multi-site context the suitability of the IBA Razor silicon diode detector for CyberKnife relative dosimetry. (ii) to fit the multi-center experimental data into a function relating the field output factors to the effective field size (EFS).

Methods And Materials: Ratio of detector readings in clinical and reference field (OF) and beam profiles were acquired on five CyberKnife units for fixed collimator diameters (range 5-60 mm), using both Razor and PTW 60017 diodes.

Driving Cells with Light-Controlled Topographies.

Cell-substrate interactions can modulate cellular behaviors in a variety of biological contexts, including development and disease. Light-responsive materials have been recently proposed to engineer active substrates with programmable topographies directing cell adhesion, migration, and differentiation. However, current approaches are affected by either fabrication complexity, limitations in the extent of mechanical stimuli, lack of full spatio-temporal control, or ease of use.

A validated prognostic classifier for BRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study.

Background: Despite the well-known negative prognostic value of the BRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined.

Methods: Two large retrospective series of BRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated.

The Stromal and Immune Landscape of Colorectal Cancer Progression during Anti-EGFR Therapy.

In this issue of Cancer Cell, Woolston et al. show that colorectal cancers that become refractory to initially effective anti-EGFR therapy contain an abundance of stromal and immune cells, irrespective of the contextual presence of resistance-conferring mutations. This reconfiguration puts forward therapeutic opportunities for patients who relapse on EGFR-targeting treatment.

Macrophages and Metabolism in the Tumor Microenvironment.

Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can account for up to 50% of some solid neoplasms. Most often, TAMs support disease progression and resistance to therapy by providing malignant cells with trophic and nutritional support. However, TAMs can mediate antineoplastic effects, especially in response to pharmacological agents that boost their phagocytic and oxidative functions.

CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy.

Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αβT lymphocytes.

Ovarian Cancer Immunotherapy: Turning up the Heat.

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed.

An unusual case of complicated rhinosinusitis of the sphenoid sinus involving the cavernous sinus and skull base: Endoscopic sinus surgery and medical therapy.

Isolated sphenoid sinus diseases are generally asymptomatic and relatively uncommon with the potential for serious complications. Patients with this condition should be monitored closely and treated aggressively and either diagnostic or therapeutic intent is often indicated. In the management of a complex, life-threatening condition that involves many different fields of expertise, the otolaryngologist plays a key role in orchestrating different specialists and gaining direct access to the affected area, thus taking the first and essential step towards diagnosis and therapy.

Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives.

The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family members of ovarian cancer patients, is the identification of carriers of pathogenic variant, who have inheredited predisposition to cancer development (test for cancer risk). These individuals with increased risk of cancer, should be encouraged to participate in dedicated high-risk surveillance clinics and specific risk-reducing measures (primary and/or secondary prevention programs).

Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models.

Background: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is an effective treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients receive clinical benefits from anti-EGFR therapies, due to the development of resistance mechanisms. In this regard, HER2 has emerged as an actionable target in the treatment of mCRC patients with resistance to anti-EGFR therapy.

The Penetration-Aspiration Scale: Adaptation to Open Partial Laryngectomy and Reliability Analysis.

A standard for assessing swallowing function after open partial horizontal laryngectomy (OPHL) is still not established. The variability in the measures used to investigate swallowing functional outcomes after OPHL limits the communication among clinicians and the possibility to compare and combine results from different studies. The study aims to adapt the PAS to the altered anatomy after OPHLs using fiberoptic endoscopic evaluation of swallowing (FEES) and to test its reliability.

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer.

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data.

Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017.

Death for life: a path from apoptotic signaling to tissue-scale effects of apoptotic epithelial extrusion.

Apoptosis plays a crucial role in clearing old or critically compromised cells, and actively maintains epithelial homeostasis and epithelial morphogenesis during embryo development. But how is the apoptotic signaling pathway able to orchestrate such complex and dynamic multi-cellular morphological events at the tissue scale? In this review we collected the most updated knowledge regarding how apoptosis controls different cytoskeletal components. We describe how apoptosis can control epithelial homeostasis though epithelial extrusion, a highly orchestrated process based on high- order actomyosin structures and on the coordination between the apoptotic and the neighboring cells.

Treating advanced breast cancer with metronomic chemotherapy: what is known, what is new and what is the future?

The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%-50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life.

Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.

Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance.

Development and characterization of a canine-specific anti-CD94 (KLRD-1) monoclonal antibody.

Natural killer (NK) cells are non-T, non-B lymphocytes are part of the innate immune system and function without prior activation. The human NK cell surface determinant, CD94, plays a critical role in regulation of NK cell activity as a heterodimer with NKG2 subclasses. Canine NK cells are not as well defined as the human and murine equivalents, due in part to the paucity of reagents specific to cell surface markers.

Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer.

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option.

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

Introduction: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.

Methods: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion.

Veliparib: a new therapeutic option in ovarian cancer?

The role of poly ADP ribose polymerase inhibitors in ovarian cancer is rapidly evolving. Three different poly ADP ribose polymerase inhibitors (olaparib, niraparib and rucaparib) have been already approved as maintenance after response to platinum-based chemotherapy; two of them (olaparib and rucaparib) also as single agents. Veliparib, a novel PARPI, showed promising results in preclinical and early clinical settings.

Salvage open partial horizontal laryngectomy after failed radiotherapy: A multicentric study.

Objectives: The primary aim of the present study was to report our multi-institutional experience in surgical salvage with open partial horizontal laryngectomies (OPHL) after failed radiotherapy (RT) for laryngeal squamous cell carcinoma (LSCC). Secondary aims were to analyze the prognostic meaning of the main clinical and pathological parameters in relation to the oncologic outcome and to compare our results with the available literature.

Study Design: A retrospective multicenter analysis of surgical oncological outcomes.