Broad-spectrum antibiotics disrupt homeostatic efferocytosis.

The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we show that large peritoneal macrophage (LPM) display impairs efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated and germ-free mice in vivo, all of which have a depleted gut microbiota.

Autophagy Is Polarized toward Cell Front during Migration and Spatially Perturbed by Oncogenic Ras.

Autophagy is a physiological degradation process that removes unnecessary or dysfunctional components of cells. It is important for normal cellular homeostasis and as a response to a variety of stresses, such as nutrient deprivation. Defects in autophagy have been linked to numerous human diseases, including cancers.

Tim-4 cavity-resident macrophages impair anti-tumor CD8 T cell immunity.

Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer; however, the majority of patients do not respond to ICB therapy. We show that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after ICB therapy. Cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), and this is associated with reduced numbers of CD8 T cells with tumor-reactive features in pleural effusions and peritoneal ascites from patients with cancer.

Immunometabolism of Tissue-Resident Macrophages - An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies.

Tissue-resident macrophages exist in unique environments, or niches, that inform their identity and function. There is an emerging body of literature suggesting that the qualities of this environment, such as the types of cells and debris they eat, the intercellular interactions they form, and the length of time spent in residence, collectively what we call , directly inform their metabolic state. In turn, a tissue-resident macrophage's metabolic state can inform their function, including whether they resolve inflammation and protect the host from excessive perturbations of homeostasis.

Publisher Correction: Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.

The monomeric GTPase RalB controls crucial physiological processes, including autophagy and invasion, but it still remains unclear how this multi-functionality is achieved. Previously, we reported that the RalGEF (Guanine nucleotide Exchange Factor) RGL2 binds and activates RalB to promote invasion. Here we show that RGL2, a major activator of RalB, is also required for autophagy.

Neoplastic Pericardial Effusion: A Monocentric Retrospective Study.

Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients.

RalB directly triggers invasion downstream Ras by mobilizing the Wave complex.

The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cancers; in particular, RalB is involved in invasion and metastasis. However, therapies targeting Ral signalling are not available yet. By a novel optogenetic approach, we found that light-controlled activation of Ral at plasma-membrane promotes the recruitment of the Wave Regulatory Complex (WRC) via its effector exocyst, with consequent induction of protrusions and invasion.

Correction: Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation.

[This corrects the article DOI: 10.18632/oncotarget.9875.

Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists.

Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL.In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs.

A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to control cell migration.

Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation.

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations.

Introduction: Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm.

Results: Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.

Direct interaction between exocyst and Wave complexes promotes cell protrusions and motility.

Coordination between membrane trafficking and actin polymerization is fundamental in cell migration, but a dynamic view of the underlying molecular mechanisms is still missing. The Rac1 GTPase controls actin polymerization at protrusions by interacting with its effector, the Wave regulatory complex (WRC). The exocyst complex, which functions in polarized exocytosis, has been involved in the regulation of cell motility.

New targeted treatments for non-small-cell lung cancer - role of nivolumab.

Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation.

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs.

Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation.

Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options.

Non-Small Cell Lung Cancer in a Very Young Woman: A Case Report and Critical Review of the Literature.

Background: Lung cancer in young patients is quite uncommon; clinical presentation and outcome in this population compared to the older group are not yet well defined and data about this setting are mostly single-institutional retrospective analyses.

Case Report: We report here a case of a very young woman with diagnosis of early-stage lung adenocarcinoma harboring EML4-ALK rearrangement; she underwent radical surgery and adjuvant chemotherapy according to the pathologic stage. Potential risk factors for lung cancer in our patient are discussed and clinico-pathologic features and outcomes of lung cancer in the young population compared to the elderly are reviewed through discussing studies with sample sizes larger than 100 patients.

Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

Background/aim: Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles.

Patients And Methods: This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution.

Inhibition of autophagy as a new means of improving chemotherapy efficiency in high-LC3B triple-negative breast cancers.

The triple-negative breast cancer (TN BC) subtype is the most aggressive form of invasive BC. Despite intensive efforts to improve BC treatments, patients with TN BC continue to exhibit poor survival, with half developing resistance to chemotherapy. Here we identify autophagy as a key mechanism in the progression and chemoresistance of a subset of TN tumors.

FDG avidity at PET/CT during adjuvant hormonal therapy in patients with breast cancer.

Background: We aim to retrospectively evaluate the impact of hormone therapy (HT) on FDG avidity of metastatic lesions in patients with breast cancer (BC) undergoing PET/CT.

Patients And Methods: Three hundred eight patients with BC were scanned with PET/CT at 2 Italian institutions (mean time from diagnosis 4 yrs, range: 1-24 yrs). Main indications for PET/CT were elevation of tumor markers (34.