Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients.

Background: Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo.

Retrospective review of metastatic melanoma patients with leptomeningeal disease treated with intrathecal interleukin-2.

Objectives: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options. Outcomes of a retrospective cohort of patients with LMD that were treated with intrathecal interleukin-2 (IT IL-2) were reviewed to assess the long-term efficacy of this therapy.

Methods: The records of metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug study were reviewed.

Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial.

Background: Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib) might provide clinical benefit in this high-risk p opulation.

Characteristics and Prognostic Factors for Patients With HER2-overexpressing Breast Cancer and Brain Metastases in the Era of HER2-targeted Therapy: An Argument for Earlier Detection.

Background: Although brain metastases (BM) are associated with poor prognosis, patients with human epidermal growth factor receptor 2 (HER2) overexpressing (HER2) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a relatively longer survival after BM diagnosis compared with other subtypes and HER2 patients previously untreated with anti-HER2 therapy. It is unclear if previously reported prognostic factors are applicable to patients with HER2 BC in the era of HER2-targeted therapy.

Patients And Methods: We evaluated 100 consecutive patients with HER2 BC with BM who underwent radiation therapy as primary BM treatment from January 2001 to December 2011 at Memorial Sloan Kettering Cancer Center by retrospective review.

The polarity protein Angiomotin p130 controls dendritic spine maturation.

The actin cytoskeleton is essential for the structural changes in dendritic spines that lead to the formation of new synapses. Although the molecular mechanisms underlying spine formation are well characterized, the events that drive spine maturation during development are largely unknown. In this study, we demonstrate that Angiomotin (AMOT-130) is necessary for spine stabilization.

Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP), the most common form of inherited retinal degeneration, is associated with different groups of genes, including those encoding proteins involved in centriole and cilium biogenesis. Exome sequencing revealed a homozygous nonsense mutation [c.304_305delGA (p.

The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals.

Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis.

Evaluation of Mir-224, Mir-215 and Mir-143 as Serum Biomarkers for HCV Associated Hepatocellular Carcinoma.

HCV induced hepatitis and hepatocellular carcinoma as its sequel are major health problems world-wide and especially in Egypt. For diagnosis and during treatment of liver diseases, liver functions are monitored through determination of serum levels of liver enzymes and α-fetoprotein although the obtained information is generally not sufficient for either early detection of hepatic insult or effective follow up of therapeutic effects. More sensitive biomarkers may help to achieve these goals.

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response.

Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade.

Background: Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy.

Case Reports: We report two patients with melanocytic nevi that regressed with pembrolizumab therapy.

Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.

CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8 T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8 T cells that express PD-1 and suppress tumor growth.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy ( = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders.

Variation-based sparse source imaging in localizing uterine activity.

Electrohysterogram source imaging, i.e., moving from the electrode/sensor space to the source space using EHG signals, provide an estimate of spatial distributions of uterine activity at millisecond scale.

Experts' Results in Blunt Thoracic Aortic Injury are Reproducible in Lower Volume Tertiary Institutions. Early and Mid-term Results of an Observational Study.

Objectives: The aim of this study was to evaluate the early and mid-term clinical results, the device performance, and the mid-term re-intervention rates of patients suffering blunt thoracic aortic injury (BTAI) managed by a multidisciplinary team in a low-volume BTAI centre.

Methods: This was a retrospective observational study in a tertiary hospital setting. From December 2005 to March 2016, all patients over 18 years old admitted with BTAI were included in the study.

Erythema nodosum-like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy-Report of 2 patients.

Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases.

Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported.

Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma.

Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade ( = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients.

New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31Annual Meeting of the Society for Immunotherapy of Cancer, 2016.

This report is a summary of 'New Cancer Immunotherapy Agents in Development' program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy.

Polo-like-kinase 1 is a proviral host factor for hepatitis B virus replication.

Unlabelled: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for chronic hepatitis B and HCC are suboptimal. Herein, we identified cellular serine/threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy.

Does rehabilitation of cervical lordosis influence sagittal cervical spine flexion extension kinematics in cervical spondylotic radiculopathy subjects?

Objective: To test the hypothesis that improvement of cervical lordosis in cervical spondylotic radiculopathy (CSR) will improve cervical spine flexion and extension end range of motion kinematics in a population suffering from CSR.

Methods: Thirty chronic lower CSR patients with cervical lordosis < 25° were included. IRB approval and informed consent were obtained.

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance.

Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance.

Lichenoid Dermatologic Toxicity From Immune Checkpoint Blockade Therapy: A Detailed Examination of the Clinicopathologic Features.

Immunotherapy targeting the programmed cell death 1 (PD-1) receptor has demonstrated tremendous promise in the treatment of advanced solid tumors. Dermatologic toxicities, however, are an emerging consequence of this therapy and have been clearly associated with immune checkpoint blockade antibodies. Distinctive clinical and histologic subtypes of dermatologic toxicity secondary to immunotherapy are emerging and include rare autoimmune bullous reactions (eg, bullous pemphigoid) and lichenoid eruptions.

Erratum to: A case report of Grover's disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1.

[This corrects the article DOI: 10.1186/s40425-016-0157-6.].

Inferior vena cava involvement in children with Wilms tumor.

Objectives: Retrospective review of children with WT thrombus involving the IVC.

Methods: We reviewed the charts of 123 patients with WT diagnosed between January 2006 and December 2015. Patients with caval tumor thrombus were identified, demographic data, radiological images, extent of thrombus, chemo- and radiotherapy, surgical approach, pathology reports and outcomes were analyzed.