Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor.

Immune checkpoint therapy has revolutionized cancer treatment by blocking inhibitory pathways in T cells that limits the an effective anti-tumor immune response. Therapeutics targeting CTLA-4 and PD1/PDL1 have progressed to first line therapy in multiple tumor types with some patients exhibiting tumor regression or remission. However, the majority of patients do not benefit from checkpoint therapy emphasizing the need for alternative therapeutic options.

Assays to Interrogate the Ability of Compounds to Inhibit the AF-2 or AF-1 Transactivation Domains of the Androgen Receptor.

Prostate cancer is the leading cause of cancer and second leading cause of cancer-related death in men in the United States. Twenty percent of patients receiving the standard of care androgen deprivation therapy (ADT) eventually progress to metastatic and incurable castration-resistant prostate cancer (CRPC). Current FDA-approved drugs for CRPC target androgen receptor (AR) binding or androgen production, but only provide a 2- to 5-month survival benefit due to the emergence of resistance.

Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response.

Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson's trichrome) and vascular (CD31) markers.

Clinical Outcomes Following Stereotactic Body Radiation Therapy (SBRT) for Stage I Medically Inoperable Small Cell Lung Carcinoma: A Multi-Institutional Analysis From the RSSearch Patient Registry.

Objectives: To utilize the RSSearch Patient Registry (RSSPR) to examine local control (LC), overall survival (OS), and toxicities following stereotactic body radiation therapy (SBRT) for stage I (T1-T2/N0) medically inoperable small cell lung carcinoma (SCLC).

Materials And Methods: We searched the RSSPR for medically inoperable stage I SCLC patients treated with definitive SBRT. Potential predictive factors of OS were estimated using the Kaplan-Meier method as well as a Cox proportional hazards model.

Three-Dimensional Nanoscale Nuclear Architecture Mapping of Rectal Biopsies Detects Colorectal Neoplasia in Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) colitis are at an increased risk of developing colorectal cancer and are currently recommended to undergo extensive annual or biennial colonoscopy, a costly and invasive procedure. Most surveillance colonoscopies are negative with no existing objective measures for assessing their risk of developing cancer. We have recently developed a less invasive, cost-effective and objective method to assess cancer risk by detecting the presence of colonic neoplasia via 3-dimensional (3D) nanoscale nuclear architecture mapping (nanoNAM) of normal-appearing rectal biopsies.

Confirmation of Selected Synergistic Cancer Drug Combinations Identified in an HTS Campaign and Exploration of Drug Efflux Transporter Contributions to the Mode of Synergy.

Systematic unbiased high-throughput screening (HTS) of drug combinations (DCs) in well-characterized tumor cell lines is a data-driven strategy to identify novel DCs with potential to be developed into effective therapies. Four DCs from a DC HTS campaign were selected for confirmation; only one appears in clinicaltrials.gov and limited preclinical in vitro data indicates that the drug pairs interact synergistically.

CD56 CD16 Natural Killer Cell Profiling in Melanoma Patients Receiving a Cancer Vaccine and Interferon-α.

Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients.

Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.

Background: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes.

Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database.

Animal and clinical studies demonstrate that cancer drug combinations (DCs) are more effective than single agents. However, it is difficult to predict which DCs will be more efficacious than individual drugs. Systematic DC high-throughput screening (HTS) of 100 approved drugs in the National Cancer Institute's panel of 60 cancer cell lines (NCI-60) produced data to help select DCs for further consideration.

The association between birth order and childhood brain tumors: a systematic review and meta-analysis.

The incidence of childhood brain tumors (CBT) has increased worldwide, likely resulting from the improvements of early diagnostics. We conducted a systematic review and meta-analysis to clarify the association between birth order and CBT. We followed established guidelines to systematically search Ovid Medline, PubMed, and the Cochrane Library for English language studies, published before March 2018.

Distinct mechanisms regulate IL1B gene transcription in lymphoid CD4 T cells and monocytes.

Interleukin 1β is a pro-inflammatory cytokine important for both normal immune responses and chronic inflammatory diseases. The regulation of the 31 kDa proIL-1β precursor coded by the IL1B gene has been extensively studied in myeloid cells, but not in lymphoid-derived CD4 T cells. Surprisingly, we found that some CD4 T cell subsets express higher levels of proIL-1β than unstimulated monocytes, despite relatively low IL1B mRNA levels.

PD-L1 Mediates Dysfunction in Activated PD-1 NK Cells in Head and Neck Cancer Patients.

Inhibitory immune-checkpoint receptors (ICRs), including programmed death 1 (PD-1), have been characterized as exhaustion markers on T cells that infiltrate the tumor microenvironment (TME) of many cancer types, including head and neck cancer (HNC). However, expression and function of ICRs, including PD-1, on natural killer (NK) cells remains less defined. NK cells are innate immune effector cells that lyse epidermal growth factor receptor-overexpressing HNC cells via cetuximab-mediated antibody-dependent cytotoxicity.

The Prognostic Significance of p16 Status in Patients With Vulvar Cancer Treated With Vulvectomy and Adjuvant Radiation.

Purpose: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT).

A prospective study of dietary polyunsaturated fatty acids intake and lung cancer risk.

Animal studies have shown that polyunsaturated fatty acids (PUFAs) have antineoplastic and anti-inflammatory properties. Results from epidemiologic studies on specific types of PUFAs for lung cancer risk, however, are inconclusive. We prospectively evaluated the association of specific types of dietary PUFA intakes and lung cancer risk in two population-based cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS) with a total of 121,970 study participants (i.

Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease.

The U.S. Food and Drug Administration (FDA) recently approved pembrolizumab, an anti- programmed cell death protein 1 cancer immunotherapeutic, for use in advanced solid tumors in patients with the microsatellite-high/DNA mismatch repair-deficient biomarker.

The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues.

That cancer cells show patterns of metabolism different from normal cells has been known for over 50 years. Yet, it is only in the past decade or so that an appreciation of the benefits of these changes has begun to emerge. Altered cancer cell metabolism was initially attributed to defective mitochondria.

Single-institutional outcomes of adjuvant brachytherapy for Stage I endometrial cancer-Are outcomes consistent with randomized studies?

Purpose: Vaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2.

Methods And Materials: We retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014.

Reputation Management and Content Control: An Analysis of Radiation Oncologists' Digital Identities.

Introduction: Google is the most popular search engine in the United States, and patients are increasingly relying on online webpages to seek information about individual physicians. This study aims to characterize what patients find when they search for radiation oncologists online.

Methods And Materials: The Centers for Medicare and Medicaid Services (CMS) Physician Comparable Downloadable File was used to identify all Medicare-participating radiation oncologists in the United States and Puerto Rico.

Pharmacodynamic analyses in a multi-laboratory network: lessons from the poly(ADP-ribose) assay.

Clinical pharmacodynamic assays need to meet higher criteria for sensitivity, precision, robustness, and reproducibility than those expected for research-grade assays because of the long duration of clinical trials and the potentially unpredictable number of laboratories running the assays. This report describes the process of making an immunoassay based on commercially available reagents "clinically ready". The assay was developed to quantify poly(ADP-ribose) (PAR) levels as a marker of PAR polymerase inhibitor activity for a proof-of-concept phase 0 clinical trial at the National Cancer Institute (NCI) and subsequent clinical trials.

A quantitative, surface plasmon resonance-based approach to evaluating DNA binding by the c-Myc oncoprotein and its disruption by small molecule inhibitors.

The use of small molecules to interfere with protein-protein interactions has tremendous therapeutic appeal and is an area of intense interest. Numerous techniques exist to assess these interactions and their disruption. Many, however, require large amounts of protein, do not allow interactions to be followed in real time, are technically demanding or require large capital expenditures and high levels of expertise.

Detection of cancer DNA in plasma of patients with early-stage breast cancer.

Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.

Experimental Design: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29).

Development of a multimarker assay for early detection of ovarian cancer.

Purpose: Early detection of ovarian cancer has great promise to improve clinical outcome.

Patients And Methods: Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.