Future cancer research priorities in the USA: a Lancet Oncology Commission.

We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine.

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma.

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma.

Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3 Protein Expression Following In Vitro Transfection.

CD4⁺CD25⁺Foxp3⁺ T regulatory (Treg) cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented that lentivirus-activated Treg cells exhibit heightened Foxp3 expression when compared to Treg cells from uninfected controls. Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs) contribute to heightened Treg cell suppressor function by stabilizing Foxp3 expression.

Lack of myeloid Fatp1 increases atherosclerotic lesion size in Ldlr mice.

Background And Aims: Altered metabolism is an important regulator of macrophage (MΦ) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated MΦs (CAM) are glycolytic while alternatively-activated MΦs (AAM) oxidize fatty acids, although overlap exists. We previously demonstrated that MΦ fatty acid transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity.

SurvivorCHESS to increase physical activity in colon cancer survivors: can we get them moving?

Purpose: This randomized controlled trial evaluated the impact of SurvivorCHESS, an eHealth intervention, on physical activity in colon cancer survivors and to explore the impact of SurvivorCHESS on quality of life and distress.

Methods: This was a two-arm single-blinded multi-site randomized controlled trial comparing a control group to an intervention group receiving a smartphone with the SurvivorCHESS program.

Results: Participants using SurvivorCHESS (n = 144) increased their moderate to vigorous physical activities from 19.

Diagnostic accuracy of contrast-enhanced ultrasound for characterization of kidney lesions in patients with and without chronic kidney disease.

Background: Patients with chronic kidney disease are at increased risk of cystic kidney disease that requires imaging monitoring in many cases. However, these same patients often have contraindications to contrast-enhanced computed tomography and magnetic resonance imaging. This study evaluates the accuracy of contrast-enhanced ultrasound (CEUS), which is safe for patients with chronic kidney disease, for the characterization of kidney lesions in patients with and without chronic kidney disease.

Financial Incentives for Adherence to Hepatitis C Virus Clinical Care and Treatment: A Randomized Trial of Two Strategies.

Background: Although rates of sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in trials and some more "real world" settings, some patients, such as those with substance use disorders, will be challenged to adhere to HCV care.

Methods: To assess the feasibility of 2 strategies for financially incentivizing adherence to HCV care, patients with a substance use history prescribed 12 weeks of a sofosbuvir-containing regimen were randomized to either fixed or lottery-based monetary incentives for attending clinic appointments, pill count adherence >90%, and SVR achievement. Electronic medication monitoring provided an objective measure of DAA adherence.

Sequencing the Biology of Entry: The Retroviral env Gene.

The surface envelope protein of any virus is major determinant of the host cell that is infected and as a result a major determinant of viral pathogenesis. Retroviruses have a single surface protein named Env. It is a trimer of heterodimers and is responsible for binding to the host cell receptor and mediating fusion between the viral and host membranes.

Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma.

Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism.

Unmet Needs in Clinical Research in Breast Cancer: Where Do We Need to Go?

This highlights areas in breast cancer research with the greatest potential for clinical and therapeutic application. The articles in this address the state of the science in a broad range of areas with a focus on "hot" although sometimes controversial topics, unanswered questions, and unmet need. From mutational signatures, the cancer genomic revolution, and new inroads in immunotherapy for breast cancer to unique concerns of vulnerable populations as well as national and global health disparities, these works represent much of the promise of breast cancer research as well as the challenges in the coming years.

Second generation stationary digital breast tomosynthesis system with faster scan time and wider angular span.

Purpose: The aim of this study was to characterize a new generation stationary digital breast tomosynthesis system with higher tube flux and increased angular span over a first generation system.

Methods: The linear CNT x-ray source was designed, built, and evaluated to determine its performance parameters. The second generation system was then constructed using the CNT x-ray source and a Hologic gantry.

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

Background: In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study.

Epigallocatechin gallate has pleiotropic effects on transmembrane signaling by altering the embedding of transmembrane domains.

Epigallocatechin gallate (EGCG) is the principal bioactive ingredient in green tea and has been reported to have many health benefits. EGCG influences multiple signal transduction pathways related to human diseases, including redox, inflammation, cell cycle, and cell adhesion pathways. However, the molecular mechanisms of these varying effects are unclear, limiting further development and utilization of EGCG as a pharmaceutical compound.

Modeling Geospatial Patterns of Late-Stage Diagnosis of Breast Cancer in the US.

In the US, about one-third of new breast cancers (BCs) are diagnosed at a late stage, where morbidity and mortality burdens are higher. Health outcomes research has focused on the contribution of measures of social support, particularly the residential isolation or segregation index, on propensity to utilize mammography and rates of late-stage diagnoses. Although inconsistent, studies have used various approaches and shown that residential segregation may play an important role in cancer morbidities and mortality.

Estimating scatter from sparsely measured primary signal.

Scatter radiation severely degrades the image quality. Measurement-based scatter correction methods sample the scatter signal at sparsely distributed points, from which the scatter profile is estimated and deterministically removed from the projection image. The estimation of the scatter profile is generally done through a spline interpolation and the resulting scatter profile is quite smooth.

Adherence to nutrition-based cancer prevention guidelines and breast, prostate and colorectal cancer risk in the MCC-Spain case-control study.

Prostate, breast and colorectal cancer are the most common tumours in Spain. The aim of the present study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and prostate, breast and colorectal cancer, in the MCC-Spain case-control study. A total of 1,718 colorectal, 1,343 breast and 864 prostate cancer cases and 3,431 population-based controls recruited between 2007 and 2012, were included in the present study.

Defective postsecretory maturation of MUC5B mucin in cystic fibrosis airways.

In cystic fibrosis (CF), airway mucus becomes thick and viscous, and its clearance from the airways is impaired. The gel-forming mucins undergo an ordered "unpacking/maturation" process after granular release that requires an optimum postsecretory environment, including hydration and pH. We hypothesized that this unpacking process is compromised in the CF lung due to abnormal transepithelial fluid transport that reduces airway surface hydration and alters ionic composition.

An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity.

α1A-ARs play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, we administered dabuzalgron to mice treated with DOX, a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to HF.

Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503).

Purpose: Tools to estimate survival, such as ePrognosis ( http://eprognosis.ucsf.edu/carey2.

Increasing JAK/STAT Signaling Function of Infant CD4 T Cells during the First Year of Life.

Most infant deaths occur in the first year of life. Yet, our knowledge of immune development during this period is scarce and derived from cord blood (CB) only. To more effectively combat pediatric diseases, a deeper understanding of the kinetics and the factors that regulate the maturation of immune functions in early life is needed.

AtSERPIN1 is an inhibitor of the metacaspase AtMC1-mediated cell death and autocatalytic processing in planta.

The hypersensitive response (HR) is a localized programmed cell death phenomenon that occurs in response to pathogen recognition at the site of attempted invasion. Despite more than a century of research on HR, little is known about how it is so tightly regulated and how it can be contained spatially to a few cells. AtMC1 is an Arabidopsis thaliana plant metacaspase that positively regulates the HR.

Using residential segregation to predict colorectal cancer stage at diagnosis: two different approaches.

Purpose: Studies have found a variety of evidence regarding the association between residential segregation measures and health outcomes in the United States. Some have focused on any individuals living in residentially segregated places, whereas others have examined whether persons of specific races or ethnicities living in places with high segregation of their own race or ethnicity have differential outcomes. This article compares and contrasts these two approaches in the study of predictors of late-stage colorectal cancer (CRC) diagnoses in a cross-national study.

Meat intake, cooking methods and doneness and risk of colorectal tumours in the Spanish multicase-control study (MCC-Spain).

Purpose: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study.

Methods: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses.

Analysis of Pre-existing IgG and IgM Antibodies against Polyethylene Glycol (PEG) in the General Population.

Circulating antibodies (Ab) that specifically bind polyethylene glycol (PEG), a biocompatible polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy of and/or adverse reactions to therapeutics modified with or containing PEG. Unlike most antidrug antibodies that are induced following initial drug dosing, anti-PEG Ab can be found in treatment-naïve individuals (i.e.

Minimal intervention delivered by 2-1-1 information and referral specialists promotes smoke-free homes among 2-1-1 callers: a Texas generalisation trial.

Background: Replication of intervention research is reported infrequently, limiting what we know about external validity and generalisability. The Smoke Free Homes Program, a minimal intervention, increased home smoking bans by United Way 2-1-1 callers in randomised controlled trials in Atlanta, Georgia and North Carolina.

Objective: Test the programme's generalisability-external validity in a different context.