SRF617 Is a Potent Inhibitor of CD39 with Immunomodulatory and Antitumor Properties.

CD39 (ENTPD1) is a key enzyme responsible for degradation of extracellular ATP and is upregulated in the tumor microenvironment (TME). Extracellular ATP accumulates in the TME from tissue damage and immunogenic cell death, potentially initiating proinflammatory responses that are reduced by the enzymatic activity of CD39. Degradation of ATP by CD39 and other ectonucleotidases (e.

CD73 Inhibits cGAS-STING and Cooperates with CD39 to Promote Pancreatic Cancer.

The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells.

The NetSage measurement and analysis framework in practice.

Data sharing is required for research collaborations, but effective data transfer performance continues to be difficult to achieve. The NetSage Measurement and Analysis Framework can assist in understanding research data movement. It collects a broad set of monitoring data and builds performance Dashboards to visualize the data.

Bile Reflux Gastropathy and Functional Dyspepsia.

Background/aims: The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. We aim to examine the association of bile reflux gastropathy with functional dyspepsia and identify predisposing factors.

Methods: In a retrospective study, patients with functional dyspepsia (Rome III) who completed symptom assessment, esophagogastroduodenoscopy, and biopsies were categorized into 3 groups; bile gastropathy (BG), non-bile gastropathy (NBG), and no gastropathy (NG).

The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a.

Background: CD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction with the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily expressed on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and immune cell homeostasis). CD47/SIRPα antagonists, commonly referred to as 'macrophage checkpoint' inhibitors, are being developed as cancer interventions.

Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics.

Background: Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national-level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates.

Methods: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension.

Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics.

Background: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate to provide annual updates on cancer occurrence and trends in the United States.

Methods: Incidence data were obtained from the CDC-funded and NCI-funded population-based cancer registry programs and compiled by NAACCR. Data on cancer deaths were obtained from the National Center for Health Statistics National Vital Statistics System.

Annual Report to the Nation on the Status of Cancer, 1975-2014, Featuring Survival.

Background: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate to provide annual updates on cancer occurrence and trends in the United States. This Annual Report highlights survival rates. Data were from the CDC- and NCI-funded population-based cancer registry programs and compiled by NAACCR.

Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer.

Background: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers.

Methods: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS).

Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits.

Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides).

Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State.

Background: The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data.

Methods: Population-based cancer trends and breast cancer incidence by molecular subtype were calculated.

Capture, isolation and electrochemical detection of industrially-relevant engineered aerosol nanoparticles using poly (amic) acid, phase-inverted, nano-membranes.

Workplace exposure to engineered nanoparticles (ENPs) is a potential health and environmental hazard. This paper reports a novel approach for tracking hazardous airborne ENPs by applying online poly (amic) acid membranes (PAA) with offline electrochemical detection. Test aerosol (Fe2O3, TiO2 and ZnO) nanoparticles were produced using the Harvard (Versatile Engineered Generation System) VENGES system.

Unusual metal-coordinated zwitterionic P-C-N-C-N-C phosphido adducts.

Rare examples of homodinuclear zwitterionic Pd(II) and Pt(II) complexes with bridging, two-coordinate P{cyclo-CH(2)N(R)CHN(R)CH(2)} ligands (R = 4-FC(6)H(4)CH(2), C(6)H(5)CH(2)) have been characterized by single-crystal X-ray diffraction using synchrotron radiation. Short N-C distances and enlarged N-C-N bond angles support electron delocalization in the central N-C-N backbone.

Indirect method to estimate specific Hispanic group cancer rates.

Introduction: Several states with large Hispanic populations have historically served as the source for US Hispanic cancer incidence rates, with aggregation of data across all states limited by different methodologies to identify Hispanic persons. Now with data available for more than 85% of the US Hispanic population, state rates suggest regional diversity in their Hispanic cancer profiles.

Method: We tested an approach of using a surrogate indicator of county residential homogeneity for Hispanic groups based on the 2000 US Census.

Intramolecular hydrogen-bonded tertiary phosphines as 1,3,5-triaza-7-phosphaadamantane (PTA) analogues.

New cationic trialkylphosphines [P(CH(2)NH(2)R){CH(2)N(R)CH(2)N(R)CH(2)}](+) (R = C(6)H(5)CH(2), a; 4-FC(6)H(4)CH(2), b), as their Cl(-) (1a, 1b), SbF(6)(-) (2a, 2b), and PF(6)(-) (3a, 3b) salts, are described. The phosphine framework is conformationally locked, in the solid state, through pairs of intramolecular N-H..

A novel fluorene-containing kappa(4)-P(2)N(2)-tetradentate platinum(II) complex.

Base induced P,N-chelation, C-C coupling and methylene C-H deprotonation affords an unusual fluorene containing square-planar Pt(II) complex Pt(kappa4-P2N2-Ph2PCH=NNCC12H8)2 which has been isolated and structurally characterised.

Method to assess identifiability in electronic data files.

The authors developed the Record Uniqueness (RU) software program to assess electronic data files for risk of confidentiality breach based on unique combinations of key variables. The underlying methodology utilized by the RU program generates a frequency distribution for every variable selected for analysis and for all combinations of the variables selected. In addition, the program provides the regression coefficient that designates the relative contribution of each variable to the unique records on the data file.

Low molecular weight fucoidan increases VEGF165-induced endothelial cell migration by enhancing VEGF165 binding to VEGFR-2 and NRP1.

Therapeutic induction of angiogenesis is a potential treatment for chronic ischemia. Heparan sulfate proteoglycans are known to play an important role by their interactions with proangiogenic growth factors such as vascular endothelial growth factor (VEGF). Low molecular weight fucoidan (LMWF), a sulfated polysaccharide from brown seaweeds that mimic some biological activities of heparin, has been shown recently to promote revascularization in rat critical hindlimb ischemia.

Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members.

Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL.

The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells.

Uterine fibroids (leiomyomas) are a major women's health problem. Currently, the standard for treatment remains hysterectomy, since no other treatment modalities can reduce both symptoms and recurrence. As leiomyomas are benign neoplasias of smooth muscle cells, we sought to understand the regulation of uterine smooth muscle cell mitogenesis by CCN5, a growth arrest-specific gene in vascular smooth muscle cells which is induced and maintained by heparin treatment.

CCN5 modulates the antiproliferative effect of heparin and regulates cell motility in vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VSMC) hyperplasia plays an important role in both chronic and acute vascular pathologies including atherosclerosis and restenosis. Considerable work has focused on the mechanisms regulating VSMC proliferation and motility. Earlier work in our lab revealed a novel growth arrest-specific (gas) gene induced in VSMC exposed to the antiproliferative agent heparin.

CCN5 is a growth arrest-specific gene that regulates smooth muscle cell proliferation and motility.

Vascular smooth muscle cell (VSMC) hyperplasia plays an important role in both chronic and acute vascular pathologies. Considerable work has focused on the mechanisms regulating VSMC growth and the search for agents that could suppress VSMC hyperproliferation. One of the several inhibitors studied is the glycosaminoglycan heparin, which inhibits VSMC proliferation and migration both in cell culture and in animal models (Mishra-Gorur K, Delmolino LM, Castellot Jr JJ: Biological functions of heparan sulfate and heparan sulfate proteoglycans.