Screening for Health-Related Social Needs: American College of Preventive Medicine's Practice Statement.

Interest is rapidly growing around screening for health-related social needs (HRSN) in direct patient care settings. The screening and provision of HRSN is often done in the context of trying to address social determinants of health (SDOH). While there is emerging evidence that screening and referral for HRSN can improve health outcomes, there are educational, operational, and systemic gaps that need to be filled in order for HRSN screening and referral to be implemented system-wide and result in meaningful improvement in population health outcomes.

Celecoxib and LLW-3-6 Reduce Survival of Human Glioma Cells Independently and Synergistically with Sulfasalazine.

Gliomas are among the most commonly diagnosed central nervous system tumors. Celecoxib has been utilized with success in the treatment of several types of cancer, including gliomas. The present study examined the antiproliferative effects of celecoxib and its benzimidazole-based analog, LLW-3-6, when used as co-treatment with sulfasalazine against human glioma LN18 cells.

LLW-3-6 and celecoxib impacts growth in prostate cancer cells and subcellular localization of COX-2.

The proliferation in human prostate carcinomas, PC3 and MDA-PCa-2b, was analyzed for cells treated with LLW-3-6 and celecoxib in the presence and absence of sulfasalazine. LLW-3-6 was more potent than celecoxib at mediating a dose-dependent reduction of viable PC3 cells. Co-treatment with a non-lethal dose of sulfasalazine diminished the potency of both drugs in this cell line.

Serine palmitoyltransferase subunit 1 is present in the endoplasmic reticulum, nucleus and focal adhesions, and functions in cell morphology.

Serine palmitoyltransferase (SPT) has been localized to the endoplasmic reticulum (ER) by subcellular fractionation and enzymatic assays, and fluorescence microscopy of epitope-tagged SPT; however, our studies have suggested that SPT subunit 1 might be present also in focal adhesions and the nucleus. These additional locations have been confirmed by confocal microscopy using HEK293 and HeLa cells, and for focal adhesions by the demonstration that SPT1 co-immunoprecipitates with vinculin, a focal adhesion marker protein. The focal adhesion localization of SPT1 is associated with cell morphology, and possibly cell migration, because it is seen in most cells before they reach confluence but disappears when they become confluent, and is restored by a standard scratch-wound healing assay.

Novel functional association of serine palmitoyltransferase subunit 1-A peptide in sphingolipid metabolism with cytochrome P4501A1 transactivation and proliferative capacity of the human Glioma LN18 brain tumor cell line.

Some chemical modulators of cytochrome P4501A1, Cyp1A1, expression also perturb the activity of serine palmitoyltransferase, SPT, a heterodimeric protein responsible for catalyzing the first reaction in sphingolipid biosynthesis. The effect of altered SPT activity on Cyp1A1 expression has generally been attributed to changes in the composition of bioactive sphingolipids, generated downstream in the SPT metabolic pathway, but the precise mechanism remains poorly defined. A generally accepted model for chemical-induced transactivation of the Cyp1A1 gene involves intracellular signaling mediated by proteins including the arylhydrocarbon receptor, AhR, whose interaction with the 90 kilo Dalton heat shock protein, Hsp90, is essential for maintaining a high affinity ligandbinding receptor conformation.

Molecular mechanisms for the regulation of aryl sulfotransferase IV expression during 2-acetylaminofluorene-induced hepatocarcinogenesis in rat.

The dietary administration of 2-acetylaminofluorene to male rats to induce hepatocarcinogenesis causes a reversible as well as persistent down-modulation of N-hydroxy-2AAF sulfotransferase activity. Studies are presented which indicate that several molecular mechanisms may be involved in the down-regulation of sulfotransferase activity and expression. These include carcinogen-mediated inactivation of sulfotransferase mRNA or protein, interference with hormonal regulation of sulfotransferase expression, and, mutation of the sulfotransferase gene.

Hypomethylation of the rat aryl sulfotransferase IV gene and amplification of a DNA sequence during multistage 2-acetylaminofluorene hepatocarcinogenesis.

Rat hepatic aryl sulfotransferase IV (AST IV), which catalyses sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene to its ultimate carcinogenic form, is differentially expressed during multistep 2-acetylaminofluorene (AAF) hepatocarcinogenesis. Two molecular mechanisms associated with this effect involve modulation of mRNA translational capacity at the early stages, and gene transcription at the late stages of the carcinogenic process. To characterize further the molecular mechanisms that may be involved in the transient regulation of the enzyme expression, an AST IV cDNA was used to assess the change in methylation profile and restriction fragment length polymorphism (RFLP) in the gene domain of genomic DNA derived from rats at different stages of carcinogenesis.

Characterization of a complementary DNA for rat liver aryl sulfotransferase IV and use in evaluating the hepatic gene transcript levels of rats at various stages of 2-acetylaminofluorene-induced hepatocarcinogenesis.

A complementary DNA (cDNA) for rat hepatic aryl sulfotransferase IV (AST IV) was isolated, characterized, and used as a hybridization probe to evaluate the molecular basis for the differential expression of AST IV during 2-acetylaminofluorine (2AAF)-induced hepatocarcinogensis. The AST IV cDNA clone was obtained by immunochemical screening of a male Sprague-Dawley rat liver cDNA library. The AST IV cDNA was found to be 1.

Hemoglobin adduct and hepatic- and urinary bladder-DNA adduct levels in rapid and slow acetylator Syrian inbred hamsters administered 2-aminofluorene.

The levels of covalently bound arylamine-hemoglobin and DNA adduct formation were used as dosimeters to measure the effect of acetylator genotype and sex on the metabolic conversion of the carcinogen, 2-aminofluorene, to reactive intermediates. A single high dose of 2-aminofluorene (60 mg/kg b.wt.

Acetylator genotype-dependent expression of arylamine N-acetyltransferase in human colon cytosol from non-cancer and colorectal cancer patients.

Human epidemiological studies suggest an association between rapid acetylator phenotype and colorectal cancer. Acetylator genotype-dependent expression by the human colon of arylamine N-acetylation capacity, catalyzed by acetyl coenzyme A-dependent N-acetyltransferase(s) (EC 2.3.

Modulation of hepatic mRNA translation activity and specific expression of arylsulfotransferase IV during acetylaminofluorene-induced rat hepatocarcinogenesis.

Enzymatic sulfation of N-hydroxylated arylamines by mammalian hepatic cytosol sulfotransferases (AST; EC 2.8.2.

Relationship of Syrian inbred hamster acetylator genotype to the mutagenic activation of 2-aminofluorene.

The genetic constitution of mammalian enzymes involved in the metabolism of xenobiotics is one of the important factors responsible for large inter-individual differences in the rate of biotransformation and consequently the magnitude of genotoxic effects exerted in target tissues. The present study examines the mutagenic activation of 2-aminofluorene (AF) with hepatic post-mitochondrial (S9) preparations derived from homozygous rapid (Patr/Patr) acetylator and homozygous slow (Pats/Pats) acetylator Syrian inbred hamsters and its relationship to acetylator genotype. These hamster strains differ in their capacities for acetyl coenzyme A (AcCoA)-dependent, N-acetylation and O-acetylation of carcinogenic arylamines and their N-hydroxyarylamine metabolites.

Polymorphic expression of acetyl coenzyme A-dependent arylamine N-acetyltransferase and acetyl coenzyme A-dependent O-acetyltransferase-mediated activation of N-hydroxyarylamines by human bladder cytosol.

Human epidemiological studies suggest a genetic predisposition to bladder cancer among slow N-acetylators. The capacity of human bladder to N-acetylate arylamines, catalyzed by acetyl coenzyme A-dependent N-acetyltransferase(s) (EC 2.3.

Kinetic characterization of acetylator genotype-dependent and -independent N-acetyltransferase isozymes in homozygous rapid and slow acetylator inbred hamster liver cytosol.

Acetyl-coenzyme A (AcCoA)-dependent arylamine N-acetyltransferase (NAT) activity (EC 2.3.1.

Identification and kinetic characterization of acetylator genotype-dependent and -independent arylamine carcinogen N-acetyltransferases in hamster bladder cytosol.

Recent studies from our laboratory have shown relatively high levels of polymorphic N-acetyltransferase (NAT)(EC 2.3.1.

Genetic control of acetyl coenzyme A-dependent arylamine N-acetyltransferase, hydrazine N-acetyltransferase, and N-hydroxy-arylamine O-acetyltransferase enzymes in C57BL/6J, A/J, AC57F1, and the rapid and slow acetylator A.B6 and B6.A congenic inbred mouse.

Acetyl coenzyme A-dependent N-acetyltransferase and O-acetyltransferase activities were examined in liver cytosols derived from homozygous rapid acetylator C57BL/6J and A.B6 congenic inbred mouse strains, from homozygous slow acetylator A/J and B6.A congenic inbred mouse strains, and from the (C57BL/6J x A/J)F1 heterozygous acetylator hybrid mouse strain.

Inheritance of acetylator genotype-dependent arylamine N-acetyltransferase in hamster bladder cytosol.

Acetyl coenzyme A-dependent arylamine N-acetyltransferase (EC 2.3.1.