Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC

Platelet-activating factor receptor in GtoPdb v.2023.1

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is an ether phospholipid mediator associated with platelet coagulation, but also subserves inflammatory roles. The PAF receptor (provisional nomenclature recommended by NC-IUPHAR [38]) is activated by PAF and other suggested endogenous ligands are oxidized phosphatidylcholine [74] and lysophosphatidylcholine [98]. It may also be activated by bacterial lipopolysaccharide [91]

Platelet-activating factor receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is an ether phospholipid mediator associated with platelet coagulation, but also subserves inflammatory roles. The PAF receptor (provisional nomenclature recommended by NC-IUPHAR [37]) is activated by PAF and other suggested endogenous ligands are oxidized phosphatidylcholine [73] and lysophosphatidylcholine [96]. It may also be activated by bacterial lipopolysaccharide [89]

Age before stage: insulin resistance rises before the onset of puberty: a 9-year longitudinal study (EarlyBird 26).

OBJECTIVE: Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS: The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L). RESULTS: IR rose progressively from age 7 years, 3-4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels. CONCLUSIONS: IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important

Association between neighborhood need and spatial access to food stores and fast food restaurants in neighborhoods of Colonias

Objective To determine the extent to which neighborhood needs (socioeconomic deprivation and vehicle availability) are associated with two criteria of food environment access: 1) distance to the nearest food store and fast food restaurant and 2) coverage (number) of food stores and fast food restaurants within a specified network distance of neighborhood areas of colonias, using ground-truthed methods. Methods Data included locational points for 315 food stores and 204 fast food restaurants, and neighborhood characteristics from the 2000 U.S. Census for the 197 census block group (CBG) study area. Neighborhood deprivation and vehicle availability were calculated for each CBG. Minimum distance was determined by calculating network distance from the population-weighted center of each CBG to the nearest supercenter, supermarket, grocery, convenience store, dollar store, mass merchandiser, and fast food restaurant. Coverage was determined by calculating the number of each type of food store and fast food restaurant within a network distance of 1, 3, and 5 miles of each population-weighted CBG center. Neighborhood need and access were examined using Spearman ranked correlations, spatial autocorrelation, and multivariate regression models that adjusted for population density. Results Overall, neighborhoods had best access to convenience stores, fast food restaurants, and dollar stores. After adjusting for population density, residents in neighborhoods with increased deprivation had to travel a significantly greater distance to the nearest supercenter or supermarket, grocery store, mass merchandiser, dollar store, and pharmacy for food items. The results were quite different for association of need with the number of stores within 1 mile. Deprivation was only associated with fast food restaurants; greater deprivation was associated with fewer fast food restaurants within 1 mile. CBG with greater lack of vehicle availability had slightly better access to more supercenters or supermarkets, grocery stores, or fast food restaurants. Increasing deprivation was associated with decreasing numbers of grocery stores, mass merchandisers, dollar stores, and fast food restaurants within 3 miles. Conclusion It is important to understand not only the distance that people must travel to the nearest store to make a purchase, but also how many shopping opportunities they have in order to compare price, quality, and selection. Future research should examine how spatial access to the food environment influences the utilization of food stores and fast food restaurants, and the strategies used by low-income families to obtain food for the household

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC

Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC