26 research outputs found
Differences in receipt of multimodality therapy by race,insurance status, and socioeconomic disadvantage in patientswith resected pancreatic cancer
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Background and Methods:Racial and socioeconomic disparities in receipt ofadjuvant chemotherapy affect patients with pancreatic cancer. However, differencesin receipt of neoadjuvant chemotherapy among patients undergoing resection arenot well�understood. A retrospective cross�sectional cohort of patients withresected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified fromthe National Cancer Database (2014–2017). Outcomes included receipt ofneoadjuvant versus adjuvant chemotherapy, or receipt of either, defined asmultimodality therapy and were assessed by univariate and multivariate analysis.Results:Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624(49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received nochemotherapy. On multivariable analysis, Black patients had lower odds ofneoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI:0.67–0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95%CI: 0.77–1.03). Patients with Medicaid or no insurance, low educational attainment,or low median income had significantly lower odds of receiving neoadjuvantchemotherapy or multimodality therapy.Conclusions:Racial and socioeconomic disparities persist in receipt of neoadjuvantand multimodality therapy in patients with resected pancreatic adenocarcinoma.Discussion:Policy and interventional implementations are needed to bridge thecontinued socioeconomic and racial disparity gap in pancreatic cancer care.ECU/Wiley Open Access Publishing Agreemen
Osteoarticular Infection in Three Young Thoroughbred Horses Caused by a Novel Gram Negative Cocco-Bacillus
© 2020 Bernard J. Hudson et al. We describe three cases of osteoarticular infection (OAI) in young thoroughbred horses in which the causative organism was identified by MALDI-TOF as Kingella species. The pattern of OAI resembled that reported with Kingella infection in humans. Analysis by 16S rRNA PCR enabled construction of a phylogenetic tree that placed the isolates closer to Simonsiella and Alysiella species, rather than Kingella species. Average nucleotide identity (ANI) comparison between the new isolate and Kingella kingae and Alysiella crassa however revealed low probability that the new isolate belonged to either of these species. This preliminary analysis suggests the organism isolated is a previously unrecognised species
The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 β-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas
<p>Abstract</p> <p>Background</p> <p>The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLe<sup>x</sup>) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 β1,6 <it>N</it>-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLe<sup>x </sup>(C2-O-sLe<sup>x</sup>). Our goal was to determine the expression profiles of C2-O-sLe<sup>x </sup>in the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLe<sup>x </sup>present in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLe<sup>x </sup>was present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 β1,6-<it>N</it>-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR).</p> <p>Results</p> <p>We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components.</p> <p>Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT-PCR. Significantly, we observed a greater than 15-fold increase in C2GnT1 mRNA levels in colorectal adenocarcinomas compared to normal colorectal tissues.</p> <p>Conclusion</p> <p>C2-O-sLe<sup>x</sup>, detected by the CHO-131 mAb, is a tumor associated antigen whose expression is highly upregulated in colorectal adenocarcinomas and metastatic liver tumors compared to normal tissues. C2-O-sLe<sup>x </sup>is a potentially useful early predictor of metastasis.</p
C2-O-sLeX Glycoproteins Are E-Selectin Ligands that Regulate Invasion of Human Colon and Hepatic Carcinoma Cells
Similar to mechanisms of recruitment of activated leukocytes to inflamed tissues, selectins mediate adhesion and extravasation of circulating cancer cells. Our objective was to determine whether sialyl Lewis X modified core 2 O-glycans (C2-O-sLeX) present on colon and hepatic carcinoma cells promote their adhesion and invasion. We examined membrane expression of C2-O-sLeX, selectin binding, invasion of human colon and hepatic carcinoma cell lines, and mRNA levels of alpha-2,3 fucosyltransferase (FucT-III) and core 2 beta-1,6 N-acetylglucosaminyltransferase (C2GnT1) genes, necessary for C2-O-sLeX synthesis, by quantitative reverse-transcriptase (RT) PCR. Synthesis of core 2 branched O-glycans decorated by sLeX is dependent on C2GnT1 function and thus we determined enzyme activity of C2GnT1. The cell lines that expressed C2GnT1 and FucT-III mRNA by quantitative RT-PCR were highly positive for C2-O-sLeX by flow cytometry, and colon carcinoma cells possessed highly active C2GnT1 enzyme. Cells bound avidly to E-selection but not to P- and L-selectin. Gene knock-down of C2GnT1 in colon and hepatic carcinoma cells using short hairpin RNAs (shRNA) resulted in a 40–90% decrease in C2-O-sLeX and a 30–50% decrease in E-selectin binding compared to control cells. Invasion of hepatic and colon carcinoma cells containing C2GnT1 shRNA was significantly reduced compared to control cells in Matrigel assays and C2GnT1 activity was down-regulated in the latter cells. The sLeX epitope was predominantly distributed on core 2 O-glycans on colon and hepatic carcinoma cells. Our findings indicate that C2GnT1 gene expression and the resulting C2-O-sLeX carbohydrates produced mediate the adhesive and invasive behaviors of human carcinomas which may influence their metastatic potential
The Association of Health Insurance and Race with Treatment and Survival in Patients with Metastatic Colorectal Cancer
BACKGROUND: Black patients and underinsured patients with colorectal cancer (CRC) present with more advanced disease and experience worse outcomes. The study aim was to evaluate the interaction of health insurance status and race with treatment and survival in metastatic CRC. MATERIALS AND METHODS: Patients diagnosed with metastatic CRC within NCDB from 2006–2016 were included. Primary outcomes included receipt of chemotherapy and 3-year all-cause mortality. Multivariable logistic regression and Cox-regression (MVR) including a two-way interaction term of race and insurance were performed to evaluate the differential association of race and insurance with receipt of chemotherapy and mortality, respectively. RESULTS: 128,031 patients were identified; 70.6% White, 14.4% Black, 5.7% Hispanic, and 9.3% Other race. Chemotherapy use was higher among White compared to Black patients. 3-year mortality rate was higher for Blacks and lower for Hispanics, in comparison with White patients. By MVR, Black patients were less likely to receive chemotherapy. When stratified by insurance status, Black patients with private and Medicare insurance were less likely to receive chemotherapy than White patients. All-cause mortality was higher in Black patients and lower in Hispanic patients, and these differences persisted after controlling for insurance and receipt of chemotherapy. CONCLUSION: Black patients and uninsured or under-insured patients with metastatic CRC are less likely to receive chemotherapy and have increased mortality. The effect of health insurance among Blacks and Whites differs, however, and improving insurance alone does not appear to fully mitigate racial disparities in treatment and outcomes
The Association of Health Insurance and Race with Treatment and Survival in Patients with Metastatic Colorectal Cancer
Altered immunophenotypic parameters in infertile women. Possible role of herpes viremia
Problem: Purpose of this study was to reveal any alteration in peripheral blood lymphocytic concentrations of a large cohort of infertile women and to investigate the possible role of herpes viremia in the peripheral immunostimulation. Method of study: The immunophenotypic characteristics and the presence of herpes viruses DNA in the peripheral blood of 168 infertile women were studied. Results: Peripheral CD56+/CD16+ natural killer (NK) cell concentration, CD56+/CD16- NK cell concentration, white blood cell (WBC) concentration and lymphocyte concentration were statistically correlated to herpes viremia. Epstein-Barr virus (EBV) viremia is related with a limited reduction of CD56+/CD16- cell levels in the peripheral blood of infertile women with regard to the rest of herpes viruses. High T-lymphocyte concentration, CD4+ T-cell concentration and CD8+ T-cell concentration was observed in women positive for three different kinds of herpes viruses (triple viremia) in the peripheral blood. Conclusions: Assuming that all women under study remained asymptomatic, these data suggest that subclinical herpesvirus viremia may be an important cause of peripheral immunostimulation in women with a history of infertility. © 2005 Blackwell Munksgaard
Differences in receipt of multimodality therapy by race,insurance status, and socioeconomic disadvantage in patientswith resected pancreatic cancer
Background and Methods:Racial and socioeconomic disparities in receipt ofadjuvant chemotherapy affect patients with pancreatic cancer. However, differencesin receipt of neoadjuvant chemotherapy among patients undergoing resection arenot well-understood. A retrospective cross-sectional cohort of patients withresected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified fromthe National Cancer Database (2014–2017). Outcomes included receipt ofneoadjuvant versus adjuvant chemotherapy, or receipt of either, defined asmultimodality therapy and were assessed by univariate and multivariate analysis.Results:Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624(49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received nochemotherapy. On multivariable analysis, Black patients had lower odds ofneoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI:0.67–0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95%CI: 0.77–1.03). Patients with Medicaid or no insurance, low educational attainment,or low median income had significantly lower odds of receiving neoadjuvantchemotherapy or multimodality therapy.Conclusions:Racial and socioeconomic disparities persist in receipt of neoadjuvantand multimodality therapy in patients with resected pancreatic adenocarcinoma.Discussion:Policy and interventional implementations are needed to bridge thecontinued socioeconomic and racial disparity gap in pancreatic cancer care
Differences in Receipt of Multimodality Therapy by Race, Insurance Status, and Socioeconomic Disadvantage in Patients with Resected Pancreatic Cancer
Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis
Barth syndrome (BTHS) is an X-linked recessive disorder that is biochemically characterized by low cellular levels of the mitochondrial phospholipid cardiolipin (CL). Previously, we discovered that the yeast disruptant of the TAZ ortholog in Saccharomyces cerevisiae not only displays CL deficiency but also accumulates monolysocardiolipins (MLCLs), which are intermediates in CL remodeling. Therefore, we set out to investigate whether MLCL accumulation also occurs in BTHS. Indeed, we observed MLCL accumulation in heart, muscle, lymphocytes, and cultured lymphoblasts of BTHS patients; however, only very low levels of these lysophospholipids were found in platelets and fibroblasts of these patients. Although the fatty acid composition of the MLCLs was different depending on the tissue source, it did parallel the fatty acid composition of the (remaining) CLs. The possible implications of these findings for the two reported CL remodeling mechanisms, transacylation and deacylation/reacylation, are discussed. Because MLCLs have been proposed to be involved in the initiation of apoptosome-mediated cell death by the sequestration of the proapoptotic protein (t)BH3-interacting domain death agonist (Bid) to the mitochondrial membrane, we used control and BTHS lymphoblasts to investigate whether the accumulation of MLCLs results in higher levels of apoptosis. We found no differences in susceptibility to death receptor-mediated apoptosis or in cellular distribution of Bid, cytochrome c, and other parameters, implying that MLCL accumulation does not lead to enhanced apoptosis in cultured BTHS lymphoblast