Cancer and Alcohol Consumption in People Aged 50 Years or More in Europe.

AIMS: To estimate the prevalence of hazardous drinking in individuals aged 50 and older who had or had had cancer in 17 European countries and Israel and to analyze the factors associated with their consumption. METHODS: Cross-sectional study based on data from 2011 to 2013 SHARE surveys. A total of 69,509 individuals aged 50 or more from 17 European countries and Israel participated in the study. Prevalence of hazardous drinking in people with cancer was estimated (adapting the SHARE questionnaire to the AUDIT-C). To ascertain whether type of cancer or time since diagnosis were associated with hazardous drinking, Poisson regression models with robust variance were estimated, obtaining prevalence ratios (PR). RESULTS: Overall, 5.4% of participants reported having been diagnosed with cancer. Prevalence of hazardous drinking in people with cancer was 18% in women and 23% in men. After adjusting for various socioeconomic and health variables, no significant differences were observed between hazardous drinking and type of cancer [PR = 0.99 (95% confidence interval (95% CI) = 0.83-1.17) in people with alcohol-related cancers compared to non-alcohol related cancers] and time since diagnosis [PR = 1.01 (95% CI = 0.82-1.25) in people with a cancer diagnosed >5 years ago compared to those diagnosed ≤5 years ago]. Significant differences were found between hazardous drinking and smoking status and self-perceived health. CONCLUSION: In total, 20% of people diagnosed with cancer were hazardous drinkers, despite the known relationship between alcohol use and a worse prognosis of the disease and an increased likelihood of recurrence. SHORT SUMMARY: Overall, 20% of people diagnosed with cancer were hazardous drinkers. There were no significant differences in the prevalence of hazardous drinking depending on the type of cancer (alcohol-related versus non-alcohol related cancers). Highest prevalence of hazardous drinking in people with cancer is found in smokers and people with good self-perceived health.

Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease.

Microbial transformation of bile acids affects intestinal immune homoeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. In addition, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.

IL-1ß enhances cell viability and decreases 5-FU sensitivity in novel colon cancer cell lines derived from African American patients.

Background: In the U.S., African Americans (AAs) present with the highest incidence and mortality rates for Colorectal Cancer (CRC). When compared to Caucasian American (CA) patients, AAs also have reduced response to the first line standard of care chemotherapeutic agent 5-Fluorouracil (5-FU). Previously, we observed differential gene expression between the two populations, suggesting that colon tumors from AA patients display a decreased antitumor immune response and an increased expression of genes encoding proteins involved in inflammatory processes, such as Interleukin-1ß (IL-1ß). Here, we investigate the role of IL-1ß in modifying chemotherapeutic response and altering expression of proteins in novel AA and well-established CA colon cancer cell lines. Methods: RNA sequencing analysis was performed to detect expression of genes involved in inflammation in AA and CA colon cancer cells. The effects of IL-1ß on 5-FU response was evaluated by assessing cell viability (MTS assay) and apoptosis (flow cytometry analysis) following treatment with 5-FU alone or in combination with the cytokine. Further, we used an IL-1 receptor antagonist (IL-1Ra) to inhibit IL-1ß-induced effects on 5-FU sensitivity and NF-kB pathway activation. Results: AA colon cancer cell lines present significant increase in expression of genes IL1R2 (373-fold change (FC), IRAK1 (3.24 FC), IKBKB, (5.33 FC) NF-KB IA (5.95 FC), MYD88, (3.72 FC), IRAK3 (161 FC), TRAF5 (4.1 FC). A significant decrease in the response to 5-FU treatment, as well as a significant increase in phosphorylation of IκBα and secretion of IL-8, was seen following IL-1ß treatment, in both AA and CA cell lines. Finally, treatment with IL-1Ra was able to reverse the effects induced by IL-1ß, by increasing the cells sensitivity to 5-FU. IL-1Ra also inhibited phosphorylation of IκBα and IL-8 secretion. Conclusions: Our results suggest a differential expression of inflammatory genes and proteins that might regulate the different response to IL-1ß between AA and CA colon cancer cell lines. Our data also demonstrates that IL-1ß is involved in modulating 5-FU response in both AA and CA colon cancer cell lines. Further investigation of these mechanisms might help elucidate the differences seen in incidence, mortality and response to therapy in AA colon cancer patients.

Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients.

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized "The Cancer Genome Atlas" (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic of effector T helper cell (Th) subsets by ELISA using plasma from each AA and CA participant. Results: Colon tumors from AA patients showed significant fold-change increase in gene expression when compared to CA for FOXP3 (6.22 vs. 3.22), IL1B (103 vs. 11.4) and IL8 (220 vs. 28.9) (p < 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and the immunotherapy targets PDL1 (CD274) and CTLA4 (p < 0.05). TCGA data validated our observed higher gene expression of GZMB and PDL1 in CA patients when compared to AA. Notably, our observations on immune cell populations show that AA tumors have significantly higher number of exhausted CD8+ cells (p < 0.01), mast cells (p < 0.02) and increased T regulatory cells when compared to CA. AA colon cancer patients differed from CA in cytokine production patterns in plasma (i.e., reduced IL-12). Conclusions: Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches.

Evaluation of the feasibility of intrapancreatic delivery of drug-loaded microparticles via EUS-guided fine needle injection using a swine model.

Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Establishment of three novel cell lines derived from African American patients with colorectal carcinoma: A unique tool for assessing racial health disparity.

The incidence and mortality rates of colorectal carcinoma (CRC) are higher among African Americans (AAs) compared with Caucasian Americans (CAs). To assess the molecular properties associated with racial health disparity, three cell lines derived from colorectal tumors of three AA subjects were established. Cellular and molecular characterization of the cell lines designated CHTN06, SB501 and SB521 was performed using standard technologies, including immunofluorescence, electron microscopy, karyotyping, reverse transcription-polymerase chain reaction, ELISA and immunoblot analysis. The histology and morphology of CHTN06 xenografts were examined by hematoxylin and eosin staining. A total of three AA CRC cell lines derived from primary tumors were established and characterized. These cell lines were successfully cultured without immortalization and were found to be tumorigenic as mouse xenografts. In the present study, immunoblotting and immunofluorescence confirmed the expression of proteins known to be dysregulated in CRC, such as p53, DNA mismatch repair proteins and villin-1. Oncogenic miRNAs (i.e., miR-17, miR-21, miR-182, miR-210 and miR-222) were overexpressed in the AA CRC lines compared with the CA CRC lines (HT-29, HCT116 and SW480). Additionally, the AA CRC cell lines exhibited a differential inflammatory profile compared with HT-29 (CA CRC cell line); specifically noted was IL-8 secretion in response to inflammatory stimuli. In conclusion, three novel cell lines derived from AA CRC tissues were generated. These cell lines were characterized as epithelial in nature and exhibited differential expression of several miRNAs and inflammatory responses compared with commercially available cell lines of CA origin. The CRC cell lines CHTN06, SB501 and SB521 represent novel tools that may be used to provide diverse in vitro and in vivo models for studying CRC and racial health disparity.

Evaluación in vitro de Ticarcilina, Ceftazidima, Piperacilina y la asociación Piperacilina+Tazobactam sobre Pseudomonas aeruginosa intrahospitalaria / In vitro evaluation of Ticarcilina, Ceftazidima, Piperacilina and the association Piperacilina+Tazobactam on Pseudo monkeys aeruginosa intrahospitalaria

El objetivo del presente estudio ha sido identificar y clasificarlos antibiofenotipos de resistencia a los betalactámicos presentes en las cepas de Pseudomonas aeruginosa, aisladas en el Hospital Arzobispo Loayza y evaluar la actividad in vitro frente a estas cepas intrahospitalarias de tres betalactámicos anti-piociánicos y de la asociación de uno de ellos con inhibidor de betalactamasas. Se estudiaron 70 cepas no repetitivas de Pseudomonas aeruginosa aisladas a partir de muestras clínicas de pacientes hospitalizados por no menos de 72 horas. Se realizaron antibiogramas por difusión en agar (método de Kirby-Bauer modificado) y se determinaron las concentraciones inhibitorias mínimas (MIC) mediante la técnica del E-test. Finalmente se identificaron y clasificaron los antibiofenotipos de Pseudomonas aeruginosa para los betalactámicos. Los resultados muestran que en 41.4% de cepas de Pseudomonas aeruginosa fue sensible a la Ticarcilina, mientras que el 60% de las cepas fueron sensibles a la Piperacilina (sola y en asociación con el Tazobactam). La Ceftazidima tuvo una actividad superior a la Ticarcilina y a la Piperacilina (70.4% de cepas sensibles). En conclusión, los porcentajes de resistencia encontrados para Ceftazidima, Ticarcilina, Piperacilina y Piperacilina + Tazobactam, invalidan el uso de estas moléculas en el tratamiento probabilístico de una infección a Pseudomonas aeruginosa. Sin embargo, una recupración parcial de los niveles de sensibilidad es posible para la Ceftazidima mediante la aplicación de ciertas restricciones.

The objetive of this study has been to identify and to classity the antibiophenotypes of resistence to the betalacams in the Pseudomonas aeruginosa strains isolated in the Hospital Arzobispo Loayza of Lima and to evaluate the in vitro activity of these nosocomial strains agaist three antiPsedudomonas betalactams and the association of one of these with an inhibitor of betalactamase. Seventy non-repetitious strains of Pseudomonas aeruginosa isolated from samples of patients hospitalized by not less than 72 hours were studies. The used antibiograms were diffusion in agar (Kirby Bauer's method) and the minimal inhibitory concentration (MIC) were determined throught the technique of the E-test. Finally, the antibiophenotypes of Pseudomonas aeruginosa for the betalactams were and classified. The results show that 41.1% of strains of Pseudomonas aeruginosa was sensitive to Ticarcilin, while 605 of the strains was sensitive to Piperacilin (alone and in association with Tazobactam). Ceftazidime had a higher activity than Ticarcilin and Piperacilin (70.4% of the sensitive strains). In conclusion, the percentages of resistance found for Ceftazidime, Ticarcilin, Piperacilin and Piperacilin + Tazobactam invalidate the use of these antibioics in the probabilistic treatment of an infection due to Pseudomonas aeruginosa. However, a partial recovery of the sensitivity levels is possible for Ceftazidime through the application of certain restrictions.

Nifedipina: una opción en útero ihibición / Nifedipine: a tocolysis option

Nifedipina, una dehidropirina, bloqueadora de la entrada de calcio, ha sido usada con frecuencia incrementada en el tratamiento del parto pretérmino; nosotros estudiamos veinticinco pacientes en este trabajo prospectivo, evaluando la efectividad de nifedipina para hacer desaparecer las contracciones uterinas, y por ende la progresión de cambios cervicales en pacientes con diagnóstico de amenaza de parto pre-término, y la presencia de efectos secundarios maternos y/o fetales con su uso. Encontramos que en 96 por ciento de pacientes el esquema usado con nifedipina fue efectivo para hacer desaparecer la actividad uterina, y los efectos adversos más frecuentes fueron: cefalea y vómitos (54 y 23 por ciento respectivamente)