British Hospital

About: British Hospital is a healthcare organization based out in Montevideo, Uruguay. It is known for research contribution in the topics: Population & Lung cancer. The organization has 445 authors who have published 358 publications receiving 7878 citations. The organization is also known as: British Hospital.

Alteration on the expression of IL-1, PDGF, TGF-beta, EGF, and FGF receptors and c-Fos and c-Myc proteins in bone marrow mesenchymal stroma cells from advanced untreated lung and breast cancer patients.

Abstract: Previously, we reported a deficient cloning capacity of the bone marrow (BM) mesenchymal stem cells to give colony-forming unit fibroblast (CFU-F) and an inefficient confluence capacity of BM stromal cells in advanced untreated lung cancer patients (LCP) and breast cancer patients (BCP). Moreover, a decreased level of bFGF at day 7 in the conditioned media from BM CFU-F cultures was found in both cancer groups when compared to the normal range. The current study was specially undertaken, to evaluate the percentage of subconfluent fibroblasts expressing receptors (R) of interleukin-1 (IL-1), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor (TGF-beta), epidermal growth factor (EGF), and the proteins c-Fos and c-Myc in BM primary cultures from untreated LCP and BCP. An immunocytochemical study on subconfluent BM fibroblast cultures from 13 healthy patients, 16 LCP, and 8 BCP was performed, using as primary antibodies, anti-type I of IL-1 R (IL-1R-1), anti-alpha, beta chains of PDGF R (PDGFR-alpha, PDGFR-beta), anti-type I of FGF R (FGFR-I), anti-type I, II, and III of TGF-beta R (TGF-betaR-I, TGF- betaR-II, and TGF-betaR-III), anti-EGF R, anti-c-Fos, and anti-c-Myc. A diminished percentage of subconfluent fibroblasts expressing PDGFR-alpha, TGFbetaR-I, II, III, EGFR, and FGFR-I was found in LCP and BCP compared to healthy patients. A diminished percentage of subconfluent fibroblasts expressing c-Fos and c-Myc was found in patients when compared to healthy patients. The alterations we describe could help to explain the deficiency regarding the proliferative and confluence capacity of BM stroma cells in cancer patients.

Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database.

Abstract: BACKGROUND Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. METHODS Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. RESULTS Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers. CONCLUSION Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

Short-Term Monotherapy with IDX184, a Liver-Targeted Nucleotide Polymerase Inhibitor, in Patients with Chronic Hepatitis C Virus Infection

Abstract: IDX184 is a liver-targeted prodrug of 2′-methylguanosine (2′-MeG) monophosphate. This study investigated the safety, tolerability, antiviral activity, and pharmacokinetics of IDX184 as a single agent in treatment-naive patients with genotype-1 chronic hepatitis C virus (HCV) infection. Forty-one patients with baseline HCV RNA ≥ 5 log10 IU/ml, alanine aminotransferase (ALT) ≤ 2.5× the upper limit of normal, and compensated liver disease were dosed. Sequential cohorts of 10 patients, randomized 8:2 (active:placebo), received 25, 50, 75, and 100 mg of IDX184 once daily for 3 days, with a 14-day follow-up. There were no safety-related treatment discontinuations or serious adverse events. The adverse events and laboratory abnormalities observed for IDX184- and placebo-treated patients were similar. At the end of the 3-day treatment period, changes from baseline in HCV RNA levels (means ± standard deviations) were −0.5 ± 0.6, −0.7 ± 0.2, −0.6 ± 0.3, and −0.7 ± 0.5 log10 for the 25-, 50-, 75-, and 100-mg doses, respectively, while viral load remained unchanged for the pooled placebo patients (−0.05 ± 0.3 log10). Patients with genotype-1a and patients with genotype-1b responded similarly. Serum ALT levels decreased, especially at daily doses ≥ 75 mg. During the posttreatment period, plasma viremia and serum aminotransferase levels returned to near pretreatment levels. No resistance mutations associated with IDX184 were detected. Plasma exposure of IDX184 and its nucleoside metabolite 2′-MeG was dose related and low. Changes in plasma viral load correlated with plasma exposure of 2′-MeG. In conclusion, the results from this proof-of-concept study show that small doses of the liver-targeted prodrug IDX184 were able to deliver significant antiviral activity and support further clinical evaluation of the drug candidate.