5-Fluorouracil degradation rate as a predictive biomarker of toxicity in breast cancer patients treated with capecitabine

Capecitabine is an oral prodrug of 5-fluorouracil with a relevant role in the treatment of breast cancer. Severe and unexpected toxicities related to capecitabine are not rare, and the identification of biomarkers is challenging. We evaluate the relationship between dihydropyrimidine dehydrogenase, thymidylate synthase enhancer region and methylenetetrahydrofolate reductase polymorphisms, 5-fluorouracil degradation rate and the onset of G3–4 toxicities in breast cancer patients. Genetic polymorphisms and the 5-fluorouracil degradation rate of breast cancer patients treated with capecitabine were retrospectively studied. Genetic markers and the 5-fluorouracil degradation rate were correlated with the reported toxicities. Thirty-seven patients with a median age of 58 years old treated with capecitabine for stages II–IV breast cancer were included in this study. Overall, 34 (91.9%) patients suffered from at least an episode of any grade toxicity while nine patients had G3–4 toxicity. Homozygous methylenetetrahydrofolate reductase 677TT was found to be significantly related to haematological toxicity (OR = 6.5 [95% IC 1.1–37.5], P = 0.04). Three patients had a degradation rate less than 0.86 ng/mL/106 cells/min and three patients greater than 2.1 ng/mL/106 cells/min. At a univariate logistic regression analysis, an altered value of 5-fluorouracil degradation rate (values < 0.86 or >2.10 ng/mL/106 cells/min) increased the risk of G3–4 adverse events (OR = 10.40 [95% IC: 1.48–7.99], P = 0.02). A multivariate logistic regression analysis, adjusted for age, comorbidity and CAPE-regimen, confirmed the role of 5-fluorouracil degradation rate as a predictor of G3–4 toxicity occurrence (OR = 10.9 [95% IC 1.2–96.2], P = 0.03). The pre-treatment evaluation of 5-fluorouracil degradation rate allows to identify breast cancer patients at high risk for severe 5-FU toxicity

The Preventative Health Care Shortage: A Look at the VT and CT Community Perspectives and Medical Student Interest

With the permission of Kenneth Palanza et al, we adapted and modified a previously generated survey that allowed us to better understand the motivations and barriers of medical students to enter primary care. The survey was dispersed to all medical students at LCOM as well as third and fourth year medical students at Ross University and American University of the Caribbean (AUC). We analyzed preliminary data from 100 respondents.https://scholarworks.uvm.edu/fmclerk/1835/thumbnail.jp

Liver injury by experimental portal bacteremia: histogenetic recovery study in the rat

Abstract - To study the histogenetic recovery of hepatic lesions due to portal bacteremia, a complication of some clinical conditions, an experimental animal model had developed. Portal bacteremia was performed in 8-week rats and the morphological recovery of liver was histologically checked 1 to 6 days after bacteria inoculation. The major injuries, such as acute inflammatory exudate of the portobiliary spaces, piecemeal necrosis of muralium, micro-abscesses and areas of hepatocyte necrosis of the liver parenchyma, and thrombosis in the centrolobular vein were recorded 1 day after inoculation. Minimal signs of vacuolar degeneration, steatosis, necrosis areas, vessel congestion and focal hemosiderosis together with a small hepatocyte proliferative activity was instead appreciable with longer time. The results seem to suggest a role of vascular structures and Kupffer cells in the morphological repair. This experimental model could serve to understand better similar clinical hepatology conditions, such as portal bacteremia.Informazioni util

Authenticating coins of the 'Roman emperor' Sponsian

The 'Roman emperor' Sponsian is known only from an assemblage of coins allegedly found in Transylvania (Romania) in 1713. They are very unlike regular Roman coins in style and manufacture, with various enigmatic features including bungled legends and historically mixed motifs, and have long been dismissed as poorly made forgeries. Here we present non-destructive imaging and spectroscopic results that show features indicative of authenticity. Deep micro-abrasion patterns suggest extensive circulation-wear. Superficial patches of soil minerals bound by authigenic cement and overlain by oxidation products indicate a history of prolonged burial then exhumation. These observations force a re-evaluation of Sponsian as a historical personage. Combining evidence from the coins with the historical record, we suggest he was most likely an army commander in the isolated Roman Province of Dacia during the military crisis of the 260s CE, and that his crudely manufactured coins supported a functioning monetary economy that persisted locally for an appreciable period

role of evaluating tumor infiltrating lymphocytes programmed death ligand 1 and mismatch repair proteins expression in malignant mesothelioma

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New immunological potential markers for triple negative breast cancer: IL18R1, CD53, TRIM, Jaw1, LTB, PTPRCAP

Breast cancer (BC) is the second leading cause of cancer death in women worldwide, and settings of specific prognostic factors and efficacious therapies are made difficult by phenotypic heterogeneity of BC subtypes. Therefore, there is a current urgent need to define novel predictive genetic predictors that may be useful for stratifying patients with distinct prognostic outcomes. Here, we looked for novel molecular signatures for triple negative breast cancers (TNBCs). By a bioinformatic approach, we identified a panel of genes, whose expression was positively correlated with disease-free survival in TNBC patients, namely IL18R1, CD53, TRIM, Jaw1, LTB, and PTPRCAP, showing specific immune expression profiles linked to survival prediction; most of these genes are indeed expressed in immune cells and are required for productive lymphocyte activation. According to our hypothesis, these genes were not, or poorly, expressed in different TNBC cell lines, derived from either primary breast tumours or metastatic pleural effusions. This conclusion was further supported in vivo, as immuno-histochemical analysis on biopsies of TNBC invasive ductal carcinomas highlighted differential expression of these six genes in cancer cells, as well as in intra- and peri-tumoral infiltrating lymphocytes. Our data open to the possibility that inter-tumour heterogeneity of immune markers might have predictive value; further investigations are recommended in order to establish the real power of cancer-related immune profiles as prognostic factors

Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies

clinical impact of whey protein and nutritional counseling in gastrointestinal cancer patients

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