Carcinoma microcítico de pulmón

El cáncer microcítico de pulmón es uno de los tumores sólidos más agresivos, por su rápido crecimiento y por su tendencia a metastatizar desde fases tempranas. Sin embargo, también es uno de los tumores más sensibles a los tratamientos de quimioterapia y radioterapia, con los cuales algunos pacientes con enfermedad limitada pueden sobre- vivir a largo plazo. Estas características han hecho de este tumor un modelo clínico sobre el cual se han probado múltiples estrategias de tratamiento, incluyendo tratamientos concomitantes con quimioterapia y radioterapia, esquemas de quimioterapia alternante o de altas dosis con soporte hematológico o la utilización de radioterapia holocraneal profi láctica. Además en los últimos años el cáncer microcítico de pulmón también se ha empleado como plataforma de desarrollo de tratamientos dirigidos contra dianas específi cas o de inmunoterapia. INGLÉS: Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches

Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy

BACKGROUND: 5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to evaluate the bioavailability of s.c. granisetron. PATIENTS AND METHODS: Patients receiving platinum-based chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance. RESULTS: From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration-time curve for 0-12 hours (AUC(0-12h)) and higher levels at 12 hours, with similar values for AUC(0-24h). The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration. CONCLUSION: Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration might be especially relevant for outpatient management of emesis in cancer patients

Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia

In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000318507https://scholar.google.com.co/citations?user=cU2KyT4AAAAJ&hl=enhttps://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000008981https://orcid.org/0000-0002-8093-054

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8. 74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88)

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede

Major dietary patterns and cardiovascular risk factors among young Brazilian adults

Purpose: Diet is one of the most important modifiable risk factors for cardiovascular diseases. The scientific literature has consistently shown the effects of certain diets on health; however, given the variety of cultures and dietary habits across the world, it is likely that much remains to be learned about dietary patterns and health outcomes. We assessed the associations between main dietary patterns and cardiovascular risk factors among 4,202 young Brazilian adults in a cross-sectional analysis. Methods: In a principle components analysis, two main dietary patterns were identified: common Brazilian and processed food. As outcomes, we examined body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, HDL cholesterol (HDL-c), and LDL cholesterol (LDL-c). Means, crude, and adjusted β coefficients and 95% CIs were estimated according to quintiles of dietary patterns. Results: Common Brazilian scores were inversely associated with BMI, WC, LDL-c, HDL-c, and total cholesterol values among men. Among women, inverse association trends were observed with SBP, DBP, LDL-c, HDL-c, and total cholesterol. The processed food pattern was positively associated with LDL-c, HDL-c, total cholesterol, BMI, and WC values among the men. Among the women, the processed food pattern was not significantly associated with cardiovascular risk factors. Conclusions: In conclusion, our findings confirm that diet has an important role on health during early adulthood. The common Brazilian pattern showed generally healthier trends regarding CVD risk factors, but the ultimate effects on risk of risk of disease are unclear because of the inverse relation with HDL-c levels

Detection of subclinical keratoconus using biometric parameters

The validation of innovative methodologies for diagnosing keratoconus in its earliest stages is of major interest in ophthalmology. So far, subclinical keratoconus diagnosis has been made by combining several clinical criteria that allowed the definition of indices and decision trees, which proved to be valuable diagnostic tools. However, further improvements need to be made in order to reduce the risk of ectasia in patients who undergo corneal refractive surgery. The purpose of this work is to report a new subclinical keratoconus detection method based in the analysis of certain biometric parameters extracted from a custom 3D corneal model. This retrospective study includes two groups: the first composed of 67 patients with healthy eyes and normal vision, and the second composed of 24 patients with subclinical keratoconus and normal vision as well. The proposed detection method generates a 3D custom corneal model using computer-aided graphic design (CAGD) tools and corneal surfaces’ data provided by a corneal tomographer. Defined bio-geometric parameters are then derived from the model, and statistically analysed to detect any minimal corneal deformation. The metric which showed the highest area under the receiver-operator curve (ROC) was the posterior apex deviation. This new method detected differences between healthy and sub-clinical keratoconus corneas by using abnormal corneal topography and normal spectacle corrected vision, enabling an integrated tool that facilitates an easier diagnosis and follow-up of keratoconus.This publication has been carried out in the framework of the Thematic Network for Co-Operative Research in Health (RETICS) reference number RD16/0008/0012 financed by the Carlos III Health Institute-General Subdirection of Networks and Cooperative Investigation Centers (R&D&I National Plan 2013–2016) and the European Regional Development Fund (FEDER)

Potent acyl-CoA synthetase 10 inhibitors kill <i>Plasmodium falciparum</i> by disrupting triglyceride formation

Identifying how small molecules act to kill malaria parasites can lead to new chemically validated targets. By pressuring Plasmodium falciparum asexual blood stage parasites with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), and performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. falciparum acyl-CoA synthetase (ACS) genes PfACS10 (PF3D7_0525100, M300I, A268D/V, F427L) and PfACS11 (PF3D7_1238800, F387V, D648Y, and E668K). Allelic replacement and thermal proteome profiling validates PfACS10 as a target of these compounds. We demonstrate that this protein is essential for parasite growth by conditional knockdown and observe increased compound susceptibility upon reduced expression. Inhibition of PfACS10 leads to a reduction in triacylglycerols and a buildup of its lipid precursors, providing key insights into its function. Analysis of the PfACS11 gene and its mutations point to a role in mediating resistance via decreased protein&nbsp;stability

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators