Factores gen��ticos y ambientales relacionados con la g��nesis de cáncer vesical

[ES] Antecedentes: La exposici��n a sustancias qu��micas es uno de los factores de riesgo m��s conocidos y relevantes del cáncer vesical (CaV). Asimismo los factores reguladores de la proliferaci��n celular (como los Insulin-like growth factors- IGF) y la expresi��n de genes involucrados en la transformaci��n de xenobi��ticos y en la angiog��nesis y proliferaci��n celular, parecen ser factores relevantes en la etiolog��a del CaV. Objetivo: Evaluar la relevancia de los h��bitos de vida, la exposici��n a contaminantes ambientales (y factores de crecimiento celular relacionados) y las caracter��sticas gen��ticas de la poblaci��n canaria como factores de riesgo de cáncer vesical en un estudio de casos y controles hospitalarios desarrollado en el Complejo Hospitalario Insular Materno Infantil de Gran Canaria.

Clasificaci��n molecular del cáncer de mama y su impacto en el control inducido por el hipofraccionamiento.

Programa de doctorado: Cáncer: Biolog��a y cl��nica.

Radioterapia hiperfraccionada en cáncer de mama: resultados cl��nicos en relaci��n con estudios moleculares y la calidad de vida

Programa de doctorado: Salud p��blica (Epidemiolog��a, planificaci��n y nutrici��n)

Biopsia selectiva del ganglio centinela con 99mTc-nanocoloides en el cáncer de mama : validaci��n de la t��cnica, implantaci��n y an��lisis del impacto sobre el pron��stico de la enfermedad

Programa de doctorado: Avances en Medicina Interna.

Microsat��lites polim��rficos : estudio de su posible papel en el cáncer de mama y la resistencia a insulina

Programa de doctorado: Cáncer: Biolog��a y cl��nica

Cáncer y tratamiento oncol��gico: Representaciones sociales de la poblaci��n general, el paciente oncol��gico y miembros del equipo de salud

Se realizaron tres estudios cualitativos que tuvieron como prop��sito conocer las representaciones que ha construido la poblaci��n general, los pacientes oncol��gicos y los profesionales de la salud, sobre el cáncer, la quimioterapia y el trasplante de m��dula ��sea y realizar un an��lisis sobre las semejanzas y diferencias entre ellos. Se realiz�� en la ciudad de Bogot�� (Colombia) con 55 personas: 20 pacientes con cáncer en proceso de trasplante de m��dula ��sea, 20 personas no diagnosticadas con cáncer y 15 personas que trabajan en la atenci��n de pacientes con cáncer. Se realiz�� una entrevista en profundidad con todos los participantes y asociaciones libres, cl��sicas y por sustituci��n sobre las palabras ���cáncer���, ���quimioterapia��� y ���trasplante de m��dula���. Los datos conseguidos se analizaron a la luz de la Teor��a de las Representaciones Sociales (TRS). El an��lisis de la informaci��n sigui�� la t��cnica de an��lisis cualitativo de contenido para encontrar significados simb��licos y construir, denominar y definir categor��as. Para los tres grupos el cáncer es una enfermedad terrible, que puede llevar a la muerte. El personal de salud y la poblaci��n general creen que la enfermedad genera terror, angustia y miedo. Los pacientes tienen conciencia de la gravedad y del temor consecuente por una enfermedad que lo cambia todo, produce sufrimiento, dolor, obliga a depender de alguien y puede conducir a la muerte. El personal de salud considera que los pacientes lo pueden vivir como un castigo y la poblaci��n general que puede ser la consecuencia de estilos de vida poco saludables. Para todos, la quimioterapia es un tratamiento para la enfermedad, que por un lado presenta efectos colaterales dif��ciles y visibles y que producen sentimientos negativos de temor y de angustia y al mismo tiempo constituye una opci��n y posibilidad de curaci��n. El Trasplante de M��dula ��sea representa para todos una oportunidad.

In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans

Early prenatal diagnosis and in utero therapy of certain fetal diseases have the potential to reduce fetal morbidity and mortality. The intrauterine transplantation of stem cells provides in some instances a therapeutic option before definitive organ failure occurs. Clinical experiences show that certain diseases, such as immune deficiencies or inborn errors of metabolism, can be successfully treated using stem cells derived from bone marrow. However, a remaining problem is the low level of engraftment that can be achieved. Efforts are made in animal models to optimise the graft and study the recipient's microenvironment to increase long-term engraftment levels. Our experiments in mice show similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC are rapidly diminished due to missing self-renewal and low differentiation capacities in the host's microenvironment. Allogeneic murine fetal liver cells have very good long-term engraftment (49.9% donor cells in peripheral blood 16 weeks after transplantation). Compared to the rodents, the sheep model has the advantage of body size and gestation comparable to the human fetus. Here, ultrasound-guided injection techniques significantly decreased fetal loss rates. In contrast to the murine in utero model, the repopulation capacities of allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral blood 3 weeks after transplantation). The effect of MHC on engraftment levels seems to be marginal, since no differences could be observed between autologous and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in peripheral blood 1 to 2 weeks after transplantation). Further research is needed to study optimal timing and graft composition as well as immunological aspects of in utero transplantation.

In utero transplantation of autologous and allogeneic fetal liver stem cells in ovine fetuses

OBJECTIVE: The purpose of this study was to assess the feasibility of autologous stem cell transplantation in fetal sheep and to compare short-term engraftment of allogeneic and autologous fetal liver stem cells in an immunocompetent large animal model. STUDY DESIGN: Fetal liver stem cells were collected from preimmune sheep fetuses with an open or ultrasound-guided technique. After being labeled with PKH26, the cells were transplanted intraperitoneally into allogeneic and autologous fetal recipients at 48 to 64 days of gestation. Engraftment was determined by flow cytometry and real-time polymerase chain reaction 1 to 2 weeks after transplantation. RESULTS: Fetal loss rate was 29% (allogeneic transplantation) and 73% (autologous transplantation). Engraftment of donor cells was found in all fetuses, with a level of < or =4.7% in fetal liver, spleen, bone marrow, blood and thymus. Overall, there was no difference between allogeneic and autologous grafts. CONCLUSION: Autologous in utero transplantation of fetal liver stem cells in fetal sheep is feasible, but yields a high loss rate. Differences in the major histocompatibility complex between donor and recipient seems not to have a major impact on stem cell engraftment early in gestation; major histocompatibility complex-independent donor/host competition might be responsible for low engraftment in immunocompetent recipients.

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg(-/-) mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg(-/-) foetal hearts. CPCs harvested from Speg(-/-) mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg(-/-) mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg(-/-) mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil.

BACKGROUND There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV-exposed but uninfected (HEU) children. The aim of this study was to evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first 2 years of life. METHODS This cohort study was conducted among HEU infants born between 1996 and 2010 in Tertiary children's hospital in Rio de Janeiro, Brazil. Weight was measured by mechanical scale, and height was measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. RESULTS A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared with infants exposed later: adjusted differences were -0.52 (95% confidence interval [CI]: -0.99 to -0.04, P = 0.02) at birth and -0.22 (95% CI: -0.47 to 0.04, P = 0.10) during follow-up. LAZ were lower during follow-up: -0.35 (95% CI: -0.63 to -0.08, P = 0.01). There were no differences in weight-for-length scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. CONCLUSIONS In HEU children, early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

AN ESTIMATION OF IN UTERO DRUG EXPOSURE BY DETERMINANTS OF FREQUENCY AND DISTRIBUTION OF MATERNAL DRUG CONSUMPTION

Data derived from 1,194 gravidas presenting at the observation unit of a city/county hospital between October 11, 1979 through December 7, 1979 were evaluated with respect to the proportion ingesting drugs during pregnancy. The mean age of the mother at the time of the interview was 22.0 years; 43.0 percent were Black; 34.0 percent Latin-American, 21.0 percent White and 2.0 percent other; mean gravida was 2.5 pregnancies; mean parity was 1.0; and mean number of previous abortions was 0.34. Completed interview data was available for 1,119 gravida, corresponding urinalyses for 997 subjects. Ninety and one-tenth percent (90.1 percent) of the subjects reported ingestion of one or more drug preparation(s) (prescription, OTC, or substances used for recreational purposes) during pregnancy with a range of 0 to 11 substances and a mean of 2.7. Dietary supplements (vitamins and minerals) were most frequently reported followed by non-narcotic analgesics. Seventy-six and one tenth percent (76.1 percent) of the population reported consumption of prescription medication, 42.5 percent reported consumption of over-the-counter medications, 45.7 percent reported consumption of a substance for recreational purposes and 4.3 percent reported illicit consumption of a substance. For selected substances, no measurable difference was found between obtaining the information from the interview method or from a urinalysis assay. ^

In-utero exposure to chemotherapy: What are the long term effects?

There is not a large body of evidence on in-utero exposure to chemotherapy for pregnancy-associated cancers to help determine the long term effects on offspring. This study is a systematic review of long term follow-up to find evidence for adverse outcomes in exposed offspring. In order for studies to be eligible for this systematic review, they had to have a median follow up of at least 24 months with the resulting child. PubMed, Medline, and Scopus were the databases used, and we included all eligible articles, regardless of the date of publication. The search resulted in six articles meeting the eligibility requirements. The review of findings of these studies suggested that there is not enough evidence to make a determination of the risk of chemotherapy for the offspring. Exposed children in the sample of reviewed papers did have some medical conditions, but the rate and type did not differ from the non-exposed population. However, a limitation of this literature review is the very small sample size of publications on this important topic. This finding of few studies on this topic is an important result of this systematic review. More research and long term follow-up studies must be conducted to address this issue.^