Obesity and Preeclampsia: Common Pathophysiological Mechanisms.

Preeclampsia is a disorder specific of the human being that appears after 20 weeks of pregnancy, characterized by new onset of hypertension and proteinuria. Abnormal placentation and reduced placental perfusion associated to impaired trophoblast invasion and alteration in the compliance of uterine spiral arteries are the early pathological findings that are present before the clinical manifestations of preeclampsia. Later on, the endothelial and vascular dysfunction responsible of the characteristic vasoconstriction of preeclampsia appear. Different nutritional risk factors such as a maternal deficit in the intake of calcium, protein, vitamins and essential fatty acids, have been shown to play a role in the genesis of preeclampsia, but also an excess of weight gain during pregnancy or a pre-pregnancy state of obesity and overweight, which are associated to hyperinsulinism, insulin resistance and maternal systemic inflammation, are proposed as one of the mechanism that conduce to endothelial dysfunction, hypertension, proteinuria, thrombotic responses, multi-organ damage, and high maternal mortality and morbidity. Moreover, it has been demonstrated that pregnant women that suffer preeclampsia will have an increased risk of future cardiovascular disease and related mortality in their later life. In this article we will discuss the results of studies performed in different populations that have shown an interrelationship between obesity and overweight with the presence of preeclampsia. Moreover, we will review some of the common mechanisms that explain this interrelationship, particularly the alterations in the L-arginine/nitric oxide pathway as a crucial mechanism that is common to obesity, preeclampsia and cardiovascular diseases.

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.

BACKGROUND: B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. METHODS: We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). RESULTS: We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. CONCLUSIONS: Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

The combined expression patterns of Ikaros isoforms characterize different hematological tumor subtypes.

A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers. In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.

Mesenchymal stem cells promote leukaemic cells aberrant phenotype from B-cell acute lymphoblastic leukaemia.

BACKGROUND AND OBJECTIVES: The role of bone marrow-mesenchymal stem cells (BM-MSC) in leukaemic cell control is controversial. The purpose of this work was to evaluate BM-MSC role regarding the viability, proliferation and immunophenotype of normal B-cell precursors from control (Ct) patients and leukaemic cells from B-acute lymphoblastic leukaemia (B-ALL) patients. PATIENTS AND METHODS: BM-MSC were isolated and characterised from voluntary donors. Mononuclear cells isolated from Ct and B-ALL bone marrow samples were cultured in the presence or absence of BM-MSC for 7days. Cell viability was determined with LIVE/DEAD and proliferation index evaluated by CFSE labelling. Cell population immunophenotypes were characterised by estimating CD19, CD10, CD20 and CD45 antigens by flow cytometry. RESULTS: After co-culture, B-ALL cells exhibited higher viability (20-40%) as compared to just cells (3-10%). Ct and B-ALL absolute cell counts were higher in the presence of BM-MSC (Ct: 25/mm(3)cf8/mm(3), B-ALL: 15/mm(3)cf3/mm(3)). Normal B-cell subpopulations in co-culture had increased expression of CD19 and CD10 (Pre-pre B) and CD45 and CD20 antigens (Pre-B). B-ALL cells co-cultured with BM-MSC showed an increase in CD19 and CD20, although the greatest increase was observed in the CD10 antigen. CONCLUSIONS: Lymphoid cell maintenance, at early stages of differentiation, was significantly promoted by BM-MSC in normal and leukaemic cells. Co-cultures also modulated the expression of antigens associated with the B-ALL asynchronous phenotype as CD10 co-expressed with CD19 and CD20. To our knowledge, this is the first time that CD10, CD19 and CD20 leukaemic antigens have been reported as being regulated by BM-MSC.

[Expression of heat shock proteins HSP72 and HSP73 in Colombian patients with Hodgkin lymphoma positive and negative for Epstein Barr virus]. / Expresión de proteínas del choque térmico HSP72 y HSP73 en casos colombianos de linfoma de Hodgkin positivos y negativos para virus de Epstein Barr.

BACKGROUND: The expression of heat shock proteins (HSP70) in tumor cells or virus infected cells is important for the induction of specific cellular immune response. They are implicated in transport of immunodominants peptides in the endoplasmic reticulum, activation of antigen presenting cells and cross priming of CD8 T cells. AIM: To analyze the expression of HSP70 protein in its constitutive (HSP73) and inducible forms (HSP72) in Hodgkin's lymphoma (HL), infected or not by Epstein Barr virus (EBV) and to assess its relationship with pathological subtype, clinical stages and treatment response. MATERIAL AND METHODS: The analysis of HSP73 and HSP72 was done by immunoperoxidase on routinely processed paraffin sections with prior antigen retrieval. RESULTS: Sixty seven cases were studied. The expression of HSP73 and HSP72 was detected in 19.4 and 17.9% of samples respectively. The infiltrating lymphocytes expressed HSP72 in 58% of cases. The pathological subtypes with the higher expression in lymphocytes were mixed cellularity and nodular sclerosis. No differences in HSP70 expression were observed, according to clinical stage, treatment response or the presence of EBV. CONCLUSIONS: The expression of HSP72 on lymphocytes suggests that this protein plays an important role in the induction and amplification of antitumor immune response.