944 resultados para Triple Alliance, 1882.


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Hrsg. vom Deutsch-israelitischen Gemeindebund

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Signatur des Originals: S 36/F10246

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Objectives. Triple Negative Breast Cancer (TNBC) lack expression of estrogen receptors (ER), progesterone receptors (PR), and absence of Her2 gene amplification. Current literature has identified TNBC and over-expression of cyclo-oxygenase-2 (COX-2) protein in primary breast cancer to be independent markers of poor prognosis in terms of overall and distant disease free survival. The purpose of this study was to compare COX-2 over-expression in TNBC patients to those patients who expressed one or more of the three tumor markers (i.e. ER, and/or PR, and/or Her2).^ Methods. Using a secondary data analysis, a cross-sectional design was implemented to examine the association of interest. Data collected from two ongoing protocols titled "LAB04-0657: a model for COX-2 mediated bone metastasis (Specific aim 3)" and "LAB04-0698: correlation of circulating tumor cells and COX-2 expression in primary breast cancer metastasis" was used for analysis. A sample of 125 female patients was analyzed using Chi-square tests and logistic regression models. ^ Results. COX-2 over-expression was present in 33% (41/125) and 28% (35/124) patients were identified as having TNBC. TNBC status was associated with elevated COX-2 expression (OR= 3.34; 95% CI= 1.40–8.22) and high tumor grade (OR= 4.09; 95% CI= 1.58–10.82). In a multivariable analysis, TNBC status was an important predictor of COX-2 expression after adjusting for age, menopausal status, BMI, and lymph node status (OR= 3.31; 95% CI: 1.26–8.67; p=0.01).^ Conclusion. TNBC is associated with COX-2 expression—a known marker of poor prognosis in patients with operable breast cancer. Replication of these results in a study with a larger sample size, or a future randomized clinical trial demonstrating an improved prognosis with COX-2 suppression in these patients would support this hypothesis.^

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In November 2010, nearly 110,000 people in the United States were waiting for organs for transplantation. Despite the fact that the organ donor registration rate has doubled in the last year, Texas has the lowest registration rate in the nation. Due to the need for improved registration rates in Texas, this practice-based culminating experience was to write an application for federal funding for the central Texas organ procurement organization, Texas Organ Sharing Alliance. The culminating experience has two levels of significance for public health – (1) to engage in an activity to promote organ donation registration, and (2) to provide professional experience in grant writing. ^ The process began with a literature review. The review was to identify successful intervention activities in motivating organ donation registration that could be used in intervention design for the grant application. Conclusions derived from the literature review included (1) the need to specifically encourage family discussions, (2) religious and community leaders can be leveraged to facilitate organ donation conversations in families, (3) communication content must be culturally sensitive and (4) ethnic disparities in transplantation must be acknowledged and discussed.^ Post the literature review; the experience followed a five step process of developing the grant application. The steps included securing permission to proceed, assembling a project team, creation of a project plan and timeline, writing each element of the grant application including the design of proposed intervention activities, and completion of the federal grant application. ^ After the grant application was written, an evaluation of the grant writing process was conducted. Opportunities for improvement were identified. The first opportunity was the need for better timeline management to allow for review of the application by an independent party, iterative development of the budget proposal, and development of collaborative partnerships. Another improvement opportunity was the management of conflict regarding the design of the intervention that stemmed from marketing versus evidence-based approaches. The most important improvement opportunity was the need to develop a more exhaustive evaluation plan.^ Eight supplementary files are attached to appendices: Feasibility Discussion in Appendix 1, Grant Guidance and Workshop Notes in Appendix 2, Presentation to Texas Organ Sharing Alliance in Appendix 3, Team Recruitment Presentation in Appendix 5, Grant Project Narrative in Appendix 7, Federal Application Form in Appendix 8, and Budget Workbook with Budget Narrative in Appendix 9.^

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Background. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% (1.38 million) of the total new cancer cases and 14% (458,400) of the total cancer deaths in 2008. [1] Triple-negative breast cancer (TNBC) is an aggressive phenotype comprising 10–20% of all breast cancers (BCs). [2-4] TNBCs show absence of estrogen, progesterone and HER2/neu receptors on the tumor cells. Because of the absence of these receptors, TNBCs are not candidates for targeted therapies. Circulating tumor cells (CTCs) are observed in blood of breast cancer patients even at early stages (Stage I & II) of the disease. Immunological and molecular analysis can be used to detect the presence of tumor cells in the blood (Circulating tumor cells; CTCs) of many breast cancer patients. These cells may explain relapses in early stage breast cancer patients even after adequate local control. CTC detection may be useful in identifying patients at risk for disease progression, and therapies targeting CTCs may improve outcome in patients harboring them. Methods . In this study we evaluated 80 patients with TNBC who are enrolled in a larger prospective study conducted at M D Anderson Cancer Center in order to determine whether the presence of circulating tumor cells is a significant prognostic factor in relapse free and overall survival . Patients with metastatic disease at the time of presentation were excluded from the study. CTCs were assessed using CellSearch System™ (Veridex, Raritan, NJ). CTCs were defined as nucleated cells lacking the presence of CD45 but expressing cytokeratins 8, 18 or 19. The distribution of patient and tumor characteristics was analyzed using chi square test and Fisher's exact test. Log rank test and Cox regression analysis was applied to establish the association of circulating tumor cells with relapse free and overall survival. Results. The median age of the study participants was 53years. The median duration of follow-up was 40 months. Eighty-eight percent (88%) of patients were newly diagnosed (without a previous history of breast cancer), and (60%) of patients were chemo naïve (had not received chemotherapy at the time of their blood draw for CTC analysis). Tumor characteristics such as stage (P=0.40), tumor size (P=69), sentinel nodal involvement (P=0.87), axillary lymph node involvement (P=0.13), adjuvant therapy (P=0.83), and high histological grade of tumor (P=0.26) did not predict the presence of CTCs. However, CTCs predicted worse relapse free survival (1 or more CTCs log rank P value = 0.04, at 2 or more CTCs P = 0.02 and at 3 or more CTCs P < 0.0001) and overall survival (at 1 or more CTCs log rank P value = 0.08, at 2 or more CTCs P = 0.01 and at 3 or more CTCs P = 0.0001. Conclusions. The number of circulating tumor cells predicted worse relapse free survival and overall survival in TNBC patients.^

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Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

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La triple frontera entre Argentina, Brasil y Paraguay, concebida como una amplia región con epicentro en la red urbana Puerto Iguazú, Foz do Iguazú y Ciudad del Este y otras localidades satélites, y que reconoce, además, dos puntos de gran importancia como Posadas/Encarnación y Bernardo de Irigoyen/Dionisio Cerqueira, comprende en realidad, un territorio muchos más vasto que abarca la provincia argentina de Misiones, la zona occidentalde los estados del sur de Brasil y el sur de Mato Grosso do Sul y el este de Paraguay. En este espacio tienen lugar múltiples relaciones transnacionales: económicas, políticas, sociales, culturales, etcétera que poseen una dilatada historia pero que, a partir de la integración y el MERCOSUR adquirieron una complejidad y densidad en permanente crecimiento y además, el surgimiento de procesos emergentes cuyo conocimiento supone un imperativo ineludible. Hemos investigado en los proyectos anteriores, ocho en total, los dos niveles en los que consideramos deben estudiarse estos procesos. Un nivel de escala mayor que trata de comprender la complejidad de una formación socioeconómica y espacial transnacional y su lugar en el ajedrez nacional e internacional del sistema imperial y, otro nivel, consistente en la profundización de problemas específicos de la región fronteriza como: redes sociales, mercado de trabajo, migraciones, exilio, solidaridad y lucha, movimientos sociales, gestión de ecosistemas compartidos, proyectos de desarrollo comunes, foros de esclarecimiento y defensa regionales, e integración del conocimiento.

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La presente investigación forma parte de un ciclo integrado por seis investigaciones precedentes, cuyas referencias están incluidas en el apartado de antecedentes. Su objetivo principal es conocer y describir la complejidad de la región de fronteras estudiada (triple frontera), las zonas de influencia directa y las acciones propias, que desde la región, protagonizan organizaciones y movimientos sociales en relación a las cada vez mas intensas amenazas de intervención militar por parte del poder hegemónico de Estados Unidos y la intensificación de los controles estatales nacionales que responden a las presiones internacionales. Qué lugar ocupa en las estrategias de la hegemonía imperial esta región y cuales son las respuestas locales tanto en acciones como en representaciones