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Candelaria M.,Instituto Nacional Of Cancerologia Mexico | Duenas-Gonzalez A.,National Autonomous University of Mexico
Expert Opinion on Drug Safety | Year: 2015

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by deregulation of apoptosis, dysplastic features in hematopoietic precursors, peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Roughly 20% of MDS are therapy related (t-MDS), and this is considered an independent adverse prognostic factor.Areas covered: This review based on a comprehensive literature search provides an overview on the main features of t-MDS, including its epidemiology, risk factors, molecular pathogenesis, prognostic classifications and therapy.Expert opinion: Increasing evidence points out that the most important event in t-MDS is genetic alterations in hematopoietic stem precursor cells, however, ineffective hematopoiesis may also result from abnormalities in the bone marrow microenvironment. Thus, novel views onto the processes of t-MDS are needed such as the osteohematology concept. On the other hand, the number of people living with and beyond cancer is increasing worldwide; thus, most emphasis should be placed on preventing secondary malignancies such as t-MDS. From this review, it becomes clear that we are in urgent need not only to deepen our understanding of the leukemogenesis mechanisms induced by exposure to chemotherapy and radiation but also to translate this knowledge into clinical strategies aimed at risk reduction. © 2015 Informa UK, Ltd.

Roma A.A.,Cleveland Clinic | Diaz De Vivar A.,Baylor College of Medicine | Park K.J.,Sloan Kettering Cancer Center | Alvarado-Cabrero I.,Mexican Oncology Hospital | And 10 more authors.
American Journal of Surgical Pathology | Year: 2015

A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma. Tumors with pattern C showed diffusely infiltrative glands with associated extensive desmoplastic response. In total, 352 cases (all FIGO stages) from 12 institutions were identified. Mean patient age was 45 years (range, 20 to 83 y). Forty-nine (13.9%) cases demonstrated lymph nodes (LNs) with metastatic endocervical carcinoma. Using this new system, 73 patients (20.7%) were identified with pattern A tumors (all stage I); none had LN metastases and/or recurrences. Ninety patients (25.6%) were identified with pattern B tumors (all stage I); only 4 (4.4%) had LN metastases; 1 had vaginal recurrence. The 189 (53.7%) remaining patients had pattern C tumors; 45 (23.8%) of them had LN metastases. This new classification system demonstrated 20.7% of patients (pattern A) with negative LNs, and patients with pattern A tumors can be spared of lymphadenectomy. Patients with pattern B tumors rarely presented with metastatic LNs, and sentinel LN examination could potentially identify these patients. Aggressive treatment is justified in patients with pattern C tumors. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

De Vivar A.D.,Baylor College of Medicine | De Vivar A.D.,University of Houston | Roma A.A.,Cleveland Clinic | Park K.J.,Sloan Kettering Cancer Center | And 16 more authors.
International Journal of Gynecological Pathology | Year: 2013

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant. © 2013 Lippincott Williams & Wilkins.

Namendys-Silva S.A.,Instituto Nacional Of Cancerologia Mexico | Namendys-Silva S.A.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran | Gonzalez-Herrera M.O.,Instituto Nacional Of Cancerologia Mexico | Garcia-Guillen F.J.,Instituto Nacional Of Cancerologia Mexico | And 2 more authors.
Annals of Hematology | Year: 2013

The prognosis for patients with hematological malignancies (HMs) admitted to the intensive care unit (ICU) is poor. The objective of this study was to evaluate the clinical characteristics and hospital outcomes of critically ill patients with HMs admitted to an oncological ICU. This is a prospective, observational cohort study. A total of 102 patients with HMs admitted to ICU from January 2008 to April 2011 were included. Univariate and multivariate logistic regressions were used to identify factors associated with hospital mortality. During the study period, 3,776 patients with HM were admitted to the Department of Hematology of the Instituto Nacional de Cancerología located in Mexico City, Mexico. After being evaluated by the intensivist, 102 (2.68 %) patients were admitted to the ICU. The ICU mortality rates for patients who had two or less organ system failures and for those with three or more organ system dysfunctions were 20 % (5/25) and 70.1 % (54/77), respectively (P < 0.0001). A multivariate analysis identified independent prognostic factors of inhospital death as neutropenia at the time of ICU admission (odds ratio (OR), 4.24; 95 % confidence interval (CI), 1.36-13.19, P = 0.012), the need for vasopressors (OR, 4.49; 95 % CI, 1.07-18.79, P = 0.040), need for invasive mechanical ventilation (OR, 4.49; 95 % CI, 1.07-18.79, P = 0.040), and serum creatinine >106 μmol/L (OR, 3.21; 95 % CI, 1.05-9.85, P = 0.041). The ICU and hospital mortality rates were 46.1 and 57.8 %, respectively. The independent prognostic factors of inhospital death were the need for invasive mechanical ventilation, the need for vasopressors, serum creatinine >106 μmol/L, and neutropenia at the time of ICU admission. © 2013 Springer-Verlag Berlin Heidelberg.

Alonso-Castro A.J.,Instituto Nacional Of Cancerologia Mexico | Alonso-Castro A.J.,National Autonomous University of Mexico | Dominguez F.,Research Center Biomedica Of Oriente | Garcia-Regalado A.,Metropolitan Autonomous University | And 4 more authors.
Pharmaceutical Biology | Year: 2014

Context: Cancer prevention remains a high priority for the scientific world. Magnolia dealbata Zucc (Magnoliaceae), a Mexican endemic species, is used for the empirical treatment of cancer. Objective: To evaluate the cytotoxic and cancer chemopreventive effects of an ethanol extract of Magnolia dealbata seeds (MDE). Materials and methods: The cytotoxic effect of MDE, at concentrations ranging from 1 to 200μg/ml, on human cancer cells and human nontumorigenic cells was evaluated using the MTT assay for 48h. The apoptotic activities of MDE 25μg/ml on MDA-MB231 breast cancer cells were evaluated using the TUNEL assay and the detection of caspase 3 using immunofluorescence analysis for 48h, each. The chemopreventive effect was evaluated by administrating different doses of MDE, between 1 and 50mg/kg, injected intraperitoneally daily into athymic mice which were implanted with MDA-MB231 cells during 28 days. The growth and weight of tumors were measured. Results: MDE showed cytotoxic effects on MDA-MB231 cells (IC50=25μg/ml) and exerted pro-apoptotic activities as determined by DNA fragmentation in MDA-MB231 cells. MDE 25μg/ml also induces the activation of caspase 3 in MDA-MB231 cells. These results suggest that Magnolia dealbata may be an optimal source of the bioactive compounds: honokiol (HK) and magnolol (MG). MDE 50mg/kg i.p. exerted chemopreventive effects by inhibiting the growth of MDA-MB231 tumor by 75% in athymic mice, compared to the control group. Conclusions: MDE exerts cytotoxic, apoptotic and chemopreventive activities on MDA-MB231 human cancer cells. © 2014 Informa Healthcare USA, Inc. All rights reserved.

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