Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz

Quiroga, Mexico

Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz

Quiroga, Mexico
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Enriquez J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Garcia G.,National Autonomous University of Mexico | Herrero B.,INCMNSZ | Larrea F.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz
Endocrine Research | Year: 2017

Background: Clinical studies have shown that gestodene (GDN), a potent third-generation synthetic progestin, affects bone resorption. However, its mode of action in bone cells is not fully understood. The aim of this study was to establish whether GDN affects bone directly or through its bioconversion to other metabolites with different biological activities. Methods: In this study, we investigated the effects of GDN and its A-ring reduced metabolites on proliferation, differentiation, and mineralization of calvarial osteoblasts isolated from neonatal rat and their capacity to displace [3H]-E2 at ER binding sites. Results: In contrast to progesterone, gestodene did exert significant effects on osteoblast activities. The most striking finding was the observation that the A-ring reduced derivatives 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN, though to a lesser extent, had greater stimulatory effects on the osteoblast activity than those observed with GDN. The effects on osteoblast proliferation and differentiation induced by GDN-reduced derivatives were abolished by the antiestrogen ICI 182780, consistent with their binding affinities for the estrogen receptor. In addition, the presence of a 5α-reductase inhibitor or inhibitors of aldo-keto hydroxysteroid dehydrogenases abolished the GDN-induced enhancement of osteoblast differentiation. These results indicated that GDN is metabolized to the A-ring reduced metabolites with estrogen-like activities and through this mechanism, GDN may affect the osteoblast activity. Conclusion: Together, the data suggest that synthetic progestins derived from 19-nortestosterone such as GDN, have beneficial effects on bone due to their biotransformation into metabolites with intrinsic estrogenic activity. © 2017 Taylor & Francis

Rodriguez-Fuentes N.,National Autonomous University of Mexico | Rodriguez-Hernandez A.G.,National Autonomous University of Mexico | Enriquez-Jimenez J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Fuentes-Mera L.,Hospital General Dr Manuel Gea Gonzalez | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Bovine bone matrix Nukbone® (NKB) is an osseous tissue-engineering biomaterial that retains its mineral and organic phases and its natural bone topography and has been used as a xenoimplant for bone regeneration in clinics. There are not studies regarding its influence of the NKB in the behavior of cells during the repairing processes. The aim of this research is to demonstrate that NKB has an osteoinductive effect in human mesenchymal stem cells from amniotic membrane (AM-hMSCs). Results indicated that NKB favors the AM-hMSCs adhesion and proliferation up to 7 days in culture as shown by the scanning electron microscopy and proliferation measures using an alamarBlue assay. Furthermore, as demonstrated by reverse transcriptase polymerase chain reaction, it was detected that two gene expression markers of osteoblastic differentiation: the core binding factor and osteocalcin were higher for AM-hMSCs co-cultured with NKB in comparison with cultivated cells in absence of the biomaterial. As the results indicate, NKB possess the capability for inducing successfully the osteoblastic differentiation of AM-hMSC, so that, NKB is an excellent xenoimplant option for repairing bone tissue defects. © 2013 Elsevier Inc. All rights reserved.

PubMed | Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz, Instituto Mexicano del Seguro Social IMSS and University of Salamanca
Type: Journal Article | Journal: Archives of medical research | Year: 2016

Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through invitro and invivo evaluations.The 69 compounds were evaluated invitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99). Four selected compounds, those that exhibited the highest potency invitro, were tested invivo using a model of progressive TB in BALB/c mice infected with the drug susceptible strain, either alone or combined with conventional chemotherapy, as well as in mice infected with the MDR strain. The acute toxicity was evaluated on male and female adult BALB/c mice.Ten of the evaluated compounds resulted more potent invitro than ethambutol. The experimental compound 2b (2-aminopalmitol benzyl ether) was the most efficacious and also showed additive effects in combination with conventional chemotherapy. It did not exhibit toxicity (LD50>2000mg/kg).Compound 2b can be considered as a new drug candidate to continue its development against M. tuberculosis MDR strains.

Hilario M.C.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Puga C.D.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Ocana A.N.,National Autonomous University of Mexico | Romo F.P.-G.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz
Journal of Dairy Research | Year: 2010

Two feeding systems trials were carried out to determine the antioxidant activity of soft goats' milk cheeses, and also to evaluate the presence of bioactive polyphenolic compounds. Two groups (A and B), each one with 20 (BW 50±5 kg) French Alpine goats were employed. All animals had between 70 to 80 milking days and were milked once a day. Group A included daily grazing on shruby rangeland vegetation, and group B was kept in full indoor confinement. Thirty kg of goats' milk from each group were collected; 15 kg from each were pasteurized and the remaining 15 kg were not pasteurized (raw), resulting in four treatments (two feeding system × two milk treatments). Soft goat's cheese antioxidant activity can be modified by the animals feeding system; grazing management represents a better option than indoor feeding to produce a healthy profile of bioactive compounds; providing an increase of total polyphenol, hydroxycinnamic acids and flavonoid concentrations. Pasteurization did have a significant effect on these metabolites, and diminished total polyphenol concentration. More research is needed to elucidate the potential of soft goat's cheese as a functional food. © 2009 Proprietors of Journal of Dairy Research.

Carrillo-Garcia A.,National Autonomous University of Mexico | Ponce-de-Leon-Rosales S.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Cantu-de-Leon D.,National Autonomous University of Mexico | Fragoso-Ontiveros V.,National Autonomous University of Mexico | And 4 more authors.
Gynecologic oncology | Year: 2014

The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk. HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination. In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone. These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL. Copyright © 2014 Elsevier Inc. All rights reserved.

Sepulveda-Mendez J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | De Murphy C.A.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Pedraza-Lopez M.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Murphy-Stack E.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | And 2 more authors.
Nuclear Medicine Communications | Year: 2012

OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the 99mTC-EDDA-HYNIC-Tyroctreotide (99mTC-TOC) to image and localize NETs and their metastases. MATERIALS AND METHODS: Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with 99mTC-TOC. The patients were injected with 500-600 MBq 99mTC-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the 99mTC-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. RESULTS: The validity of 99mTC-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76.8% (64-87%). CONCLUSION: Because of these high values, we strongly recommend scintigraphy with the Mexican-produced 99mTC-TOC for the localization of NETs and their metastases, and we conclude that it is a good tool for detecting neuroendocrine disease in a Mexican population. Copyright © 2011 by Lippincott Williams & Wilkins.

Maldera J.A.,CONICET | Maldera J.A.,German Cancer Research Center | Munoz M.W.,CONICET | Chirinos M.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | And 7 more authors.
Molecular Human Reproduction | Year: 2014

Human epididymal CRISP1 (hCRISP1) associates with sperm during maturation and participates in gamete fusion through egg complementary sites. Its homology with both rodent epididymal CRISP1 and CRISP4 reported to participate in the previous stage of sperm binding to the zona pellucida (ZP), led us to further investigate the functional role of hCRISP1 by studying its involvement in human sperm- ZP interaction. Human hemizona (HZ) were inseminated with human capacitated sperm in the presence of either anti-hCRISP1 polyclonal antibody to inhibit sperm hCRISP1, or bacterially-expressed hCRISP1 (rec-hCRISP1) to block putative hCRISP1 binding sites in the ZP. Results revealed that both anti-hCRISP1 and rec-hCRISP1 produced a significant inhibition in the number of sperm bound per HZ compared with the corresponding controls. The finding that neither anti-hCRISP1 nor rec-hCRISP1 affected capacitation-associated events (i.e. sperm motility, protein tyrosine phosphorylation or acrosome reaction) supports a specific inhibition at the sperm-egg interaction level. Moreover, immunofluorescence experiments using human ZP-intact eggs revealed the presence of complementary sites for hCRISP1 in the ZP. To identify the ligand of hCRISP1 in the ZP, human recombinant proteins ZP2, ZP3 and ZP4 expressed in insect cells were co-incubated with hCRISP1 and protein- protein interaction was analyzed by ELISA. Results revealed that rec-hCRISP1 mainly interacted with ZP3 in a dose-dependent and saturable manner, supporting the specificity of this interaction. Altogether, these results indicate that hCRISP1 is a multifunctional protein involved not only in sperm-egg fusion but also in the previous stage of sperm-ZP binding through its specific interaction with human ZP3. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Mitre-Aguilar I.B.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Mitre-Aguilar I.B.,National University of Costa Rica | Cabrera-Quintero A.J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz | Cabrera-Quintero A.J.,National University of Costa Rica | And 3 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2015

Glucocorticoids (GC) are essential steroid hormones for human life. They regulate a series of important processes by binding with three glucocorticoid receptors (GR) and activating genomic and non-genomic pathways. Activated cytoplasmic GR can directly bind DNA and transactivate or transrepress specific genes. Additionally, it can interact with other transcription factors to affect gene expression indirectly. The two membrane GR can interact with mitogen-activated protein (MAP) kinases or activate cAMP and Ca2+-dependent pathways, respectively. Glucocorticoids have been widely used as co-treatment of patients with breast cancer (BC) due to reduction of chemotherapy-induced side effects such as nausea, lack of appetite, and inflammation. However, GC may exert a direct effect on tumor response to chemotherapy. In vitro, GC inhibits chemotherapy, radiation and cytokine-induced apoptosis by upregulating antiapoptotic genes and detoxifying proteins. They also upregulate the proto-oncogene c-fms, tumor suppressor gene Nm23, several members of the epidermal growth factor (EGF) signaling pathway and the estrogen sulfotransferase signaling pathway, thus indirectly inhibiting estrogen receptor activation. They inhibit the proangiogenic gene (vascular endothelial growth factor (VEGF); Therefore, they could play a role in reducing angiogenesis. Interestingly, the phosphorylation status of ser-211 in the GR is dependent on the expression of the BRCA1 gene, a tumor suppressor gene that is mutated in the majority of patients with triple negative BC. Some clinical randomized trials have also attempted to address the effect of GC on patients with BC. Thus, in this review we summarize GC mechanisms of action and their participation in several facets of BC.

PubMed | Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz
Type: Journal Article | Journal: Revista brasileira de hematologia e hemoterapia | Year: 2016

Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

PubMed | CINVESTAV, Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran Incmnsz, National Autonomous University of Mexico and Instituto Nacional Of Medicina Genomica Inmegen
Type: Journal Article | Journal: International journal of oncology | Year: 2016

Tumor microenvironment is an important promoter of tumorigenesis in all forms of breast cancer and has been associated with the risk of metastasis in the different breast cancer subtypes including the more frequent luminal subtypes that encompass 60% of cancer patients. Adhesive properties of endothelial cells(ECs) are strikingly affected during cancer cell dissemination and are related to functional changes of adhesion receptors. The contribution of tumor secreted factors to tumorEC adhesion represents a therapeutic opportunity for breast cancer metastasis. Conditioned medium(CM) of tumor cells can be used as a model to study the role of the secreted molecules to the tumor microenvironment. We explored transcriptomic changes associated to a proadhesive phenotype in primary human umbilical vein endothelial cells(HUVECs) treated with CM of the breast cancer cell line ZR75.30 or with TNF for 3h. Selected genes were used to validate the microarray through RTqPCR. The bioinformatic analysis identified NFB as the main regulator of the pro-adhesive phenotype and this was confirmed by pharmacological inhibition of NFB pathway with BAY117085. The changes induced by ZR75.30CM mimic those promoted by TNF and display changes in the expression of genes related to inflammatory response, wound healing, extracellular matrix, cytokines, metabolism and cell communication. Despite the abundance of GCSF, IL8, IL6 and VEGF in the ZR75.30CM and the confirmed activation of STAT3 and VEGFR2 pathways, our results suggest dominance of NFB as a central controller of the transcriptomic response of ECs to breast cancer cells leading to expression of cell adhesion receptors.

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