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Biomedical subjects

Luis Benítez-Bribiesca

Publications and source records attributed to Luis Benítez-Bribiesca.

15 recordsLinked to original sources
PubMed2003

Kinetics of hematopoiesis in bone marrow cultures from patients with chronic myeloid leukemia: effect of recombinant cytokines in dexter-type long-term cultures.

Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation of a hematopoietic stem cell. It is characterized by the expansion of the myeloid lineage, which results in the accumulation of mature and immature granulocytes in peripheral blood and bone marrow. However, when CML marrow cells are cultured in Dexter-type long-term cultures (LTMC) hematopoiesis is defective and can be sustained for only a few weeks. One possible explanation for the deficient growth of hematopoietic cells in CML LTMC is that some factors that act as key regulators of hematopoiesis are absent in this experimental system. Thus, we tested this hypothesis by adding recombinant cytokines to these cultures. As a first approach, we added recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), rhGranulocyte-CSF (rhG-CSF) and rhErythropoietin (rhEPO); each factor was added individually once a week. Addition of rhGM-CSF and rhG-CSF resulted in a significant increase in the levels of nucleated cells and myeloid progenitors; the highest effects were seen in the presence of rhGM-CSF. Interestingly, such a cytokine also induced a significant decrease in the levels of erythroid progenitors. Recombinant hEPO had no significant effects on nucleated cells or myeloid progenitors, however, it induced a significant, although transient, increase in the levels of erythroid cells. The above results indicate that the hematopoietic regulators used here (rhGM-CSF, rhG-CSF and rhEPO) are capable of stimulating the growth of hematopoietic cells in LTMC from CML patients. Thus, this study demonstrates that it is, indeed, possible to manipulate CML LTMC by the addition of recombinant cytokines; this observation may be of particular relevance, since this in vitro experimental system has already been used as a method for purging of leukemic cells in autologous transplant settings. By using specific recombinant hematopoietic modulators it might be possible to make LTMC a more efficient system for such a clinical purpose.

Adult↗
PubMedDate not supplied

Role of infectious diseases in human carcinogenesis.

The burden of human infectious diseases remains a public health problem worldwide. At least 2 billion people are affected by viral infections, and a similar number by bacteria or helminths. The long-term effects of these maladies have raised particular concern since some infectious agents have been associated with chronic human diseases, especially cancer. It is estimated that 13-20% of the world cancer cases are associated with some virus, bacteria, or helminth, e.g., human papillomavirus, Helicobacter pylori, and Schistosoma haematobium that cause cervical, stomach, and urinary bladder cancer, respectively. Certain associations between infection and malignancy are strong and irrefutable; others are still speculative. This article reviews the infectious agents that have been associated with cancer and current knowledge about the mechanisms underlying these associations.

Animals↗
PubMedDate not supplied

DNA damage in peripheral lymphocytes of untreated breast cancer patients.

BACKGROUND: Using the alkaline comet assay, DNA single-strand breaks (ssb) have been described in peripheral blood lymphocytes (PBL) from breast cancer patients without treatment, but there is no information concerning the occurrence of double-strand breaks (dsb) in the same patients. The purpose of this study was to investigate whether PBL of untreated sporadic breast cancer patients harbor an elevated number of both DNA strand breaks. METHODS: Forty breast cancer patients without family history of cancer in clinical stage III devoid of treatment and 60 age-matched healthy subjects without history of breast cancer were included. PBL from freshly drawn blood were processed following two different methods: the alkaline and the neutral comet assay. Percentage and tail moment were assessed under fluorescence microscopy and a computer-based image analysis system. RESULTS: In controls, ssb were found in 18 +/- 4.67% of PBL, and dsb at 7.99 +/- 3.67% of PBLs. Cancer patients had higher values of both ssb 24.08 +/- 4.96 (p <0.05) and dsb 13.11 +/- 3.2% (p <0.01). Tail moment for ssb was 6.23 +/- 1.44 and dsb, 2.31 +/- 1.09 for controls. For breast cancer patients, tail moment for ssb was 11.73 +/- 2.40 and for dsb, 6.33 +/- 1.75 (p <0.01). On plotting individual measurements of comet percentage against tail moment for alkaline and neutral comet assays, clear separation of control group from cancer patients can be seen in both assays. CONCLUSIONS: Demonstration of two types of DNA damage in PBL of breast cancer patients devoid of treatment or without exposure to environmental genotoxic agents provides a better picture of the degree of DNA damage present in somatic cells of these patients.

Breast Neoplasms↗
PubMedDate not supplied

RET oncogene mutations in medullary thyroid carcinoma in Mexican families.

BACKGROUND: Different RET oncogene mutations have been found to be associated with inherited medullary thyroid carcinoma (MTC) in the context of three different syndromes including multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). These mutations have been recorded in different populations, but to date there is no corresponding study in Mexican families. Our purpose was identification of RET mutations in Mexican families with inherited or sporadic MTC (SMTC) and search for RET protein expression as prognostic marker in MTC tumors. METHODS: Nine unrelated families with MTC corresponding either to two MEN 2A, three MEN 2B, or four SMTC were studied. Screening of exons 10, 11, and 13-16 of RET oncogene in DNA from circulating lymphocytes and tumor samples were analyzed. Immuno- staining for RET was performed in the corresponding tumor. RESULTS: Germline 918 ATG-->ACG RET mutation was present in three unrelated MEN 2B individuals and corresponding somatic mutation in one individual with SMTC; 634 TGC-->TTC RET mutation was detected in two related patients in an MEN 2A family and the 634 TGC-->TAC RET mutation was detected in 12 related individuals from a second MEN 2A family. RET protein expression was detected in all MTC tumors showing different staining intensity. CONCLUSIONS: RET mutations found in Mexican patients with MTC are similar to those previously reported in several MTC families worldwide. This indicates that RET mutations are highly conserved and that MTC etiology does not depend to a great extent on environmental factors or ethnic differences. Detection of RET protein in MTC tissue sections is not useful as prognostic marker.

Adolescent↗
PubMedDate not supplied

Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection and its role in carcinogenesis.

Genetic and epigenetic regulations are essential mechanisms that ensure proper early and subsequent mammalian programming of diverse cellular processes. These mechanisms affect transcriptional regulation, stem cell determination and cell cycle control, including senescence and aging. It is not surprising that perturbation of the exquisite balance between genetic and epigenetic regulation can lead to diverse diseases, including cancer. Histone covalent modifications and DNA methylation do not explain all epigenetic phenomena. We describe a previously unsuspected epigenetic factor and propose the incorporation of the 11-zinc finger CCCTC-binding factor, known as CTCF as a novel and multifunctional epigenetic regulator.

Alleles↗
PubMedDate not supplied

[Is evidence based medicine a new paradigm in medical teaching?].

A great deal of enthusiasm has been generated by a learning strategy named Evidence-based medicine (EBM). It is claimed that EBM is a new paradigm that has revolutionized the practice of medicine. In this essay, we review the most stringent criticisms of these claims, opposing the generalized optimism prevalent among the followers of this trend. EBM is neither a new paradigm nor a revolutionary way of practicing medicine. It should be remembered that medicine has sought the best evidence available throughout history. Evidence used by EBM is only that based on meta-analysis and randomized clinical trials and ignores other types of useful evidence such as basic research and clinical experience. Promoting EBM as a new way of practicing medicine is treacherous and endangers the classical approach of the patient-physician relationship.

Education, Medical↗
PubMedDate not supplied

[Molecular hemato-oncology and new specific treatment strategies for leukemia].

Leukemia-associated fusion genes are detected in a significant proportion of newly diagnosed cases, where genes encoding transcription factors are usually found at one of the breakpoints. Activated fusion proteins such as Pml-Raralpha have been shown to inhibit cellular differentiation by recruitment of nuclear corepressor complexes, which maintain local histone deacetylase (HDAC) in a variety of hematologic lineage-specific gene promoters. This HDAC-dependent transcriptional repression appears as a common pathway in the development of leukemia and could constitute an important target for new therapeutic agents. Alternatively, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways normally involved in both apoptosis and proliferation. This aberrant activity is affected by signal transduction inhibitors (STIs), which block or prevent the oncogenic pathway. In this review, we shed some light on our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction pathway. In addition, the administration of low molecular weight drugs for human leukemia treatment based on this knowledge brings about a significant long-term clinical remission and an acceptable risk of toxic effects that should increase the cure rate.

Chromatin Assembly and Disassembly↗