1,720,986 research outputs found
Implications of heat shock proteins in carcinogenesis and cancer progression
No full textHeat shock proteins (Hsp) participate in many events related to cancer as molecular chaperones, starting from the very beginning of carcinogenesis. Several etiological factors involve the Hsp family in their mechanisms of action, including oncogenic viruses, hereditary and non hereditary alterations in tumor suppressors or oncoproteins, hypermethylation, radiation and carcinogenic agents. All of them produce changes in the Hsp response with consequences in cell proliferation, differentiation, inflammation, apoptosis, DNA repair, angiogenesis, metastasis, and drug resistance and in the immunological response mounted by the host. In this chapter we will examine the participation of the Hsp response in tumor cell transformation, either by up-regulation or down-regulation of specific Hsp. This can explain the variations in Hsp expression found in pre-neoplastic and neoplastic human tumors in different tissues and organs. These variations have important clinical consequences in cancer progression, and the exploitation of such knowledge may improve anticancer treatment strategies.Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Calderwood, S. K.. Harvard Medical School; Estados Unidos. University Of Boston. School Of Medicine.; Estados Unido
Autovaccination against tumors using a mineral/protein composite
No full textIn this Chapter we describe the use of a mineral to purify heat shock proteins to be used, in conjunction with the mineral compound, as autovaccine in cancer patients.Fil: Frayssinet, P.. No especifíca;Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Laquerriere, Patricia. Inserm; FranciaFil: Grandjean Laquerriere, Alexia. Inserm; FranciaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
A silver staining method for single-cell gel assay
Get PDFThe single-cell gel assay (comet assay) is a very useful microelectrophoretic technique for evaluation of DNA damage and repair in individual cells. Usually, the comets are visualized and evaluated with fluorescent DNA stains. This staining requires specific equipment (e.g., a high-quality fluorescence microscope), the slides must be analyzed immediately, and they cannot be stored for long periods of time. Here we describe, using human lymphocytes, some modifications of the silver staining for comets that significantly increase the sensitivity/reproducibility of the assay. This silver staining was compared with fluorescence staining and commercial silver stains.The single-cell gel assay (comet assay) is a very useful microelectrophoretic technique for evaluation of DNA damage and repair in individual cells. Usually, the comets are visualized and evaluated with fluorescent DNA stains. This staining requires specific equipment (e.g., a high-quality fluorescence microscope), the slides must be analyzed immediately, and they cannot be stored for long periods of time. Here we describe, using human lymphocytes, some modifications of the silver staining for comets that significantly increase the sensitivity/reproducibility of the assay. This silver staining was compared with fluorescence staining and commercial silver stains.Fil: Nadin, Silvina Beatriz. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); ArgentinaFil: Nadin, Silvina Beatriz. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); ArgentinaFil: Vargas Roig, Laura Maria. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); ArgentinaFil: Vargas Roig, Laura Maria. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); ArgentinaFil: Ciocca, Daniel Ramon. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); ArgentinaFil: Ciocca, Daniel Ramon. Fundación Argentina para la Investigación del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Laboratorio de Reproducción y Lactancia (i); Argentin
Participation of heat shock proteins in DNA repair mechanisms in cancer
No full textHeat shock proteins (HSPs) are well known as molecular chaperones, playing important roles in cellular metabolism, escorting other proteins during aggregation, disaggregation, folding, and unfolding. They have been classified in families according to their molecular weight, i.e. HSPA (HSP70) and HSPH (HSP110), HSP90/HSPC, HSPD1 (HSP60), DNAJ (HSP40), and HSPB (small heat shock proteins including HSP27). HSPs are produced under normal conditions (constitutive) and in response to various stressful conditions/agents such as heat (inducible form). Several HSPs have been involved in cytoprotection, having antiapoptotic roles, and in addition some have been involved in drug resistance to antineoplastic drugs. More recently, it has been also studied the relationship of the HSPs with DNA repair proteins. DNA is constantly subject to numerous insults from endogenous sources (cellular metabolism) and exogenous sources (environmental agents), if this damage is not corrected can lead to genome instability and cancer. Fortunately, our cells count with several DNA-repair pathways to correct the DNA damage and to prevent its consequences. Although the participation of HSPs in DNA repair has received little attention, they are now receiving more interest as possible targets for cancer therapy. Here, we review the participation of HSPs in DNA repair pathways and their implications in cancer therapy and drug sensitivity. Some of the HSPs can travel to the nucleus and it is clear that although the HSPs are not capable of repairing the DNA damages by themselves, they efficiently contribute to the different mechanisms of DNA repair as part of their molecular chaperone capabilities, interacting with DNA repair proteins producing their stimulation and reactivation.Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Resistencia a drogas en pacientes con cáncer de mama
Get PDFEl cáncer de mama sigue siendo una de las principales causas de muerte en la mujer. Uno de los tratamientos que se utiliza en la actualidad para combatir esta enfermedad es la quimioterapia. Lamentablemente en muchos casos esta terapia fracasa porque las células tumorales desarrollan múltiples mecanismos de resistencia a las drogas antitumorales. Existen diversos genes/proteínas que cuando se expresan anormalmente en los tumores impiden que las drogas antitumorales cumplan su función. Entre las proteínas relacionadas con resistencia a drogas antineoplásicas figuran la proteína P170, la proteína HER-2/neu y las proteínas de golpe de calor. Nuestro grupo de trabajo estudia diversas moléculas que se expresan en los tumores de mama y que podrían predecir la sensibilidad/resistencia a la quimioterapia. El objetivo es poder orientar a los oncólogos en la selección de las terapias más efectivas para cada paciente.Breast cancer is one of the principal causes of death in women. Chemotherapy is one of the effective treatments used in breast cancer patients. However, in several cases chemotherapy fails because tumor cells may develop several mechanisms of antitumor drug resistance. There are different genes/proteins that, when abnormally expressed in the tumors, prevent the function of the antitumor drugs. Among the proteins related with chemotherapy resistance is the proteins P170, HER-2/neu, and heat shock. Our research group is studying molecules expressed in breast tumors that can be associated with sensitivity/resistance to chemotherapy.Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
The reality of scientific research in Latin America; an insider’s perspective
Get PDFThere is tremendous disparity in scientific productivity among nations, particularly in Latin America. At first sight, this could be linked to the relative economic health of the different countries of the region, but even large and relatively rich Latin American countries do not produce a good level of science. Although Latin America has increased the number of its scientists and research institutions in recent years, the gap between developed countries and Latin American countries is startling. The prime importance of science and technology to the development of a nation remains unacknowledged. The major factors contributing to low scientific productivity are the limited access to grant opportunities, inadequate budgets, substandard levels of laboratory infrastructure and equipment, the high cost and limited supply of reagents, and inadequate salaries and personal insecurity of scientists. The political and economic instability in several Latin America countries results in a lack of long-term goals that are essential to the development of science. In Latin America, science is not an engine of the economy. Most equipment and supplies are imported, and national industries are not given the incentives to produce these goods at home. It is a pity that Latin American society has become accustomed to expect new science and technological developments to come from developed countries rather than from their own scientists. In this article, we present a critical view of the Latin American investigator’s daily life, particularly in the area of biomedicine. Too many bright young minds continue to leave Latin America for developed countries, where they are very successful. However, we still have many enthusiastic young graduates who want to make a career in science and contribute to society. Governments need to improve the status of science for the sake of these young graduates who represent the intellectual and economic future of their countries.Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Delgado, Gabriela. Universidad Nacional de Colombia; Colombi
Heat shock proteins: Stress proteins with Janus-like properties in cancer
Get PDFHeat shock proteins (HSPs) were first identified as stress proteins that confer resistance to physical stresses such as elevated temperatures in all cellular organisms. HSPs are rapidly elevated after stress and confer a temperature resistant phenotype. Temperature resistance is dependent on the ability of HSPs to function as molecular chaperones and prevent aggregation and on the capacity of Hsp27 and Hsp70 to act as wide spectrum inhibitors of the cell death pathways. HSP expression becomes deregulated in cancer leading to elevated expression. Elevated HSP expression promotes cancer by inhibiting programmed cell death (Hsp27, Hsp70) and by promoting autonomous growth (Hsp90) and leads to resistance to chemotherapy and hyperthermia. Tumor HSPs have another property that can be exploited in therapy. They are immunogenic and can be used to form the basis of anticancer vaccines. Elevation in HSP levels may thus have competing effects in tumor growth, being required for tumor cell survival but conferring a hazard for cancer cells due to their immunogenic properties. This dichotomy is also reflected by the approaches used to target HSP in therapy. Pharmacological approaches are being employed to inhibit activity or expression of tumor HSP. Immunological approaches aim at increasing HSP levels in cells and tissues with the aim of increasing tumor antigen presentation to the immune system.Fil: Calderwood, Stuart K.. Harvard Medical School; Estados UnidosFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Fundación Argentina para la Investigación del Cáncer; Argentin
Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update
Get PDFHeat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress. HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1). During the progression of many types of cancer, thisheat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell. Concerted activation of HSF1 and the accumulation of HSPs then participate in many of the traits that permit the malignant phenotype. Thus, cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic. We review here the extensive work that has been carried out and is still in progress aimed at (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1/HSP in malignant transformation and (3) discovering approaches to therapy based on disrupting the influence of the HSF1-controlled transcriptome in cancer.Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Arrigo, Andre Patrick. Cancer Research Center of Lyon, Apoptosis Cancer and Development; Francia. Claude Bernard University; FranciaFil: Calderwood, Stuart K.. Beth Israel Deaconess Medical Center. Department of Radiation Oncology; Estados Unido
Progesterone receptors: Their localization, binding activity and expression in the pig oviduct during follicular and luteal phases
Get PDFEstrogens (E) and progesterone (P) are known to require their respective steroid receptors in order to exert structural and functional effects on the oviduct. Cyclic changes in progesterone receptor (PR) localization in the oviductal tissue of female pigs were determined using an immunohistochemical technique with mouse monoclonal antibody mPRI against PR. The variations observed during the estrous cycle in the progesterone receptor (PR) intensity and proportion between ampulla and isthmus probably reflect different response of these regions to progesterone. Immediately before ovulation, during follicular phase, no staining was observed in either the ampulla or the isthmus stroma. However, a low expression of PR in the epithelium of the ampulla was observed. After ovulation, during luteal phase, PR immunostaining was more intense in the whole oviduct. According to immunohistochemical assays, the binding assays for nuclear and cytosolic PR (PRn and PRc, respectively), by using [3H] R5020 at 4°C for 15 h, also showed a higher specific binding during luteal phase. However, the PR mRNA in the oviduct, analyzed by RT-PCR, showed similar levels at both stages of the estrous cycle. Although this methods could not be quantitative, indicate the possibility that a post-transcriptional control could differentially regulate the PR in the pig oviduct.Fil: Peralta, Luisa E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Roldan Olarte, Eugenia Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Argañaraz, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Miceli, Dora Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin
Small stress proteins, biomarkers of cancer
No full textMany oncogenic agents/events generate in cancer cells stress-responsive proteins, also known as heat shock proteins (HSPs). These proteins are implicated in the genesis as well as in the progression of cancer; the small HSPs share the chaperone activity of the other HSPs and thus the small HSPs should also be described as chaperones of tumorigenesis. Since the small HSPs are found at relatively high levels in tumor cells, the study of the expression of these proteins is of high interest as biomarkers of cancer. In this chapter we have analysed the evidence regarding its usefulness: 1) to detect in fluids and tissues the early changes in cell transformation, 2) to help in the diagnosis of the disease, 3) in predicting the recurrence, aggressiveness and the development of metastasis, and 4) to predict the response to therapies and to monitor the efficacy/safety of therapeutic agents. In breast cancer, earlier studies and more recent proteomic studies reveal that the small HSPs are mainly implicated in the response to therapies, HSPB1 (HSP27) appears as a biomarker of resistance to different anticancer therapies. In other tumors, like in prostate cancer, they appear as biomarkers of disease prognosis, while in uterine cervical cancer HSPB1 appears as a marker of cell differentiation. The molecular pathways implicated in the small HSPs activation and the association of these proteins with other proteins result in a unique molecular context in each cancer cell type and ultimately in each patient appearing as biomarkers of different situations. Overall, it is evident that more studies on the topic of biomarkers of anticancer therapies are needed to change the way we treat cancer patients, but so far it seems that the small HSPs, in conjunction with other biomarkers, have a great future to achieve tailored-treatment strategies.Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Castro, Gisela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
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