Biomedical subjects

Alicia Gutiérrez

Publications and source records attributed to Alicia Gutiérrez.

7 recordsLinked to original sources

PubMed2005

Hexachlorobenzene is a tumor co-carcinogen and induces alterations in insulin-growth factors signaling pathway in the rat mammary gland.

Hexachlorobenzene (HCB) is a widespread environmental pollutant. Controversy still exists about the breast carcinogenic properties of organochlorines in humans. The ligands, receptors, and related signaling proteins of the insulin growth factor family are involved in the regulation of breast-cancer cell growth. The aims of this study were to determine: (1) whether HCB is co-carcinogenic in a medium term assay of N-nitroso N-methylurea (NMU)-induced mammary tumors in rats; (2) the effect of HCB on insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR) and insulin receptor substrate-1 (IRS-1) levels and on IRS-1 phosphorylation; (3) microsomal and cytosolic Protein Tyrosine Kinase (PTK) activities in mammary glands and NMU-induced tumors. Sprague Dawley rats were injected with 50 mg/kg body weight of NMU at 50, 80, and 110 days old. HCB (100 mg/kg body weight) was administered three times a week from 65 to 110 days of age. Rats were separated in four groups: control, NMU, HCB, and NMU-HCB. HCB alone did not induce tumor development. Parameters of tumor development were increased in NMU-HCB compared to NMU rats. A higher cellular undifferentiation was observed in NMU-HCB tumors. IR, IGF-IR, and IRS-1 levels were higher in HCB than in controls. Conversely IGF-IR levels decreased in NMU-HCB vs. NMU group. The IRS-1 phosphorylation increased in HCB rats; however, it decreased in NMU-HCB vs. NMU. HCB decreased microsomal PTK activity in tumors. This study showed for the first time that HCB is a co-carcinogenic agent in NMU-induced mammary tumors in rats. Our results suggest that the IR and/or IGF-IR signaling pathway may be involved in the mechanism of action of HCB.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Effect of glibenclamide on N-nitroso-N-methylurea-induced mammary tumors in diabetic and nondiabetic rats.

The objective of this study was to evaluate the antitumor effect of glibenclamide (Gli) alone or in combination with tamoxifen (Tam) on experimental mammary tumors induced by N-nitroso-N-methylurea (NMU) in nondiabetic and diabetic rats. For experimental diabetes induction, Sprague-Dawley rats were injected with streptozotocin (STZ) on the second day of life. For experimental mammary tumor induction, nondiabetic and diabetic rats were injected IP with NMU at 50, 80, and 110 days of life. Nondiabetic and diabetic rats bearing mammary tumors were treated with 0.06 mg/day of Gli orally, Tam 1 mg/kg/day SC, or with the combined treatment (Gli + Tam). After 20 days of treatment, different responses were observed. In nondiabetic rats, 64% of tumors were responsive to Gli treatment (they regressed or remained stable), whereas 57% of tumors under treatment with Tam exhibited a response. Results of the combined Gli + Tam treatment indicated that all tumors were responsive: 58% regressed and 42% remained stable. Diabetic rats receiving Gli treatment did not show response to this treatment, while 65% of the tumors of Tam-treated diabetic rats showed regression. Histopathologic observation indicated an important intratumor secretion in all tumors of Gli-, Tam-, or Gli + Tam-treated rats. No secondary toxic effect was observed after treatment at any assayed doses. In conclusion, the present data demonstrate the in vivo antitumor action of Gli treatment on the experimental mammary tumors employed, indicating that Gli exerted a direct effect on tumor cells in nondiabetic rats. The combined Gli + Tam treatment potentiated the antitumor effect of each drug alone. Future research will examine the molecular aspects of these findings.

Animals↗

PubMed2005

Mitochondrial apoptotic pathways.

Apoptosis or programmed cell death (PCD) is a physiological process characteristic of pluricellular organisms leading to self-destruction of the cell. It is therefore involved in development, homeostasis and host defense. However, a significant difference has been shown between mammalian cell apoptosis and non-mammalian cell apoptosis: mitochondria are implicated only in the former. Execution of PCD includes the release of several proapoptotic proteins from the intermembrane space of mitochondria. They could exert their actions through a caspase dependent as well as a caspase independent way. On the other hand, regulation of PCD is mainly given by the Bcl-2 family members, which are in turn essentially regulated by activation of death receptors and/or DNA damage. Nowadays, execution of apoptosis is better known than its regulation. Nevertheless, we are still far of a complete understanding of the apoptotic process.

Animals↗

PubMed2003

Suppression of mammary gland tumorigenesis in diabetic rats.

The aim of this study was to compare mammary gland tumorigenesis in diabetic and non-diabetic rats. Streptozotocin and N-nitroso-N-methylurea were used to induce diabetes and mammary tumors, respectively. A suppression of mammary carcinogenesis in diabetic rats was shown by a longer latency period, a lower number of tumors per animal and a smaller final tumor volume. An 84% of the lesions developed in diabetic animals were benign tumors. Eighty day-old diabetic rats had significantly lower plasma levels of total-IGF-I and insulin versus non-diabetic rats. We postulate that the decrease in the total IGF-I and insulin levels during the promotion phase of carcinogenesis in this model plays an important role in retarding the tumor development in diabetic animals and in favoring the development of benign mammary lesions.

Alkylating Agents↗

PubMedDate not supplied

IGF-I in mammary tumorigenesis and diabetes.

Insulin growth factors (IGFs) are important mediators of growth, development, differentiation and survival of normal and transformed cells. Many complex and diverse types of molecules modulate these actions. In vitro and in vivo experiments have demonstrated that this system (IGF) is strongly related to the establishment of the transformed phenotype. Recent studies confirmed the association between serum levels of IGF-I and diverse malignant diseases while some relationships with other pathologies since Diabetes Mellitus have been described. Currently, IGFs are considered important targets for the study of new therapeutic drugs and strategies for cancer treatment. In this review, we have summarized the latest data specially linking IGF-I and its receptor with breast cancer.

Animals↗

PubMedDate not supplied

Insulin-like growth factor-I receptor expression and localization in benign and malignant rat mammary tumors.

The aim of this study was to investigate the expression and localization of the insulin growth factor type 1 receptor (IGF-IR) in malignant and benign mammary tumors induced in rats by N-nitroso-N-methylurea (NMU) and its correlation with histopathology and hormone dependence. Also, protein tyrosine kinase activities (PTKs) were analyzed in order to study the activation of the intracellular cascade. The results showed that IGF-IR is present in NMU tumors (analyzed by binding assay and Western blot), that a variable content is expressed in tumors that continued growing post-ovariectomy (OVX) of rats, and that it is undetectable in tumors that regressed post-OVX. IGF-IR was principally localized (by immunohistochemistry) in the epithelial cells of malignant tumors and in the fibrous cells of benign ones. Also, a significantly lower expression of both cytosolic and microsomal PTKs were found in benign tumors. Our results suggest a different expression and role of IGF-IR in benign and malignant tumors.

Animals↗

PubMedDate not supplied

Effect of rosiglitazone on N-nitroso-N-methylurea-induced mammary tumors in rat.

The objective of this study was to evaluate the in vivo antitumor action of rosiglitazone (Rosi) alone or in combination with tamoxifen (Tam) on experimental mammary tumors induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Animals bearing mammary tumors were treated with 0.06 mg/kg/day or 0.12 mg/kg/day of Rosi orally, 1 mg/kg/day of Tam s.c., or with the combined treatment (Rosi+Tam). After 25 days of treatment, the following responses were observed: 45% of tumors were responsive to 0.06 mg/kg/day of Rosi treatment, while 55% of tumors under Tam treatment responded. The results of the combined Rosi+Tam treatment indicated that 75% of tumors were responsive. Similar results were obtained with 0.12 mg/kg/day of Rosi. Apoptosis, necrosis and glandular hypersecretion were observed in Rosi-treated tumors. In all cases, the combined Rosi+Tam treatment potentiated the antitumor effect of Tam alone. No side-effects were observed after treatment at any assayed dose.

Animals↗