RESUMO
Cancer is a disease characterized by a very little apoptosis, ie, genetically programmed cell death. Aberrations in apoptotic pathways are central to tumorigenesis, tumor progression, and overall tumor growth and regression in response to chemotherapy. It is now increasingly accepted that chemotherapeutic drug efficacy is partially related to its ability to induce apoptosis. Apoptosis, therefore, represents not only a vital target in cancer therapy but also a unique biomarker opportunity that has thus far been largely unexploited. In response to therapy, tumor cells undergo apoptosis and release their cellular components in the circulation. As such, these materials may serve as biomarkers to assess response. Apoptosis markers in breast cancer include circulating soluble FasL, granzyme B, and cytochrome c that increase following chemotherapy. Unfortunately, there is a paucity of information in the literature with respect to this approach. As such, large-scale prospective studies are clearly needed to validate this approach and more fully elucidate clinical usefulness.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Proteínas de Neoplasias/genética , Antineoplásicos/classificação , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Citocromos c/sangue , Citocromos c/genética , Progressão da Doença , Proteína Ligante Fas/sangue , Proteína Ligante Fas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Granzimas/sangue , Granzimas/genética , Humanos , Proteínas de Neoplasias/sangue , Transdução de SinaisRESUMO
BACKGROUND: Anticancer agents used in chemotherapy for tumors induce apoptosis in malignant cells. Soluble Fas ligand, granzyme B and cytochrome c are key elements in the process of apoptosis. The objective of this preliminary study was to evaluate the changes in the serum concentrations of these parameters in breast cancer patients undergoing adjuvant chemotherapy. MATERIALS AND METHODS: Sixty patients with histopathologically proven breast cancer were included in the present study. The blood samples were taken after surgery before chemotherapy and after 3weeks of administration of the first cycle of chemotherapy. Thirty healthy female controls were selected for comparison. Soluble FasL, granzyme B and cytochrome c were estimated from serum by ELISA. RESULTS: Significantly increased concentrations of soluble FasL, granzyme B and cytochrome c were found in stage II and stage III of breast cancer patients after chemotherapy compared with concentrations before chemotherapy (P<0.0001). A significant positive correlation was found between soluble FasL and cytochrome c as well as between granzyme B and cytochrome c in breast cancer patients after chemotherapy. CONCLUSION: Serum concentrations of apoptotic markers such as soluble FasL, granzyme B and cytochrome c were increased after administration of the first cycle of chemotherapeutic drugs. The measurement of these circulating apoptotic markers may help clinicians in evaluating treatment efficacy in breast cancer.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Citocromos c/sangue , Proteína Ligante Fas/sangue , Granzimas/sangue , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/enzimologia , Estudos de Casos e Controles , Quimioterapia Adjuvante , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: [corrected] Alcoholic liver diseases (ALD) are very common in lower socio-economical strata due to heavy drinking habits and multiple nutritional deficiencies. Ethanol causes liver damage by many mechanisms. The generation of lipid peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. These free radicals are destroyed by anti-oxidants. Many anti-oxidants are present in the diet, e.g., vitamin E, vitamin C etc. However, poor nutrition or malabsorption leads to deficiency of these vitamins. This may impair the anti-oxidative defense leading to ethanol induced oxidative stress and then to liver damage. METHODS: Oxidative stress and antioxidant defense were assessed in patients with alcoholic liver disease. Serum malondialdehyde (MDA) concentrations were measured as an index of lipid peroxidation, i.e., oxidative stress; and serum vitamins E and C concentrations were measured as an index of antioxidant status. RESULTS: Serum MDA concentrations were increased with the increase in severity of the disease. Concentrations of serum vitamins E and C were decreased in patients with alcoholic liver disease as compared to controls. CONCLUSIONS: Our observations may be due to increased demands of the same or increased utilization.
