RESUMO
Cancer research concerning short non-coding RNA sequences and functionally linked to RNA interference (RNAi) have reached explosive breakthrough in the past decade. Molecular technology applies microRNA in extremely wide spectrum from molecular tumor prediction, diagnostics, progression monitoring and prevention. Functional analysis of tissue miRNA and cell-free serum miRNA in posttranscription and translation regulation innovated and restructured the knowledge on the field. This review focuses on molecular epidemiology and primary prevention aspects of the small non-coding RNA sequences.
Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/metabolismo , Neoplasias/genética , Interferência de RNA , Pequeno RNA não Traduzido/metabolismo , Biomarcadores/metabolismo , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/biossíntese , MicroRNAs/sangue , Epidemiologia Molecular , Neoplasias/prevenção & controle , Valor Preditivo dos TestesRESUMO
Despite modern diagnostic procedures and up-to-date therapy, the survival of head and neck tumour patients is unfavourable. This can be explained by several factors, one of which is the late recognition of the tumour. This study related to the changes in expression of the c-myc and Ha-ras oncogenes and the p53 tumour suppressor gene as biomarkers in head and neck cancer cases. The gene expressions were investigated on RNA gained from peripheral white blood cells of head and neck cancers patients before and after definitive treatment. The results were compared with those on a control group of patients with non-tumorous diseases. The gene expressions were significantly higher in the cancer group than that in the control group (volunteer medical staff and medical students). After definitive treatment, the expressions of all these genes were decreased in patients in whom there was no recurrence of the tumour, but enhanced in the event of recurrence. Such measurement may serve as reliable biomarkers to monitor tumour development and the efficiency of therapy. The method may also be useful for the early identification of populations exposed to noxe, which may lead to the development of head and neck cancers.
Assuntos
Carcinoma/genética , Genes myc/genética , Genes p53/genética , Genes ras/genética , Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Biomarcadores/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Estudos de Casos e Controles , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , RNA/genética , RNA/metabolismoRESUMO
BACKGROUND: Cancer therapies and cancer progression can increase oxidative stress that might account for renal toxicity in cancer patients. Flavin 7 (F7) is a natural polyphenol-containing dietary supplement with potential antioxidant activity. Therefore, it might help to attenuate renal toxicity of chemotherapeutics. MATERIALS AND METHODS: Cultured mouse renal proximal tubule cells were subjected to H(2)O(2)-mediated oxidative stress. Potential antioxidant effects of F7 were assessed by measuring the production of reactive oxygen species (ROS), mitochondrial depolarization and injury (lactate dehydrogenase release as well as trypan blue exclusion) in cells that were pretreated with F7 prior to treatment with H(2)O(2). RESULTS: F7 pretreatment significantly attenuated H(2)O(2)-induced ROS production, mitochondrial depolarization and consequent injury in renal proximal tubule cells. CONCLUSION: F7 supplementation might be beneficial for cancer patients in order to prevent renal toxicity of anticancer drug- or cancer progression-related oxidative stress.
Assuntos
Antioxidantes/farmacologia , Frutas/química , Túbulos Renais Proximais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Benzimidazóis/metabolismo , Carbocianinas/metabolismo , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/metabolismo , Peróxido de Hidrogênio/toxicidade , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , L-Lactato Desidrogenase/metabolismo , Camundongos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
CASE REPORT: A middle-aged man presented with the diagnosis of typical spontaneous pneumothorax in the left chest. His management was initiated as usual with a chest drain and he had an uneventful recovery with good expansion of the affected lung up until the third postoperative day. But due to a fatal accident, the patient connected the oxygene supply tube into his thoracic drain. This high pressure caused a left, and a consequent bilateral pneumothorax with massive subcutanous emphysema, being the cause of a preterminal status. Cardio-pulmonary resuscitation was unsuccesfull and the patient died. Intentional suicide was excluded by forensic investigations. DISCUSSION: According to our knowledge, no similar case with this mechanism of tension pnemuthorax has been published in the literature so far. The pathophysiology is similar to lung damage due to high-pressure ventillation with consecutive tension pneumothorax.
Assuntos
Acidentes , Tubos Torácicos , Oxigênio/efeitos adversos , Pneumotórax/etiologia , Pneumotórax/terapia , Enfisema Pulmonar/etiologia , Insuficiência Respiratória/etiologia , Reanimação Cardiopulmonar , Tubos Torácicos/efeitos adversos , Desenho de Equipamento , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Pneumotórax/diagnóstico , Enfisema Pulmonar/terapia , Insuficiência Respiratória/terapiaRESUMO
7,12-Dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea (MNU) are important environmental carcinogens. Their different biological effects were examined in CBA/Ca H-2(K) haplotype inbred mice on the gene expression of c-myc, Ha-ras and p53 through a 24 hour period. Elevated expression of c-myc and Ha-ras genes was found in the spleen, lung, thymus and lymph nodes 6 and 12 hours after DMBA treatment and in the lung and thymus 3 hours after MNU treatment. In the liver, DMBA induced strong onco/suppressor gene expression as early as 6 hours after the treatment, but MNU increased the p53 gene expression 12 hours after the treatment. The gene expression patterns reflected the different mechanism of the direct acting MNU and metabolically activated DMBA. This phenomenon provides evidence as to the usefulness of detection of onco/supressor key gene expression as early molecular epidemiological biomarkers of carcinogenesis and carcinogenic exposure in animal model, useful in human cancer prevention practice as well.
Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Carcinógenos/toxicidade , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , 9,10-Dimetil-1,2-benzantraceno/química , Alquilantes/química , Alquilantes/toxicidade , Animais , Carcinógenos/química , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Metilnitrosoureia/química , Metilnitrosoureia/toxicidade , Camundongos , Camundongos Endogâmicos CBARESUMO
BACKGROUND: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. RESULTS: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). CONCLUSION: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Glutationa Transferase/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Alelos , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Feminino , Genes p53 , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo Genético , Taxa de SobrevidaRESUMO
Gastric cancer is one of the most frequent cause of mortality, survival data are insufficient. Several chemotherapeutic combinations were applied successfully in advanced gastric cancer, following total tumor regression and radical resection, but there are very few cases with total regression after a disease forming carcinosis and causing ascites. In our report, a middle age patient suffering from locally advanced gastric cancer with peritonitis carcinomatosa and ascites was treated with neoadjuvant chemotherapy (DCF: docetaxel, cisplatin, fluorouracil protocol) successfully, as at the restaging examination total tumor regression was found. Ascites and carcinosis disappeared, so we performed radical distal surgical resection. The histological preparation resulted in 100% tumor regression of the specimen. Postoperatively the patient was given adjuvant DCF chemotherapy. The therapeutic modality of cases with advanced gastric cancer, especially with carcinosis must be reassessed, because according to our and some international reports, these patients are also candidates for effective neoadjuvant therapy and curative resection. In our own and in the experience of some others the combinations with taxanes and its derivatives are one of the most effective.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Peritoneais/tratamento farmacológico , Peritonite/etiologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Ascite/etiologia , Carcinoma/secundário , Carcinoma/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel , Fluoruracila/administração & dosagem , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
The aim of the study was to monitor the early effect of cytostatics containing platinum on oncogenes in inbred CBA/Ca mice. In human head-neck tumors after treatment with the Cisplatin supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol, further surgeries are often necessary due to regional recurrence. Body weight equivalent amounts of human dose of Cisplatin were administered intraperitoneally to 6-8-week-old, inbred, female CBA/Ca mice. Twenty four 48 and 72 hours after the treatment RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes was examined by dot-blotting in potential target tissues. Significant overexpression of Ha-ras and p53 genes was measured in the bone marrow. Regarding the expression of Ha-ras gene, a significant increase was also found in the lymph nodes after 48 hours. The p53 expression in the lungs was down-regulated compared to the control group. In the "short-term" in vivo test, 24-hour examination of gene expression and amplification is suitable for detecting the early effects of carcinogenetic exposure. Cisplatin-induced gene expression alterations call attention to its possible role in the development of regional recurrence in patients treated with cisplatin-containing regimens.