RESUMO
Heat shock proteins are ubiquitous molecular chaperones involved in posttranslational folding, stability, activation and maturation of many proteins that are essential mediators of signal transduction and cell cycle progression. Hsp90 proteins are the best studied proteins of this family. A growing number of Hsp90 client proteins have been shown to be important for the development, proliferation and survival of several types of cancer. Inhibition of Hsp90 leads to the degradation of known oncogene products, such as Her2, BRAF and others, leading to the simultaneous blockade of multiple oncogenic transduction pathways. Hsp90 inhibitors, derived from the natural compound geldanamycin, are attractive targets for anticancer drug development. We will review the clinical data on Hsp90 inhibitors in different malignancies. The best known of them, 17-AAG, has shown significant antitumour activity against a broad variety of cancers in preclinical studies, including breast, myeloma, melanoma, prostate and lung cancers. Hsp90 inhibitors can be used as single agents or in combination with other targeted treatments or chemotherapy and radiotherapy. The results of clinical phase II and III trials evaluating the effi cacy of these drugs in different types of tumours are awaited.
Assuntos
Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais/fisiologia , Animais , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , HumanosRESUMO
INTRODUCTION: Recent studies have suggested a rise in the incidence of testicular germ-cell tumors (TGTs) in the last years, mainly due to an increase of early stage cases. We analysed the time trends in biological features of these patients in order to confirm this tendency in our environment. MATERIALS AND METHODS: The clinical records of 136 consecutive patients with TGTs treated at a single institution over a 20-year period (1984-2003) were retrospectively reviewed. Pathological, clinical, therapeutic and outcome data were collected. Patients were allocated into four consecutive 5- year intervals and their characteristics were compared by means of the chi-squared test. The survival analysis was performed with the method of Kaplan and Meier. RESULTS: A progressive increase in the incidence of new cases, and a more frequent diagnosis of stage I versus stage II-IV disease was confirmed within this time period. It was also observed a greater use of postorchiectomy chemotherapy, mainly due to an increase in the adjuvant indications. A significant decrease in the recurrence rate was noted. Ten-year overall survival was 86.5%. There was a trend for improved outcome, but the differences among the two decades were not statistically significant. CONCLUSIONS: A real increase in the incidence of TGTs and in the proportion of early stages was confirmed. This may be due to an epidemiological change or to an earlier diagnosis. This new pattern is associated with a more frequent use of adjuvant chemotherapy and with a reduction in the relapse rate.
Assuntos
Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Testiculares/epidemiologia , Adolescente , Adulto , Diagnóstico Precoce , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapiaRESUMO
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Introduction. Recent studies have suggested a risein the incidence of testicular germ-cell tumors(TGTs) in the last years, mainly due to an increaseof early stage cases. We analysed the time trendsin biological features of these patients in order toconfirm this tendency in our environment.Materials and methods. The clinical records of136 consecutive patients with TGTs treated at asingle institution over a 20-year period (1984-2003)were retrospectively reviewed. Pathological, clinical,therapeutic and outcome data were collected.Patients were allocated into four consecutive 5-year intervals and their characteristics were comparedby means of the chi-squared test. The survivalanalysis was performed with the method ofKaplan and Meier.Results. A progressive increase in the incidence ofnew cases, and a more frequent diagnosis of stageI versus stage II-IV disease was confirmed withinthis time period. It was also observed a greater useof postorchiectomy chemotherapy, mainly due toan increase in the adjuvant indications. A significantdecrease in the recurrence rate was noted.Ten-year overall survival was 86.5%. There was atrend for improved outcome, but the differencesamong the two decades were not statistically significant.Conclusions. A real increase in the incidence of TGTsand in the proportion of early stages was confirmed.This may be due to an epidemiological change or toan earlier diagnosis. This new pattern is associatedwith a more frequent use of adjuvant chemotherapyand with a reduction in the relapse rate
Assuntos
Masculino , Humanos , Células Intersticiais do Testículo/patologia , Neoplasias Testiculares/epidemiologia , Germinoma/patologia , Estudos Retrospectivos , Estudos de Coortes , Estadiamento de NeoplasiasRESUMO
Oligodendrogliomas are primary brain tumours derived from oligodendroglial cells, or precursors, and represent 2%-5% of brain tumours. This type of glioma has a favourable prognosis compared to other brain tumours. The treatment is multidisciplinary and is based on three therapeutic arms: surgery, radiotherapy and chemotherapy. We present a patient who had received treatment previously for a lowgrade glioma and who subsequently developed an anaplastic oligoastrocytoma in the same zone together with skull and extra-cranial involvement in the disease progression.
Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Segunda Neoplasia Primária/patologia , Neoplasias Cranianas/patologia , Osso Temporal , Lobo Temporal , Evolução Fatal , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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Oligodendrogliomas are primary brain tumours derived from oligodendroglial cells, or precursors, and represent 2%-5% of brain tumours. This type of glioma has a favourable prognosis compared to other brain tumours. The treatment is multidisciplinary and is based on three therapeutic arms: surgery, radiotherapy and chemotherapy. We present a patient who had received treatment previously for a lowgrade glioma and who subsequently developed an anaplastic oligoastrocytoma in the same zone together with skull and extra-cranial involvement in the disease progression