RESUMO
In this perspective I look back on the twists and turns that influenced the direction of my scientific career over the past 40 years. From my early ambition to be a chemist to my training in Philadelphia and Bethesda as a molecular biologist, I benefited enormously from generous and valuable mentoring. In my independent career in Philadelphia and Princeton, I was motivated by a keen interest in the changes in gene expression that direct the development of the mammalian embryo and inspired by the creativity and energy of my students, fellows, and research staff. After twelve years as President of Princeton University, I have happily returned to the faculty of the Department of Molecular Biology.
Assuntos
Biologia Molecular/história , Universidades/história , Sequência de Aminoácidos , Animais , Canadá , Passeio de Cromossomo , Desenvolvimento Embrionário/genética , Proteínas do Olho/genética , Proteínas do Olho/história , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , História do Século XX , História do Século XXI , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/história , Humanos , Camundongos , Dados de Sequência Molecular , National Institutes of Health (U.S.) , New Jersey , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/história , Splicing de RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/história , Proteínas Repressoras/genética , Proteínas Repressoras/história , Estados Unidos , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/história , Globinas beta/genética , Globinas beta/históriaRESUMO
Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.
Assuntos
Antígenos Glicosídicos Associados a Tumores/história , Biomarcadores Tumorais/história , Antígeno Carcinoembrionário/história , Neoplasias do Sistema Digestório/história , alfa-Fetoproteínas/história , Animais , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/história , Antígeno Carcinoembrionário/sangue , Neoplasias do Sistema Digestório/sangue , Neoplasias do Sistema Digestório/diagnóstico , Neoplasias do Sistema Digestório/terapia , História do Século XX , Humanos , Mucina-1/história , Fosfopiruvato Hidratase/história , Precursores de Proteínas/história , Protrombina/história , alfa-Fetoproteínas/análiseRESUMO
alpha-Fetoprotein (AFP) is an embryonic serum protein. Only traces of AFP are present in blood of adult man or animal, but its level substantially increases during liver regeneration and in cases of primary liver carcinoma or embryonic carcinomas. Different aspects of AFP studies (localization of its synthesis, structure and functions, genetic control of its synthesis and its use for cancer diagnostics) are reviewed. The main consideration is given to the cellular mechanisms of regulation of AFP synthesis. Hypothesis of "structural repression of AFP" is substantiated. According to it formation of liver trabeculae leads to suppression of AFP synthesis in hepatocytes, whereas escape of hepatocyte from trabecula results in activation of AFP synthesis. A new experimental model is described: AFP synthesis is activated in primary hepatocyte culture and is suppressed during three-dimensional growth of hepatocytes in collagen gel or mixed culture with nonparenchymal liver cells.
Assuntos
alfa-Fetoproteínas/história , Animais , História do Século XX , Humanos , Fígado/fisiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/fisiopatologia , Regeneração Hepática/fisiologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/fisiopatologia , Pesquisa/história , alfa-Fetoproteínas/fisiologiaRESUMO
A historical account of the finding of alphafetoprotein is presented. The problems in its initial isolation, purification and source are described. Some interesting potential future studies are also discussed.