RESUMO
The educational environment has been increasingly acknowledged as vital for high-quality medical education. As a result, several instruments have been developed to measure medical educational environment quality. However, there appears to be no consensus about which concepts should be measured. The absence of a theoretical framework may explain this lack of consensus. Therefore, we aimed to (1) find a comprehensive theoretical framework defining the essential concepts, and (2) test its applicability. An initial review of the medical educational environment literature indicated that such frameworks are lacking. Therefore, we chose an alternative approach to lead us to relevant frameworks from outside the medical educational field; that is, we applied a snowballing technique to find educational environment instruments used to build the contents of the medical ones and investigated their theoretical underpinnings (Study 1). We found two frameworks, one of which was described as incomplete and one of which defines three domains as the key elements of human environments (personal development/goal direction, relationships, and system maintenance and system change) and has been validated in different contexts. To test its applicability, we investigated whether the items of nine medical educational environment instruments could be mapped unto the framework (Study 2). Of 374 items, 94% could: 256 (68%) pertained to a single domain, 94 (25%) to more than one domain. In our context, these domains were found to concern goal orientation, relationships and organization/regulation. We conclude that this framework is applicable and comprehensive, and recommend using it as theoretical underpinning for medical educational environment measures.
Assuntos
Modelos Teóricos , Avaliação de Programas e Projetos de Saúde/métodos , Faculdades de Medicina , Educação de Graduação em Medicina , HumanosRESUMO
BACKGROUND: To cope with a lack of doctors and in anticipation of the Bachelor-Master structure for Medicine, several Dutch universities offer graduate entry programmes for students with degrees in areas related to Medicine. The graduate entry programme is a four-year programme: after a transition period of one year students enroll in the fourth year of the regular six-year training programme. AIM: The research questions in this study were (1) whether and when graduate entry students' knowledge reached a level comparable to that of regular medical students and (2) whether there were differences in knowledge levels between graduate entry students with a university or HBO (college) degree. METHODS: The progress test results of ninety graduate entry students who were enrolled in the transitional programme between 2002 and 2004 were compared to those of regular third-year students. RESULTS: Initially, graduate entry students scored significantly lower on the progress tests, but differences disappeared within a year. No differences were found between graduate entry students with a university or HBO degree. CONCLUSIONS: The results of this study indicate that the increase in knowledge after a one-year transitional period is sufficient to enroll students with related degrees in the fourth year of the regular medical training programme.
Assuntos
Currículo/estatística & dados numéricos , Educação de Graduação em Medicina/organização & administração , Educação de Graduação em Medicina/estatística & dados numéricos , Critérios de Admissão Escolar/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Adulto , Estudos de Coortes , Avaliação Educacional/estatística & dados numéricos , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países BaixosRESUMO
Homozygous deletions or loss of heterozygosity (LOH) at human chromosome band 3p12 are consistent features of lung and other malignancies, suggesting the presence of a tumor suppressor gene(s) (TSG) at this location. Only one gene has been cloned thus far from the overlapping region deleted in lung and breast cancer cell lines U2020, NCI H2198, and HCC38. It is DUTT1 (Deleted in U Twenty Twenty), also known as ROBO1, FLJ21882, and SAX3, according to HUGO. DUTT1, the human ortholog of the fly gene ROBO, has homology with NCAM proteins. Extensive analyses of DUTT1 in lung cancer have not revealed any mutations, suggesting that another gene(s) at this location could be of importance in lung cancer initiation and progression. Here, we report the discovery of a new, small, homozygous deletion in the small cell lung cancer (SCLC) cell line GLC20, nested in the overlapping, critical region. The deletion was delineated using several polymorphic markers and three overlapping P1 phage clones. Fiber-FISH experiments revealed the deletion was approximately 130 kb. Comparative genomic sequence analysis uncovered short sequence elements highly conserved among mammalian genomes and the chicken genome. The discovery of two EST clusters within the deleted region led to the isolation of two noncoding RNA (ncRNA) genes. These were subsequently found differentially expressed in various tumors when compared to their normal tissues. The ncRNA and other highly conserved sequence elements in the deleted region may represent miRNA targets of importance in cancer initiation or progression.
Assuntos
Cromossomos Humanos Par 3 , Deleção de Genes , Genes Supressores de Tumor , RNA Neoplásico/genética , RNA não Traduzido/genética , Animais , Neoplasias da Mama/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Pequenas/genética , Linhagem Celular Tumoral , Galinhas , Mapeamento Cromossômico , Sequência Conservada , Homozigoto , Humanos , Íntrons , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , Família Multigênica , Proteínas do Tecido Nervoso/genética , Receptores Imunológicos/genética , Proteínas RoundaboutRESUMO
OBJECTIVE: Binding of Fas ligand or agonistic anti-Fas antibody to the death receptor Fas can activate a caspase-cascade resulting in apoptosis. In the present study, the functionality of the Fas pathway was studied in human cervical cancer cells with different HPV and p53 status. METHODS: HeLa (HPV-18 positive), CaSki, and SiHa (both HPV-16 positive) contain wild-type p53, while C33A (HPV negative) expresses mutant p53. Fas cell surface expression was determined by flow cytometry. Expression of proteins involved in the apoptotic pathway was analyzed by Western blotting and apoptosis was measured by acridine orange staining of nuclear chromatin. RESULTS: Despite high Fas membrane expression in the HPV-positive cells, CaSki was highly sensitive, HeLa slightly sensitive, and SiHa and C33A were resistant for agonistic anti-Fas antibody. Almost undetectable Fas membrane levels can explain the non-responsiveness of C33A for anti-Fas. Although interferon-gamma (IFNgamma) strongly and cisplatin to a lesser extend enhanced Fas membrane expression in all HPV-positive cells, sensitization to anti-Fas by IFNgamma or cisplatin was only observed in HeLa. Analysis of the Fas apoptotic pathway showed that anti-Fas treatment induced caspase-8 activation and concomitantly Bid cleavage, caspase-9 and caspase-3 activation, PARP cleavage and apoptosis in HeLa and CaSki. IFNgamma plus anti-Fas treatment, in contrast to anti-Fas alone, facilitated caspase-8 activation in HeLa and SiHa, while an increase in Bid cleavage, caspase-9 activation and apoptosis was only observed in HeLa. Apoptotic failure in SiHa (even in the presence of IFNgamma) was probably due to low caspase-8, almost undetectable Bid protein levels and therefore lack of caspase-9 activation. CONCLUSION: Sensitivity to anti-Fas depends on Fas, caspase-8, and Bid protein levels in cervical cancer cells. Additionally, IFNgamma and cisplatin can increase sensitivity to anti-Fas in a subset of HPV-positive cervical cancer cell lines by upregulation of Fas and caspase-8 expression without major changes in p53 levels.
Assuntos
Anticorpos Monoclonais/farmacologia , Apoptose/fisiologia , Proteínas de Transporte/biossíntese , Caspases/biossíntese , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Receptor fas/fisiologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3 , Caspase 8 , Caspases/metabolismo , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Terapia Combinada , Cicloeximida/farmacologia , Ativação Enzimática , Feminino , Citometria de Fluxo , Células HeLa , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Interferon gama/administração & dosagem , Interferon gama/farmacologia , Papillomaviridae , Infecções por Papillomavirus/metabolismo , Proteínas Recombinantes , Sensibilidade e Especificidade , Proteína Supressora de Tumor p53/fisiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Receptor fas/genética , Receptor fas/imunologiaRESUMO
Fas is a membrane protein belonging to the death receptor family. Cross-linking of Fas by its ligand, FasL, or agonistic anti-Fas antibodies, induces apoptosis of cells expressing Fas on the membrane by triggering a cascade of caspases. Since many different tumours express Fas on their membrane, targeting Fas-mediated apoptosis by anti-Fas antibodies may be a promising anticancer therapy. Unfortunately, not all Fas-expressing cells are sensitive to Fas-mediated apoptosis. This has resulted in the discovery of many different inhibition mechanisms of Fas-mediated apoptosis. In addition, mutations in the Fas or p53 gene can also influence the sensitivity for Fas-mediated apoptosis. However, the role of wild-type p53 in Fas expression is still controversial. Because several different cytotoxic drugs are able to induce Fas membrane expression, combination therapy of anticancer drugs with anti-Fas antibodies or FasL is conceivable as an anticancer strategy. The efficiency of the induction of Fas-mediated apoptosis by anti-Fas antibodies, FasL-expressing cells or recombinant FasL (rFasL) in tumours has been demonstrated in vivo in solid tumours implanted in mice. Unfortunately, systemic treatment with anti-Fas antibodies or rFasL causes severe damage to the liver, so most preclinical studies are now focusing on circumvention of this problem by local administration of FasL, or on the use of inducible FasL-expressing vectors as gene therapy.