Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ESMO Open ; 9(3): 102923, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452438

RESUMO

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Prognóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Biomarcadores Tumorais , Quimioterapia Adjuvante
2.
Fam Cancer ; 18(2): 193-196, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30560308

RESUMO

Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir-Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens' disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of a 33-year-old woman with LS and a proven MSH2 germline mutation, presenting with a SCC on the right cheek. Immunohistochemistry lacked MSH2 and MSH6 protein staining. The tumor showed a discordance between immunohistochemistry and micro-satellite instability status, for which a clear explanation cannot be provided yet. To conclude whether this pattern is indicative for SCC occurring in LS patients, further analyses of other LS patients presenting with SCC should be carried out. Our patient's young age and skin type (Fitzpatrick phototype VI) suggest a possible link between LS and cutaneous SCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteína 2 Homóloga a MutS/genética , Neoplasias Cutâneas/genética , Adulto , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Bochecha , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Feminino , Humanos , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
3.
Br J Cancer ; 112(8): 1358-66, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25871546

RESUMO

BACKGROUND: Human papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established. The objective of this study was to determine the prognostic significance of tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with SCCAC receiving (chemo)radiotherapy. METHODS: Human papillomavirus DNA was determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with locally advanced SCCAC. Patients were treated with radiotherapy, with or without concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C. Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11 of TP53 in tumour tissue were sequenced. RESULTS: DNA of high-risk HPV types was detected in 93 out of 107 tumours (87%), all of which overexpressed p16 (HPV+/p16+). Of 14 HPV-negative (HPV-) tumours (13%), 10 (9%) were p16-negative (HPV-/p16-) and 4 (4%) overexpressed p16 (HPV-/p16+). Patients with HPV-/p16- disease had inferior 3-year locoregional control (LRC) (15%) compared with patients with HPV+/p16+ tumours (82%, P<0.001) and HPV-/p16+ tumours (75%, P=0.078). Similarly, 3-year overall survival (OS) was 35% (HPV-/p16-) vs 87% (HPV+/p16+, P<0.001) and 75% (HPV-/p16+, P=0.219). Disruptive mutations in TP53 were found in 80% of HPV-/p16- tumours vs 6% of HPV+/p16+ tumours (P<0.001). In multivariate analysis, HPV-/p16- status was an independent predictor of inferior LRC and OS. CONCLUSIONS: HPV- tumours are frequently TP53 mutated. HPV-/p16- status is a strong predictor for reduced LRC and OS, and alternative treatment strategies for patients with HPV-/p16- disease need to be explored.


Assuntos
Alphapapillomavirus/isolamento & purificação , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/classificação , Neoplasias do Ânus/genética , Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Tratamento Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Radioterapia , Resultado do Tratamento
4.
Mol Genet Metab ; 91(1): 1-6, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17336114

RESUMO

Guanidinoacetate methyltransferase (GAMT) deficiency (MIM 601240), an autosomal recessive disorder of creatine biosynthesis, presents with mental retardation, extrapyramidal symptoms, autistic-like behavior and epilepsy. Other hallmarks are cerebral creatine deficiency, increased levels of guanidinoacetate in body fluids and mutations in the GAMT gene. Creatine supplementation partially restores cerebral creatine content. Worldwide, 29 patients have been identified and 15 different mutations have been reported in the GAMT gene. Ten out of these 29 patients are of Portuguese origin. Likely, a founder effect and a high carrier rate in Portugal exist, since in 17 out of the 20 Portuguese alleles the c.59G>C; p.Trp20Ser mutation was found. We investigated the carrier rate of the c.59G>C; p.Trp20Ser mutation in different regions of Portugal and confirmed the pathogenic nature of this missense mutation by transient transfections. Anonymous bloodspots (1002) were screened for the presence of the c.59G>C; p.Trp20Ser mutation by SNaPshot (Single Nucleotide Polymorphism Multiplex Kit). Eight carriers of c.59G>C; p.Trp20Ser were detected of which four are derived from the Archipelagos. This suggests that the carrier rate of the c.59G>C; p.Trp20Ser mutation is relatively high in these islands, as well as in other parts of Portugal. It also implies that newborn screening in these regions is warranted for this treatable disorder.


Assuntos
Guanidinoacetato N-Metiltransferase/genética , Mutação de Sentido Incorreto , Sequência de Aminoácidos , Sequência de Bases , Análise Mutacional de DNA , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/genética , Geografia , Guanidinoacetato N-Metiltransferase/deficiência , Células HeLa , Humanos , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Portugal , Prevalência , Alinhamento de Sequência , Serina/genética , Serina/metabolismo , Transfecção , Triptofano/genética , Triptofano/metabolismo
5.
Mol Genet Metab ; 89(4): 392-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16899382

RESUMO

Guanidinoacetate methyltransferase deficiency (MIM 601240) is an autosomal recessive disorder of creatine biosynthesis. Patients present with mental retardation, extrapyramidal symptoms, autistic-like behavior, epilepsy, cerebral creatine deficiency and increased levels of guanidinoacetate. So far 15 mutations have been reported, including six missense variants that are highly likely to be pathogenic mutations. To prove that mutations in the GAMT gene are responsible for GAMT deficiency we overexpressed the GAMT open reading frame in GAMT-deficient fibroblasts by stable transfection. In addition, HeLa cells were transiently transfected with the same expression vector. In contrast to mock transfectants transfection of primary GAMT-deficient fibroblasts with wild-type GAMT results in the restoration of GAMT activity as measured by GC-MS using stable isotope labeled substrates. Moreover, the expression of the GAMT-EGFP fusion protein was analyzed by Western blot, confirming the presence of GAMT fusion protein, both in the stable as well as in the transient transfectants. Here, we prove that mutations in the GAMT gene are responsible for GAMT deficiency, since overexpression of the GAMT open reading frame restores GAMT activity in GAMT-deficient fibroblasts. Furthermore, the transient transfection of HeLa cells will be important for functional analysis of variants of unknown consequence (i.e., missense mutations).


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Creatina/deficiência , Guanidinoacetato N-Metiltransferase/deficiência , Guanidinoacetato N-Metiltransferase/genética , Fibroblastos/enzimologia , Células HeLa , Humanos , Mutação , Transfecção
7.
Genes Chromosomes Cancer ; 31(3): 274-81, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11391798

RESUMO

Hereditary paragangliomas or glomus tumors are usually benign slow-growing tumors in the head and neck region. The inheritance pattern of hereditary paraganglioma is autosomal dominant with imprinting. Recently, we have identified the SDHD gene encoding subunit D of the mitochondrial respiratory chain complex II as one of the genes involved in hereditary paragangliomas. Here, we demonstrate that two founder mutations, Asp92Tyr and Leu139Pro, are responsible for paragangliomas in 24 and 6 of the 32 independently ascertained Dutch paraganglioma families, respectively. These two mutations were also detected among 20 of 55 isolated patients. Ten of the isolated patients had multiple paragangliomas, and in eight of these SDHD germline mutations were found, indicating that multicentricity is a strong predictive factor for the hereditary nature of the disorder in isolated patients. In addition, we demonstrate that the maternally derived wild-type SDHD allele is lost in tumors from mutation-carrying patients, indicating that SDHD functions as a tumor suppressor gene.


Assuntos
Efeito Fundador , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/genética , Complexos Multienzimáticos/genética , Mutação/genética , Oxirredutases/genética , Paraganglioma/enzimologia , Paraganglioma/genética , Succinato Desidrogenase/genética , Análise Mutacional de DNA , Complexo II de Transporte de Elétrons , Heterogeneidade Genética , Humanos , Perda de Heterozigosidade/genética
10.
J Psychol ; 112(2d Half): 245-50, 1982 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7175766

RESUMO

Attempts to clarify structural differentiations in human experience and, more relevantly, in psychotherapy, have been many. These clarifications have depended, in part, on examining the limits of what is abstract in specific experiential areas. Personal history has often been structurally delineated and used as an apparently nonabstract vehicle for describing the patient, the therapist, and as a basis for communicating an understanding of the therapeutic encounter. This paper examines the concept of personal history as one example of a kind of abstraction that suggests communicative understanding when in fact it is often only the maintenance of an illusion.


Assuntos
Comunicação , Relações Profissional-Paciente , Psicoterapia/métodos , Humanos , Acontecimentos que Mudam a Vida
13.
Med Educ ; 13(5): 329-35, 1979 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-522683

RESUMO

Attitudes of first year Israeli Medical School students are investigated using the Semantic Differential technique to differentiate their perceptions of the roles of doctor, patient and the mentally ill. Students also selected from among thirty-four behavioural traits those roles considered most characteristic of doctor and/or patient. A high degree of certainty and of role stereotyping is found of doctor image. This may be associated with past experiences as child-patient, with idealizations and identifications and with future aspirations. There is less consensus with the role of patient but there are clear attitudinal boundaries among students between roles. The doctor is perceived as an idealized, if authoritarian, person meeting with a rather negatively but more flexibly perceived person of the patient. Behavioural traits selected by the students are consonant with this finding. The results are discussed in the context of identification patterns and the educational process.


Assuntos
Transtornos Mentais , Pacientes , Papel do Médico , Papel (figurativo) , Percepção Social , Estudantes de Medicina , Adulto , Humanos , Israel
14.
Am J Psychother ; 30(3): 452-62, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-970506

RESUMO

Gossip, a phenomenon as old as history itself, is reflected upon in terms of its need-fulfilling functions for persons and social groups. It is seen as one of the sources of knowledge about life that has potentials for wisdom, and its interpersonal and intrapsychic functions are shown to have similarities to many salient functions of psychotherapy.


Assuntos
Comunicação , Psicoterapia , Biografias como Assunto , Empatia , Humanos , Relações Interpessoais , Ciúme , Estilo de Vida , Relações Profissional-Paciente , Ciência , Autoimagem , Autorrevelação , Isolamento Social , Comportamento Verbal , Voyeurismo
15.
Can Med Assoc J ; 111(12): 1323-4, 1974 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-4442017

RESUMO

In two patients with bilateral parotid gland swelling of unknown etiology the diagnosis of sarcoidosis was established by lip biopsy of the minor salivary glands. This simple, innocuous biopsy procedure may prove useful in tissue documentation of sarcoidosis.


Assuntos
Lábio/patologia , Glândulas Salivares/patologia , Sarcoidose/diagnóstico , Adulto , Biópsia/métodos , Humanos , Masculino , Parotidite , Radiografia Torácica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...