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[PMID]: 28459074 [Au] Autor: Rosenthal KS; Stone S; Koski G; Zimmerman DH [Ad] Endereço: College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, NV 89135, USA. [Ti] Título: LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model. [So] Source: J Immunol Res;2017:3613505, 2017. [Is] ISSN: 2314-7156 [Cp] País de publicação: Egypt [La] Idioma: eng [Ab] Resumo: The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu H-2 CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human 2 microglobulin peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of J-HER one week after challenge with TUBO breast cancer cells limited the spread of the tumors and the morbidity and the mortality in the challenged mice. The ability to elicit responses that prevent spread of the TUBO tumor by J-HER suggests its utility as a neoimmunoadjuvant therapy to surgery. Individual or mixtures of J-LEAPS vaccines can be readily prepared to include different CD8 T cell epitopes to optimize tumor therapy and customize treatment for individuals with different HLA types. [Mh] Termos MeSH primário: Vacinas Anticâncer Neoplasias Mamárias Experimentais/prevenção & controle Neoplasias Mamárias Experimentais/terapia [Mh] Termos MeSH secundário: Animais Neoplasias da Mama/genética Neoplasias da Mama/imunologia Neoplasias da Mama/prevenção & controle Neoplasias da Mama/terapia Linfócitos T CD8-Positivos/imunologia Vacinas Anticâncer/genética Vacinas Anticâncer/imunologia Vacinas Anticâncer/uso terapêutico Linhagem Celular Tumoral Modelos Animais de Doenças Progressão da Doença Epitopos de Linfócito T/imunologia Feminino Genes erbB-2 Imunoglobulina G/sangue Neoplasias Mamárias Experimentais/imunologia Neoplasias Mamárias Experimentais/patologia Camundongos Camundongos Endogâmicos BALB C Metástase Neoplásica/prevenção & controle Estudo de Prova de Conceito Linfócitos T Citotóxicos/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cancer Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (Immunoglobulin G) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180208 [Lr] Data última revisão: 180208 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170502 [St] Status: MEDLINE [do] DOI: 10.1155/2017/3613505

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[PMID]: 28599900 [Au] Autor: Halle MK; Ojesina AI; Engerud H; Woie K; Tangen IL; Holst F; Høivik E; Kusonmano K; Haldorsen IS; Vintermyr OK; Trovik J; Bertelsen BI; Salvesen HB; Krakstad C [Ad] Endereço: Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Norway. [Ti] Título: Clinicopathologic and molecular markers in cervical carcinoma: a prospective cohort study. [So] Source: Am J Obstet Gynecol;217(4):432.e1-432.e17, 2017 Oct. [Is] ISSN: 1097-6868 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Cervical cancer is a major health problem worldwide. Identification of effective clinicopathologic and molecular markers is vital to improve treatment stratification. OBJECTIVES: The purpose of this study was to validate a set of well-defined clinicopathologic features in a large population-based, prospectively collected cervical cancer cohort to support their use in the clinic. Further, we explored p53 and human epidermal growth factor receptor 2 as potential prognostic markers in cervical cancer. STUDY DESIGN: Tissue was collected from 401 patients with cervical cancer. Clinical data that included follow-up evaluations were collected from patient journals. Histopathologic data were evaluated and revised by an expert pathologist. The prognostic impact of selected clinicopathologic variables was analyzed in the whole cohort. Tissue microarrays were prepared from 292 carcinomas, and p53 and human epidermal growth factor receptor 2 protein levels were evaluated by immunohistochemistry. Fresh frozen samples from overlapping cervical carcinomas previously were subjected to human papilloma virus typing (n=94), whole exome (n=100) and RNA (n=79) sequencing; the results were available for our analyses. RESULTS: Among the clinicopathologic variables, vascular space invasion, histologic type, and tumor size were verified as strong independent prognostic markers. High p53 protein levels were associated significantly with markers for aggressive phenotype and survival, also in multivariate survival analysis, but did not reflect TP53 mutational status. High human epidermal growth factor receptor 2 protein levels were identified in 21% of all tumors. ERBB2 amplification was associated with poor outcome (P=.003); human epidermal growth factor receptor 2 protein level was not. CONCLUSIONS: Our findings support that the Féderation Internationale de Gynécologie et d'Obstétrique s guidelines should include vascular space invasion and tumor size 2-4 cm and that careful selection of histologic type is essential for stratification of patient risk groups. High p53 levels independently predict poor survival yet do not reflect mutational status in cervical cancer. Amplified ERBB2 significantly links to poor survival, while HercepTest does not. With optimal stratification, human epidermal growth factor receptor 2-based therapy may improve cervical cancer treatment. [Mh] Termos MeSH primário: Neoplasias do Colo do Útero/genética Neoplasias do Colo do Útero/metabolismo [Mh] Termos MeSH secundário: Adulto Biomarcadores Tumorais/genética Biomarcadores Tumorais/metabolismo Carcinoma/genética Carcinoma/metabolismo Carcinoma/mortalidade Carcinoma/patologia Estudos de Coortes Feminino Deleção de Genes Genes erbB-2 Genes p53 Papillomavirus Humano 16/isolamento & purificação Papillomavirus Humano 18/isolamento & purificação Seres Humanos Imuno-Histoquímica Meia-Idade Mutação Invasividade Neoplásica Tumores Neuroendócrinos/genética Tumores Neuroendócrinos/metabolismo Tumores Neuroendócrinos/mortalidade Tumores Neuroendócrinos/patologia Prognóstico Receptor ErbB-2/metabolismo Análise de Sequência Análise Serial de Tecidos Proteína Supressora de Tumor p53/metabolismo Neoplasias do Colo do Útero/mortalidade Neoplasias do Colo do Útero/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE; VALIDATION STUDIES [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Tumor Suppressor Protein p53); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171002 [Lr] Data última revisão: 171002 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170611 [St] Status: MEDLINE

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[PMID]: 28595742 [Au] Autor: Ngo C; Laé M; Ratour J; Hamel F; Taris C; Caly M; Le Cunff A; Reyal F; Kirova Y; Pierga JY; Vincent-Salomon A [Ad] Endereço: Institut Curie, service d'anatomie et de cytologie pathologiques, 26, rue d'Ulm, 75005 Paris, France. Electronic address: carine2708@gmail.com. [Ti] Título: [Internal quality control on HER2 status determination in breast cancers: Experience of a cancer center]. [Ti] Título: Contrôle de qualité interne de la détermination du statut HER2 dans les cancers du sein : expérience d'un centre de lutte contre le cancer.. [So] Source: Bull Cancer;104(7-8):608-617, 2017 Jul - Aug. [Is] ISSN: 1769-6917 [Cp] País de publicação: France [La] Idioma: fre [Ab] Resumo: INTRODUCTION: The implementation of an internal quality control is mandatory to guarantee the accuracy of HER2 status in invasive breast cancers. OBJECTIVES: To evaluate the impact of our quality control assurance on HER2 status results in invasive breast carcinomas from 2008 to 2014. METHODS: HER2 status was determined by immunohistochemistry as the first-line indication, completed by fluorescence in situ hybridization (FISH) for scores 2+ by immunohistochemistry. Internal quality control of HER2 status relied on the standardization of pre-analytical phases, the use of external controls with a known number of HER2 gene copies determined by FISH and continued monitoring of concordance between immunohistochemistry and FISH. RESULTS: The proportion of HER2-positive cases corresponding to scores 3+ by immunohistochemistry and 2+ amplified by FISH varied from 10.6% to 13.8% (median of 11.3%). The proportion of scores 2+ amplified by FISH varied from 13.3% to 32.7% during period of study. The rate of concordance between FISH and immunohistochemistry for score 0/1+ and 3+ cases were≥97%. Eight among 12 discordant cases were false positive resulting from errors in interpretation of immunohistochemistry (score 2+ instead of 3+). DISCUSSION: Calibration of immunohistochemistry on FISH for HER2 status contributes to limit variability of immunohistochemistry results due to technical issues or interpretation. The implementation of an external control of score 3+ on each slide enables accurate interpretation of score 2+ and 3+ by immunohistochemistry. [Mh] Termos MeSH primário: Algoritmos Neoplasias da Mama/genética Carcinoma Ductal de Mama/genética Amplificação de Genes Genes erbB-2 Controle de Qualidade Receptor ErbB-2/análise [Mh] Termos MeSH secundário: Neoplasias da Mama/química Carcinoma Ductal de Mama/química Sistemas de Apoio a Decisões Clínicas Feminino Seres Humanos Imuno-Histoquímica/métodos Imuno-Histoquímica/normas Imuno-Histoquímica/estatística & dados numéricos Hibridização in Situ Fluorescente/métodos Hibridização in Situ Fluorescente/normas Hibridização in Situ Fluorescente/estatística & dados numéricos Receptor ErbB-2/metabolismo [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: EC 2.7.10.1 (Receptor, ErbB-2) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170815 [Lr] Data última revisão: 170815 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170610 [St] Status: MEDLINE

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[PMID]: 28570680 [Au] Autor: Wang XY; Hu Q; Fang MY; He Y; Wei HM; Chen XX; Zhang B [Ad] Endereço: Department of Ultrasound, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China. [Ti] Título: The correlation between HER-2 expression and the CEUS and ARFI characteristics of breast cancer. [So] Source: PLoS One;12(6):e0178692, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: The purpose of the present study was to explore the correlation between the contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) characteristics of breast cancers and the expression of human epidermal growth factor receptor 2 (HER-2). METHODS: HER-2 expression levels in the tumor masses of 167 clearly diagnosed cases of breast cancer were measured and analyzed. The enhancement features and time intensity curve (TIC) of CEUS and virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ) technology of ARFI were employed to analyze the relationship between HER-2 expression and the CEUS and ARFI characteristics of breast cancer. RESULTS: (1) Statistically significant differences in the distribution of the contrast agent, perforator blood flow, the overranging phenomenon and perfusion defects between the study groups with different HER-2 expression levels (P < 0.05) were observed on CEUS. In addition, statistically significant differences in the TIC peak time (PT), slope of the ascending branch (K) and area under the curve (AUC) were found in the groups expressing different levels of HER-2 (P < 0.05). In contrast, the degree of contrast agent enhancement and TIC peak intensity (PI) were found to be independent of the expression status of HER-2, as they were not statistically significant (P > 0.05). (2) Statistically significant differences in the VTQ results between the groups with different HER-2 expression levels were found (P < 0.05). However, no statistically significant differences in VTI image characteristics were detected between the groups expressing different levels of HER-2 (P > 0.05). CONCLUSION: A correlation was found between the CEUS and ARFI characteristics of breast cancer and HER-2 expression levels. This correlation was principally reflected in perfusion defects, perforator blood flow, PI, PT, K and VTQ. [Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo Genes erbB-2 [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Neoplasias da Mama/diagnóstico por imagem Neoplasias da Mama/genética Neoplasias da Mama/patologia Feminino Seres Humanos Meia-Idade Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170928 [Lr] Data última revisão: 170928 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170602 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0178692

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[PMID]: 28406988 [Au] Autor: Yang X; Wang Z; Xiang Z; Li D; Hu Z; Cui W; Geng L; Fang Q [Ad] Endereço: CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, China. [Ti] Título: Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2 positive tumor imaging. [So] Source: PLoS Comput Biol;13(4):e1005441, 2017 Apr. [Is] ISSN: 1553-7358 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a ß hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein. Combined the use of one-bead-one-compound library screening, among all the mutations, a peptide (58F63Y) with the lowest binding free energy was confirmed experimentally to have the highest affinity, and it may be used as a new probe in diagnosing and treating HER2-positive breast cancer. [Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/química Genes erbB-2 Sondas Moleculares Neoplasias/diagnóstico por imagem Peptídeos/química [Mh] Termos MeSH secundário: Sequência de Aminoácidos Animais Linhagem Celular Tumoral Xenoenxertos Seres Humanos Camundongos Camundongos Nus Simulação de Dinâmica Molecular Mutação Neoplasias/genética Homologia de Sequência de Aminoácidos Ressonância de Plasmônio de Superfície [Pt] Tipo de publicação: JOURNAL ARTICLE; VALIDATION STUDIES [Nm] Nome de substância: 0 (Antibodies, Monoclonal, Humanized); 0 (Molecular Probes); 0 (Peptides); K16AIQ8CTM (pertuzumab) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170504 [Lr] Data última revisão: 170504 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170414 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pcbi.1005441

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[PMID]: 28388952 [Au] Autor: Majid RA; Hassan HA; Muhealdeen DN; Mohammed HA; Hughson MD [Ad] Endereço: Department of Pathology, Shorsh General Hospital and the Hiwa Regional Oncology Center, Qirga Road, 46001, Sulaimaniyah, Kurdistan, Iraq. [Ti] Título: Breast cancer in Iraq is associated with a unimodally distributed predominance of luminal type B over luminal type A surrogates from young to old age. [So] Source: BMC Womens Health;17(1):27, 2017 Apr 07. [Is] ISSN: 1472-6874 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Breast cancer has recently increased in post-menopausal Iraqi women. In Western countries at high-risk for breast cancer, there is a bimodal increase in estrogen receptor (ER) positive tumors with a peak of low proliferation rate luminal A over higher proliferation rate luminal B tumors after 60 years of age. The aim of this study was to analyze in Iraqi women whether shifts are occurring in immunohistochemical (IHC) surrogates of molecular breast cancer subtypes toward a high-risk profile. METHODS: Age specific and age standardized womens breast cancer incidence was estimated for the years 2006 through 2012. IHC results of ER, PR, HER2, and Ki67 testing were analyzed on the breast cancers of 125 Arabic and 725 Kurdish women by frequency of distribution and by age. RESULTS: Between 2006 and 2012, age standardized incidence of breast cancer in Iraq increased from 30 to 40/100,000 women with the increase specifically occurring in women ≥ 60 years old (P < 0.001). Breast cancers in Kurdish women ≥ 60 years old may also have increased (P = 0.047) with urban exceeding rural rates by 2:1. For both Kurdish and Arabic women, there was a marked predominance of luminal B tumors at all ages in which luminal B and luminal A tumors were asymmetric skewed toward older age but with no late luminal A age peak. CONCLUSIONS: Older Iraqi women do not show the bimodal shift toward higher rates of luminal A breast cancers seen in the West. The modest increase in age standardized incidence of breast cancer in Iraqi is being seen specifically in older women and may be better attributed to a trend for care in urban cancer centers rather than changing tumor characteristics. [Mh] Termos MeSH primário: Neoplasias da Mama/classificação Neoplasias da Mama/genética Incidência [Mh] Termos MeSH secundário: Adulto Idoso Neoplasias da Mama/epidemiologia Feminino Genes erbB-2 Seres Humanos Iraque/epidemiologia Meia-Idade Gradação de Tumores Fenobarbital Receptores Estrogênicos/genética Sistema de Registros [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptors, Estrogen); YQE403BP4D (Phenobarbital) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170808 [Lr] Data última revisão: 170808 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170409 [St] Status: MEDLINE [do] DOI: 10.1186/s12905-017-0376-0

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[PMID]: 28318327 [Au] Autor: Turner BM; Hicks DG [Ad] Endereço: a Department of Pathology and Laboratory Medicine , University of Rochester Medical Center , Rochester , New York. [Ti] Título: Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward "precision" cancer therapy. [So] Source: Biotech Histochem;92(3):175-200, 2017. [Is] ISSN: 1473-7760 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: We present an updated account of breast cancer treatment and of progress toward "precision" cancer therapy; we focus on new developments in diagnostic molecular pathology and breast cancer that have emerged during the past 2 years. Increasing awareness of new prognostic and predictive methodologies, and introduction of next generation sequencing has increased understanding of both tumor biology and clinical behavior, which offers the possibility of more appropriate therapeutic choices. It remains unclear which of these testing methodologies provides the most informative and cost-effective actionable results for predictive and prognostic pathology. It is likely, however, that an integrated "step-wise" approach that uses the traditional clinical-pathologic paradigms coordinated with molecular characterization of breast tumor tissue, will offer the most comprehensive and cost-effective options for individualized, "precision" therapy for patients with breast cancer. [Mh] Termos MeSH primário: Biomarcadores Tumorais/análise Neoplasias da Mama/diagnóstico Neoplasias da Mama/terapia Medicina de Precisão [Mh] Termos MeSH secundário: Biomarcadores Tumorais/genética Neoplasias da Mama/patologia Receptor alfa de Estrogênio/genética Feminino Genes erbB-2/genética Sequenciamento de Nucleotídeos em Larga Escala Seres Humanos Imuno-Histoquímica/normas Imuno-Histoquímica/tendências Família Multigênica Receptores de Progesterona/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Estrogen Receptor alpha); 0 (Receptors, Progesterone); 0 (estrogen receptor alpha, human) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170515 [Lr] Data última revisão: 170515 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170321 [St] Status: MEDLINE [do] DOI: 10.1080/10520295.2017.1290276

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[PMID]: 28222158 [Au] Autor: Chan DL; Sjoquist KM; Goldstein D; Price TJ; Martin AJ; Bang YJ; Kang YK; Pavlakis N [Ad] Endereço: Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia. [Ti] Título: The effect of anti-angiogenic agents on overall survival in metastatic oesophago-gastric cancer: A systematic review and meta-analysis. [So] Source: PLoS One;12(2):e0172307, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Studies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed outcomes. We undertook systematic review and meta-analysis to determine their overall benefits and harms. METHODS: Randomized controlled trials in mOGC were sought investigating the addition of AAs to standard therapy (best supportive care or chemo). The primary endpoint was overall survival (OS) with secondary endpoints progression-free survival (PFS), overall response rate (ORR) and toxicity. Estimates of treatment effect from individual trials were combined using standard techniques. Subgroup analyses were performed by line of therapy, region, age, performance status, histological type, number of metastatic sites, primary site, mechanism of action and HER2 status. RESULTS: Fifteen trials evaluating 3502 patients were included in quantitative analysis. The addition of AAs was associated with improved OS: HR 0·81 (95% CI 0·75-0·88, p<0·00001) and improved PFS: HR 0·68 (95% CI 0·63-0·74, p<0·00001). Subgroup analyses favoured greater benefit for OS in 2nd/3rd line settings (HR 0·74) compared to 1st-line settings (HR 0·91) (X2 = 6·00, p = 0·01). OS benefit was seen across all regions-Asia (HR 0·83) and rest of world (HR 0·75)-without significant subgroup interaction. Results from 8 trials evaluating 2602 patients were pooled for toxicity > = Grade 3: with OR 1·39 (95% CI 1·17-1·65). CONCLUSIONS: The addition of AAs to standard therapy in mOGC improves OS. Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting. Consistent OS benefit was present across all geographical regions. This benefit is at the expense of increased overall toxicity. [Mh] Termos MeSH primário: Inibidores da Angiogênese/uso terapêutico Antineoplásicos/uso terapêutico Carcinoma/secundário Neoplasias Esofágicas/tratamento farmacológico Neoplasias Gástricas/tratamento farmacológico [Mh] Termos MeSH secundário: Inibidores da Angiogênese/efeitos adversos Antineoplásicos/efeitos adversos Carcinoma/tratamento farmacológico Carcinoma/genética Carcinoma/mortalidade Intervalo Livre de Doença Neoplasias Esofágicas/genética Neoplasias Esofágicas/mortalidade Genes erbB-2 Seres Humanos Viés de Publicação Qualidade de Vida Ensaios Clínicos Controlados Aleatórios como Assunto Neoplasias Gástricas/genética Neoplasias Gástricas/mortalidade Análise de Sobrevida Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; REVIEW [Nm] Nome de substância: 0 (Angiogenesis Inhibitors); 0 (Antineoplastic Agents) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170222 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0172307

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[PMID]: 28214007 [Au] Autor: Boudin L; Chabannon C; Sfumato P; Sabatier R; Bertucci F; Tarpin C; Provansal M; Houvenaeghel G; Lambaudie E; Tallet A; Resbeut M; Charafe-Jauffret E; Calmels B; Lemarie C; Boher JM; Extra JM; Viens P; Gonçalves A [Ad] Endereço: Institut Paoli-Calmettes (IPC), département d'oncologie médicale, 232, boulevard de Sainte-Marguerite, 13009 Marseille cedex 9, France. [Ti] Título: [Impact of Her2 and BRCA1/2 status in high-dose chemotherapy and autologous stem cells transplantation in the treatment of breast cancer: The Institut Paoli Calmettes' experience]. [Ti] Título: Expérience de l'institut Paoli-Calmettes concernant la chimiothérapie à haute dose et autogreffe de cellules souches hématopoïétiques pour la prise en charge des cancers mammaires : impact du statut Her2 et BRCA1/2.. [So] Source: Bull Cancer;104(4):332-343, 2017 Apr. [Is] ISSN: 1769-6917 [Cp] País de publicação: France [La] Idioma: fre [Ab] Resumo: INTRODUCTION: Studies evaluating chemotherapy high dose chemotherapy with autologous haematopoietic stem cell transplantation (HDC-ACSH) in the treatment of metastatic (MBC), locally advanced (LABC) and inflammatory (IBC) breast cancer have in common lack of biomarker information, in particular the HER2 status. PATIENTS AND METHODS: All consecutive female patients treated for breast cancer with HDC and AHSCT at Institut Paoli Calmettes between 2003 and 2012 were included. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: luminal, (HR+/HER2-), HER2 (HER2+, any HR) and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the IHC subtypes. RESULTS: Three hundred and seventy-seven patients were included. For MBC, the TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95 % CI 11.76-44.4) compared to 44.64 months (95 % CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (P<0.01). For IBC, HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89 % (95 % CI 64-97) compared to 57 % (95 % CI 33-76) for the TN subgroup (HR 5.38, 95 % CI 1.14-25.44; P=0.034). For CSLA, luminal subgroup appeared to have the best prognosis with a 5-year OS of 92 % (95 % CI 71-98) against 75 % (95 % CI 46-90) for HER 2 subtype and 70 % (95 %CI 97-88) for TN subtype (P=0.301). CONCLUSION: The HDC-ACSH does not change the prognosis value of IHC subtype in breast cancer patients. [Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem Neoplasias da Mama/mortalidade Genes BRCA1 Genes BRCA2 Genes erbB-2 Transplante de Células-Tronco Hematopoéticas [Mh] Termos MeSH secundário: Adulto Idoso Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Autoenxertos Neoplasias da Mama/tratamento farmacológico Neoplasias da Mama/patologia Neoplasias da Mama/cirurgia Institutos de Câncer Carcinoma/tratamento farmacológico Carcinoma/mortalidade Carcinoma/secundário Carcinoma/cirurgia Terapia Combinada/métodos Ciclofosfamida/administração & dosagem Feminino Seres Humanos Melfalan/administração & dosagem Meia-Idade Mitoxantrona/administração & dosagem Prognóstico Estudos Retrospectivos Tiotepa/administração & dosagem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 8N3DW7272P (Cyclophosphamide); 905Z5W3GKH (Thiotepa); BZ114NVM5P (Mitoxantrone); Q41OR9510P (Melphalan) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170421 [Lr] Data última revisão: 170421 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170219 [St] Status: MEDLINE

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[PMID]: 28152008 [Au] Autor: Takase Y; Usui K; Shimizu K; Kimura Y; Ichihara T; Ohkawa T; Atsumi J; Enokida Y; Nakazawa S; Obayashi K; Ohtaki Y; Nagashima T; Mitani Y; Takeyoshi I [Ad] Endereço: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. [Ti] Título: Highly sensitive detection of a HER2 12-base pair duplicated insertion mutation in lung cancer using the Eprobe-PCR method. [So] Source: PLoS One;12(2):e0171225, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Somatic mutation in human epidermal growth factor receptor-related 2 gene (HER2) is one of the driver mutations in lung cancer. HER2 mutations are found in about 2% of lung adenocarcinomas (ADCs). Previous reports have been based mainly on diagnostic screening by Sanger sequencing or next-generation sequencing (NGS); however, these methods are time-consuming and complicated. We developed a rapid, simple, sensitive mutation detection assay for detecting HER2 12 base pair-duplicated insertion mutation based on the Eprobe-mediated PCR method (Eprobe-PCR) and validated the sensitivity of this assay system for clinical diagnostics. We examined 635 tumor samples and analyzed HER2 mutations using the Eprobe-PCR method, NGS, and Sanger sequencing. In a serial dilution study, the Eprobe-PCR was able to detect mutant plasmid DNA when its concentration was reduced to 0.1% by mixing with wild-type DNA. We also confirmed amplification of the mutated plasmid DNA with only 10 copies per reaction. In ADCs, Eprobe-PCR detected the HER2 mutation in 2.02% (9/446), while Sanger sequencing detected it in 1.57% (7/446). Eprobe-PCR was able to detect the mutation in two samples that were undetectable by Sanger sequencing. All non-ADC samples were wild-type. There were no discrepancies between frozen and formalin-fixed paraffin-embedded tissues in the nine samples. HER2 mutations detected by NGS data validated the high sensitivity of the method. Therefore, this new technique can lead to precise molecular-targeted therapies. [Mh] Termos MeSH primário: Genes erbB-2/genética Neoplasias Pulmonares/genética Mutagênese Insercional/genética [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Feminino Sequenciamento de Nucleotídeos em Larga Escala/métodos Seres Humanos Masculino Meia-Idade Reação em Cadeia da Polimerase/métodos Reprodutibilidade dos Testes Sensibilidade e Especificidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170821 [Lr] Data última revisão: 170821 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170203 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0171225

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