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1.
Int J Mol Sci ; 24(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37445737

RESUMO

There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Seleção de Pacientes , Hiperplasia/patologia , Mama/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Desenvolvimento de Medicamentos , Proteínas Proto-Oncogênicas , Proteínas de Homeodomínio
2.
J Cancer Educ ; 30(4): 736-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25417824

RESUMO

Skin cancer is the most common cancer in the USA and is increasing in children and young adults. Adolescents are an important target population for sun-safety interventions with ultraviolet radiation as the strongest risk factor for developing skin cancer. Schools are an ideal setting to intervene with adolescents. A novel Arizona skin cancer prevention in-class education-activity program, Project 'Students are Sun Safe' (SASS), was designed to be delivered by university students for middle school and high school students. Participant students completed the pre- and post-program tests and a satisfaction questionnaire; teachers completed reviews. The evaluation examined the program's influence on participants' sun-safety knowledge, perceptions, and behaviors; satisfaction with the program; and intent to change. After exposure to Project SASS, participants were more likely to perceive a high risk of skin cancer, report negative attitudes toward tanned skin, and answer knowledge-based questions correctly. There were minimal differences in self-reported sun-safety behaviors, though participants did report intent to change. Both participants and teachers were satisfied with the program. Project SASS appears to be an effective sun-safety program for middle school and high school students for knowledge and perceptions, and the results confirm that appropriately tailoring program components to the target population has strong potential to impact adolescent perceived susceptibility, knowledge, and behavioral intent. The strengths and weaknesses of Project SASS have many implications for public health practice, and Project SASS may hold promise to be a model for skin cancer prevention in adolescents.


Assuntos
Comportamentos Relacionados com a Saúde , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde Escolar/normas , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Fatores de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/psicologia , Estudantes , Universidades , Adulto Jovem
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