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1.
Anticancer Res ; 40(1): 27-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892550

RESUMO

BACKGROUND/AIM: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. MATERIALS AND METHODS: A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. CONCLUSION: IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.


Assuntos
Afro-Americanos/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias da Próstata/etiologia , Fumar/efeitos adversos , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
2.
Cancer Genomics Proteomics ; 16(4): 245-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31243105

RESUMO

BACKGROUND/AIM: Vitamin D receptor (VDR) is present in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to prostate cancer. Also, analyses of single nucleotide polymorphisms (SNPs) in VDR revealed ethnicity-associated polymorphisms. The aim of this study was to identify VDR SNPs in African American men with and without prostate cancer. MATERIALS AND METHODS: The entire VDR gene was screened for germline mutations in a case-control study by denaturing high performance liquid chromatography and DNA sequencing. Logistic regression was used to estimate the association of SNPs, age, family history, and Gleason score with prostate cancer risk. RESULTS: Six SNPs in the non-coding regions, and one SNP in the coding region, were detected. SNP 1 (c.278-69G>A) and SNP 4 (c.907+75C>T) have not been previously reported. SNP 4 had a significant protective effect (ß=-0.6, p<0.05); whereas, SNP 7 (rs7975232) showed an increase association with prostate cancer risk and high Gleason score (ß=0.32, p<0.05). SNP 4, SNP 7 and age were better predictors of prostate cancer risk than family history with a high degree of sensitivity (74.7%) and specificity (92.4%). CONCLUSION: SNP 4 and SNP 7 could be promising markers for prediction of reduced or increased prostate cancer risk, respectively.


Assuntos
Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Receptores de Calcitriol/genética , Afro-Americanos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
3.
PLoS One ; 13(9): e0203322, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30204798

RESUMO

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARß2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated. Six genes tested achieved significant difference in DNA methylation levels between the PCa compared to control cases (P < 0.05). The TIMP3 loci demonstrated significant correlation of DNA methylation with age for all cases analyzed (p < 0.05). We observed an inverse correlation between CDH13 methylation (p = 0.045; r = -0.21) and serum vitamin D level whereas TIMP3 methylation (p = 0.021; r = -0.24) and DRD2 methylation (p = 0.056; r = -0.201) showed inverse correlation with supplementary vitamin D in the cancer cases. We also observed a direct correlation between methylation of RARß2 (p = 0.0036; r = 0.293) and SPARC (p = 0.0134; r = 0.20) loci with PSA level in the controls but not the cancer cases. In addition, alcohol cases significantly correlated with higher RARß2 methylation (p = 0.0314) in comparison with non-alcohol cases. Furthermore, we observed an inverse correlation of DRD2 methylation (p = 0.0349; r = -0.343) and Gleason score. Our data suggests that promoter methylation occurred more frequently in the blood of AA PCa and is associated with various clinicopathological features in AA men with PCa.


Assuntos
Afro-Americanos/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Metilação de DNA , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Adulto , Idoso , Caderinas/genética , Estudos de Casos e Controles , Citocinas/genética , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Osteonectina/genética , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Receptores de Dopamina D2/genética , Receptores do Ácido Retinoico/genética , Fatores de Risco , Inibidor Tecidual de Metaloproteinase-3/genética , Proteínas Supressoras de Tumor/genética , Vitamina D/sangue
4.
ACS Sens ; 3(8): 1510-1521, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-29979037

RESUMO

A high-throughput multiconstriction microfluidic channels device can distinguish human breast cancer cell lines (MDA-MB-231, HCC-1806, MCF-7) from immortalized breast cells (MCF-10A) with a confidence level of ∼81-85% at a rate of 50-70 cells/min based on velocity increment differences through multiconstriction channels aligned in series. The results are likely related to the deformability differences between nonmalignant and malignant breast cells. The data were analyzed by the methods/algorithms of Ridge, nonnegative garrote on kernel machine (NGK), and Lasso using high-dimensional variables, including the cell sizes, velocities, and velocity increments. In kernel learning based methods, the prediction values of 10-fold cross-validations are used to represent the difference between two groups of data, where a value of 100% indicates the two groups are completely distinct and identifiable. The prediction value is used to represent the difference between two groups using the established algorithm classifier from high-dimensional variables. These methods were applied to heterogeneous cell populations prepared using primary tumor and adjacent normal tissue obtained from two patients. Primary breast cancer cells were distinguished from patient-matched adjacent normal cells with a prediction ratio of 70.07%-75.96% by the NGK method. Thus, this high-throughput multiconstriction microfluidic device together with the kernel learning method can be used to perturb and analyze the biomechanical status of cells obtained from small primary tumor biopsy samples. The resultant biomechanical velocity signatures identify malignancy and provide a new marker for evaluation in risk assessment.


Assuntos
Neoplasias da Mama/diagnóstico , Aprendizado de Máquina , Microfluídica/métodos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Tamanho Celular , Feminino , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação
5.
Ann Diagn Pathol ; 34: 170-174, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29715580

RESUMO

OBJECTIVES: Proteins p27 and c-Myc are both key players in the cell cycle. While p27, a tumor suppressor, inhibits progression from G1 to S phase, c-Myc, a proto-oncogene, plays a key role in cell cycle regulation and apoptosis. The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 AA women. Five micrometer sections were stained with a mouse monoclonal antibody against p27 and a rabbit monoclonal antibody against c-Myc. The sections were evaluated for intensity of nuclear reactivity (1-3) and percentage of reactive cells; an H-score was derived from the product of these measurements. RESULTS: Loss of p27 expression and c-Myc overexpression showed statistical significance with ER negative (p < 0.0001), PR negative (p < 0.0001), triple negative (TN) (p < 0.0001), grade 3 (p = 0.038), and overall survival (p = 0.047). There was no statistical significant association between c-Myc expression/p27 loss and luminal A/B and Her2 overexpressing subtypes. CONCLUSION: In our study, a statistically significant association between c-Myc expression and p27 loss and the triple negative breast cancers (TNBC) was found in AA women. A recent study found that constitutive c-Myc expression is associated with inactivation of the axin 1 tumor suppressor gene. p27 inhibits cyclin dependent kinase2/cyclin A/E complex formation. Axin 1 and CDK inhibitors may represent possible therapeutic targets for TNBC.


Assuntos
Carcinoma Ductal de Mama/metabolismo , Ciclinas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Anticorpos Monoclonais , Carcinoma Ductal de Mama/patologia , Ciclo Celular , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Coelhos , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
6.
Cancer Genomics Proteomics ; 15(3): 185-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29695400

RESUMO

BACKGROUND/AIM: Prostate cancer is the most common malignancy in US males. African American men have higher incidence and mortality rates than European Americans. Five single nucleotide polymorphisms are associated with PCa. We hypothesized haplotypes inferred from these SNPs are also associated with PCa. PATIENTS AND METHODS: We genotyped SNPs in a case-control admixture mapping study. SNP haplotypes inferred for 157 PCa cases and 150 controls were used in the regression analysis. RESULTS: We found an association between "GTCCC", "ATTCT", and "ACCCC" haplotypes and PCa after ancestry adjustment (OR=3.62, 95%CI=1.42-9.21, p=0.0070; OR=7.89, 95%CI=2.36-26.31, p=0.0008; OR=4.34, 95%CI=1.75-10.78, p=0.0016). The rs615382 variant disrupts the recombination signal binding protein with immunoglobulin kappa J binding site in Rac GTPase activating protein 1 (RACGAP1). CONCLUSION: Disruption of notch 1 mediated-repression of RACGAP1 may contribute to PCa in African Americans.


Assuntos
Afro-Americanos/genética , Mapeamento Cromossômico/métodos , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Receptor Notch1/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/patologia
7.
Pathol Res Pract ; 214(5): 673-678, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29653745

RESUMO

INTRODUCTION: PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). RESULTS: Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. CONCLUSION: In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.


Assuntos
Carcinoma Ductal de Mama/patologia , PTEN Fosfo-Hidrolase/genética , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Afro-Americanos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
8.
J Health Care Poor Underserved ; 29(1): 509-529, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503315

RESUMO

The aim of this study was to determine the impact of race and socioeconomic status on breast tumor clinicopathological features and survival outcomes. This study used breast cancer data from the Washington D.C. Cancer Registry (2000- 2010). Logistic regression and survival analysis assessed the association between race, socioeconomic (SES) variables, clinicopathological variables, recurrence-free survival and overall survival. African American (AA) breast cancer patients had an increased risk for stage III, ER-, and PR-breast cancer compared with White and Hispanic breast cancer patients. Additionally, D.C. geographical areas of lower socioeconomic status had higher incidences of stage III and stage IV breast cancer. A nested analysis demonstrated that AAs with higher median incomes compared with AAs with lower incomes revealed no differences for clinicopathological variables, nor were differences found between overall and recurrence-free survival. This study suggests that the biology of breast cancer in AAs could be driving breast cancer disparities.


Assuntos
Afro-Americanos/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/terapia , Classe Social , Idoso , Neoplasias da Mama/patologia , District of Columbia/epidemiologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Análise de Sobrevida , Resultado do Tratamento
9.
BMC Cancer ; 18(1): 274, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523126

RESUMO

BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling. RESULTS: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4). CONCLUSIONS: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.


Assuntos
Afro-Americanos/genética , Neoplasias da Mama/genética , Amplificação de Genes , Proteínas Proto-Oncogênicas c-myc/genética , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
10.
Cancer Genomics Proteomics ; 14(6): 461-467, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29109096

RESUMO

BACKGROUND/AIM: Denaturing high-performance liquid chromatography (DHPLC) is a technique that is used to detect mutations. The aim of the present study was to determine whether DHPLC elution patterns of vitamin D receptor (VDR) gene PCR products can serve as indicators of susceptibility to prostate cancer (PCa) risk. MATERIALS AND METHODS: DNA samples of PCa cases and controls were screened for mutations and/or polymorphisms in coding exons of VDR gene using DHPLC analysis. Logistic regression, phi-coefficient (ϕ), and Backward Wald models were used to analyze the data. RESULTS: Similar elution patterns of exons 1, 6, 7 and 9 along with higher prevalence of heteroduplex DNA were observed in PCa samples than in controls. Exons 4 and 8 had highly significant protective effects (p<0.05). Whereas, exons 5, 7, and 9 were perfectly positively correlated with PCa risk (ϕ=1), thus presenting candidate exons significantly associated with susceptibility to PCa. CONCLUSION: DHPLC elution patterns of the selected exons could be useful to predict susceptibility to develop PCa.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Reação em Cadeia da Polimerase/métodos , Receptores de Calcitriol/genética , Adulto , Afro-Americanos , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
11.
In Vivo ; 31(4): 661-668, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652435

RESUMO

BACKGROUND/AIMS: Breast cancer (BCa) prognostication is a vital element for providing effective treatment for patients with BCa. Studies suggest that ethnicity plays a greater role in the incidence and poor prognosis of BCa in younger women than in their older counterparts. Therefore, the goal of this study was to assess the association between age and ethnicity on the overall final prognosis. MATERIALS AND METHODS: Nottingham Prognostic Index (NPI) was used to analyze BCa prognosis using Howard University Cancer Center Tumor Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results BCa datasets. Patients were grouped according to their predicted prognosis based on NPI scheme. RESULTS: There was no correlation between the younger patients compared to their older counterparts for any of the prognostic clusters. The significance of ethnicity in poorer prognosis for younger age is not conclusive either. CONCLUSION: An extended prognostic tool/system needs to be evaluated for its usefulness in a clinical practice environment.


Assuntos
Fatores Etários , Neoplasias da Mama/epidemiologia , Grupos Étnicos , Prognóstico , Adulto , Afro-Americanos , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
12.
Ethn Dis ; 27(2): 169-178, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439188

RESUMO

BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants. RESULTS: Using next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). CONCLUSIONS: Knowing a patient's BRCA mutation status is important for prevention and treatment decision-making. Improving the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Americans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies.


Assuntos
Afro-Americanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , DNA de Neoplasias/genética , Mutação , Adulto , Idade de Início , Alelos , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Neoplasias da Mama/etnologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
13.
Clin Breast Cancer ; 17(3): 232-238, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28189497

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) tumors are estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor-negative. TNBC is responsive to chemotherapy, but chemotherapy might be underused in some patient subgroups. The goal of the present study was to characterize the patterns of chemotherapy use (uptake and completion) in TNBC patients. PATIENTS AND METHODS: Women with primary invasive, nonmetastatic breast cancer were recruited in Washington, DC, and Detroit. Data were collected using a standardized telephone survey that captured sociocultural and health care process factors. Clinical data were abstracted from the medical records. We used χ2 tests to access the association between the receipt of chemotherapy use (initiation and completion) and categorical variables, and t tests were used for continuous variables. Logistic regression models were used to evaluate the factors associated with chemotherapy uptake. RESULTS: Women with TNBC (16% of sample) were more likely to be black than white (68% vs. 32%; P < .05). Among women with TNBC, 60% underwent chemotherapy. Chemotherapy uptake was greater for black than for white women (48.3% vs. 11.7%; P = .01) and in women without (vs. with) healthcare discrimination (35% vs. 25%; P = .04). In multivariable models, only race was associated with the receipt of chemotherapy. Black women were more likely to receive chemotherapy than were white women. The odds ratio of receiving chemotherapy by race was 4.1 (95% confidence interval, 1.3-13.1). Each 1-year increase in age was associated with a lower likelihood of chemotherapy completion (odds ratio, 0.9; 95% confidence interval, 0.826-0.981; P = .02). Women with at least some college were less likely to complete chemotherapy than were those with other education levels (P = .02). CONCLUSION: A substantial number of TNBC patients failed to receive and/or complete chemotherapy. Differences in chemotherapy uptake by race and sociocultural factors diminished in multivariable models but age and stage remained significant. Suboptimal treatment among women with TNBC could contribute to adverse outcomes. Future investigations are necessary to assess whether the noninitiation and/or noncompletion of chemotherapy is clinically warranted.


Assuntos
Afro-Americanos/estatística & dados numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Neoplasias de Mama Triplo Negativas/etnologia , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
14.
Anticancer Res ; 35(9): 4723-32, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26254362

RESUMO

BACKGROUND/AIM: Prostate cancer is one of the leading causes of death in American males. Emetine, a naturally-derived alkaloid from the Ipecacuanha plant, has been shown to have potential for anti-tumorigenic effects for cancer treatments. The objective of this study was to characterize novel emetine dithiocarbamate (EMTDTC) analogs for potent anti-tumorigenic activity with minimal toxicity to normal prostate cells and identify targeted apoptotic regulatory genes. The leading key compounds, EMTDTC-55 and EMTDTC-56 were studied. MATERIALS AND METHODS: Established methods of cell flow cytometry were used to analyze apoptotic potential in prostate cancer cell lines (DU145, PC3 and LNCaP) and real time-polymerase chain reaction (PCR) for identifying key genes mediating apoptosis. RESULTS: The effect of EMTDTC-55 on DU145, LNCaP and PC3 revealed significant anti-tumorigenic activities. Both compounds showed highly significant apoptotic potential on days 3 and 5 in the prostate cancer cells. Key apoptotic genes were differentially regulated suggestive of cell-cycle arrest and apoptotic induction in androgen-independent cell lines, DU145 and PC3, by both compounds. However, in the androgen-dependent cell line LNCaP, cells were marginally affected by EMTDTC-55, but significant apoptosis was observed by EMTDTC-56 leading to cell-cycle arrest. CONCLUSION: Both dithiocarbamate compounds EMTDTC-55 and EMTDTC-56 have significant chemotherapeutic potential in moderately metastatic DU145 and highly metastatic PC3 cells.


Assuntos
Apoptose/efeitos dos fármacos , Ditiocarb/análogos & derivados , Ditiocarb/farmacologia , Emetina/farmacologia , Neoplasias da Próstata/patologia , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/genética
15.
Anticancer Res ; 35(7): 3811-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26124326

RESUMO

BACKGROUND/AIM: Several studies reported that patients with benign prostatic hyperplasia (BPH) experienced a 10% increased incidence of prostate cancer (PCa) after the first 5 years of diagnosis. We investigated the association between single nucleotide polymorphisms (SNPs) in the promoter of Serine Protease Inhibitor Kazal Type 1 (SPINK1) and the increased risk of BPH and PCa. MATERIALS AND METHODS: We genotyped three SNPs in a cases-control study, including BPH and PCa cases. Multiple logistic regression models were applied to analyze clinical and genotypic data. RESULTS: We found an inverse association between SNP rs10035432 and BPH under the log-additive (p=0.007) model. No association was found between these SNPs and PCa risk. However, we observed a possible association between rs1432982 and lower-grade PCa (p=0.05) under the recessive model. CONCLUSION: SPINK1 promoter variants are likely to be associated with the risk of BPH.


Assuntos
Proteínas de Transporte/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/genética , Risco , Inibidor da Tripsina Pancreática de Kazal
16.
Anticancer Res ; 35(3): 1549-58, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25750310

RESUMO

BACKGROUND/AIM: Several studies have revealed an association between single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer (PCa) risk in European and Asian populations. To investigate whether VDR SNPs are associated with PCa risk in African-American (AA) men, nine VDR SNPs were analyzed in a case-control study. MATERIALS AND METHODS: Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs731236 and rs7975232 were significantly associated with PCa risk (p<0.05). In the analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly associated with high PSA level (p<0.05), whereas rs1544410 and rs2239185 showed a statistically significant association with high Gleason score (p<0.05). Haplotype analysis revealed several VDR haplotypes associated with PCa risk. Additionally, a trend existed, where as the number of risk alleles increased in the haplotype, the greater was the association with risk (p-trend=0.01). CONCLUSION: These results suggest that the VDR SNPs may be associated with PCa risk and other clinical phenotypes of PCa in AA men.


Assuntos
Afro-Americanos/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Receptores de Calcitriol/genética , Idoso , Estudos de Casos e Controles , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Risco
17.
Anticancer Res ; 35(3): 1453-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25750297

RESUMO

BACKGROUND/AIM: Roots of Fagara zanthoxyloides and Pseudocedrela kotchyii are used as chewing sticks and as medicinal remedies for diarrhea, cough and fever in West Africa. Extracts of the two plants also possess anti-bacterial, anti-fungal and anti-malarial activities. The aim of the present study was to determine the effects of such extracts on the growth, proliferation and induction of apoptosis in four prostate cancer cell lines. Materials and Methods. Androgen-independent PC3 and DU-145 and androgen-dependent LNCaP and CWR-22 prostate cancer cell lines were cultured for five days with different concentrations of the extracts and examined for growth inhibition and evidence of apoptosis. RESULTS: Irrespective of their androgen dependence, all four cancer cell lines exhibited a dose-dependent decrease in cell proliferation and viability by the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay and in induction of apoptosis. The results also show that LNCap cells were the most sensitive to the two extracts, with highest inhibition at day 3 and exhibiting the highest rate of apoptosis. Conclusion. These observations suggest that F. zanthoxyloides and P. kotchyii could serve as potential chemopreventive agents in the treatment of prostate cancer.


Assuntos
Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Zanthoxylum , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Fitoterapia , Raízes de Plantas , Neoplasias da Próstata/patologia
18.
Cancer Genomics Proteomics ; 11(6): 279-94, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25422359

RESUMO

Expression of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) can subdivide breast carcinomas into clinically meaningful classes. Cancers lacking expression of all three of these receptors (triple-negative breast cancer; TNBC) is of particular interest for molecular research because these tumors currently have no effective targets for therapy. Furthermore, TNBCs are relatively more prevalent among African-American women and can account for some of the health disparities associated with breast cancer. We approached a molecular understanding of how TNBC differs from ER(+) breast cancer through a comprehensive gas chromatography (GC)-mass spectrometry (MS) and liquid chromatography (LC)/MS/MS-based and unbiased metabolomic analysis of a series of breast carcinomas from African-American patients. Remarkably, global metabolomic profiling of tumor tissues identified a total of 418 distinct metabolites, out of which 133 (31.8%) were shown to differ between the ER(+) and TNBC tumors with statistical probability of p<0.05. Specific biochemical pathways affected included those reflecting general increases in energy metabolism and transmethylation in the TNBC tumors when compared to ER(+) tumors. Additionally, biochemicals associated with increased proliferation, redox balance and the recently proposed oncometabolites, sarcosine and 2-hydroxyglutarate, were also detected at higher levels in the TNBC versus ER(+) tumors. These studies demonstrate that TNBC tumors have metabolic signatures that distinguish them from ER(+) tumors and suggest that distinctive metabolic characteristics of these tumors might offer new targets for treatment.


Assuntos
Afro-Americanos , Biomarcadores Tumorais/metabolismo , Metabolômica/métodos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Aminoácidos/metabolismo , Dipeptídeos/metabolismo , Metabolismo Energético , Feminino , Glutationa/metabolismo , Humanos , Redes e Vias Metabólicas , Metaboloma , Metilação , Pessoa de Meia-Idade , NAD/metabolismo , Invasividade Neoplásica , Oxirredução
19.
In Vivo ; 28(6): 1181-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25398820

RESUMO

BACKGROUND/AIM: Vitamin D deficiency in African-Americans is common due to the high melanin content of the skin that reduces the absorption of UV radiation. To determine if there is a correlation between UV exposure, tanning potential and vitamin D with prostate cancer (PC) risk, we conducted a case-control study of 183 African-American men aged 40 years and older residing in the Washington, DC area. PATIENTS AND METHODS: PC status was described as a binary variable as the presence or absence of cancer and the environmental factors as continuous variables. We used a logistic regression model describing PC as the response, while age, tanning potential, sunlight and vitamin D were treated as the predictors. RESULTS: Men aged 60 years and older had a seven-fold increased risk for developing PC compared to those aged 50 years and less (p<0.003). Tanning potential was a significant (p=0.05) risk factor for PC, while sunlight exposure and vitamin D were not. Tanning potential was also significant (p=0.044) when adjusted for vitamin D and age. However, tanning potential was only marginally significant when adjusted for sunlight exposure (p=0.064) CONCLUSION: The findings of this study indicate that tanning potential may be a predictor for PC risk in African-American men.


Assuntos
Afro-Americanos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Bronzeado , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Luz Solar , Raios Ultravioleta , Vitamina D/sangue , Vitamina D/metabolismo
20.
Hum Mol Genet ; 23(15): 4043-50, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24626632

RESUMO

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.


Assuntos
Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Osteopontina/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Alelos , Linhagem Celular , Estrogênios/farmacologia , Exercício , Feminino , Expressão Gênica , Genótipo , Humanos , Inflamação/genética , Inflamação/fisiopatologia , Contração Isométrica , Imagem por Ressonância Magnética , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Mioblastos/efeitos dos fármacos , Mioblastos/patologia , Osteopontina/metabolismo , Transcrição Genética , Adulto Jovem
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