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Keywords = Caucasian American (CA)

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13 pages, 689 KiB  
Article
Mediation Analysis to Investigate Differences in Prostate Cancer Diagnosis Stage Through Environmental Risk Factors in Louisiana
by Nubaira Rizvi, Randy Hamilton, Xiao-Cheng Wu, Michael D. Celestin, Tung-Sung Tseng and Qingzhao Yu
Curr. Oncol. 2025, 32(8), 416; https://doi.org/10.3390/curroncol32080416 - 24 Jul 2025
Viewed by 249
Abstract
Prostate Cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death among men. In Louisiana (LA), Black men are disproportionately diagnosed at later stages compared to White men. This study explores environmental risk factors as potential intermediate [...] Read more.
Prostate Cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death among men. In Louisiana (LA), Black men are disproportionately diagnosed at later stages compared to White men. This study explores environmental risk factors as potential intermediate variables linking race to cancer diagnosis stage. The Louisiana Tumor Registry data included 24,647 male patients diagnosed with PCa in LA between 2010 and 2018. Among them, 15,875 (64.40%) were Caucasian American (CA) and 8772 (35.59%) African American (AA). Mediation analysis using multiple additive regression trees (MART) identified possible intermediate variables that potentially explain the observed disparity. The study found that individual characteristics and environmental factors jointly explained 84% (95% CI: 44.1%, 94.6%) and 18.6% (95% CI: 7.3%, 53.7%) of the observed racial disparity in PCa stage at diagnosis, respectively. Individual factors included BMI (35.9%), marital status (28.5%), CDI (8.2%), female-headed households (2.3%), comorbidity (3.9%), and insurance status (6.3%). Environmental contributors included cancer risk due to air toxicity exposure (7.2%), asthma prevalence (6.6%), acetaldehyde levels (2.1%), railroad proximity (2.1%), walkability (0.3%), and ozone level (−0.1%). Environmental factors jointly played a significant role in the observed racial disparity. The factors such as air toxicity, acetaldehyde levels, and asthma prevalence highlight the need to address industrial pollutants to reduce the differences. Full article
(This article belongs to the Special Issue New and Emerging Trends in Prostate Cancer)
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14 pages, 3375 KiB  
Article
Diversity and Characteristics of the Oral Microbiome Associated with Self-Reported Ancestral/Ethnic Groups
by Qingguo Wang, Bing-Yan Wang, She’Neka Williams and Hua Xie
Int. J. Mol. Sci. 2024, 25(24), 13303; https://doi.org/10.3390/ijms252413303 - 11 Dec 2024
Viewed by 1265
Abstract
Periodontitis disproportionately affects genetic ancestral/ethnic groups. To characterize the oral microbiome from different genetic ancestral/ethnic groups, we collected 161 dental plaque samples from self-identified African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an [...] Read more.
Periodontitis disproportionately affects genetic ancestral/ethnic groups. To characterize the oral microbiome from different genetic ancestral/ethnic groups, we collected 161 dental plaque samples from self-identified African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. DNA was extracted from these samples, and then DNA libraries were prepared and sequenced using an Illumina NovaSeq high-throughput sequencer. We found significant differences in the diversity and abundance of microbial taxa among dental plaque samples of the AA, CA, and HA groups. We also identified unique microbial species in a self-reported ancestral/ethnic group. Moreover, we revealed variations in functional potentials of the oral microbiome among the three ancestral/ethnic groups, with greater diversity and abundance of antibiotic-resistant genes in the oral microbiome and significantly more genes involved in the modification of glycoconjugates and oligo- and polysaccharides in AAs than in CAs and HAs. Our observations suggest that the variations in the oral microbiome associated with ancestral/ethnic backgrounds may directly relate to their virulence potential including their abilities to induce host immune responses and to resist antibiotic treatment. These finding can be a steppingstone for developing precision medicine and personalized periodontal prevention/treatment and for reducing oral health disparities. Full article
(This article belongs to the Section Molecular Biology)
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13 pages, 1153 KiB  
Article
Quantitative Multi-Parametric MRI of the Prostate Reveals Racial Differences
by Aritrick Chatterjee, Xiaobing Fan, Jessica Slear, Gregory Asare, Ambereen N. Yousuf, Milica Medved, Tatjana Antic, Scott Eggener, Gregory S. Karczmar and Aytekin Oto
Cancers 2024, 16(20), 3499; https://doi.org/10.3390/cancers16203499 - 16 Oct 2024
Cited by 1 | Viewed by 1422
Abstract
Purpose: This study investigates whether quantitative MRI and histology of the prostate reveal differences between races, specifically African Americans (AAs) and Caucasian Americans (CAs), that can affect diagnosis. Materials and Methods: Patients (98 CAs, 47 AAs) with known or suspected prostate cancer (PCa) [...] Read more.
Purpose: This study investigates whether quantitative MRI and histology of the prostate reveal differences between races, specifically African Americans (AAs) and Caucasian Americans (CAs), that can affect diagnosis. Materials and Methods: Patients (98 CAs, 47 AAs) with known or suspected prostate cancer (PCa) underwent 3T MRI (T2W, DWI, and DCE-MRI) prior to biopsy or prostatectomy. Quantitative mpMRI metrics: ADC, T2, and DCE empirical mathematical model parameters were calculated. Results: AAs had a greater percentage of higher Gleason-grade lesions compared to CAs. There were no significant differences in the quantitative ADC and T2 values between AAs and CAs. The cancer signal enhancement rate (α) on DCE-MRI was significantly higher for AAs compared to CAs (AAs: 13.3 ± 9.3 vs. CAs: 6.1 ± 4.7 s−1, p < 0.001). The DCE signal washout rate (β) was significantly lower in benign tissue of AAs (AAs: 0.01 ± 0.09 s−1 vs. CAs: 0.07 ± 0.07 s−1, p < 0.001) and significantly elevated in cancer tissue in AAs (AAs: 0.12 ± 0.07 s−1 vs. CAs: 0.07 ± 0.08 s−1, p = 0.02). DCE significantly improves the differentiation of PCa from benign in AAs (α: 52%, β: 62% more effective in AAs compared to CAs). Histologic analysis showed cancers have a greater proportion (p = 0.04) of epithelium (50.9 ± 12.3 vs. 44.7 ± 12.8%) and lower lumen (10.5 ± 6.9 vs. 16.2 ± 6.8%) in CAs compared to AAs. Conclusions: This study shows that AAs have different quantitative DCE-MRI values for benign prostate and prostate cancer and different histologic makeup in PCa compared to CAs. Quantitative DCE-MRI can significantly improve the performance of MRI for PCa diagnosis in African Americans but is much less effective for Caucasian Americans. Full article
(This article belongs to the Special Issue MRI in Prostate Cancer)
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13 pages, 5953 KiB  
Article
Racial Disparities in Plasma Cytokine and Microbiome Profiles
by Kevin D. Fan, Elizabeth Ogunrinde, Zhuang Wan, Chao Li and Wei Jiang
Microorganisms 2024, 12(7), 1453; https://doi.org/10.3390/microorganisms12071453 - 17 Jul 2024
Cited by 2 | Viewed by 1277
Abstract
Background: Many health issues prevalent in African American (AA) populations are associated with chronic inflammation and related health conditions, including autoimmune diseases, infectious diseases, neurologic disorders, metabolic syndromes, and others. The current study aims to understand plasma microbiome translocation as a potential trigger [...] Read more.
Background: Many health issues prevalent in African American (AA) populations are associated with chronic inflammation and related health conditions, including autoimmune diseases, infectious diseases, neurologic disorders, metabolic syndromes, and others. The current study aims to understand plasma microbiome translocation as a potential trigger for chronic inflammation. Methods: In this study, 16 Caucasian American (CA) and 22 African American (AA) healthy individuals were recruited. Microbial DNA was isolated from the plasma samples and sequenced via microbial 16S rRNA V3-4 sequencing. The plasma levels of 33 cytokines and chemokines were evaluated. The proinflammatory microbiomes were verified using human THP-1 cells in vitro. Results: The plasma levels of IL-6, IL-15, MIP-1α, MIP-1β, and MIP-3α were higher in the AA people, whereas IL-1α and IL-27 were elevated in the CA people. The plasma microbiomes exhibited eight bacterial genera/phyla differentially enriched in the CA and AA people. Given the critical role of IL-6 in chronic inflammation and associated diseases, we identified five bacteria genera significantly associated with IL-6. The abundance of Actinomyces was positively correlated with the plasma IL-6 level (r = 0.41, p = 0.01), while the abundance of Kurthia (r = −0.34, p = 0.04), Noviherbaspirillum (r = −0.34, p = 0.04), Candidatus Protochlamydia (r = −0.36, p = 0.03), and Reyranella (r = −0.39, p = 0.02) was negatively correlated with this. Finally, the THP-1 cells treated with heat-killed bacteria produced higher levels of IL-6 in vitro in response to the Actinomyces species compared to the species in the genus either uncorrelated or negatively correlated with IL-6. Conclusions: This is the first study to report potential blood microbiome translocation as a driver for persistently elevated IL-6 levels in the periphery in healthy AA versus CA people. Understanding the plasma microbiome linked to the IL-6 levels in people with different racial backgrounds is essential to unraveling the therapeutic approaches to improve precision medicine. Full article
(This article belongs to the Special Issue Advances in Human Microbiomes)
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18 pages, 3007 KiB  
Article
Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
by Camilo Tapia-Valladares, Guillermo Valenzuela, Evelin González, Ignacio Maureira, Jessica Toro, Matías Freire, Gonzalo Sepúlveda-Hermosilla, Diego Ampuero, Alejandro Blanco, Iván Gallegos, Fernanda Morales, José I. Erices, Olga Barajas, Mónica Ahumada, Héctor R. Contreras, Jaime González, Ricardo Armisén and Katherine Marcelain
Int. J. Mol. Sci. 2024, 25(9), 4695; https://doi.org/10.3390/ijms25094695 - 25 Apr 2024
Cited by 2 | Viewed by 2366
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of [...] Read more.
Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10−5) and MSK-IMPACT cohorts (p-value = 3.062 × 10−2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients. Full article
(This article belongs to the Special Issue Cancer Genomics and Precision Oncology)
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12 pages, 988 KiB  
Article
Bayesian Mediation Analysis with an Application to Explore Racial Disparities in the Diagnostic Age of Breast Cancer
by Wentao Cao, Joseph Hagan and Qingzhao Yu
Stats 2024, 7(2), 361-372; https://doi.org/10.3390/stats7020022 - 19 Apr 2024
Viewed by 1751
Abstract
A mediation effect refers to the effect transmitted by a mediator intervening in the relationship between an exposure variable and a response variable. Mediation analysis is widely used to identify significant mediators and to make inferences on their effects. The Bayesian method allows [...] Read more.
A mediation effect refers to the effect transmitted by a mediator intervening in the relationship between an exposure variable and a response variable. Mediation analysis is widely used to identify significant mediators and to make inferences on their effects. The Bayesian method allows researchers to incorporate prior information from previous knowledge into the analysis, deal with the hierarchical structure of variables, and estimate the quantities of interest from the posterior distributions. This paper proposes three Bayesian mediation analysis methods to make inferences on mediation effects. Our proposed methods are the following: (1) the function of coefficients method; (2) the product of partial difference method; and (3) the re-sampling method. We apply these three methods to explore racial disparities in the diagnostic age of breast cancer patients in Louisiana. We found that African American (AA) patients are diagnosed at an average of 4.37 years younger compared with Caucasian (CA) patients (57.40 versus 61.77, p< 0.0001). We also found that the racial disparity can be explained by patients’ insurance (12.90%), marital status (17.17%), cancer stage (3.27%), and residential environmental factors, including the percent of the population under age 18 (3.07%) and the environmental factor of intersection density (9.02%). Full article
(This article belongs to the Section Bayesian Methods)
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12 pages, 740 KiB  
Article
Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men
by Nischal Mahaveer Chand, Poornima K. Tekumalla, Matt T. Rosenberg, Albert Dobi, Amina Ali, Gregory M. Miller, Juan J. Aristizabal-Henao, Elder Granger, Stephen J. Freedland, Mark D. Kellogg, Shiv Srivastava, David G. McLeod, Niven R. Narain and Michael A. Kiebish
Cancers 2024, 16(4), 712; https://doi.org/10.3390/cancers16040712 - 8 Feb 2024
Cited by 3 | Viewed by 2090
Abstract
Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an [...] Read more.
Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA’s screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7–10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses. Full article
(This article belongs to the Special Issue Liquid Biopsy of Genitourinary Tumors)
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14 pages, 3739 KiB  
Article
Influence of Race and High Laminar Shear Stress on TNFR1 Signaling in Endothelial Cells
by Maitha Aldokhayyil, Dulce H. Gomez, Marc D. Cook, Andreas N. Kavazis, Michael D. Roberts, Thangiah Geetha and Michael D. Brown
Int. J. Mol. Sci. 2023, 24(19), 14723; https://doi.org/10.3390/ijms241914723 - 29 Sep 2023
Cited by 1 | Viewed by 1662
Abstract
Tumor necrosis factor (TNF) binding to endothelial TNF receptor-I (TNFR-I) facilitates monocyte recruitment and chronic inflammation, leading to the development of atherosclerosis. In vitro data show a heightened inflammatory response and atherogenic potential in endothelial cells (ECs) from African American (AA) donors. High [...] Read more.
Tumor necrosis factor (TNF) binding to endothelial TNF receptor-I (TNFR-I) facilitates monocyte recruitment and chronic inflammation, leading to the development of atherosclerosis. In vitro data show a heightened inflammatory response and atherogenic potential in endothelial cells (ECs) from African American (AA) donors. High laminar shear stress (HSS) can mitigate some aspects of racial differences in endothelial function at the cellular level. We examined possible racial differences in TNF-induced monocyte adhesion and TNFR1 signaling complex expression/activity, along with the effects of HSS. Tohoku Hospital Pediatrics-1 (THP-1) monocytes were used in a co-culture system with human umbilical vein ECs (HUVECs) from Caucasian American (CA) and AA donors to examine racial differences in monocyte adhesion. An in vitro exercise mimetic model was applied to investigate the potential modulatory effect of HSS. THP-1 adherence to ECs and TNF-induced nuclear factor kappa B (NF-κB) DNA binding were elevated in AA ECs compared to CA ECs, but not significantly. We report no significant racial differences in the expression of the TNFR-I signaling complex. Application of HSS significantly increased the expression and shedding of TNFR-I and the expression of TRAF3, and decreased the expression of TRAF5 in both groups. Our data does not support TNF-induced NF-κB activation as a potential mediator of racial disparity in this model. Other pathways and associated factors activated by the TNFR1 signaling complex are recommended targets for future research. Full article
(This article belongs to the Special Issue New Insights into Endothelial Injury)
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9 pages, 3394 KiB  
Article
Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer
by Farhan Khan, Obianuju Mercy Anelo, Qandeel Sadiq, Wendy Effah, Gary Price, Daniel L. Johnson, Suriyan Ponnusamy, Brandy Grimes, Michelle L. Morrison, Jay H. Fowke, D. Neil Hayes and Ramesh Narayanan
Biomedicines 2023, 11(3), 648; https://doi.org/10.3390/biomedicines11030648 - 21 Feb 2023
Cited by 3 | Viewed by 2341
Abstract
Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are [...] Read more.
Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive/potentially lethal PCa and have shorter disease-free survival. Expression of a truncated AR in an aggressively growing patient-derived xenograft developed with a primary PCa specimen from an AA patient led us to hypothesize that the expression of AR-SVs could be an indicator of aggressive growth both in PCa progression and at the CRPC stage in AA men. Tissue microarrays (TMAs) were created from formalin-fixed paraffin-embedded (FFPE) prostatectomy tumor blocks from 118 AA and 115 CA treatment-naïve PCa patients. TMAs were stained with AR-V7-speicifc antibody and with antibodies binding to the N-terminus domain (NTD) and ligand-binding domain (LBD) of the AR. Since over 20 AR-SVs have been identified, and most AR-SVs do not as yet have a specific antibody, we considered a 2.0-fold or greater difference in the NTD vs. LBD staining as indication of potential AR-SV expression. Two AA, but no CA, patient tumors stained positively for AR-V7. AR staining with NTD and LBD antibodies was robust in most patients, with 21% of patients staining at least 2-fold more for NTD than LBD, indicating that AR-SVs other than AR-V7 are expressed in primary treatment-naïve PCa. About 24% of the patients were AR-negative, and race differences in AR expression were not statistically significant. These results indicate that AR-SVs are not restricted to CRPC, but also are expressed in primary PCa at higher rate than previously reported. Future investigation of the relative expression of NTD vs. LBD AR-SVs could guide the use of newly developed treatments targeting the NTD earlier in the treatment paradigm. Full article
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18 pages, 533 KiB  
Review
Biomarkers of Aggressive Prostate Cancer at Diagnosis
by Brock E. Boehm, Monica E. York, Gyorgy Petrovics, Indu Kohaar and Gregory T. Chesnut
Int. J. Mol. Sci. 2023, 24(3), 2185; https://doi.org/10.3390/ijms24032185 - 22 Jan 2023
Cited by 47 | Viewed by 10762
Abstract
In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, [...] Read more.
In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate specific antigen in prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 times higher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications)
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11 pages, 910 KiB  
Article
African American Females Are Less Metabolically Flexible Compared with Caucasian American Females following a Single High-Fat Meal: A Pilot Study
by Alyssa A. Olenick, Regis C. Pearson, Nuha Shaker, Maire M. Blankenship, Rachel A. Tinius, Lee J. Winchester, Evie Oregon and Jill M. Maples
Int. J. Environ. Res. Public Health 2022, 19(19), 12913; https://doi.org/10.3390/ijerph191912913 - 9 Oct 2022
Cited by 2 | Viewed by 4324
Abstract
The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study [...] Read more.
The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study aimed to compare the metabolic response of AA and CA females after a high-fat meal. Eleven AA (25.6 (5.6) y, 27.2 (6.0) kg/m2, 27.5 (9.7) % body fat) and twelve CA (26.5 (1.5) y, 25.7 (5.3) kg/m2, 25.0 (7.4) % body fat) women free of cardiovascular and metabolic disease and underwent a high-fat meal challenge (55.9% fat). Lipid oxidation, insulin, glucose, and interleukin (IL)-8 were measured fasted, 2 and 4 h postprandial. AA females had a significantly lower increase in lipid oxidation from baseline to 2 h postprandial (p = 0.022), and trended lower at 4 h postprandial (p = 0.081) compared with CA females, indicating worse MF. No group differences in insulin, glucose or HOMA-IR were detected. IL-8 was significantly higher in AA females compared with CA females at 2 and 4 h postprandial (p = 0.016 and p = 0.015, respectively). These findings provide evidence of metabolic and inflammatory disparities among AA females compared with CA females that could serve as a predictor of chronic disease in individuals with a disproportionately higher risk of development. Full article
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19 pages, 2504 KiB  
Article
YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer
by Priyanka Shailendra Rana, Wei Wang, Akram Alkrekshi, Vesna Markovic, Amer Khiyami, Ricky Chan, Adam Perzynski, Natalie Joseph and Khalid Sossey-Alaoui
Cancers 2021, 13(24), 6262; https://doi.org/10.3390/cancers13246262 - 14 Dec 2021
Cited by 8 | Viewed by 3964
Abstract
Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic [...] Read more.
Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments. Full article
(This article belongs to the Special Issue Breast Development and Cancer)
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19 pages, 1739 KiB  
Article
Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men
by Hamdy E. A. Ali, Mohamed S. A. Gaballah, Rofaida Gaballa, Shahenda Mahgoub, Zeinab A. Hassan, Eman A. Toraih, Bettina F. Drake and Zakaria Y. Abd Elmageed
Cancers 2021, 13(20), 5236; https://doi.org/10.3390/cancers13205236 - 19 Oct 2021
Cited by 11 | Viewed by 2664
Abstract
The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive [...] Read more.
The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan–Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS. Full article
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23 pages, 3534 KiB  
Article
Gene Expression Alterations Associated with Oleuropein-Induced Antiproliferative Effects and S-Phase Cell Cycle Arrest in Triple-Negative Breast Cancer Cells
by Samia S. Messeha, Najla O. Zarmouh, Abrar Asiri and Karam F. A. Soliman
Nutrients 2020, 12(12), 3755; https://doi.org/10.3390/nu12123755 - 7 Dec 2020
Cited by 37 | Viewed by 5103
Abstract
It is known that the Mediterranean diet is effective in reducing the risk of several chronic diseases, including cancer. A critical component of the Mediterranean diet is olive oil, and the relationship between olive oil consumption and the reduced risk of cancer has [...] Read more.
It is known that the Mediterranean diet is effective in reducing the risk of several chronic diseases, including cancer. A critical component of the Mediterranean diet is olive oil, and the relationship between olive oil consumption and the reduced risk of cancer has been established. Oleuropein (OL) is the most prominent polyphenol component of olive fruits and leaves. This compound has been shown to have potent properties in various types of cancers, including breast cancer. In the present study, the molecular mechanism of OL was examined in two racially different triple-negative breast cancer (TNBC) cell lines—African American (AA, MDA-MB-468) and Caucasian American (CA, MDA-MB-231). The data obtained showed that OL effectively inhibits cell growth in both cell lines, concomitant with S-phase cell cycle arrest-mediated apoptosis. The results also showed that OL-treated MDA-MB-468 cells were two-fold more sensitive to OL antiproliferative effect than MDA-MB-231 cells were. At lower concentrations, OL modified the expression of many apoptosis-involved genes. OL was more effective in MDA-MB-468, compared to MDA-MB-231 cells, in terms of the number and the fold-change of the altered genes. In MDA-MB-468 cells, OL induced a noticeable transcription activation in fourteen genes, including two members of the caspase family: caspase 1 (CASP1) and caspase 14 (CASP14); two members of the TNF receptor superfamily: Fas-associated via death domain (FADD) and TNF receptor superfamily 21 (TNFRSF21); six other proapoptotic genes: growth arrest and DNA damage-inducible 45 alpha (GADD45A), cytochrome c somatic (CYCS), BCL-2 interacting protein 2 (BNIP2), BCL-2 interacting protein 3 (BNIP3), BH3 interacting domain death agonist (BID), and B-cell lymphoma/leukemia 10 (BCL10); and the CASP8 and FADD-like apoptosis regulator (CFLAR) gene. Moreover, in MDA-MB-468 cells, OL induced a significant upregulation in two antiapoptotic genes: bifunctional apoptosis regulator (BFAR) and B-Raf proto-oncogene (BRAF) and a baculoviral inhibitor of apoptosis (IAP) repeat-containing 3 (BIRC3). On the contrary, in MDA-MB-231 cells, OL showed mixed impacts on gene expression. OL significantly upregulated the mRNA expression of four genes: BIRC3, receptor-interacting serine/threonine kinase 2 (RIPK2), TNF receptor superfamily 10A (TNFRSF10A), and caspase 4 (CASP4). Additionally, another four genes were repressed, including caspase 6 (CASP6), pyrin domain (PYD), and caspase recruitment domain (CARD)-containing (PAYCARD), baculoviral IAP repeat-containing 5 (BIRC5), and the most downregulated TNF receptor superfamily member 11B (TNFRSF11B, 16.34-fold). In conclusion, the data obtained indicate that the two cell lines were markedly different in the anticancer effect and mechanisms of oleuropein’s ability to alter apoptosis-related gene expressions. The results obtained from this study should also guide the potential utilization of oleuropein as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression. Full article
(This article belongs to the Special Issue Plant-Based Foods in Cancer Prevention and Treatment)
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12 pages, 514 KiB  
Article
Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico
by Ruifang Zheng, Zhiwei Yin, Albert Alhatem, Derek Lyle, Bei You, Andrew S. Jiang, Dongfang Liu, Zsolt Jobbagy, Qing Wang, Seena Aisner and Jie-Gen Jiang
Cancers 2020, 12(12), 3492; https://doi.org/10.3390/cancers12123492 - 24 Nov 2020
Cited by 12 | Viewed by 3254
Abstract
Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, [...] Read more.
Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described. Full article
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