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BACKGROUND: In the U.S. there are significant racial and gender disparities in the uptake of pre-exposure prophylaxis (PrEP). Black Americans represented 14% of PrEP users in 2022, but accounted for 42% of new HIV diagnoses in 2021 and in the South, Black people represented 48% of new HIV diagnoses in 2021 but only 21% of PrEP users in 2022. Women who use drugs may be even less likely than women who do not use drugs have initiated PrEP. Moreover, women involved in community supervision programs (CSP) are less likely to initiate or use PrEP, More PrEP interventions that focus on Black women with recent history of drug use in CSPs are needed to reduce inequities in PrEP uptake. METHODS: We conducted a secondary analysis from a randomized clinical trial with a sub-sample (n = 336) of the total (N = 352) participants from the parent study (E-WORTH), who tested HIV negative at baseline were considered PrEP-eligible. Black women were recruited from CSPs in New York City (NYC), with recent substance use. Participants were randomized to either E-WORTH (n = 172) an HIV testing plus, receive a 5-session, culturally-tailored, group-based HIV prevention intervention, versus an HIV testing control group (n = 180). The 5 sessions included an introduction to PrEP and access. This paper reports outcomes on improved awareness of PrEP, willingness to use PrEP, and PrEP uptake over the 12-month follow-up period. HIV outcomes are reported in a previous paper. RESULTS: Compared to control participants, participants in this study assigned to E-WORTH had significantly greater odds of being aware of PrEP as a biomedical HIV prevention strategy (OR = 3.25, 95% CI = 1.64-6.46, p = 0.001), and indicated a greater willingness to use PrEP as an HIV prevention method (b = 0.19, 95% CI = 0.06-0.32, p = 0.004) over the entire 12-month follow-up period. CONCLUSIONS: These findings underscore the effectiveness of a culturally-tailored intervention for Black women in CSP settings in increasing awareness, and intention to initiate PrEP. Low uptake of PrEP in both arms highlight the need for providing more robust PrEP-on-demand strategies that are integrated into other services such as substance abuse treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02391233 .
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Negro o Afroamericano , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Femenino , Infecciones por VIH/prevención & control , Infecciones por VIH/etnología , Adulto , Ciudad de Nueva York , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/etnología , Trastornos Relacionados con Sustancias/prevención & control , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Asistencia Sanitaria Culturalmente Competente , Adulto Joven , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Black women in the USA experience some of the poorest health outcomes and this is especially true for those involved in the carceral system who are at elevated risks for HIV/STIs, reproductive health, and chronic diseases. This study aimed to investigate Black women's experience accessing healthcare services. We conducted semi-structured interviews with 43 women from Project EWORTH under community supervision in New York City. We analysed responses focusing on barriers to healthcare engagement. All interviews were recorded, and data analysis was conducted using NVivo. Themes influencing Black women's ability to engage with healthcare providers and systems included: 1) disclosed provider mistrust/judgement; 2) feeling disrespected by providers and the medical system; 3) mistrust of medical providers/system/hospital/government; 4) lack of health communication; 5) low health literacy; 6) provider gender preference. Findings highlight the need to improve trust and collaboration between healthcare providers and Black women. This study addresses the critical gap in understanding perceptions of discrimination, stigma, and barriers to attaining health care. Funders and accreditation agencies must hold providers and organisations accountable for acquiring and making available diversity, equity and inclusion training for providers, demonstrating increasingly equitable medical relationships through responsiveness to patient feedback, and increasing the number of Black providers.
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OBJECTIVES: Doulas are a potential resource for addressing substance use and mental health challenges that pregnant and postpartum individuals experience. We sought to review peer-reviewed literature that examines Doulas' role in addressing these challenges to highlight the need for more research in this area. METHODS: We conducted a scoping review (2001-2021) to identify articles that examine the way in which Doulas address maternal substance use and mental health challenges in their clients. The articles were reviewed by two members of the research team. RESULTS: Nine articles describing Doulas' role in addressing substance use and mental health challenges were identified. Six described Doulas' role in addressing mental health, five of which saw positive mental health outcomes due to Doula involvement. One additional article recommended Doulas be considered in the future to address mental health challenges. While the minority of articles addressed substance use (n = 2), it was reported that Doulas were a positive addition to interdisciplinary teams addressing substance use challenges with pregnant individuals. CONCLUSIONS: While the literature showed that Doulas can improve substance use and mental health outcomes among pregnant or postpartum individuals, a significant gap remains in research, practice, and peer-reviewed literature addressing this issue.
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Doulas , Embarazo , Femenino , Humanos , Doulas/psicología , Salud Mental , Periodo Posparto , FamiliaRESUMEN
INTRODUCTION: This study utilizes a machine learning model to predict unhealthy alcohol use treatment levels among women of childbearing age. METHODS: In this cross-sectional study, women of childbearing age (n = 2397) were screened for alcohol use over a 2-year period as part of the AL-SBIRT (screening, brief intervention, and referral to treatment in Alabama) program in three healthcare settings across Alabama for unhealthy alcohol use severity and depression. A support vector machine learning model was estimated to predict unhealthy alcohol use scores based on depression score and age. RESULTS: The machine learning model was effective in predicting no intervention among patients with lower Patient Health Questionnaire (PHQ)-2 scores of any age, but a brief intervention among younger patients (aged 18-27 years) with PHQ-2 scores >3 and a referral to treatment for unhealthy alcohol use among older patients (between the ages of 25 and 50) with PHQ-2 scores >4. CONCLUSIONS: The machine learning model can be an effective tool in predicting unhealthy alcohol use treatment levels and approaches.
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Alcoholismo , Humanos , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Alcoholismo/prevención & control , Alabama/epidemiología , Estudios Transversales , Consumo de Bebidas Alcohólicas/epidemiología , Derivación y ConsultaRESUMEN
This study examines cross-sectional clusters and longitudinal predictions using an expanded SAVA syndemic conceptual framework-SAVA MH + H (substance use, intimate partner violence, mental health, and homelessness leading to HIV/STI/HCV risks)-among women recently released from incarceration (WRRI) (n = 206) participating in the WORTH Transitions (WT) intervention. WT combines two evidence-based interventions: the Women on the Road to Health HIV intervention, and Transitions Clinic. Cluster analytic and logistic regression methods were utilized. For the cluster analyses, baseline SAVA MH + H variables were categorized into presence/absence. For logistic regression, baseline SAVA MH + H variables were examined on a composite HIV/STI/HCV outcome collected at 6-month follow-up, controlling for lifetime trauma and sociodemographic characteristics. Three SAVA MH + H clusters were identified, the first of which had women with the highest overall levels of SAVA MH + H variables, 47% of whom were unhoused. Hard drug use (HDU) was the only significant predictor of HIV/STI/HCV risks in the regression analyses. HDUs had 4.32-fold higher odds of HIV/STI/HCV outcomes than non-HDUs (p = 0.002). Interventions such as WORTH Transitions must differently target identified SAVA MH + H syndemic risk clusters and HDU to prevent HIV/HCV/STI outcomes among WRRI.
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Women on the Road to Health Transitions combines two evidence-based strategies, WORTH and Transitions Clinic Network into an intervention for women involved in the criminal legal system with substance use and HIV risks. Led by peer community health workers (CHWs), Women on the Road to Health Transitions also links participants to primary care. We describe the impact of the program from the perspective of the CHWs. As integral research team members, the CHWs learned to successfully recruit, retain, and empower participants, facilitate the intervention, administer surveys, and help them link with and navigate the healthcare system. Simultaneously, the CHWs developed professional skills and self-efficacy.
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Servicios de Salud Comunitaria , Agentes Comunitarios de Salud , Humanos , Femenino , Investigación Participativa Basada en la Comunidad , Grupo Paritario , Investigación CualitativaRESUMEN
Background: U.S. women recently released from incarceration experience significantly higher rates of trauma and exacerbation of mental health conditions, and the period following release has been identified as a window of heightened risk for mental health distress and human immunodeficiency virus (HIV), sexually transmitted infections (STI) and hepatitis C (HCV) transmissions. Despite these vulnerabilities, and an urgent need for supports, optimal engagement strategies remain unclear. WORTH Transitions is a program made up of two evidence-based interventions focused on improving the health of women returning to the community from incarceration with substance use disorders. Combining the two was designed to reduce HIV/STIs/HCV risks and increase overall health treatment engagement using a community health worker led intervention. Methods: We examined associations between trauma, mental health symptomology, and HIV/STI/HCV outcomes among women who engaged in the WORTH Transitions intervention (N = 206) Specifically, bivariate and longitudinal multivariate models were created to examine associations between trauma and mental health distress (defined as depressive and PTSD symptoms), on (1) types of engagement in HIV/STIs/HCV prevention and behavioral health services; and (2) HIV/STIs/HCV risk outcomes. The women who engaged in the intervention were 18 years and older and some were White, Black and other racial or ethnic minority. Results: PTSD symptomology and being a Black or indigenous woman of color was significantly (p = 0.014) associated with individual or group session engagement. Neither trauma nor PTSD symptoms were associated with higher HIV/STIs/HCV risks. Instead, relative to those who did not engage in HIV/STI/HCV risky behaviors, PTSD symptomology (p = 0.040) was associated with more than 3-fold increase in the probability of being lost to follow up (relative risk ratio = 3.722). Conclusion: Given the impact of PTSD-related symptoms on driving both engagement in HIV/STIs/HCV prevention services and intervention attrition among women leaving incarceration, physical and behavioral health interventions must be both overtly trauma- and mental health-informed. As was the case with WORTH Transitions, physical and behavioral health services for this population must include intentional and active support of the forms of treatment participants endorse to ensure maximal engagement.
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This study explored homeless people's (N = 164) spiritual well-being (SWB) in relation to race, mental illness, physical disease, resilience, and trait mindfulness. The results of hierarchical regression analysis revealed that variables of race (p = 0.003), mental illness (p = 0.04), resilience (p < 0.001) and trait mindfulness (p < 0.001) contributed to participants' SWB. These findings were critical to research related to homelessness and service provisions in finding that homeless people with certain backgrounds (e.g., mental illness) might have lower SWB than their counterparts. This research also revealed protective factors (e.g., resilience) that could help promote SWB.
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Personas con Mala Vivienda , Trastornos Mentales , Humanos , Análisis de RegresiónRESUMEN
PURPOSE OF REVIEW: Globally, the majority of those who need mental health care worldwide lack access to high-quality mental health services. Stigma, human resource shortages, fragmented service delivery models, and lack of research capacity for implementation and policy change contribute to the current mental health treatment gap. In this review, we describe how health systems in low- and middle-income countries (LMICs) are addressing the mental health gap and further identify challenges and priority areas for future research. RECENT FINDINGS: Common mental disorders are responsible for the largest proportion of the global burden of disease; yet, there is sound evidence that these disorders, as well as severe mental disorders, can be successfully treated using evidence-based interventions delivered by trained lay health workers in low-resource community or primary care settings. Stigma is a barrier to service uptake. Prevention, though necessary to address the mental health gap, has not solidified as a research or programmatic focus. Research-to-practice implementation studies are required to inform policies and scale-up services. Four priority areas are identified for focused attention to diminish the mental health treatment gap and to improve access to high-quality mental health services globally: diminishing pervasive stigma, building mental health system treatment and research capacity, implementing prevention programs to decrease the incidence of mental disorders, and establishing sustainable scale up of public health systems to improve access to mental health treatment using evidence-based interventions.
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Salud Global , Trastornos Mentales/terapia , Servicios de Salud Mental , Salud Mental , Personal de Salud , Humanos , Salud PúblicaRESUMEN
Pleuroparenchymal fibroelastosis (PPFE) is a rare condition currently described as an upper lobe subpleural and interstitial proliferation of predominantly elastic fibers. The etiology is unknown, and no specific diagnostic criteria have been reported. Here we report 5 cases of PPFE, 1 man and 4 women, 3 of them diagnosed at the time autopsy, 1 diagnosed in an explanted lung, and 1 diagnosed on a surgical wedge biopsy. The average age of diagnosis among this series is 73 years, and the duration of pulmonary symptoms ranged from 14 months to at least 9 years. Two patients had been exposed to specific medications (daptomycin and dapsone) preceding the development of pulmonary symptoms, and 1 patient developed eosinophilic pneumonia in the course of the disease. Four patients had clinical evidence of fibrous interstitial pneumonia. We found evidence of diffuse parenchymal fibroelastosis involving both upper and lower lobes in all 5 cases, suggesting that the disease may be a more diffuse condition than previously reported. PPFE may actually represent a pattern of chronic lung injury rather than a specific entity and may be seen in association with a variety of clinicoradiologic conditions. Based on our findings in this series and the most recent publications of the subject, we propose the following set of diagnostic criteria for PPFE: multilobar subpleural and/or centrilobular fibrous interstitial pneumonia characterized by an extensive (>80%) proliferation of elastic fibers in nonatelectatic lung, along with absent to mild chronic inflammation, and absent to rare granulomas.
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Tejido Elástico/patología , Enfermedades Pulmonares Intersticiales/patología , Lesión Pulmonar/patología , Pulmón/patología , Fibrosis Pulmonar/patología , Anciano , Anciano de 80 o más Años , Autopsia , Biopsia , Resultado Fatal , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/terapia , Lesión Pulmonar/diagnóstico por imagen , Lesión Pulmonar/etiología , Lesión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/terapia , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS: Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS: Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS: In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment.
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Inhibidores de 5-alfa-Reductasa/farmacología , Finasterida/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Receptores Androgénicos/biosíntesis , Anciano , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Calicreínas/metabolismo , Queratina-5/metabolismo , Masculino , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/genética , Hiperplasia Prostática/patología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Análisis de Regresión , Estudios RetrospectivosRESUMEN
⺠Ovarian angiosarcomas are rare and clinically aggressive neoplasms. ⺠In addition to surgery, taxol is the most studied adjuvant chemotherapy. ⺠Anti-angiogenic therapies can be considered as an option.
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BACKGROUND AND AIMS: Convergent floral traits hypothesized as attracting particular pollinators are known as pollination syndromes. Floral diversity suggests that the Australian epacrid flora may be adapted to pollinator type. Currently there are empirical data on the pollination systems for 87 species (approx. 15 % of Australian epacrids). This provides an opportunity to test for pollination syndromes and their important morphological traits in an iconic element of the Australian flora. METHODS: Data on epacrid-pollinator relationships were obtained from published literature and field observation. A multivariate approach was used to test whether epacrid floral attributes related to pollinator profiles. Statistical classification was then used to rank floral attributes according to their predictive value. Data sets excluding mixed pollination systems were used to test the predictive power of statistical classification to identify pollination models. KEY RESULTS: Floral attributes are correlated with bird, fly and bee pollination. Using floral attributes identified as correlating with pollinator type, bird pollination is classified with 86 % accuracy, red flowers being the most important predictor. Fly and bee pollination are classified with 78 and 69 % accuracy, but have a lack of individually important floral predictors. Excluding mixed pollination systems improved the accuracy of the prediction of both bee and fly pollination systems. CONCLUSIONS: Although most epacrids have generalized pollination systems, a correlation between bird pollination and red, long-tubed epacrids is found. Statistical classification highlights the relative importance of each floral attribute in relation to pollinator type and proves useful in classifying epacrids to bird, fly and bee pollination systems.
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Ericaceae/fisiología , Flores/fisiología , Polinización , Animales , Australia , Abejas , Aves , Interpretación Estadística de Datos , Flores/anatomía & histología , Modelos Biológicos , Herencia Multifactorial , Análisis MultivarianteRESUMEN
It is well established that the combined del(1)(p36) and del(19)(q13) is a positive prognostic molecular event in oligodendroglial tumors. However, very little is known about the frequency or impact of polysomy status for chromosomes 1/19. We examined 84consecutive pure oligodendrogliomas (68 World Health Organization [WHO] grade II and 16 WHO grade III) and analyzed them for del(1)(p36) and del(19)(q13) by fluorescent in situ hybridization. Polysomy status was recorded with accompanying deletion status, WHO grade, recurrence-free survival, and overall survival. Codeletion of 1p/19q was detected in 48% of cases and correlated with superior patient survival (p < 0.01), as expected. Of 84 cases, 36 (43%) showed polysomy of chromosome 1, 30 (36%) demonstrated polysomy of chromosome 19, and 28 (33%) had copolysomies of chromosomes 1/19. The presence of polysomy of either/or both chromosomes, regardless of deletion status, correlated with younger patient age at initial diagnosis (p < 0.01). Combined polysomy was associated with higher histologic tumor grade (p = 0.04) and conferred poor survival likelihood (p = 0.03). We conclude that polysomy of 1 and/or 19 is a relatively frequent occurrence in oligodendrogliomas and usually confers an unfavorable outcome.
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Neoplasias Encefálicas/genética , Deleción Cromosómica , Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 1/genética , Hibridación Fluorescente in Situ , Oligodendroglioma/genética , Adolescente , Adulto , Factores de Edad , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Niño , Aberraciones Cromosómicas , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oligodendroglioma/diagnóstico , Oligodendroglioma/mortalidad , Estudios Retrospectivos , Factores Sexuales , Análisis de Supervivencia , Adulto JovenRESUMEN
For the predominantly southern hemisphere plant group Styphelioideae (Ericaceae) published sequence datasets of five markers are now available for all except one of the 38 recognised genera. However, several markers are highly incomplete therefore missing data is problematic for producing a genus level phylogeny. We explore the relative utility of supertree and supermatrix approaches for addressing this challenge, and examine the effects of missing data on tree topology and resolution. Although the supertree approach returned a more conservative hypothesis, overall, both supermatrix and supertree analyses concurred in the topologies they returned. Using multiple genes and a dataset of variably complete taxa we found improved support for the monophyly and position of the tribes and genus level relationships. However, there was mixed support for the Richeeae tribe appearing one node basal to the Cosmelieae tribe or vice versa. It is probable that this will only be resolved through further sequencing. Our study supports previous findings that the amount of data is more critical than the completeness of the dataset in estimating well-resolved trees. Our results suggest that a "serendipitous" scaffolding approach that includes a mixture of well and poorly sequenced taxa can lead to robust phylogenetic hypotheses.
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Ericaceae/clasificación , Ericaceae/genética , Filogenia , Teorema de Bayes , ADN Espaciador Ribosómico/genética , Funciones de Verosimilitud , Modelos Genéticos , Tipificación de Secuencias Multilocus , Proteínas de Plantas/genética , ARN Ribosómico 18S/genética , Alineación de SecuenciaRESUMEN
OBJECTIVE: In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 produced a large number of false-positive tests. We examined relationships between histopathologic diagnoses, false-positive test group, and participant and screening test characteristics. METHODS: The PLCO ovarian cancer screening arm included 39,105 women aged 55-74 years assigned to annual CA-125 and TVU. Histopathologic diagnoses from women with false-positive tests and subsequent surgery were reviewed in this analysis: all CA125+ (n=121); all CA125+/TVU+ (n=46); and a random sample of TVU+ (n=373). Demographic and ovarian cancer risk factor data were self-reported. Pathologic diagnoses were abstracted from surgical pathology reports. We compared participant characteristics and pathologic diagnoses by category of false-positive using Pearson χ2, Fisher's exact, or Wilcoxon-Mann-Whitney tests. RESULTS: Women with a false-positive TVU were younger (P<0.001), heavier (P<0.001), and reported a higher frequency of prior hysterectomy (P<0.001). Serous cystadenoma, the most common benign ovarian diagnosis, was more frequent among women with TVU+ compared to CA-125+ and CA-125+/TVU+ (P<0.001). Benign non-ovarian findings were commonly associated with all false-positives, although more frequently with CA-125+ than TVU+ or CA-125+/TVU+ groups (P=0.019). Non-ovarian cancers were diagnosed most frequently among CA-125+ (P<0.001). CONCLUSIONS: False-positive ovarian cancer screening tests were associated with a range of histopathologic diagnoses, some of which may be related to patient and screening test characteristics. Further research into the predictors of false-positive ovarian cancer screening tests may aid efforts to reduce false-positive results.
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Neoplasias Ováricas/patología , Anciano , Antígeno Ca-125/sangre , Reacciones Falso Positivas , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/diagnóstico por imagen , Ultrasonografía , Vagina/diagnóstico por imagenRESUMEN
With biomolecular evidence accumulating at an exponential rate, there will be a surge in the development of targeted cancer prevention drugs and interventions in the next decade. Promising results from clinical treatment trials identify a spectrum of targeted cancer therapies in several broad categories. These include both small molecule inhibitors of either key receptors or enzyme binding sites, as well as intravenously delivered monoclonal antibodies that block a specific binding interaction between ligands and their receptors. These targeted interventions conform to a basic translational algorithm: biomarker present, biomarker modulated, and biomarker clinically relevant. A review of solid tumor targets provides a manageable list of factors that are critical to cancer cell survival. As such, these targets represent factors that are not only clinically relevant but also may play a critical role in early tumor development prior to the evolution of frank invasive malignancy. This possibility qualifies these targets for consideration in the development of cancer prevention interventions. Among solid tumors, the treatment of breast cancer with targeted drugs has a long record benchmarked by the initial US Food and Drug Administation (FDA) approval of tamoxifen for metastatic breast cancer treatment in 1977. Since then, the list of oncology drug targets has expanded to include aromatase, androgen receptor, the epidermal growth factor receptor (EGFR) family, and others. It is not surprising that tamoxifen was the first of the modern targeted therapies to be approved for cancer risk reduction and additional approvals are anticipated. The focus of this review is the pharmacologic manipulation of targets within epithelial tumor cells and the implication of those targets for intervening to suppress and eliminate premalignant cells in human tissue. Major obstacles to prevention drug development can be addressed by attention to two important areas. One of these is the refinement of early phase prevention trials to identify drug targets in epithelial cells that are at demonstrated risk of evolving into cancer cells, ie, cells from a developmental niche in cancer ontogeny. Early results suggest that molecular risk signatures may allow the investigational identification of molecular targets in premalignant tissue, with the possibility that chemoprevention agents can be used to eliminate the risk signature. To the extent that this approach can be developed, it will allow for cancer risk reduction in a way that is analogous to the measurement of tumor response to treatment. Even with improvements in the efficiency of clinical trials that come from using molecular risk signatures, there is an ever-growing list of chemoprevention agents that are candidates for evaluation. Improved prevention drug screening methodologies are therefore needed to prioritize agents for clinical testing. In addition to drug targets located in epithelial tumor cells, another list of malignancy-associated targets could be generated by considering targets in tumor-associated stromal and endothelial cells (eg, fibroblast growth factor [FGF], vascular endothelial growth factor [VEGF]), as well as targets related to a systemic reservoir of circulating cells that can be recruited to carcinogenic influence by inflammatory factors such as nuclear factor (NF)kappaB. The complementarities of target-related processes within tumors cells, in the tumor microenvironment, and beyond suggests that there is great potential for multi-targeted approaches that may be more effective than single agents and also less prone to resistance. Additional options, related to drug dose and schedule, remain to be established. As long as multiple agents can be used in combination for optimal effect with acceptable toxicity, the co-targeting of the epithelial cell compartment along with other compartments of oncogenic activity is expected to expand the dimensions of targeted prevention and enhance the overall opportunity to eliminate precancer or cells at risk of eventually transitioning to invasive cancer.
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Anticarcinógenos/uso terapéutico , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Neoplasias/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Neoplasias/metabolismoRESUMEN
Breast cancer is the most common cancer in women worldwide, accounting for just over 1 million new cases annually. Population-based statistics show that globally, when compared to whites, women of African ancestry tend to have more aggressive breast cancers that present more frequently as estrogen receptor-negative (ER(-)) tumors. ER(-) tumors fail to respond to current established targeted therapies, whether for treatment or prevention. Subsets of the ER(-) phenotype include those that are also negative for the progesterone receptor (PR) and human epidermal growth factor receptor (HER2); these are called "triple-negative" (TN) breast cancers. The ER(-), TN, and basal-like phenotypic categories are important because they carry worse prognoses than estrogen receptor-positive (ER(+)) tumors, in addition to lacking obvious molecular targets for known therapies. Furthermore, among premenopausal women, the three subsets occur more frequently in women of African descent compared to white women with breast cancer. The contribution of these three subtypes of poor-prognosis tumors to the higher breast cancer mortality in black women is the focus of this review. Epidemiologic and lifestyle risk factors such as diet and physical activity and ER(-) breast cancer risk are reviewed. We will attempt to clarify some of the issues, in terms of their contribution to that component of health disparities that involves biological differences in breast cancer between women of African ancestry and white women.