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1.
BMC Public Health ; 24(1): 2533, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289635

RESUMEN

BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. RESULTS: All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65-4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). CONCLUSION: The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.


Asunto(s)
Población Negra , Pruebas Genéticas , Disparidades en Atención de Salud , Neoplasias de la Próstata , Humanos , Masculino , África/etnología , Negro o Afroamericano , Técnica Delphi , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Estados Unidos
2.
JCO Precis Oncol ; 8: e2300552, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38452310

RESUMEN

PURPOSE: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services. METHODS: Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers. RESULTS: The analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was -0.04 (one-sided 95% CI, -∞ to 2.54; P = .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm. CONCLUSION: The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.


Asunto(s)
Asesoramiento Genético , Neoplasias de la Próstata , Humanos , Masculino , Asesoramiento Genético/métodos , Pruebas Genéticas , Células Germinativas , Conocimientos, Actitudes y Práctica en Salud , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia
3.
Artículo en Inglés | MEDLINE | ID: mdl-38172199

RESUMEN

BACKGROUND: Germline testing is important in prostate cancer and evaluation can be complex. METHODS: We instituted a monthly multi-disciplinary virtual genetics tumor board (7/2021-3/2022). Participants and panelists were surveyed on usefulness and acceptability. RESULTS: 101 participants attended a session, and 77 follow-up surveys were completed. Over 90% participants and 100% panelists endorsed usefulness of the case discussions and usability of the technology. The majority felt it provided new information they will use. CONCLUSIONS: A multidisciplinary genetics board was successfully developed to address complexity in prostate cancer genetics. The virtual platform may enhance dissemination of expertise where there are regional gaps.

4.
Biotechnol Rep (Amst) ; 37: e00780, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36619904

RESUMEN

SARS-CoV-2 receptor binding domain (RBD) recognizes the angiotensin converting enzyme 2 (ACE2) receptor in host cells that enables infection. Due to its antigenic specificity, RBD production is important for development of serological assays. Here we have established a system for stable RBD production in HEK 293T mammalian cells that simultaneously express the recombinant fluorescent protein dTomato, which enables kinetic monitoring of RBD expression by fluorescence microscopy. In addition, we have validated the use of this recombinant RBD in an ELISA assay for the detection of anti-RBD antibodies in serum samples of COVID-19 convalescent patients. Recombinant RBD generated using this approach can be useful for generation of antibody-based therapeutics against SARS-CoV-2, as well serological assays aimed to test antibody responses to this relevant virus.

5.
J Community Genet ; 13(6): 547-556, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35869324

RESUMEN

Patients with prostate cancer (PCA) are increasingly being offered germline genetic testing for precision therapy, precision management, and clinical trial options. Genetic test results also have implications for family members. How men with PCA perceive their genetic test results and decide whether to share recommendations with family members is not well studied. We interviewed 12 patients who had PCA and genetic testing and received a positive variant/likely positive variant (PV/LPV) (n = 7) or a variant of unknown significance (VUS) (n = 5) result. The semi-structured interview had five sections: genetic testing experience, impact, and interpretation of the test result, deciding whether to communicate test results to family members, impact of communication on family members, and suggestions for genetic counselors and other PCA patients. Interviews were transcribed verbatim and thematic analysis was completed using NVivo software v10. Receipt of PV/LPV or VUS genetic test results was not as emotional as receiving the diagnosis of PCA itself. Seven of the 12 participants chose to share their test results with all relevant family members, 4 chose to share with select family members, and one chose to not disclose to any family members. The majority of family members who were aware of participants' genetic results have not undergone cascade genetic testing or sought cancer screening. Participants with PCA and positive or VUS genetic test results typically share their results with at least immediate family members, but some communication barriers exist. Understanding the best way to provide actionable and relevant information about genetic testing to family members remains a challenge.

6.
Contemp Clin Trials ; 119: 106821, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35710085

RESUMEN

BACKGROUND: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing. METHODS: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing. RESULTS: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results. CONCLUSION: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling. CLINICALTRIALS: gov Identifier: NCT04447703.


Asunto(s)
Asesoramiento Genético , Neoplasias de la Próstata , Aceleración , Pruebas Genéticas , Células Germinativas , Humanos , Masculino , Tecnología
7.
Clin Genitourin Cancer ; 20(2): e104-e113, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35012874

RESUMEN

BACKGROUND: Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice. MATERIALS AND METHODS: A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing. RESULTS: Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use. CONCLUSION: Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.


Asunto(s)
Pruebas Genéticas , Neoplasias de la Próstata , Asesoramiento Genético/psicología , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Oncólogos de Radiación , Urólogos
8.
FEBS Open Bio ; 11(12): 3262-3275, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34709730

RESUMEN

Bacterial phospholipases and sphingomyelinases are lipolytic esterases that are structurally and evolutionarily heterogeneous. These enzymes play crucial roles as virulence factors in several human and animal infectious diseases. Some bacterial phospholipases C (PLCs) have both phosphatidylcholinesterase and sphingomyelinase C activities. Among them, Listeria monocytogenes PlcB, Clostridium perfringens PLC, and Pseudomonas aeruginosa PlcH are the most deeply understood. In silico predictions of substrates docking with these three bacterial enzymes provide evidence that they interact with different substrates at the same active site. This review discusses structural aspects, substrate specificity, and the mechanism of action of those bacterial enzymes on target cells and animal infection models to shed light on their roles in pathogenesis.


Asunto(s)
Esfingomielina Fosfodiesterasa/metabolismo , Esfingomielina Fosfodiesterasa/fisiología , Fosfolipasas de Tipo C/metabolismo , Fosfolipasas de Tipo C/fisiología , Animales , Clostridium perfringens/enzimología , Clostridium perfringens/patogenicidad , Humanos , Listeria monocytogenes/enzimología , Listeria monocytogenes/patogenicidad , Fosfolipasas , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/patogenicidad , Fosfolipasas de Tipo C/genética
9.
Artículo en Inglés | MEDLINE | ID: mdl-34589662

RESUMEN

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.


Asunto(s)
Conducta de Elección , Educación del Paciente como Asunto/normas , Neoplasias de la Próstata/diagnóstico , Anciano , Distribución de Chi-Cuadrado , Asesoramiento Genético/métodos , Asesoramiento Genético/psicología , Asesoramiento Genético/normas , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Neoplasias de la Próstata/genética , Encuestas y Cuestionarios
10.
Toxicon ; 197: 48-54, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33862027

RESUMEN

Phospholipases A2 (PLA2s) and PLA2-like proteins are significant components of snake venoms. Some of these proteins act as potent toxins causing muscle necrosis, which may lead to amputation in severe envenomings. Fundamental aspects of the mechanism of action of these toxins are still not completely known. Myotoxin-I is a catalytically active Asp49 PLA2 from the venom of Bothrops asper, a medically relevant pit viper from Central America. Myotoxin-II is a catalytically inactive Lys49 PLA2-homolog also present in the venom of this snake. For the first time, the in vivo cellular localization of these myotoxins was studied in mouse skeletal muscle using immunofluorescence. Results showed that after 5 min of injection in the gastrocnemius muscle, both toxins initially interacted with the sarcolemma, and some colocalization with nuclei was already evident, especially for Mt-II. After 3 h of injection, a significant colocalization with the nuclei was observed for both toxins. These in vivo results confirm the importance of the initial interaction of these toxins with the sarcolemma and furthermore highlight the internalization and interaction of the toxins with nuclei during their pathophysiological activities, as observed in recent studies using cell culture.


Asunto(s)
Bothrops , Venenos de Crotálidos , Animales , América Central , Venenos de Crotálidos/toxicidad , Modelos Animales de Enfermedad , Fosfolipasas A2 Grupo II , Ratones , Proteínas de Reptiles/toxicidad
11.
Support Care Cancer ; 29(4): 2145-2151, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32876733

RESUMEN

BACKGROUND: Genetic counseling (GC) presents an opportunity to address modifiable cancer risk factors, such as obesity, which is impacted by non-adherence to physical activity (PA) guidelines. Adherence to PA guidelines has not been assessed among men undergoing GC for prostate cancer (PCA). We conducted a targeted analysis of men undergoing PCA GC to assess adherence to PA recommendations. METHODS: Using a cross-sectional design, a total of 158 men from the Genetic Evaluation of Men (GEM) study at two academic cancer centers with a diagnosis or at risk for PCA completed a structured lifestyle survey, including questions about the number of days and intensity of PA over the past year. One-sample t tests assessed adherence of participants to PA recommendations. Chi-square analyses compared differences in PA adherence by PCA status, aggressiveness, family history, and body mass index. Logistic regression analyses identified predictors of PA adherence. RESULTS: High proportions of GEM participants were overweight (44.9%) or obese (38.0%, p = 0.002). Men with PCA engaged in less moderate (p = 0.019) and vigorous (p = 0.005) aerobic activity than men without PCA. Higher education was predictive of adherence to light (p = 0.008), moderate (p = 0.019), and vigorous (p = 0.002) intensity PA. Older age (p = 0.015) and higher education (p = 0.001) were predictive of adherence to strength-based recommendations. CONCLUSIONS: High proportions of men receiving PCA GC were overweight/obese and lacked adherence to PA recommendations. GC represents a teachable moment to address PA to reduce cancer risk and promote cancer survivorship.


Asunto(s)
Ejercicio Físico/fisiología , Asesoramiento Genético/métodos , Neoplasias de la Próstata/terapia , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Factores de Riesgo , Supervivencia
12.
Eur Urol Oncol ; 3(3): 291-297, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31278035

RESUMEN

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing. OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands. DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher's exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx. RESULTS AND LIMITATIONS: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes. CONCLUSIONS: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies. PATIENT SUMMARY: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families.


Asunto(s)
Mutación de Línea Germinal , Síndromes Neoplásicos Hereditarios/epidemiología , Neoplasias de la Próstata/genética , Femenino , Pruebas Genéticas , Humanos , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico , Linaje , Prevalencia , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico
13.
Prostate ; 79(7): 778-783, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30905089

RESUMEN

BACKGROUND: Genetic counseling (GC) and genetic testing (GT) for prostate cancer (PCA) is a rapidly growing, affording opportunity for healthy lifestyle promotion in men aligned with cancer survivorship and cancer prevention goals. We conducted a targeted dietary analysis of men undergoing GC/GT for PCA for adherence to the United States Department of Agriculture (USDA) Food Pattern recommendations which align with preventing cancer and recurrences in the Genetic Evaluation of Men (GEM) study at two academic centers to inform future strategies for diet intervention. METHODS: Participants of GEM with PCA or at-risk for PCA completed a structured food frequency questionnaire indicating number of servings consumed per day or per week of fruits, vegetables, red meat, seafood, processed meat, and foods high in saturated fat. Adherence to the USDA recommendations was assessed for the total sample and by PCA status and aggressiveness, family history, and body mass index (BMI) through χ 2 contingency analyses. One-sample t tests were used to compare the dietary behaviors of men to USDA Recommendations. Levels of α were set a priori at P < 0.05. RESULTS: Of 239 males undergoing GC on the study, surveys were completed by 197 men (82.4%), and complete survey data was available on 113 men (47.3%). By the Centers for Disease Control and Prevention BMI classification, 82.3% of the cohort was overweight (45.1%) or obese (37.2%). GEM participants reported consuming less fruits (P = 0.015), less vegetables ( P < 0.001), less seafood ( P < 0.001), more processed meats ( P < 0.001), and more foods high in saturated fats ( P < 0.001) than recommended. CONCLUSION: A high proportion of men receiving GC/GT for PCA were overweight and/or obese with lack of adherence to national diet recommendations for cancer risk and recurrence, affording a teachable moment and supporting the systematic focus of introducing nutrition intervention during GC to promote survivorship.


Asunto(s)
Evaluación Nutricional , Obesidad/complicaciones , Neoplasias de la Próstata/dietoterapia , Neoplasias de la Próstata/prevención & control , Anciano , Índice de Masa Corporal , Asesoramiento Genético , Pruebas Genéticas , Estilo de Vida Saludable , Humanos , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Sobrepeso/complicaciones , Sobrepeso/dietoterapia , Cooperación del Paciente , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/terapia , Medición de Riesgo
14.
Sci Rep ; 8(1): 10619, 2018 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-30006575

RESUMEN

Phospholipases A2 are a major component of snake venoms. Some of them cause severe muscle necrosis through an unknown mechanism. Phospholipid hydrolysis is a possible explanation of their toxic action, but catalytic and toxic properties of PLA2s are not directly connected. In addition, viperid venoms contain PLA2-like proteins, which are very toxic even if they lack catalytic activity due to a critical mutation in position 49. In this work, the PLA2-like Bothrops asper myotoxin-II, conjugated with the fluorophore TAMRA, was found to be internalized in mouse myotubes, and in RAW264.7 cells. Through experiments of protein fishing and mass spectrometry analysis, using biotinylated Mt-II as bait, we found fifteen proteins interacting with the toxin and among them nucleolin, a nucleolar protein present also on cell surface. By means of confocal microscopy, Mt-II and nucleolin were shown to colocalise, at 4 °C, on cell membrane where they form Congo-red sensitive assemblies, while at 37 °C, 20 minutes after the intoxication, they colocalise in intracellular spots going from plasmatic membrane to paranuclear and nuclear area. Finally, nucleolin antagonists were found to inhibit the Mt-II internalization and toxic activity and were used to identify the nucleolin regions involved in the interaction with the toxin.


Asunto(s)
Venenos de Crotálidos/metabolismo , Fosfolipasas A2 Grupo II/metabolismo , Neurotoxinas/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Reptiles/metabolismo , Animales , Bothrops , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Venenos de Crotálidos/toxicidad , Fosfolipasas A2 Grupo II/toxicidad , Células HeLa , Humanos , Hidrólisis , Microscopía Intravital , Ratones , Microscopía Confocal , Fibras Musculares Esqueléticas , Neurotoxinas/toxicidad , Fosfoproteínas/antagonistas & inhibidores , Fosfoproteínas/genética , Cultivo Primario de Células , Unión Proteica/efectos de los fármacos , Dominios Proteicos , Células RAW 264.7 , Interferencia de ARN , Proteínas de Unión al ARN/antagonistas & inhibidores , Proteínas de Unión al ARN/genética , Proteínas de Reptiles/toxicidad , Nucleolina
15.
Prostate ; 78(12): 879-888, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29655297

RESUMEN

BACKGROUND: Genetic testing (GT) for prostate cancer (PCA) is rising, with limited insights regarding genetic counseling (GC) needs of males. Genetic Evaluation of Men (GEM) is a prospective multigene testing study for inherited PCA. Men undergoing GC were surveyed on knowledge of cancer risk and genetics (CRG) and understanding of personal GT results to identify GC needs. METHODS: GEM participants with or high-risk for PCA were recruited. Pre-test GC was in-person, with video and handout, or via telehealth. Post-test disclosure was in-person, by phone, or via telehealth. Clinical and family history data were obtained from participant surveys and medical records. Participants completed measures of knowledge of CRG, literacy, and numeracy pre-test and post-test. Understanding of personal genetic results was assessed post-test. Factors associated with knowledge of CRG and understanding of personal genetic results were examined using multivariable linear regression or McNemar's test. RESULTS: Among 109 men who completed pre- and post-GT surveys, multivariable analysis revealed family history meeting hereditary cancer syndrome (HCS) criteria was significantly predictive of higher baseline knowledge (P = 0.040). Of 101 men who responded definitively regarding understanding of results, 13 incorrectly reported their result (McNemar's P < 0.001). Factors significantly associated with discordance between reported and actual results included having a variant of uncertain significance (VUS) (P < 0.001) and undergoing GC via pre-test video and post-test phone disclosure (P = 0.015). CONCLUSIONS: While meeting criteria for HCS was associated with higher knowledge of CRG, understanding of personal GT results was lacking among a subset of males with VUS. A more exploratory finding was lack of understanding of results among men who underwent GC utilizing video and phone. Studies optimizing GC strategies for males undergoing multigene testing for inherited PCA are warranted.


Asunto(s)
Asesoramiento Genético , Pruebas Genéticas , Mutación de Línea Germinal/genética , Neoplasias de la Próstata/genética , Adulto , Anciano , Anciano de 80 o más Años , Predisposición Genética a la Enfermedad , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Herencia Multifactorial/genética , Educación del Paciente como Asunto
16.
J Health Psychol ; 23(14): 1800-1809, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-28810355

RESUMEN

Despite conflicting guidelines, a significant subset of high-risk men decide to undergo routine prostate cancer screening. Yet, there is a scarcity of available programs, and no studies evaluating interventions to support men in dealing with the psychosocial impact of screening. In this study, one of the first to explore the responses of high-risk men enrolling in a Prostate Cancer Risk Assessment Program ( N = 128), patients underwent a prostate cancer risk counseling visit immediately followed by either a cognitive-affective preparation session designed to help them process the information they received or a general health education session. All men in this self-selected sample chose to participate in prostate cancer screening. Men were assessed 3 weeks and 6 months post-counseling. The impact of the enhanced counseling condition on knowledge, perceived risk, expectancies, and intrusive ideation was a function of racial and coping style group. Implications for tailored interventions to maximize preparedness for risk and screening counseling are discussed.


Asunto(s)
Consejo/métodos , Detección Precoz del Cáncer/psicología , Neoplasias de la Próstata/psicología , Adaptación Psicológica , Adulto , Negro o Afroamericano , Anciano , Cognición , Detección Precoz del Cáncer/efectos adversos , Estudios de Seguimiento , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/etnología , Riesgo
17.
Nat Commun ; 8(1): 607, 2017 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-28928360

RESUMEN

In melanoma, therapies with inhibitors to oncogenic BRAFV600E are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3. Consistently, resistance of melanomas to BRAF and/or MEK inhibitors is associated with increased CD20 and IGF-1 transcript levels in tumors and IGF-1 expression in tumor-associated B cells. Furthermore, first clinical data from a pilot trial in therapy-resistant metastatic melanoma patients show anti-tumor activity through B-cell depletion by anti-CD20 antibody. Our findings establish a mechanism of acquired therapy resistance through tumor-associated B cells with important clinical implications.Resistance to BRAFV600E inhibitors often occurs in melanoma patients. Here, the authors describe a potential mechanism of acquired drug resistance mediated by tumor-associated B cells-derived IGF-1.


Asunto(s)
Antineoplásicos/uso terapéutico , Linfocitos B/metabolismo , Resistencia a Antineoplásicos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Melanoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Supervivencia Celular , Cisplatino/uso terapéutico , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Técnicas In Vitro , Melanoma/genética , Paclitaxel/uso terapéutico , Proyectos Piloto , Proteínas Proto-Oncogénicas B-raf/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Neoplasias Cutáneas/genética , Microambiente Tumoral
18.
Appl Nurs Res ; 35: 94-98, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28532736

RESUMEN

Current research indicates a relationship between EI, stress, coping strategies, well-being and mental health. Emotional intelligence skills and knowledge, and coping strategies can be increased with training. OBJECTIVE: The aims of this study were to use a controlled design to test the impact of theoretically based training on the different components of EI and coping styles in a sample of nurses working with older adults. METHODS: A group of 92 professionals (RN and CAN) who attended a workshop on EI were included in the study. They completed a self-reported measure of EI and coping styles on three occasions: pre- and post-workshop and at one year follow-up. The EI workshop consisted of four 4-h sessions conducted over a four-week period. Each session was held at the one-week interval. This interval allowed participants to apply what was taught during the session to their daily life. The instruments to measure the EI and coping were the Trait Meta-Mood Scale and the CAE test. RESULTS: There were significant differences between the pre- and post-workshop measures both at the end of the workshop and up to one year for both the Trait Meta-Mood Scale scores and the CAE test. There was a significant increase in the EI and coping styles after the workshop and one year thereafter. CONCLUSION: The workshop was useful for developing EI in the professionals. The immediate impact of the emotional consciousness of individuals was particularly significant for all participants. The long-term impact was notable for the significant increase in EI and most coping styles.


Asunto(s)
Adaptación Psicológica , Actitud del Personal de Salud , Inteligencia Emocional , Enfermería Geriátrica/métodos , Personal de Enfermería/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
19.
JCO Precis Oncol ; 12017 May.
Artículo en Inglés | MEDLINE | ID: mdl-34164591

RESUMEN

PURPOSE: Multigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy. PATIENTS AND METHODS: Eligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution. RESULTS: Of 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was significantly associated with mutation status (P = .004), and FH that met criteria for hereditary breast and ovarian cancer syndrome was significantly associated with PCA (odds ratio, 2.33; 95% CI, 1.05 to 5.18). Variants of uncertain significance were reported in 70 men (35.0%). Among mutation carriers, 45.5% had personal/FH concordant with the gene. A tailored GC model was developed based on emerging findings. CONCLUSION: Multigene testing for PCA identifies mutations mostly in DNA repair genes, with implications for precision therapy. The study highlights the importance of comprehensive genetic evaluation for PCA beyond metastatic disease, including early-stage disease with strong FH. Detailed FH is important for referrals of men for genetic evaluation. The results inform precision GC and cancer screening for men and their male and female blood relatives.

20.
Microbiol Mol Biol Rev ; 80(3): 597-628, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27307578

RESUMEN

Bacterial sphingomyelinases and phospholipases are a heterogeneous group of esterases which are usually surface associated or secreted by a wide variety of Gram-positive and Gram-negative bacteria. These enzymes hydrolyze sphingomyelin and glycerophospholipids, respectively, generating products identical to the ones produced by eukaryotic enzymes which play crucial roles in distinct physiological processes, including membrane dynamics, cellular signaling, migration, growth, and death. Several bacterial sphingomyelinases and phospholipases are essential for virulence of extracellular, facultative, or obligate intracellular pathogens, as these enzymes contribute to phagosomal escape or phagosomal maturation avoidance, favoring tissue colonization, infection establishment and progression, or immune response evasion. This work presents a classification proposal for bacterial sphingomyelinases and phospholipases that considers not only their enzymatic activities but also their structural aspects. An overview of the main physiopathological activities is provided for each enzyme type, as are examples in which inactivation of a sphingomyelinase- or a phospholipase-encoding gene impairs the virulence of a pathogen. The identification of sphingomyelinases and phospholipases important for bacterial pathogenesis and the development of inhibitors for these enzymes could generate candidate vaccines and therapeutic agents, which will diminish the impacts of the associated human and animal diseases.


Asunto(s)
Bacterias/patogenicidad , Hongos/patogenicidad , Fosfolipasa D/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Fosfolipasas de Tipo C/metabolismo , Bacterias/enzimología , Firmicutes/enzimología , Firmicutes/patogenicidad , Hongos/enzimología , Proteobacteria/enzimología , Proteobacteria/patogenicidad , Staphylococcus aureus/enzimología , Staphylococcus aureus/patogenicidad , Factores de Virulencia/metabolismo
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