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1.
Nutrients ; 16(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38613081

RESUMO

Cancer screening is pivotal for early detection and improved survival rates. While socio-ecological factors are known to influence screening uptake, the role of lifestyle, dietary habits, and general health in shaping these decisions remains underexplored. Utilizing the 2019 Korea National Health and Nutrition Examination Survey (KNHANES), this study examined the myriad of factors impacting cancer screening utilization. Data from 274,872 adults aged 40 years or older were scrutinized, highlighting demographics, income, lifestyle behaviors, health-related variables, nutrient intake, and dietary quality. A combination of descriptive statistics and logistic regression helped us ascertain influential determinants. Higher educational attainment and income quartiles were positively correlated with cancer screening rates. Regular walkers, those engaged in moderate physical activity, and individuals with a previous cancer diagnosis were more likely to get screened. High-risk drinkers and smokers were less inclined towards screening. Dietary habits also influenced screening decisions. Notably, participants with healthier eating behaviors, indicated by factors such as regular breakfasts and fewer meals out, were more likely to undergo screening. Additionally, nutrient intake analysis revealed that those who had undergone screening consumed greater quantities of most nutrients, bar a few exceptions. For individuals aged 50-64, nutritional assessment indicators highlighted a higher mean adequacy ratio (MAR) and index of nutritional quality (INQ) value among those who participated in screening, suggesting better nutritional quality. This study elucidates the complex socio-ecological and nutritional landscape influencing cancer screening decisions. The results underscore the importance of a holistic approach, emphasizing lifestyle, dietary habits, and socio-economic considerations. It provides a roadmap for policymakers to craft more inclusive screening programs, ensuring equal access and promoting early detection.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Adulto , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Ingestão de Alimentos , Ingestão de Energia , República da Coreia
2.
JAMA Netw Open ; 7(4): e245295, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38625704

RESUMO

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Pessoa de Meia-Idade , Idoso , Grupos Raciais , Etnicidade
3.
Am J Ind Med ; 67(5): 483-495, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530105

RESUMO

BACKGROUND: Although firefighters have increased risk for colon and prostate cancer, limited information exists on screening practices for these cancers in volunteer firefighters who compose two-thirds of the US fire service. We estimated the prevalence of colon and prostate cancer screening among volunteer firefighters using eligibility criteria from 4 evidence-based screening recommendations and evaluated factors influencing screening. METHODS: We evaluated colon (n = 569) and prostate (n = 498) cancer screening prevalence in a sample of US volunteer firefighters using eligibility criteria from the US Preventive Services Taskforce (USPSTF), National Fire Protection Association, American Cancer Society, and National Comprehensive Cancer Network. We assessed associations with fire service experience, demographics, and cancer risk perception based on USPSTF guidelines. RESULTS: For those eligible based on USPSTF guidelines, colon and prostate cancer screening prevalence was 51.7% (95% CI: 45.7, 57.8) and 48.8% (95% CI: 40.0, 57.6), respectively. Higher odds of colon and prostate cancer screening were observed with older age and with some college education compared to those with less education. Fire service experience and cancer risk perception were not associated with screening practices. CONCLUSION: This is the first large study to assess colon and prostate cancer screening among US volunteer firefighters based on different screening guidelines. Our findings suggest gaps in cancer prevention efforts in the US volunteer fire service. Promoting cancer screening education and opportunities for volunteer firefighters by their fire departments, healthcare professionals, and public health practitioners, may help to address the gaps.


Assuntos
Bombeiros , Neoplasias da Próstata , Masculino , Humanos , Estados Unidos/epidemiologia , Detecção Precoce de Câncer , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/prevenção & controle , Prevalência , Antígeno Prostático Específico , Voluntários , Colo
4.
Syst Rev ; 13(1): 88, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493159

RESUMO

PURPOSE: Lung cancer is the leading cause of cancer deaths in Canada, and because early cancers are often asymptomatic screening aims to prevent mortality by detecting cancer earlier when treatment is more likely to be curative. These reviews will inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for lung cancer. METHODS: We will update the review on the benefits and harms of screening with CT conducted for the task force in 2015 and perform de novo reviews on the comparative effects between (i) trial-based selection criteria and use of risk prediction models and (ii) trial-based nodule classification and different nodule classification systems and on patients' values and preferences. We will search Medline, Embase, and Cochrane Central (for questions on benefits and harms from 2015; comparative effects from 2012) and Medline, Scopus, and EconLit (for values and preferences from 2012) via peer-reviewed search strategies, clinical trial registries, and the reference lists of included studies and reviews. Two reviewers will screen all citations (including those in the previous review) and base inclusion decisions on consensus or arbitration by another reviewer. For benefits (i.e., all-cause and cancer-specific mortality and health-related quality of life) and harms (i.e., overdiagnosis, false positives, incidental findings, psychosocial harms from screening, and major complications and mortality from invasive procedures as a result of screening), we will include studies of adults in whom lung cancer is not suspected. We will include randomized controlled trials comparing CT screening with no screening or alternative screening modalities (e.g., chest radiography) or strategies (e.g., CT using different screening intervals, classification systems, and/or patient selection via risk models or biomarkers); non-randomized studies, including modeling studies, will be included for the comparative effects between trial-based and other selection criteria or nodule classification methods. For harms (except overdiagnosis) we will also include non-randomized and uncontrolled studies. For values and preferences, the study design may be any quantitative design that either directly or indirectly measures outcome preferences on outcomes pertaining to lung cancer screening. We will only include studies conducted in Very High Human Development Countries and having full texts in English or French. Data will be extracted by one reviewer with verification by another, with the exception of result data on mortality and cancer incidence (for calculating overdiagnosis) where duplicate extraction will occur. If two or more studies report on the same comparison and it is deemed suitable, we will pool continuous data using a mean difference or standardized mean difference, as applicable, and binary data using relative risks and a DerSimonian and Laird model unless events are rare (< 1%) where we will pool odds ratios using Peto's method or (if zero events) the reciprocal of the opposite treatment arm size correction. For pooling proportions, we will apply suitable transformation (logit or arcsine) depending on the proportions of events. If meta-analysis is not undertaken we will synthesize the data descriptively, considering clinical and methodological differences. For each outcome, two reviewers will independently assess within- and across-study risk of bias and rate the certainty of the evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation), and reach consensus. DISCUSSION: Since 2015, additional trials and longer follow-ups or additional data (e.g., harms, specific patient populations) from previously published trials have been published that will improve our understanding of the benefits and harms of screening. The systematic review of values and preferences will allow fulsome insights that will inform the balance of benefits and harms. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378858.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Adulto , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Qualidade de Vida , Canadá , Revisões Sistemáticas como Assunto , Tomografia Computadorizada por Raios X , Serviços Preventivos de Saúde , Tomografia , Metanálise como Assunto
5.
Methods Mol Biol ; 2777: 135-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478341

RESUMO

Prostate cancer (PCa) is the second most common malignancy and the fifth leading cause of cancer death in men worldwide. Despite its prevalence, the highly heterogenic PCa has shown difficulty to establish representative cell lines that reflect the diverse phenotypes and different stages of the disease in vitro and hence hard to model in preclinical research. The patient-derived organoid (PDO) technique has emerged as a groundbreaking three-dimensional (3D) tumor modeling platform in cancer research. This versatile assay relies on the unique ability of cancer stem cells (CSCs) to self-organize and differentiate into organ-like mini structures. The PDO culture system allows for the long-term maintenance of cancer cells derived from patient tumor tissues. Moreover, it recapitulates the parental tumor features and serves as a superior preclinical model for in vitro tumor representation and personalized drug screening. Henceforth, PDOs hold great promise in precision medicine for cancer. Herein, we describe the detailed protocol to establish and propagate organoids derived from isolated cell suspensions of PCa patient tissues or cell lines using the 3D semisolid Matrigel™-based hanging-drop method. In addition, we highlight the relevance of PDOs as a tool for evaluating drug efficacy and predicting tumor response in PCa patients.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Próstata , Masculino , Humanos , Avaliação Pré-Clínica de Medicamentos/métodos , Neoplasias da Próstata/patologia , Organoides
6.
Ann Fam Med ; 22(2): 103-112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527820

RESUMO

PURPOSE: Many individuals who are eligible for lung cancer screening have comorbid conditions complicating their shared decision-making conversations with physicians. The goal of our study was to better understand how primary care physicians (PCPs) factor comorbidities into their evaluation of the risks and benefits of lung cancer screening and into their shared decision-making conversations with patients. METHODS: We conducted semistructured interviews by videoconference with 15 PCPs to assess the extent of shared decision-making practices and explore their understanding of the intersection of comorbidities and lung cancer screening, and how that understanding informed their clinical approach to this population. RESULTS: We identified 3 themes. The first theme was whether to discuss or not to discuss lung cancer screening. PCPs described taking additional steps for individuals with complex comorbidities to decide whether to initiate this discussion and used subjective clinical judgment to decide whether the conversation would be productive and beneficial. PCPs made mental assessments that factored in the patient's health, life expectancy, quality of life, and access to support systems. The second theme was that shared decision making is not a simple discussion. When PCPs did initiate discussions about lung cancer screening, although some believed they could provide objective information, others struggled with personal biases. The third theme was that ultimately, the decision to be screened was up to the patient. Patients had the final say, even if their decision was discordant with the PCP's advice. CONCLUSIONS: Shared decision-making conversations about lung cancer screening differed substantially from the standard for patients with complex comorbidities. Future research should include efforts to characterize the risks and benefits of LCS in patients with comorbidities to inform guidelines and clinical application.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Tomada de Decisões , Multimorbidade , Qualidade de Vida , Atenção Primária à Saúde
7.
BMC Health Serv Res ; 24(1): 336, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481315

RESUMO

BACKGROUND: Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities. Here we discuss the implementation of various recruitment strategies for enrolling participants into a large, prospective cohort study, assessing the need for adaptations and making them in real-time, while maintaining high adherence to the protocol and high participant satisfaction. METHODS: While conducting a large, prospective trial of a multi-cancer early detection blood test at Geisinger, an integrated health system in central Pennsylvania, we monitored recruitment progress, adherence to the protocol, and participants' satisfaction. Tracking mechanisms such as paper records, electronic health records, research databases, dashboards, and electronic files were utilized to measure each outcome. We then reviewed study procedures and timelines to list the implementation strategies that were used to address barriers to recruitment, protocol adherence and participant satisfaction. RESULTS: Adaptations to methods that contributed to achieving the enrollment goal included offering multiple recruitment options, adopting group consenting, improving visit convenience, increasing the use of electronic capture and the tracking of data and source documents, staffing optimization via leveraging resources external to the study team when appropriate, and integrating the disclosure of study results into routine clinical care without adding unfunded work for clinicians. We maintained high protocol adherence and positive participant experience as exhibited by a very low rate of protocol deviations and participant complaints. CONCLUSION: Recruiting rapidly for large studies - and thereby facilitating clinical translation - requires a nimble, creative approach that marshals available resources and changes course according to data. Planning a rigorous assessment of a study's implementation outcomes prior to study recruitment can further ground study adaptations and facilitate translation into practice. This can be accomplished by proactively and continuously assessing and revising implementation strategies.


Assuntos
Detecção Precoce de Câncer , Testes Hematológicos , Humanos , Pennsylvania , Estudos Prospectivos , Neoplasias
8.
Sci Rep ; 14(1): 6768, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514638

RESUMO

Breast cancer, the prevailing malignant tumor among women, is linked to progesterone and its receptor (PR) in both tumorigenesis and treatment responsiveness. Despite thorough investigation, the precise molecular mechanisms of progesterone in breast cancer remain unclear. The human progesterone receptor (PR) serves as an essential therapeutic target for breast cancer treatment, warranting the rapid design of small molecule therapeutics that can effectively inhibit HPR. By employing cutting-edge computational techniques like molecular screening, simulation, and free energy calculation, the process of identifying potential lead molecules from natural products has been significantly expedited. In this study, we employed pharmacophore-based virtual screening and molecular simulations to identify natural product-based inhibitors of human progesterone receptor (PR) in breast cancer treatment. High-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases was performed, leading to the identification of potential lead compounds. The analysis of binding modes for the top five compounds from both database provides valuable structural insights into the inhibition of HPR for breast cancer treatment. The top five hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as HPR inhibitors.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Farmacóforo , Receptores de Progesterona , Progesterona/uso terapêutico , Detecção Precoce de Câncer , Ligantes
9.
Womens Health Issues ; 34(3): 268-275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38448251

RESUMO

PURPOSE: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. METHODS: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FINDINGS: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. CONCLUSION: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation.


Assuntos
Neoplasias da Mama , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Neoplasias Ovarianas , Atenção Primária à Saúde , Pesquisa Qualitativa , Humanos , Feminino , Adulto , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Medição de Risco , Adulto Jovem , Grupos Focais , Programas de Rastreamento , Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico
10.
J Transl Med ; 22(1): 132, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310289

RESUMO

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Fosfatidilinositol 3-Quinases/genética , Avaliação Pré-Clínica de Medicamentos , Proteínas Proto-Oncogênicas p21(ras)/genética , Detecção Precoce de Câncer , Biópsia Líquida , Inibidores de Fosfoinositídeo-3 Quinase , Biomarcadores , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação/genética
11.
Urol Oncol ; 42(5): 158.e11-158.e16, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38365461

RESUMO

INTRODUCTION: Prostate cancer screening has routinely identified men with very low- or low-risk disease, per the National Comprehensive Cancer Network guidelines. Current literature has demonstrated that the most appropriate management strategy for these patients is active surveillance (AS). The mainstay of AS includes periodic biopsies and biannual prostate-specific antigen tests. However, multiparametric magnetic resonance imaging (mpMRI) is uniquely posed to improve patient surveillance. This study aimed to evaluate the utility of an annual mpMRI in patients on AS, focusing on radiologic upgrading and Prostate Imaging-Reporting and Data System (PI-RADS) trends as indicators of clinically significant disease. METHODS: This prospective, single intuition, study enrolled 208 patients on AS who had at least two biopsies and 1 mpMRI with a median follow-up of 5.03 years. The main outcome variable was time to Gleason grade (GG) reclassification. RESULTS: After delineating patients on their initial PI-RADS score, men with score 3 and 5 lesions at first MRI had comparable GG reclassification-free survival to their counterparts. Conversely, men with initial PI-RADS 4 lesions showed a lower 5-year GG reclassification-free survival compared to those with PI-RADS score 1-2. The cohort was then subset to 70 patients who obtained ≥2 mpMRIs on protocol. Men experiencing uptrending mpMRI scores had an increased risk of GG reclassification, with a 35.4% difference in 5 year GG reclassification-free survival probability on the Kaplan-Meier curve analysis. CONCLUSION: In conclusion, this study demonstrates that for men on AS with stable recapitulated disease, an annual MRI may replace repeat biopsies after confirmatory sampling has been obtained. On the other hand, men who initiate AS with PI-RADS 4 and/or who display uptrending mpMRI scores require periodic biopsies along with repeat imaging. This study highlights the utility of integrating an annual MRI into AS protocols, thus promising a more effective approach to management.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico , Estudos Prospectivos , Detecção Precoce de Câncer , Biópsia Guiada por Imagem/métodos , Estudos Retrospectivos
12.
Cancer Med ; 13(2): e6967, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38348960

RESUMO

RATIONALE AND OBJECTIVES: Computer-aided detection (CAD) of pulmonary nodules reduces the impact of observer variability, improving the reliability and reproducibility of nodule assessments in clinical practice. Therefore, this study aimed to assess the impact of CAD on inter-observer agreement in the follow-up management of subsolid nodules. MATERIALS AND METHODS: A dataset comprising 60 subsolid nodule cases was constructed based on the National Cancer Center lung cancer screening data. Five observers independently assessed all low-dose computed tomography scans and assigned follow-up management strategies to each case according to the National Comprehensive Cancer Network (NCCN) guidelines, using both manual measurements and CAD assistance. The linearly weighted Cohen's kappa test was used to measure agreement between paired observers. Agreement among multiple observers was evaluated using the Fleiss kappa statistic. RESULTS: The agreement of the five observers for NCCN follow-up management categorization was moderate when measured manually, with a Fleiss kappa score of 0.437. Utilizing CAD led to a notable enhancement in agreement, achieving a substantial consensus with a Fleiss kappa value of 0.623. After using CAD, the proportion of major and substantial management discrepancies decreased from 27.5% to 15.8% and 4.8% to 1.5%, respectively (p < 0.01). In 23 lung cancer cases presenting as part-solid nodules, CAD significantly elevates the average sensitivity in detecting lung cancer cases presenting as part-solid nodules (overall sensitivity, 82.6% vs. 92.2%; p < 0.05). CONCLUSION: The application of CAD significantly improves inter-observer agreement in the follow-up management strategy for subsolid nodules. It also demonstrates the potential to reduce substantial management discrepancies and increase detection sensitivity in lung cancer cases presenting as part-solid nodules.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Reprodutibilidade dos Testes , Detecção Precoce de Câncer , Variações Dependentes do Observador , Seguimentos , Computadores
13.
Bioorg Chem ; 144: 107176, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330721

RESUMO

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.


Assuntos
Neoplasias da Próstata , Uracila-DNA Glicosidase , Humanos , Masculino , Uracila-DNA Glicosidase/química , Oligonucleotídeos , Gluconato de Antimônio e Sódio , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Detecção Precoce de Câncer
14.
Breast Cancer Res Treat ; 205(1): 169-179, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38347257

RESUMO

PURPOSE: Breast cancer, a common malignancy in Indian women, is preventable and curable upon early diagnosis. Screening is the best control strategy against breast cancer, but its uptake is low in India despite dedicated strategies and programmes. We explored the impact of socio-cultural and financial issues on the uptake of breast cancer screening behaviour among Indian women. METHODS: Breast cancer screening-uptake and relevant social, cultural, and financial data obtained from the National Family Health Survey (NFHS) round 5 were used for analysis. We studied 399,039 eligible females to assess their breast cancer screening behavior and determine the impact of socio-cultural and financial issues on such behavior using multivariable logistic regression. RESULTS: Most participants were 30-34-year-old (27.8%), educated to the secondary level (38.0%), and 81.5% had bank accounts. A third (35.0%) had health insurance, and anaemia was the most common comorbidity (56.1%). Less than 1.0% had undergone breast cancer screening. Higher age, education, urban residence, employment, less privileged social class, and access to the Internet and mass media were predictors of positive screening-uptake behavior (p < 0.05). Mothers of larger number of children, tobacco- and alcohol-users, the richer and having health insurance had negative uptake behavior (p < 0.05). CONCLUSION: A clear impact of socio-cultural and financial factors on breast cancer screening behavior is evident among Indian women. Therefore, apart from the ongoing health system strengthening efforts, our findings call for targeted interventions against prevailing misconceptions and taboos along with economic and social empowerment of women for the holistic success of India's cancer screening strategy.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Fatores Socioeconômicos , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Índia/epidemiologia , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/economia , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Programas de Rastreamento/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Comportamentos Relacionados com a Saúde
15.
BMC Public Health ; 24(1): 525, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378542

RESUMO

INTRODUCTION: Africa has one of the highest burdens of cervical cancer in the world. The unacceptably high incidence and mortality rates could be reduced through implementing a comprehensive approach to its prevention and control that includes screening, which however, is low in most low-and-middle-income countries. Hence, this systematic review aims at exploring factors that prevent women from utilising cervical cancer screening services in the region. METHODS: A mixed method systematic review was conducted. A search was performed on PubMed (Medline), EMBASE, CINAHL (EBSCOHOST) and Scopus databases for articles published until May 2019 without time, language or study design limits. Two reviewers critically appraised the included studies independently using the standard quality assessment criteria for evaluating primary research papers. Results of the quantitative and mixed methods studies were transformed into qualitative data and synthesised using thematic analysis. RESULTS: From a potential 2 365 studies, 24 from 11 countries met the eligibility criteria and were selected; eight qualitative, 13 quantitative, and three that used the mixed-method approach. The primary barriers were identified as poor access to screening services, lack of awareness and knowledge on cervical cancer and screening, and socio-cultural influences. Service providers perceived lack of skills, screening equipment and supplies, and staff shortages as the major barriers to the provision of screening services. CONCLUSION: Barriers to cervical cancer screening in Africa are multifaceted and require a holistic approach that will address them concurrently at the health system, individual, interpersonal, community and structural levels. Political will complimented by stakeholder involvement is required in the development and implementation of strategies that will ensure acceptability, availability, accessibility, and affordability of screening to minimise barriers in accessing the service.


Assuntos
Detecção Precoce de Câncer , Neoplasias do Colo do Útero , Feminino , Humanos , Acessibilidade aos Serviços de Saúde , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , África , Custos e Análise de Custo
16.
BMC Public Health ; 24(1): 211, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233805

RESUMO

BACKGROUND: Cervical cancer is a global disease and it is well established that cervical cancer is caused by human papillomavirus (HPV). In Sweden self-sampling for HPV is now used as a complement to sampling performed by a midwife. However, there is a lack of knowledge on how older women perceive the self-sampling compared to the sampling performed by a midwife. Therefore, the aim of the study was to describe how women, aged 64 years and older, perceived the process of self-sampling and sampling performed by a midwife for HPV-testing. METHODS: Eighteen women were included in a qualitative interview study, and a phenomenographic approach was used for the analysis of the interviews. RESULTS: Three descriptive categories emerged: Confidence in sampling, Facilitating participation and Being informed. Within the categories, eight conceptions emerged describing the variation relating to how the women perceived the process of self-sampling and sampling performed by a midwife. CONCLUSIONS: Women in this study describe confidence in self-sampling for HPV-testing and that the self-sampling was saving time and money, both for themselves and for society. Information in relation to an HPV-positive test result is of importance and it must be kept in mind that women affected by HPV may feel guilt and shame, which health care professionals should pay attention to. This knowledge can be used in education of health care staff. TRIAL REGISTRATION: https://researchweb.org/is/fourol/project/228071 . Reg. no 228,071.


Assuntos
Tocologia , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Gravidez , Idoso , Papillomavirus Humano , Neoplasias do Colo do Útero/diagnóstico , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Manejo de Espécimes , Detecção Precoce de Câncer , Programas de Rastreamento , Autocuidado
17.
J Cancer Surviv ; 18(1): 11-16, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38294600

RESUMO

Roswell Park Comprehensive Cancer Center (Roswell) is the only NCI-designated cancer center in New York State outside of the New York City metropolitan area. The Cancer Screening and Survivorship Program combines cancer screening services with survivorship care in a freestanding centralized clinic with providers also dispersed to see survivors in other clinical areas. The aims of the program are to provide comprehensive, patient-centered care to cancer survivors and their families and caregivers by addressing symptoms, supporting wellness, prevention and quality of life, and engaging community primary care providers in a shared-care model. The clinic is led by an onco-generalist, defined as an internal medicine trained physician serving cancer survivor's medical issues from all cancer disease sites. Roswell's Cancer Screening and Survivorship Program growth and development is guided by ongoing research related to patient needs and barriers to care, overall quality of life, health promotion and prevention, as well as education and training to build a more robust cancer survivorship workforce. The cancer center leadership has identified the expansion of cancer survivorship paired with community outreach and engagement, PCP outreach and education, and comprehensive cancer screening services as one of the key strategic areas of growth over the next decade. With the investment in our long-term strategic plan, we expect to continue to grow and serve a broader community of cancer survivors and further our research related to the structure and outcomes of our programmatic activities. IMPLICATIONS FOR CANCER SURVIVORS: This program provides robust whole-person care for cancer survivors and provides an example of successful infrastructure for cancer survivorship.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Sobrevivência , Detecção Precoce de Câncer , Qualidade de Vida , Sobreviventes , Neoplasias/diagnóstico , Neoplasias/prevenção & controle
18.
Biochim Biophys Acta Gen Subj ; 1868(4): 130566, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38244703

RESUMO

BACKGROUND: Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine. METHODS: PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs. RESULTS: We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone. CONCLUSION: PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Avaliação Pré-Clínica de Medicamentos , Detecção Precoce de Câncer , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Organoides
19.
Gut ; 73(4): 622-628, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38176899

RESUMO

OBJECTIVE: We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative. DESIGN: Study participants were patients aged 45-75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3-9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups. RESULTS: We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). CONCLUSION: Among adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests. TRIAL REGISTRATION NUMBER: NCT05987709.


Assuntos
Neoplasias Colorretais , Prestação Integrada de Cuidados de Saúde , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Detecção Precoce de Câncer , Colonoscopia , Sangue Oculto , Programas de Rastreamento , Neoplasias Colorretais/diagnóstico , Cooperação do Paciente
20.
ChemMedChem ; 19(5): e202300527, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241069

RESUMO

A novel series of N-(4-cyano-1,3-oxazol-5-yl)sulfonamides have been synthesized and characterized by IR, 1 H NMR, 13 C NMR spectroscopy, elemental analysis and chromato-mass-spectrometry. The anticancer activities of all newly synthesized compounds were evaluated via a single high-dose assay (10 µM) against 60 cancer cell lines by the National Cancer Institute (USA) according to its screening protocol. Among them, compounds 2 and 10 exhibited the highest activity against the 60 cancer cell lines panel in the one-dose assay. Compounds 2 and 10 showed inhibitory activity within the GI50 parameter and in five dose analyses. However, their cytostatic activity was only observed against some cancer cell lines, and cytotoxic concentration was outside the maximum used, i. e., >100 µM. The COMPARE analysis showed that the average graphs of the tested compounds have a moderate positive correlation with compounds with the L-cysteine analog and vinblastine (GI50 ) as well as paclitaxel (TGI), which target microtubules. Therefore, disruption of microtubule formation may be one of the mechanisms of the anticancer activity of the tested compounds, especially since among tubulin inhibitors with antitumor activity, compounds with an oxazole motif are widely represented. Therefore, N-(4-cyano-1,3-oxazol-5-yl)sulfonamides may be promising for further functionalization to obtain more active compounds.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Detecção Precoce de Câncer , Estrutura Molecular , Relação Estrutura-Atividade , Sulfanilamida/farmacologia , Sulfonamidas/química , Humanos
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