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1.
Cell ; 178(1): 160-175.e27, 2019 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-31155233

RESUMEN

Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.


Asunto(s)
Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Microambiente Tumoral , Animales , Proliferación Celular , Técnicas de Cocultivo , Transición Epitelial-Mesenquimal , Femenino , Células HEK293 , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas Quinasas Activadas por Mitógenos/metabolismo , RNA-Seq , Factor de Transcripción STAT3/metabolismo , Células del Estroma/metabolismo , Transfección
2.
Mol Cell ; 73(5): 985-1000.e6, 2019 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-30711375

RESUMEN

Hyper-phosphorylation of RB controls its interaction with E2F and inhibits its tumor suppressor properties. However, during G1 active RB can be mono-phosphorylated on any one of 14 CDK phosphorylation sites. Here, we used quantitative proteomics to profile protein complexes formed by each mono-phosphorylated RB isoform (mP-RB) and identified the associated transcriptional outputs. The results show that the 14 sites of mono-phosphorylation co-ordinate RB's interactions and confer functional specificity. All 14 mP-RBs interact with E2F/DP proteins, but they provide different shades of E2F regulation. RB mono-phosphorylation at S811, for example, alters RB transcriptional activity by promoting its association with NuRD complexes. The greatest functional differences between mP-RBs are evident beyond the cell cycle machinery. RB mono-phosphorylation at S811 or T826 stimulates the expression of oxidative phosphorylation genes, increasing cellular oxygen consumption. These results indicate that RB activation signals are integrated in a phosphorylation code that determines the diversity of RB activity.


Asunto(s)
Neoplasias de la Mama/metabolismo , Proteína de Retinoblastoma/metabolismo , Transducción de Señal , Neoplasias de la Mama/genética , Línea Celular Tumoral , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Mutación , Fosforilación Oxidativa , Fosforilación , Unión Proteica , Proteómica/métodos , Proteína de Retinoblastoma/genética , Transducción de Señal/genética , Transcripción Genética
3.
J Public Health Manag Pract ; 30(2): E54-E64, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38032233

RESUMEN

CONTEXT: Opportunities to reduce the risk of cancer, including cervical, liver, and skin cancer, start early in life. To encourage adoption of primary prevention activities in childhood to reduce cancer risk later in life, Centers for Disease Control and Prevention conducted a demonstration project with 3 National Comprehensive Cancer Control Program (NCCCP) recipients. PROGRAM: Iowa, Northwest Portland Area Indian Health Board (NPAIHB), and Pennsylvania NCCCP recipients implemented evidence-based primary prevention activities for cervical, liver, and skin cancer among children using health care provider education, patient education, and policy development. IMPLEMENTATION: Iowa implemented an announcement approach to improve provider education on human papillomavirus (HPV) vaccination. Pennsylvania focused on patient education for reducing skin cancer risk and both provider and patient education for liver cancer prevention. NPAIHB created a sun safety intervention for tribal organizations, including a policy guide, media materials, and patient education. RESULTS: In Iowa, health care providers taking the announcement approach reported significantly higher mean scores on a posttest compared with a pretest regarding perceptions about HPV vaccination, self-efficacy, and behavioral intentions related to vaccination. Pennsylvania integrated sun safety education and sunscreen dispenser programs as a health and wellness initiative in 8 state parks and the Pennsylvania Department of Conservation and Natural Resources incorporated the program in its Pennsylvania Outdoor Recreation Plan. Pennsylvania also implemented health care provider education on the primary prevention of liver cancer through hepatitis B and hepatitis C screening and hepatitis B vaccination. The NPAIHB skin cancer policy guide was created and distributed for use to all 43 federally recognized tribes of Oregon, Washington, and Idaho served by NPAIHB. DISCUSSION: The identification, dissemination, and implementation of these efforts can serve as best practices for future childhood primary prevention programs. NCCCP recipients and public health professionals can use health care provider education, patient education, and policy development to reduce future risk for cervical, liver, and skin cancer among children.


Asunto(s)
Carbonil Cianuro m-Clorofenil Hidrazona/análogos & derivados , Hepatitis B , Neoplasias Hepáticas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias Cutáneas , Niño , Humanos , Infecciones por Papillomavirus/prevención & control , Neoplasias Cutáneas/prevención & control , Prevención Primaria , Vacunas contra Papillomavirus/uso terapéutico
4.
Cancer ; 129(12): 1821-1835, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37063057

RESUMEN

BACKGROUND: Depression is common among breast cancer patients and can affect concordance with guideline-recommended treatment plans. Yet, the impact of depression on cancer treatment and survival is understudied, particularly in relation to the timing of the depression diagnosis. METHODS: The Kentucky Cancer Registry data was used to identify female patients diagnosed with primary invasive breast cancer who were 20 years of age or older in 2007-2011. Patients were classified as having no depression, depression pre-cancer diagnosis only, depression post- cancer diagnosis only, or persistent depression. The impact of depression on receiving guideline-recommended treatment and survival was examined using multivariable logistic regression and Cox regression, respectively. RESULTS: Of 6054 eligible patients, 4.1%, 3.7%, and 6.2% patients had persistent depression, depression pre-diagnosis only, and depression post-diagnosis only, respectively. A total of 1770 (29.2%) patients did not receive guideline-recommended cancer treatment. Compared to patients with no depression, the odds of receiving guideline-recommended treatment were decreased in patients with depression pre-diagnosis only (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.54-1.04) but not in patients with post-diagnosis only or persistent depression. Depression post-diagnosis only (hazard ratio, 1.51; 95% CI, 1.24-1.83) and depression pre-diagnosis only (hazard ratio, 1.26; 95% CI, 0.99-1.59) were associated with worse survival. No significant difference in survival was found between patients with persistent depression and patients with no depression (p > .05). CONCLUSIONS: Neglecting depression management after a breast cancer diagnosis may result in poorer cancer treatment concordance and worse survival. Early detection and consistent management of depression is critical in improving patient survival.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico , Kentucky/epidemiología , Modelos de Riesgos Proporcionales , Sistema de Registros
5.
Proc Natl Acad Sci U S A ; 116(12): 5223-5232, 2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30819896

RESUMEN

Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single-cell RNA sequencing in an orthotopic mouse prostate cancer model, we find up-regulation of prolactin receptor as cancer cells that have disseminated to the lungs expand into micrometastases. Secretion of the ligand prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E2 (PGE2). PGE2 treatment of fibroblasts activates the orphan nuclear receptor NR4A (Nur77), with prolactin as a major transcriptional target for the NR4A-retinoid X receptor (RXR) heterodimer. Ectopic expression of prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor celecoxib abrogates prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, prolactin, and prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine cross-talk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression.


Asunto(s)
Carcinogénesis/metabolismo , Prolactina/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Transducción de Señal/fisiología , Células del Estroma/metabolismo , Animales , Carcinogénesis/efectos de los fármacos , Celecoxib/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Ratones , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Receptores X Retinoide/metabolismo , Transducción de Señal/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología
6.
Proc Natl Acad Sci U S A ; 116(52): 26835-26845, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31843922

RESUMEN

Transcriptional profiling has defined pancreatic ductal adenocarcinoma (PDAC) into distinct subtypes with the majority being classical epithelial (E) or quasi-mesenchymal (QM). Despite clear differences in clinical behavior, growing evidence indicates these subtypes exist on a continuum with features of both subtypes present and suggestive of interconverting cell states. Here, we investigated the impact of different therapies being evaluated in PDAC on the phenotypic spectrum of the E/QM state. We demonstrate using RNA-sequencing and RNA-in situ hybridization (RNA-ISH) that FOLFIRINOX combination chemotherapy induces a common shift of both E and QM PDAC toward a more QM state in cell lines and patient tumors. In contrast, Vitamin D, another drug under clinical investigation in PDAC, induces distinct transcriptional responses in each PDAC subtype, with augmentation of the baseline E and QM state. Importantly, this translates to functional changes that increase metastatic propensity in QM PDAC, but decrease dissemination in E PDAC in vivo models. These data exemplify the importance of both the initial E/QM subtype and the plasticity of E/QM states in PDAC in influencing response to therapy, which highlights their relevance in guiding clinical trials.

7.
J Cancer Educ ; 37(6): 1629-1633, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-33768471

RESUMEN

At our institution, we aim to foster interest in oncology through the Student Oncology Society (SOS). The SOS was formed in 2010 and since then has hosted numerous oncology-related events, such as career panels, patient survivorship celebrations, and movie screenings. The purpose of this study is to report the experiences from former student leaders of the SOS, particularly how their participation informed their career choice. Complete survey responses were obtained from 26 of 32 former SOS student leaders (response rate 81.3%). Out of the 26 respondents, 19 (73.1%) are pursuing an oncology-related specialty. The three most common competencies that were affected by participation in SOS, noted by 21 (80.8%) respondents, were learning about pathways to careers in oncology, understanding the multidisciplinary approach to cancer care, and coordinating events. By mean Likert score, the most important factors in career choice for respondents who eventually pursued an oncology field were having a mentor in oncology (4.44), a clinical rotation in oncology (4.31), research involvement (4.22), and SOS involvement (3.17). While SOS involvement played a role in career choice among our student leaders, having a mentor was cited to be the most important factor for choosing an oncology career. Thus, implementation of formal mentorship initiatives within the framework of oncology interest groups should be explored.


Asunto(s)
Estudiantes de Medicina , Humanos , Liderazgo , Opinión Pública , Selección de Profesión , Mentores
8.
Cancer ; 126(19): 4379-4389, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32725630

RESUMEN

BACKGROUND: Although pediatric cancer mortality and survival have improved in the United States over the past 40 years, differences exist by age, race/ethnicity, cancer site, and economic status. To assess progress, this study examined recent mortality and survival data for individuals younger than 20 years. METHODS: Age-adjusted death rates were calculated with the National Vital Statistics System for 2002-2016. Annual percent changes (APCs) and average annual percent changes (AAPCs) were calculated with joinpoint regression. Five-year relative survival was calculated on the basis of National Program of Cancer Registries data for 2001-2015. Death rates and survival were estimated overall and by sex, 5-year age group, race/ethnicity, cancer type, and county-based economic markers. RESULTS: Death rates decreased during 2002-2016 (AAPC, -1.5), with steeper declines during 2002-2009 (APC, -2.6), and then plateaued (APC, -0.4). Leukemia and brain cancer were the most common causes of death from pediatric cancer, and brain cancer surpassed leukemia in 2011. Death rates decreased for leukemia and lymphoma but were unchanged for brain, bone, and soft-tissue cancers. From 2001-2007 to 2008-2015, survival improved from 82.0% to 85.1%. Survival was highest in both periods among females, those aged 15 to 19 years, non-Hispanic Whites, and those in counties in the top 25% by economic status. Survival improved for leukemias, lymphomas, and brain cancers but plateaued for bone and soft-tissue cancers. CONCLUSIONS: Although overall death rates have decreased and survival has increased, differences persist by sex, age, race/ethnicity, cancer type, and economic status. Improvements in pediatric cancer outcomes may depend on improving therapies, access to care, and supportive and long-term care.


Asunto(s)
Neoplasias/mortalidad , Adolescente , Adulto , Historia del Siglo XXI , Humanos , Masculino , Análisis de Supervivencia , Estados Unidos , Adulto Joven
9.
Cancer ; 126(15): 3471-3482, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32453441

RESUMEN

BACKGROUND: Approximately 50% of children with cancer in the United States who are aged <15 years receive primary treatment on a therapeutic clinical trial. To the authors' knowledge, it remains unknown whether trial enrollment has a clinical benefit compared with the best alternative standard therapy and/or off trial (ie, clinical trial effect). The authors conducted a retrospective matched cohort study to compare the morbidity and mortality of pediatric patients with cancer who are treated on a phase 3 clinical trial compared with those receiving standard therapy and/or off trial. METHODS: Subjects were aged birth to 19 years; were diagnosed between 2000 and 2010 with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, or neuroblastoma; and had received initial treatment at the Children's Hospital of Philadelphia. On-trial and off-trial subjects were matched based on age, race, ethnicity, a diagnosis of Down syndrome (for patients with ALL or AML), prognostic risk level, date of diagnosis, and tumor type. RESULTS: A total of 428 participants were matched in 214 pairs (152 pairs for ALL, 24 pairs for AML, 32 pairs for rhabdomyosarcoma, and 6 pairs for neuroblastoma). The 5-year survival rate did not differ between those treated on trial versus those treated with standard therapy and/or off trial (86.9% vs 82.2%; P = .093). On-trial patients had a 32% lower odds of having worse (higher) mortality-morbidity composite scores, although this did not reach statistical significance (odds ratio, 0.68; 95% confidence interval, 0.45-1.03 [P = .070]). CONCLUSIONS: There was no statistically significant difference in outcomes noted between those patients treated on trial and those treated with standard therapy and/or off trial. However, in partial support of the clinical trial effect, the results of the current study indicate a trend toward more favorable outcomes in children treated on trial compared with those treated with standard therapy and/or off trial. These findings can support decision making regarding enrollment in pediatric phase 3 clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias/tratamiento farmacológico , Pediatría , Pronóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/patología , Masculino , Neoplasias/epidemiología , Neoplasias/patología , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/epidemiología , Neuroblastoma/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Estudios Retrospectivos , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/epidemiología , Rabdomiosarcoma/patología , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto Joven
10.
Prev Med ; 135: 106078, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32247009

RESUMEN

With increased understanding of the natural history of cervical cancer, cervical cancer screening recommendations have evolved (Schiffman & Wentzensen, 2013). As research better quantified the balance of benefits and harms of screening, new recommendations called for longer intervals between screening tests. Adherence to longer screening intervals detects similar numbers of abnormalities and decreases harms associated with overscreening/overtreatment. In this descriptive study, we examined the cervical cancer screening intervals from 2010 to 2018 in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). There were 1,397,899 women aged 21-64 who were screened for cervical cancer from 2010 to 2018 and 556,743 rescreenings of average risk women were performed. The median cervical screening interval increased from 2.02 years in 2010 to 3.88 years in 2018. Providers serving uninsured women in a national screening program are following the recommendations of longer intervals between cervical cancer screenings.


Asunto(s)
Detección Precoz del Cáncer , Guías como Asunto , Pacientes no Asegurados/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Femenino , Guías como Asunto/normas , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou/estadística & datos numéricos , Factores de Tiempo , Estados Unidos
11.
J Community Health ; 44(3): 552-560, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30767102

RESUMEN

PURPOSE: To examine smoking and use of smoking cessation aids among tobacco-associated cancer (TAC) or non-tobacco-associated cancer (nTAC) survivors. Understanding when and if specific types of cessation resources are used can help with planning interventions to more effectively decrease smoking among all cancer survivors, but there is a lack of research on smoking cessation modalities used among cancer survivors. METHODS: Kentucky Cancer Registry data on incident lung, colorectal, pancreatic, breast, ovarian, and prostate cancer cases diagnosed 2007-2011, were linked with health administrative claims data (Medicaid, Medicare, private insurers) to examine the prevalence of smoking and use of smoking cessation aids 1 year prior and 1 year following the cancer diagnosis. TACs included colorectal, pancreatic, and lung cancers; nTAC included breast, ovarian, and prostate cancers. RESULTS: There were 10,033 TAC and 13,670 nTAC survivors. Smoking before diagnosis was significantly higher among TAC survivors (p < 0.0001). Among TAC survivors, smoking before diagnosis was significantly higher among persons who: were males (83%), aged 45-64 (83%), of unknown marital status (84%), had very low education (78%), had public insurance (89%), Medicaid (85%) or were uninsured (84%). Smoking cessation counseling and pharmacotherapy were more common among TAC than nTAC survivors (p < 0.01 and p = 0.05, respectively). DISCUSSION: While smoking cessation counseling and pharmacotherapy were higher among TAC survivors, reducing smoking among all cancer survivors remains a priority, given cancer survivors are at increased risk for subsequent chronic diseases, including cancer. Tobacco cessation among all cancer survivors (not just those with TAC) can help improve prognosis, quality of life and reduce the risk of further disease. Health care providers can recommend for individual, group and telephone counseling and/or pharmacotherapy recommendations. These could also be included in survivorship care plans.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Cese del Hábito de Fumar/métodos , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Supervivientes de Cáncer/psicología , Consejo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Calidad de Vida , Cese del Hábito de Fumar/psicología , Factores Socioeconómicos , Productos de Tabaco , Estados Unidos , Adulto Joven
12.
Prev Chronic Dis ; 16: E15, 2019 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-30730830

RESUMEN

INTRODUCTION: Nearly 5 million people are treated for skin cancer each year in the United States. Agricultural and construction workers (ACWs) may be at increased risk for skin cancer because of high levels of ultraviolet radiation exposure from the sun. This is the first study that uses nationally representative data to assess sun-protection behaviors among ACWs. METHODS: We analyzed data from the 2015 National Health Interview Survey Cancer Control Supplement to examine the prevalence of sun-protection behaviors among ACWs. We calculated national, weighted, self-reported prevalence estimates. We used χ2 tests to assess differences between ACWs by industry and occupation. RESULTS: Most of the 2,298 agricultural and construction workers studied were male (by industry, 72.4% in agriculture and 89.3% in construction; by occupation, 66.1% in agriculture and 95.6% in construction) and non-Hispanic white. About one-third had at least 1 sunburn in the past year. The prevalence of sunscreen use and shade seeking was low and did not significantly differ among groups, ranging from 15.1% to 21.4% for sunscreen use and 24.5% to 29.1% for shade seeking. The prevalence of wearing protective clothing was significantly higher among agricultural workers than among construction workers by industry (70.9% vs 50.7%) and occupation (70.5% vs 53.0%). CONCLUSION: Our findings could be used to improve occupational health approaches to reducing skin cancer risk among ACWs and to inform education and prevention initiatives addressing skin cancer. Sun-safety initiatives may include modifying work sites to increase shade and adding sun safety to workplace policies and training. Employers can help reduce occupational health inequities and protect workers by creating workplaces that facilitate sun protection.


Asunto(s)
Industria de la Construcción/estadística & datos numéricos , Agricultores/estadística & datos numéricos , Conductas Relacionadas con la Salud , Enfermedades Profesionales/prevención & control , Neoplasias Cutáneas/prevención & control , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Ropa de Protección/estadística & datos numéricos , Conducta de Reducción del Riesgo , Quemadura Solar/epidemiología , Quemadura Solar/prevención & control , Luz Solar/efectos adversos , Protectores Solares/uso terapéutico , Estados Unidos/epidemiología , Adulto Joven
13.
Oncologist ; 23(1): 121-127, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28860411

RESUMEN

BACKGROUND: Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a "liquid biopsy" for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes. MATERIALS AND METHODS: We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA-seq) detection and enumeration. RESULTS: Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA-seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions. CONCLUSION: Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification. IMPLICATIONS FOR PRACTICE: This work describes a high-sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Células Epiteliales/patología , Células Neoplásicas Circulantes/patología , Neoplasias Pancreáticas/diagnóstico , Lesiones Precancerosas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
14.
Cancer Causes Control ; 29(12): 1277-1285, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30506490

RESUMEN

PURPOSE: As of 2016, an estimated 15.5 million cancer survivors were living in the United States and the number of cancer survivors is expected to increase to 20.3 million by 2026. Numerous clinical studies have shown that comorbidities, such as obesity and diabetes, and unhealthy lifestyle choices, such as physical inactivity and heavy smoking, negatively influence overall quality of life and long-term survival of cancer survivors. Accordingly, survivorship programs seek to focus on overall wellness, including symptom management, monitoring for late effects of treatment, monitoring for recurrence, helping patients adapt healthy behaviors, and quality of life. This paper provides a broad overview of public health efforts to address the needs of cancer survivors. METHODS: To describe a range of examples of survivorship initiatives in comprehensive cancer control, we analyzed documents from comprehensive cancer control programs and coalitions and solicited detailed examples from several national partners. RESULTS: Comprehensive cancer control programs, coalitions, and partners are undertaking myriad initiatives to address cancer survivorship and building upon evidence-based interventions to promote healthy behaviors for cancer survivors across the country. CONCLUSION: A coordinated public health approach to caring for the growing population of cancer survivors can help address the long-term physical, psychosocial, and economic effects of cancer treatment on cancer survivors and their families.


Asunto(s)
Supervivientes de Cáncer/psicología , Neoplasias/epidemiología , Calidad de Vida , Comorbilidad , Atención a la Salud , Conductas Relacionadas con la Salud , Humanos , Estilo de Vida , Obesidad/epidemiología , Salud Pública , Estados Unidos
15.
MMWR Morb Mortal Wkly Rep ; 67(25): 707-713, 2018 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-29953430

RESUMEN

Approximately 15,000 persons aged <20 years receive a cancer diagnosis each year in the United States (1). National surveillance data could provide understanding of geographic variation in occurrence of new cases to guide public health planning and investigation (2,3). Past research on pediatric cancer incidence described differences by U.S. Census region but did not provide state-level estimates (4). To adequately describe geographic variation in cancer incidence among persons aged <20 years in the United States, CDC analyzed data from United States Cancer Statistics (USCS) during 2003-2014 and identified 171,432 cases of pediatric cancer during this period (incidence = 173.7 cases per 1 million persons). The cancer types with the highest incidence rates were leukemias (45.7), brain tumors (30.9), and lymphomas (26.2). By U.S. Census region, pediatric cancer incidence was highest in the Northeast (188.0) and lowest in the South (168.0), whereas by state (including the District of Columbia [DC]), rates were highest in New Hampshire, DC, and New Jersey. Among non-Hispanic whites (whites) and non-Hispanic blacks (blacks), pediatric cancer incidence was highest in the Northeast, and the highest rates among Hispanics were in the South. The highest rates of leukemia were in the West, and the highest rates of lymphoma and brain tumors were in the Northeast. State-based differences in pediatric cancer incidence could guide interventions related to accessing care (e.g., in states with large distances to pediatric oncology centers), clinical trial enrollment, and state or regional studies designed to further explore variations in cancer incidence.


Asunto(s)
Neoplasias/epidemiología , Vigilancia de la Población , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Neoplasias/etnología , Sistema de Registros , Estados Unidos/epidemiología , Adulto Joven
16.
Pediatr Blood Cancer ; 65(8): e27074, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29667766

RESUMEN

In the United States, adolescent and young adult (AYA) patients with cancer have the lowest clinical trial participation rate of all age groups and slower progress in survival improvement than younger patients. Ominously, AYA clinical trial participation has been steadily decreasing since 2010, except in 15-19 year olds and AYAs with acute lymphoblastic leukemia. In order to reverse the accrual trend, multiple changes are necessary, including convincing community oncologists to pursue clinical trials on behalf of their AYA patients and to have the new National Community Oncology Research Program and National Clinical Trials Network lead a coordinated effort to increase accrual.


Asunto(s)
Ensayos Clínicos como Asunto , Neoplasias/terapia , Selección de Paciente , Adolescente , Adulto , Femenino , Humanos , Masculino , Estados Unidos , Adulto Joven
17.
Cancer ; 123 Suppl 24: 5178-5189, 2017 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-29205314

RESUMEN

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. This report describes the survival of children with ALL in the United States using the most comprehensive and up-to-date cancer registry data. METHODS: Data from 37 state cancer registries that cover approximately 80% of the US population were used. Age-standardized survival up to 5 years was estimated for children aged 0-14 years who were diagnosed with ALL during 2 periods (2001-2003 and 2004-2009). RESULTS: In total, 17,500 children with ALL were included. The pooled age-standardized net survival estimates for all US registries combined were 95% at 1 year, 90% at 3 years, and 86% at 5 years for children diagnosed during 2001-2003, and 96%, 91%, and 88%, respectively, for those diagnosed during 2004-2009. Black children who were diagnosed during 2001-2003 had lower 5-year survival (84%) than white children (87%) and had less improvement in survival by 2004-2009. For those diagnosed during 2004-2009, the 1-year and 5-year survival estimates were 96% and 89%, respectively, for white children and 96% and 84%, respectively, for black children. During 2004-2009, survival was highest among children aged 1 to 4 years (95%) and lowest among children aged <1 year (60%). CONCLUSIONS: The current results indicate that overall net survival from childhood ALL in the United States is high, but disparities by race still exist, especially beyond the first year after diagnosis. Clinical and public health strategies are needed to improve health care access, clinical trial enrollment, treatment, and survivorship care for children with ALL. Cancer 2017;123:5178-89. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.


Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Sistema de Registros , Población Blanca/estadística & datos numéricos , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Estados Unidos/epidemiología
18.
Int J Health Geogr ; 16(1): 29, 2017 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-28784135

RESUMEN

BACKGROUND: Transforming spatial data from one scale to another is a challenge in geographic analysis. As part of a larger, primary study to determine a possible association between travel barriers to pediatric cancer facilities and adolescent cancer mortality across the United States, we examined methods to estimate mortality within zones at varying distances from these facilities: (1) geographic centroid assignment, (2) population-weighted centroid assignment, (3) simple areal weighting, (4) combined population and areal weighting, and (5) geostatistical areal interpolation. For the primary study, we used county mortality counts from the National Center for Health Statistics (NCHS) and population data by census tract for the United States to estimate zone mortality. In this paper, to evaluate the five mortality estimation methods, we employed address-level mortality data from the state of Georgia in conjunction with census data. Our objective here is to identify the simplest method that returns accurate mortality estimates. RESULTS: The distribution of Georgia county adolescent cancer mortality counts mirrors the Poisson distribution of the NCHS counts for the U.S. Likewise, zone value patterns, along with the error measures of hierarchy and fit, are similar for the state and the nation. Therefore, Georgia data are suitable for methods testing. The mean absolute value arithmetic differences between the observed counts for Georgia and the five methods were 5.50, 5.00, 4.17, 2.74, and 3.43, respectively. Comparing the methods through paired t-tests of absolute value arithmetic differences showed no statistical difference among the methods. However, we found a strong positive correlation (r = 0.63) between estimated Georgia mortality rates and combined weighting rates at zone level. Most importantly, Bland-Altman plots indicated acceptable agreement between paired arithmetic differences of Georgia rates and combined population and areal weighting rates. CONCLUSIONS: This research contributes to the literature on areal interpolation, demonstrating that combined population and areal weighting, compared to other tested methods, returns the most accurate estimates of mortality in transforming small counts by county to aggregated counts for large, non-standard study zones. This conceptually simple cartographic method should be of interest to public health practitioners and researchers limited to analysis of data for relatively large enumeration units.


Asunto(s)
Censos , Neoplasias/mortalidad , Vigilancia de la Población/métodos , Análisis Espacial , Adolescente , Femenino , Georgia/epidemiología , Humanos , Masculino , Neoplasias/diagnóstico , Estados Unidos/epidemiología , Adulto Joven
19.
Prev Chronic Dis ; 11: E200, 2014 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-25393748

RESUMEN

INTRODUCTION: Knowing the human immunodeficiency virus (HIV) serostatus of patients at the time of cancer diagnosis or cancer recurrence is prerequisite to coordinating HIV and cancer treatments and improving treatment outcomes. However, there are no published data about HIV testing among cancer survivors in the United States. We sought to provide estimates of the proportion of cancer survivors tested for HIV and to characterize factors associated with having had HIV testing. METHODS: We used data from the 2009 Behavioral Risk Factor Surveillance System to calculate the proportion of cancer survivors under age 65 who had undergone HIV testing, by demographic and health-related factors and by state. Adjusted proportion estimates were calculated by multivariable logistic regression. RESULTS: Only 41% of cancer survivors in the United States under the age of 65 reported ever having had an HIV test. The highest proportion of survivors tested was among patients aged 25 to 34 years (72.2%), non-Hispanic blacks (59.5%), and cervical cancer survivors (51.2%). The proportion tested was highest in the District of Columbia (68.3%) and lowest in Nebraska (24.1%). Multivariable analysis showed that factors associated with HIV testing included being non-Hispanic black or Hispanic, being younger, having higher education, not being married or living with a partner, not being disabled, and having medical cost concerns. Having an AIDS-related cancer was associated with HIV testing only among females. CONCLUSION: The proportions of HIV testing varied substantially by demographic and health-related factors and by state. Our study points to the need for public health interventions to promote HIV testing among cancer survivors.


Asunto(s)
Infecciones por VIH/diagnóstico , Neoplasias , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Sistema de Vigilancia de Factor de Riesgo Conductual , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Conductas Relacionadas con la Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos , Adulto Joven
20.
Artículo en Inglés | MEDLINE | ID: mdl-39321033

RESUMEN

Purpose: In 2018, a "survival cliff" in the United States was identified among older adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). This study reassessed the cliff and associated putative causes. Methods: Survival data were obtained using the U.S. Surveillance Research Program, National Cancer Institute (NCI) SEER 22 Registries. Accrual data on cancer treatment trials conducted by the NCI cooperative groups and NCI-designated cancer centers were obtained from the NCI Cancer Therapy Evaluation Program. Trend and average percent changes and statistical significances were identified with the NCI Joinpoint Regression Program. Results: A previous cliff-like decrement in the survival of 17- to 20-year-olds is no longer apparent, overall and in all racial and ethnic groups. The "survival cliff" age range was coincident with a clinical trial accrual cliff, and both diminished when more clinical trials were available to, and participated in by, young adult patients. Older AYA patients of ages 30-39 had minimal improvement in clinical trial accrual and least survival gain among the AYA age group. Conclusion: The survival cliff has abated, resulting in thousands of fewer premature deaths and tens of thousands of years of life saved-a remarkable achievement. The survival improvement may be attributed to improved clinical trial availability for and recruitment and participation of AYAs on treatment trials, application of pediatric-inspired ALL treatment regimens to AYAs, expanded national health insurance for -18 to 25 year olds, improved AYA cancer services, and a national focus on AYA oncology.

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