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2.
Cancer Immunol Immunother ; 69(2): 293-306, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31953578

RESUMEN

Cancer immunotherapies are promising treatments for many forms of cancer. Nevertheless, the response rates to, e.g., immune checkpoint inhibitors (ICI), are still in low double-digit percentage. This calls for further therapy optimization that should take into account combination of immunotherapies with classical tumor therapies such as radiotherapy. By designing multimodal approaches, immune modulatory properties of certain radiation schemes, additional immune modulation by immunotherapy with ICI and hyperthermia, as well as patient stratification based on genetic and immune constitutions have to be considered. In this context, both the tumor and its microenvironment including cells of the innate and adaptive immune system have to be viewed in synopsis. Knowledge of immune activation and immune suppression by radiation is the basis for well-elaborated addition of certain immunotherapies. In this review, the focus is set on additional immune stimulation by hyperthermia and restoration of an immune response by ICI. The impact of radiation dose and fractionation on immune modulation in multimodal settings has to be considered, as the dynamics of the immune response and the timing between radiotherapy and immunotherapy. Another big challenge is the patient stratification that should be based on matrices of biomarkers, taking into account genetics, proteomics, radiomics, and "immunomics". One key aim is to turn immunological "cold" tumors into "hot" tumors, and to eliminate barriers of immune-suppressed or immune-excluded tumors. Comprehensive knowledge of immune alterations induced by radiation and immunotherapy when being applied together should be utilized for patient-adapted treatment planning and testing of innovative tumor therapies within clinical trials.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Diseño de Drogas , Inmunomodulación/efectos de los fármacos , Neoplasias/etiología , Neoplasias/terapia , Animales , Antineoplásicos Inmunológicos/farmacología , Biomarcadores de Tumor , Terapia Combinada , Humanos , Hipertermia Inducida/métodos , Inmunidad , Factores Inmunológicos/farmacología , Inmunomodulación/efectos de la radiación , Inmunoterapia , Neoplasias/patología , Proyectos de Investigación , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de la radiación
3.
Cancer Immunol Immunother ; 69(2): 163-174, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31848656

RESUMEN

B7 homolog 4 (B7H4) is considered a negative regulator of immune responses, but the immunoregulatory role of B7H4 in the tumor microenvironment is not clear. Here, we assessed B7H4 expression cell types in human breast cancer tissues and addressed its potential mechanisms in the CD8 T cell immune response. The results from flow cytometry and immunohistochemistry demonstrated that B7H4 was highly expressed in 26 out of 30 (86.7%) breast invasive ductal carcinomas, and B7H4 surface expression on tumor cells was inversely correlated with CD8 T lymphocytes infiltration (p < 0.0001). In vivo, B7H4-overexpressing tumor cells showed enhanced tumor growth in immunocompetent mice with impaired CD8 T cell infiltration of the tumor. Further investigation showed that activation and expansion of CD8 T cells within the lymph nodes were suppressed in B7H4-overexpessing tumor-bearing mice. An in vitro killing assay showed that the cytotoxicity of CD8 T cells was inhibited in B7H4-overexpressing tumor cells. These findings suggest that B7H4 in tumor cells is a negative regulator of CD8 T cell activation, expansion and cytotoxicity, indicating that tumor cell-associated B7H4 might be a target for T cell-based cancer immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Expresión Génica , Inmunidad/genética , Neoplasias/etiología , Neoplasias/metabolismo , Inhibidor 1 de la Activación de Células T con Dominio V-Set/genética , Animales , Biomarcadores , Línea Celular Tumoral , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Neoplasias/patología , Neoplasias/terapia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Inhibidor 1 de la Activación de Células T con Dominio V-Set/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Int J Cancer ; 146(6): 1730-1740, 2020 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-31840816

RESUMEN

Immune checkpoint blockade (ICB) has shown long-term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment-induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti-CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti-CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti-CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.


Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Antígeno CTLA-4/antagonistas & inhibidores , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Neoplasias/etiología , Neoplasias/metabolismo , Neovascularización Patológica/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores , Línea Celular Tumoral , Eosinófilos/inmunología , Femenino , Humanos , Inmunidad , Inmunomodulación/efectos de los fármacos , Inmunofenotipificación , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Depleción Linfocítica , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neovascularización Patológica/tratamiento farmacológico , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
5.
Int J Cancer ; 146(3): 646-656, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30882889

RESUMEN

Cancer is a major contributing cause of morbidity and mortality in the Eastern Mediterranean region. The aim of the current study was to estimate the cancer burden attributable to major lifestyle and environmental risk factors. We used age-, sex- and site-specific incidence estimates for 2012 from IARC's GLOBOCAN, and assessed the following risk factors: smoking, alcohol, high body mass index, insufficient physical activity, diet, suboptimal breastfeeding, infections and air pollution. The prevalence of exposure to these risk factors came from different sources including peer-reviewed international literature, the World Health Organization, noncommunicable disease Risk Factor Collaboration, and the Food and Agriculture Organization. Sex-specific population-attributable fraction was estimated in the 22 countries of the Eastern Mediterranean region based on the prevalence of the selected risk factors and the relative risks obtained from meta-analyses. We estimated that approximately 33% (or 165,000 cases) of all new cancer cases in adults aged 30 years and older in 2012 were attributable to all selected risk factors combined. Infections and smoking accounted for more than half of the total attributable cases among men, while insufficient physical activity and exposure to infections accounted for more than two-thirds of the total attributable cases among women. A reduction in exposure to major lifestyle and environmental risk factors could prevent a substantial number of cancer cases in the Eastern Mediterranean. Population-based programs preventing infections and smoking (particularly among men) and promoting physical activity (particularly among women) in the population are needed to effectively decrease the regional cancer burden.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Neoplasias/epidemiología , Conducta Sedentaria , Fumar Tabaco/epidemiología , Adulto , Factores de Edad , Contaminación del Aire/efectos adversos , Consumo de Bebidas Alcohólicas/efectos adversos , Índice de Masa Corporal , Ejercicio/fisiología , Conducta Alimentaria/fisiología , Femenino , Humanos , Incidencia , Masculino , Región Mediterránea/epidemiología , Neoplasias/etiología , Neoplasias/prevención & control , Prevalencia , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Fumar Tabaco/efectos adversos
6.
Int J Cancer ; 146(3): 682-691, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30919451

RESUMEN

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02-2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.


Asunto(s)
Neoplasias/mortalidad , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/mortalidad , Receptores de Trasplantes/estadística & datos numéricos , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Complicaciones Posoperatorias/etiología , Sistema de Registros/estadística & datos numéricos , Factores de Riesgo , Análisis de Supervivencia , Suecia/epidemiología , Adulto Joven
7.
JAMA ; 322(22): 2203-2210, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31821431

RESUMEN

Importance: An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility. Objective: To examine the association between different types of fertility treatments and cancer risk in children. Design, Setting, and Participants: A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015). Exposures: Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women. Main Outcomes and Measures: Hazard ratios and incidence rate differences for childhood cancer. Results: After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined. Conclusions and Relevance: Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.


Asunto(s)
Transferencia de Embrión/efectos adversos , Neoplasias/etiología , Técnicas Reproductivas Asistidas , Adulto , Niño , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro , Humanos , Incidencia , Masculino , Neoplasias/epidemiología , Embarazo , Técnicas Reproductivas Asistidas/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Inyecciones de Esperma Intracitoplasmáticas
9.
Nat Med ; 25(12): 1822-1832, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31806905

RESUMEN

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.


Asunto(s)
Enfermedad Crónica/epidemiología , Inflamación/fisiopatología , Longevidad/genética , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/fisiopatología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus/etiología , Diabetes Mellitus/fisiopatología , Humanos , Inflamación/complicaciones , Inflamación/epidemiología , Estilo de Vida , Longevidad/fisiología , Neoplasias/etiología , Neoplasias/fisiopatología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo
10.
Semin Oncol ; 46(4-5): 334-340, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31703932

RESUMEN

Cancer is a leading cause of death for people with HIV (PWH). The Veterans Healthcare System (VA) is the largest single institutional provider of HIV care in the United States. Cancer among Veterans with HIV is major issue and clinical research has expanded significantly during the antiretroviral therapy (ART) era providing numerous insights regarding cancer incidence, risk factors, prevention, treatment and outcomes for this unique group of patients. This work has been greatly facilitated by the availability of national VA data sources. Notably, patterns of cancer incidence have changed for Veterans with HIV during the ART era; non-AIDS defining malignancies now are the most common tumors. Despite better HIV control in the ART era, immunosuppression measured by low CD4 counts and HIV viremia have been associated with increased cancer risk. Cancer outcomes for Veterans with HIV may now be similar to uninfected Veterans, but information on outcomes and cancer treatment patterns remains limited, requiring further study to help inform prevention and treatment strategies.


Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Neoplasias/epidemiología , Neoplasias/etiología , Salud de los Veteranos/estadística & datos numéricos , Veteranos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Incidencia , Masculino , Neoplasias/prevención & control , Investigación , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiología
11.
Medicine (Baltimore) ; 98(44): e17735, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689818

RESUMEN

BACKGROUND: Several studies have reported the association of Behcet disease (BD) with the risk of diverse kinds of cancers. However, its association is controversial. Therefore, we conducted a bioinformatics-analysis to explore any possible association. METHODS: We obtained relevant findings published before October 2018 through literature survey of the PubMed, EMBASE, and Web of Science databases. STATA 12.0 software was used for statistical analysis. RESULTS: After screening, the meta-analysis comprised 5 studies. We observed a significant positive association between BD and enhanced malignancy risk (pooled relative risk [RR], 1.19; 95% confidence interval [CI]: 1.09-1.30), especially for hematological cancer (pooled RR, 2.58; 95% CI: 1.61-3.55) and thyroid cancer (pooled RR, 1.25; 95% CI: 1.04-1.47). However, high heterogeneity was also observed in the results (I = 81.3%). Subgroup analysis indicated that female BD patients from Korean population are at highest predisposition to overall malignancy. Besides, publication bias was not observed with our choice of surveys. CONCLUSION: We conclude that patients suffering from BD have an overall increased risk for malignancy. Greater numbers of exhaustive temporal studies are essential for definitive inferences.


Asunto(s)
Síndrome de Behçet/complicaciones , Neoplasias Hematológicas/etiología , Neoplasias/etiología , Neoplasias de la Tiroides/etiología , Biología Computacional , Femenino , Humanos , Masculino , Riesgo , Factores de Riesgo
12.
Semin Oncol ; 46(4-5): 385-392, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31739997

RESUMEN

There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.


Asunto(s)
Inmunoterapia , Neoplasias/terapia , Inmunidad Adaptativa , Animales , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Terapia Combinada , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunidad Innata , Inmunomodulación , Inmunoterapia/métodos , Ligandos , Neoplasias/etiología , Neoplasias/metabolismo , Neoplasias/patología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Receptores Toll-Like/metabolismo , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
13.
Nat Commun ; 10(1): 4648, 2019 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-31641120

RESUMEN

Breast cancer (BC) patients diagnosed between two screenings (interval cancers) are more likely than screen-detected patients to carry rare deleterious mutations in cancer genes potentially leading to increased risk for other non-breast cancer (non-BC) tumors. In this study, we include 14,846 women diagnosed with BC of which 1,772 are interval and 13,074 screen-detected. Compared to women with screen-detected cancers, interval breast cancer patients are more likely to have a non-BC tumor before (Odds ratio (OR): 1.43 [1.19-1.70], P = 9.4 x 10-5) and after (OR: 1.28 [1.14-1.44], P = 4.70 x 10-5) breast cancer diagnosis, are more likely to report a family history of non-BC tumors and have a lower genetic risk score based on common variants for non-BC tumors. In conclusion, interval breast cancer is associated with other tumors and common cancer variants are unlikely to be responsible for this association. These findings could have implications for future screening and prevention programs.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Tamizaje Masivo , Neoplasias/epidemiología , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Mamografía , Persona de Mediana Edad , Neoplasias/etiología , Neoplasias/genética , Oportunidad Relativa , Factores de Riesgo , Factores Socioeconómicos , Suecia/epidemiología
14.
Ecotoxicol Environ Saf ; 186: 109748, 2019 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-31606640

RESUMEN

Oral ingestion is the main exposure pathway through which humans ingest trace metals in the soil, particularly for children. Metals in different soil particle size fractions may vary in terms of concentration and properties. Urban school/kindergarten soil samples were collected from three cities: Lanzhou in northwest China, Wuhan in central China, and Shenzhen in southeast China. Soil samples were classified according to particle size (<63 µm, 63-150 µm, 150-250 µm, and 250-2000 µm) to estimate the effects of soil particle size on the total content and bioaccessibility of metals (Cd, Cr, Cu, Ni, Pb, and Zn). Based on the results, we assessed whether the standard size <150 µm (containing < 63 µm and 63-150 µm), recommended by the Technical Review Workgroup (TRW) of the Environmental Protection Agency (EPA), and <250 µm (containing < 63 µm, 63-150 µm, and 150-250) recommended by the Bioaccessibility Research Group of Europe (BARGE), are suitable where the largest proportion adhering to hands is the finest soil (<63 µm). The results showed that different metals exhibited different relationships between soil particle size and content and between soil particle size and bioaccessibility. Pb and Zn generally exhibited the greatest bioaccessibility in the coarsest particle sizes (250-2000 µm); whereas the highest Ni bioaccessibility occurred in the finest sizes (<63 µm); the bioaccessibility of other metals did not exhibit any obvious relationships with particle size. When assessing health risks using bioaccessible metal content in the recommended soil particle size ranges (<150 µm and <250 µm) and in finer particles (<63 µm), the results for noncarcinogenic risks to children exhibited no obvious difference, while the actual carcinogenic risks may be underestimated with the use of soil particle size ranges < 150 µm and <250 µm. Therefore, when choosing an optimal particle size fraction to evaluate the health risk of oral soil ingestion, we recommend the use of the bioaccessible metal content in <63 µm soil fraction.


Asunto(s)
Salud del Niño , Monitoreo del Ambiente/métodos , Metales Pesados/farmacocinética , Tamaño de la Partícula , Contaminantes del Suelo/farmacocinética , Suelo/química , Oligoelementos/farmacocinética , Disponibilidad Biológica , Niño , China , Ciudades , Monitoreo del Ambiente/normas , Europa (Continente) , Humanos , Metales Pesados/efectos adversos , Metales Pesados/análisis , Neoplasias/etiología , Medición de Riesgo , Contaminantes del Suelo/efectos adversos , Contaminantes del Suelo/análisis , Oligoelementos/efectos adversos , Oligoelementos/análisis
15.
Bull Cancer ; 106(11): 975-982, 2019 Nov.
Artículo en Francés | MEDLINE | ID: mdl-31607391

RESUMEN

While improvements in the environment and living conditions have contributed to a significant increase in human longevity for over a century, the role of environmental factors in the occurrence of cancer has become a public health concern. It is recognized that a number of environmental factors such as environmental quality (air, water, soil), or environmental changes contribute to the occurrence of certain cancers. Despite this awareness, their potential impacts on health raise many scientific questions. The development of new methodological tools for the characterization of exposure, the study of the association between environmental agents and cancer through an exposure-cancer approach and the health impacts associated, have led to changes in scientific paradigms including the concept of exposome. This concept, at the heart of health and environmental issues, takes into account the determinants of health related to the quality of populations' living environments and provides assistance in public policy decision-making. Ultimately, the aim is to develop measures likely to reduce exposure and prevent health risks and damage to the most vulnerable populations, both in their physical environment and in their living environment, including the economic and social determinants.


Asunto(s)
Carcinógenos Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Neoplasias/etiología , Causalidad , Salud Ambiental , Humanos , Neoplasias/genética , Neoplasias/prevención & control , Factores de Riesgo
16.
J Cancer Res Clin Oncol ; 145(12): 3125-3135, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31587105

RESUMEN

PURPOSE: Solid organ (SOT) and allogeneic haematopoietic stem cell (HSCT) transplant recipients have elevated risks of de novo or secondary cancer. We explored risk factors hereof. METHODS: Among SOT and HSCT between January 2004 and December 2014, standardised incidence ratio (SIR) of de novo/secondary cancer compared with the Danish population was determined and risk factors were identified using Poisson regression. RESULTS: During a median of 3.4 (IQR 1.3-6.4) and 2.6 (0.8-5.4) person-years (PY) after SOT and HSCT, a total of 212/1656 (13%) and 75/992 (8%) persons developed cancer; SIR 3.61 (3.0-4.3) and 2.2 (1.6-3.0), resp.). SIR correlated with younger age and was highest for skin and haematological cancers for both types of transplantation. Within the cohort, cancer was associated with older age (adjusted incidence rate ratio > 50 vs ≤ 19 years, among SOT and HSCT: 9.4 (3.4-25.7) and 25.4 (5.1-126.0), resp.) and current elevated C-reactive protein (CRP) (≥ 10 vs < 10 mg/L: 2.5 (1.8-3.4) and 2.3 (1.4-3.9), resp.), but neither with prior cancer nor type of immunosuppressants. CONCLUSION: Rates of de novo or secondary cancers are elevated in both SOT and HSCT compared with the general population and mainly for skin and haematological cancers. Among transplant recipients, older age and current elevated CRP are risk factors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Primarias Secundarias/etiología , Neoplasias/etiología , Trasplante de Órganos/efectos adversos , Adulto , Estudios de Cohortes , Femenino , Humanos , Inmunosupresores/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Receptores de Trasplantes , Adulto Joven
17.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519556

RESUMEN

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.


Asunto(s)
Neoplasias/metabolismo , Neoplasias/mortalidad , Sistema Renina-Angiotensina/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Clínicos como Asunto , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Estadificación de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiología , Pronóstico , Resultado del Tratamiento
18.
Chem Biol Interact ; 313: 108824, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31542397

RESUMEN

Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Inflamación/complicaciones , Insectos/química , Animales , Artritis/tratamiento farmacológico , Artritis/etiología , Productos Biológicos/farmacología , Colitis/tratamiento farmacológico , Colitis/etiología , Humanos , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/etiología
19.
J Cancer Res Clin Oncol ; 145(12): 3047-3054, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31506741

RESUMEN

BACKGROUND: Etiological factors, such as a malignant disease, in young stroke patients are often neglected. Therefore, in this study, we aimed to investigate the risk of developing cancer in young stroke survivors. METHODS: The current case-control study sample included patients who received an initial ischemic stroke diagnosis documented in the Disease Analyzer database (IQVIA), which compiles data such as risk factors, drug prescriptions, and diagnoses obtained from general practitioners and specialists. RESULTS: The stroke and non-stroke groups included 18,668 patients each; each group had 2836 (15.3%) participants ≤ 55 years. The cancer incidence in the stroke group over the age of 55 years was higher than in the younger subgroup (29.4% versus 17.3%). The proportions of cancer patients within 10 years of follow-up were higher in the stroke group versus the non-stroke group, as well as in the subgroup of patients aged ≤ 55 versus patients > 55 years (17.3% versus 9.5% and 29.4% versus 24.9%, respectively). The calculated hazard ratio for developing cancer within 10 years of follow-up was higher in the younger stroke population (≤ 55 years) than in the older population (hazard ratio: 1.47 (CI 1.18-1.83) versus 1.17 (CI 1.10-1.25). CONCLUSION: In our cohort, young individuals aged ≤ 55 years who suffered a stroke had twice as high risk for developing cancer within 10 years after the index event compared to the control group. Stroke might have implication regarding the subsequent development of cancer and vice versa.


Asunto(s)
Neoplasias/etiología , Accidente Cerebrovascular/complicaciones , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Incidencia , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sobrevivientes
20.
Cancer Causes Control ; 30(11): 1213-1221, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31494748

RESUMEN

PURPOSE: Skin cancer has repeatedly been observed to be a marker of increased risk for developing an internal malignancy. The purpose of our study was to further investigate this association while also characterizing the potential role of family history of skin cancer in relation to risk for non-cutaneous malignancies. METHODS: Our study used data from 8,408 participants from the NHANES I epidemiological follow-up study. Cox-proportional hazards models were used to estimate the risk for developing an internal cancer associated with a personal history and family history of skin cancer during follow-up. RESULTS: A personal history of skin cancer was associated with significantly increased risk of developing an internal cancer in adjusted models [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.09-1.61] but a family history of skin cancer was not associated with increased risk (HR 0.80, 95% CI 0.58-1.11). CONCLUSIONS: Consistent with prior reports, a personal history of skin cancer was associated with increase of developing internal malignancies, but this did not hold true for a family history of skin cancer. Further research is needed to understand why a personal history of skin cancer acts as a marker for increased risk for internal cancer.


Asunto(s)
Neoplasias/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Anamnesis , Persona de Mediana Edad , Neoplasias/etiología , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Factores de Riesgo
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