Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.989
Filtrar
1.
Tumour Biol ; 42(10): 1010428320965284, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33028168

RESUMO

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells' bioenergetics differently. Tumor cells' dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.


Assuntos
Antineoplásicos/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Medicina de Precisão , Antineoplásicos/farmacologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Metabolismo Energético/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias/etiologia , Neoplasias/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Via de Pentose Fosfato/efeitos dos fármacos , Medicina de Precisão/métodos
2.
PLoS One ; 15(8): e0231510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32818954

RESUMO

With increasing medical radiation exposures, it is important to understand how different modes of delivery of ionizing radiation as well as total doses of exposure impact health outcomes. Our lab studied the risks associated with ionizing radiation by analyzing the Northwestern University Radiation Archive for animals (NURA). NURA contains detailed data from a series of 10 individual neutron and gamma irradiation experiments conducted on over 50,000 mice. Rigorous statistical testing on control mice from all Janus experiments enabled us to select studies that could be compared to one another and uncover unexpected differences among the controls as well as experimental animals. For controls, mice sham irradiated with 300 fractions died significantly earlier than those with fewer sham fractions and were excluded from the pooled dataset. Using the integrated dataset of gamma irradiated and control mice, we found that fractionation significantly decreased the death hazard for animals dying of lymphomas, tumors, non-tumors, and unknown causes. Gender differences in frequencies of causes of death were identified irrespective of irradiation and dose fractionation, with female mice being at a greater risk for all causes of death, except for lung tumors. Irradiated and control male mice were at a significantly greater risk for lung tumors, the opposite from observations noted in humans. Additionally, we discovered that lymphoma deaths can occur quickly after exposures to high doses of gamma rays. This study systematically cross-compared outcomes of different modes of fractionation evaluated across different Janus experiments and across a wide span of total doses. It demonstrates that protraction modulated survival and disease status differently based on the total dose, cause of death, and sex of an animal. This novel method for analyzing the Janus datasets will lead to insightful new mechanistic hypotheses and research in the fields of radiation biology and protection.


Assuntos
Relação Dose-Resposta à Radiação , Neoplasias/etiologia , Exposição à Radiação/efeitos adversos , Animais , Bases de Dados Factuais , Modelos Animais de Doenças , Fracionamento da Dose de Radiação , Feminino , Raios gama , Incidência , Masculino , Camundongos , Morbidade , Nêutrons , Exposição à Radiação/estatística & dados numéricos , Radiação Ionizante , Eficiência Biológica Relativa
3.
PLoS Med ; 17(7): e1003178, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32701947

RESUMO

BACKGROUND: Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers. METHODS AND FINDINGS: We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.59-2.03; p = 2.26 × 10-21) and UK Biobank (OR 2.26; 95% CI 1.92-2.65; p = 1.17 × 10-22). Additionally, genetic predisposition to smoking was associated with statistically significant higher odds of cancer of the oesophagus (OR 1.83; 95% CI 1.34-2.49; p = 1.31 × 10-4), cervix (OR 1.55; 95% CI 1.27-1.88; p = 1.24 × 10-5), and bladder (OR 1.40; 95% CI 1.92-2.65; p = 9.40 × 10-5) and with statistically nonsignificant higher odds of head and neck (OR 1.40; 95% CI 1.13-1.74; p = 0.002) and stomach cancer (OR 1.46; 95% CI 1.05-2.03; p = 0.024). In contrast, there was an inverse association between genetic predisposition to smoking and prostate cancer in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (OR 0.90; 95% CI 0.83-0.98; p = 0.011) and in UK Biobank (OR 0.90; 95% CI 0.80-1.02; p = 0.104), but the associations did not reach statistical significance. We found no statistically significant association between genetically predicted alcohol consumption and overall cancer (n = 75,037 cases; OR 0.95; 95% CI 0.84-1.07; p = 0.376). Genetically predicted alcohol consumption was statistically significantly associated with lung cancer in the International Lung Cancer Consortium (OR 1.94; 95% CI 1.41-2.68; p = 4.68 × 10-5) but not in UK Biobank (OR 1.12; 95% CI 0.65-1.93; p = 0.686). There was no statistically significant association between alcohol consumption and any other site-specific cancer. The main limitation of this study is that precision was low in some analyses, particularly for analyses of alcohol consumption and site-specific cancers. CONCLUSIONS: Our findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Análise da Randomização Mendeliana/métodos , Neoplasias/etiologia , Fumar/genética , Bancos de Espécimes Biológicos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Reino Unido
4.
Artigo em Inglês | MEDLINE | ID: mdl-32517176

RESUMO

Continued tobacco use after cancer diagnosis is detrimental to treatment and survivorship. The current reach of evidence-based tobacco treatments in cancer patients is low. As a part of the National Cancer Institute Cancer Center Cessation Initiative, the Mayo Clinic Cancer Center designed an electronic health record (EHR, Epic©)-based process to automatically refer ambulatory oncology patients to tobacco use treatment, regardless of intent to cease tobacco use("opt out"). The referral and patient scheduling, accomplished through a best practice advisory (BPA) directed to staff who room patients, does not require a co-signature from clinicians. This process was piloted for a six-week period starting in July of 2019 at the Division of Medical Oncology, Mayo Clinic, Rochester, MN. All oncology patients who were tobacco users were referred for tobacco treatment by the rooming staff (n = 210). Of these, 150 (71%) had a tobacco treatment appointment scheduled, and 25 (17%) completed their appointment. We conclude that an EHR-based "opt-out" approach to refer patients to tobacco dependence treatment that does not require active involvement by clinicians is feasible within the oncology clinical practice. Further work is needed to increase the proportion of scheduled patients who attend their appointments.


Assuntos
Registros Eletrônicos de Saúde , Neoplasias/complicações , Neoplasias/epidemiologia , Encaminhamento e Consulta , Abandono do Hábito de Fumar/métodos , Tabagismo/diagnóstico , Tabagismo/terapia , Humanos , Sistemas Computadorizados de Registros Médicos , Neoplasias/etiologia , Neoplasias/patologia , Uso de Tabaco , Interface Usuário-Computador
5.
Ann Biol Clin (Paris) ; 78(3): 243-252, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540813

RESUMO

Adiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.


Assuntos
Adiponectina/fisiologia , Animais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia
6.
PLoS One ; 15(6): e0234015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497122

RESUMO

Cigarette smoking is among the leading risk factors for mortality and morbidity. While men have a higher smoking prevalence, mechanistic experiments suggest that women are at higher risk for health problems due to smoking. Moreover, the comparison of smoking effects on multiple conditions and mortality for men and women has not yet been done in a population-based group with race/ethnic diversity. We used proportional hazards models and restricted mean survival time to assess differences in smoking effects by sex for multiple health outcomes using data from the U.S. Health and Retirement Study (HRS), a population-representative cohort of individuals aged 50+ (n = 22,708, 1992-2014). Men had experienced more smoking pack-years than women (22.0 vs 15.6 average pack-years). Age of death, onset of lung disorders, heart disease, stroke, and cancer showed dose-dependent effects of smoking for both sexes. Among heavy smokers (>28 pack-years) women had higher risk of earlier age of death (HR = 1.3, 95%CI:1.03-1.65) and stroke (HR = 1.37, 95%CI:1.02-1.83). Risk of cancer and heart disease did not differ by sex for smokers. Women had earlier age of onset for lung disorders (HR = 2.83, 95%CI:1.74-4.6), but men risk due to smoking were higher (Smoking-Sex interaction P<0.02) than women. Passive smoke exposure increased risk of earlier heart disease (HR = 1.33, 95%CI:1.07-1.65) and stroke (HR:1.54, 95%CI:1.07-2.22) for non-smokers, mainly in men. Smoking cessation after 15 years partially attenuated the deleterious smoking effects for all health outcomes. In sum, our results suggest that women are more vulnerable to ever smoking for earlier death and risk of stroke, but less vulnerable for lung disorders. From an epidemiological perspective, sex differences in smoking effects are important considerations that could underlie sex differences in health outcomes. These findings also encourage future mechanistic experiments to resolve potential mechanisms of sex-specific cigarette smoke toxicity.


Assuntos
Fumar Cigarros/efeitos adversos , Fatores Etários , Idoso , Envelhecimento , Fumar Cigarros/epidemiologia , Feminino , Cardiopatias/etiologia , Humanos , Pneumopatias/etiologia , Pessoa de Meia-Idade , Neoplasias/etiologia , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/etiologia
7.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188388, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32589907

RESUMO

Bacteria have long been known as one of the primary causative agents of cancer, however, recent studies suggest that they can be used as a promising agent in cancer therapy. Because of the limitations that conventional treatment faces due to the specific pathophysiology and the tumor environment, there is a great need for the new anticancer therapeutic agents. Bacteriotherapy utilizes live, attenuated strains or toxins, peptides, bacteriocins of the bacteria in the treatment of cancer. Moreover, they are widely used as a vector for delivering genes, peptides, or drugs to the tumor target. Interestingly, it was found that their combination with the conventional therapeutic approaches may enhance the treatment outcome. In the genome editing era, it is feasible to develop a novel generation of therapeutic bacteria with fewer side effects and more efficacy for cancer therapy. Here we review the current knowledge on the dual role of bacteria in the development of cancer as well as cancer therapy.


Assuntos
Bactérias/metabolismo , Neoplasias/microbiologia , Neoplasias/terapia , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Bactérias/genética , Bactérias/patogenicidade , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Terapia Biológica , Carcinogênese , Sistemas de Liberação de Medicamentos , Engenharia Genética , Humanos , Imunoterapia , Neoplasias/etiologia
8.
Med Hypotheses ; 143: 109882, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485314

RESUMO

The current SARS-CoV-2 has put significant strain on healthcare services worldwide due to acute COVID-19. However, the potential long-term effects of this infection haven't been extensively discussed. We hypothesize that SARS-CoV-2 may be able to cause persistent infection in some individuals, and should this be the case, that in a few years we may see a rise in cancer incidence due to carcinogenic effects of this coronavirus. Non-retroviral RNA viruses such as Coronaviridae have been shown to cause persistent infection in hosts. Empirical evidence of viral genomic material shedding weeks after apparent clinical and laboratorial resolution of COVID-19 may be an indirect proof for persistent viral infection. Furthermore, tropism towards certain immune-privileged territories may facilitate immune evasion by this virus. Structural homology with SARS-CoV-1 indicates that SARS-CoV-2 may be able to directly impair pRb and p53, which are key gatekeepers with tumor suppressor functions. Additionally, COVID-19 features preeminent inflammatory response with marked oxidative stress, which acts as both as initiator and promotor of carcinogenesis. Should there be a carcinogenic risk associated with SARS-CoV-2, the implications for public health are plenty, as infected patients should be closely watched during long periods of follow-up. Additional investigation to establish or exclude the possibility for persistent infection is paramount to identify and prevent possible complications in the future.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Neoplasias/etiologia , Pneumonia Viral/complicações , Betacoronavirus/patogenicidade , Carcinogênese , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Modelos Biológicos , Estresse Oxidativo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Receptores Virais/metabolismo , Fatores de Risco
9.
Cancer Sci ; 111(9): 3155-3163, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594560

RESUMO

The eukaryotic nucleus is not a homogenous single-spaced but a highly compartmentalized organelle, partitioned by various types of membraneless structures, including nucleoli, PML bodies, paraspeckles, DNA damage foci and RNA clouds. Over the past few decades, these nuclear structures have been implicated in biological reactions such as gene regulation and DNA damage response and repair, and are thought to provide "microenvironments," facilitating these reactions in the nucleus. Notably, an altered morphology of these nuclear structures is found in many cancers, which may relate to so-called "nuclear atypia" in histological examinations. While the diagnostic significance of nuclear atypia has been established, its nature has remained largely enigmatic and awaits characterization. Here, we review the emerging biophysical principles that govern biomolecular condensate assembly in the nucleus, namely, liquid-liquid phase separation (LLPS), to investigate the nature of the nuclear microenvironment. In the nucleus, LLPS is typically driven by multivalent interactions between proteins with intrinsically disordered regions, and is also facilitated by protein interaction with nucleic acids, including nuclear non-coding RNAs. Importantly, an altered LLPS leads to dysregulation of nuclear events and epigenetics, and often to tumorigenesis and tumor progression. We further note the possibility that LLPS could represent a new therapeutic target for cancer intervention.


Assuntos
Núcleo Celular/metabolismo , Suscetibilidade a Doenças , Neoplasias/etiologia , Neoplasias/metabolismo , Biomarcadores , Núcleo Celular/genética , Cromatina/genética , Cromatina/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Extração Líquido-Líquido , Mitose , Neoplasias/patologia , Proteômica/métodos , RNA não Traduzido
11.
Croat Med J ; 61(2): 159-166, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32378382

RESUMO

Health can be defined as a harmony, or homeostasis, of the activities of thousands of different proteins, whereas aging and diseases result from their disharmony manifested at the levels of cells and tissues. Such disharmony is caused primarily by dysfunction and toxicity of misfolded proteins damaged by oxidation. This is an overview of key data that inspired new concepts allowing interpretation and integration of the scientific literature on aging and age-related diseases. These concepts suggest strategies for prevention and attenuation of age-related degenerative and malignant diseases mimicking the life of super-centenarians.


Assuntos
Envelhecimento/fisiologia , Neoplasias , Doenças Neurodegenerativas , Proteínas , Idoso , Dano ao DNA , Humanos , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Oxirredução , Redobramento de Proteína , Proteínas/química , Proteínas/metabolismo , Proteólise
12.
Med J Aust ; 212(11): 528-534, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32388913

RESUMO

Psoriasis is a chronic inflammatory disease that is commonly encountered in primary care and is associated with significant morbidity that extends beyond the skin manifestations. Psoriasis is associated with an elevated risk of psoriatic arthritis, cardiovascular disease, obesity, insulin resistance, mental health disorders, certain types of malignancy, inflammatory bowel disease and other immune-related disorders, and hepatic and renal disease. Enhanced recognition of these comorbidities may lead to earlier diagnosis and potentially better overall health outcomes. Psoriatic nail involvement, severe skin disease and obesity are associated with a greater risk of psoriatic arthritis. Individuals with psoriasis should be routinely screened for psoriatic arthritis to allow for early intervention to improve long term prognosis. Life expectancy is reduced in people with psoriasis due to a variety of causes, with cardiovascular disease and malignancy being the most common aetiologies. Psoriasis affects several factors that contribute to worsened quality of life and increased risk of depression and anxiety. Effective therapies are now available that have been shown to concurrently improve skin disease, quality of life and psychiatric symptoms. As the concordance between psychosocial impact and objective disease severity does not always correlate, it is essential to tailor management strategies specifically to the needs of each individual. Cigarette smoking and excess alcohol consumption are among the most important modifiable risk factors that increase the likelihood of psoriasis development and severity of skin disease. This provides a compelling rationale for smoking cessation and limiting alcohol intake in people with psoriasis beyond their traditional harmful health consequences.


Assuntos
Artrite Psoriásica/epidemiologia , Doenças Cardiovasculares/epidemiologia , Neoplasias/epidemiologia , Obesidade/epidemiologia , Psoríase/epidemiologia , Artrite Psoriásica/etiologia , Doenças Cardiovasculares/etiologia , Comorbidade , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Resistência à Insulina , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Neoplasias/etiologia , Obesidade/etiologia , Prognóstico , Psoríase/complicações , Fatores de Risco
13.
Cancer Sci ; 111(7): 2212-2222, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391619

RESUMO

The innate immune system, the first line of defense against pathogens, is activated by nucleic acids from microbial invaders that are recognized by nucleic acid-sensing receptors. Recent evidence affirms the ability of these receptors to respond to nucleic acids released by damaged cancer cells. The innate immune system is also involved in cancer immunosurveillance, and could be modulated for devising effective antitumor therapies by targeting nucleic acid-sensing pathways. A systematic, comprehensive analysis of dysregulation in nucleic acid-sensing pathways in cancer is required to fully understand its role. Based on multidimensional data of The Cancer Genome Atlas pan-cancer cohort, we revealed that upregulation of cytosolic DNA-sensing genes like AIM2 and CGAS was common in tumor tissues. We used 15 genes in the nucleic acid-sensing pathway to cluster all tumor patients into 2 subgroups and found that the subgroup with higher expression of nucleic acid-sensing pathway genes was associated with poorer prognosis across cancer types. However, in homologous recombination deficient patients, the nucleic acid recognition activated subgroup was associated with better prognosis, which confirms the therapeutic effect of nucleic acid recognition. This study contributes to a better understanding of the functions and mechanisms of nucleic acid recognition in cancer, lays the foundation for new therapeutic strategies, and enlarges the scope of development of new drugs.


Assuntos
Regulação Neoplásica da Expressão Gênica , Imunidade Inata , Neoplasias/etiologia , Neoplasias/metabolismo , Ácidos Nucleicos/imunologia , Ácidos Nucleicos/metabolismo , Transdução de Sinais , Biomarcadores , Análise por Conglomerados , Biologia Computacional/métodos , Metilação de DNA , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias/mortalidade , Prognóstico
14.
Cancer Causes Control ; 31(8): 767-776, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462559

RESUMO

PURPOSE: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM2.5) exposure, smoking, and cancer mortality. METHODS: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014. A sub-cohort of 341,665 never-smokers from the full cohort was also created. Individuals were assigned modeled PM2.5 exposure based on average exposure from 1999 to 2015 at residential census tract. Cox Proportional Hazard models were utilized to estimate hazard ratios for cancer-specific mortality controlling for age, sex, race, smoking status, body mass, income, education, marital status, rural versus urban, region, and survey year. RESULTS: The risk of all cancer mortality was adversely associated with PM2.5 (per 10 µg/m3 increase) in the full cohort (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22) and the never-smokers' cohort (HR 1.19, 95% CI 1.06-1.33). PM2.5-morality associations were observed specifically for lung, stomach, colorectal, liver, breast, cervix, and bladder, as well as Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia. The PM2.5-morality association with lung cancer in never-smokers was statistically significant adjusting for multiple comparisons. Cigarette smoking was statistically associated with mortality for many cancer types. CONCLUSIONS: Exposure to PM2.5 air pollution contributes to lung cancer mortality and may be a risk factor for other cancer types. Cigarette smoking has a larger impact on cancer mortality than PM2.5 , but is associated with similar cancer types.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Fumar Cigarros/efeitos adversos , Fumar Cigarros/mortalidade , Neoplasias/etiologia , Neoplasias/mortalidade , Material Particulado/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
15.
J Biomed Sci ; 27(1): 63, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389123

RESUMO

Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.


Assuntos
Endometriose/fisiopatologia , Cardiopatias/fisiopatologia , Hipóxia/fisiopatologia , Nefropatias/fisiopatologia , Doenças Metabólicas/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Neoplasias/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Doença Crônica , Endometriose/etiologia , Feminino , Cardiopatias/etiologia , Humanos , Hipóxia/complicações , Nefropatias/etiologia , Masculino , Doenças Metabólicas/etiologia , Isquemia Miocárdica/etiologia , Neoplasias/etiologia , Pré-Eclâmpsia/etiologia , Gravidez
16.
Mutat Res ; 784: 108299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32430100

RESUMO

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single event in which one or more chromosomes go through severe DNA damage very much resembling rogue cells (RC) described more than 50 years ago. In this review, we for the first time compare these two multi-aberrant cells types, RC versus chromothriptic cells, giving insight into the similarities of the mechanisms involved in their etiology. In order to make a better comparison, data on RC in 3366 subjects from studies on cancer patients, Chernobyl liquidators, child victims of the Chernobyl nuclear plant accident, residentially and occupationally exposed population have been summarized for the first time. Results of experimental and epidemiological analysis show that chromothriptic cells and RC may be caused by exposure to high LET ionizing radiation. Experience and knowledge collected on RC may be used in future for further investigations of chromothripsis, introducing a new class of cells which include both chromothriptic and RC, and better insight into the frequency of chromothriptic cell per subject, which is currently absent. Both cell types are relevant in investigations of cancer etiology, biomonitoring of accidentally exposed population to ionizing radiation and biomonitoring of astronauts due to their exposure to high LET ionizing radiation during interplanetary voyages.


Assuntos
Biomarcadores Tumorais/análise , Cromotripsia , Análise Citogenética , Dano ao DNA , Linfócitos/efeitos da radiação , Neoplasias/patologia , Animais , Biomarcadores Tumorais/genética , Humanos , Neoplasias/etiologia
17.
J Cancer Res Clin Oncol ; 146(7): 1765-1779, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356175

RESUMO

PURPOSE: As the number of cancer survivors in the United States increases, quantifying the risks and burden of second primary cancers (SPCs) among cancer survivors will help develop long-term prevention and surveillance strategies. We describe the risk of developing a SPC among survivors of 10 cancer sites with the highest survival rates in the United States. METHODS: Adult patients diagnosed with an index smoking-related (urinary bladder, kidney and renal pelvis, uterine cervix, oral cavity and pharynx, and colon and rectum) and index non-smoking-related (prostate, thyroid, breast, corpus and uterus, and non-Hodgkin lymphoma) cancers were identified from Surveillance, Epidemiology, and End Results (2000-2015). SPC risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). RESULTS: A cohort of 2,903,241 patients was identified and 259,685 (8.9%) developed SPC (7.6% of women and 10.3% of men). All index cancer sites (except prostate) were associated with a significant increase in SPC risk for women and men. Patients diagnosed with smoking-related index cancers (SIR range 1.20-2.16 for women and 1.12-1.91 for men) had a higher increased risk of SPC than patients with non-smoking-related index cancers (SIR range 1.08-1.39 for women and 1.23-1.38 for men) relative to the general population. CONCLUSION: We found that 1-in-11 cancer survivors developed a SPC. Given the increasing number of cancer survivors and the importance of SPC as a cause of cancer death, there is a need for increased screening for and prevention of SPC.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias/epidemiologia , Adulto , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Medição de Risco , Fatores de Risco , Programa de SEER , Fumar/efeitos adversos
18.
Surg Clin North Am ; 100(3): 469-481, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402294

RESUMO

The incidence of many types of cancer continues to increase, and despite many successes in the realms of screening, prevention, and treatment, cancer remains the second leading cause of death in North America. Cancer types affecting this population have varied over time, with a trend toward more malignancies caused by modifiable risk factors related to a western lifestyle. Despite the increasing incidence of cancer, a combination of population-based screening and improved therapeutics has made the disease more survivable, and created an ever-increasing community of cancer survivors. These cancer survivors face unique challenges and require ongoing care.


Assuntos
Neoplasias/epidemiologia , Causas de Morte/tendências , Comparação Transcultural , Humanos , Incidência , Neoplasias/etiologia , Neoplasias/mortalidade , Neoplasias/prevenção & controle , América do Norte , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida
19.
BMC Public Health ; 20(1): 376, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32238154

RESUMO

BACKGROUND: Health warning labels (HWLs) using images and text to depict the negative health consequences of tobacco consumption are effective and acceptable for changing smoking-related outcomes. There is currently limited evidence concerning their potential use for reducing consumption of alcoholic drinks and energy-dense foods. The aim of this research was to describe the potential effectiveness and acceptability of image-and-text (also known as pictorial or graphic) HWLs applied to: i. alcoholic drinks and ii. energy-dense snack foods. METHODS: Two online studies were conducted using between-subjects designs with general population samples. Participants rated one of 21 image-and-text HWLs on alcoholic drinks (n = 5528), or one of 18 image-and-text HWLs on energy-dense snacks (n = 4618). HWLs comprised a graphic image with explanatory text, depicting, respectively, seven diseases linked to excess alcohol consumption, and six diseases linked to excess energy intake. Diseases included heart disease and various cancers. Outcomes were negative emotional arousal, desire to consume the labelled product, and acceptability of the label. Free-text comments relating to HWLs were content analysed. RESULTS: For both alcoholic drinks and energy-dense snacks, HWLs depicting bowel cancer generated the highest levels of negative emotional arousal and lowest desire to consume the product, but were the least acceptable. Acceptability was generally low for HWLs applied to alcohol, with 3 of 21 rated as acceptable, and was generally high for snacks, with 13 of 18 rated as acceptable. The majority of free-text comments expressed negative reactions to HWLs on alcohol or energy-dense snacks. CONCLUSIONS: Image-and-text health warning labels depicting bowel cancer showed greatest potential for reducing selection and consumption of alcoholic drinks and energy-dense snacks, although they were the least acceptable. Laboratory and field studies are needed to assess their impact on selection and consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Bebidas Alcoólicas/efeitos adversos , Comunicação , Dieta , Fast Foods/efeitos adversos , Rotulagem de Produtos/métodos , Lanches , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Atitude Frente a Saúde , Dieta/psicologia , Emoções , Ingestão de Energia , Etanol/efeitos adversos , Comportamento Alimentar/psicologia , Feminino , Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Prevenção do Hábito de Fumar , Lanches/psicologia , Fumar Tabaco , Uso de Tabaco
20.
Cancer Sci ; 111(7): 2234-2247, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32333709

RESUMO

Natural killer group 2 member D (NKG2D) ligands (NKG2DLs) on tumor cells engage NKG2D and mediate killing by NKG2D+ immune cells. However, tumor cells with high levels of NKG2DLs are still malignant and proliferate rapidly. We investigated the reason for NKG2DL-expressing cell progression. Tumor cells in mice were assessed for their NKG2DL expression, ability to attract immune cells, tumorigenicity, mTOR, and signal transducer and activator of transcription 3 (STAT3) signaling activation. Antibody blockade was used to determine the effect of NKG2DL-NKG2D interaction on signaling activation in vitro. Retinoic acid early inducible gene 1 (Rae1) was related to the expression of other NKG2DLs, the promotion of tumorigenicity, Mmp2 expression, mTOR and STAT3 phosphorylation in GL261 cells, and the recruitment of NKG2D+ cells in mice. Rae1 also induced NKG2DL expression, mTOR, and STAT3 phosphorylation in GL261 cells and LLC cells, but not in B16 and Pan02 cells, which did not express NKG2DLs, when cocultured with PBMCs; the induced phosphorylation was eliminated by Rae1-NKG2D blockade. Inhibition of mTOR and/or STAT3 decreased PBMC-induced migration and proliferation of GL261 cells in vitro. Rae1, a NKG2DL on tumor cells, plays a driving role in the expression of other NKG2DLs and in tumor development in mice by activating mTOR and STAT3 pathways, relying on its interaction with NKG2D on immune cells.


Assuntos
Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Neoplasias/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Testes Imunológicos de Citotoxicidade , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Neoplasias/etiologia , Neoplasias/patologia , Proteínas Associadas à Matriz Nuclear/genética , Proteínas de Transporte Nucleocitoplasmático/genética , Ligação Proteica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA