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2.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519556

RESUMO

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.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Prognóstico , Resultado do Tratamento
3.
J Cancer Res Clin Oncol ; 145(10): 2413-2422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492983

RESUMO

PURPOSE: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer. METHODS: The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo. CONCLUSIONS: PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.


Assuntos
Biomarcadores Tumorais , Neoplasias/etiologia , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Centrossomo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Especificidade de Órgãos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
4.
Artigo em Alemão | MEDLINE | ID: mdl-31410522

RESUMO

BACKGROUND: Cancer information services (CISs) are a valuable source of evidence-based information. Previous studies in the field of CISs often investigate only short periods of time. However, there is a need for long-term analyses to identify changes in the use of CISs. OBJECTIVES: The purpose of this study was to analyze trends in the inquiries of patients and surrogate seekers to a CIS. METHOD: We conducted a secondary data analysis of the inquiry records of the German CIS (Krebsinformationsdienst, KID) hosted by the German Cancer Research Center from 1992 until 2016 (N = 545,070). Trends in the number of inquiries were described using the whole sample, while the description of further characteristics is based on a sample (n = 55,046) of patients, their family members, and friends. RESULTS: The inquiries increased in the period examined (1992: 11,344 inquiries; 2016: 34,869 inquiries). Since 2005, a greater share of patients (between 52 and 60%) than surrogate seekers have been contacting the CIS. The mean age of both self-seeking and supported patients increased from under 55 years between 1992 and 2000 up to over 60 years in the year 2016. Breast cancer is at all times the most frequently inquired cancer type (patients: n = 11,319, 39%; surrogate seekers: n = 4173, 17%). Even after the implementation of e­mail as an additional communication channel, the majority of inquirers still prefer contact by phone (between 80 and 98%). CONCLUSIONS: Changes in the utilization of a CIS over time are discussed against the background of structural changes, such as shifts in prevalence rates, family structures, or media environments.


Assuntos
Comportamento do Consumidor , Serviços de Informação/estatística & dados numéricos , Neoplasias/terapia , Educação de Pacientes como Assunto/métodos , Pesquisa , Família , Feminino , Alemanha , Linhas Diretas/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/prevenção & controle
5.
Artigo em Japonês | MEDLINE | ID: mdl-31434811

RESUMO

Recently, the main air pollutant has been fine particulate matter (PM2.5), which is taken up by the whole body with severe adverse health effects. The main chemical components of PM2.5 are salts of sulfate (and nitrate) and carbons. However, it remains unknown which components are toxic. Here, the author reviewed the literatures to determine which components are toxic and the main mechanisms underlying their toxicity. Many epidemiological studies have shown that sulfate concentration is strongly related to mortality. However, there is no experimental evidence showing that sulfate at environmental concentrations of PM2.5 causes cardiovascular disease or other disease. On the other hand, carbon components such as elementary carbon (EC) produces high concentrations of reactive oxygen species (ROS) via its phagocytosis by macrophages, and organic carbon (OC) also produces high concentrations of ROS during its metabolic processes, and the ROS cause acute and chronic inflammation. They cause many diseases including cardiovascular disease, asthma and cancer. Furthermore, there are many lines of evidence showing that epigenetic changes such as DNA methylation or microRNA expression induced by particulate matters also induce the development of many diseases such as those mentioned above. It has been reported that carbon components are incorporated into the brain and produce ROS, and that the ROS cause damage to brain cells and Alzheimer's disease and cognitive disorders in the elderly.From these lines of evidence, the author would like to emphasize that the main toxicity of PM2.5 is due to carbon components, and it is important to take countermeasures to decrease the concentration of carbon components in ambient air.


Assuntos
Poluentes Atmosféricos/toxicidade , Carbono/toxicidade , Material Particulado/toxicidade , Sulfatos/toxicidade , Doença de Alzheimer/etiologia , Animais , Asma/etiologia , Doenças Cardiovasculares/etiologia , Epigênese Genética , Cobaias , Humanos , Camundongos , Neoplasias/etiologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
6.
Chem Biol Interact ; 310: 108736, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278902

RESUMO

The linear non-threshold (LNT) dose response model for cancer risk assessment has been a controversial concept since its initial proposal during the 1930s. It was long advocated by the radiation genetics community in the 1950s, some two decades prior to being generally adopted within the chemical toxicology community. This paper explores possible reasons for such major differences in the acceptance of LNT for cancer risk assessment by these two key groups of scientists.


Assuntos
Modelos Lineares , Neoplasias/etiologia , Radiação Ionizante , Medição de Risco/normas , United States Environmental Protection Agency/normas , Relação Dose-Resposta à Radiação , Humanos , Radiogenética/normas , Toxicologia/normas , Estados Unidos
7.
Bull Cancer ; 106(7-8): 635-646, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31227175

RESUMO

In the past decades, obesity and overweight prevalence has been rising worldwide, in both men and women. In France, the prevalence of overweight in adults was 49% in 2015 (54% among men and 44% among women), including 17% of obese adults. According to the last evaluation performed by IARC in 2017, overweight and obesity are established risk factors for 13 cancer sites with risk estimates per 5kg/m2 varying largely depending on the cancer site. In 2015 in France, 5.4% of cancer cases could be attributed to excess weight, corresponding to 18,600 cases, including 3400 colon cancers, 2600 kidney cancers, 4500 breast cancers and 2500 endometrial cancers. Obesity is also related to worse prognosis for some cancers, in particular breast and colon cancers. Obesity in children and adolescents, also rising in many countries, has also been associated to an increase in adult cancer risk. A major cause of obesity is a disequilibrium in energy balance favoured by a diet rich in processed food, red meat, trans and saturated fatty acids, sweetened foods and beverages and poor in fruits and vegetables, legumes and whole grains. Main national and international recommendations to reduce the prevalence of obesity are to have a balanced diet and regular physical activity.


Assuntos
Neoplasias/epidemiologia , Sobrepeso/epidemiologia , Adulto , Criança , Cocarcinogênese , Comorbidade , Dieta/efeitos adversos , Metabolismo Energético , Exercício , Feminino , Saúde Global , Hormônios Esteroides Gonadais/fisiologia , Guias como Assunto , Humanos , Inflamação , Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Neoplasias/etiologia , Neoplasias/prevenção & controle , Especificidade de Órgãos , Sobrepeso/complicações , Sobrepeso/fisiopatologia , Prevalência , Fatores de Risco , Organização Mundial da Saúde
8.
Nat Rev Cancer ; 19(7): 392-404, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209264

RESUMO

The potential of cancer immunotherapy relies on the mobilization of immune cells capable of producing antitumour cytokines and effectively killing tumour cells. These are major attributes of γδ T cells, a lymphoid lineage that is often underestimated despite its major role in tumour immune surveillance, which has been established in a variety of preclinical cancer models. This situation notwithstanding, in particular instances the tumour microenvironment seemingly mobilizes γδ T cells with immunosuppressive or tumour-promoting functions, thus emphasizing the importance of regulating γδ T cell responses in order to realize their translation into effective cancer immunotherapies. In this Review we outline both seminal work and recent advances in our understanding of how γδ T cells participate in tumour immunity and how their functions are regulated in experimental models of cancer. We also discuss the current strategies aimed at maximizing the therapeutic potential of human γδ T cells, on the eve of their exploration in cancer clinical trials that may position them as key players in cancer immunotherapy.


Assuntos
Imunoterapia , Neoplasias/terapia , Linfócitos T/fisiologia , Microambiente Tumoral/fisiologia , Humanos , Neoplasias/etiologia , Neoplasias/patologia
9.
Hematol Oncol ; 37 Suppl 1: 101-104, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187537

RESUMO

In recent years, many new antibodies, either naked or armed with toxin or radionuclides have been investigated to enhance the field of active agents directed against already identified ("old") targets. This was particularly the case for the antigens CD19 and CD20 but also some other ones. The success of these developments has been variable and underlines the need to better characterize the mode of action of these molecules. Combinations studies of these new agents with other molecules, in particular those with an immunomodulatory potential, are also currently developed with some promising results.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Animais , Antígenos CD19 , Antígenos CD20 , Antígenos de Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Humanos , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Imunomodulação/efeitos dos fármacos , Neoplasias/etiologia , Neoplasias/metabolismo , Tetraspaninas
10.
Eur J Epidemiol ; 34(8): 753-763, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152367

RESUMO

Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Cafeína/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Medição de Risco/métodos , Chá/efeitos adversos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , População Rural , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Fumar Tabaco/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia
11.
Transplant Proc ; 51(4): 1231-1233, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101203

RESUMO

INTRODUCTION: Immunosuppressive therapy used after organ transplantation represents a considerable oncological risk. Abdominal ultrasound examinations play an essential role in the oncological screening of organ transplant patients. Our aim was to study the effectiveness of the ultrasound screening protocol currently used in our clinic. METHODS: Reports of screening abdominal ultrasound examinations of kidney transplant recipients were processed at the Department of Transplantation and Surgery of Semmelweis University from January 2012 to December 2015. RESULTS: In 1478 studies, 14 patients were diagnosed with a malignant tumor, 11 of which were formed in the native shrunken kidney. The mean age for tumor diagnosis was 55.6 ± 12.6 years, and 80% of the patients diagnosed with tumor were male. On average, 7.5 ± 4.6 years passed between the transplantation and recognition of the tumor. All of the kidney tumors were diagnosed at an early stage: histologic examination of removed kidneys showed 73% pT1a- and 17% pT1b-stage tumors. CONCLUSION: In our study, early stage shrunken kidney cancers were outstandingly the most common post-transplant malignancies found by ultrasound screening. Annual ultrasound examinations as part of our current screening protocol allowed the detection of tumors at an early stage in kidney transplant recipients.


Assuntos
Imunossupressão/efeitos adversos , Neoplasias Renais/diagnóstico por imagem , Transplante de Rim , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/etiologia , Nefrectomia , Estudos Retrospectivos , Transplantados
12.
BMC Public Health ; 19(1): 360, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935404

RESUMO

BACKGROUND: The incidence of cancer is rising but data available regarding prevalence of cancer and patient perception of the disease in Pakistan is limited. It is difficult to deal with Cancer if the main causes are negligence towards risk factors and bizarre myths. This study was aimed to investigate common cancer presentations at a government sector hospital and to gain insight into patient knowledge of the disease. METHODS: This was a cross-sectional study conducted on cancer patients from Jinnah Postgraduate Medical Centre. A self-made questionnaire was used to assess the norms related to cancer prevalence in our society, associated myths, and the most common risk factors per them. RESULTS: A total of 402 participants consented to participate in the study (mean age 42.3 ± 15.07 years), 204(50.7%) were females and 190(47.3%) were illiterate. Biomass exposure was found in 147(37%), drug abuse in 132(33%) and smoking in 63(16%). We found 103(25.6%) had positive family histories of cancer. The most common primary tumor site was breast for females 98(48%) and Head and neck 66(33.3%) for males. Patients considered fate 328(82%), gutka 284(71%) and injuries 282(70%) as the most common causes for cancer; while 222(55.5%) considered black magic and 236(58.75%) considered evil eye as a risk factor for cancer. Cancer treatment caused significant financial stress in 376(93.5%) patients. CONCLUSION: Breast and head and neck cancers were found to be prevalent among patients. It was noted that patients are negligent in daily life regarding the consumption of substances that commonly cause cancer. Individuals had diminished knowledge and majority linked cancer to unrelated causes and myths like black magic and fate. Almost all the patients complained of severe financial stress imposed by the disease.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Gastos em Saúde , Humanos , Incidência , Magia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Paquistão/epidemiologia , Percepção , Prevalência , Fatores de Risco , Inquéritos e Questionários , Centros de Atenção Terciária , Tabaco sem Fumaça
13.
Ann Ist Super Sanita ; 55(1): 70-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968841

RESUMO

INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders. METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills. DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites. CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.


Assuntos
Asbestos/efeitos adversos , Asbestose/epidemiologia , Educação em Saúde/estatística & dados numéricos , Asbestose/prevenção & controle , Comunicação , Exposição Ambiental , Humanos , Incidência , Itália/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Exposição Ocupacional , Vigilância em Saúde Pública
14.
J Cancer Res Ther ; 15(2): 269-271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964096

RESUMO

Although this is an exciting time for translational medicine, systematic approaches and strategies to conduct translational research are sparse. We highlight in this editorial the opportunities to collaborate across disciplines and to forge new interdisciplinary collaborative ventures from the perspective of epidemiology. We specifically outline some feasible research areas, wherein Translational Epidemiology may readily speed up the translation of research for Precision Medicine.


Assuntos
Neoplasias/epidemiologia , Pesquisa Médica Translacional , Suscetibilidade a Doenças , Humanos , Longevidade , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/terapia , Farmacogenética , Medicina de Precisão , Pesquisa Médica Translacional/estatística & dados numéricos
15.
Prev Chronic Dis ; 16: E45, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30974072

RESUMO

INTRODUCTION: Burden of disease is often defined by using epidemiologic measures. However, there may be latent aspects of disease burden that are not factored into these types of estimates. This study quantified environmental burden of disease by using population health indicators and exploratory factor analysis at the county level across the United States. METHODS: Ninety-nine variables drawn from public use data sets from 2010 to 2016 were used to create a multifactor index - the burden index. We applied principal components analysis with promax rotation to allow the factors to correlate. Correlation coefficients for each factor and the outcome of interest, age-adjusted cancer death rate, were calculated. We used both unadjusted and adjusted linear regression techniques. RESULTS: The final additive county-level index included 9 factors that explained 68.3% of the variance in the counties and county equivalents. The burden index had a moderate association with the age-adjusted cancer death rates (r =.48, P <.001), and adjusted linear regression with all 9 factors explained 34% of the variance in the age-adjusted cancer death rate. Results were mapped, and the geographic distribution of both the burden index and age-adjusted cancer mortality were assessed. There are distinct geospatial patterns for both. CONCLUSIONS: Results from this study show potential areas of need, as well as the importance of including environmental variables in the study of cancer etiology. Future studies can aim to validate these findings by quantifying burden as it relates to overall cancer mortality by using epidemiologic measures, along with other confirmatory statistical methods.


Assuntos
Efeitos Psicossociais da Doença , Indicadores Básicos de Saúde , Neoplasias/mortalidade , Análise Fatorial , Feminino , Humanos , Masculino , Neoplasias/etiologia , Fatores de Risco , Fatores Socioeconômicos , Análise Espacial , Estados Unidos/epidemiologia
16.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013796

RESUMO

Telomerase, an enzyme responsible for the synthesis of telomeres, is activated in many cancer cells and is involved in the maintenance of telomeres. The activity of telomerase allows cancer cells to replicate and proliferate in an uncontrolled manner, to infiltrate tissue, and to metastasize to distant organs. Studies to date have examined the mechanisms involved in the survival of cancer cells as targets for cancer therapeutics. These efforts led to the development of telomerase inhibitors as anticancer drugs, drugs targeting telomere DNA, viral vectors carrying a promoter for human telomerase reverse transcriptase (hTERT) genome, and immunotherapy targeting hTERT. Among these novel therapeutics, this review focuses on immunotherapy targeting hTERT and discusses the current evidence and future perspectives.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Telomerase/antagonistas & inibidores , Animais , Antígenos de Neoplasias/imunologia , Antineoplásicos/farmacologia , Vacinas Anticâncer/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Terapia Genética , Humanos , Imunoterapia , Terapia de Alvo Molecular , Neoplasias/metabolismo , Telomerase/genética , Telomerase/metabolismo , Vacinas de DNA/imunologia
17.
EBioMedicine ; 42: 431-442, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935888

RESUMO

BACKGROUND: Prior studies showed that tumor glycolysis and tumor immune evasion are interdependent. However, a systematic investigation of the association between tumor glycolysis and tumor immunity in various cancers remains lacking. METHODS: Using the Cancer Genome Atlas (TCGA) datasets, we explored the association between glycolytic activity and immune signatures in 14 cancer types. We also explored the associations between glycolytic activity and tumor immunity associated genetic features, including PD-L1 expression, tumor mutation burden (TMB), and tumor aneuploidy. Moreover, we performed in vitro experiments to verify some findings from bioinformatics analysis. Furthermore, we explored the association between tumor glycolytic activity and immunotherapy response. FINDINGS: Glycolytic activity was likely correlated with active immune signatures in various cancers and highly glycolytic tumors presented an immune-stimulatory tumor microenvironment. Compared to TMB and aneuploidy, glycolytic activity was a stronger and more consistent predictor for immune signatures in diverse cancers. Both computational and experimental analyses showed that glycolysis could increase PD-L1 expression in tumor. Glycolytic activity had a strong correlation with apoptosis which was a strong positive predictor for immune signatures, suggesting that apoptosis could be an important medium connecting glycolytic activity with immune activity in cancer. Finally, highly glycolytic tumors exhibited a better immunotherapy response and a favorable survival in the immunotherapy setting. INTERPRETATION: Tumor glycolysis may increase tumor immunity in diverse cancers. Glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-1/PD-L1 immunotherapy response. Thus, the tumor glycolytic activity could be a predictive biomarker for immunotherapy response in diverse cancers. FUND: This work was supported by the China Pharmaceutical University (grant numbers 3150120001, 2632018YX01 to XW).


Assuntos
Imunidade , Neoplasias/etiologia , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Biologia Computacional/métodos , Metabolismo Energético , Predisposição Genética para Doença , Glicólise , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Neoplasias/mortalidade , Neoplasias/patologia
18.
Exp Oncol ; 41(1): 3-6, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30932417

RESUMO

Quinazolines are among the most useful heterocyclic compounds due to their diverse chemical reactivity and a wide range of biological activity. Despite a large number of publications devoted to quinazolines and their derivatives, information is presented predominantly regarding the features of the synthesis of these compounds and their structure. The studies of specific pharmacological activity and antitumor activity of these compounds are mainly limited to primary screening using enzyme systems and cell lines. In this mini review information concerning the potential targets for antitumor action of quinazoline compounds is summarized and discussed.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias/metabolismo , Quinazolinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Estudos Clínicos como Assunto , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/patologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/química , Quinazolinas/uso terapêutico , Resultado do Tratamento
19.
J Cancer Res Clin Oncol ; 145(5): 1087-1109, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903319

RESUMO

PURPOSE: Cancer is a serious health issue and a leading cause of death worldwide. Most of the cancer patients (approximately 90%) do not die from the consequences of the primary tumor development, but due to a heavily treatable metastatic invasion. During the lengthy multistep process of carcinogenesis, there are a lot of opportunities available to reverse or slow down the tissue invasion or the process of tumor metastasis formation. RESULTS: Current research has brought many promising results from anti-metastatic experimental studies, and has shown that chemoprevention by natural or semisynthetic phytochemicals with plethora of biological activities could be one of the potentially effective options in the fight against this problem. However, there is a lack of clinical trials to confirm these findings. In this review, we focused on summarization and discussion of the general features of metastatic cancer, and recent preclinical and clinical studies dealing with anti-metastatic potential of various plant-derived compounds. CONCLUSIONS: Based on our findings, we can conclude and confirm our hypothesis that phytochemicals with pleiotropic anticancer effects can be very useful in retarding and/or reversing the metastasis process, and can also be used to prevent tissue invasion and metastases. But, further studies in this area are certainly necessary and desirable.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias/metabolismo , Neoplasias/terapia , Compostos Fitoquímicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Quimioprevenção , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/etiologia , Neoplasias/patologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Resultado do Tratamento , Microambiente Tumoral
20.
Environ Sci Pollut Res Int ; 26(13): 12648-12661, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903465

RESUMO

Ambient air pollution is nowadays one of the most crucial contributors to deteriorating health status worldwide. The components of air pollution include PM2.5 and PM10, NO2, SO2, CO, O3, and organic compounds. They are attributed to several health outcomes, for instance, cardiovascular diseases (CVD), respiratory diseases, birth outcomes, neurologic diseases, and psychiatric diseases. The objective of this study is to evaluate the association between different ambient air pollutants and the above-mentioned health outcomes. In this systematic review, a total of 76 articles was ultimately selected from 2653 articles, through multiple screening steps by the aid of a set of exclusion criteria as non-English articles, indoor air pollution assessment, work-related, occupational and home-attributed pollution, animal studies, tobacco smoking effects, letters to editors, commentaries, animal experiments, reviews, case reports and case series, out of 19,862 published articles through a systematic search in PubMed, Web of Science, and Scopus. Then, the associations between air pollution and different health outcomes were measured as relative risks and odds ratios. The association between air pollutants, PM2.5 and PM10, NO2, SO2, CO, O3, and VOC with major organ systems health was investigated through the gathered studies. Relative risks and/or odds ratios attributed to each air pollutant/outcome were ultimately reported. In this study, a thorough and comprehensive discussion of all aspects of the contribution of ambient air pollutants in health outcomes was proposed. To our knowledge up to now, there is no such comprehensive outlook on this issue. Growing concerns in concert with air pollution-induced health risks impose a great danger on the life of billions of people worldwide. Should we propose ideas and schemes to reduce ambient air pollutant, there will be dramatic reductions in the prevalence and occurrence of health-threatening conditions.


Assuntos
Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/efeitos adversos , Doenças do Sistema Nervoso/epidemiologia , Doenças Respiratórias/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Exposição Ambiental/análise , Feminino , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Doenças do Sistema Nervoso/etiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Gravidez , Resultado da Gravidez , Doenças Respiratórias/etiologia
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