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1.
Cancer Sci ; 111(4): 1165-1179, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994822

RESUMO

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling.


Assuntos
Luteolina/farmacologia , Serina-Treonina Quinases TOR/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas rho de Ligação ao GTP/genética , Animais , Apoptose/efeitos dos fármacos , Butilidroxibutilnitrosamina/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Antígeno Ki-67/genética , Luteolina/metabolismo , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Tiorredoxinas/genética , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1247-1252, 2019 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-31795581

RESUMO

Objective: To estimate the burden attributed to the dietary inorganic arsenic exposure with lung cancer, bladder cancer and skin cancer as end points. Methods: Inorganic arsenic, food or diet were used as Chinese keywords and arsenic, food and China were used as English keywords to search for literatures related to the dietary inorganic arsenic exposure published by China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed Database. Using the data from the China National Nutrition and Health Survey (CNNHS) in 2002 to estimate the dietary inorganic arsenic exposure in Chinese residents. The annual cancer cases attributed to the dietary inorganic arsenic exposure were calculated based on the data from Chinese Cancer Registry Annual Report in 2013. The disability adjusted life year (DALY) was calculated using tools built by WHO. Results: The total DALY of cancer caused by the dietary inorganic arsenic exposure was 419.4 thousand, and the DALY rate was 31.47 per 100 000. The DALY of lung cancer in males and females was 237.7 thousand and 102.5 thousand. The DALY of bladder cancer in males and females was 13.2 thousand and 3.9 thousand. The DALY of skin cancer in males and females was 29.4 thousand and 32.8 thousand. Conclusion: In 2013, the Chinese population had a lower burden of cancer due to the dietary exposure to inorganic arsenic.


Assuntos
Arsênico/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente , Arsênico/administração & dosagem , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/psicologia , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/psicologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/psicologia
3.
Mutat Res ; 782: 108281, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31843138

RESUMO

Cigarette smoking is a strong risk factor for bladder cancer. It has been shown that the duration of smoking is associated with a poor prognosis and a higher risk of recurrence. This is due to tobacco carcinogens forming adducts with DNA and proteins that participate in the DNA repair mechanisms. Additionally, polymorphisms of genes responsible for methyl group transfer in the methionine cycle and dosages of vitamins (from diet and supplements) can cause an increased risk of bladder cancer. Upregulated DNA methyltransferase 1 expression and activity results in a high level of methylated products of metabolism, as well as hypermethylation of tumor suppressor genes. The development of a market that provides new inhibitors of DNA methyltransferase or alternatives for current smokers is essential not only for patients but also for people who are under the danger of secondhand smoking and can experience its long-term exposure consequences.


Assuntos
Carcinógenos/toxicidade , Metionina/metabolismo , Tabaco/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Reparo do DNA/efeitos dos fármacos , Humanos , Fatores de Risco
4.
Am J Cardiol ; 124 Suppl 1: S45-S52, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31741440

RESUMO

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a well-defined safety profile based on data obtained from numerous clinical trials, including cardiovascular outcomes trials (CVOTs) and postmarketing pharmacovigilance reporting. Adverse events including risk of genital mycotic infection and volume depletion-related events are consistent with the mechanism of action of this drug class. However, several emergent (albeit infrequent) serious safety issues have also been reported. In their respective CVOTs, the proportion of patients with reported diabetic ketoacidosis was similar in empagliflozin or canagliflozin compared with their placebo groups, but it was higher for dapagliflozin. Canagliflozin may be associated with an increased risk of bone fracture and lower limb amputation; however, data are inconclusive. There is no evidence linking SGLT2 inhibitors with an increased risk of cancer, but these agents, particularly dapagliflozin, should be used with caution in patients with hematuria or a history of bladder cancer. Postmarketing reports of acute kidney injury have occurred in patients receiving SGLT2 inhibitors, and cases identified in recent CVOTs occurred with similar frequency in SGLT2 inhibitor and placebo groups. Common adverse events associated with SGLT2 inhibitors (such as genital infections or volume depletion) are generally mild and manageable by patients or by primary care physicians, and the risk of rare events (such as ketoacidosis) can be minimized by appropriate patient selection and early recognition of symptoms. When selecting treatment, it is important that clinicians weigh the known risks of SGLT2 inhibitors against their proven benefits, including the reduction of adverse cardiovascular and renal outcomes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Amputação/estatística & dados numéricos , Cetoacidose Diabética/induzido quimicamente , Gangrena de Fournier/induzido quimicamente , Fraturas Ósseas/induzido quimicamente , Humanos , Hipoglicemia/induzido quimicamente , Hipovolemia/induzido quimicamente , Extremidade Inferior , Micoses/induzido quimicamente , Infecções do Sistema Genital/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente , Infecções Urinárias/induzido quimicamente
5.
Genome Biol Evol ; 11(9): 2468-2479, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31384924

RESUMO

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests-PBSn1 and an ancestry-enrichment test-in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10-9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.


Assuntos
Arsênico/toxicidade , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Poluentes Químicos da Água/toxicidade , Adaptação Fisiológica , Arsênico/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Clima Desértico , Ambientes Extremos , Feminino , Humanos , Índios Norte-Americanos/genética , Masculino , Metiltransferases , Neoplasias/induzido quimicamente
6.
Urology ; 130: 148-150, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30986487

RESUMO

Alveolar soft part sarcoma (ASPS) is a rare malignancy with high rates of metastasis at presentation, defined by an unclear cellular origin and a unique unbalanced ASPSCR1-TFE3 translocation (der(17)t(X:17)(p11:q25)).1 ASPS is insensitive to chemotherapy and has been reported to involve the bladder only twice in the pediatric literature; once as a primary malignancy,2 and once as a secondary malignancy after cytotoxic chemotherapy.3 Herein, we report the third case of pediatric bladder ASPS in a female patient who received cytotoxic chemotherapy for low-risk neuroblastoma. This would represent the second case of pediatric bladder ASPS as a secondary malignancy after prior chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Segunda Neoplasia Primária/induzido quimicamente , Sarcoma Alveolar de Partes Moles/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Neuroblastoma/tratamento farmacológico
7.
Toxicol Sci ; 169(2): 456-464, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30796441

RESUMO

Acetoaceto-o-toluidide (AAOT) is made from ortho-toluidine (OTD) and is used for the synthesis of pigments. A report of occupational urinary bladder carcinomas in Japanese workers chronically exposed to OTD and AAOT has recently been published. OTD is a well-known human urinary bladder carcinogen; however, little is known about the toxicity and the carcinogenicity of AAOT. The aim of the present study is to evaluate the toxic effects of AAOT on urinary bladder epithelium. In vitro, the cytotoxicities of AAOT and OTD were evaluated in rat (MYP3) and human (1T1) urothelial cells. The LC50 of AAOT was higher than that of OTD in both MYP cells and 1T1 cells. In vivo, 6-week-old male and female F344 rats were fed diets supplemented with 0%, 1.5%, or 3% AAOT for 4 weeks. Incidences of simple hyperplasia, cell proliferative activity, and γ-H2AX expression, which is a novel marker for the prediction of carcinogenicity, were significantly increased in a dose-dependent manner in the bladder urothelium of male and female rats administered AAOT. Furthermore, in male and female rats administered AAOT, the major urine metabolite of AAOT was OTD. These results demonstrate that AAOT has proliferation-enhancing activity and suggest that OTD metabolized from AAOT may play a pivotal role in the deleterious effects of AAOT in rats. The results of the present study also indicate that AAOT, like other carcinogenic aromatic amines, is likely to be a human bladder carcinogen.


Assuntos
Toluidinas/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Histonas/análise , Humanos , Antígeno Ki-67/análise , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia
9.
Regul Toxicol Pharmacol ; 103: 166-173, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685222

RESUMO

Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is indicated to improve glycaemic control in adults of type 2 diabetes. In nonclinical studies, dapagliflozin was neither genotoxic nor carcinogenic. However, in some clinical studies, an increased incidence of bladder cancer was observed in the dapagliflozin group vs. the placebo. Therefore, this study was undertaken to determine if dapagliflozin can act as a promoter in a 2-stage bladder cancer model in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Rats given BBN (100 or 400 mg/kg, po) twice weekly for 6 weeks in Phase 1 were assigned in Phase 2 to receive daily dose of vehicle, dapagliflozin (0.5 mg/kg, po) or uracil (positive control, 3% in diet) from weeks 8-34. All bladders were evaluated by histopathology. Verifying the validity of the model, uracil increased the incidence of bladder cancer, while dapagliflozin had no effect on the incidence or invasiveness of transitional cell carcinoma. The exposure of dapagliflozin at 0.5 mg/kg/day in rats was 7 times the clinical exposure at maximal therapeutic dose (10 mg). In conclusion, dapagliflozin does not act as promoter or progressor of bladder cancer in a validated bladder cancer model in rats.


Assuntos
Compostos Benzidrílicos/administração & dosagem , Modelos Animais de Doenças , Glucosídeos/administração & dosagem , Neoplasias da Bexiga Urinária/induzido quimicamente , Administração Oral , Animais , Compostos Benzidrílicos/efeitos adversos , Butilidroxibutilnitrosamina/administração & dosagem , Butilidroxibutilnitrosamina/efeitos adversos , Relação Dose-Resposta a Droga , Glucosídeos/efeitos adversos , Masculino , Ratos , Ratos Sprague-Dawley
10.
Oncol Rep ; 41(3): 1863-1874, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628699

RESUMO

Intravesical treatment with bacillus Calmette­Guerin (BCG) is the most common treatment for preventing progression and recurrence of non­muscle invasive bladder cancer. Our previous study using the N­butyl­N­(4­hydroxybutyl) nitrosamine (BBN)­induced orthotopic bladder cancer model demonstrated that intravesical treatment with mitomycin C (MMC) and adriamycin (ADM) suppressed pro­tumoral immunity, including the aggregation of tumor­associated macrophages (TAMs) and regulatory T cells (Tregs) in the tumor microenvironment. Previous evidence supports the association of resistance to intravesical treatment of BCG with TAMs and Tregs. In the present study, we investigated the antitumoral efficacy of sequential intravesical treatments with chemotherapeutic agents and BCG in a BBN­induced orthotopic bladder cancer model. Thirty­six C57BL/6J mice bearing bladder cancer were randomly divided into six treatment groups as follows: control, BCG, MMC, ADM, MMC­BCG and ADM­BCG. Intravesical treatment was performed once a week for six weeks. One week after the completion of intravesical treatment, bladder and blood were harvested. MMC­BCG and ADM­BCG were more effective antitumor activities than BCG monotherapy. Bladders were subjected to immunohistochemical analysis and revealed that intravesical BCG treatment combined with MMC/ADM promoted the local recruitment of NK cells to the bladder as effectively as BCG monotherapy and reduced TAMs and Tregs in the bladder. Interleukin (IL)­17 and granulocyte­colony stimulating factor (G­CSF) in serum were analyzed by enzyme­linked immunosorbent assay and these levels were revealed to be elevated in mice treated with sequential treatments similar to levels following monotherapy with MMC and ADM. Our findings indicated that intravesical sequential treatment could suppress the resistance to BCG through the enhancement of antitumor immunity (induction of NK cells) and inhibition of pro­tumoral immunity (reduction of TAMs and Tregs). Systemic changes in IL­17 and G­CSF may be involved in topical immunomodulation. Further studies including clinical trials may be required to establish an appropriate strategy based on the immunomodulation of the tumor microenvironment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Vacina BCG/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Microambiente Tumoral/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacina BCG/uso terapêutico , Butilidroxibutilnitrosamina/toxicidade , Carcinoma de Células de Transição/induzido quimicamente , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Progressão da Doença , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Recidiva Local de Neoplasia/imunologia , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Bexiga Urinária/citologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/imunologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
11.
Eur J Cancer Prev ; 28(2): 76-80, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29280915

RESUMO

The aim of this study was to investigate the relation between bladder cancer risk and the use of selected drugs for cardiovascular disease (CVD) prevention, such as aspirin, statins, and calcium channel blockers (CCBs). We analyzed data from a multicentric case-control study carried out in Italy between 2003 and 2014, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) of bladder cancer and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. The ORs for bladder cancer were 1.21 (95% CI: 0.87-1.68) for regular use of aspirin, 0.72 (95% CI: 0.54-0.97) for use of any CCBs, and 1.32 (95% CI: 0.87-1.99) for use of any statins. A slight inverse association was found with duration of use of CCBs, whereas no consistent association was found with duration of use, age at first use, and frequency for aspirin and statin use, or with indication of use for aspirin (as an analgesic or, for CVD prevention). No significant association was found for various combinations of drugs or for all drugs combined (OR=1.23, 95% CI: 0.31-4.85). Our data indicate the lack of a relevant association between the use of selected drugs for CVD prevention and bladder cancer risk, although suggest a potential favorable role for CCBs.


Assuntos
Aspirina/efeitos adversos , Cardiotônicos/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Neoplasias da Bexiga Urinária/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia
12.
Int Arch Occup Environ Health ; 92(3): 347-359, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506367

RESUMO

PURPOSE: The main risk factor for bladder cancer (BC) is cigarette smoking, but also occupational exposure to carcinogens is relevant, causing about 4-10% of BC. We aimed at investigating the association between BC risk, occupations held in the past and exposure to occupational carcinogens, also assessing whether these associations were influenced by tumour grade. METHODS: We pooled data from two Italian case-control studies on male BC, analyzing 893 cases and 978 controls. Occupations were classified using the International Standard Classification of Occupations and exposure to carcinogens was assigned using a validated Job Exposure Matrix. Logistic regression approach was used as well as a semi-Bayesian model, based on a priori information on exposure. RESULTS: A significantly increased BC risk was found for chemical engineering technicians, postmen, and lathe operators, but only, for the latter, the association remained significant after Bayesian control for type I error. Among carcinogens, cadmium and trichloroethylene were associated with BC. When analyzing data by grade, exposure to these carcinogens was associated with low-grade BC only. CONCLUSIONS: Our results suggest that monitoring workplaces to prevent exposure to carcinogenic agents is still an important task, which should be still given adequate importance in public health.


Assuntos
Carcinógenos/toxicidade , Exposição Ocupacional/efeitos adversos , Ocupações/estatística & dados numéricos , Neoplasias da Bexiga Urinária/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cádmio/efeitos adversos , Estudos de Casos e Controles , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Exposição Ocupacional/estatística & dados numéricos , Fatores de Risco , Tricloroetileno/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/classificação
13.
Diabet Med ; 36(1): 22-35, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30378165

RESUMO

AIM: To conduct a systematic review of all observational studies on the effect of pioglitazone on the risk of bladder cancer. METHODS: The MEDLINE and EMBASE databases were queried for papers published between 1 January 2000 and 30 October 2017. We took into consideration observational studies (both retrospective and prospective) that included participants with Type 2 diabetes prescribed anti-hyperglycaemic drugs. RESULTS: While some studies reported an association, others did not, and meta-analyses of these studies showed a significantly increased risk; however, while meta-analysis is a powerful and practical statistical tool, its results should be considered with caution when applied to widely heterogeneous studies. We describe how many of these studies are affected by different types of bias, most notably time-related biases, which should preclude a pooled analysis that would result in biased estimation of the risk. CONCLUSIONS: Given existing data, it is not appropriate to pool the outcomes of highly heterogeneous studies and further rigorously conducted observational research is needed to clarify the role of pioglitazone use on the incidence of bladder cancer.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Pioglitazona/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Relação Dose-Resposta a Droga , Humanos , Incidência , Estudos Observacionais como Assunto , Fatores de Risco
14.
World J Urol ; 37(6): 1127-1135, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30276543

RESUMO

INTRODUCTION: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). METHODS: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. RESULTS: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29-95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83-2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). CONCLUSION: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Segunda Neoplasia Primária/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Bexiga Urinária/induzido quimicamente , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , Incidência , Masculino , Segunda Neoplasia Primária/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias da Bexiga Urinária/epidemiologia
15.
Eur J Cancer Prev ; 28(1): 40-44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28683008

RESUMO

Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis Programme 575 non-muscle-invasive bladder cancer (NMIBC) cases, 139 muscle-invasive bladder cancer (MIBC) cases and 130 BC-free controls with retrospective data on smoking behaviour and cigarette brand were identified. Independently measured TNCO yields of cigarettes sold in the UK were obtained through the UK Department of Health and merged with the Bladder Cancer Prognosis Programme dataset to estimate the daily intake of TNCO. BC risk increased by TNCO intake category for NMIBC cases (P <0.050 in all multivariate models), but only for the daily intake of tar for MIBC cases (P=0.046) in multivariate models. No difference in risk was observed between smokers of low-tar/low-nicotine and high-tar/high-nicotine cigarettes compared with never smokers, either for NMIBC (P=0.544) or MIBC (P=0.449). High daily intake of TNCO additionally increases the risk of both NMIBC and MIBC compared with low daily intake. However, as there is no difference in BC risk between low-tar/low-nicotine and high-tar/high-nicotine cigarette smokers, it remains unclear whether smoking behaviour or TNCO yield of cigarettes explains this association.


Assuntos
Monóxido de Carbono/efeitos adversos , Nicotina/efeitos adversos , Alcatrões/efeitos adversos , Produtos do Tabaco/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia , Idoso , Monóxido de Carbono/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Nicotina/análise , Inquéritos e Questionários , Alcatrões/análise , Reino Unido/epidemiologia , Neoplasias da Bexiga Urinária/diagnóstico
16.
Nihon Eiseigaku Zasshi ; 73(3): 265-268, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30270290

RESUMO

Arsenic is widely distributed in nature, and humans are exposed to arsenic through air, water, beverages, and food. On the bases of previous studies of highly exposed populations, arsenic is designated as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), and IARC has established a causal role for arsenic in cancers of the urinary bladder, lung, and skin in humans. However, there are very few epidemiological studies of the association between low-moderate arsenic exposure and cancer. In particular, there is only one study of the association between arsenic intake from food and cancer. Further epidemiological studies are needed.


Assuntos
Arsenicais/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente , Idoso , Arsenicais/análise , Estudos de Coortes , Feminino , Análise de Alimentos , Contaminação de Alimentos/análise , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia
17.
Biochem Soc Trans ; 46(5): 1213-1224, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30287511

RESUMO

Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA-DNA or DNA-protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.


Assuntos
Carcinógenos/química , Dano ao DNA , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Aminas/efeitos adversos , Animais , Ácidos Aristolóquicos/efeitos adversos , Benzo(a)pireno/efeitos adversos , Reagentes para Ligações Cruzadas/química , DNA , Reparo do DNA , Dieta , Feminino , Humanos , Inflamação , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Masculino , Neoplasias/induzido quimicamente , Neoplasias/genética , Estresse Oxidativo , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/genética , Fumar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética
18.
Mol Nutr Food Res ; 62(24): e1800427, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30302904

RESUMO

SCOPE: Gut microbiota imbalance, inflammation, and gut barrier deficiency play an important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has been proven to be highly effective in inhibiting cancer. The objective of this study is to investigate the potential roles of the gut microbiota in the inhibition of BBN-induced bladder cancer by SFN. METHODS AND RESULTS: N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates the histological changes characteristic of bladder cancer, resulting in fewer submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN-induced bladder cancer with a significant increase in Bacteroides fragilis and Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon, and repairs the injury to the mucosal epithelium of the colon and cecum through the upregulation of the expression of tight junction proteins and GLP2. SFN greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A in the mice with bladder cancer. CONCLUSION: These results suggest that SFN protects against chemical-induced bladder cancer through normalizing the composition of gut microbiota and repairing the physiological destruction of the gut barrier, as well as decreasing inflammation and the immune response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Isotiocianatos/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Anticarcinógenos/farmacologia , Butilidroxibutilnitrosamina/toxicidade , Ácido Butírico/metabolismo , Células CACO-2 , Microbioma Gastrointestinal/genética , Humanos , Imunoglobulina A Secretora/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas de Junções Íntimas/metabolismo , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/microbiologia
19.
Am J Epidemiol ; 187(11): 2297-2305, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30084889

RESUMO

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.


Assuntos
Arsênico/toxicidade , Bronquiectasia/induzido quimicamente , Exposição Ambiental/efeitos adversos , Neoplasias/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Bronquiectasia/mortalidade , Criança , Pré-Escolar , Chile , Água Potável , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/mortalidade , Neoplasias Laríngeas/induzido quimicamente , Neoplasias Laríngeas/mortalidade , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Masculino , Exposição Materna/efeitos adversos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Distribuição por Sexo , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/mortalidade , Adulto Jovem
20.
Cancer Epidemiol Biomarkers Prev ; 27(11): 1371-1375, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30131436

RESUMO

Background: There is growing evidence suggesting that soy isoflavones play a protective role in the development of cancer. However, few epidemiological studies have investigated the association between soy isoflavone intake and bladder cancer.Methods: We evaluated the associations of soy and isoflavone intakes with bladder cancer incidence in a population-based prospective study in Japan. Subjects were 14,233 men and 16,584 women age 35 years or older in September 1992. Soy and isoflavone intakes were assessed via a validated food-frequency questionnaire, while controlling for total energy intake. Cancer incidence was mainly confirmed through regional population-based cancer registries. Bladder cancer was defined as code C67 according to the International Classification of Diseases and Health Related Problems, 10th Revision.Results: During mean follow-up of 13.6 years, 120 men and 41 women had developed bladder cancer. After adjustments for multiple confounders, compared with the lowest quartile of soy food intake, the estimated hazard ratios for the second, third, and highest quartiles of soy food intake were 0.74, 0.52, and 0.55, respectively, in men (P-trend: 0.023). The corresponding values were 0.60, 0.75, and 0.64, respectively, in women (P-trend: 0.43). Similar inverse associations were observed between isoflavone intake and bladder cancer risk.Conclusions: A significant decreased risk of bladder cancer was observed among men who had higher intakes of total soy and isoflavones.Impact: Our finding on the potential benefit of consuming soy foods against bladder cancer is promising and warrants further studies. Cancer Epidemiol Biomarkers Prev; 27(11); 1371-5. ©2018 AACR.


Assuntos
Isoflavonas/efeitos adversos , Alimentos de Soja/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Adulto , Feminino , Humanos , Japão , Masculino , Fatores de Risco , Neoplasias da Bexiga Urinária/patologia
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