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1.
J Mater Chem B ; 12(21): 5039-5060, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38716622

RESUMO

Graphene quantum dot (GQD) integration into hydrogel matrices has become a viable approach for improving drug delivery and bioimaging in cancer treatment in recent years. Due to their distinct physicochemical characteristics, graphene quantum dots (GQDs) have attracted interest as adaptable nanomaterials for use in biomedicine. When incorporated into hydrogel frameworks, these nanomaterials exhibit enhanced stability, biocompatibility, and responsiveness to external stimuli. The synergistic pairing of hydrogels with GQDs has created new opportunities to tackle the problems related to drug delivery and bioimaging in cancer treatment. Bioimaging plays a pivotal role in the early detection and monitoring of cancer. GQD-based hydrogels, with their excellent photoluminescence properties, offer a superior platform for high-resolution imaging. The tunable fluorescence characteristics of GQDs enable real-time visualization of biological processes, facilitating the precise diagnosis and monitoring of cancer progression. Moreover, the drug delivery landscape has been significantly transformed by GQD-based hydrogels. Because hydrogels are porous, therapeutic compounds may be placed into them and released in a controlled environment. The large surface area and distinct interactions of graphene quantum dots (GQDs) with medicinal molecules boost loading capacity and release dynamics, ultimately improving therapeutic efficacy. Moreover, GQD-based hydrogels' stimulus-responsiveness allows for on-demand medication release, which minimizes adverse effects and improves therapeutic outcomes. The ability of GQD-based hydrogels to specifically target certain cancer cells makes them notable. Functionalizing GQDs with targeting ligands minimizes off-target effects and delivers therapeutic payloads to cancer cells selectively. Combined with imaging capabilities, this tailored drug delivery creates a theranostic platform for customized cancer treatment. In this study, the most recent advancements in the synergistic use of GQD-based hydrogels are reviewed, with particular attention to the potential revolution these materials might bring to the area of cancer theranostics.


Assuntos
Antineoplásicos , Grafite , Hidrogéis , Neoplasias , Pontos Quânticos , Hidrogéis/química , Pontos Quânticos/química , Humanos , Grafite/química , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Imagem Óptica , Portadores de Fármacos/química
2.
Cancer Rep (Hoboken) ; 7(2): e1973, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38214217

RESUMO

BACKGROUND: Cervical cancer is a common, and fatal cancer in women worldwide. This cancer is the fourth most common cancer in women after breast, colorectal, and lung cancer. AIMS: This study aims to investigate the age-standardized incidence rate (ASR) and the geographical distribution of Cervical Cancer in Iran. METHODS: This study was designed as a descriptive cross-sectional investigation. The study sample comprised all individuals registered as cervical cancer patients in the National Cancer Registry system in 2016. The crude rate and ASR for each province were computed independently. Furthermore, we employed ArcMap10.5 software and geographic information system to conduct an analysis of the gathered data. In order to ascertain the spatial distribution and clustering of cervical cancer incidence, we utilized Moran's I, which measures spatial autocorrelation. RESULTS: We studied a total of 808 cases of cervical cancer with a median age to be 52.19 years (IQR≈1.35). Among these cases, 685 (84.7%) were diagnosed based on the pathological reports with morphological verification, while 81 patients (10.1%) were clinically identified, and 42 cases (5.2%) were diagnosed using the death certificate-only method. Squamous cell carcinoma accounted for 61% of all cases (n = 497). The ASR of cervical cancer in Iran was 1.90 per 100 000 populations. The provincial ASR ranged from 0.29 to 5.03 per 100 000, with the highest rates observed in Golestan (5.03), East Azerbaijan (4.07), and Ilam (3.72). We found no clustering patterns in the distribution of provincial crude, age-specific, and age-standardized incidence rates (p > .05). CONCLUSION: The incidence of cervical cancer in Iran was lower than the global average, and we did not identify any significant disparities in the incidence rates among the provinces. Although there were differences in incidence rates among the areas, these were not clustered. It is crucial to remember that cervical cancer is still a major public health issue in Iran, and in order to lessen the disease's burden, national initiatives to enhance screening, early identification, and access to efficient treatment should continue to be top priorities.


Assuntos
Neoplasias Pulmonares , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Incidência , Irã (Geográfico)/epidemiologia , Estudos Transversais
3.
ChemMedChem ; 19(1): e202300359, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37916531

RESUMO

Exosomes are essential indicators of molecular mechanisms involved in interacting with cancer cells and the tumor environment. As nanostructures based on lipids and nucleic acids, exosomes provide a communication pathway for information transfer by transporting biomolecules from the target cell to other cells. Importantly, these extracellular vesicles are released into the bloodstream by the most invasive cells, i. e., cancer cells; in this way, they could be considered a promising specific biomarker for cancer diagnosis. In this matter, CRISPR-Cas systems and microfluidic approaches could be considered practical tools for cancer diagnosis and understanding cancer biology. CRISPR-Cas systems, as a genome editing approach, provide a way to inactivate or even remove a target gene from the cell without affecting intracellular mechanisms. These practical systems provide vital information about the factors involved in cancer development that could lead to more effective cancer treatment. Meanwhile, microfluidic approaches can also significantly benefit cancer research due to their proper sensitivity, high throughput, low material consumption, low cost, and advanced spatial and temporal control. Thereby, employing CRISPR-Cas- and microfluidics-based approaches toward exosome monitoring could be considered a valuable source of information for cancer therapy and diagnosis. This review assesses the recent progress in these promising diagnosis approaches toward accurate cancer therapy and in-depth study of cancer cell behavior.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Exossomos/genética , Microfluídica , Sistemas CRISPR-Cas/genética , Transporte Biológico , Neoplasias/diagnóstico , Neoplasias/genética
4.
BMC Urol ; 23(1): 102, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37270552

RESUMO

BACKGROUND: Pure testicular choriocarcinoma is a rare type of non-seminomatous germ cell tumor extremely poor prognostic with the tendency to bleed at the metastatic site. At the time of the diagnosis, 70% of patients have metastatic lesions. Depending on the site of the metastasis, symptoms vary. Gastrointestinal involvement is seen in less than 5% of cases, mostly in the duodenum. CASE PRESENTATION: We present a 47 years old male with testicular choriocarcinoma involving the jejunum, lung, liver, and kidney presenting with acute abdominal pain, melena, and dyspnea with some paraneoplastic symptoms. The patient had increased, severe and constant pain in the right lower quadrant for the previous four days. Additionally, he was complaining of nausea, vomiting, anorexia, and a history of melena for the last 10 days. Dyspnea on exertion, hemoptysis, and dry cough were the symptoms he was suffering from, for almost one year. The patient's general appearance was pale, ill, and thin with 10 kg of weight loss during the last some months. The computed tomography (CT) scan reported multiple metastatic lesions in both liver lobes and the left kidney. Pathologic study of the samples of small bowel lesions showed metastatic choriocarcinoma. Following the patient had been referred to an oncologist to start the chemotherapy regime. Finally, the patient has expired after 40 days of his first admission. CONCLUSIONS: Testicular choriocarcinoma is a rare but fatal malignancy among young men. Gastrointestinal metastases are infrequent involvement represented by melena and acute abdominal pain, obstruction, and mass. Physicians should consider it as a differential diagnosis for acute abdomen and gastrointestinal bleeding causation.


Assuntos
Coriocarcinoma , Neoplasias Gastrointestinais , Neoplasias Testiculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Melena , Neoplasias Testiculares/complicações , Neoplasias Testiculares/diagnóstico , Coriocarcinoma/complicações , Coriocarcinoma/diagnóstico , Coriocarcinoma/tratamento farmacológico , Dor Abdominal
5.
Cancer Rep (Hoboken) ; 6(6): e1836, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37191384

RESUMO

BACKGROUND AND AIMS: Oral cancer is now a top priority for non-communicable illnesses and universal health care plans, according to the WHO. There is no general estimate of the incidence of oral cavity cancer in Iran, despite multiple investigations. The purpose of this study is to evaluate the age-standardized incidence rate (ASR) of oral cavity cancers in Iran. METHOD: In accordance with the MOOSE (Meta-analyses of Observational Studies in Epidemiology) Checklist recommendations, this systematic review was conducted. PubMed/MEDLINE, Web of Science, ScienceDirect, Embase, Scopus, ProQuest, and Google Scholar were used as the international databases for the systematic literature search, while SID (Scientific Information Database), Magiran and element were used as the Iranian databases. The heterogeneity of the research will be evaluated by means of the inverse variance and Cochran Q tests, along with random-effect models. It was determined what caused the heterogeneity using a meta-regression model. By eliminating experiments one at a time, sensitivity analysis was used. The meta-analysis was corrected utilizing the Trim-and-fill method due to the identification of noteworthy publication bias via the Egger's test and asymmetry of the funnel plot. RESULTS: This research incorporated a total of 22 journal articles. The pooled ASR of oral cavity cancer for males and females was estimated at 1.96 (95% CI: 1.65-2.26) (Q statistic = 1118.09, df = 25, p < .0001, I2 = 97.8%), and 1.46 (95% CI: 1.14-1.77) (Q statistic = 2576.99, df = 26, p < .0001, I2 = 99.0%), respectively. According to the funnel plots and Egger's test, there is no evidence of publication bias in studies reporting on males (bias = 1.3220, 95% CI: -3.9571, 6.6012, p = .610), but for ASR in females, Egger's test was significant (bias = -7.6366, 95% CI: 2.2141, 13.05904, p = .008). Based on Trim-and-fill methods, overall ASR corrected in females was estimated to be 1.36 (95% CI: 1.05%-1.66%). CONCLUSION: Iran's oral cavity cancer incidence was lower than the global average, but owing to variables including an aging population, a rise in life expectancy, and exposure to risk factors like smoking, we anticipate an increasing trend.


Assuntos
Neoplasias Bucais , Masculino , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Incidência , Fatores de Risco , Neoplasias Bucais/epidemiologia
6.
Biosensors (Basel) ; 12(9)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36140128

RESUMO

In today's world, the use of biosensors occupies a special place in a variety of fields such as agriculture and industry. New biosensor technologies can identify biological compounds accurately and quickly. One of these technologies is the phenomenon of surface plasmon resonance (SPR) in the development of biosensors based on their optical properties, which allow for very sensitive and specific measurements of biomolecules without time delay. Therefore, various nanomaterials have been introduced for the development of SPR biosensors to achieve a high degree of selectivity and sensitivity. The diagnosis of deadly diseases such as cancer depends on the use of nanotechnology. Smart MXene quantum dots (SMQDs), a new class of nanomaterials that are developing at a rapid pace, are perfect for the development of SPR biosensors due to their many advantageous properties. Moreover, SMQDs are two-dimensional (2D) inorganic segments with a limited number of atomic layers that exhibit excellent properties such as high conductivity, plasmonic, and optical properties. Therefore, SMQDs, with their unique properties, are promising contenders for biomedicine, including cancer diagnosis/treatment, biological sensing/imaging, antigen detection, etc. In this review, SPR biosensors based on SMQDs applied in biomedical applications are discussed. To achieve this goal, an introduction to SPR, SPR biosensors, and SMQDs (including their structure, surface functional groups, synthesis, and properties) is given first; then, the fabrication of hybrid nanoparticles (NPs) based on SMQDs and the biomedical applications of SMQDs are discussed. In the next step, SPR biosensors based on SMQDs and advanced 2D SMQDs-based nanobiosensors as ultrasensitive detection tools are presented. This review proposes the use of SMQDs for the improvement of SPR biosensors with high selectivity and sensitivity for biomedical applications.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Pontos Quânticos , Técnicas Biossensoriais/métodos , Nanoestruturas/química , Nanotecnologia , Ressonância de Plasmônio de Superfície/métodos
7.
Artigo em Inglês | LILACS, CUMED | ID: biblio-1410305

RESUMO

Splenectomy is necessary in beta thalassemia major patients when the spleen becomes hyperactive, leading to extreme destruction of erythrocytes. This study assessed the ferritin effect on serum pneumococcal antibody response following pneumococcal vaccination, in patients with beta thalassemia major after splenectomy. In this case series study, convenience sampling was used to recruit 347 splenectomised beta thalassemia patients under the auspices of Jahrom University of Medical Sciences. Demographic data such as age, sex, and time after splenectomy were recorded by a questionnaire. All participants had been splenectomised and received a dose of Pneumovax1 23 vaccine 14 days before surgery. The IgG antibody responses to pneumococcal vaccine and levels of serum specific ferritin were determine by commercial enzyme immunoassay kits. For the analysis, SPSS software version 16 was used. A p-value less than 0.05 was considered statistically significant. Most of the participants (63.4 percent) were hypo-responders to pneumococcal vaccine. Also, serum anti-pneumococcal IgG antibody was related to post splenectomy duration and serum ferritin (p 0.05). An important result was a relation of serum anti-pneumococcal IgG antibody to serum ferritin according to post splenectomy duration groups. Therefore, in three groups of post splenectomy duration, the serum ferritin was higher in hypo-responder than in good responder subjects. Our results indicate that serum anti-pneumococcal IgG antibody decreased with increment of serum ferritin and post splenectomy duration. Thus, there is a need to re-address the approach towards revaccination in this immune-compromised group of patients by administering a booster pneumococcal vaccination in an attempt to recover immunity and reduce morbidity(AU)


La esplenectomía es necesaria en pacientes con beta talasemia mayor cuando el bazo se vuelve hiperactivo, lo que lleva a una destrucción extrema de los eritrocitos. Este estudio evaluó el efecto de la ferritina sobre la respuesta de anticuerpos antineumocócicos en suero después de la vacunación antineumocócica, en pacientes con talasemia beta mayor a los que se les realizó esplenectomía. En este estudio de serie de casos, se utilizó un muestreo de conveniencia para reclutar a 347 pacientes con beta talasemia esplenectomizados bajo los auspicios de la Universidad de Ciencias Médicas de Jahrom. Los datos demográficos como la edad, el sexo y el tiempo después de la esplenectomía se registraron mediante un cuestionario. Todos los participantes fueron esplenectomizados y recibieron una dosis de la vacuna Pneumovax® 23, 14 días antes de la cirugía. Las respuestas de anticuerpos IgG a la vacuna neumocócica y los niveles de ferritina sérica específica se determinaron mediante estuches comerciales de inmunoensayo enzimático. Para el análisis se utilizó el programa SPSS versión 16. Un valor de p inferior a 0,05 se consideró estadísticamente significativo. La mayoría de los participantes (63,4 por ciento) resultaron hiporrespondedores a la vacuna antineumocócica. Además, el anticuerpo sérico antineumocócico IgG se relacionó con la duración de la esplenectomía y la ferritina sérica (p0,05). Un resultado importante fue la relación del anticuerpo sérico IgG antineumocócico con la ferritina sérica según los grupos de duración postesplenectomía. Por lo tanto, en tres grupos de duración posterior a la esplenectomía, la ferritina sérica fue mayor en los sujetos con hiporrespuesta que en los sujetos con buena respuesta. Nuestros resultados indican que el anticuerpo sérico IgG antineumocócico disminuyó con el incremento de la ferritina sérica y la duración posterior a la esplenectomía. Por lo tanto, existe la necesidad de volver a abordar el enfoque hacia la revacunación en este grupo de pacientes inmunocomprometidos mediante la administración de una vacunación antineumocócica de refuerzo en un intento por recuperar la inmunidad y reducir la morbilidad(AU)


Assuntos
Humanos , Masculino , Feminino , Esplenectomia/métodos , Talassemia beta/epidemiologia , Vacinas Pneumocócicas/uso terapêutico , Ferritinas/uso terapêutico , Irã (Geográfico)
8.
Biosensors (Basel) ; 12(7)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35884264

RESUMO

Inflammatory diseases are some of the most common diseases in different parts of the world. So far, most attention has been paid to the role of environmental factors in the inflammatory process. The diagnosis of inflammatory changes is an important goal for the timely diagnosis and treatment of various metastatic, autoimmune, and infectious diseases. Graphene quantum dots (GQDs) can be used for the diagnosis of inflammation due to their excellent properties, such as high biocompatibility, low toxicity, high stability, and specific surface area. Additionally, surface-enhanced Raman spectroscopy (SERS) allows the very sensitive structural detection of analytes at low concentrations by amplifying electromagnetic fields generated by the excitation of localized surface plasmons. In recent years, the use of graphene quantum dots amplified by SERS has increased for the diagnosis of inflammation. The known advantages of graphene quantum dots SERS include non-destructive analysis methods, sensitivity and specificity, and the generation of narrow spectral bands characteristic of the molecular components present, which have led to their increased application. In this article, we review recent advances in the diagnosis of inflammation using graphene quantum dots and their improved detection of SERS. In this review study, the graphene quantum dots synthesis method, bioactivation method, inflammatory biomarkers, plasma synthesis of GQDs and SERS GQD are investigated. Finally, the detection mechanisms of SERS and the detection of inflammation are presented.


Assuntos
Grafite , Pontos Quânticos , Grafite/química , Humanos , Inflamação/diagnóstico , Pontos Quânticos/química , Análise Espectral Raman
9.
BMC Nephrol ; 23(1): 203, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681145

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is one of the major global causes of mortality, described as the most neglected chronic disease. This study aimed to determine the prevalence and determinants of CKD in the setting of the Shahedieh cohort study in Yazd, Iran. METHODS: This cross-sectional study was conducted on adults in the baseline phase of the Shahedieh cohort study in Yazd, Iran. In this study, 9781 participants aged 30-73-year-old were investigated. The data used in this study included demographic and clinical variables and blood samples. Adjusted odds ratios were employed using multivariate logistic regression; meanwhile, population attributable risks for CKD were calculated and reported. RESULTS: CKD prevalence was 27.5% (95%CI: 26.57-28.34) in all participants, 24% in male, and 30.3% in female. The results of multivariate logistic regression analysis identified age (OR = 1.89, 95%CI:1.082-1.96), women (OR = 1.62, 95%CI: 1.45-1.79), BMI ≥ 30 (OR = 1.40,95%CI: 1.20-1.62), diabetes (OR = 1.38, 95%CI: 1.22-1.57), hypertriglyceridemia(OR = 1.20, 95%CI: 1.01-1.43), history of cardiovascular disease (OR = 1.20, 95%CI: 1.01-1.43), hypertension (OR = 1.18, 95%CI: 1.04-1.33), smoking (OR = 1.17, 95% CI: 1.02-1.33), LDL ≥ 130 (OR = 1.15, 95%CI: 1.01-1.31), history of kidney stone (OR = 1.14, 95%CI: 1.01-1.32) and hypercholesterolemia (OR = 1.14, 95%CI: 1.01-1.32) as risk factors for CKD. Among individual factors, obesity (11.25%), Hypertriglyceridemia (9.21%), LDL ≥ 130 (7.12%) had the greatest Population-Attributable Fraction, followed by Hypercholesterolemia (5.2%), diabetes (5.05%), smoking (3.73%) and high blood pressure (2.82%). CONCLUSION: The results showed that the main determinants of CKD are potentially modifiable risk factors. Therefore, implementing early detection and screening programs in people at risk as well as preventive measures such as lifestyle modification programs and risk factors controlling can prevent the disease.


Assuntos
Diabetes Mellitus , Hipercolesterolemia , Hipertensão , Hipertrigliceridemia , Insuficiência Renal Crônica , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco
10.
Life Sci ; 278: 119649, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043989

RESUMO

Lung cancer (LC) is a leading cause of death worldwide with high mortality and morbidity. A wide variety of risk factors are considered for LC development such as smoking, air pollution and family history. It appears that genetic and epigenetic factors are also potential players in LC development and progression. AMP-activated protein kinase (AMPK) is a signaling pathway with vital function in inducing energy balance and homeostasis. An increase in AMP:ATP and ADP:ATP ratio leads to activation of AMPK signaling by upstream mediators such as LKB1 and CamKK. Dysregulation of AMPK signaling is a common finding in different cancers, particularly LC. AMPK activation can significantly enhance LC metastasis via EMT induction. Upstream mediators such as PLAG1, IMPAD1, and TUFM can regulate AMPK-mediated metastasis. AMPK activation can promote proliferation and survival of LC cells via glycolysis induction. In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling. This is due to double-edged sword role of AMPK signaling in LC cells. Furthermore, AMPK signaling can regulate response of LC cells to chemotherapy and radiotherapy that are discussed in the current review.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia
11.
Life Sci ; 277: 119430, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33789144

RESUMO

Although chemotherapy is a first option in treatment of cancer patients, drug resistance has led to its failure, requiring strategies to overcome it. Cancer cells are capable of switching among molecular pathways to ensure their proliferation and metastasis, leading to their resistance to chemotherapy. The molecular pathways and mechanisms that are responsible for cancer progression and growth, can be negatively affected for providing chemosensitivity. Small interfering RNA (siRNA) is a powerful tool extensively applied in cancer therapy in both pre-clinical (in vitro and in vivo) and clinical studies because of its potential in suppressing tumor-promoting factors. As such oncogene pathways account for cisplatin (CP) resistance, their targeting by siRNA plays an important role in reversing chemoresistance. In the present review, application of siRNA for suppressing CP resistance is discussed. The first priority of using siRNA is sensitizing cancer cells to CP-mediated apoptosis via down-regulating survivin, ATG7, Bcl-2, Bcl-xl, and XIAP. The cancer stem cell properties and related molecular pathways including ID1, Oct-4 and nanog are inhibited by siRNA in CP sensitivity. Cell cycle arrest and enhanced accumulation of CP in cancer cells can be obtained using siRNA. In overcoming siRNA challenges such as off-targeting feature and degradation, carriers including nanoparticles and biological carriers have been applied. These carriers are important in enhancing cellular accumulation of siRNA, elevating gene silencing efficacy and reversing CP resistance.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , RNA Interferente Pequeno/genética , Animais , Biomarcadores Tumorais/genética , Humanos , Neoplasias/genética , Neoplasias/patologia
12.
Ann Glob Health ; 85(1)2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31298827

RESUMO

BACKGROUND: Bladder cancer is the ninth most common cancer in the world. OBJECTIVES: This study aimed to determine the correlation between age-standardized incidence rates of bladder cancer and some risk factors in Asian countries through an extensive ecological analysis. METHODS: This ecological study evaluated the correlation between age-standardized incidence rates of bladder cancer and obesity, overweight, physical inactivity, and tobacco use in 30 Asian countries. To determine the factors that were significantly related to age-standardized incidence rate of bladder cancer, a univariate analysis was performed using simple linear regression. In the next step, variables with p-values less than 0.25 were entered into a multivariate linear regression model. RESULTS: The incidence of bladder cancer was higher in countries with higher prevalence of overweight (r2 = 0.36, p < 0.001), obesity (r2 = 0.34, p = 0.001), current daily tobacco use (r2 = 0.17, p = 0.03), and physical inactivity (r2 = 0.13, p = 0.04). The results of multiple regression analysis indicated a direct correlation between the incidence of bladder cancer and overweight (ß = 0.15, p < 0.001) and current daily tobacco use (ß = 0.21, p = 0.001). CONCLUSIONS: There was a significant relationship between the incidence of bladder cancer and overweight and current daily tobacco use. Further epidemiological studies are needed to confirm this relationship.


Assuntos
Sobrepeso/epidemiologia , Uso de Tabaco/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Ásia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Comportamento Sedentário
13.
Biochemistry ; 57(17): 2549-2563, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28945358

RESUMO

Many cancer-causing chromosomal translocations result in transactivating protein products encoding FET family (FUS, EWSR1, TAF15) low-complexity (LC) domains fused to a DNA binding domain from one of several transcription factors. Recent work demonstrates that higher-order assemblies of FET LC domains bind the carboxy-terminal domain of the large subunit of RNA polymerase II (RNA pol II CTD), suggesting FET oncoproteins may mediate aberrant transcriptional activation by recruiting RNA polymerase II to promoters of target genes. Here we use nuclear magnetic resonance (NMR) spectroscopy and hydrogel fluorescence microscopy localization and fluorescence recovery after photobleaching to visualize atomic details of a model of this process, interactions of RNA pol II CTD with high-molecular weight TAF15 LC assemblies. We report NMR resonance assignments of the intact degenerate repeat half of human RNA pol II CTD alone and verify its predominant intrinsic disorder by molecular simulation. By measuring NMR spin relaxation and dark-state exchange saturation transfer, we characterize the interaction of RNA pol II CTD with amyloid-like hydrogel fibrils of TAF15 and hnRNP A2 LC domains and observe that heptads far from the acidic C-terminal tail of RNA pol II CTD bind TAF15 fibrils most avidly. Mutation of CTD lysines in heptad position 7 to consensus serines reduced the overall level of TAF15 fibril binding, suggesting that electrostatic interactions contribute to complex formation. Conversely, mutations of position 7 asparagine residues and truncation of the acidic tail had little effect. Thus, weak, multivalent interactions between TAF15 fibrils and heptads throughout RNA pol II CTD collectively mediate complex formation.


Assuntos
RNA Polimerase II/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Transcrição Gênica , Translocação Genética/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/química , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Humanos , Lisina/química , Lisina/genética , Espectroscopia de Ressonância Magnética , Complexos Multiproteicos , Mutação , Neoplasias/genética , Neoplasias/patologia , Regiões Promotoras Genéticas , Ligação Proteica , Domínios Proteicos/genética , RNA Polimerase II/química , Fatores Associados à Proteína de Ligação a TATA/química
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