RESUMEN
Objective: To detect the expression level of the Mfn2 gene in hepatocellular carcinoma (HCC) and adjacent normal liver tissues and further analyze its anticancer effects. Methods: The expression levels of Mfn2, GLS1 and the autophagy-related proteins lc3b and Beclin1 in liver cancer and adjacent tissues in patients with liver cancer were detected by real-time-quantitative polymerase chain reaction (RT-qPCR). The HepG2 human HCC cell line was cultured in vitro, and the Mfn2 protein was stably expressed through transfection of a high Mfn2 expression plasmid. The Cell-Counting Kit-8 (CCK-8) method was used to observe the effect of Mfn2 overexpression on the activity of HepG2 cells. Furthermore, RT-qPCR and Western blotting were performed to detect the effects of Mfn2 overexpression on the protein expression of GLS1, Beclin1 and lc3b. Results: Compared with tissues adjacent to cancer tissues, the mRNA levels of Mfn2, GLS1, Beclin1 and lc3b in liver cancer tissues were lower. Compared with normal hepatocytes, the expression of Mfn2, Beclin1 and lc3b in HCC cells was decreased, but the expression of GLS1 was increased. Compared with the control group (NC) transfected with empty plasmid, Mfn2 overexpression led to significant time-dependent inhibition of HepG2 cell activity and GLS1 protein expression (P < .05). In addition, Mfn2 overexpression induced autophagy by triggering the expression of autophagy-related proteins Beclin-1 and lc3b in HCC cells (all P < .05). The effect of transfection with a high-dose Mfn2 plasmid was more obvious than that of transfection with a low-dose Mfn2 plasmid (all P < .05). Conclusions: The expression of Mfn2, GLS1, Beclin1 and lc3b in HCC was lower than in normal liver tissue. The expression of Mfn2, Beclin1 and lc3b in HCC cells was decreased, but the expression of GLS1 was increased. Overexpression of Mfn2 inhibited GLS1 gene expression by inhibiting the activity of HCC cells and promoted the expression of Beclin1 and lc3b to induce autophagy, thereby exerting an anticancer effect. Further research is needed to clarify the mechanism of Mfn2 activity.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Autofagia/genética , Beclina-1/genética , Beclina-1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , GTP Fosfohidrolasas/genética , Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas Mitocondriales/genéticaRESUMEN
The alterations of nitrogen sources and cycling within the Three Gorges Reservoir (TGR) and downstream the Changjiang were investigated to understand the impacts of the construction of the Three Gorges Dam (TGD) and anthropogenic inputs from the associated watershed. Water samples collected in October 2016 were analyzed for hydrologic parameters, nutrient concentrations, and stable isotopes of nitrate (NO3-), ammonium (NH4+) and particulate matter. Nitrate dual stable isotope values ranged from +5.8 to +7.1 and -1.9 to +0.4 for δ15N and δ18O, respectively. δ15N values in particulate nitrogen (PN) ranged from +0.5 to +8.5, with slightly lower values before the dam. δ15N-NH4+ values ranged between +10.5 and +19.4, likely reflecting the presence of ammonium assimilation throughout the TGR. The contribution of different nitrogen sources was calculated using a Bayesian mixing model. These sources, including soil organic nitrogen, ammonium fertilizer, and sewage effluent, contributed to elevated DIN concentrations within the TGR (83.2 µM-178.5 µM). The construction of the dam has also likely induced changes in the river environment such as ammonium assimilation in the surface waters and nitrification and/or remineralization within the deep waters of the TGR. Overall, during this investigation period, the TGR acted as a sink of PN (retaining 29%), yet negligibly influenced levels of TDN with ~96.5% of TDN exported to the downstream Changjiang and estuary. It is important to understand the long-term impacts of the TGD on the ecological environment of the Changjiang. This study highlights the influence that anthropogenic nitrogen sources have on the natural biogeochemical cycling within the TGR, showing the urgent need to reduce anthropogenic nitrogen pollution.
Asunto(s)
Monitoreo del Ambiente , Contaminantes Químicos del Agua , Teorema de Bayes , China , Nitratos/análisis , Nitrógeno/análisis , Isótopos de Nitrógeno/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Spectrum sensing plays an essential role in the detection of unused spectrum whole in cognitive radio networks, including cooperative spectrum sensing (CSS) and independent spectrum sensing. In cognitive radio ad hoc networks (CRAHNs), CSS enhances the sensing performance of cognitive nodes by exploring the spectrum partial homogeneity and fully utilizing the knowledge of neighboring nodes, e.g., sensing results and topological information. However, CSS may also open a door for malicious nodes, i.e., spectrum sensing data falsification (SSDF) attackers, which report fake sensing results to deteriorate the performance of CSS. Generally, the performance of CSS has an inverse relationship with the fraction of SSDF attackers. On the contrary, independent spectrum sensing is robust to SSDF attacks. Therefore, it is desirable to choose a proper sensing strategy between independent sensing and collaborative sensing for CRAHNs coexisting with various fractions of SSDF attackers. In this paper, a novel algorithm called Spectrum Sensing Strategy Selection (4S) is proposed to select better sensing strategies either in a collaborative or in an independent manner. To derive the maximum a posteriori estimation of nodes' spectrum status, we investigated the graph cut-based CSS method, through which the topological information cost function and the sensing results cost function were constructed. Moreover, the reputation value was applied to evaluate the performance of CSS and independent sensing. The reputation threshold was theoretically analyzed to minimize the probability of choosing the sensing manner with worse performance. Simulations were carried out to verify the viability and the efficiency of the proposed algorithm.
RESUMEN
Glucose oxidase (GOD, EC.1.1.3.4) specifically catalyzes the reaction of ß-d-glucose to gluconic acid and hydrogen peroxide in the presence of oxygen, which has become widely used in the food industry, gluconic acid production and the feed industry. However, the poor thermostability of the current commercial GOD is a key limiting factor preventing its widespread application. In the present study, amino acids closely related to the thermostability of glucose oxidase from Penicillium notatum were predicted with a computer-aided molecular simulation analysis, and mutant libraries were established following a saturation mutagenesis strategy. Two mutants with significantly improved thermostabilities, S100A and D408W, were subsequently obtained. Their protein denaturing temperatures were enhanced by about 4.4 °C and 1.2 °C, respectively, compared with the wild-type enzyme. Treated at 55 °C for 3 h, the residual activities of the mutants were greater than 72%, while that of the wild-type enzyme was only 20%. The half-lives of S100A and D408W were 5.13- and 4.41-fold greater, respectively, than that of the wild-type enzyme at the same temperature. This work provides novel and efficient approaches for enhancing the thermostability of GOD by reducing the protein free unfolding energy or increasing the interaction of amino acids with the coenzyme.
Asunto(s)
Diseño Asistido por Computadora , Glucosa Oxidasa/metabolismo , Calor , Biología Computacional , Simulación por Computador , Estabilidad de Enzimas , Industria de Alimentos , Proteínas Fúngicas/metabolismo , Penicillium chrysogenum/enzimologíaRESUMEN
Intensive anthropogenic activities, such as excessive nitrogen input and dam construction, have altered the nitrogen cycle in the global river system. However, the focus on the source, transformation and fate of nitrogen in the Yellow River is still scarce. In this study, the multiple isotopes (δ15N-NO3-, δ18O-NO3-, δ15N-NH4+ and δ15N-PN) were deciphered to explore the nitrogen cycling processes and the driving factors in the thermally stratified cascade reservoirs (Sanmenxia Reservoir: SMXR and Xiaolangdi Reservoir: XLDR) and Lower Yellow River (LYR) during the drainage period of the XLDR. In the SMXR, algal bloom triggered the assimilation process in the upper layer before the SMX Dam, followed by remineralization and subsequent nitrification processes in the lower water layers. The nitrification reaction in the XLDR progressively increased along both longitudinal and vertical directions to the lower layer of the XLD Dam, which was linked to the variation in the water residence time of riverine, transition and lentic zones. The robust nitrification rates in the lower layer of the lentic zone coincided with the substantial depletion of nitrate isotopic composition and enrichment of both δ15N-PN and δ15N-NH4+, indicating the longer water residence time not only promoted the growth of the nitrifying population but also facilitated the remineralization to enhance NH4+ availability. In the LYR, the slight nitrate assimilation, as indicated by nitrate isotopic composition and fractionation models, was the predominant nitrogen transformation process. The Bayesian isotope mixing model results showed that manure and sewage was the dominant nitrate source (50 %) in the middle and lower Yellow River. Notably, the in-reservoir nitrification was a significant nitrate source (27 %) in the XLDR and LYR. Our study deepens the understanding of anthropogenic activities impacting the nitrogen cycle in the river-reservoir system, providing valuable insight into water quality management and nitrogen cycle mechanisms in the Yellow River.
RESUMEN
Lactobacillus ß-galactosidases are mostly heterodimeric proteins, which are encoded by the two overlapping genes, lacL and lacM, and produced in recombinant prokaryotic systems for higher yield. This is the first report on the expression of a heterodimeric ß-galactosidase from Lactobacillus crispatus B470 in Pichia pastoris. The overlapping consecutive genes, lacL and lacM, that shared 17 nucleotides were cloned from the genomic DNA of L. crispatus. A recombinant plasmid harboring both expression cassettes of lacL and lacM was constructed and transformed into P. pastoris GS115 competent cells. Two recombinant P. pastoris strains (GSLac01 and GSLac02) showed the highest ß-galactosidase activities of 24.5 and 31.0 U/ml in the culture supernatants, respectively. The recombinant ß-galactosidase (LcLacLM) from GSLac02 was purified to electrphoretic homogeneity by ion-exchange chromatography and molecular sieve chromatography. Similar to most Lactobacillus ß-galactosidases that operate at moderately thermophilic and weak acid to neutral conditions, LcLacLM showed optimal activity at 50°C and pH 5.5-6.5. It's the first report on functional and secretory expression of LacLM-type ß-galactosidase in eukaryotic system. This strategy might be applied to the expression of other overlapping genes.
Asunto(s)
Lactobacillus/enzimología , Pichia/genética , beta-Galactosidasa/genética , Secuencia de Aminoácidos , Clonación Molecular , Genes Bacterianos , Lactobacillus/genética , Datos de Secuencia Molecular , Plásmidos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , beta-Galactosidasa/química , beta-Galactosidasa/aislamiento & purificación , beta-Galactosidasa/metabolismoAsunto(s)
Coristoma/diagnóstico por imagen , Miofibroblastos/patología , Páncreas , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Coristoma/patología , Coristoma/cirugía , Errores Diagnósticos , Resección Endoscópica de la Mucosa , Femenino , Gastroscopía , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/cirugíaRESUMEN
OBJECTIVES: We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP). METHODS: In this retrospective cohort study, we used Kaplan-Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above. RESULTS: In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408-3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748-3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group ( P = 0.018) or the low-risk group ( P < 0.001). CONCLUSIONS: Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.
Asunto(s)
Diabetes Mellitus , Pancreatitis , Estado Prediabético , Enfermedad Aguda , Glucemia/análisis , Índice de Masa Corporal , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Ayuno , Humanos , Pancreatitis/diagnóstico , Estado Prediabético/diagnóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: The incidence of Hashimoto's thyroiditis (HT) in patients with polycystic ovary syndrome (PCOS) is significantly higher than in normal controls, and there is a risk of more severe metabolic symptoms when the two diseases occur together. This study compares insulin secretion, insulin resistance (IR) and thyroid function in patients with PCOS with and without HT. METHODS: A total of 164 patients (52 patients with HT (HT+) and 112 patients without HT diagnosed PCOS at our hospital were enrolled for testing of oral glucose tolerance, insulin release, thyroid function, the presence of thyroglobulin and thyroid peroxidase antibodies, and blood lipid levels. RESULTS: Patients with PCOS and HT had higher insulin secretion and IR levels than those without HT, while free thyroxine and thyrotropin levels were significantly lower. The ratio of free thyroxine to thyrotropin was higher in patients with HT. CONCLUSION: HT may related with IR and relatively low thyroid function in patients with PCOS. Thus, thyroid function and autoimmune status in patients with PCOS should be evaluated in clinical practice.
RESUMEN
Nitrate is the major chemical form of N-nutrient to sustain primary production in Changjiang Estuary and adjacent seawaters. We employed δ15N-NO3- and δ18O-NO3- to constrain the source, cycling, and sink of nitrate in early spring. Both δ15N-NO3- and δ18O-NO3- differentiate significantly among Changjiang Diluted Water (CDW), Yellow Sea Coastal Current (YSCC), and Taiwan Warm Current (TWC). In coastal areas, nitrate distribution and its isotopes are mainly affected by Changjiang inputs. Chemical fertilizers and sewage & manure originated nitrate jointly contribute the most nitrate in CDW. In offshore areas, nitrification contributes 44 ± 21% of the nitrate in YSCC and 17 ± 16% in TWC; assimilation is the dominant process to remove nitrate in TWC (35 ± 16%). Overall, nitrification and assimilation are the key nitrate cycling processes in early spring and co-shape the offshore distribution pattern of nitrate and its dual isotopes.
Asunto(s)
Ríos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Estuarios , Nitratos/análisis , Isótopos de Nitrógeno/análisis , Taiwán , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVES: To investigate the mechanisms for human telomerase reverse transcriptase (hTERT) RNA interference (RNAi) in increasing hepatocellular carcinoma cell apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). METHODS: Cell apoptosis was identified by flow cytometry analysis after annexin V/PI double staining. Expression of apoptosis-related proteins, procaspase-8, -9, -3, Bax, Bcl-2 and hTERT, were identified by Western blotting analysis; telomerase activity and telomere length were detected by telomeric repeat amplification protocol (TRAP) and telomere amount and length assay (TALA) methods. RESULTS: Hepatocellular carcinoma cell apoptosis induced by TRAIL were all significantly increased by hTERT RNAi (P less than 0.05). For example, apoptosis rates were enhanced from 5.53% (untransformed) to 10.35% (transformed) in HepG 2 cells and from 14.73% to 77.24% in SMMC 7721 cells after being treated by 100 ng/ml TRAIL for 24 h. Moreover, activation of procaspase-8, -9 and -3 in transformed cells after being treated by TRAIL were all significantly raised (P less than 0.05) in a dose-dependent manner. The expression of procaspase-8, -9 and Bcl-2 were effectively augmented (P less than 0.05), but expressions of Bax and hTERT were strikingly decreased (P less than 0.05). Meanwhile, telomerase activity was apparently suppressed and telomere length was markedly shortened (P less than 0.05). There were no remarkable differences in these effects between control cells and the untransformed cells (P more than 0.05). CONCLUSION: Enhanced cell apoptosis induced by TRAIL through hTERT RNAi may be related to up-regulation of procaspase-8 and -9 expressions. However the down-regulation of hTERT expression, reduced telomerase activity and shortened telomere length may not be related to expressions of Bcl-2 and Bax.
Asunto(s)
Apoptosis , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Interferencia de ARN , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Telomerasa/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Humanos , Telomerasa/genéticaRESUMEN
Increasing evidence has confirmed the existence of cancer stem cells (CSCs) in both hematological malignancies and solid tumors. However, the origin of CSCs is still uncertain, and few agents have been capable of eliminating CSCs till now. The aim of this study was to investigate whether bulk pancreatic cancer cells could convert into CSCs under certain conditions and explore whether metformin and curcumin can kill pancreatic CSCs. Aspc1, Bxpc3 and Panc1 pancreatic cancer cells were cultured in stem cell culture medium (serum-free Dulbecco's modified Eagle medium/Nutrient Mixture F-12 containing basic fibroblast growth factor, epidermal growth factor, B27 and insulin) for 5 days and it was found that all the pancreatic cancer cells aggregated into spheres and expressed pancreatic cancer stem cell surface markers. Then characteristics of Panc1 sphere cells were analyzed and cytotoxicity assays were performed. The results show that Panc1 sphere cells exhibited CSC characteristics and were more resistant to conventional chemotherapy and more sensitive to metformin and curcumin than their parent cells. These findings suggested that bulk pancreatic cancer cells could acquire CSC characteristics under certain conditions, which may support the "yin-yang" model of CSCs (interconversion between bulk cancer cells and CSCs). These results also showed that metformin and curcumin could be candidate drugs for targeting pancreatic CSCs.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Metformina/farmacología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/uso terapéutico , Humanos , Antígeno Ki-67/metabolismo , Metformina/uso terapéutico , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-bcr/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is an alkylating agent that can induce gastric carcinoma. As a well-known human carcinogen, MNNG has been universally recognized as a methylating agent and is believed to act through methylation mechanism. In the present study, the epigenetic status of the human telomerase reverse transcriptase (hTERT) promoter was investigated in MNNG-treated normal human gastric mucosal epithelial cells. After 4 h exposure to MNNG at different concentrations, 6.8 and 68 µM, bisulfite sequencing polymerase chain reaction showed that five methylated cytosines outside the CpG dinucleotides in the 290-bp fragment from the hTERT promoter were demethylated and all the methylated cytosines in CpG dinucleotides remained intact. Furthermore, the epigenetic status of the target region following MNNG exposure was extremely similar to those of the BGC-823, SGC-7901 and MKN-28 lines; the three cell lines from human gastric adenocarcinoma. The result indicates that MNNG-induced demethylation in cytosines outside the CpG dinucleotides may be an early molecular lesion with the potential for impacting malignant transformation and a possible underlying carcinogenic mechanism of MNNG. Thus, it may provide another insight into the mechanisms of MNNG carcinogenesis.
RESUMEN
AIM: To investigate telomerase activity and human telomerase reverse transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells (nhGMECs) and fibroblasts (nhGMFs). METHODS: nhGMECs and nhGMFs were isolated and cultured from specimens obtained during routine surgery for bleeding peptic ulcer. Telomerase activity in nhGMFs, nhGMECs, and the tumor cell lines BGC-823, SGC-7901 and MKN-28 cells was analyzed using the telomeric repeat amplification protocol assay. hTERT protein was determined in nhGMECs, nhGMFs, BGC-823, SGC-7901 and MKN-28 cells by indirect immunofluorescence. RESULTS: A similar level of telomerase activity was observed in nhGMECs, nhGMFs and BGC-823, SGC-7901, MKN-28 cell lines. Positive hTERT immunostaining was detected in nhGMECs, nhGMFs, BGC-823, SGC-7901 and MKN-28 cell lines. CONCLUSION: The use of telomerase or hTERT as diagnostic markers for gastric cancer may require further studies.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Fibroblastos/metabolismo , Mucosa Gástrica/patología , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/genética , Telomerasa/metabolismo , Adulto , Anciano , Línea Celular Tumoral , Supervivencia Celular , Células Cultivadas , Femenino , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy.
Asunto(s)
Neoplasias/patología , Neoplasias/terapia , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/fisiología , Animales , Humanos , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/virología , Transducción de SeñalRESUMEN
Diabetes mellitus (DM) is widely considered to be associated with pancreatic cancer, however, whether DM is a cause or consequence of pancreatic cancer is controversial. In the present study, 1458 patients with pancreatic ductal adenocarcinoma (PDAC) and 1528 age-, sex- and sociodemographic variables-matched controls were recruited in two university-affiliated hospitals from 1st January 2000 to 31st December 2009. DM was defined as fasting blood glucose (FBG) level of 7.0 mmol/L or greater. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs) and 95% confidence interval (CI). Compared with controls, a moderate increased risk of PDAC was observed among cases with long-standing diabetes (≥ 2-year duration), with an AOR (95% CI) of 2.11 (1.51-2.94). Interestingly, a significant higher risk was observed among cases with new-onset DM (<2-year duration), with an AOR of 4.43 (3.44-5.72) compared to controls without DM. In addition, we found a synergistic interaction between cigarette smoking and DM on modifying the risk of pancreatic cancer development (AOR=6.17, 95% CI 3.82-9.94). Similarly, a synergistic interaction between new-onset DM and family history of pancreatic cancer was found for pancreatic cancer risk, with an AOR (95% CI) of 11.04 (2.51-48.53). This study suggested that DM could be both an early manifestation of pancreatic cancer and an aetiologic factor. Possible effect modification on DM by family history of pancreatic cancer and smoking status should be further explored in future aetiologic studies.
Asunto(s)
Carcinoma Ductal Pancreático/etiología , Complicaciones de la Diabetes/complicaciones , Neoplasias Pancreáticas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Factores de Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND: Diabetes mellitus (DM) is widely considered to be associated with risk of pancreatic cancer (PaC), however, whether DM is a cause or a consequence of PaC is still controversial. We examined this association by conducting a detailed meta-analysis of cohort studies. METHODS: Studies were identified by searching Medline and Embase through November 30, 2010. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of thirty-five cohort studies were included in this meta-analysis. DM was associated with an increased risk of PaC (the summary RRs=1.94; 95% CI, 1.66-2.27), with significant evidence of heterogeneity among these studies (p<0.001, I²=93.6%). Subgroup analyses revealed that the increased risk of PaC was independent of geographic locations, sex, study design, alcohol consumption, body mass index (BMI) and smoking status. In addition, the relative risk of PaC was correlated negatively with the duration of DM, with the highest risk of PaC found among patients diagnosed within less than 1 year. There was no significant publication bias (p=0.136 for Egger's regression asymmetry test). CONCLUSIONS: Findings from this meta-analysis strongly support that diabetes is associated with an increased risk of PaC in both males and females and that DM is both an early manifestation and an etiologic factor of pancreatic cancer.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Neoplasias Pancreáticas/epidemiología , Adulto , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/etiología , Factores de RiesgoRESUMEN
Telomeres are the end structures of linear chromosomes in eukaryotic cells. The integrity of a telomere is essential for the overall stability of the chromosome. The human protection of telomeres 1 (hPOT1) protein, a single-stranded telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. Here, we show that the loss of hPOT1 by RNA interference in BGC823 (poorly differentiated human gastric adenocarcinoma) cells leads to an increase in multinucleated giant cells, a decrease in cell proliferation and colony formation, induction of senescence and apoptosis, shortened telomere length, upregulation of the TRF1 gene and downregulation of the TRF2, tankyrase1 and hTERT genes. These results suggest that the loss of hPOT1 results in a decrease in the viability of BGC823 cells; hPOT1 regulates telomere length positively and has an influence on the expression of other telomere-associated genes in the cells.