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1.
Biochem Pharmacol ; 174: 113811, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954719

RESUMO

Pyruvate kinase M2 (PKM2) is a key enzyme responsible for the final step of glycolysis. It is still unclear whether PKM2 is involved in reactive oxygen species (ROS)-mediated cytotoxicity in gastrointestinal cancer, and what mechanisms are involved. One duodenal (AZ521) and two gastric (NUGC and SCM-1) cancer cell lines were treated with an indole-3-carbinol derivative OSU-A9, which caused cytotoxicity in acute myeloid leukemia through ROS generation. OSU-A9 caused a dose- and time-dependent cytotoxicity and induced apoptosis in duodenal and gastric cancer cells through ROS generation. Pretreatment with ROS scavengers rescued cancer cells from apoptosis and concomitant poly (ADP-ribose) polymerase cleavage, implying a key role of ROS in OSU-A9-induced cell death. Moreover, OSU-A9-induced ROS generation decreased protein levels of pTyr105-PKM2, and this effect was rescued by pretreatment with ROS scavengers. Interestingly, pTyr105-PKM2 protein levels decreased in the cell nucleus rather than in the cytoplasm. PKM2 overexpression partially rescued the survival of duodenal and gastric cancer cells treated with OSU-A9. Furthermore, the anticancer activity of OSU-A9 extended in vivo, as OSU-A9 administered by oral gavage suppressed the growth of AZ521 xenograft tumors in nude mice without obvious toxicity. In conclusion, OSU-A9 inhibited duodenal and gastric cancer cell proliferation through ROS generation and caused a subsequent decrease in nuclear pTyr105-PKM2 protein. These findings provide evidence for the non-canonical activity of PKM2 in cancer cell survival. Furthermore, they highlight the potential role of PKM2 as a future therapeutic target for duodenal and gastric cancer.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31976914

RESUMO

This article investigates the event-triggered synchronization of delayed neural networks (NNs). A novel integral-based event-triggered scheme (IETS) is proposed where the integral of the system states, and past triggered data over a period of time are used. With the proposed IETS, the integral event-triggered synchronization problem becomes a distributed delay problem. Using the Bessel-Legendre inequalities, sufficient conditions for the existence of a controller that ensures asymptotic synchronization are provided in the form of linear matrix inequalities (LMIs). Illustrative examples are used to demonstrate the advantages of the proposed IETS method over other event-triggered scheme (ETS) methods. Moreover, this IETS method is applied to the image encryption and decryption. A novel encryption algorithm is proposed to enhance the quality of the encryption process.

3.
Curr Microbiol ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31982968

RESUMO

The soil organic carbon is associated with the plant quality and the microbial community structure. In the present study, carbon fertilizers were applied to paddy soil to elucidate the relationship between soil carbon and neutral aroma substances in both tobacco and soil microbiome by transcriptome sequencing and 16S rDNA-based analysis, respectively. Our results showed that (1) the increase in soil carbon content was closely correlated with the abundance of microorganisms belonging to two classes (which could potentially affect tobacco plants), namely Gammaproteobacteria and Chloroflexia, (2) soil carbon apparently affected tobacco neutral aroma substances, and (3) soil carbon improved neutral aroma substances by affecting the transcriptional processes of sesquiterpenoid and chlorophyll biosyntheses. These results suggest that increased soil carbon-especially active organic carbon-resulted in desirable improvements in aroma substances in tobacco leaves.

4.
Eur J Cancer ; 124: 123-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765987

RESUMO

BACKGROUND: This phase I/II study evaluated the feasibility and efficacy of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG), a triplet regimen, for treating patients with metastatic pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with chemo-naive, metastatic PDAC were eligible to receive fixed-rate infusion (10 mg/m2/min) of gemcitabine of 800 mg/m2 followed by oxaliplatin of 85 mg/m2 on day 1 plus oral S-1 and leucovorin (20 mg/m2) twice daily from days 1 to 7 in a 2-week cycle. The dose of S-1 would be escalated from 20, 30, 35 to 40 mg/m2 in a 3 + 3 designed phase I part to determine the maximum tolerated dose (MTD) for phase II study, in which the primary end-point was objective response rate (ORR). The recommended dose of S-1 was from phase I. This trial is registered at ClinicalTrials.gov: NCT01415713. RESULTS: Seventy-three patients were enrolled. In the phase I study (n = 19), the MTD of S-1 was 35 mg/m2 twice daily. Of 54 patients in phase II, the ORR was 40.7% (95% confidence interval [CI], 28%-55%). The median progression-free survival and overall survival were 7.6 (95% CI, 5.6-11.0) and 11.4 (95% CI, 8.1-16.3) months, respectively. The most common grade III/IV adverse event was neutropenia (40.7%). Twenty-four percent of patients had SLOG treatment for more than 1 year. The mean relative dose intensities of gemcitabine, oxaliplatin, and S-1 were 92%, 92% and 89%, respectively. CONCLUSION: Biweekly SLOG is a feasible regimen with promising activity and safety profiles. A randomised study comparing SLOG versus modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) in advanced PDAC is ongoing (ClinicalTrials.gov: NCT03443492).

5.
Cancer Sci ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789476

RESUMO

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).

6.
Oncologist ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852810

RESUMO

BACKGROUND: The discovery of effective therapeutic options for treating metastatic poorly differentiated neuroendocrine carcinoma (NEC) after prior platinum-based chemotherapy remains elusive. This study analyzed the efficacy of TLC388 (Lipotecan) Hydrochloride, a novel camptothecin analog, for pretreated patients with metastatic NEC. METHODS: This single-arm, two-stage, phase II clinical trial was conducted at four community and academic centers in Taiwan. Patients aged 20 years or older with confirmed metastatic NEC and who had received prior systemic therapy with etoposide plus cisplatin were enrolled between July 2015 and May 2018. Patients received 40 mg/m2 of TLC388 intravenously on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxic effects. Gene mutations were analyzed by next-generation sequencing. RESULTS: Twenty-three patients with a median age of 61 (range, 44-73) years, 18 of whom were men (78%), were enrolled. Patients received a median of 2 (range, 0-6) treatment cycles. Among 20 evaluable patients, 3 patients exhibited stable disease and no patient experienced a complete or partial remission, resulting in a disease control rate of 15%. Median progression-free survival was 1.8 (95% confidence interval [CI], 0.4-15) months, and the median overall survival was 4.3 (95% CI, 1.7-15) months. The most common treatment-related hematologic adverse events at grade 3 or higher were leukopenia (22.7%), anemia (31.8%), and thrombocytopenia (18.2%). The most frequent mutated genes in 35 patients with NEC were ARSA, DPYD, HEXB, BRCA1, HPD, MYBPC3, BBS2, IL7R, HSD17B4, and PRODH. CONCLUSION: TLC388 demonstrates limited antitumor activity in metastatic NEC. ClinicalTrials.gov identifier: NCT02457273. IMPLICATIONS FOR PRACTICE: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive. Currently, effective therapeutic options for treating metastatic poorly differentiated NECs beyond platinum-based chemotherapy remain elusive. In this single-arm, multicenter, phase II study, 23 patients with NEC were enrolled and received TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog. The results demonstrated the disease control rate of 15%, the median progression-free survival of 1.8 (95% confidence interval [CI], 0.4-15) months, and the median overall survival of 4.3 (95% CI, 1.7-15) months. Most importantly, several novel genetic mutations and pathways were identified. These results offer the opportunity to develop future treatment strategies in this rare cancer.

7.
PLoS One ; 14(10): e0224556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31671156

RESUMO

The application of biochar is one of the most useful methods for improving soil quality, which is of the utmost significance for the continuous production of crops. As there are no conclusive studies on the specific effects of biochar application on tobacco quality, this study aimed to improve the yield and quality of tobacco as a model crop for economic and genetic research in southern China, by such application. We used transcriptome sequencing to reveal the effects of applied biochar on tobacco development before and after topping. Our results showed that topping affected carbon and nitrogen metabolism, photosynthesis and secondary metabolism in the tobacco plants, while straw biochar-application to the soil resulted in amino acid and lipid synthesis; additionally, it affected secondary metabolism of the tobacco plants through carbon restoration and hormonal action, before and after topping. In addition to the new insights into the impact of biochar on crops, our findings provide a basis for biochar application measures in tobacco and other crops.

8.
Theranostics ; 9(24): 7168-7183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695760

RESUMO

Background: The dense fibrotic stroma enveloping pancreatic tumors is a major cause of drug resistance. Pancreatic stellate cells (PSCs) in the stroma can be activated to induce intra-tumor fibrosis and worsen patient survival; however, the molecular basics for the regulation of PSC activation remains unclear. Methods: The in vitro coculture system was used to study cancer cell-PSC interactions. Atomic force microscopy was used to measure the stiffness of tumor tissues and coculture gels. Cytokine arrays, qPCR, and Western blotting were performed to identify the potential factors involved in PSC activation and to elucidate underlying pathways. Results: PSC activation characterized by α-SMA expression was associated with increased pancreatic tumor stiffness and poor prognosis. Coculture with cancer cells induced PSC activation, which increased organotypic coculture gel stiffness and cancer cell invasion. Cancer cells-derived PAI-1 identified from coculture medium could activate PSCs, consistent with pancreatic cancer tissue microarray analysis showing a strong positive correlation between PAI-1 and α-SMA expression. Suppression by knocking down PAI-1 in cancer cells demonstrated the requirement of PAI-1 for coculture-induced PSC activation and gel stiffness. PAI-1 could be upregulated by KRAS in pancreatic cancer cells through ERK. In PSCs, inhibition of LRP-1, ERK, and c-JUN neutralized the effect of PAI-1, suggesting the contribution of LRP-1/ERK/c-JUN signaling. Furthermore, activated PSCs might exacerbate malignant behavior of cancer cells via IL-8 because suppression of IL-8 signaling reduced pancreatic tumor growth and fibrosis in vivo. Conclusions: KRAS-mutant pancreatic cancer cells can activate PSCs through PAI-1/LRP-1 signaling to promote fibrosis and cancer progression.

9.
PeerJ ; 7: e7576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565561

RESUMO

Background: The increasing demand for food production has resulted in the use of large quantities of chemical fertilizers. This has created major environmental problems, such as increased ammonia volatilization, N2O emission, and nitrogen (N) leaching from agricultural soil. In particular, the utilization rate of N fertilizer is low in subtropical southern parts of China due to high rainfall. This causes not only large financial losses in agriculture, but also serious environmental pollution. Methods: In this study, 16S rDNA-based analysis and static-chamber gas chromatography were used to elucidate the effects of continuous straw biochar application on the N pool and bacteria environment in two typical soil types, purple and paddy soils, in southern China. Results: Straw biochar application (1) improved the soil N pool in both rhizosphere and non-rhizosphere soils; (2) significantly reduced the emission of N2O, with no difference in emission between 1 and 2 years of application; (3) increased the abundance of N-processing bacteria in the soil and altered the bacterial community structure; and (4) improved the tobacco yield and N use efficiency in paddy soil. These findings suggest that, in southern China, the application of straw biochar can promote N transformation in purple and paddy soils and reduce the emission of the greenhouse gas N2O.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31531121

RESUMO

Objective: To explore the effect of Tripterygium wilfordii polycoride (TWP) on the NADPH oxidases (NOXs)-reactive oxygen species (ROS)-NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway and the possibility of using TWP to treat ulcerative colitis (UC). Methods: BALB/c mice were randomly divided into five groups: model control, low TWP, middle TWP, high TWP, and normal control groups. A UC model was established with dextran sulfate sodium. The determination of ROS was carried out by using the fluorescent probe DCFH-DA, and NOXs activity was detected based on the NADPH consumption rate. The mRNA expression levels of NLRP3, ASC, and caspase-1 in the colon tissues and neutrophils were assessed via real-time PCR. Results: The colon tissues were abnormal with different degrees in TWP groups with disease activity index and histopathological scores lower than those in the model group. In TWP groups, ROS generation, NOXs activity, and the mRNA expression levels of NLRP3, ASC, and caspase-1 in the colon tissues and colon-isolated neutrophils were remarkably lower than those in the model control group (P < 0.05) and higher than those in the normal group (P < 0.05). The results of pairwise comparison for the efficacy of TWP administration showed that the above indexes were statistically significant with the lowest expression in the high TWP group (P < 0.05) and the highest expression in the low TWP group (P < 0.05). Conclusion: TWP demonstrated anti-inflammatory effects on UC by decreasing the expression of proinflammatory factors in the NOXs-ROS-NLRP3 signaling pathway.

11.
R Soc Open Sci ; 6(7): 181499, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31417689

RESUMO

Soil carbon reserves are the largest terrestrial carbon pools. Common agricultural practices, such as high fertilization rates and intensive crop rotation, have led to global-scale environmental changes, including decreased soil organic matter, lower carbon/nitrogen ratios and disruption of soil carbon pools. These changes have resulted in a decrease in soil microbial activity, severe reduction in soil fertility and transformation of soil nutrients, thereby causing soil nutrient imbalance, which seriously affects crop production. In this study, 16S rDNA-based analysis and static chamber-gas chromatography were used to elucidate the effects of continuous application of straw biochar on soil carbon pools and the soil microbial environments of two typical soil types (purple and paddy soils) in southern China. Application of biochar (1) improved the soil carbon pool and its activity, (2) significantly promoted the release of soil CO2 and (3) improved the soil carbon environment. Soil carbon content was closely correlated with the abundance of organisms belonging to two orders, Lactobacillales and Bacteroidales, and, more specifically, to the genus Lactococcus. These results suggest that biochar affects the soil carbon environment and soil microorganism abundance, which in turn may improve the soil carbon pool.

12.
J Pathol ; 249(4): 498-508, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31465125

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment-resistant malignancy. The lack of pathway-informed biomarkers hampers the development of rational diagnostics or therapies. Recently, the protein abnormal spindle-like microcephaly-associated (ASPM) was identified as a novel Wnt and stemness regulator in PDAC, while the pathogenic roles of its protein isoforms remain unclarified. We developed novel isoform-specific antibodies and genetic knockdown (KD) of putative ASPM isoforms, whereby we uncovered that the levels of ASPM isoform 1 (iI) and ASPM-iII are variably upregulated in PDAC cells. ASPM isoforms show remarkably different subcellular locations; specifically, ASPM-iI is exclusively localized to the cortical cytoplasm of PDAC cells, while ASPM-iII is predominantly expressed in cell nuclei. Mechanistically, ASPM-iI co-localizes with disheveled-2 and active ß-catenin as well as the stemness marker aldehyde dehydrogenase-1 (ALDH-1), and its expression is indispensable for the Wnt activity, stemness, and the tumorigenicity of PDAC cells. By contrast, ASPM-iII selectively regulates the expression level of cyclin E and cell cycle progression in PDAC cells. The expression of ASPM-iI and ASPM-iII displays considerable intratumoral heterogeneity in PDAC tissues and only that of ASPM-iI was prognostically significant; it outperformed ALDH-1 staining and clinico-pathological variables in a multivariant analysis. Collectively, the distinct expression patterns and biological functions of ASPM isoforms may illuminate novel molecular mechanisms and prognosticators in PDAC and may pave the way for the development of therapies targeting this novel oncoprotein. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

13.
Oncogene ; 38(38): 6550-6565, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31363162

RESUMO

Gastrointestinal stromal tumors (GISTs) are frequently driven by auto-activated, mutant KIT and have durable response to KIT tyrosine kinase inhibitor. However, acquired resistance is an increasing clinical issue in GIST patients receiving front-line imatinib therapy. Our previous studies showed the colocalization of KIT with DAPI-stained nuclei in GIST cells without knowing the role of nuclear KIT in GIST tumorigenesis. In this article, we first identified the binding of nuclear KIT to the promoter of NFKB inhibitor beta (NFKBIB) by chromatin immunoprecipitation (ChIP) sequencing and ChIP assays, which was accompanied with enhanced NFKBIB protein expression in GIST cells. Clinically, high NCCN risk GISTs had significantly higher mean expression levels of nuclear phospho-KIT and NFKBIB as compared with those of intermediate or low/very low-risk GISTs. Conversely, downregulation of NFKBIB by siRNA led to RELA nuclear translocation that could bind to the KIT promoter region and subsequently reduced KIT transcription/expression and the viability of GIST cells. These findings were further confirmed by either RELA overexpression or NFKB/RELA inducer, valproic acid, treatment to result in reduced KIT expression and relative cell viability of imatinib-resistant GIST cells. Combining valproic acid with imatinib showed significantly better growth inhibitory effects on imatinib-resistant GIST48 and GIST430 cells in vitro, and in the GIST430 animal xenograft model. Taken together, these results demonstrate the existence of a nuclear KIT-driven NFKBIB-RELA-KIT autoregulatory loop in GIST tumorigenesis, which are potential targets for developing combination therapy to overcome imatinib-resistant of KIT-expressing GISTs.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Proteínas I-kappa B/metabolismo , Mesilato de Imatinib/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/fisiologia , Fator de Transcrição RelA/metabolismo , Animais , Células COS , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Retroalimentação Fisiológica/efeitos dos fármacos , Retroalimentação Fisiológica/fisiologia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Homeostase/efeitos dos fármacos , Homeostase/genética , Humanos , Mesilato de Imatinib/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
14.
J Hematol Oncol ; 12(1): 79, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324208

RESUMO

BACKGROUND: The biological function of protein arginine methyltransferase 3 (PRMT3) is not well known because very few physiological substrates of this methyltransferase have been identified to date. METHODS: The clinical significance of PRMT3 in pancreatic cancer was studied by database analysis. The PRMT3 protein level of human pancreatic tumors was detected by immunoblotting and immunohistochemical staining. PRMT3-associated proteins and the methylation sites on the proteins were investigated using mass spectrometry. Seahorse Bioscience analyzed the metabolic reprogramming. Combination index analysis and xenograft animal model were conducted to explore the effects of combination of inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and oxidative phosphorylation on tumor growth. RESULTS: We found that the expression of PRMT3 is upregulated in pancreatic cancer, and its expression is associated with poor survival. We identified GAPDH as a PRMT3-binding protein and demonstrated that GAPDH is methylated at R248 by PRMT3 in vivo. The methylation of GAPDH by PRMT3 enhanced its catalytic activity while the mutation of R248 abolished the effect. In cells, PRMT3 overexpression triggered metabolic reprogramming and enhanced glycolysis and mitochondrial respiration simultaneously in a GAPDH-dependent manner. PRMT3-overexpressing cancer cells were addicted to GAPDH-mediated metabolism and sensitive to the inhibition of GAPDH and mitochondrial respiration. The combination of inhibitors of GAPDH and oxidative phosphorylation induced a synergistic inhibition on cellular growth in vitro and in vivo. CONCLUSION: Our results suggest that PRMT3 mediates metabolic reprogramming and cellular proliferation through methylating R248 of GAPDH, and double blockade of GAPDH and mitochondrial respiration could be a novel strategy for the treatment of PRMT3-overexpressing pancreatic cancer.

15.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1694-1703, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31350264

RESUMO

BACKGROUND: Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype. METHODS: The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer. RESULTS: The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P < 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease. CONCLUSIONS: The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex. IMPACT: The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.

16.
PLoS One ; 14(7): e0219551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314810

RESUMO

The hypothesis of data probability density distributions has many effects on the design of a new statistical method. Based on the analysis of a group of real gene expression profiles, this study reveal that the primary density distributions of the real profiles are normal/log-normal and t distributions, accounting for 80% and 19% respectively. According to these distributions, we generated a series of simulation data to make a more comprehensive assessment for a novel statistical method, maximal information coefficient (MIC). The results show that MIC is not only in the top tier in the overall performance of identifying differentially expressed genes, but also exhibits a better adaptability and an excellent noise immunity in comparison with the existing methods.

17.
Medicine (Baltimore) ; 98(23): e15828, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169684

RESUMO

BACKGROUND: The K channel, subfamily J, member-11 (KCNJ11) E23K and ß1 subunit of large-conductance Ca-activated K channel (KCNMB1) E65K polymorphisms were shown to be associated with the risk of essential hypertension (EH). However, the results were inconclusive with relatively small sample size. Thus, we carried out a meta-analysis to investigate the genetic association between KCNJ11 E23K and KCNMB1 E65K polymorphisms and essential hypertension risk. METHODS: Relative studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure and Embase databases. Pooled odds ratios with 95% confidence intervals were used to assess the strength of associations. RESULTS: The dominant models of KCNJ11 E23K (P = .006, OR [95%CI] = 0.45 [0.25, 0.79]) and KCNMB1 E65K (P = .04, OR [95%CI] = 0.91 [0.83, 1.00]) were significantly associated with essential hypertension risk. No significant association was detected between the allelic and recessive models of KCNJ11 E23K and KCNMB1 E65K and the susceptibility of EH. Subgroup analysis stratified by ethnicity showed that the dominant model of KCNMB1 E65K was associated with EH risk in Asian population (P = .003, OR [95%CI] = 0.83 [0.74, 0.94]), but not in Caucasian (P = .74, OR [95%CI] = 1.02 [0.89, 1.18]). CONCLUSIONS: The dominant model of KCNJ11 E23K and KCNMB1 E65K might be susceptible factors for essential hypertension. To confirm this result, large-scale case-control studies with more subjects are necessary.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipertensão Essencial/genética , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade
19.
Environ Toxicol ; 34(8): 902-911, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31044527

RESUMO

Osteosarcoma (OS) is a tumor entity that can cause a large number of cancer-related deaths. Although chemotherapy can decrease proliferation and increase apoptosis of human OS cells, the clinical prognosis remains poor. Fisetin is a flavonol found in fruits and vegetables and is reported to inhibit cell growth in numerous cancers. But the molecular mechanism underlying fisetin in human OS cells is not clear. It is known that sterile-alpha motif and leucine zipper containing kinase (ZAK), a kinase in the MAP3K family, is involved in various cell processes, including proliferation and apoptosis. In our lab, we have demonstrated that overexpression of ZAK can induce apoptosis in human OS cells. In the previous studies, MAP4K, the upstream of MAP3K, can act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Turning on the Hippo pathway can decrease proliferation and otherwise cause cell apoptosis in cancer cells. In this study, we found that fisetin can upregulate ZAK expression to induce the Hippo pathway and mediate the activation of JNK/ERK, the downstream of ZAK, to trigger cell apoptosis via AP-1 dependent manner in human OS cells. These findings reveal a novel molecular mechanism underlying fisetin effect on human OS cells.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/metabolismo , Flavonoides/farmacologia , Sistema de Sinalização das MAP Quinases , Osteossarcoma/metabolismo , Proteínas Quinases/metabolismo , Apoptose , Neoplasias Ósseas/enzimologia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Osteossarcoma/enzimologia , Osteossarcoma/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Proteínas Supressoras de Tumor/metabolismo
20.
Transbound Emerg Dis ; 66(5): 1971-1981, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31077561

RESUMO

Bovine coronavirus (BCoV) is the causative agent of diarrhoea in newborn calves, winter dysentery in adult cattle and respiratory tract illnesses in cattle across the world. In this study, a total of 190 faecal samples from dairy calves with diarrhoea were collected from 14 farms in six Chinese provinces, and BCoV was detected in 18.95% (36/190) of the samples by reverse transcriptase polymerase chain reaction. Full-length spike, hemagglutinin/esterase (HE), nucleocapsid and transmembrane genes were simultaneously cloned from 13 clinical samples (eight farms in four provinces), and most of the BCoV strains showed a unique evolutionary pattern based on the phylogenetic analysis of these genes. Interesting, 10 of the 13 strains were identified as HE recombinant strains, and these strains had experienced the same recombination event and carried the same recombination sites located between the esterase and lectin domain. They also shared an identical aa variant (F181V) in the R2-loop. Moreover, 9/10 strains displayed another identical aa variant (P, S158A) in the adjacent R1-loop of the HE gene, which differs from the other available BCoV HE sequences in the GenBank database. Our results showed that BCoV is widely circulating in dairy cattle in China, contributing to the diagnosis and control of dairy calves diarrhoea. Furthermore, a BCoV strain that carries a recombinant HE gene has spread in dairy calves in China. To the best of our knowledge, this is the first description of an HE recombination event occurring in BCoV; this is also the first description of the molecular prevalence of BCoV in China. Our findings will enhance current understanding about the genetic evolution of BCoV.


Assuntos
Doenças dos Bovinos/epidemiologia , Infecções por Coronavirus/veterinária , Coronavirus Bovino/genética , Diarreia/veterinária , Evolução Molecular , Animais , Bovinos , Doenças dos Bovinos/virologia , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Indústria de Laticínios , Diarreia/virologia , Fezes/virologia , Hemaglutininas Virais/análise , Filogenia , Prevalência , Proteínas Recombinantes/análise , Análise de Sequência de DNA/veterinária , Proteínas Virais de Fusão/análise , Proteínas Virais/análise
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