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| 1 | Oxidative stress,insulin resistance,dyslipidemia and type 2 diabetes mellitus显示文摘Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus(T2DM) and this appears to underlie the development of cardiovascular disease,T2 DM and diabetic complications.Increased oxidative stress appears to be a deleterious factor leading toinsulin resistance,dyslipidemia,β-cell dysfunction,impaired glucose tolerance and ultimately leading to T2 DM.Chronic oxidative stress,hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant,have high oxidative energy requirements,decrease the gene expression of key β-cell genes and induce cell death.If β-cell functioning is impaired,it results in an under production of insulin,impairs glucose stimulated insulin secretion,fasting hyperglycemia and eventually the development of T2 DM. | Surapon Tangvarasittichai | 2015 | World Journal of Diabetes2015,6,3: | 95 |
| 2 | Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: A prospective serial study显示文摘AIM:To determine the resistance patterns of Helicobacter pylori(H.pylori) strains isolated from patients in Beijing and monitor the change of antibiotic resistance over time.METHODS:In this prospective,serial and crosssectional study,H.pylori cultures were successfully obtained from 371 and 950 patients(never receiving eradication) during 2009-2010 and 2013-2014,respectively.Resistance to amoxicillin,clarithromycin,metronidazole,levofloxacin,tetracycline,and rifampicin was determined by Epsilometer test.RESULTS:The resistance rates of isolates obtained during 2009-2010 were 66.8%,39.9%,34.5%,15.4%,6.7%,and 4.9% to metronidazole,clarithromycin,levofloxacin,rifampicin,amoxicillin and tetracycline,respectively; and the corresponding rates for isolates during 2013-2014 were 63.4%,52.6%,54.8%,18.2%,4.4% and 7.3%,respectively.The resistance rates to clarithromycin and levofloxacin were significantly increased after four years.In 2009-2010,14.6% of H.pylori isolates were susceptible to all tested antibiotics,with mono(33.7%),double(28.3%),triple(16.7%),quadruple(6.2%),quintuple(0.3%) and sextuple resistance(0.3%) also being detected.In 2013-2014,9.4% were susceptible to all tested antibiotics,and mono(27.6%),double(28.4%),triple(24.9%),quadruple(7.3%),quintuple(2.3%) and sextuple resistance(0.1%) was also observed.More multiple resistant H.pylori isolates were found during 2013-2014.Gender(to levofloxacin and metronidazole),age(to levofloxacin) and endoscopic findings(to clarithromycin) were independent factors influencing antibiotic resistance.CONCLUSION:H.pylori resistance to commonly used antibiotics in Beijing is high with increased multiple antibiotic resistance. | Yue-Xi Zhang Li-Ya Zhou Zhi-Qiang Song Jian-Zhong Zhang Li-Hua He Yu Ding | 2015 | World Journal of Gastroenterology2015,21,9: | 138 |
| 3 | Autophagy and multidrug resistance in cancer显示文摘Multidrug resistance(MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence.Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells. | Ying-Jie Li Yu-He Lei Nan Yao Chen-Ran Wang Nan Hu Wen-Cai Ye Dong-Mei Zhang Zhe-Sheng Chen | 2017 | Chinese Journal of Cancer2017,36,8: | 54 |
| 4 | Antimicrobial resistance in Acinetobacter baumannii : From bench to bedside显示文摘Acinetobacter baumannii(A. baumannii) is undoubtedly one of the most successful pathogens in the modern healthcare system. With invasive procedures, antibiotic use and immunocompromised hosts increasing in recent years, A. baumannii has become endemic in hospitals due to its versatile genetic machinery, which allows it to quickly evolve resistance factors, and to its remarkable ability to tolerate harsh environments. Infections and outbreaks caused by multidrugresistant A. baumannii(MDRAB) are prevalent and have been reported worldwide over the past twenty or more years. To address this problem effectively, knowledge of species identification, typing methods, clinical manifestations, risk factors, and virulence factors is essential. The global epidemiology of MDRAB is monitored by persistent surveillance programs. Because few effective antibiotics are available, clinicians often face serious challenges when treating patients with MDRAB. Therefore, a deep understanding of the resistance mechanisms used by MDRAB can shed light on two possible strategies to combat the dissemination of antimicrobial resistance: stringent infection control and antibiotic treatments, of which colistin-based combination therapy is the mainstream strategy. However, due to the current unsatisfying therapeutic outcomes, there is a great need to develop and evaluate the efficacy of new antibiotics and to understand the role of other potential alternatives, such as antimicrobial peptides, in the treatment of MDRAB infections. | Ming-Feng Lin Chung-Yu Lan | 2014 | World Journal of Clinical Cases2014,2,12: | 55 |
| 5 | Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations显示文摘Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components.Up to80%of patients with NAFLD are obese,defined as a body mass index(BMI)>30 kg/m2.However,the distribution of fat tissue plays a greater role in insulin resistance than the BMI.The large amount of visceral adipose tissue(VAT)in morbidly obese(BMI>40 kg/m2)individuals contributes to a high prevalence of NAFLD.Free fatty acids derived from VAT tissue,as well as from dietary sources and de novo lipogenesis,are released to the portal venous system.Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD.In addition,secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways,which are also activated by free fatty acids,and contribute to insulin resistance.Most NAFLD patients are asymptomatic on clinical presentation,even though some may present with fatigue,dyspepsia,dull pain in the liver and hepatosplenomegaly.Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications,anti-obesity medication and bariatric surgery.This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease.The relative contribution of visceral and liver fat to insulin resistance is discussed,and recommendations for clinical evaluation of affected individuals is provided. | Sandra Milic Davorka Lulic Davor Stimac | 2014 | World Journal of Gastroenterology2014,20,28: | 52 |
| 6 | Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies显示文摘BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality. | Fan, Jian-Gao Peng, Yong-De | 2007 | Hepatobiliary & Pancreatic Diseases International2007,6,6: | 42 |
| 7 | Targeting inflammation in diabetes: Newer therapeutic options显示文摘Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resis-tance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflamma-tion.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. In-terleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce in-flammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabe-tes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory mark-ers. Retinopathy drugs are used to target vascular en-dothelial growth factor, angiopoietin-2, various protein-ases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapa-mycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, per-oxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory thera-pies represent a potential approach for the therapy of diabetes and its complications. | Neeraj Kumar Agrawal Saket Kant | 2014 | World Journal of Diabetes2014,5,5: | 41 |
| 8 | Anatomical and chemical characteristics associated with lodging resistance in wheat显示文摘Anatomical and chemical characteristics of stems affect lodging in wheat(Triticum aestivum L.) cultivars. Traits associated with lodging resistance, such as plant height, stem strength, culm wall thickness, pith diameter, and stem diameter, were extensively investigated in earlier studies. However, the solid stem trait was rarely considered. In this study, we measured a range of anatomical and chemical characteristics on solid and hollow stemmed wheat cultivars. Significant correlations were detected between resistance to lodging and several anatomical features, including width of mechanical tissue, weight of low internodes, and width of stem walls. Morphological features that gave the best indication of improved lodging resistance were increased stem width, width of mechanical tissue layer, and stem density. Multiple linear regression analysis showed that 99% of the variation in lodging resistance could be explained by the width of the mechanical tissue layer, suggesting that solid stemmed wheat has several anatomical features for increasing resistance to lodging. In addition, microsatellite markers GWM247 and GWM340 were linked to a single solid stem QTL on chromosome 3BL in a population derived from the cross Xinongshixin(solid stem)/Line 3159(hollow stem). These markers should be valuable in breeding wheat for solid stem. | Eryan Kong Dongcheng Liu Xiaoli Guo Wenlong Yang Jiazhu Sun Xin Li Kehui Zhan Dangqun Cui Jinxing Lin Aimin Zhang | 2013 | The Crop Journal2013,1,1: | 43 |
| 9 | Mechanisms of resistance to EGFR tyrosine kinase inhibitors显示文摘Since the discovery that non-small cell lung cancer(NSCLC) is driven by epidermal growth factor receptor(EGFR) mutations, the EGFR tyrosine kinase inhibitors(EGFR-TKIs, e.g., ge fi tinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation(T790M), activation of alternative pathways(c-Met, HGF, AXL), aberrance of the downstream pathways(K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway(BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette(ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies. | Lihua Huang Liwu Fu | 2015 | Acta Pharmaceutica Sinica B2015,5,5: | 42 |
| 10 | Clinical importance of aspirin and clopidogrel resistance显示文摘Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked 'aspirin and/or clopidogrel resistance', as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel. | Gergely Feher Andrea Feher Gabriella Pusch Katalin Koltai Antal Tibold Beata Gasztonyi Elod Papp Laszlo Szapary Gabor Kesmarky Kalman Toth | 2010 | World Journal of Cardiology2010,2,7: | 36 |
| 11 | Androgen receptor: structure, role in prostate cancer and drug discovery显示文摘Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. | MH Eileen TAN Jun LI H Eric XU Karsten MELCHER Eu-leong YONG | 2015 | Acta Pharmacologica Sinica2015,36,1: | 39 |
| 12 | Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma显示文摘Autophagy is a 'self-degradative' process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients. | Fang Huang Bing-Rong Wang Yi-Gang Wang | 2018 | World Journal of Gastroenterology2018,24,41: | 37 |
| 13 | Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance显示文摘The gram-negative bacterium Helicobacter pylori(H.pylori)causes chronic gastritis,gastric and duodenal ulcers,gastric cancer and mucosa-associated lymphoid tissue lymphoma.Treatment is recommended in all symptomatic patients.The current treatment options for H.pylori infection are outlined in this review in light of the recent challenges in eradication success,largely due to the rapid emergence of antibiotic resistant strains of H.pylori.Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H.pylori antibiotic resistance varies significantly from country to country,and even between regions within the same country.In addition,recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H.pylori.Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy.Antimicrobial resistance is assessed by H.pylori culture and antimicrobial susceptibility testing.Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H.pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material.Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H.pylori infection. | Sinéad M Smith Colm O’Morain Deirdre McNamara | 2014 | World Journal of Gastroenterology2014,20,29: | 40 |
| 14 | WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?显示文摘Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from'common soil'.The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients. | Iciar Martín-Timón Cristina Sevillano-Collantes Amparo Segura-Galindo Francisco Javier del Caizo-Gómez | 2014 | World Journal of Diabetes2014,5,4: | 32 |
| 15 | Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis显示文摘AIM:To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus(HBV)-related cirrhosis and esophageal varices.METHODS:Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing,China,the Chinese Second Artillery General Hospital and Chinese PLA General Hospital,were enrolled in the study from January 2005 to December 2009. Of 117 patients,79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate,change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding.antiviral group compared to the control group(29.1%vs 65.8%,P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis(HR = 11.3,P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group(1.0 ± 1.3 vs 1.7 ± 1.2,P = 0.003). Nonbleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group,all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates(17.2% and 28.6%,respectively) than the control(P < 0.001 and P = 0.006,respectively),whereas lamivudine(53.3%) did not(P = 0.531).CONCLUSION:Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis,however,high-resistance agents tend to be ineffective for long-term treatment. | Chang-Zheng Li Liu-Fang Cheng Qing-Shan Li Zhi-Qiang Wang Jun-Hong Yan | 2013 | World Journal of Gastroenterology2013,19,40: | 31 |
| 16 | Analysis of aerodynamic and thermodynamic parameters on the grassy marshland surface of Tibetan Plateau | TSUKAMOTO Osamu ISHIKAWA Hirohiko TAMAGAWA Ichiro | 2002 | Progress in Natural Science:Materials International2002,12,1: | 34 |
| 17 | MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside显示文摘MicroRNAs(miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer(CRC). MiR NAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage Ⅱ CRC is potentially curable by surgical resection, a significant percentage of stage Ⅱ CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs. | Kenneth KW To Christy WS Tong Mingxia Wu William CS Cho | 2018 | World Journal of Gastroenterology2018,24,27: | 29 |
| 18 | Nonalcoholic fatty liver disease as a multi-systemic disease显示文摘Nonalcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease. NAFLD includes a wide spectrum of liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis and advanced hepatic fibrosis. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome linked with insulin resistance. NAFLD should be considered not only a liver specific disease but also an early mediator of systemic diseases. Therefore, NAFLD is usually associated with cardiovascular disease, chronic kidney disease, type 2 diabetes, obesity, and dyslipidemia. NAFLD is highly prevalent in the general population and is associated with increased cardiovascular morbidity and mortality. The underlying mechanisms and pathogenesis of NAFLD with regard to other medical disorders are not yet fully understood. This review focuses on pathogenesis of NAFLD and its relation with other systemic diseases. | Hakan Fotbolcu Elcin Zorlu | 2016 | World Journal of Gastroenterology2016,22,16: | 29 |
| 19 | Mechanisms of drug resistance in colon cancer and its therapeutic strategies显示文摘Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATPbinding cassette(ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics. | Tao Hu Zhen Li Chun-Ying Gao Chi Hin Cho | 2016 | World Journal of Gastroenterology2016,22,30: | 29 |
| 20 | Constructal entransy dissipation rate and flow-resistance minimizations for cooling channels显示文摘Based on constructal theory,a construct of a volume that generates heat at every point and is cooled by the coolant in the constant or tapered channel is optimized by minimizing entransy dissipation rate and flow resistance.The optimal constructs of the rectangular elements with dimensionless mean thermal resistance minimization as well as the first-,secondand thirdorder assemblies with dimensionless global flow resistance minimizations are obtained respectively.The results show that both the mean temperature difference and the limiting temperature difference of rectangular elements based on EDR (entransy dissipation rate) and MTD (maximum temperature difference) minimizations respectively are almost equal.Comparing heat transfer performances from the two optimization procedures,the dimensionless global flow resistance is decreased more for the former procedure when the assembly’s order is high.It may create great superiority for constructal optimization to combine the entransy dissipation extreme principle with heat convection. | XIAO QingHua,CHEN LinGen & SUN FengRui Postgraduate School,Naval University of Engineering,Wuhan 430033,China | 2010 | Science China(Technological Sciences)2010,53,9: | 27 |