Objective To summarize the development of gallbladder carcinoma related resistance genes and targeted therapy. Methods Domestic and international publications online involving resistance genes and targeted therapy of gallbladder carcinoma in recent years were collected and reviewed. Results Recent studies had shown that chemotherapy drug resistance of gallbladder carcinoma mainly involved lysosome protein transmembrane β4 （LAPTM4B） gene， NF-E2-related factor 2 （Nrf2） gene， and cancer stem cells （CSCs）. While the latest gene targets of treatment for gallbladder carcinoma mainly involved LAPTM4B， Nemo-like kinase （NLK）， tissue factor way inhibitor-2 （TFPI-2）， vascular endothelial growth factor-D （VEGF-D）， epidermal growth factor receptor （EGFR）， and melanoma differentiation-associated gene 7/interleukin 24 （mda-7/IL-24） gene. Conclusion The research involving resistance genes and targeted therapy of gallbladder carcinoma has make a certain progress， which broaden the concept of traditional treatment of gallbladder carcinoma.
Objective To summarize the role of nuclear factor kappa B (NF-κB) in the occurrence and progression of various sorts of liver injury. Methods Literatures on the structures, property of molecular biology and function of NF-κB, as well as its relationships with liver injury were collected and reviewed. Results NF-κB was an important nuclear factor existed in cells widely distributed in most cell types. The activation of NF-κB was induced by various sorts of liver injury. The activated NF-κB could affect the liver injury by regulating cytokines, adhesion molecules, and activating factor involving in immunologic reaction， inflammatory reaction and the apoptosis. Conclusion NF-κB plays an important role during the occurrence and progression of liver injury， and may become a new target in the treatment of liver injury.
ObjectiveTo investigate target gene therapy for hepatocellular carcinoma (HCC). MethodsHerpes simplex virus thymidine kinase (HSVTK) gene was inserted into the gene of AFP enhancer/ALB promoter with adenoassociated virus (AAV) plasmid (WAV2) as a carrier, and a hybrid plasmid pWAV2/AFPALB/HYTK was constructed. Besides, plasmid pEGFP1/AFPALB was also constructed. Two kinds of plasmids were transferred into AFP positive cells HepG2 and AFP negative cells 7721, SPC and 7901.ResultsIt was found that enhance green fluorescence protein could only be seen in AFP positive cells HepG2. 710 bp DNA was amplified only in AFP positive HepG2 cells.ConclusionPlasmid pWAV2/AFPALB/HYTK for HCC demonstrates specificity in vitro.
Objective To review the advances of target gene therapy of liver cancer. MethodsWe analyze and compare the tissuespecific carrier system or cellspecific gene expressing system from current researches of liver cancer gene therapy. ResultsArtificial synthetic DNA transfer system and modified viral vectors could efficiently transfect target cells and get highlevel expression. The ciselements of alpha fetal protein or albumin gene have been often adopted in the regulation of therapeutic gene and have shown their effectiveness. Some other gene therapy strategies also promised a good future. Conclusion Searching for more specific and universal liver cancer antigens is the key to improve the target gene therapy efficiency. The individual situation is the basis to select the best transfer system or regulatory elements in the future.
Abstract： Surgery is an effective therapy for non-small cell lung cancer (NSCLC). The standard operation includes lobectomy and systematic dissection of lymph nodes. However, postoperative tumor recurrence is common even among incipient patients due to incomplete dissection of lymph nodes and micrometastasis of lymph nodes. Injecting a carbon nanoparticles suspension is a new technique aimed at preventing this recurrence. The carbon nanoparticles carry lymph node tracers that help surgeons locate lymph nodes in order to clean them thoroughly. The tracers also target the lymph nodes for chemotherapy, thus killing residual tumor cells intraoperatively to avoid postoperative cancer recurrence. Carbon nanoparticles suspension injection is already widely and successfully used in surgery for gastrointestinal and mammary gland tumors, and is being tested for effectiveness in NSCLC patients. Some studies have indicated that carbon nanoparticles suspension injection is effective in NSCLC patients and improves their prognoses. We reviewed the features, application methods, and clinical applications of studies of carbon nanoparticles suspension injection for NSCLC.
Objective To clarify the trends of expression levels of several up-regulated micro RNA (miRNA) in tissues of atrophic bone nonunion and mRNAs and proteins of their related target genes in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), and to explore their biological functions. Methods The hBMSCs were isolated from bone marrow of il iac bone by gradient centrifugation, and cultured. Osteogenic culture medium was used for osteogenic differentiation of the 4th generation of hBMSCs. The changes of corresponding miRNAs, mRNA and protein expression levels of related target genes were observed at 0 hour, 12 hours, 1 day, 2 days, 4 days, 7 days, and 14 days, by quantitative real-time PCR and Western blot. Results In the process of hBMSCs osteogenic differentiation, the mRNA and protein expression levels of osteoblastic target genes [alkal ine phosphatase l iver/bone/kidney (ALPL), bone morphogeneticprotein 2 (BMP-2), and platelet-derived factor alpha polypeptide (PDGF-A)] at most time points increased significantly whencompared with the values at 0 hour except that of BMP-2 decreased at 12 hours and 1 day, with maximum changes at 1 to 7 days. The miRNA expression levels, mRNA and protein expression levels changed significantly at different time points, while the trends of hsa-miRNA-149 and hsa-miRNA-654-5p changes were negatively correlated with the trends of ALPL and BMP-2 mRNA and protein expression changes respectively (P lt; 0.05). There was no obviously negative correlation between the trends of hsa-miRNA-221 change and PDGF-A change (P gt; 0.05). Conclusion In the osteogenic differentiation process of hBMSCs, hsa-miRNA-149 and hsa-miRNA-654-5p are closely related with the mRNA and protein regulation of ALPL and BMP-2, respectively.
Objective To evaluate the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents for advanced renal cell carcinoma. Methods We searched MEDLINE, EMbase, The Cochrane Library, CBMdisc and China Academic Periodical database from the establishment of each database to April 2009. We included randomized controlled trials (RCTs) that evaluated anti-VEGF agents (sunitinib, sorafenib and bevacizumab). The quality of the included trials was evaluated by two reviewers independently. Meta-analyses were conducted by the Cochrane Collaboration’s RevMan 4.2 software. Results Four RCTs involving 2 320 patients were identified. According to the different interventions for advanced renal cell carcinoma, we divided the patients into two groups: anti-VEGF agents monotherapy and anti-VEGF agents plus interferon combination treatment. Our meta-analyses showed: monotherapy was superior to interferon on inhibition of tumor progression [OR=0.38, 95%CI (0.29, 0.51), Plt;0.01] and control of tumor [OR=2.53, 95%CI (1.87, 3.43), Plt;0.01], but was not significantly different from interferon on the overall effective rate [OR=1.97, 95%CI (0.20, 19.57), P=0.56] and serious side effects [OR=1.98, 95%CI (0.90, 4.34), P=0.09]. There were significant differences between anti-VEGF agents plus interferon and interferon alone on inhibition of tumor progression [OR=0.67, 95%CI (0.53, 0.84), P=0.000 5], overall effective rate [OR=2.65, 95%CI (1.94, 3.61), Plt;0.01], control of tumor [OR=2.14, 95%CI (1.65, 2.78), Plt;0.01] and serious side effects [OR=2.63, 95%CI (2.09, 3.31), Plt;0.01]. Conclusion Compared with interferon, anti-VEGF agents could inhibit tumor progression more effectively. Moreover, the combination therapy with interferon could offer a more favorable overall effective rate for advanced renal cell carcinoma, but then followed by more serious side effects. We need to weigh the merits and demerits of drugs before making a clinical decision for advanced renal cell carcinoma.
Objectives To describe the mechanism of means testing used in health programs for targeting poor population and to describe how the authors have assessed effects of means testing approaches where applicable. Method We searched 24 electronic resources which included evidence-based, health, economic and social databases, 7 international institution websites, grey literature review resources and Google. Screening and data extraction were conducted by two reviewers separately, and the differences were discussed by the third person or a review group. We systematically analyzed the included studied by theme analysis method from different dimensions. We also described the evaluation outcomes by the authors. Result A total of 10244 records were searched, and 58 studies were included after screening by title, abstract and full texts. A total of 13 studies described verified means testing (VMT) conducted as a targeting method in the US; simple testing method (SMT) was conducted in 16 countries; 26 studies described how proxy means testing (PMT) was used in 14 countries; andmixed means testing (MA) was conducted in 14 countries. Means testing as a targeting method was widely used in four health programs which included health insurance, cash transfer, provision of free health service and fee structure. The target population was poor. Only few studies analyzed the outcomes of means testing; 3 studies analyzed under-coverage and 11studies analyzed leakage as their indicators. Scare cost information could be obtained from the included studies. Conclusion Means testing is widely used in various health programs for targeting the eligible population in distributing benefits, especially in developing countries. Targeting as a means for allocating health resources is particularly important in LMICs for their constraints in budgets available for health. Meanwhile, a universal coverage strategy has become a worldwide issue, and how current health resources can be used equitably and efficiently is a concern from the policy practice. Means testing, as one of the tools in targeting eligible population, would help in this process.
Objective To explore the effect of antihypertensive treatment on target-organ damage in very elderly patients (gt;80 years). Methods One hundred and sixty-seven very elderly hypertensive patients were randomized into two groups, i.e. anti-hypertension treatment group and placebo-control group. All the patients received echocardiographic examination of left ventricular mass index, laboratory tests of urinary creatinine and urinary albumin and 24-hour ambulatory blood pressure monitoring 2 months after placebo washout period and at the end of the one year treatment, respectively. Results After treatment, the improvement in all the dynamic blood pressure parameters except daytime diastolic blood pressure and heart rate(24 h, daytime and night time), were significantly better than that of placebo-control group(Plt;0.05).The improvement in left ventricular and renal functional parameters were significantly better than that of placebo-control group(Plt;0.05). Conclusion Anti-hypertension treatment may significantly improve left ventricular pachynsis and renal function damage in very elderly hypertensive patients.
【摘要】 目的 探讨肺动脉高压患者药物靶向治疗的效果与耐受性。 方法 回顾分析2008年1月〖CD3/5〗2009年8月期间8例肺动脉高压患者分别接受波生坦及西地那非治疗的临床资料,评估其临床表现、WHO肺动脉高压功能分级、6 min步行距离及肺动脉收缩压在基线及治疗3个月后的变化。 结果 治疗后3个月,患者均能耐受药物治疗,无严重不良反应发生。WHO肺动脉高压功能分级在治疗前平均(31±04),治疗后为(23±09),明显得到改善(Plt;005)。肺动脉收缩压在治疗前平均(695±112 ) mm Hg(1 mm Hg=0133 kPa),治疗后为(483±124) mm Hg,明显降低(Plt;005)。6 min步行距离在治疗前平均(324±48) m,治疗后为(400±43) m,明显延长(Plt;005)。 结论 肺动脉高压患者药物靶向治疗的疗效显著,且耐受良好。【Abstract】 Objective To examine the effects of target medical therapy in patients with pulmonary arterial hypertension(PAH). Methods To determine the safety and efficacy of bosentan and sildenafil in eight patients with PAH.The patients’ clinical features, six minutes walking diastance, WHO functional class and systolic pulmonary arterial pressure (SPAP) were measured at baseline and at three months after initiating target medial treatment. Results At the three months followup assessments, WHO functional class was improved with 31±04 vs 23±09 (Plt;005); SPAP was significantly decreased with(695±112 ) mm Hg vs (483±124) mm Hg (Plt;005), the six minutes walking distance was significantly increased with(324±48) m vs(400±43) m (Plt;005). Target medical treatment was well tolerated. Conclusion Target medical treatment is well tolerated and has beneficial effects on PAH.