Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

Wang, Wei-Lan,Tang, Zhi-Hui,Xie, Ting-Ting,Xiao, Bing-Kun,Zhang, Xin-Yu,Guo, Dai-Hong,Wang, Dong-Xiao,Pei, Fei,Si, Hai-Yan,Zhu, Man Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

Study on an Optimal Control Method for Energy Injection Resonant AC/AC High Frequency Converters

Su, Yu-Gang,Dai, Xin,Wang, Zhi-Hui,Tang, Chun-Sen,Sun, Yue The Korean Institute of Power Electronics 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.2

In energy injection resonant AC-AC converters, due to the low frequency effect of the AC input envelope and the low energy injection losses requirement, the constant and steady control of the high frequency AC output envelope is still a problem that has not been solved very well. With the aid of system modeling, this paper analyzes the mechanism of the envelope pit on the resonant AC current. The computing methods for the critical damping point, the falling time and the bottom value of the envelope pit are presented as well. Furthermore, this paper concludes the stability precondition of the system AC output. Accordingly, an optimal control method for the AC output envelope is put forward based on the envelope prediction model. This control method can predict system responses dynamically under different series of control decisions. In addition, this control method can select best series of control decisions to make the AC output envelope stable and constant. Simulation and experimental results for a contactless power transfer system verify the control method.

Cloning and Distribution of Facilitative Glucose Transporter 2 (SLC2A2) in Pigs

Zuo, Jianjun,Huang, Zhiyi,Zhi, Aimin,Zou, Shigeng,Zhou, Xiangyan,Dai, Fawen,Ye, Hui,Feng, Dingyuan Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.9

Glucose is the main energy source for mammalian cells and its absorption is co-mediated by two different families of glucose transporters, sodium/glucose co-transporters (SGLTs) and facilitative glucose transporters (GLUTs). Here, we report the cloning and tissue distribution of porcine GLUT2. The GLUT2 was cloned by RACE and its cDNA was 2,051 bp long (GenBank accession no. EF140874). An AAATAA consensus sequence at nucleotide positions 1936-1941 was located upstream of the poly $(A)^+$ tail. Open reading frame analysis suggested that porcine GLUT2 contained 524 amino acids, with molecular weight of 57 kDa. The amino acid sequence of porcine GLUT2 was 87% and 79.4% identical with human and mouse GLUT2, respectively. GLUT2 mRNA was detected at highest level in porcine liver, at moderate levels in the small intestine and kidney, and at low levels in the brain, lung, muscle and heart. In the small intestine, the highest level was in the jejunum. In conclusion, the mRNA expression of GLUT2 was not only differentially regulated by age, but also differentially distributed along the small intestine of piglets, which may be related to availability of different intestinal luminal substrate concentrations resulting from different food sources and digestibility.

Study on an Optimal Control Method for Energy Injection Resonant AC/AC High Frequency Converters

Yu-Gang Su,Xin Dai,Zhi-Hui Wang,Chun-Sen Tang,Yue Sun 전력전자학회 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.2

In energy injection resonant AC-AC converters, due to the low frequency effect of the AC input envelope and the low energy injection losses requirement, the constant and steady control of the high frequency AC output envelope is still a problem that has not been solved very well. With the aid of system modeling, this paper analyzes the mechanism of the envelope pit on the resonant AC current. The computing methods for the critical damping point, the falling time and the bottom value of the envelope pit are presented as well. Furthermore, this paper concludes the stability precondition of the system AC output. Accordingly, an optimal control method for the AC output envelope is put forward based on the envelope prediction model. This control method can predict system responses dynamically under different series of control decisions. In addition, this control method can select best series of control decisions to make the AC output envelope stable and constant. Simulation and experimental results for a contactless power transfer system verify the control method.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Combined fine-needle aspiration with core needle biopsy for assessing thyroid nodules: a more valuable diagnostic method?

Zhe Chen,Jia-jia Wang,Dong-ming Guo,Yu-xia Zhai,Zhuo-zhi Dai,Hong-hui Su 대한초음파의학회 2023 ULTRASONOGRAPHY Vol.42 No.2

Purpose: This study aimed to evaluate the diagnostic value of combined fine-needle aspiration (FNA) with core needle biopsy (CNB) in thyroid nodules. Methods: FNA and CNB were performed simultaneously on 703 nodules. We compared the proportions of inconclusive results and the diagnostic performance for malignancy among FNA, CNB, and combined FNA/CNB for different nodule sizes. Results: Combined FNA/CNB showed lower proportions of inconclusive results than CNB for all nodules (2.8% vs. 5.7%, P<0.001), nodules ≤1.0 cm (4.9% vs. 7.3%, P=0.063), nodules >1.0 cm (2.0% vs. 5.0 %, P<0.001), nodules ≤1.5 cm (3.8% vs. 7.9 %, P<0.001), and nodules >1.5 cm (2.1% vs. 3.9 %, P=0.016). The sensitivity of combined FNA/CNB in predicting malignancy was significantly higher than that of CNB (89.0% vs. 80.0%, P<0.001) and FNA (89.0% vs. 58.1%, P<0.001) for all nodules. Within American College of Radiology Thyroid and Imaging Reporting and Data System grades 4-5, in the subgroup of nodules ≤1.5 cm, combined FNA/ CNB showed the best sensitivity in predicting malignancy (91.4%), significantly higher than that of CNB (81.0%, P<0.001) and FNA (57.8%, P<0.001). However, in the subgroup of nodules >1.5 cm, the difference between combined FNA/CNB and CNB was not significant (84.2% vs. 78.9%, P=0.500). Conclusion: Regardless of nodule size, combined FNA/CNB tended to yield lower proportions of inconclusive results than CNB or FNA alone and exhibited higher performance in diagnosing malignancy. The combined FNA/CNB technique may be a more valuable diagnostic method for nodules ≤1.5 cm and nodules with a risk of malignancy than CNB and FNA alone.

Circular RNA cFAM210A, degradable by HBx, inhibits HCC tumorigenesis by suppressing YBX1 transactivation

Yu Jian,Li Wen,Hou Guo-jun,Sun Da-peng,Yang Yuan,Yuan Sheng-xian,Dai Zhi-hui,Yin Hao-zan,Sun Shu-han,Huang Gang,Zhou Wei-ping,Yang Fu 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.