Phase II Study on Voriconazole for Treatment of Chinese Patients with Malignant Hematological Disorders and Invasive Aspergillosis

Zhang, Xue-Zhong,Huang, Xin-En,Xu, Yan-Li,Zhang, Xiu-Qun,Su, Ai-ling,Shen, Zheng-Shan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To investigate the efficacy and safety of voriconazole in treating Chinese patients with hematological malignancies and invasive aspergillosis. Methods: From March 2007 to April 2012, patients with diagnoses confirmed by CT, GM test and/or PCR assays, were recruited into this study. Aspergillosis of all patients were treated with voriconazole 6 mg/kg intravenous infusion (iv) every 12 h for 1 day, followed by 4 mg/kg IV every 12 h for 10-15 days; Then, switch to oral administration that was 200mg every 12h for 4-12 weeks. Efficacy and safety were evaluated according to Practice Guideline of Infectious Diseases Society of America. Results: The overall response rate of 38 patients after voriconazole treatment was 81.6%. The median time to pyretolysis was 4.5 days. Treatment related side effects were mild and found in only 15.8% of cases. No treatment related deaths occurred. Conclusions: Voriconazole can considered to be a safe and effective front-line therapy to treat patients with hematological malignancies and invasive aspergillosis. Alternatively it could be used as a remedial treatment when other antifungal therapies are ineffective.

Role of a Novel Pyridostigmine Bromide-Phospholipid Nanocomplex in Improving Oral Bioavailability

Qun-you Tan,Jing-qing Zhang,Ni-ni Hu,Guo-dong Liu,Hua-feng Yin,Li Zhang,Hong Wang,Lu-yang Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.3

A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X1, X2, and X3 were 8, 40oC, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and −25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (Tmax) 2 h vs 2 h, the maximum concentration (Cmax) 22.79 μg/mL vs 6.00 μg/mL, and the value of the area under the concentration vs time curve (AUC0-∞) 7128.21 μg·min/mL vs 1772.36 μg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.

Histone Deacetylase Inhibitor Trichostatin A Enhances Antitumor Effects of Docetaxel or Erlotinib in A549 Cell Line

Zhang, Qun-Cheng,Jiang, Shu-Juan,Zhang, Song,Ma, Xiao-Bin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

Analysis on Postoperative Efficacy of Radical Hepatectomy for Patients with Non-HBV/HCV Hepatocellular Carcinoma

Zhang, Zhi-Ming,Zhang, Yu-Mei,Yao, Feng,Yi, Ping,Huang, Shang,Liu, Jian-Yong,Xiang, Bang-De,Yuan, Wei-Ping,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Objective: Patients with hepatocellular carcinoma (HCC) in stage Barcelona Clinic Liver Cancer (BCLC)-A were grouped based on whether they were accompanied with hepatitis B virus (HBV) infection or not so as to explore the clinical characteristics and prognostic conditions of HCC patients with non-HBV/hepatitis C virus (HCV). Materials and Methods: Clinical data of 64 stage BCLC-A HCC patients with non-HBV/HCV infection (observation group) who received radical hepatectomy in the Affiliated Cancer Hospital of Guangxi Medical University from January, 2006 to November, 2014 were retrospectively analyzed and compared with those of 409 stage BCLC-A HCC patients with HBV infection (control group) in corresponding period. Results: The postoperative 1-, 3- and 5-year recurrent rates of the observation group were 25%, 38.6% and 48.8%, with postoperative mean and median disease-free survival time being 49.1 months and 62.0 months, respectively. Additionally, the postoperative 1-, 3- and 5-year survival rates of observation group were 90.1%, 72.7% and 62.0%, with the mean and median survival times being 54.4 months and 70.0 months, respectively. Conclusions: The 1-year recurrent rate is the highest in HCC patients with non-HBV/HCV, and almost half of the patients have recurrence within 1 year, after which the recurrent rate decreases along with the time.

Clinical Value of Dual-phase ¹⁸F-FDG SPECT with Serum Procalcitonin for Identification of Etiology in Tumor Patients with Fever of Unknown Origin

Zhang, Qun,Shan, Chun,Wu, Pei,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Objective: The purpose of the study was to evaluate clinical value of dual-phase $^{18}F$-FDG SPECT with serum procalcitonin (PCT) in identifying cancers in patients with fever of unknown origin (FUO). Methods: PCT test and dual-phase $^{18}F$-FDG SPECT were sequentially performed on 50 consecutive patients with FUO. Two radiologists evaluated all $^{18}F$-FDG SPECT data independently. A consensus was reached if any difference of opinions existed. Final diagnosis was based on a comprehensive analysis of results for the PCT test, dual-phase $^{18}F$-FDG SPECT and bacterial cultivation, regarded as a gold standard. Results: Among 50 patients, 34 demonstrated PCT ${\geq}0.5{\mu}g/L$. Coincidence imaging showed in 37 patients with inflammatory lesions, and 13 with malignancy. Finally, 36 bacterial, 1 fungal and 1 viral infections, as well as 12 cancerous fevers were confirmed by dual-phase $^{18}F$-FDG SPECT with PCT, combined with bacterial cultivation and clinical follow-up. Conclusion: Our study demonstrated that dual-phase $^{18}F$-FDG SPECT in association with PCT could be a valuable tool for diagnosis in tumor patients with FUO.

Elevated Serum Ferritin Levels in Patients with Hematologic Malignancies

Zhang, Xue-Zhong,Su, Ai-Ling,Hu, Ming-Qiu,Zhang, Xiu-Qun,Xu, Yan-Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Purpose: To retrospectively analyze variability and clinical significance of serum ferritin levels in Chinese patients with hematologic malignancies. Materials and Methods: Serum ferritin were measured by radioimmunoassay, using a kit produced by the Beijing Institute of Atomic Energy. Patients with hematologic malignancies, and treated in the Department of Hematology in Nanjing First Hospital and fulfilled study criteria were recruited. Results: Of 473 patients with hematologic malignancies, 262 patients were diagnosed with acute leukemia, 131 with lymphoma and 80 with multiple myeloma. Serum ferritin levels of newly diagnosed and recurrent patients were significantly higher than those entering complete remission stage or in the control group (p<0.001). Conclusions: Serum ferritin lever in patients with hematologic malignancies at early stage and recurrent stage are significantly increased, so that detection and surveillance of changes of serum ferritin could be helpful in assessing conditions and prognosis of this patient cohort.

Influence of Expression Plasmid of Connective Tissue Growth Factor and Tissue Inhibitor of Metalloproteinase-1 shRNA on Hepatic Precancerous Fibrosis in Rats

Zhang, Qun,Shu, Fu-li,Jiang, Yu-Feng,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: In this study, influence caused by expression plasmids of connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) short hairpin RNA (shRNA) on mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII in hepatic tissue with hepatic fibrosis, a precancerous condition, in rats is analyzed. Materials and Methods: To screen and construct shRNA expression plasimid which effectively interferes RNA targets of CTGF and TIMP-1 in rats. 50 cleaning Wistar male rats are allocated randomly at 5 different groups after precancerous fibrosis models and then injection of shRNA expression plasimids. Plasmid psiRNA-GFP-Com (CTGF and TIMP-1 included), psiRNA-GFP-CTGF, psiRNA-GFP-TIMP-1 and psiRNA-DUO-GFPzeo of blank plasmid are injected at group A, B, C and D, respectively, and as model control group that none plasimid is injected at group E. In 2 weeks after last injection, to hepatic tissue at different groups, protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PC III is tested by immunohistochemical method and,mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII is measured by real-time PCR. One-way ANOVA is used to comparison between-groups. Results: Compared with model group, there is no obvious difference of mRNA expression among CTGF,TIMP-1,procol-${\alpha}1$, PC III and of protein expression among CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue at group injected with blank plasmid. Expression quantity of mRNA of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII at group A, B and C decreases, protein expression of CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue is lower, where the inhibition of combination RNA interference group (group A) on procol-${\alpha}1$ mRNA transcription and procol-${\alpha}1$ protein expression is superior to that of single interference group (group B and C) (P<0.01 or P<0.05). Conclusions: RNA interference on CTGF and/or TIMP-1 is obviously a inhibiting factor for mRNA and protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII. Combination RNA interference on genes of CTGF and TIMP-1 is superior to that of single RNA interference, and this could be a contribution for prevention of precancerous condition.

무형문화재의 체험요소가 지각된 가치와 만족 및 행동의도에 미치는 영향: 안동 하회별신굿탈놀이를 대상으로

장췬(Zhang Qun),이형룡(Lee, Hyung-Ryong) 한국관광레저학회 2022 관광레저연구 Vol.34 No.1

Chimerism Evaluation of ‘Hongrou Huyou’, a Grafted Chimera between Citrus changshan-huyou and Citrus unshiu

Min Zhang,Zequn Zhang,Qun Wu,Fuzhi Ke,Jianguo Xu,Siqing Zhao,Gang Wang,Chi Zhang 한국원예학회 2020 원예과학기술지 Vol.38 No.1

Chimeras occur spontaneously or artificially and are valuable in horticultural crop breeding. A new diploid citrus chimera, named ‘Hongrou Huyou’ (abbreviated HH) (Citrus changshan-huyou + C. unshiu), was found during a bud sports investigation in China. The morphology, flesh carotenoid content, and molecular markers were evaluated in HH and the two grafted donors. The results showed that characteristics derived from L2/L3, such as the fruit size, winged leaf, seed, pollen, and rind aroma, were similar to those of C. changshan-huyou (CH), whereas the juice sac and stomatal characteristics originating from L1 were the same as those of the satsuma mandarin. High-performance liquid chromatography analysis of carotenes from the flesh of HH showed that the content was the same as that of the satsuma mandarin, with β-cryptoxanthin producing the main carotenoid spectrum, whereas lutein and violaxanthin were the main carotenoids in CH. Nuclear simple sequence repeat, chloroplast simple sequence repeat, and mitochondrial simple sequence repeat analyses showed that the leaves, outer pericarp (epidermis and flavedo), segment wall, and juice sac of HH contained the nuclear, chloroplast, and mitochondrial genomes of both donors; however, the albedo of HH only contained the genetic material of CH. Thus, HH is confirmed to be a periclinal chimera that consists of L1 from C. unshiu and L2/L3 from CH.

CK2 phosphorylates AP-2α and increases its transcriptional activity

( Kai Qun Ren ),( Shuang Lin Xiang ),( Fang Li He ),( Wen Feng Zhang ),( Xiao Feng Ding ),( Yan Yang Wu ),( Li Ping Yang ),( Jian Lin Zhou ),( Xiang Gao ),( Jian Zhang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.7

Transcription factor AP-2α involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-2α functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit β of protein casein kinase 2 (CK2β) was identified as an interacting protein of AP-2α; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit α of protein casein kinase 2 (CK2α) also exists in the complex. Phosphorylation analysis revealed that AP-2α was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both CK2α and CK2β enhanced the transcription activity of AP-2α; moreover, CK2β increased the stability of AP-2α. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-2α.