Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Publications in this journal

• Article: Pharmacokinetics of a self-microemulsifying drug delivery system of tacrolimus.

  Marietta von Suesskind-Schwendi, Michael Gruber, Didier Touraud, Werner Kunz, Christof Schmid, Stephan W Hirt, Karla Lehle
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  ABSTRACT: This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf(®)) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration-time curve in the SEDDM Tac group and the Prograf(®) group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf(®) group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Prokaryotic expression and refolding of EGFR extracellular domain and generation of phage display human scFv against EGFR.

  Yaqiong Zhou, Juan Zhang, Haizhen Jin, Zhiguo Chen, Qinhang Wu, Weiguang Li, Ming Yue, Chen Luo, Min Wang
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  ABSTRACT: The epidermal growth factor receptor (EGFR), overexpressed in many epithelial tumors, is emerging as an attractive target for cancer therapy. Antibodies to the extracellular region of EGFR play a key role in the development of a mechanistic understanding and cancer therapy. In the present study, we demonstrated for the first time that EGFR-truncated extracellular domain (EGFR-tED), which was expressed in Escherichia coli BL21 (DE3) cells in the form of inclusion bodies, could be purified and renatured. The EGFR-tED protein was purified by gel filtration and Ni-NTA affinity chromatography with high purity (>90%) and refolded by a urea gradient size-exclusion chromatography, which could bind its ligand EGF in a concentration-dependent manner. The renatured EGFR was used for biopanning anti-EGFR scFvs from a human synthetic antibody phage display library. Combined with an additional cell-based ELISA screen, a novel scFv, E10, was obtained with two-fold more potent on the binding to EGFR-bearing tumor cells (the epidermoid carcinoma cell line A431) and the inhibition of A431 cells proliferation than scFv 11F8, suggesting that the E10 has the potential to be developed as therapeutic agents to solid tumors associated with EGFR overexpression.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Metastasis-related miR-185 is a potential prognostic biomarker for hepatocellular carcinoma in early stage.

  Qiaoming Zhi, Junjie Zhu, Xiaobo Guo, Songbing He, Xiaofeng Xue, Jin Zhou, Bo Hu, Hongying Li, Shaoji Chen, Hong Zhao, Yuting Kuang
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  ABSTRACT: We previously reported that miR-185 is associated with hepatocellular carcinoma (HCC) venous metastasis analysed by miRNA-array profile. The aim of this study is to further investigate the clinicopathological significance and prognostic value of miR-185 in early stage HCC. We classified 95 patients with early stage HCC into treated recurrence group (TR) and none treated recurrence group (NTR), and detected the miR-185 expression levels in TR and NTR groups. We found that low miR-185 expression correlated with more tumor recurrence (37/46), while high miR-185 level led to lower recurrence rate (17/49) (P<0.05). There was no direct relationship between miR-185 and clinicopathological features, including age, gender, ALT, AFP, liver cirrhosis, tumor size, tumor encapsulation, tumor differentiation (P>0.05). Kaplan-Meier analysis showed that low miR-185 group had a remarkable lower survival rate and shorter time to recurrence than high miR-185 group (P<0.05). Univariate and multivariate analysis, using Cox's proportional hazards model, also indicated that low miR-185 expression was a sensitive prognostic factor for survival and recurrence in early stage HCC (P<0.05). We upregulated or downregulated miR-185 expression by transfected miR-185 mimics or inhibitor into HCC cell lines, and observed the influence of miR-185 on HCC cells in vitro. Our results manifested that miR-185 could suppress the tumor cell growth and invasive ability (P<0.05). Therefore, miR-185 might be an effective and sensitive biomarker of HCC in early stage, and the upregulation of miR-185 might be considered to be a potentially important molecular treatment strategy for patients with HCC.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Pentoxifylline inhibits melanoma tumor growth and angiogenesis by targeting STAT3 signaling pathway.

  Mohammad Zahid Kamran, Rajiv P Gude
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  ABSTRACT: Pentoxifylline (PTX), a phosphodiesterase inhibitor has been shown to have anti-metastatic or anti-angiogenic activity against many human cancers. However, the underlying mechanisms are unknown. In this study we report that, PTX at sub-toxic doses, can inhibit melanoma tumor growth and angiogenesis by targeting the STAT3 signaling pathway. Despite minimal cytotoxicity against normal cells, PTX suppressed phosphorylation and DNA binding of STAT3 in a dose-dependent manner. Also, PTX inhibited phosphorylation of the upstream kinases JAK1 and JAK2 and increased the expression of pSHP-2 phosphatase. Expression of various STAT3 regulated gene products, such as cylinD1, CDK6, cMyc, BclXL, and VEGF was downregulated following PTX treatment. Tumor microenvironment favours tumor growth and metastasis. PTX alters tumor microenvironment by limiting IL6 secretion and also by disrupting VEGF-VEGFR2 autocrine/paracrine signaling. PTX treatment significantly inhibited tumor growth and angiogenesis in intra-dermal xenograft mouse model in vivo without having any visible toxicity. These findings identified STAT3 signalling as a target of PTX and have thus augmented its potential application in the treatment of melanoma and other cancers.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B.

  Ming-Yi Xu, Ying Qu, Xiao-Fang Jia, Mei-Ling Wang, Heng Liu, Xing-Peng Wang, Li-Jun Zhang, Lun-Gen Lu
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  ABSTRACT: BACKGROUND AND AIM: Because of the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are needed. The aim of this study was to identify such markers by the use of serum proteomics in chronic hepatitis B (CHB). METHODS: Two-dimensional gel electrophoresis (2-DE) was used to identify differentially expressed protein spots in sera from 40 CHB patients [20 with mild fibrosis (S0-S1) and 20 with severe fibrosis (S3-S4)]. Mass spectrometry (MS) based multiple reaction monitoring (MRM) was used to quantify peptide ions of differential protein spots in another set of sera from 86 CHB patients with different liver fibrosis (S0-S4). RESULTS: Seven differentially expressed protein spots were found by 2-DE. Fourteen peptide ions of seven target protein spots were quantified by MS-based MRM. Summed peak areas ratio (SPAR) values of peptide ions from protein spot 1, 4 and 8, identified as apo serum transferrin, complement component C3c and transferrin, were significantly different from non-fibrosis (S0) to fibrosis stage 4. AUROCs of models established by peptide ions (protein spot 1, 4, 8) and model consisting of a combination of all ions were 0.848~0.966 (S2-S4 versus S0-S1) and 0.785~0.875 (S3-S4 versus S0-S2). Only the peptide ions model of transferrin had better sensitivity and specificity for predicting fibrosis stages than did aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forn's index. CONCLUSIONS: Serum peptide ions of transferrin, detected by proteomic MRM, are new and promising biomarkers for staging liver fibrosis in CHB patients.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: The role of inflammatory chemokines in lymphoid neoorganogenesis in breast cancer.

  S K Gantsev, K Umezawa, D V Islamgulov, E K Khusnutdinova, R S Ishmuratova, V Y Frolova, S R Kzyrgalin
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  ABSTRACT: The expression profiling analysis of inflammatory chemokines and their receptors in newly formed lymph nodes in breast cancer was carried out. The analysis revealed the increase in expression of the genes CCL16, XCR1, CYFIP2, TNFSF14 and the reduction in expression of chemokine ligands CXCL5 and CXCL12 in tertiary lymphoid organs. The obtained results allow us to suggest that the process of induction of lymph nodes neogenesis is identical (in its key mechanisms) to the process of lymphoid tissue neogenesis in autoimmune diseases and in some infections, but may have different triggers.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Bioequivalence evaluation of two formulations of pidotimod using a limited sampling strategy.

  Ji-Han Huang, Xiao-Hui Huang, Kun Wang, Jian-Chun Li, Xue-Feng Xie, Chen-Lin Shen, Lu-Jin Li, Qing-Shan Zheng
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  ABSTRACT: The aim of this study was to develop a limited sampling strategy (LSS) to assess the bioequivalence of two formulations of pidotimod. A randomized, two-way, cross-over study was conducted in healthy Chinese volunteers to compare two formulations of pidotimod. A limited sampling model was established using regression models to estimate the pharmacokinetic parameters and assess the bioequivalence of pidotimod. The model was internally validated by the Jack-knife method and graphical methods. The traditional non-compartmental method was also used to analyze the data and compared with LSS method. The results indicate that following oral administration of a single 800mg dose, the plasma AUC0-12h and Cmax of pidotimod can be predicted accurately using only two to four plasma samples. The bioequivalence assessment based on the LSS models provided results very similar to that obtained using all the observed concentration-time data points and indicate that the two pidotimod formulations were bioequivalent. A LSS method for assessing the bioequivalence of pidotimod formulations was established and proved to be applicable and accurate. This LSS method could be considered appropriate for a pidotimod bioequivalence study, providing an inexpensive cost of sampling acquisition and analysis. And the methodology presented here may also be applicable to bioequivalence evaluation of other medications.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Targeted therapies of metastatic breast cancer: Relationships with cancer stem cells.

  Paola Ferrari, Andrea Nicolini, Angelo Carpi
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  ABSTRACT: In the last years, many targeted agents have been developed for metastatic breast cancer (MBC) treatment and are being tested in clinical trials. In spite of this, apart from epidermal growth factor receptor 2 (HER2) positive subset, no significant increase in the median overall survival (OS) has been reported. Similarly to conventional chemo- and radiotherapy, the cancer stem cell theory has been evoked to explain the frustrating results often obtained with this emerging category of drugs. This review examines the results in MBC of the approved targeted therapies or those currently under evaluation in experimental studies or in clinical trials, in the light of their relationships with breast CSCs and of the efforts to circumvent the development of resistance. In the next, there is the principal need to investigate if the effects on CSCs may be used to overcome cancer resistance and it will be opportune to consider whether molecular targeted therapies should be used alone or combined with conventional therapy, or with a different target drug specific for CSCs.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: MiR-223/Ect2/p21 signaling regulates osteosarcoma cell cycle progression and proliferation.

  Jianli Xu, Qi Yao, Yu Hou, Meng Xu, Sheng Liu, Longqiu Yang, Lei Zhang, Hui Xu
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  ABSTRACT: Osteosarcoma is one of the most common tumors. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that miRNAs play important roles in regulating tumor growth. In this study we found that miRNA-223 was downregulated in both osteosarcoma patients' tumor tissues and osteosarcoma cell lines. Overexpression of miRNA-233 greatly inhibited the proliferation of Saos-2 cells. Cell cycle analysis by flow cytometry showed the arrest of cell cycle progression at the G1 phase. Further mechanistic study indicated that Ect2 was directly targeted by miR-223. Downregulation of Ect2 by miR-223 induces the expression of p21, p27 and the phospharylation of retinoblastoma, which are involved in the G1 block. We concluded that miR-223 functions as a tumor suppresser in osteosarcoma and miR-223/Ect2/p21 signaling is an important pathway that regulates the osteosarcoma cell cycle progression and proliferaion.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Nuclear localization of P-glycoprotein is responsible for protection of the nucleus from doxorubicin in the resistant LoVo cell line.

  Witold Szaflarski, Patrycja Sujka-Kordowska, Radosław Januchowski, Karolina Wojtowicz, Małgorzata Andrzejewska, Michał Nowicki, Maciej Zabel
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  ABSTRACT: The high expression of P-glycoprotein (P-gp) belongs to one of the most important factors causing multidrug-resistant (MDR) of cancer cells. P-gp is primarily associated with plasma membrane; however, small fraction of that protein is present in the nuclear envelope. Such phenomenon is observed in cancer cells and may result in the selection of MDR cells as the secondary tumor and/or resistant metastasis that significantly shorten patient survival rate. Here, we confirmed nuclear localization of P-gp in resistant LoVo cells and demonstrated its impact on doxorubicin efflux from the nucleus to cytoplasm. Furthermore, we showed that P-gp located at the nuclear envelope might have a different glycoside chain when compared to the form located in the cytoplasm. It suggests that the glycoside chain plays a role in the intracellular trafficking of P-gp and may decide about the destination place in the cell.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: S1 kills MCF-7/ADR cells more than MCF-7 cells: A protective mechanism of endoplasmic reticulum stress.

  Ting Song, Furong Liang, Zhichao Zhang, Yubo Liu, Hongkun Sheng, Mingzhou Xie
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  ABSTRACT: Drug resistance in chemotherapy for breast cancer is associated with high levels of P-glycoprotein (P-gp) as well as endoplasmic reticulum (ER) stress. In this paper, we aimed to evaluate the efficacy of a pan-BH3 mimetic S1 on drug-resistant MCF-7/ADR cells, and the roles of S1-induced ER stress in cell death. S1 exhibited greater and faster mitochondrial apoptosis in MCF-7/ADR cells than in MCF-7 cells. We demonstrated by Bax/Bak activation and cyrochrome c release that the p-glycprotein had little influence on S1 entering cells and hitting its targets in MCF-7/ADR cells. An IRE1-mediated ER stress response followed by c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) activation was specifically induced by S1 in MCF-7 cells, but not in MCF-7/ADR cells. Coimmunoprecipitation and western blotting analysis determined that ER stress played a protective role in S1-induced apoptosis by triggering Bcl-2 phosphorylation, which grabbed more pro-apoptotic proteins. The synergism effect of ERK inhibitor PD98059 with S1 confirmed the protective role of ER stress. Defective ER stress in MCF-7/ADR cells confers the more sensitivity toward S1.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: A novel all-trans retinoid acid derivatives inhibits the migration of breast cancer cell lines MDA-MB-231 via myosin light chain kinase involving p38-MAPK pathway.

  Bei Wang, Yunwen Yan, Jiali Zhou, Qing Zhou, Shuyu Gui, Yuan Wang
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  ABSTRACT: OBJECTIVE: To explore the effect and its probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) on the migration of human breast cancer MDA-MB-231 cells. METHODS: MTT assay was performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. The effect of ATPR and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, an inhibitor of p38, on the migration of MDA-MB-231 cells were analyzed by wound healing assay. The expression of MLCK and phosphorylation of myosin light chain (MLC), ERK, JNK, p38 proteins were detected by western blot RESULTS: After the cells were treated by ATRA and ATPR, the proliferation and migration of breast cancer MDA-MB-231 cells were inhibited significantly. The IC 50 of ATRA and ATPR is 34.08 μmol/l and 18.06 μmol/l respectively. The relative migration rate of MDA-MB-231 cells treated with ATPR reached 50% at 48 h while the ATRA group is over 90%. The relative migration rate of ML-7 group and SB group had significant decrease compared with control group. The expression level of MLCK and phosphorylation of MLC of breast cancer cells was reduced when the cells were treated by ATPR with 48 h, the phosphorylation of ERK, JNK and p38 in breast cancer also reduced when cells were treated by ATPR with 2 h. In addition, ML-7 (50 μmol/l) could inhibit the phosphorylation of p38 and SB (50 μmol/l) could inhibit the expression of MLCK and phosphorylation of MLC. CONCLUSIONS: ATPR had a better inhibition on the proliferation and the migration of breast cancer MDA-MB-231 cells than ATRA, and its probable mechanism was associated with the down regulation of expression of MLCK and phosphorylation of MLC protein involving p38-MAPK pathway.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: Icotinib, a potent and specific EGFR tyrosine kinase inhibitor, inhibits growth of squamous cell carcinoma cell line A431 through negatively regulating AKT signaling.

  Zhenzhen Gao, Wei Chen, Xiaohua Zhang, Peifen Cai, Xianying Fang, Qiang Xu, Yang Sun, Yanhong Gu
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  ABSTRACT: Icotinib is a potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. In this study, we reported that icotinib had the antitumor activity on human squamous cell carcinoma cell line A431 in vitro. Meanwhile, adhesion to fibronectin and expression of integrin α3 and β1 were significantly reduced in a dose-dependent manner after the treatment of icotinib. Moreover, icotinib induced cell cycle arrested and affected expression of various cell cycle related proteins in squamous cancer cell line A431, whereas it did not cause apoptosis. Furthermore, icotinib remarkably down-regulated phosphorylation of protein kinase B (AKT) though blocking the interaction between 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in A431 cells. Taken together, it is shown that the small molecular compound, icotinib, has an anti-squamous cell carcinoma activity in vitro and its antitumor mechanism is associated with the blockage of the interaction between PDK1 and AKT. These results provide a novel strategy for anti-squamous cell carcinoma therapy.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2013;
• Article: The comparison of chronic hepatitis C treatment outcome between intravenous drug users and non-intravenous drug users.

  K Bojovic, J Simonovic, N Katanic, I Milosevic, I Pesic, D Delic, N Svirtlih, D J Jevtovic
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  ABSTRACT: Despite the fact that the majority of prevalent and incident cases of HCV are associated with intravenous drug use (IVDU), these patients have largely been excluded from HCV care. The aim of this study was to examine the treatment outcome of chronic hepatitis C in IVDUs compared to non-IVDUs. PATIENTS AND METHODS: Patients with chronic hepatitis C (CHC) who initiated and completed combination antiviral therapy with pegilated interferon and ribavirin, at the Hepatology Department of the University Hospital for Infectious and Tropical Diseases in Belgrade, were retrospectively analyzed. The study included a series of 254 patients of which 100 (39.4%) were former IVDU. RESULTS: Sustained virological response (SVR) was recorded in a total of 172 patients (67.7%). The analyses of the favorable treatment outcome, regarding particular viral genotypes, revealed that among those with genotype 1 and/or 4, including patients with genotype 1 recombinants with genotype 3, SVR was achieved in 114 (63.3%), while it was almost equally distributed between subgroups of former IVDU and all others (P=0.079). Among patients infected with HCV genotypes 2 and/or 3 the SVR rate was as high as 86.6%. CONCLUSION: IVDU with CHC infection should be treated with standard combination antiviral therapy for CHC, since the success rate is equal or even better than in non-IVDU patients.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: MicroRNA-21 activates hepatic stellate cells via PTEN/Akt signaling.

  Jun Wei, Lisha Feng, Zhong Li, Guoxiong Xu, Xiaoming Fan
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  ABSTRACT: Activation of hepatic stellate cells is the key event in the liver fibrosis. miRs have been shown to play fundamental role in diverse biological and pathological processes. In the present study, we investigated the fibrogenic role of miR-21 in human hepatic stellate LX-2 cells and explored underlying mechanisms. The results showed that treatment of LX-2 cells with platelet-derived growth factor (PDGF)-BB significantly stimulated α1(I) collagen mRNA synthesis and the protein expression of α-SMA, which are characteristics of activation of hepatic stellate cells and simultaneously increased miR-21 expression. Downregulation of miR-21 expression by transfection of anti-miR-21 into LX-2 cells prevented PDGF-BB-induced LX-2 cell activation. Overexpression of miR-21 expression alone also stimulated LX-2 cell activation, while downregulation of miR-21 expression suppressed LX-2 cell activation. miR-21 also played a role in mRNA expression and activity of matrix metalloproteinase 2 (MMP2) in LX-2 cells. Moreover, overexpression of miR-21 decreased protein expression of PTEN in LX-2 cells, resulting in activation of the Akt. Inhibition of Akt signaling by specific inhibitor LY 294002 blocked miR-21-induced fibrogenic effects in LX-2 cells. In summary, miR-21 is an important mediator in LX-2 cell activation. The fibrogenic effects of miR-21 on LX-2 cell activation are mediated through PTEN/Akt pathway. miR-21 may be a potential novel molecular target for the liver fibrosis.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: The effects of combined treatment with sevoflurane and cisplatin on growth and invasion of human adenocarcinoma cell line A549.

  Hua Liang, Han Bing Wang, Hong Zhen Liu, Xian Jie Wen, Qiao Ling Zhou, Cheng Xiang Yang
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  ABSTRACT: Sevoflurane, an inhalational anesthetic, and cisplatin (DDP)-based chemotherapy have been widely used during lung cancer surgery. However, the effect of sevoflurane on the sensitivity of lung cancer cells to DDP chemotherapy remains unclear. In this study, the effects of combined treatment with sevoflurane and cisplatin on the growth and invasion of human lung adenocarcinoma A549 cell line have been investigated. The underlying mechanism has also been explored. In our experiment, A549 cells were treated with 2.5% sevoflurane, 10μmol/L DDP, or the co-treatment of sevoflurane and DDP for 4h, respectively. Cell proliferation was evaluated by the MTT assay and colony formation assay. Apoptosis was assessed by flow cytometry. Cell invasion was detected by Transwell assay. The expressions of X-linked inhibitor of apoptosis protein (XIAP), Survivin, matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Our results showed that sevoflurane combined with DDP resulted in a more pronounced inhibition of tumor cells growth and invasion as compared with either drug alone. Besides, XIAP, Survivin, MMP-2, and MMP-9 were downregulated more significantly by the co-treatment of the two drugs as compared to sevoflurane treatment or DDP treatment alone. Taken together, the growth-inhibitory and invasion-inhibitory synergy between sevoflurane and DDP in human adenocarcinoma A549 cell line was found in this study. Furthermore, we showed that the growth-inhibitory synergy between sevoflurane and DDP might be associated with the downregulation of XIAP and Survivin, and the invasion-inhibitory synergy between sevoflurane and DDP might be involved in the downregulation of MMP-2 and MMP-9.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: MicroRNA-22 is down-regulated in hepatitis B virus-related hepatocellular carcinoma.

  Cailing Shi, Xudong Xu
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  ABSTRACT: MicroRNAs (miRNAs) are a new class of short noncoding RNAs with post-transcriptional regulation and participate in diverse physiological and pathological processes. MiR-22, ubiquitously expressed in various tissues, plays a functional important role in life processes and is recently proved to involve in many cancers. In present study, we had shown that miR-22 was down-regulated much more obviously in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines as well as in clinical tissues. Cyclin-dependent kinase inhibitor 1A (CDKN1A) was found to be inversely correlated with miR-22 and was identified as a target of miR-22. Overexpression of miR-22 in vitro effectively suppressed CDKN1A expression and inhibited cell proliferation. We conclude that miR-29c may play an important role as a tumor suppressive microRNA in the development and progression of HBV-related HCC by targeting CDKN1A.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: Nanoparticle and liposome formulations of doxycycline: Transport properties through Caco-2 cell line and effects on matrix metalloproteinase secretion.

  Ciğ dem Yücel, Zelihagül Değ Im, Sükran Yilmaz
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  ABSTRACT: Nanoparticle and liposome formulations containing doxycycline or doxycycline and sodium taurocholate (NaTC) were developed in this study. The anticancer effects of doxycycline and penetration properties from those formulations through Caco-2 cell monolayers were investigated. Matrix metalloproteinases (MMPs) have been reported to play a role in the negative prognosis of many malignant tumors including glioblastoma multiforme (GBM). This study is presented to demonstrate that these developed nanoparticle and liposome formulations of doxycycline are capable of inhibiting MMP-2 release from cultured Caco-2 cells. In this study, Caco-2 cells were used as model cell cultures. A MTT test was performed to determine the effect of doxycycline on the viability of Caco-2 cells. Doxycycline nanoparticles were prepared using emulsion polymerization and doxycycline liposomes were prepared using the dry film hydration method. Transport studies of doxycycline through Caco-2 cells were investigated. MMP-2 was found to be inhibited more with doxycycline if NaTC is present in the formulation. NaTC was also found to be useful to increase penetration due to the inhibition of efflux by interacting with p-glycoproteins, in addition to the penetration enhancing effect as a result of opening tight junctions. These developed formulations were proposed to use for the treatment of tumors and GBM.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection.

  Saber A Sakr, Gamal A Badrah, Rania A Sheir
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  ABSTRACT: Hepatitis C is an infectious disease affecting the liver. Chronic infection can progress fibrosis and cirrhosis, liver failure or liver cancer. Helicobacter pylori (H. pylori) is a spiral bacterium infects the stomach of more than 50% of the human population worldwide. H. pylori DNA has been identified in human livers and has been implicated in chronic liver disease and liver cancer. The present work was aimed to study the histological and histochemical alterations in liver of HCV patients with or without H. pylori infection. Immunohistochemical detection of H. pylori showed positive reactivity in 62 biopsies out of 100 biopsies (38% HCV patients and 62% HCV patients coinfected with H. pylori). Histological examination of liver of HCV patients showed microvesicular and macrovesicular steatosis, lymphocytic infiltrations, fibrosis and cirrhosis. Cirrhotic nodules and impairment of hepatic parenchyma were common in HCV patients coinfected with H. pylori. HCV patients coinfected with H. pylori recorded higher NIC score and pronounced fibrosis stages than HCV patients. Glycogen and total proteins decreased in hepatocytes and cirrhotic nodules in HCV patients. Such decrease was marked in liver of HCV patients coinfected with H. pylori. So it is recommended to perform a complete analysis for H. pylori in HCV patients suggesting that it will help in therapy of this disease.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;
• Article: Native human interferon-α is a strong inductor of endogenous cytokines involved in the suppression of procollagen type I.

  G Santak, M Santak, D Forčić
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  ABSTRACT: Native human interferon-α (nHuIFN-α) has a stronger reductive effect on procollagen type I mRNA expression than recombinant human interferon-α (rHuIFN-α). It is partially due to the additive activity of interleukin-1β (IL-1β), which is present in small concentrations in nHuIFN-α. Here, we show that the reductive effect is also the result of the endogenous cytokines induced by the activity of nHuIFN-α. In the culture of MRC5 fibroblasts, we have further found that nHuIFN-α induces endogenous interferons in higher amounts than rHuIFN-α, measured with PCR. That is more pronounced when interferon-γ (IFN-γ) is measured. This result puts a new light on IFN-γ activity in the nHuIFN-α treatment because its role was neglected due to the loss of its activity during the nHuIFN-α preparation process. The findings lead to the conclusion that endogenous cytokines play a significant role in the nHuIFN-α -mediated reduction of procollagen type I mRNA and are therefore an important factor in potential therapeutic usage.
  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2013;