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Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter,open-label,phase Ⅲ study

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Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 607-616页

作者： Meng-Su Zeng Hui-Yi Ye Liang Guo Wei-Jun Peng Jian-Ping Lu Gao-Jun Teng Josy Breuer Yi Huan Ping Li Jian-Rong Xu Chang-Hong Liang Department of Radiology Zhongshan HospitalFudan UniversityNo.180 Fenglin Road Departmentof Radiology General Hospital of PLA Department of Radiology First Affiliated HospitalSoochowUniversity Department of Radiology Cancer HospitalFudan University Department of Radiology Changhai HospitalSecond Military MedicalUniversity Department of Radiology Zhongda HospitalSoutheast University bayer HealthCare bayer Schering pharma AG Department of Radiology Xijing HospitalFourth Military MedicalUniversity bayer HealthCare CompanyLtd Department of Radiology RenjiHospitalShanghai Jiaotong University Department of Radiology Guangdong General Hospital

BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)***,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy *** study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese ***:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR *** imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded *** primary efficacy endpoint was sensitivity in lesion ***:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than ***-EOB-DTPA improved diagnostic accuracy in lesion ***:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 ***-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

关键词： gadoxetate disodium magnetic resonance imaging liver focal liver lesions

布地奈德缓释干粉吸入剂的制备及乳糖用量的影响

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药学学报 2015年第9期50卷 1180-1185页

作者：梁铮林王秀花倪睿张兰 Uwe Muenster 毛世瑞沈阳药科大学药学院辽宁沈阳110016 Global Chemical and pharmaceutical Development Research Center Wuppertal-Aprath Bayer Pharma AG

采用高压匀质联合喷雾干燥法制备载有布地奈德的壳聚糖微粒并考察其体外释放行为,用涡旋混合器使之与乳糖混合,以药物回收率和含量均匀度为指标考察混合速度与混合时间的影响,以药物回收率、含量均匀度、粉末流动性和体外沉积分布为指... 详细信息

采用高压匀质联合喷雾干燥法制备载有布地奈德的壳聚糖微粒并考察其体外释放行为,用涡旋混合器使之与乳糖混合,以药物回收率和含量均匀度为指标考察混合速度与混合时间的影响,以药物回收率、含量均匀度、粉末流动性和体外沉积分布为指标考察乳糖用量的影响。制得微粒具有一定的体外缓释效果,可吸入组分百分比为46.0%,但流动性较差,加入10倍乳糖进行混合后,药物回收率高达96.5%,药物含量的相对标准偏差为2.5%,流动性较好,可吸入组分百分比提高至59.6%。结果表明,采用涡旋混合器可制备回收率及含量均匀度均较高的布地奈德缓释干粉吸入剂,处方具有较好的流动性,适于肺部吸入。

关键词：布地奈德壳聚糖乳糖涡旋混合器体外沉积

Epigenetics and pancreatic cancer:Pathophysiology and novel treatment aspects

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World Journal of Gastroenterology 2014年第24期20卷 7830-7848页

作者： Daniel Neureiter Tarkan Jger Matthias Ocker Tobias Kiesslich Institute of Pathology Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Department of Surgery Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Experimental Medicine Oncology Bayer Pharma AG13342 BerlinGermany Department of Internal Medicine I Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Institute of Physiology and Pathophysiology Paracelsus Medical University5020 SalzburgAustria

An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16ink4a, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

关键词： Pancreatic cancer Epigenetics DNA methylation Histone modification microRNA Targeted therapy Epithelial-mesenchymal transition

钆对比剂向健康鼠脑脊液的渗透及其分布:一种进入脑组织的潜在途径

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国际医学放射学杂志 2017年第5期 606-607页

作者： G.Jost T.Frenzel J.Lohrke D.C.Lenhard S.Naganawa H.Pietsch 华蓓 MR and CT Contrast Media Research Bayer Pharma AG

摘要目的有研究报道注射多种钆对比剂(GBCA)后,部分(并非全部)GBCA可使特定脑区非增强MRI上显示为高信号。本临床前实验系统性评估GBCA进入脑组织的一条

关键词：脑组织 CSF 对比剂健康鼠脑脊液

Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

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Signal Transduction and Targeted Therapy 2018年第1期3卷 237-245页

作者： Nicholas LSyn Pei Li Lim Li Ren Kong Lingzhi Wang Andrea Li-Ann Wong Chwee Ming Lim Thomas Kwok Seng Loh Gerhard Siemeister Boon Cher Goh Wen-Son Hsieh Cancer Science Institute of Singapore National University of SingaporeSingaporeSingapore Department of Haematology-Oncology National University Cancer InstituteSingaporeSingapore Department of pharmacology Yong Loo Lin School of MedicineNational University Health SystemSingaporeSingapore Department of Otolaryngology-Head and Neck Surgery National University Health SystemSingaporeSingapore Drug Discovery TRG OncologyBayer Pharma AGBerlinGermany

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human ***,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)*** of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/*** anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic *** enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug *** roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)*** administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the *** summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.

关键词： cisplatin nasopharyngeal doses

啮齿类动物应用钆对比剂后钆在皮肤长期滞留的研究

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国际医学放射学杂志 2009年第4期32卷 412-412页

作者： H.Pietsch P.Lengsfeld G.Jost T.Frenzel J.Hütter M.A.Sieber 王萍 bayer Schering pharma AG Contrast Media Research

一些文献提示含钆对比剂（GBCA）与一种罕见但严重的疾病——肾源性系统性纤维化（NSF）有潜在联系。本研究目的是确定大鼠注射GBCA后皮肤组织钆的清除时间。将目前市场应用的7种含钆对比剂以2．5mmol／kg的剂量连续5d注入Han—Wistar... 详细信息

一些文献提示含钆对比剂（GBCA）与一种罕见但严重的疾病——肾源性系统性纤维化（NSF）有潜在联系。本研究目的是确定大鼠注射GBCA后皮肤组织钆的清除时间。将目前市场应用的7种含钆对比剂以2．5mmol／kg的剂量连续5d注入Han—Wistar大鼠尾静脉中，于最后1次注射后1年内的不同时间点．取皮肤活检应用电感耦合等离子体质谱（ICP—MS）进行钆的浓度测定。皮肤内大部分注射的钆在2个月左右的时间内排除。

关键词：含钆对比剂钆存留肾源性系统性纤维化稳定性

比较不同类型的钆对比剂在体内引发肾源性系统性纤维化样病变的临床前期研究

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国际医学放射学杂志 2008年第A6期31卷 522-522页

作者： M.A.Sieber P.Lengsfeld T.Frenzel S.Golfier H.Schmitt-Willich F.Siegmund 蒋新华 TRG Diagnostic Imaging Bayer Schering Pharma AG 13353 Berlin Germany.

最近的研究表明,肾源性系统性纤维化(NSF)与以钆为基础的对比剂(GBCAs)相关,特别是与其稳定性相关。

关键词：钆肾源性系统性纤维化对比剂稳定-周期

A drospirenone-containing oral contraceptive improved bleeding pattern and personal satisfaction in 914 women from Jordan, Lebanon and Syria

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Health 2013年第7期5卷 39-44页

作者： Ramzi Finan Abeer Wasfi Annab Salwa Abdalla Farid Bedran Mazen El-Zibdeh Lina Shahen Christoph Gerlinger Erich Solomayer Kubilay Ertan Jan Endrikat Universite St.Joseph Hotel Dieu de FranceBeirutLebanon 2.Al Amal Maternity HospitalAmmanJordan 3.Private Clinic—Al-ShahBandar SquareDamascusSyria 4.Serhal Hospital-RabiehBeirutLebanon 5.Islamic HospitalAmmanJordan 6.Private Clinic—Al-Enshaat-Ragheb Al-Jamali StreetHomsSyria 7.Bayer HealtcareBayer AGBerlinGermany Department of OB/GYN Universitatskliniken des SaarlandesHomburg/SaarGermany 9.Department of OB/GYNLeverkusen Municipal HospitalLeverkusenGermany

Aim: We assessed bleeding pattern, tolerance and patient satisfaction of an oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol (DRSP/EE) under real-life conditions. Study Design: We performed a multicenter, prospective, 6-cycle, observational study in Canada, Europe and the Middle East. Detailed analyses of the three Middle East countries, Jordan, Lebanon andSyriawere presented here. The efficacy variables included an assessment of bleeding patterns, premenstrual symptoms of water retention and patient satisfaction, as determined by a visual analogue scale. Results: A total of 914 women were enrolled. The percentage of women with intermenstrual bleeding decreased from 37.4%, 48.7% and 32.2% at baseline to 9.7%, 6.1% and 10.9% at the end of cycle6 inJordan, Lebanon and Syria, respectively (creased sharply in all three countries (p Amenorrhea decreased significantly in Lebanon and Syria (p < 0.005). In addition, signs of water retention like abdominal bloating, breast tenderness and swelling of extremities decreased significantly over the course of 6 treatment cycles (p < 0.001). Patient satisfaction increased for all investigated items. Upon completion of the study, 82.7% of women answered “Yes” to continue treatment with this oral contraceptive. Conclusion: The oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol has beneficial effects on bleeding pattern, symptoms of water retention and patient satisfaction.

关键词： Bleeding Pattern Tolerance Drospirenone Oral Contraception