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UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

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World Journal of Gastroenterology 2009年第40期15卷 5058-5066页

作者： Christoph Schulz volker heinemann Andreas Schalhorn Nikolas Moosmann Thomas Zwingers Stefan Boeck Clemens Giessen Hans-Joachim Stemmler Department of Haematology & Oncology Ludwig-Maximilians University of MunichCampus Grosshadern Estimate GmbH Konrad-Adenauer-Allee 1

AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.

关键词： Irinotecan Colorectal cancer UGTIA1 Gene polymorphism Toxicity Efficacy Delayed diarrhoea Neutropenia

Translational research in pancreatic ductal adenocarcinoma: current evidence and future concepts

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World Journal of Gastroenterology 2014年第31期20卷 10769-10777页

作者： Stephan Kruger Michael Haas Steffen Ormanns Sibylle Bchmann Jens T Siveke Thomas Kirchner volker heinemann Stefan Boeck Department of Internal Medicine Ⅲ and Comprehensive Cancer Center Klinikum Grosshadern Ludwig-Maximilians-University of Munich Department of Pathology Ludwig-Maximilians-University of Munich Department of Internal Medicine Ⅱ Klinikum Rechts der Isar Technical University of Munich

Pancreatic ductal adenocarcinoma(PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.

关键词： Biomarker Erlotinib Gemcitabine Human equilibrative nucleoside transporter 1 KRAS Nab-paclitaxel p53 Pancreatic cancer SMAD4 SPARC

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行为状态对晚期胰腺癌治疗结局的重要性

继续医学教育 2007年第9期21卷 1-3页

作者： Stefan Boeck Axel Hinke Ralf Wilkowski volker heinemann 德国慕尼黑大学Klinikum Grosshadern医院内三科 81377

1 引言晚期胰腺癌（PC）是一种难以治愈的疾病，没有合适的治疗方法，其生存期仅限于3～4个月。自从Burris等证明Gem疗效优于大剂量5-氟尿嘧啶（5-Fu）后，Gem单一化疗已成标准治疗方案。多项试验始终支持Gem单一化疗可使中位总生存期... 详细信息

1 引言晚期胰腺癌（PC）是一种难以治愈的疾病，没有合适的治疗方法，其生存期仅限于3～4个月。自从Burris等证明Gem疗效优于大剂量5-氟尿嘧啶（5-Fu）后，Gem单一化疗已成标准治疗方案。多项试验始终支持Gem单一化疗可使中位总生存期（OS）达5～7个月，一年生存率达11％～25％的主张。已有研究人员应用联合化疗改善这一疗效。目前为止，与单一Gem相比，只有两种联合化疗方案：Gem联合埃罗替尼（Erlotinib）以及Gem联合卡培他滨（Capecittabine）可显著延长生存期。

关键词：晚期胰腺癌治疗方法行为状态联合化疗方案 5-氟尿嘧啶标准治疗方案总生存期 Gem

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苹果擦伤拉曼光谱无损检测虚拟系统研究

农业工程学报 2005年第3期21卷 130-133页

作者：高晓阳 Paul heinemann Joseph Irudayaraj 甘肃农业大学工学院机电工程系 Department of Agricultural and BiologicalEngineering College of Engineering College of Agricultural Science University Park PA16802 USA

为检测苹果品质并依据擦伤进行分级,研发了一个基于拉曼光谱的实时无损自动检测分类虚拟仪器分级系统样机。采用一台Nicolet傅氏变换拉曼光谱仪进行苹果擦伤光谱检测。测试集和训练集的苹果光谱用WinDAS的典型变量分析(CVA)和主成分分析... 详细信息

为检测苹果品质并依据擦伤进行分级,研发了一个基于拉曼光谱的实时无损自动检测分类虚拟仪器分级系统样机。采用一台Nicolet傅氏变换拉曼光谱仪进行苹果擦伤光谱检测。测试集和训练集的苹果光谱用WinDAS的典型变量分析(CVA)和主成分分析法(PCA)进行分类处理。分析得出的模型经UNEQ分类检验,'马氏平方图'和χ2检验结果该分类模型。其次,应用LabVIEW设计苹果虚拟仪器分级控制系统,并制作了样机。试验结果表明拉曼光谱分析能用于苹果擦伤无损检测和类别确定;虚拟仪器分级系统能对苹果进行准确分级处理。

关键词：苹果拉曼光谱擦伤检测典型变量分析不等离中趋势分类虚拟仪器

Novel Isatin-Schiff Base Cu (II) and Ni(II) Complexes. X-ray Crystal Structure of Bis[3-(4-hexylphenylimino)-1H-indol-2(3H)-one]-dichlorocopper(II) Complex

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Chinese Chemical Letters 2006年第2期17卷 243-246页

作者： Ayse ERCAG Sema Oztürk YILDIRIM Mehmet AKKURT Mahmure Ustün OZGUR Frank W. heinemann Istanbul University Engineering Faculty Chemistry Department Avcilar Istanbul Turkey 34320 Department of Physics Faculty of Arts and Sciences Erciyes University Kayseri Turkey 38039 Yildiz Technical University Faculty of Arts and Sciences Chemistry Department Davutpasa Istanbul Turkey 34210 Institut für Inorganische Chemie UniversittErlangen-Nürnberg Egerlandstrasse 1 D-91058 Erlangen Germany

Schiff base ligand （HL） derived from 4-hexylaniline with isatin （1H-indole-2,3-dione） and its complexes with Cu（Ⅱ）, Ni（Ⅱ） were prepared and characterized by analytical, spectroscopic （IR, UV-Vis, Mass） techniques, electrical conductivity, magnetic and thermal measurements. The crystal and molecular structure of [Cu（HL）2Cl2] was determined by a single-crystal X-ray diffraction study. The molecular structure of the title compound has an inversion center on the Cu atom.

关键词： Mononuclear Cu(Ⅱ) and Ni(Ⅱ) complexes isatin-anilines Schiff base crystal structure.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients

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World Journal of Gastroenterology 2018年第13期24卷 1410-1418页

作者： Matthias Buechter Paul Manka Falko Markus heinemann Monika Lindemann Hideo Andreas Baba Martin Schlattjan Ali Canbay Guido Gerken Alisan Kahraman Department of Gastroenterology and Hepatology University Clinic of Essen Division of Transplantation Immunology and Mucosal Biology King’s CollegeLondon Institute of Transfusion Medicine University Clinic of Essen Institute of Pathology University Clinic of Essen Department of Gastroenterology Hepatology and Infectious Diseases Otto-von-Guericke University

AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our *** The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

关键词： Acute liver failure Autoimmune hepatitis Drug-induced liver injury Triggering factors MELD-score

Environmentally applied nucleic acids and proteins for purposes of engineering changes to genes and other genetic material

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Biosafety and Health 2019年第3期1卷 113-123页

作者： Jack A.heinemann Sophie Walker Centre for Integrated Research in Biosafety and School of Biological Sciences University of CanterburyChristchurchNew Zealand Defence Technology Agency AucklandNew Zealand

In this article we summarize the development of vehicles for penetrating living cells,tissue and organisms with nucleic acids(DNA and RNA)and proteins that damage or repair *** purpose in doing so is to provide an assessment of the potential for these technologies to unintentionally cause harm to human health or the environment or to be retasked with an intention to cause *** new types of biological-molecule-based products are being developed for use in medicine,agriculture and food production or *** first type are genetically modified organisms,such as those that express *** produce molecules and that are difficult to alter at scale after *** of this type are usually evaluated by both food and environmental *** second type comprises topical chemical or physical *** of these are in pre-commercial testing *** applied products use nucleic acids and/or proteins wherein the active biological is transferred by contact,ingestion or *** a survey of the research and patent literature we suggest that chemical formulations and physical manipulations that can be used to ferry nucleic acid and protein cargo into cells,tissues or organisms could be assembled de novo or repurposed from existing commercial products and loaded with proteins and/or nucleic acids designed using publicly available genome *** actives may evade risk assessment and regulatory review because they are often excluded from the category of hazardous chemicals and are actively being excluded as agents of genetic *** emerging gap in oversight could lead to either dual use appropriation or unintended harm to human health or the environment.

关键词： RNAi Genome editing Penetration technologies Ecosystem engineering Transient expression Parental RNAi Topical dsRNA

Intake of Minerals from Food Supplements in a German Population—A Nationwide Survey

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Food and Nutrition Sciences 2015年第2期6卷 205-215页

作者： Janina Willers Michaela heinemann Norman Bitterlich Andreas Hahn Institute of Food Science and Human Nutrition Leibniz University Hannover Germany Medizin & Service GmbH Department of Biostatistics Chemnitz Germany

Introduction: Studies indicate that 17.9% - 60% of adults in Germany and Europe regularly use food supplements. Some reports suggest that their use might be responsible for excessive nutrient intake. The purpose of this survey was to examine the quantitative mineral intakes from food supplements: whether the tolerable upper intake levels (ULs) with supplements alone, or in combination with food was exceeded was checked. Methods: The survey was carried out by the Association for Consumer Research, Nürnberg, Germany. Anonymous data of 1070 supplement users (40.8% men, 59.2% women) aged 18 - 93 years were available. Three groups were examined based on dietary and supplemental mineral intakes: average, middle-high and high intake. Results: The mean number of supplements reported was 1.6 ± 1.1 products in men and 1.5 ± 0.9 products in women. The minerals most frequently consumed were magnesium, followed by calcium, zinc and selenium. The percentage of the supplement users with total intakes greater than the UL was minimal for all minerals. Supplement use in 143 cases increased the likelihood of intakes above the UL only for magnesium. Subjects particularly in the high intake group—as a worst case scenario—had intakes above the UL in the case of calcium (n = 23) and zinc (n = 34). The percentage of subjects taking several products was greater in subjects exceeding the UL than in those below (P < 0.001). Multiple use was seen significantly more often in men than in women (P < 0.01). Conclusions: In this survey, supplement use was generally not associated with excessive intake. Supplement use resulted in intakes above the UL in only a few cases relating to magnesium, calcium and zinc. This applies more often to elderly subjects and particularly to those who already have a high mineral intake from food in the model calculation.

关键词： Food Supplements Minerals Survey Tolerable Upper Intake Level Multiple Uses

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基于LabVIEW的苹果擦伤分级系统设计

农业机械学报 2006年第4期37卷 152-154页

作者：高晓阳 Paul H heinemann Joseph Irudayaraj 甘肃农业大学工学院 Department of Agricultural and Biological Engineering Pennsylvania State UniversityState College.ProfessorPh.D.Doctorate Candidate AdviserPA16802. Department of Agricultural and Biological Engineering Pennsylvania State UniversityState College.Associate ProfessorPh.D.Doctorate Candidate Adviser.

基于美国USDA苹果分级标准研制了苹果擦伤检测分级系统样机。系统依据所研究的苹果表面擦伤拉曼光谱PLS/CVA处理和UNEQ模型分类,通过设计的LabVIEW虚拟仪器控制系统实时完成苹果分级。对48个预先分级的美国红元帅苹果(reddelicious#4167... 详细信息

基于美国USDA苹果分级标准研制了苹果擦伤检测分级系统样机。系统依据所研究的苹果表面擦伤拉曼光谱PLS/CVA处理和UNEQ模型分类,通过设计的LabVIEW虚拟仪器控制系统实时完成苹果分级。对48个预先分级的美国红元帅苹果(reddelicious#4167)分别进行两轮实际分级实验来评估该系统的性能。实验结果表明该分级检测系统对无擦伤、轻擦伤和重擦伤苹果组的分级平均准确率分别为100%、99%、97%。分级系统每分钟可分级苹果3～6个,对运动苹果分级误判率较低,是实施苹果自动检测分级生产线的基本模块。

关键词：苹果分级系统擦伤拉曼光谱虚拟仪器