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21. Comparative analysis of pancreatic cancer stroma in humans and in genetically engineered mouse models

Author

Wanner, Laura, Erkan, Mert (Priv.-Doz. Dr.), and Friess, Helmut (Prof. Dr.)

Subjects
Pancreatic cancer, tumor stroma, extracellular matrix, Medizin und Gesundheit, ddc:610, Pankreaskrebs, Tumorstroma, extrazelluläre Matrix
Abstract

Die Tumor-supportive Rolle des Stromas beim pankreatischen duktalen Adenokarzinom (PDAC) ist umstritten. Der Einfluss der Stromaproliferation auf die Tumorbiologie beim Menschen sowie bei Mausmodellen wurde untersucht. Der Epithelial Stromal Proliferation Index (ESPI) wurde als das Verhältnis der Ki67-Expression von Tumorzellen und pankreatischen Sternzellen definiert. Das Stroma beim humanen PDAC ist nicht einheitlich. Bestimmte Ausprägungen können einen protektiven Effekt haben. Der ESPI ist ein neuer unabhängiger prognostischer Faktor beim PDAC. Zwischen humanem und murinem Stroma bestehen signifikante Unterschiede. The protumorigenic role of the pancreatic ductal adenocarcinoma (PDAC) stroma is disputed. Impact of stromal proliferation on tumor biology in humans and mouse models was analyzed. The Epithelial Stromal Proliferation Index (ESPI) was defined as ratio of Ki67-expression in tumor cells and pancreatic stellate cells. Stroma in human PDAC is not uniform. Certain types can have a protective effect. ESPI is a novel independent prognostic factor in PDAC. There are significant differences between human and murine stroma.

Published
2020

22. Vergleichende Analyse des Tumorstromas beim pankreatischen duktalen Adenokarzinom beim Menschen und bei genetisch modifizierten Mausmodellen

Author

Erkan, Mert (Priv.-Doz. Dr.), Friess, Helmut (Prof. Dr.), Wanner, Laura, Erkan, Mert (Priv.-Doz. Dr.), Friess, Helmut (Prof. Dr.), and Wanner, Laura

Abstract

Die Tumor-supportive Rolle des Stromas beim pankreatischen duktalen Adenokarzinom (PDAC) ist umstritten. Der Einfluss der Stromaproliferation auf die Tumorbiologie beim Menschen sowie bei Mausmodellen wurde untersucht. Der Epithelial Stromal Proliferation Index (ESPI) wurde als das Verhältnis der Ki67-Expression von Tumorzellen und pankreatischen Sternzellen definiert. Das Stroma beim humanen PDAC ist nicht einheitlich. Bestimmte Ausprägungen können einen protektiven Effekt haben. Der ESPI ist ein neuer unabhängiger prognostischer Faktor beim PDAC. Zwischen humanem und murinem Stroma bestehen signifikante Unterschiede., The protumorigenic role of the pancreatic ductal adenocarcinoma (PDAC) stroma is disputed. Impact of stromal proliferation on tumor biology in humans and mouse models was analyzed. The Epithelial Stromal Proliferation Index (ESPI) was defined as ratio of Ki67-expression in tumor cells and pancreatic stellate cells. Stroma in human PDAC is not uniform. Certain types can have a protective effect. ESPI is a novel independent prognostic factor in PDAC. There are significant differences between human and murine stroma.

Published
2020

27. Review of unusual intraoperative and postoperative complications associated with endosseous implant placement.

Author

Wanner, Laura, Manegold-Brauer, Gwendolin, and Ulrich Brauer, Hans

Subjects
DENTAL implants, INFORMATION storage & retrieval systems, MEDICAL databases, MEDLINE, SURGICAL complications, SYSTEMATIC reviews
Abstract

Objectives: Common complications associated with dental implant surgery are well recognized and are usually explained to patients during the process of informed consent. For the general dental practitioner, the periodontist, and the oral and maxillofacial surgeon, it is relevant to also be familiar with less frequent complications. This review gathers unusual complications of this surgical procedure and presents unique complications from single case reports. Method and Materials: Studies were located using systematic searches in Medline and the Cochrane Library electronic databases. Key words included the terms "implant", "dental", "oral", "complication", "unusual", and "rare". References from the relevant articles were also double-checked. The review was limited to English and German language articles, published within the last 15 years. Results: 17 different unusual complications were identified. The majority of studies report five different complications: permanent nerve injury, damage to teeth adjacent to the implant, excessive bleeding resulting in hematoma of the floor of the mouth, mandibular fracture, and displacement of implants into the maxillary sinus. Benign paroxysmal positional vertigo and a plunging ranula were reported sporadically. Another 10 complications were only described once in our literature search. Conclusion: Unusual complications are challenging. It is important for the dental practitioner to be aware of all the possible complications and to recognize them early so that adequate therapy can immediately be ensured. [ABSTRACT FROM AUTHOR]

Published
2013
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32. Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays

Author

Kiris, Erkan, primary, Nuss, Jonathan E., additional, Stanford, Stephanie M., additional, Wanner, Laura M., additional, Cazares, Lisa, additional, Maestre, Michael F., additional, Du, Hao T., additional, Gomba, Glenn Y., additional, Burnett, James C., additional, Gussio, Rick, additional, Bottini, Nunzio, additional, Panchal, Rekha G., additional, Kane, Christopher D., additional, Tessarollo, Lino, additional, and Bavari, Sina, additional

Published
2015
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35. Multi-Faceted Proteomic Characterization of Host Protein Complement of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors

Author

Nuss, Jonathan E., primary, Kehn-Hall, Kylene, additional, Benedict, Ashwini, additional, Costantino, Julie, additional, Ward, Michael, additional, Peyser, Brian D., additional, Retterer, Cary J., additional, Tressler, Lyal E., additional, Wanner, Laura M., additional, McGovern, Hugh F., additional, Zaidi, Anum, additional, Anthony, Scott M., additional, Kota, Krishna P., additional, Bavari, Sina, additional, and Hakami, Ramin M., additional

Published
2014
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36. Supplementary data for article: Opsenica, I.; Burnett, J. C.; Gussio, R.; Opsenica, D. M.; Todorović, N.; Lanteri, C. A.; Sciotti, R. J.; Gettayacamin, M.; Basilico, N.; Taramelli, D.; et al. A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. Falciparum Malaria, and the Ebola Filovirus. Journal of Medicinal Chemistry 2011, 54 (5), 1157–1169. https://doi.org/10.1021/jm100938u

Author

Opsenica, Igor, Burnett, James C., Gussio, Rick, Opsenica, Dejan M., Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan A., Bavari, Sina, Opsenica, Igor, Burnett, James C., Gussio, Rick, Opsenica, Dejan M., Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan A., and Bavari, Sina

Published
2011

37. A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus

Author

Opsenica, Igor, Burnett, James C., Gussio, Rick, Opsenica, Dejan M., Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan A., Bavari, Sina, Opsenica, Igor, Burnett, James C., Gussio, Rick, Opsenica, Dejan M., Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan A., and Bavari, Sina

Abstract

A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.

Published
2011

39. A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus

Author

Opsenica, Igor, primary, Burnett, James C., additional, Gussio, Rick, additional, Opsenica, Dejan, additional, Todorović, Nina, additional, Lanteri, Charlotte A., additional, Sciotti, Richard J., additional, Gettayacamin, Montip, additional, Basilico, Nicoletta, additional, Taramelli, Donatella, additional, Nuss, Jonathan E., additional, Wanner, Laura, additional, Panchal, Rekha G., additional, Šolaja, Bogdan A., additional, and Bavari, Sina, additional

Published
2011
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44. Pharmacophore Refinement Guides the Rational Design of Nanomolar-Range Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease.

Author

Nuss JE, Dong Y, Wanner LM, Ruthel G, Wipf P, Gussio R, Vennerstrom JL, Bavari S, and Burnett JC

Abstract

Botulinum neurotoxins (BoNTs) are the deadliest of microbial toxins. The enzymes' Zinc(II) metalloprotease, referred to as the light chain (LC) component, inhibits acetylcholine release into neuromuscular junctions, resulting in the disease botulism. Currently, no therapies counter BoNT poisoning post-neuronal intoxication; however, it is hypothesized that small molecules may be used to inhibit BoNT LC activity in the neuronal cytosol. Herein, we describe the pharmacophore-based design and chemical synthesis of potent (non-Zinc(II) chelating) small molecule (non-peptidic) inhibitors (SMNPIs) of the BoNT serotype A LC (the most toxic of the BoNT serotype LCs). Specifically, the three-dimensional superimpositions of 2-[4-(4-amidinephenoxy)-phenyl]-indole-6-amidine-based SMNPI regioisomers (K(i) = 0.600 μM (± 0.100 μM)), with a novel lead bis-[3-amide-5-(imidazolino)-phenyl]-terephthalamide (BAIPT)-based SMNPI (K(i) = 8.52 μM (± 0.53 μM)), resulted in a refined 4-zone pharmacophore. The refined model guided the design of BAIPT-based SMNPIs possessing K(i) values = 0.572 μM (± 0.041 μM) and 0.900 μM (± 0.078 μM).

Published
2010
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