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M E Bembenek

Kelly L Damm-Ganamet, Scott D Bembenek, Jennifer W Venable, Glenda G Castro, Lieve Mangelschots, Daniëlle C G Peeters, Heather M Mcallister, James P Edwards, Daniel Disepio, Taraneh Mirzadegan
Here, we report a high-throughput virtual screening (HTVS) study using phosphoinositide 3-kinase (both PI3Kγ and PI3Kδ). Our initial HTVS results of the Janssen corporate database identified small focused libraries with hit rates at 50% inhibition showing a 50-fold increase over those from a HTS (high-throughput screen). Further, applying constraints based on "chemically intuitive" hydrogen bonds and/or positional requirements resulted in a substantial improvement in the hit rates (versus no constraints) and reduced docking time...
May 12, 2016: Journal of Medicinal Chemistry
Bi-Chang Chen, Wesley R Legant, Kai Wang, Lin Shao, Daniel E Milkie, Michael W Davidson, Chris Janetopoulos, Xufeng S Wu, John A Hammer, Zhe Liu, Brian P English, Yuko Mimori-Kiyosue, Daniel P Romero, Alex T Ritter, Jennifer Lippincott-Schwartz, Lillian Fritz-Laylin, R Dyche Mullins, Diana M Mitchell, Joshua N Bembenek, Anne-Cecile Reymann, Ralph Böhme, Stephan W Grill, Jennifer T Wang, Geraldine Seydoux, U Serdar Tulu, Daniel P Kiehart, Eric Betzig
Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster...
October 24, 2014: Science
Mark D Rosen, Hariharan Venkatesan, Hillary M Peltier, Scott D Bembenek, Kimon C Kanelakis, Lucy X Zhao, Barry E Leonard, Frances M Hocutt, Xiaodong Wu, Heather L Palomino, Theresa I Brondstetter, Peter V Haugh, Laurence Cagnon, Wen Yan, Lisa A Liotta, Andrew Young, Tara Mirzadegan, Nigel P Shankley, Terrance D Barrett, Michael H Rabinowitz
HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). Certain benzimidazole-2-pyrazole carboxylates were discovered to be PHD2 inhibitors using ligand- and structure-based methods and found to be potent, orally efficacious stimulators of erythropoietin secretion in vivo.
December 9, 2010: ACS Medicinal Chemistry Letters
Ahmed A M Mohamed, Qiushi Wang, Jadwiga Bembenek, Naoyuki Ichihara, Susumu Hiragaki, Takeshi Suzuki, Makio Takeda
Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release...
2014: PloS One
R T Grundmann, A H Hölscher, A Bembenek, E Bollschweiler, O Drognitz, S Feuerbach, I Gastinger, P Hermanek, U T Hopt, M Hünerbein, G Illerhaus, T Junginger, M Kraus, A Meining, S Merkel, H J Meyer, S P Mönig, P Piso, J Roder, C Rödel, A Tannapfel, C Wittekind, G Woeste
AIM: This review comments on the diagnosis and treatment of gastric cancer in the classical meaning--excluding adenocarcinoma of the -oesophagogastric junction. Algorithms of diagnosis and care with respect to tumour stage are presented. PREOPERATIVE DIAGNOSIS: Besides oesophagogastroduodenoscopy, endoscopic ultrasonography is necessary for the accurate diagnosis of T categories and as a selection criterion for neoadjuvant chemotherapy. Computed tomography is recommended for preoperative evaluation of tumours > T1, laparoscopy has become an effective stag-ing tool in T3 and T4 tumours avoiding unnecessary laparotomies and improving the detection of small -liver and peritoneal metastases...
August 2009: Zentralblatt Für Chirurgie
S Gretschel, P Warnick, A Bembenek, S Dresel, S Koswig, A String, M Hünerbein, P M Schlag
AIM: Although 15-25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB. METHODS: Forty patients with anal cancer underwent 1 ml Tc(99m)-Nanocolloid injection in four sites around the tumour...
August 2008: European Journal of Surgical Oncology
Andreas E Bembenek, Robert Rosenberg, Elke Wagler, Stephan Gretschel, Andreas Sendler, Joerg-Ruediger Siewert, Jörg Nährig, Helmut Witzigmann, Johann Hauss, Christian Knorr, Arno Dimmler, Jörn Gröne, Heinz-Johannes Buhr, Jörg Haier, Hermann Herbst, Juergen Tepel, Bence Siphos, Axel Kleespies, Alfred Koenigsrainer, Nikolas H Stoecklein, Olaf Horstmann, Robert Grützmann, Andreas Imdahl, Daniel Svoboda, Christian Wittekind, Wolfgang Schneider, Klaus-Dieter Wernecke, Peter M Schlag
INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor...
June 2007: Annals of Surgery
Stephan Gretschel, Andreas Bembenek, Michael Hünerbein, Stefan Dresel, Wolfgang Schneider, Peter M Schlag
BACKGROUND: The clinical impact of sentinel lymph node biopsy (SLNB) in gastric cancer is controversial. We performed a prospective trial to compare different methods: radiocolloid method (RM), dye method (DM), and both methods simultaneously (dual method, or DUM) for reliability and therapeutic consequences. METHODS: RM and DM were applied in 35 gastric cancer patients. After endoscopic peritumoral injection of (99m)Tc-colloid and Patent Blue V, the positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs microscopically examined by hematoxylin and eosin, step sections, and immunohistochemistry...
July 2007: Annals of Surgical Oncology
A Bembenek, J Fischer, H Albrecht, E Kemnitz, S Gretschel, U Schneider, S Dresel, P M Schlag
BACKGROUND: The evidence on which to base guidelines for sentinel lymph node biopsy (SLNB) in breast cancer is still limited. In order to facilitate the further implementation of renewed guidelines, we evaluated patient- and disease-specific factors for their impact on the results of SLNB. MATERIALS AND METHODS: Prospective data acquisition from patients undergoing surgery for primary invasive breast cancer was performed. All patients underwent SLNB using the radiocolloid or the combined technique...
February 2007: World Journal of Surgery
Andreas Bembenek, Ulrike Schneider, Stephan Gretschel, Joerg Fischer, Peter M Schlag
About 20% to 30% of colon cancer patients classified as node negative by routine hematoxylin-eosin (H&E) staining are found to have micrometastases (MM) or isolated tumor cells (ITC) in sentinel lymph nodes (SLNs) if analyzed by step sections and immunohistochemistry (IHC). Whether SLNs are in this respect representative for all lymph nodes was addressed in this study. SLNs were identified using the intraoperative blue dye detection technique. If all lymph nodes (SLNs and non-SLNs) of a patient were negative by routine H&E staining, they were step-sectioned and analyzed by IHC using pancytokeratin antibodies...
September 2005: World Journal of Surgery
S Gretschel, A Bembenek, Ch Ulmer, M Hünerbein, J Markwardt, U Schneider, P M Schlag
AIMS: The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. METHODS: Thirty four patients with stage I-IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of (99m)Tc-colloid, and 19 patients were injected of Patent blue V...
May 2005: European Journal of Surgical Oncology
A Bembenek, S Gretschel, C Ulmer, P M Schlag
Lymph node status as an important prognostic factor in colon and rectal cancer is affected by the selection and number of lymph nodes examined and by the quality of histopathological assessment. The multitude of influences is accompanied by an elevated risk of quality alterations. Sentinel lymph node biopsy (SLNB) is currently under investigation for its value in improving determination of the nodal status. Worldwide, the data of 800 to 1000 patients from about 20 relatively small studies are available that focus rather on colon than rectal cancer patients...
August 2004: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
Michael E Bembenek, Stephen Schmidt, Ping Li, Jennifer Morawiak, Andrea Prack, Sadhana Jain, Rebecca Roy, Thomas Parsons, Linda Chee
We have characterized a recombinantly expressed N-terminally tagged GST fusion of the tyrosine kinase domain of human EphB3. The EphB3 kinase domain was shown to phosphorylate a group of synthetic tyrosine-containing peptides derived from a proprietary biotinylated kinase-biased peptide substrate library. In addition, the enzyme activity was stimulated by the divalent cation, manganese, and inhibited by addition of magnesium. The most active tyrosine-containing peptide, a biotinylated 49-mer, displayed saturation kinetics with an apparent K(m) of approximately 0...
August 2003: Assay and Drug Development Technologies
P M Schlag, U Liebeskind, A Bembenek, W Slisow, T Benhidjeb, C Kettelhack, P U Tunn
Advances in surgical tumor therapy are founded on a very close interaction between different surgical subspecialties as well as the inclusion of surgical into modern multimodality treatment concepts. The ongoing development of surgical techniques, e.g. microsurgical flap transfers or pouch reconstructions of intestinal reservoirs, has increasingly enabled organ- and function-preserving surgery. In addition, new materials (e.g. modular tumor endoprosthesis) has supported this development. The broad application of the sentinel node technique in melanoma and breast cancer and also in gastrointestinal tract cancers opens new concepts of diagnosis and therapy for lymphatic metastasized tumors...
August 2002: Onkologie
J Wciórka, M Anczewska, A Bembenek, M Gołebiewska, A Hochlewicz, K Nurowska, E Schaeffer, J Skowrońska, I Stanikowska, K Tarczyńska
AIM: The aim of the study was an evaluation of validity measures of the CASS (Clinical Assessment of Schizophrenic Syndromes)--a new multi-purpose and multi-level clinical diagnostic instrument consisting of a diagnostic questionnaire (CASS-D) allowing to analyze a diagnosis of schizophrenia according to DSM-IV and ICD-10 criteria as well as of three rating scales designed for description and intensity evaluation of schizophrenic syndromes on the global (CASS-G), dimensional (CASS-P, a profile of 13 basic dimensions) or symptomatological (CASS-S, a set of 31 symptoms) level...
March 2000: Psychiatria Polska
J Wciórka, M Anczewska, A Bembenek, M Gołebiewska, A Hochlewicz, K Nurowska, E Schaeffer, J Skowrońska, I Stanikowska, K Tarczyńska
UNLABELLED: The CASS (Clinical Assessment of Schizophrenic Syndromes) is a new multi-purpose and multi-level clinical diagnostic instrument consisting of a diagnostic questionnaire (CASS-D) allowing for analysis of a diagnosis of schizophrenia according to DSM-IV and ICD-10 criteria, as well as of three rating scales designed for description and intensity evaluation of schizophrenic syndromes on the global (CASS-G), dimensional (CASS-P, a profile of 13 basic dimensions) or symptomatological (CASS-S, a set of 31 symptoms) level...
March 2000: Psychiatria Polska
P M Schlag, A Bembenek
The promising results of various studies applying different methods of SN biopsy in heterogeneous patient subpopulations, show that sentinel lymph node biopsy is a reliable and minimally invasive method for the determination of the nodal status in breast cancer patients. While multicenter studies for the evaluation of the method's accuracy are still ongoing, future indications and contraindications are discussed. Based on our own experience, we try to give an actual overview of the potentials and problems of sentinel node biopsy in breast cancer...
2000: Recent Results in Cancer Research
A Bembenek, T Reuhl, J Markwardt, U Schneider, P M Schlag
During the last years, the efficacy and reliability of the sentinel lymph node biopsy (snb) as a minimal invasive diagnostic procedure for the nodal status has been intensively evaluated. After the widespread clinical use in the staging of melanoma patients the snb is currently introduced in the clinical management of breast cancer patients. We present our experience with this method during 3, 5 years and discuss its potential and pitfalls. From 11/95 to 3/99 we performed sentinel node detection in 146 patients with breast cancer stage I to III, consisting of 127 patients with pT1/2-tumors and 19 patients with pT3/4-tumors...
1999: Swiss Surgery, Schweizer Chirurgie, Chirurgie Suisse, Chirurgia Svizzera
S T Safrany, J J Caffrey, X Yang, M E Bembenek, M B Moyer, W A Burkhart, S B Shears
Diphosphoinositol pentakisphosphate (PP-InsP5 or 'InsP7') and bisdiphosphoinositol tetrakisphosphate ([PP]2-InsP4 or 'InsP8') are the most highly phosphorylated members of the inositol-based cell signaling family. We have purified a rat hepatic diphosphoinositol polyphosphate phosphohydrolase (DIPP) that cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (Km = 340 nM) and [PP]2-InsP4 (Km = 34 nM). Inositol hexakisphophate (InsP6) was not a substrate, but it inhibited metabolism of both [PP]2-InsP4 and PP-InsP5 (IC50 = 0...
November 16, 1998: EMBO Journal
C F Huang, S M Voglmaier, M E Bembenek, A Saiardi, S H Snyder
Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) were recently identified as inositol phosphates which possess pyrophosphate bonds. The molecular mechanisms that regulate the cellular levels of these compounds are not yet characterized. To pursue this question, we have previously purified an inositol hexakisphosphate (IP6) kinase from rat brain supernatants [Voglmaier, S. M., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 4305-4310]. We now report the identification and purification of another novel kinase, diphosphoinositol pentakisphosphate (PP-IP5) kinase, which uses PP-IP5 as a substrate to form bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) in soluble fractions of rat forebrain...
October 20, 1998: Biochemistry
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