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Full-Text Articles in Medicine and Health Sciences

Metabotropic Glutamate Receptor-1 As A Novel Target For The Antiangiogenic Treatment Of Breast Cancer, Cecilia L. Speyer, Ali H. Hachem, Ali A. Assi, Jennifer S. Johnson, John Austin Devries, David H. Gorski Mar 2014

Metabotropic Glutamate Receptor-1 As A Novel Target For The Antiangiogenic Treatment Of Breast Cancer, Cecilia L. Speyer, Ali H. Hachem, Ali A. Assi, Jennifer S. Johnson, John Austin Devries, David H. Gorski

Department of Surgery

Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. In addition to cancer cells, brain endothelial cells express mGluR1. In light of these studies, and because angiogenesis is both a prognostic indicator in cancer correlating with a poorer …


Cone Beam Computertomography (Cbct) In Interventional Chest Medicine – High Feasibility For Endobronchial Real Time Navigation, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Thomas Vogl, J. Francis Turner, Robert Browning, Bernd Linsmeier, Haidong Huang, Qiang Li, Kaid Darwiche, Lutz Freitag, Michael Simoff, Ioannis Kioumis, Konstantinos Zarogoulidis, Johannes Brachmann Mar 2014

Cone Beam Computertomography (Cbct) In Interventional Chest Medicine – High Feasibility For Endobronchial Real Time Navigation, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Thomas Vogl, J. Francis Turner, Robert Browning, Bernd Linsmeier, Haidong Huang, Qiang Li, Kaid Darwiche, Lutz Freitag, Michael Simoff, Ioannis Kioumis, Konstantinos Zarogoulidis, Johannes Brachmann

Internal Medicine Faculty Publications

Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT)-guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules …


Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi Mar 2014

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …


Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske Feb 2014

Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske

Center for Molecular Medicine and Genetics

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and …


Radiation Exposure Of Patients By Cone Beam Ct During Endobronchial Navigation - A Phantom Study, Wolfgang Hohenforst-Schmidt, Rosemarie Banckwitz, Paul Zarogoulidis, Thomas Vogl, Kaid Darwiche, Eugene Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Lutz Freitag, J. Francis Turner, Patrick Le Pivert, Lonny Yarmus, Konstantinos Zarogoulidis, Johannes Brachmann Feb 2014

Radiation Exposure Of Patients By Cone Beam Ct During Endobronchial Navigation - A Phantom Study, Wolfgang Hohenforst-Schmidt, Rosemarie Banckwitz, Paul Zarogoulidis, Thomas Vogl, Kaid Darwiche, Eugene Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Lutz Freitag, J. Francis Turner, Patrick Le Pivert, Lonny Yarmus, Konstantinos Zarogoulidis, Johannes Brachmann

Internal Medicine Faculty Publications

Rationale: Cone Beam Computed Tomography imaging has become increasingly important in many fields of interventional therapies. Objective: Lung navigation study which is an uncommon soft tissue approach. Methods: As no effective organ radiation dose levels were available for this kind of Cone Beam Computed Tomography application we simulated in our DynaCT (Siemens AG, Forchheim, Germany) suite 2 measurements including 3D acquisition and again for 3D acquisition and 4 endobronchial navigation maneuvers under fluoroscopy towards a nodule after the 8th segmentation in the right upper lobe over a total period of 20 minutes (min). These figures reflect the average complexity and …


Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski Jan 2014

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …


Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou Jan 2014

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …


Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell Jan 2014

Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell

Wayne State University Dissertations

Senescence is a permanent withdrawal from cell cycle that occurs naturally in cells in response to the shortening of telomeres. This natural "clock" serves to limit the number of cell divisions and therefore protects the cell from potentially carcinogenic mutations. However, senescence also occurs in response to external stresses to the cell, which is known as induced senescence. This study compares the mechanisms of natural senescence, a response to the shortening of telomeres during replication, with induced senescence by using various drugs to induce senescence: 5-aza-2-deoxycytidine (a demethylating agent), Adriamycin (a chemotherapeutic drug), and H2O2 (an agent causing oxidative stress). …


Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt Jan 2014

Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt

Wayne State University Dissertations

The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …


Tmprss2-Erg Regulation Of Androgen Biosynthetic Enzyme Expression, Dht Synthesis, And Androgen Receptor Activation In Prostate Cancer, Katelyn Ann Powell Jan 2014

Tmprss2-Erg Regulation Of Androgen Biosynthetic Enzyme Expression, Dht Synthesis, And Androgen Receptor Activation In Prostate Cancer, Katelyn Ann Powell

Wayne State University Dissertations

Intratumoral androgen synthesis in prostate cancer (PCa) contributes to the development of castration-resistant prostate cancer (CRPC). Several enzymes responsible for androgen biosynthesis have been shown to be overexpressed in CRPC, thus, contributing to CRPC in a castrated environment. Although intratumoral androgen synthesis is thought to contribute to the development and progression of CRPC, currently little is known regarding the regulation of androgen biosynthetic enzyme gene expression in PCa. The TMPRSS2-ERG transcription factor has been shown to be present in primary PCa tumors as well as CRPC tumors. The hypothesis was investigated that TMPRSS2-ERG fusions regulate androgen biosynthetic enzyme (ABE) gene …


Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden Jan 2014

Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden

Wayne State University Dissertations

Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment …