Medicine and Health Sciences Commons^™

Breast Cancer And Colorectal Cancer Screening In Arab Americans From 2021-2023, Nicole Oska, Hasti Nema, Deni Peterson, Kendall Brothers, Mohammed Najeeb Al Hallek

Medical Student Research Symposium

Breast Cancer and Colorectal Cancer Screening in Arab Americans from 2021-2023

Nicole Oska¹, Hasti Nema¹, Deni Peterson¹, Kendall Brothers¹, Mohammed Najeeb Al Hallak^1,2

¹Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA; ²Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

Introduction:

Breast cancer (BC) and colorectal cancer (CRC) are among the most commonly diagnosed cancers in the United States^1,2; screening for these cancers is a pivotal component of preventative healthcare. Arab Americans represent a diverse, yet understudied, patient population that may encounter distinct barriers …

Flash Radiation Ultra-High Dose Rate Radiation With Potential For Sensitization By Platinum, Abigail A. Jaczkowski, Stephen Brown Ph.D.

Medical Student Research Symposium

External beam radiation therapy, a cornerstone in cancer treatment for 50% of patients, poses challenges due to its toxicity to both cancer and healthy cells. Seeking to mitigate side effects, the emerging FLASH radiation technology employs ultra-high dose rates, promising quicker treatments with reduced impact on surrounding normal tissue. Platinum, recognized as a radiation sensitizer, enhances the effectiveness of radiation therapy by increasing sensitization at higher energy levels through pair-production.

This study explores the hypothesis that Cisplatin, a platinum-based chemotherapy agent, will exhibit a synergistic effect when combined with FLASH radiation. Using A549 cells from non-small cell lung cancer, the …

Analysis Of Antibody Drug Conjugate On Cellular Senescent Human Glioblastoma, Ariel P. Walker, Renee Hirte, Cecile Riviere-Cazaux, Authur Warrington, Terry Burns

Medical Student Research Symposium

Background: Glioblastoma Multiforme (GBM) is an aggressive and malignant brain tumor known for its rapid progression and unfavorable prognosis. The standard treatment options primarily involve radiation and temozolomide, however recurrence is inevitable.

B7H3/CD276, an immunomodulatory transmembrane glycoprotein, demonstrates tumor-specific expression, with limited presence in normal healthy tissue, making it a promising and attractive treatment target in GBM. AbbV155 is an antibody drug conjugate that inhibits BCL-XL and specifically targets B7H3 (CD276) on GBM cells with the goal of selectively eliminating viable tumor cells.

Objectives: First, we sought to confirm the presence of B7H3/CD276 in our selected cell line via …

Tumor Vasculature Changes Before Or During Treatment To Predict Response To Systemic Therapy, Avinash Ramkissoon, Faria Ali, Thomas Vander Woude, Stephen Brown, James Ewing, Lisa Rogers

Medical Student Research Symposium

A diagnosis of non-small cell lung cancer (NSCLC) carries a grim prognosis, with 5-year survival rates of 25%. 25-30% of NSCLC patients have brain metastases at initial presentation, which carries an even worse prognosis. New systemic therapies such as targeted-therapies and immuno-therapies have potential to provide better outcomes, but are not without challenges. First, efficacy is limited to a subset of patients. Second, the blood-brain barrier limits penetration, which varies among patients. Third, toxicities can be considerable. Current practice involves waiting 3-6 months to follow-up and assess tumor response; however, by then, it is later than ideal to try other …

Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann

Medical Student Research Symposium

ATRX is a histone chaperone protein recurrently mutated in pediatric glioma. The mechanism which mediates the proliferative advantage of ATRX loss in pediatric glioma remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53^-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p < 0.0001) and CpG islands (p < 0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric glioblastoma (GBM) cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably, the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.

H3k4 Demethylase Kdm5b Regulates Global Dynamics Of Transcription Elongation And Alternative Splicing In Embryonic Stem Cells, Runsheng He, Benjamin L. Kidder

Oncology Faculty Publications

Epigenetic regulation of chromatin plays a critical role in controlling embryonic stem (ES) cell selfrenewal and pluripotency. However, the roles of histone demethylases and activating histone modifications such as trimethylated histone 3 lysine 4 (H3K4me3) in transcriptional events such as RNA polymerase II (RNAPII) elongation and alternative splicing are largely unknown. In this study, we show that KDM5B, which demethylates H3K4me3, plays an integral role in regulating RNAPII occupancy, transcriptional initiation and elongation, and alternative splicing events in ES cells. Depletion of KDM5B leads to altered RNAPII promoter occupancy, and decreased RNAPII initiation and elongation rates at active genes and …

Innate Immune Pathways Associated With Lung Radioprotection By Soy Isoflavones, Lisa M. Abernathy, Matthew D. Fountain, Michael C. Joiner, Gilda G. Hillman

Oncology Faculty Publications

Introduction: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radio- protection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury.

Methods: BALB/c mice (5–6 weeks old) received a single 10 Gy dose of thoracic irra- diation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day. Arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 were detected in lung tissue by western …

Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang

Oncology Faculty Publications

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of …

Drug Eluding Stents For Malignant Airway Obstruction: A Critical Review Of The Literature, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Georgia Pitsiou, Bernd Linsmeier, Drosos Tsavlis, Ioannis Kioumis, Eleni Papadaki, Lutz Freitag, Theodora Tsiouda, J. Francis Turner, Robert Browning, Michael Simoff, Nikolaos Sachpekidis, Kosmas Tsakiridis, Bojan Zaric, Lonny Yarmus, Sofia Baka, Grigoris Stratakos, Harald Rittger

Internal Medicine Faculty Publications

Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin …

Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer

Pharmaceutical Sciences Faculty Publications

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo …

Characteristics Of A Novel Treatment System For Linear Accelerator–Based Stereotactic Radiosurgery, Ning Wen, Haisen Li, Kwang Song, Karen Chin-Snyder, Yujiao Qin, Jinkoo Kim, Maria Bellon, Misbah Gulam, Stephen Gardner, Anthony Doemer, Suneetha Devpura, James Gordon, Indrin Cherry, Farzan Siddiqui, Munther Ajlouni, Robert Pompa, Zane Hammoud, Michael Simoff, Steven Kalkanis, Benjamin Movsas, M. Salim Siddiqui

Internal Medicine Faculty Publications

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the …

Polymeric Nanoparticle-Based Delivery Of Microrna-199a-3p Inhibits Proliferation And Growth Of Osteosarcoma Cells, Linlin Zhang, Arun K. Iyer, Xiaoqian Yang, Eisuke Kobayashi, Yuqi Guo, Henry Mankin, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain …

Metformin Prevents Aggressive Ovarian Cancer Growth Driven By High-Energy Diet: Similarity With Calorie Restriction, Zaid Al-Wahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Robert T. Morris, Rouba Ali-Fehmi, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan

Department of Obstetrics and Gynecology Research Publications

Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking …

Mdr1 Sirna Loaded Hyaluronic Acid-Based Cd44 Targeted Nanoparticle Systems Circumvent Paclitaxel Resistance In Ovarian Cancer, Xiaoqian Yang, Arun K. Iyer, Amit Singh, Edwin Choy, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of …

The Effect Of Caffeine On Cisplatin-Induced Apoptosis Of Lung Cancer Cells, Gan Wang, Vanitha Bhoopalan, David Wang, Le Wang, Xiaoxin Xu

Institute for Environmental Health Sciences

Background: Cisplatin is an important DNA-damaging anticancer drug that has been used to treat many cancer types. However, the effectiveness of cisplatin treatment diminishes quickly as cancer cells develop resistance to the drug, which eventually results in treatment failure. Caffeine is an ingredient contained in many food sources. Caffeine can inhibit activities of both ATM and ATR, two important protein kinases involved in DNA damage-induced cell cycle arrest and apoptosis. The effect of caffeine on cisplatin-based cancer treatment is not well known.

Methods: Caspase-3 activation and cell growth inhibition assays were used to determine the effect of caffeine …

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

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

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

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

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

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

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. …

Resistance Of Human Cytomegalovirus To Cyclopropavir Maps To A Base Pair Deletion In The Open Reading Frame Of Ul97, Brian G. Gentry, Laura E. Vollmer, Ellie D. Hall, Katherine Z. Borysko, Jiri Zemlicka, Jeremy P. Kamil, John C. Drach

Oncology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen in the human population, affecting many immunologically immature and immunocompromised patients, and can result in severe complications, such as interstitial pneumonia and mental retardation. Current chemotherapies for the treatment of HCMV infections include ganciclovir (GCV), foscarnet, and cidofovir. However, the high incidences of adverse effects (neutropenia and nephrotoxicity) limit the use of these drugs. Cyclopropavir (CPV), a guanosine nucleoside analog, is 10-fold more active against HCMV than GCV (50% effective concentrations [EC₅₀s] = 0.46 and 4.1 μM, respectively). We hypothesize that the mechanism of action of CPV is similar to that …

Combination Of Sirna-Directed Gene Silencing With Cisplatin Reverses Drug Resistance In Human Non-Small Cell Lung Cancer, Shanthi Ganesh, Arun K. Iyer, Jan Weller, David V. Morrissey, Mansoor M. Amiji

Pharmaceutical Sciences Faculty Publications

One of the most challenging aspects of lung cancer therapy is the rapid acquisition of multidrug-resistant (MDR) phenotype. One effective approach would be to identify and downregulate resistance-causing genes in tumors using small interfering RNAs (siRNAs) to increase the sensitivity of tumor cells to chemotherapeutic challenge. After identifying the overexpressed resistance-related antiapoptotic genes (survivin and bcl-2) in cisplatin-resistant cells, the siRNA sequences were designed and screened to select the most efficacious candidates. Modifications were introduced in them to minimize off-target effects. Subsequently, the combination of siRNA and cisplatin that gave the maximum synergy was identified in resistant cells. We then …

Intratumoral Chemotherapy For Lung Cancer: Re-Challenge Current Targeted Therapies, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Kaid Darwiche, Thomas Vogl, Eugene P. Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Francis J. Turner, Patrick Le Pivert, Dionysios Spyratos, Konstantinos Zarogoulidis, Seyhan I. Celikoglu, Firuz Celikoglu, Johannes Brachmann

Internal Medicine Faculty Publications

Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based …

Gambogic Acid Is A Tissue-Specific Proteasome Inhibitor In Vitro And In Vivo, Xiaofen Li, Shouting Liu, Hongbiao Huang, Ningning Liu, Chong Zhao, Siyan Liao, Changshan Yang, Yurong Liu, Canguo Zhao, Shujue Li, Xiaoyu Lu, Chunjiao Liu, Lixia Guan, Kai Zhao, Xiaoqing Shi, Wenbin Song, Ping Zhou, Xiaoxian Dong, Haiping Guo, Guanmei Wen, Change Zhang, Lili Jiang, Ningfang Ma, Bing Li, Shunqing Wang, Huo Tan, Xuejun Wang, Q. Ping Dou, Jinbao Lin

Oncology Faculty Publications

Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues …

Quantitative Measures Of Estrogen Receptor Expression In Relation To Breast Cancer-Specific Mortality Risk Among White Women And Black Women, Huiyan Ma, Yani Lu, Polly A. Marchbanks, Suzanne G. Folger, Brian L. Strom, Jill A. Mcdonald, Michael S. Simon, Linda K. Weiss, Kathleen E. Malone, Ronald T. Burkman, Jane Sullivan-Halley, Dennis M. Deapen, Michael F. Press, Leslie Bernstein

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.

Methods

We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of …

Characterizing Inflammatory Breast Cancer Among Arab Americans In The California, Detroit And New Jersey Surveillance, Epidemiology And End Results (Seer) Registries (1988–2008), Kelly A. Hirko, Amr S. Soliman, Mousumi Banerjee, Julie Ruterbusch, Joe B. Harford, Robert M. Chamberlain, John J. Graff, Sofia D. Merajver, Kendra Schwartz

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, little is known about disease patterns among Arab Americans because a racial category is rarely considered for this group. The aim of this study was to advance our understanding of the burden of IBC in Arab ethnic populations by describing the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology …

Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th₁ enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th₁ microenvironment.

Methods

We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …

Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.

Methods

Murine prostate epithelial cells from PTEN^+/+, PTEN ^+/− , and PTEN^−/− (prostate …