Medical Specialties Commons^™

Wwox Binding To The Murine Brca1-Brct Domain Regulates Timing Of Brip1 And Ctip Phospho-Protein Interactions With This Domain At Dna Double-Strand Breaks, And Repair Pathway Choice, Dongju Park, Mehdi Gharghabi, Colleen R Reczek, Rebecca Plow, Charles Yungvirt, C Marcelo Aldaz, Kay Huebner

Faculty, Staff and Student Publications

Wwox-deficient human cells show elevated homologous recombination, leading to resistance to killing by double-strand break-inducing agents. Human Wwox binds to the Brca1 981-PPLF-984 Wwox-binding motif, likely blocking the pChk2 phosphorylation site at Brca1-S988. This phosphorylation site is conserved across mammalian species; the PPLF motif is conserved in primates but not in rodents. We now show that murine Wwox does not bind Brca1 near the conserved mouse Brca1 phospho-S971 site, leaving it open for Chk2 phosphorylation and Brca1 activation. Instead, murine Wwox binds to Brca1 through its BRCT domain, where pAbraxas, pBrip1, and pCtIP, of the A, B, and C binding …

Anti-Tumor Activity Of Cetuximab Plus Avelumab In Non-Small Cell Lung Cancer Patients Involves Innate Immunity Activation: Findings From The Cave-Lung Trial, Carminia Maria Della Corte, Morena Fasano, Vincenza Ciaramella, Flora Cimmino, Robert Cardnell, Carl M Gay, Kavya Ramkumar, Lixia Diao, Raimondo Di Liello, Giuseppe Viscardi, Vincenzo Famiglietti, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Concetta Tuccillo, Teresa Troiani, Erika Martinelli, Jing Wang, Lauren Byers, Floriana Morgillo, Fortunato Ciardiello

Faculty, Staff and Student Publications

BACKGROUND: We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC). Among the 6 responding patients, 3 had progressed after initial response to a previous treatment with single agent anti-PD-1, nivolumab or pembrolizumab.

METHODS: We report long-term clinical follow-up and additional …

Efficacy And Safety Of Direct Oral Anticoagulants With And Without Aspirin: A Systematic Review And Meta-Analysis, Talal Almas, Adeena Musheer, Arooba Ejaz, Fahd Niaz Shaikh, Anousheh Awais Paracha, Fizza Raza, Maryam Sarwar Khan, Fahad Masood, Faiza Siddiqui, Muhammad Hasnain Mankani

Medical College Documents

Background: Various anticoagulant therapies are prescribed to patients under physicians' discretion and recently Direct Oral Anticoagulants(DOAC) have been under trials to evaluate their safety and efficacy. In addition to this, the regimen of DOACs and Aspirin is of keen interest as researchers continue to find an optimal regimen to treat blood clots in patients. This study is a systematic review and meta-analysis of randomized controlled trials and observational studies that asses the safety and efficacy of DOAC with and without Aspirin.
Methods: We queried MEDLINE and Cochrane CENTRAL from their inception to April 2021, for published and randomized controlled …

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation For B-Lineage Acute Lymphoblastic Leukemia, Mahmoud R Gaballa, Pinaki Banerjee, Denái R Milton, Xianli Jiang, Christina Ganesh, Sajad Khazal, Vandana Nandivada, Sanjida Islam, Mecit Kaplan, May Daher, Rafet Basar, Amin Alousi, Rohtesh Mehta, Gheath Alatrash, Issa Khouri, Betul Oran, David Marin, Uday Popat, Amanda Olson, Priti Tewari, Nitin Jain, Elias Jabbour, Farhad Ravandi, Hagop Kantarjian, Ken Chen, Richard Champlin, Elizabeth Shpall, Katayoun Rezvani, Partow Kebriaei

Faculty, Staff and Student Publications

Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the …

Coeliac Plexus Radiosurgery For Pain Management In Patients With Advanced Cancer : Study Protocol For A Phase Ii Clinical Trial, Galia Jacobson, Ronen Fluss, Amira Dany-Benshushan, Talia Golan, Tikva Meron, Camilla Zimmermann, Laura A Dawson, Aisling Barry, Marcin Miszczyk, Michael Buckstein, Dayssy Diaz Pardo, Artur Aguiar, Liat Hammer, Adam Dicker, Maoz Ben-Ailan, Ofir Morag, David Hausner, Zvi Symon, Yaacov R Lawrence

Department of Radiation Oncology Faculty Papers

Introduction: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.

Methods and …

Endocrine-Disrupting Chemicals And Breast Cancer: Disparities In Exposure And Importance Of Research Inclusivity, Ashlie Santaliz Casiano, Annah Lee, Dede Teteh, Zeynep Madak Erdogan, Lindsey Trevino

Health Sciences and Kinesiology Faculty Articles

Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. EDC exposures commonly occur through food packaging, cookware, fabrics, and personal care products as well as through the environment. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues to lack the inclusion necessary to positively impact treatment response and overall survival in these socially disadvantaged populations. Additionally, the inequity in environmental exposures has yet to be remedied. Exposure to EDCs due to structural racism poses an unequivocal risk to marginalized communities. In this review, we summarize recent epidemiological and molecular studies on two lesser-studied …

Micrornas In Leukemias: A Clinically Annotated Compendium, Aleksander Turk, George A Calin, Tanja Kunej

Faculty, Staff and Student Publications

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved …

Targeted Dual-Modal Pet/Spect-Nir Imaging: From Building Blocks And Construction Strategies To Applications, Syed Muhammad Usama, Sierra C Marker, Servando Hernandez Vargas, Solmaz Aghaamiri, Sukhen C Ghosh, Naruhiko Ikoma, Hop S Tran Cao, Martin J Schnermann, Ali Azhdarinia

Faculty, Staff and Student Publications

Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal …

Differences In Distress Between Rural And Non-Rural Appalachian Breast Cancer Patient / Caregiver Dyads During The First Year Of Treatment, Jordan Tasman, Callie D. Mcadams, Jillian Lloyd, Ashton J. Brooks, Patricia Nola Eugene Roberson

Journal of Appalachian Health

Introduction: Breast cancer patients and their caregivers living in rural Appalachia face substantial health disparities compared to their non-rural Appalachian counterparts. However, there is limited research on how these specific health disparities in rural Appalachian communities may impact patient psychological distress and caregiver strain during the first year of breast cancer treatment.

Purpose: The purpose of the current study was to assess differences in patient psychological distress (depression and anxiety) and caregiver strain between rural non-rural Appalachian breast-cancer-affected dyads (patients and their caregivers) during the first year of treatment.

Methods: A total of 48 Appalachian breast cancer patients (with a …

Precision Dosimetry In Yttrium-90 Radioembolization Through Ct Imaging Of Radiopaque Microspheres In A Rabbit Liver Model, E Courtney Henry, Matthew Strugari, George Mawko, Kimberly Brewer, David Liu, Andrew C Gordon, Jeffrey N Bryan, Charles Maitz, James J Karnia, Robert Abraham, S Cheenu Kappadath, Alasdair Syme

Faculty, Staff and Student Publications

Purpose: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.

Materials and methods: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity …

Spatially Resolved Transcriptomics Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K Sood

Faculty, Staff and Students Publications

Bulk and single-cell RNA sequencing do not provide full characterization of tissue spatial diversity in cancer samples, and currently available in situ techniques (multiplex immunohistochemistry and imaging mass cytometry) allow for only limited analysis of a small number of targets. The current study represents the first comprehensive approach to spatial transcriptomics of high-grade serous ovarian carcinoma using intact tumor tissue. We selected a small cohort of patients with highly annotated high-grade serous ovarian carcinoma, categorized them by response to neoadjuvant chemotherapy (poor or excellent), and analyzed pre-treatment tumor tissue specimens. Our study uncovered extensive differences in tumor composition between the …

Skp2 Stabilizes Mcl-1 And Confers Radioresistance In Colorectal Cancer, Xinfang Yu, Li Zhou, Wenbin Liu, Lijun Liu, Feng Gao, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of …

Breast And Prostate Cancer Screening: Recommendations From The American Cancer Society Versus The U.S. Preventive Services Task Force, Eric Chung, Elizabeth Kramer, Katlyn Brown, Farabi Alam, Olivia Henton, Natalie Dipietro Mager

Pharmacy and Wellness Review

Over the past decades, opportunities for pharmacists to be actively involved in screening, education and referral for patients have grown. As these opportunities have increased, so too has the importance of being knowledgeable about the corresponding recommendations and guidelines. At times, various expert organizations may publish contradicting guidelines for a particular disease state or preventive medicine recommendation. This article focuses on the general background and history of two such expert groups, the American Cancer Society and the U.S. Preventive Services Task Force, and compares the two entities’ recommendations for breast and prostate cancer as of April 2017. It is critical …

Proteomic Profiling Based Classification Of Cll Provides Prognostication For Modern Therapy And Identifies Novel Therapeutic Targets, Ti'ara L Griffen, Fieke W Hoff, Yihua Qiu, James W Lillard, Alessandra Ferrajoli, Philip Thompson, Endurance Toro, Kevin Ruiz, Jan Burger, William Wierda, Steven M Kornblau

Faculty, Staff and Student Publications

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered. SG membership superseded other prognostic factors (Rai Staging, …

Targeting Sox10-Deficient Cells To Reduce The Dormant-Invasive Phenotype State In Melanoma, Claudia Capparelli, Timothy J. Purwin, Mckenna Glasheen, Signe Caksa, Manoela Tiago, Nicole A. Wilski, Danielle Pomante, Sheera Rosenbaum, Mai Q Nguyen, Weijia Cai, Janusz Franco-Barraza, R. Zheng, Md, Gaurav Kumar, I Chervoneva, Ayako Shimada, Vito W Rebecca, Adam E. Snook, Kim Hookim, Xiaowei Xu, Edna Cukierman, Meenhard Herlyn, A E Aplin

Department of Cancer Biology Faculty Papers

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor …

Landscape Of Molecular Crosstalk Perturbation Between Lung Cancer And Covid-19, Aditi Kuchi, Jiande Wu, Jyotsna Fuloria, Chindo Hicks

School of Medicine Faculty Publications

Background: Lung cancer patients have the worst outcomes when affected by coronavirus disease 2019 (COVID-19). The molecular mechanisms underlying the association between lung cancer and COVID-19 remain unknown. The objective of this investigation was to determine whether there is crosstalk in molecular perturbation between COVID-19 and lung cancer, and to identify a molecular signature, molecular networks and signaling pathways shared by the two diseases. Methods: We analyzed publicly available gene expression data from 52 severely affected COVID-19 human lung samples, 594 lung tumor samples and 54 normal disease-free lung samples. We performed network and pathways analysis to identify molecular networks …

Clinical Evaluation Of An Auto-Segmentation Tool For Spine Sbrt Treatment., Yingxuan Chen, Yevgeniy Vinogradskiy, Yan Yu, Wenyin Shi, Haisong Liu

Department of Radiation Oncology Faculty Papers

Purpose: Spine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.

Methods: Twenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the …

Clinical Evaluation Of An Auto-Segmentation Tool For Spine Sbrt Treatment, Yingxuan Chen, Yevgeniy Vinogradskiy, Yan Yu, Wenyin Shi, Haisong Lui

Department of Radiation Oncology Faculty Papers

Purpose: Spine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.

Methods: Twenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the …

Synergy Of Venetoclax And 8-Chloro-Adenosine In Aml: The Interplay Of Rrna Inhibition And Fatty Acid Metabolism, Dinh Hoa Hoang, Corey Morales, Ivan Rodriguez Rodriguez, Melissa Valerio, Jiamin Guo, Min-Hsuan Chen, Xiwei Wu, David Horne, Varsha Gandhi, Lisa S Chen, Bin Zhang, Vinod Pullarkat, Steven T Rosen, Guido Marcucci, Ralf Buettner, Le Xuan Truong Nguyen

Faculty, Staff and Student Publications

It is known that 8-chloro-adenosine (8-Cl-Ado) is a novel RNA-directed nucleoside analog that targets leukemic stem cells (LSCs). In a phase I clinical trial with 8-Cl-Ado in patients with refractory or relapsed (R/R) AML, we observed encouraging but short-lived clinical responses, likely due to intrinsic mechanisms of LSC resistance. LSC homeostasis depends on amino acid-driven and/or fatty acid oxidation (FAO)-driven oxidative phosphorylation (OXPHOS) for survival. We recently reported that 8-Cl-Ado and the BCL-2-selective inhibitor venetoclax (VEN) synergistically inhibit FAO and OXPHOS in LSCs, thereby suppressing acute myeloid leukemia (AML) growth in vitro and in vivo. Herein, we report that 8-Cl-Ado …

A Novel Proton-Integrating Radiography System Design Using A Monolithic Scintillator Detector: Experimental Studies, Chinmay D Darne, Daniel G Robertson, Fahed Alsanea, Charles-Antoine Collins-Fekete, Sam Beddar

Faculty, Staff and Student Publications

Research on proton-based imaging systems aims to improve treatment planning, internal anatomy visualization, and patient alignment for proton radiotherapy. The purpose of this study was to demonstrate a new proton radiography system design consisting of a monolithic plastic scintillator volume and two optical cameras for use with scanning proton pencil beams. Unlike the thin scintillating plates currently used for proton radiography, the plastic scintillator volume (20 × 20 × 20 cm

Genetic Variants Associated Mrna Stability In Lung, Jian-Rong Li, Mabel Tang, Yafang Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

BACKGROUND: Expression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs).

RESULTS: Here, we presented a computational framework that takes advantage of recently developed methods to infer the mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the …

Cytokines In The Pathogenesis Of Large Granular Lymphocytic Leukemia, Colleen Isabelle, Amy Boles, Nitin Chakravarti, Pierluigi Porcu, Jonathan Brammer, Anjali Mishra

Department of Medical Oncology Faculty Papers

Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. In recent years, it has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. The exact initiation process of LGLL is unknown, although several cytokine-driven mechanisms have emerged. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may also contribute to the co-occurrence of a wide range of autoimmune …

Blood-Based Biomarker Panel For Personalized Lung Cancer Risk Assessment, Johannes F Fahrmann, Tracey Marsh, Ehsan Irajizad, Nikul Patel, Eunice Murage, Jody Vykoukal, Jennifer B Dennison, Kim-Anh Do, Edwin Ostrin, Margaret R Spitz, Stephen Lam, Sanjay Shete, Rafael Meza, Martin C Tammemägi, Ziding Feng, Samir M Hanash

Faculty, Staff and Student Publications

Purpose: To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics.

Methods: A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was …

Measurable Residual Disease Response And Prognosis In Treatment-Naïve Acute Myeloid Leukemia With Venetoclax And Azacitidine, Keith W Pratz, Brian A Jonas, Vinod Pullarkat, Christian Recher, Andre C Schuh, Michael J Thirman, Jacqueline S Garcia, Courtney D Dinardo, Vladimir Vorobyev, Nicola S Fracchiolla, Su-Peng Yeh, Jun Ho Jang, Muhit Ozcan, Kazuhito Yamamoto, Arpad Illes, Ying Zhou, Monique Dail, Brenda Chyla, Jalaja Potluri, Hartmut Döhner

Faculty, Staff and Student Publications

PURPOSE: There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10

METHODS: The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10

RESULTS: One hundred …

Analysis Of The Circrna And T-Ucr Populations Identifies Convergent Pathways In Mouse And Human Models Of Rett Syndrome, Edilene Siqueira, Aida Obiols-Guardia, Olga C Jorge-Torres, Cristina Oliveira-Mateos, Marta Soler, Deepthi Ramesh-Kumar, Fernando Setién, Daniëlle Van Rossum, Ainhoa Pascual-Alonso, Clara Xiol, Cristina Ivan, Masayoshi Shimizu, Judith Armstrong, George A Calin, R Jeroen Pasterkamp, Manel Esteller, Sonia Guil

Faculty, Staff and Student Publications

Noncoding RNAs play regulatory roles in physiopathology, but their involvement in neurodevelopmental diseases is poorly understood. Rett syndrome is a severe, progressive neurodevelopmental disorder linked to loss-of-function mutations of the MeCP2 gene for which no cure is yet available. Analysis of the noncoding RNA profile corresponding to the brain-abundant circular RNA (circRNA) and transcribed-ultraconserved region (T-UCR) populations in a mouse model of the disease reveals widespread dysregulation and enrichment in glutamatergic excitatory signaling and microtubule cytoskeleton pathways of the corresponding host genes. Proteomic analysis of hippocampal samples from affected individuals confirms abnormal levels of several cytoskeleton-related proteins together with key …

High Cd44 Immunoexpression Correlates With Poor Overall Survival: Assessing The Role Of Cancer Stem Cell Markers In Oral Squamous Cell Carcinoma Patients From The High-Risk Population Of Pakistan, Yumna Mirza, Syed Adnan Ali, Hasnain Ahmed Farooqui, Hammad A. Kayani, Romana Idress, Mohammad Sohail Awan

Department of Surgery Docs

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment …

Ezh2 And Endometrial Cancer Development: Insights From A Mouse Model, Xin Fang, Nan Ni, Xiaofang Wang, Yanan Tian, Ivan Ivanov, Monique Rijnkels, Kayla J Bayless, John P Lydon, Qinglei Li

Faculty, Staff and Students Publications

Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of Ezh2 deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (PTEN), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both Ezh2 and Pten using Cre recombinase driven by the progesterone receptor …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …

Interaction Analysis Of Mrp1 With Anticancer Drugs Used In Ovarian Cancer: In Silico Approach, Absarul Haque, Ghazanfar Ali Baig, Abdulelah Saleh Alshawli, Khalid Hussain Wali Sait, Bilal B. Hafeez, Manish Tripathi, Badrah Saeed Alghamdi, Hani S. H. Mohammed Ali, Mahmood Rasool

School of Medicine Publications

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against …

Prospective Comparison Of Geriatric Assessment And Provider's Assessment Of Older Adults With Metastatic Breast Cancer In The Community, Rino S Seedor, Caitlin R Meeker, Bianca Lewis, Elizabeth A Handorf, Kelly A Filchner, Ramya Varadarajan, Jack Hensold, Aruna Padmanabhan, Benjamin Negin, Kenneth Blankstein, Neha R Chawla, Wei Frank Song, Jessica Epstein, Jennifer Winn, Lori J Goldstein, Efrat Dotan

Department of Medical Oncology Faculty Papers

Background: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP).

Methods: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA.

Results: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of …