Medical Specialties Commons^™

Announcing The Isev2020 Special Achievement Award Recipients: Andrew Hill And Edit Buzás; And The Recipient Of The Isev2020 Special Education Award: Carolina Soekmadji., Kenneth W Witwer, Lucia R Languino, Alissa M Weaver, Marca H Wauben

Kimmel Cancer Center Faculty Papers

No abstract provided.

Role Of Fine Needle Aspiration Cytology In The Diagnosis Of Parotid Gland Tumors: Analysis Of 193 Cases, Rahim Dhanani, Haissan Iftikhar, Mohammad Sohail Awan, Nida Zahid, Sehrish Nizar Ali Momin

Section of Otolaryngology, Head & Neck Surgery

Introduction: Parotid gland tumors include a wide variety of inflammatory and neoplastic diseases. The majority of these tumors are benign (80%), which usually require superficial parotidectomy, while the incidence of malignant tumors is lower (20%), requiring more radical surgery with or without neck dissection. The diagnosis cannot be established on the basis of clinical history and simple physical examination and requires complementary diagnostic methods. Fine needle aspiration cytology (FNAC) guided by ultrasound is a widely used diagnostic tool to evaluate parotid swellings.
Objective: To determine the sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of FNAC in the …

Prognostic Impact Of Single And Multiple Descriptors In Pathologically Staged T3n0m0 Non-Small Cell Lung Cancer, Takefumi Komiya Md, Emily Powell Phd, Shinkichi Takamori Md Phd

PCI Publications and Projects

Background

T components of the current 8th edition of lung cancer American Joint Commission on Cancer (AJCC) staging assignment include size of primary tumor and others such as chest wall invasion. The role of the presence of multiple T3 descriptors in prognosis remains unknown.

Materials and methods

Using National Cancer Database (NCDB) and of AJCC 7th edition, pathologically staged (R0) N0M0 non-small cell lung cancer (NSCLC) cases diagnosed in 2010-2016 were analyzed. Selected cases had primary size larger than 5cm or staged as T3 by AJCC 7th edition despite size <5cm. T3 descriptor status by 8th edition was defined as single descriptor (“T3-single”) as primary size 5-7cm or size <5cm and T3 per 7th edition (“T3-other”), or multiple descriptor (“T3-multi”) as presence of both descriptors. Survival analysis was performed with validation of multivariate analyses.

Results

Of the 108,632 surgically resected pathologically staged N0M0R0 NSCLC …

Breast Carcinoma Metastasis In A Resected Meningioma With Early Diagnosis Of Oligometastatic Disease: A Case Report., Christian Fernandez, Louis Cappelli, Sara Chapin,, Lawrence Kenyon, Christopher J Farrell, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Tumor-to-tumor metastasis describes the ability of primary tumors to metastasize to other primary tumors. These events generally occur in aggressive and widely-metastatic disease, with the appropriate management and significance of these events unknown. A 56-year-old woman with a history of bilateral, localized, invasive lobular breast carcinoma treated with surgery, systemic therapy, and adjuvant radiation presented five and two years post-treatment with progressive neurological symptoms. Imaging revealed an intracranial meningioma, and the patient underwent resection. Pathology revealed metastatic invasive lobular carcinoma cells within the resected meningioma, and the patient was treated with postoperative radiation without sequelae. Subsequent staging scans revealed a …

Site-Specific Multi Disciplinary Tumour Board Is An Important Milestone In Cancer Patient's Treatment Journey, Ahmed Nadeem Abbasi, Sehrish Abrar, Bilal Mazhar Qureshi

Department of Radiation Oncology

No abstract provided.

Superficial Basal Cell Carcinoma Of The Face Successfully Treated With Ingenol Mebutate 005% Gel: Case Report And A Review Of The Literature, Theodore Rosen, Kami Lowery

Faculty, Staff and Students Publications

A 64 year-old Caucasian male patient with a long history of ultraviolet light exposure and multiple actinic keratoses presented with a large, erythematous, and scaly plaque on his forehead. Biopsies revealed superficial basal cell carcinoma (sBCC). Because the patient wanted the shortest possible topical regimen, his sBCC was treated with two overnight ingenol mebutate (IM) 0.05% gel applications. He tolerated the local skin reaction (LSR) well, and at approximately six weeks post-treatment, biopsies showed no evidence of sBCC. The patient was happy with the cosmetic outcome and has remained free of clinical recurrence for 18 months. Although IM gel is …

Human Genes Differ By Their Uv Sensitivity Estimated Through Analysis Of Uv-Induced Silent Mutations In Melanoma, Ivan P Gorlov, Christopher I Amos, Spiridon Tsavachidis, Colin Begg, Eva Hernando, Chao Cheng, Ronglai Shen, Irene Orlow, Li Luo, Marc S Ernstoff, Joel Parker, Nancy E Thomas, Olga Y Gorlova, Marianne Berwick

Faculty, Staff and Students Publications

We hypothesized that human genes differ by their sensitivity to ultraviolet (UV) exposure. We used somatic mutations detected by genome-wide screens in melanoma and reported in the Catalog Of Somatic Mutations In Cancer. As a measure of UV sensitivity, we used the number of silent mutations generated by C>T transitions in pyrimidine dimers of a given transcript divided by the number of potential sites for this type of mutations in the transcript. We found that human genes varied by UV sensitivity by two orders of magnitude. We noted that the melanoma-associated tumor suppressor gene CDKN2A was among the top …

Assessing Time From Door-To-Antibiotic Administration For Adult Cancer Patients With Neutropenic Fever In The Emergency Department, Sarah Roy, Tina Magsarili

All Nursing Boot Camp Posters

Background:

Infection, related to febrile neutropenia, in patients receiving chemotherapy for cancer remains a common complication and is a medical emergency. Fever is often the only sign of severe underlying infection in neutropenic patients due to the patient’s immunosuppressed state (Butts, et.al, 2017). Vigilant nursing assessment and immediate medical attention for neutropenic fever (NF) is imperative because the rate of major organ complication and mortality is as high as 30% and 11% respectively (Freifield et.al, 2011 & Taplitz et.al, 2018). In the setting of severe sepsis or septic shock the mortality rate may be as high as 50% (Taplitz et.al, …

Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo

Pharmacy Faculty Articles and Research

Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCA-like” (or “BRCAness”) describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with tumors being …

Identification Of Plasma Glycosphingolipids As Potential Biomarkers For Prostate Cancer (Pca) Status, Ashley J. Snider, Michael C. Seeds, Laurel Johnstone, Justin M. Snider, Brian Hallmark, Rahul Dutta, Cristina Moraga Franco, John S. Parks, Jeannette T. Bensen, Corey D. Broeckling, James L. Mohler, Gary J. Smith, Elizabeth T.H. Fontham, Hui Kuan Lin, William Bresette, Susan Sergeant, Floyd H. Chilton

School of Public Health Faculty Publications

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in United States men. Controversy continues over the effectiveness of prostate-specific antigen (PSA) for distinguishing aggressive from indolent PCa. There is a critical need for more specific and sensitive biomarkers to detect and distinguish low-versus high-risk PCa cases. Discovery metabolomics were performed utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) on plasma samples from 159 men with treatment naïve prostate cancer participating in the North Carolina-Louisiana PCa Project to determine if there were metabolites associated with aggressive PCa. Thirty-five identifiable plasma small molecules were …

Unexpected Hope For A Multiple Myeloma Patient, Minodora Cezarina Onisâi, Iuliana Iordan, Mihaela Gaman, Horia Bumbea, Ana-Maria Vlădăreanu

Journal of Mind and Medical Sciences

Multiple myeloma (MM) is a plasma cell neoplasm, characterized by periods of remission and relapses. The emergence of novel therapies, with multiple mechanisms of action and fewer adverse reactions, brings more and better options and also a higher survival rate. However, MM is still an incurable disease, and patients eventually become refractory to an extensive range of therapies. We present the case of a patient diagnosed with MM standard risk, who was at first refractory to multiple treatment regimens, and then had an unexpected and stable complete response to a newer drug of the same class.

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

Clinical Features, Pathology, And Surgical Management Of Periocular Giant Basal Cell Carcinoma, Oxana Madalina Grosu, Vladimir Poroch, Natalia Velenciuc, Sorinel Lunca

Journal of Mind and Medical Sciences

Objectives. Basal cell carcinomas (BCCs) are malignant tumors which rarely metastasize, are slow-growing, and extensively locally destructive. BCCs more than 5 cm in diameter are defined as giant. Most often they arise as a result of neglect, as the patient avoids, delays, or refuses to see a doctor. The large tumor diameter and consequently of the post-excisional defect make these lesions difficult to treat surgically with respect to selecting the surgical reconstruction technique. Method. We studied a group of 9 patients, aged 60 to 85 years, diagnosed with giant basal cell carcinomas (GBCCs) with periocular location in which surgery was …

Indicators Of Psychological Distress And Body Image Disorders In Female Patients With Breast Cancer, Helena Van Oers, Lourens Schlebusch

Journal of Mind and Medical Sciences

Breast cancer patients are vulnerable to elevated stress related to receiving the diagnosis, unfamiliar and invasive treatment, and coping with the side-effects of treatment, which may find various forms of expression. Another common feature of this patient population is body image dysphoria. Both the disease and treatment lead to impairments in physical appearance and general bodily functioning. This study aimed to explore the differential manifestations of stress and the nature of body image dysphoria within a sample of female breast cancer patients (n=80), compared to female patients with other sites of disease (n=80) in order to examine differences in the …

Estrogen/Progesterone Receptor And Her2 Discordance Between Primary Tumor And Brain Metastases In Breast Cancer And Its Effect On Treatment And Survival, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).

METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the …

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff

Radiology Faculty Publications

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained …

Clinical Efficacy Of Direct-Acting Antiviral Therapy For Recurrent Hepatitis C Virus Infection After Liver Transplantation In Patients With Hepatocellular Carcinoma, Mohamed Saleh Ismail, Manal Hassan, Saira Aijaz Khaderi, Wael Ahmed Yousry, Maha Mohsen Kamal El-Din, Mohamed Mohamed Bahaa El-Din, Osama Aboelfotoh El Sayed, Ahmed Omar Kaseb, John Alan Goss, Fasiha Kanwal, Prasun Kumar Jalal

Faculty, Staff and Students Publications

BACKGROUND: Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.

AIM: To demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.

METHODS: A total of 106 LT recipients given DAAs for recurrent …

Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, …

Organic Field-Effect Transistors As Flexible, Tissue-Equivalent Radiation Dosimeters In Medical Applications, Andrew M. Zeidell, Tong Ren, David S. Filston, Hamna F. Iqbal, Emma Holland, J. Daniel Bourland, John E. Anthony, Oana D. Jurchescu

Chemistry Faculty Publications

Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors …

Soluble Glycoprotein Vi Is A Predictor Of Major Bleeding In Patients With Suspected Heparin-Induced Thrombocytopenia, Allyson M Pishko, Robert K Andrews, Elizabeth E Gardiner, Daniel S Lefler, Adam Cuker

Department of Medical Oncology Faculty Papers

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day …

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G Pestell, Yunguang Sun, Jun Zhao, Mathew C Casimiro, Zhiping Li, Michael P Lisanti, Peter Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G Pestell

Department of Cancer Biology Faculty Papers

The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1-S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine …

Intratumoral Translocation Positive Heterogeneity In Pediatric Alveolar Rhabdomyosarcoma Tumors Correlates To Patient Survival Prognosis, Katrina Gleditsch, Jorge Peñas, Danielle Mercer, Ayesha Umrigar, James Briscoe, Matthew Stark, Fern Tsien, Andrew D. Hollenbach

School of Medicine Faculty Publications

Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. Consistent with this fact, previous work concluded that a molecular analysis of RMS translocation status is essential for the accurate determination of prognosis and diagnosis. However, despite this knowledge, most diagnoses rely on histology and in some cases utilize fluorescence in situ hybridization (FISH) probes unable to differentiate between translocation products. Along these same lines, diagnostic RT-PCR analysis, which can differentiate …

Etv6 Germline Mutations Cause Hdac3/Ncor2 Mislocalization And Upregulation Of Interferon Response Genes., Marlie H. Fisher, Gregory D. Kirkpatrick, Brett Stevens, Courtney Jones, Michael Callaghan, Madhvi Rajpurkar, Joy M. Fulbright, Megan A. Cooper, Jesse Rowley, Christopher C. Porter, Arthur Gutierrez-Hartmann, Kenneth Jones, Craig Jordan, Eric M. Pietras, Jorge Di Paola

Manuscripts, Articles, Book Chapters and Other Papers

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation …

Endogenous Cyclin D1 Promotes The Rate Of Onset And Magnitude Of Mitogenic Signaling Via Akt1 Ser473 Phosphorylation., Ke Chen, Xuanmao Jiao, Agnese Di Rocco, Duanwen Shen, Shaohua Xu, Adam Ertel, Zuoren Yu, Gabriele Di Sante, Min Wang, Zhiping Li, Timothy G Pestell, Mathew C Casimiro, Emmanuel Skordalakes, Samuel Achilefu, Richard G Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1-but not nuclear-localized cyclin D1-recapitulates Akt1 …

Challenges In Teaching Palliative Care Module Virtually During Covid-19 Era, Shanaz Hussein Cassum, Khairunnisa Mansoor, Amina Hirji, Amber David, Amina Aijaz Khowaja

School of Nursing & Midwifery

With the COVID-19 pandemic hitting the global community, routine activities of universities, offices, and industries have been hindered. People are being forced to rethink the ways of working virtually from home for providing education, business, and health services in this social distancing during the COVID era. This sudden shift also posed challenges of online teaching in a private university, in urban Karachi, Pakistan. The Aga Khan University, School of Nursing and Midwifery recently conducted an online palliative care module using a virtual learning environment and Microsoft Teams for Trainee Nurse Interns. Although the first experience of online teaching and learning …

Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of …

Lenvatinib Plus Pembrolizumab In Patients With Advanced Endometrial Cancer., Vicky Makker, Matthew H Taylor, Carol Aghajanian, Ana Oaknin, James Mier, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Christopher Disimone, Mark Messing, Daniel E Stepan, Corina E Dutcus, Jane Wu, Emmett V Schmidt, Robert Orlowski, Pallavi Sachdev, Robert Shumaker, Antonio Casado Herraez

Articles, Abstracts, and Reports

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR

RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR

CONCLUSION: Lenvatinib plus pembrolizumab showed …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …