Medicine and Health Sciences Commons^™

Cluster Of Differentiation 163 Expression In Breast Carcinoma: An Immunohistochemical Study, Dalia R. Al-Sharaky, Enas A. El Khouly, Hayam A. Aiad, Marwa M. Dawoud, Norhan S. Kasem

Menoufia Medical Journal

Objective To determine the expression of the cluster of differentiation 163 (CD163) in invasive breast carcinoma and to correlate it with the clinicopathological parameters, biological markers, and molecular subtypes of breast carcinoma. Background CD163 is a transmembrane scavenger receptor that is specifically expressed by non-neoplastic monocytes/macrophages and by neoplasms with monocytic/histiocytic differentiation. Theory of cell fusion between neoplastic and normal cells has been suggested to play a role in the acquisition of the malignant phenotype. Patients and methods This retrospective case–control study was conducted on formalin-fixed, paraffin-embedded blocks of tissues from 71 patients with invasive breast carcinoma retrieved from the …

Targeting Oncogenic Gαq/11 In Uveal Melanoma, Dominic Lapadula, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Uveal melanoma is the most common intraocular cancer in adults and arises from the transformation of melanocytes in the uveal tract. While treatment of the primary tumor is often effective, 36–50% of patients develop metastatic disease primarily to the liver. While various strategies have been used to treat the metastatic disease, there remain no effective treatments that improve survival. Significant insight has been gained into the pathways that are altered in uveal melanoma, with mutually exclusive activating mutations in the GNAQ and GNA11 genes being found in over 90% of patients. These genes encode the alpha subunits of the hetetrotrimeric …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations & Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …

Prognostic Values Of G-Protein Mutations In Metastatic Uveal Melanoma, Mizue Terai, Ayako Shimada, I Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B Wedegaertner, Jeffrey L Benovic, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and …

Molecular Mechanism Of Action Of The Natural Polyphenolic Compound And The P300 Inhibitor “Carnosol” Against The Triple Negative Breast Cance, Halima Ali Mohammed Salem Alsamri

Dissertations

Carnosol, a naturally occurring Phyto polyphenol found in sage, oregano, and rosemary, has been extensively studied by our laboratory for its anticancer effects in various types of cancer. In human Triple-Negative Breast Cancer (TNBC), carnosol was shown to inhibit cellular viability, colony growth, induced cell cycle arrest, autophagy, and apoptosis. Nonetheless, very little is known about the molecular mechanism of action. In the current study, the ability of carnosol to inhibit metastasis and tumour growth was examined. Wound healing and invasion assays revealed that carnosol inhibited migration and invasion at non-cytotoxic concentrations of MDA-MB-231 cells. Also, carnosol was found to …

The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato

Department of Medical Oncology Faculty Papers

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit …

Induction Of Hypopituitarism Following Ipilimumab/ Nivolumab Therapy Followed By Radiation In The Treatment Of Metastatic Scalp Melanoma, Joshua K. Salabei, Dhaval Upadhyay, Sripal A. Padam

HCA Healthcare Journal of Medicine

Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to …

Choroidal Melanoma: Screening For Metastasis And Frequency Of Incidental Second Primary Cancer Diagnosis., Ethan Leyda Od

Optometric Clinical Practice

Background: Choroidal melanoma is the most common primary intraocular malignancy in adults. This case report reviews clinical diagnostic features, imaging techniques, treatment, prognosis, and systemic work-up of choroidal melanomas. It also addresses choroidal melanoma metastasis and the incidental finding of second primary cancers through whole-body screening.

Case Report: A 71-year-old white male reported to the Cleveland VA Medical Center optometry retina clinic for a second opinion exam of an asymptomatic choroidal lesion in the right eye. The lesion was a 6 mm gray choroidal mass in the inferior peripheral fundus, with orange pigmentation, retinal pigmented epithelial hypertrophy along the superior …

Epigenetic Regulation And Post-Translational Modifications Of Snai1 In Cancer Metastasis, Bo Dong, Yadi Wu

Pharmacology and Nutritional Sciences Faculty Publications

SNAI1, a zinc finger transcription factor, not only acts as the master regulator of epithelialmesenchymal transition (EMT) but also functions as a driver of cancer progression, including cell invasion, survival, immune regulation, stem cell properties, and metabolic regulation. The regulation of SNAI1 occurs at the transcriptional, translational, and predominant post-translational levels including phosphorylation, acetylation, and ubiquitination. Here, we discuss the regulation and role of SNAI1 in cancer metastasis, with a particular emphasis on epigenetic regulation and posttranslational modifications. Understanding how signaling networks integrate with SNAI1 in cancer progression will shed new light on the mechanism of tumor metastasis and help …

Insights Into Cutaneous Squamous Cell Carcinoma Pathogenesis And Metastasis Using A Bedside-To-Bench Approach, Marissa Lobl

Theses & Dissertations

Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer, affecting 1,000,000 people in the United States annually and causing approximately 9,000 deaths. SCC and basal cell carcinoma are the most common types of skin cancer arising in the superficial squamous cells or deeper basal cells of the epidermis, respectively. SCC is more likely to invade and metastasize, while basal cell cancer tends to grow locally. While the majority of cases of SCC are cured by surgery alone, approximately 2-5% of SCCs metastasize, at which point outcomes may be poor. Specific patient groups, particularly immunosuppressed patients, have a …

Our Experience Of Treating Adult Bone Lymphoma, A Retrospective Cross-Sectional Study In A Tertiary Care Center, Aga Khan University Hospital, Karachi, Masood Umer, Muhammad Younus Khan Durrani, Javeria Saeed, Nasir Ud Din

Section of Orthopaedic Surgery

Objective: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone.
Methodology: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study.
Results: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours …

Characterizing The Role Of Uchl5 In Metastatic Melanoma, Seenya Vincent

Dissertations & Theses (Open Access)

Metastatic melanoma is one of the most aggressive cancers. In recent years, the survival rate has improved with the introduction of immunotherapy. Our lab conducted an in vivo ORF screen to identify potential drivers of metastasis. UCHL5/UCH37 was identified as one of the top candidates. UCHL5 is a deubiquitinating enzyme and interacts with the 26S proteasome complex and the INO80 chromatin remodeling complex. While UCHL5 has been shown to be overexpressed in many cancers, it has not been well characterized in melanoma. We investigated the role of UCHL5 in metastatic melanoma in vitro through overexpressing and knocking down UCHL5 in …

Metastatic Renal Cell Carcinoma To Pancreas And Gastrointestinal Tract: A Clinicopathological Study Of 3 Cases And Review Of Literature, Jamshid Abdul Ghafar, Nasir Ud Din, Ramin Saadaat, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Background: Renal Cell Carcinoma (RCC) metastasizes in approximately 20-30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC.
Methods: Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and …

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells …

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …

Redefining Cancer Of Unknown Primary: Is Precision Medicine Really Shifting The Paradigm?, Timothée Olivier, Eugenio Fernandez, Intidhar Labidi-Galy, Pierre-Yves Dietrich, Veronica Rodriguez-Bravo, Giulia Baciarello, Karim Fizazi, Anna Patrikidou

Department of Cancer Biology Faculty Papers

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group. CUP features significant oncological challenges, such as unravelling biological and transversal issues, and most importantly, improving patient's outcomes. In that regard, CUP patients’ outcomes regrettably showed minimal improvement for decades and CUP remains a cancer group of very poor prognosis. The biology …

Long Non-Coding Rna Zfas1 Is A Major Regulator Of Epithelial-Mesenchymal Transition Through Mir-200/Zeb1/E-Cadherin, Vimentin Signaling In Colon Adenocarcinoma, Stephen J. O'Brien, Casey Fiechter, James Burton, Jacob Hallion, Mason Paas, Ankur Patel, Ajay Patel, Andre Rochet, Katharina Scheurlen, Sarah Gardner, Maurice Eichenberger, Harshini Sarojini, Sudhir Srivastava, Shesh Rai, Theodore S. Kalbfleisch, Hiram C. Polk, Susan Galandiuk

Veterinary Science Faculty Publications

Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found …

Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark

Honors College Theses

Metastasis- the spread of cancer cells from the primary tumor to the surrounding tissues- is responsible for 90% of cancer deaths. Integrin alpha-6 (ITGA6) is a specific transmembrane cell surface protein that functions in cell surface adhesion and signaling. ITGA6 is upregulated in many types of cancers and promotes the migration and invasion of cancer cells to surrounding tissues. It is my objective to determine the mechanism through which ITGA6 facilitates the migration of cancer cells through the extracellular matrix (ECM). These experiments helped to establish the role of ITGA6 in tumor development and provide focus for possible chemotherapeutic treatment. …

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

Role Of Contrast Enhanced Computed Tomography In Assessing Cervical Lymph Node Metastases In Oral Cavity Squamous Cell Carcinoma, Talha Ahmed Qureshi, Muhammad Wasif, Mohammad Sohail Awan, Adnan Yar Muhammad, Ainulakbar Mughal, Abdullah Ameen

Section of Otolaryngology, Head & Neck Surgery

Objective: To evaluate the diagnostic accuracy of contrast-enhanced computed tomography scan in detecting cervical nodal metastasis in oral cavity squamous cell carcinoma.
Methods: The retrospective cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. and comprised records from January 1, 2015, to October 31, 2016, of patients diagnosed with oral cavity squamous cell carcinoma and who underwent surgical resection of primary tumour along with neck dissection after having a contrast-enhanced computed tomography scan of head and neck. Diagnostic accuracy of the scans was calculated using final histopathology as the gold standard. All scans were reviewed by a consultant …

Printing The Pathway Forward In Bone Metastatic Cancer Research: Applications Of 3d Engineered Models And Bioprinted Scaffolds To Recapitulate The Bone-Tumor Niche., Anne M. Hughes, Alexus D. Kolb, Alison B. Shupp, Kristy M. Shine, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone-tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. …

'Educated' Osteoblasts Reduce Osteoclastogenesis In A Bone-Tumor Mimetic Microenvironment., Alexus D. Kolb, Jinlu Dai, Evan T. Keller, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on …

Long Noncoding Rna Ak001796 As A Mediator Of Epithelial-To-Mesenchymal Transition In Metastatic Breast Cancer, Sumayya Adib Alchalabi

Legacy Theses & Dissertations (2009 - 2024)

Long noncoding RNAs (lncRNAs) are emerging as key molecules regulating several cellular pathways and contributing to the development and progression of different diseases including cancer. The epithelial-to- mesenchymal transition (EMT), a molecular reprogramming process that plays a critical role in cancer metastasis, involves a complex interaction between protein coding and non-coding transcripts including lncRNAs. Understanding the biological significance of those lncRNAs of relatively unknown function, may help to uncover potential therapeutic targets for the aggressive subtypes of breast and other cancers. In this study, we examined the expression profiles of more than 17,000 lncRNAs in a large set of patients’ …

Targeting Oncogenic Microrna In Lung Cancer, Mackenzie Lauren Davenport

All ETDs from UAB

Lung cancer is the leading cause of cancer-related death both in the United Statesand the world. While several genetic drivers of lung cancer have been identified, major improvements in patient outcome are lacking, highlighting the need to further understand the genetic and molecular mechanisms of this disease. The microRNA miR-31 has been implicated in oncogenesis in a variety of cancer types, and prior data from our laboratory has shown it to be overexpressed in human lung adenocarcinoma tumors compared to normal lung, high miR-31 levels correlate with decreased patient survival, and overexpression of miR-31 alone in the mouse lung epithelium …