Medicine and Health Sciences Commons^™

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Combined Systemic And Ocular Chemotherapy For Anterior Segment Metastasis Of Systemic Mantle Cell Lymphoma., Aniruddha Agarwal, Mohammad Ali Sadiq, William R. Rhoades, Loren S. Jack, Mostafa Hanout, Philip J. Bierman, William W. West, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature.

FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and …

Characterization Of Erbb4 Expression In Osteosarcoma, Nupur Lala

Dissertations & Theses (Open Access)

ERBB4 (Her-4) is a member of the ERBB family of Class I receptor tyrosine kinases. ERBB4 is unique within the ERBB family for alternate splicing in its juxtamembrane and cytoplasmic regions, which produces four juxtamembrane isoforms and two cytoplasmic isoforms. The cleavable juxtamembrane isoforms, Jm-a and Jm-d, can undergo proteolytic cleavage and produce an 80-kDa cytoplasmic fragment referred to as “p80,” which has been demonstrated to enhance cellular survival and malignant behavior in many solid tumors [44]. ERBB4 was almost exclusively 80 kDa in size and localized to the nucleus in primary tumors and metastases in studies characterizing ERBB4 expression …

The Effects Of Ketorolac And Its Enantiomers On Breast Cancer Proliferation And Metastasis, Amanda Peretti

Biomedical Sciences ETDs

Breast cancer is the second leading cause of cancer related deaths in women. Advanced breast cancer can metastasize to the lungs, liver, bones and brain becoming fatal conditions for many patients. There is a dire need for metastasis preventing medications, however the process required for a medication to become FDA approved for clinical use is long and arduous. Studies have found promising benefits for breast cancer patients given ToradolTM, or racemic ketorolac, as an NSAID during resection surgery. However, long-term use of racemic ketorolac is not recommended. Currently FDA-approved for use in the racemic form, ketorolac has the potential to …

Evidence For Differential Viral Oncolytic Efficacy In An In Vitro Model Of Epithelial Ovarian Cancer Metastasis, Jessica G. Tong, Yudith Ramos Valdes, John W. Barrett, John C. Bell, David Stojdl, Grant Mcfadden, J. Andrea Mccart, Gabriel E. Dimattia, Trevor G. Shepherd

Obstetrics & Gynaecology Publications

Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses—Myxoma virus, double-deleted vaccinia virus, and Maraba virus—using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and …

Registered Report: Biomechanical Remodeling Of The Microenvironment By Stromal Caveolin-1 Favors Tumor Invasion And Metastasis, Steven Fiering, Lay-Hong Ang, Judith Lacoste, Tim D. Smith, Erin Griner

Dartmouth Scholarship

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replicating selected results from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012 were selected on the basis of citations and Altimetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ by Goetz and colleagues, published in Cell in 2011 (Goetz et al., 2011). The key experiments …

An Unusual Initial Presentation Of Hepatocellular Carcinoma As A Sellar Mass, Nihar Shah Md, Yana Cavanagh, Hamid Shaaban, Beth Stein, Sohail N. Shaikh, Dharmesh H. Kaswala, Walid Baddoura

Gastroenterology

Sellar masses are frequently adenomatous pituitary tumors. Metastatic disease is unusual, often mimicking the presentations of adenomas. Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy but unusual to have a pituitary metastasis (PM). A 65-year-old man presented with headache, diplopia, ptosis, decreased vision in the right eye and unintentional weight loss of 32lbs. Preliminary out-patient work-up revealed a mass in the pituitary region. Cranial imaging showed 3.1 cm × 3.2 cm × 4.4 cm lesion. Abdominal imaging (computed tomography and magnetic resonance imaging) demonstrated a lobulated, nodular and heterogeneous right lobe of the liver. Trans-sphenoidal resection of the …

The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio

Electronic Thesis and Dissertation Repository

The majority of breast cancer deaths occur due to metastasis, with the most common site of breast cancer metastasis being bone. Previous work in our laboratory has established that stem-like breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and expression of a CD44⁺CD24^- phenotype have enhanced metastatic capacity. This study tested the hypothesis that bone-derived osteopontin (OPN) promotes the migration and stem-like behavior of breast cancer cells. We demonstrate that bone- derived OPN promotes migration, tumorsphere-forming ability and colony-forming ability of whole population and ALDH^hiCD44⁺CD24^- breast cancer cells in bone marrow- …

A Novel Cytokine Profile Associated With Cancer Metastasis To Mediastinal And Hilar Lymph Nodes Identified Using Fine Needle Aspiration Biopsy, Ali Imran Saeed

Biomedical Sciences ETDs

Introduction: Cancer metastasis to mediastinal and hilar lymph nodes is indicative of a poor prognosis. It is thus important to understand the pathogenesis of cancer metastasis on a cellular and molecular level with a goal to develop novel therapies directed towards prevention and treatment. In this study we compared cytokine expression in benign versus malignant mediastinal and hilar lymph nodes using EBUS-FNA biopsy specimen. Methods: In this prospective, single center study, we collected EBUS-FNA biopsies from patients recruited using a convenience sampling approach. Cytokines were assayed using Bio-Plex Pro human cancer biomarker panels 1 and 2 in a Bio-Rad 200 …

Nfat1 Contributes To Melanoma Tumor Growth And Metastasis By Regulating Il-8 And Mmp-3, Einav Shoshan

Dissertations & Theses (Open Access)

Studies from our laboratory have recently demonstrated that Gal-3 regulates autotaxin through NFAT1 and support melanoma progression. These findings prompted us to further study the role of NFAT1 in melanoma progression and metastasis. NFAT1 is a transcription factor that was first identified in immune cells, acting as a positive regulator of interleukin-2 by binding to its promoter during T cell activation. NFAT1 has an important role in the innate and adaptive immune response. In this dissertation I studied the mechanisms by which NFAT1 contributes to the acquisition of the melanoma metastatic phenotype.

To identify the role of NFAT1 in melanoma …

In Vivo Characterization Of G Protein-Coupled Estrogen Receptor In Mammary Tumorigenesis, Nicole Marjon

Biomedical Sciences ETDs

The steroid hormone, estrogen (17β-estradiol or E2), is involved in numerous and varied physiological processes. Until recently, all E2-dependent effects were thought to be propagated exclusively through the classical estrogen receptors (ERs), ERα and ERβ. However, in double ERα/β knockout mice, select E2-dependent effects remain, suggesting the existence of additional E2 receptors, such as the G protein-coupled estrogen receptor (GPER) 1. E2 plays a central role in the progression of breast cancer, and inhibiting E2 signaling in women with breast cancer increases long-term survival. The role of GPER in breast cancer is largely unknown. E2 stimulation of GPER activates the …

Activation Of The Nf-Κb Pathway As A Mechanism Of Alcohol Enhanced Progression And Metastasis Of Human Hepatocellular Carcinoma, Fei Wang, Jin-Lian Yang, Ke-Ke Yu, Mei Xu, You-Zhi Xu, Li Chen, Yan-Min Lu, Hao-Shu Fang, Xin-Yi Wang, Zhong-Qian Hu, Fei-Fei Li, Lixin Kan, Jia Luo, Si-Ying Wang

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.

METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in …

Human Cytomegalovirus Interleukin-10 Promotes Proliferation And Migration Of Mcf-7 Breast Cancer Cells, Robin K. Bishop, Cendy A. Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that is widespread in the general population and has been linked to several forms of cancer. While HCMV DNA has been found in some breast cancer tissue specimens, we wanted to investigate whether a secreted viral cytokine might have an effect on cancerous or even pre-cancerous cells. HCMV encodes an ortholog of the human cellular cytokine interleukin-10 (IL-10). The …

Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby

All ETDs from UAB

Curative approaches for metastatic breast cancer remain elusive. Adiponectin is the most abundant of the adipocyte-secreted adipokines, and there is recent interest in development of adiponectin-based therapies for this disease. Yet, while multiple epidemiological studies have indicated that low levels of circulating plasma adiponectin portend poorer prognosis, recent work has reported that elevated adiponectin expression in breast tissue correlates with advanced disease. Further, isoform-specific roles of this molecule are not well understood. Thus, the overarching purpose of this work was to elucidate how adiponectin isoforms contribute to the microenvironmental regulation of the early steps of breast cancer metastasis. We show …

Malignant Ectopic Thyroid Tissue With Distant Metastasis: A Case Report, Shehla Tabassum, Najmul Islam, Saulat H. Fatimi, Mubasher Ikram, Arsalan Ahmed, Maseehuz Zaman

Department of Medicine

Introduction: Ectopic thyroid tissue is the most common form of thyroid dysgenesis. But primary malignant transformation in ectopic thyroid tissue is quite a rare entity, with follicular malignancy being the dominant form at ectopic sites. Very infrequently, malignant ectopic thyroid tissue can present with metastasis to lymph nodes. But we report a case of malignant ectopic thyroid tissue over manubrium sterni with distant metastasis.
Case presentation: A 42-year-old Pakistani female presented with gradually increasing swelling on anterior aspect of manubrium sterni for last 6 months. She had no goitre and was clinically and biochemically euthyroid. Rest of systemic exam …