Medicine and Health Sciences Commons^™

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …

Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …

Prognostic Impact Of Matrix Metalloproteinases (Mmp-9 And Mmp-2) And Vascular Endothelial Growth Factor Expression In Non-Small Cell Lung Cancer, Ahmet Yurdakul, Nalan Akyürek, Şenay Yilmaz, Jale Karakaya, Leyla Memi̇ş, Can Öztürk

Turkish Journal of Medical Sciences

To investigate the role of matrix metalloproteinases (MMPs), MMP-9 and MMP-2, and vascular endothelial growth factor (VEGF) in metastasis and their relationship with survival. Early metastasis is the most common cause of lung cancer death. Angiogenesis and basement membrane damage are necessary for growth and invasion of the tumoral cells. VEGF, involved in angiogenic activity, and MMPs, involved in matrix destruction, are important for metastasis in lung cancer. Materials and methods: Using immunohistochemistry analysis, we evaluated MMP-9, MMP-2, and VEGF expressions in paraffin specimens from 91 patients with histopathologically confirmed non-small cell lung cancer and the relationship between MMP-9, MMP-2, …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …

Genetic Factors In Metastatic Progression Of Cutaneous Melanoma: The Future Role Of Circulating Melanoma Cells In Prognosis And Management, A Ireland, M Millward, R Pearce, M Lee, Mel Ziman

Research outputs pre 2011

The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material …

Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook

All ETDs from UAB

Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells metastasize to distant organ sites. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. Thus Brms1 transgenic mice (derived on C57BL/6 background) were generated by utilizing MMTV promoter expression (for mammary-selective overexpression) or the beta-actin promoter (for ubiquitous …

Time Interval Between Staging Fdg Positron Emission Tomography (Pet) And Initiation Of Stereotactic Lung Radiotherapy (Sbrt) Impacts The Risk Of Recurrence And Metastasis In Non-Small Cell Lung Cancer (Nsclc), B. Belderbos, A. Hope, L. L. Kestin, M. Guckenberger, M. Werner-Wasik, J. J. Sonke, J. P. Bissonnette, Y. Xiao, D. Yan, I. S. Grills

Bodine Journal

Background: To study influence of time interval from staging PET scanning to RT start time on recurrence and survival in patients with NSCLC undergoing lung SBRT.

American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, CA

Metastasis Suppression In Carcinoma And Melanoma Cells, Sherry Marie Baker

Undergraduate Honors Capstone Projects

No abstract provided.

P66shc--A Longevity Redox Protein In Human Prostate Cancer Progression And Metastasis : P66shc In Cancer Progression And Metastasis., Mythilypriya Rajendran, Paul Thomes, Li Zhang, Suresh Veeramani, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common …

Nm23-H1 Blocks Cell Motility Independently Of Its Known Enzymatic Activities In A Cohort Of Human Melanoma Cells, Joseph Robert Mccorkle

University of Kentucky Doctoral Dissertations

The metastasis suppressor gene NM23-H1 has been shown to possess three enzymatic activities including nucleoside diphosphate kinase, histidine-dependent protein kinase and 3’-5’ exonuclease activity. While these properties have been demonstrated in vitro using recombinant proteins, the contribution of these activities to suppression of metastatic dissemination is unknown. Site-directed mutagenesis studies were used to identify amino acid residues which are required for proper function of each enzymatic activity associated with H1, providing a platform for studying the importance of each function on an individual basis. To assess the relevance of these activities to melanoma progression, a panel of mutants harboring selective …

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

All ETDs from UAB

Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …

Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine

All ETDs from UAB

Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …

Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds

All ETDs from UAB

The majority of cancer related mortality is attributed to complications associated with metastatic disease. Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple cancer types in vivo and loss of nuclear BRMS1 is associated with ER-negative cancers and a high rate of proliferation. Many groups have shown BRMS1 to regulate the expression of multiple metastatic genes, yet until now no one has been able to account for how these many changes in gene expression occur. In this work, we report that BRMS1 regulates a select set of genes called microRNA (miRNA), and these miRNA themselves can regulate metastasis. Using …

High Aldehyde Dehydrogenase And Expression Of Cancer Stem Cell Markers Selects For Breast Cancer Cells With Enhanced Malignant And Metastatic Ability, Alysha K. Croker, David Goodale, Jenny Chu, Carl Postenka, Benjamin D. Hedley, David A. Hess, Alison L. Allan

Anatomy and Cell Biology Publications

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

The Relationship Of Serum Cea And Ca 19-9 Levels To Liver Metastasis And Pancreatic Invasion In Esophageal Cancer, Ati̇la Türkyilmaz, Ati̇lla Eroğlu, Yener Aydin, Nuretti̇n Karaoğlanoğlu

Turkish Journal of Medical Sciences

Aim: Previous studies have examined levels of CEA and CA 19-9 in esophageal cancer patients, but have not determined a significant relationship between CEA and CA 19-9 levels and liver metastasis and pancreatic invasion in patients with esophageal cancer. In this study, we compared the serum levels of CEA and CA 19-9 in patients with esophageal cancer with and without liver and pancreatic metastasis. Materials and methods: The serum levels of CEA and CA 19-9 were measured in clinic patients between January 2007 and January 2008, including 10 patients with liver metastasis (4) and pancreas invasion (6), and 40 patients …

Survival In Esophageal Cancer Patients With Hematogenous Distant Organ Metastases, Ati̇la Türkyilmaz, Ati̇lla Eroğlu, Yener Aydin, Ömer Yilmaz, Nuretti̇n Karaoğlanoğlu

Turkish Journal of Medical Sciences

Objective: Esophageal cancer is a rapidly progressive cancer. In the majority of patients local invasion or distant metastasis may be present at the time of diagnosis. The present study reviewed the records of esophageal cancer patients with hematogenous distant organ metastases with the aim of reporting primary tumor location, histological type, location of metastases, and survival rates, according to treatment administered. Method: Distant organ metastasis was detected in 50 of 316 consecutive patients that presented to the Thoracic Surgery Department of Atatürk University between 2002 and 2007. Patient age and gender, tumor location, history of esophagectomy, metastasis organ, treatment type, …

General Anesthesia For Cesarean Delivery Followed By Anterior And Posterior Spinal Cord Decompression Of A Parturient With Symptomatic Spinemetastasis Due To Breast Cancer, Berri̇n Günaydin, Sema Öncül, Mehmet Erdem, Memduh Kaymaz, Hakan Emmez, Zerri̇n Özköse

Turkish Journal of Medical Sciences

Cesarean delivery of a parturient suffering from paraplegia followed by anterior corpectomy and posterior spinal cord decompression because of spine metastasis at T1 due to breast cancer was presented. General anesthesia was uneventfully completed after rapid sequence anesthesia induction with propofol, ketamine, and succinylcholine, which was maintained by isoflurane inhalation in 50% oxygen-air mixture until delivery of the newborn. After delivery, remifentanil infusion was added to isoflurane inhalation in approximately 33%/66% oxygen:air until skin closure of the latter operation. Consequently, satisfactory recovery of paraplegia resulting from spine metastasis and delivery of a healthy baby were provided by successful and uneventful …

Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya

All ETDs from UAB

Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, …

Surgical Management Of Metastatic Disease To The Adrenal Gland, Paul R. Gittens Jr., Allison F. Solish, Edouard Trabulsi

Department of Urology Faculty Papers

Metastatic disease to the adrenal glands can occur in a wide array of malignancies. With the increased use of abdominal imaging, these lesions are diagnosed with more frequency. Diagnostic and laboratory evaluation is essential for the differentiation of benign lesions from primary malignant adrenal tumors or extra-adrenal metastasis. Computed tomography (CT) and magnetic resonance imaging (MRI) characteristics, as well as the adjunctive use of immunocytochemical techniques on biopsy specimens, can allow accurate identification of metastatic lesions. Surgical management of metastastic lesions is appropriate in selected patients, primarily when representing the solitary site of metastatic disease. The surgical approach, while debatable, …

Uterine And Ovarian Metastasis Of Transmissible Venereal Tumor In A Bitch, Ayhan Baştan, Duygu Baki̇ Acar, Mehmet Cengi̇z

Turkish Journal of Veterinary & Animal Sciences

In this case report, metastasis of a transmissible venereal tumor (TVT) to the uterus and ovaries is presented. A 7-year-old female boxer dog with hemorrhagic vulvar discharge and a vaginal mass was brought to Ankara University Faculty of Veterinary Medicine, Clinics of Gynecology and Obstetrics. TVT was diagnosed by clinical findings and cytologic examination. Multifocal nodules in the uterus and enlargements of the uterine wall were detected by ultrasonographic examination. Ovariohysterectomy was performed because of uterine pathology. Histopathologic examination of the uterus and ovarium showed that the multifocal masses in the uterus and ovaries originated from vaginal TVT.

Targeted Therapies In The Management Of Metastatic Bladder Cancer., Matteo Fassan, Edouard J. Trabulsi, Leonard G Gomella, Raffaele Baffa

Department of Urology Faculty Papers

The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of …

Role Of Heparanase And Heparanase-Degraded Heparan Sulfate In Brain-Metastatic Melanoma, Madhuchhanda Roy

LSU Doctoral Dissertations

Cancer metastasis is a frequent manifestation of malignant melanoma progression. Successful invasion into distant organs by tumor cells must include attachment to microvessel endothelial cells, and degradation of extracellular matrix. Heparan sulfate proteoglycans are ubiquitous macromolecules associated with cell surface and extracellular matrix of a wide range of cells and tissues. Heparanase is an extracellular matrix degradative enzyme which degrades the heparan sulfate chains of heparan sulfate proteoglycans. To investigate effects of changes in heparanase gene expression in metastatic melanoma cells, we constructed adenoviral vectors containing the full-length human heparanase cDNA in both sense (Ad-S/hep) and anti-sense orientations (Ad-AS/hep). We …

Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams

Biochemistry and Microbiology

Background

The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …

Recurrence And Metastases Of A Basal Cell Carcinoma In A Variable Squirrel (Callosciurus Finlaysoni Floweri): A Case Report, Sawang Kesdangsakonwut, Anudep Rungsipipat, Nopadon Pirarat, Komkrich Teankum, Wijit Banlunara

The Thai Journal of Veterinary Medicine

A dead, 9-year-old, female, Variable squirrel, weighing 190 g, had a skin swelling in the left inguinal area. Surgical excision of a similar skin mass in the right inguinal area had taken place 87 days previously. The squirrel had showed signs of severe dyspnea and inappetence for 7 days prior to death. At necropsy, as well as the skin mass in the left inguinal area, metastases were found in the inguinal lymph node and the lung together with a hemothorax. The tumor based on the clinical data, macroscopic and microscopic lesions was diagnosed as a basal cell carcinoma, Immunohistochemistry showed …

Proliferating Cell Nuclear Antigen (Pcna) And P53 In Epithelial Dysplasia And Squamous Cell Carcinoma Of Oral Mucosa - A Marker For Poor Tumor Differentiation, Increasing Nuclear Atypia And Invasiveness?, Lan H. A., Rosnah Binti Zain, Saitoh M., Muramatsu Y., Shrestha P., Mori M.

Prof. Dr. Rosnah Binti Zain

The immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and p53 was investigated in 9 cases of epithelial dysplasia and 38 cases of squamous cell carcinoma of the oral cavity. The intensity of immunoreactivity for each marker was assessed using a semiquantitative grading system, and was correlated with tumor differentiation, nuclear atypia and the patterns of invasive margins in the underlying connective tissue. PCNA expression, in dysplastic epithelium, was observed in the suprabasal and lower spinous layers; and the labeling grade and intensity of staining increased along the degree of cellular atypia. In 2 cases of dysplasia, weak positive immunoreactivity …

Introductory For 1844-5, On The Present Position Of Some Of The Most Important Of The Modern Operations Of Surgery., Thomas Dent Mutter, Md

Jefferson Medical College Opening Addresses

No abstract provided.