Medicine and Health Sciences Commons^™

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

The Kuala Lumpur Qigong Trial For Women In The Cancer Survivorship Phase-Efficacy Of A Three-Arm Rct To Improve Qol, Siew Yim Loh Assoc Prof

Siew Yim Loh

Background: Qigong is highly favoured among Asian breast cancer survivors for enhancing health. This study examined the hypothesis that quality of life (QoL) in the Qigong group is better than the placebo (aerobic) or usual care group. Materials and Methods: A total of 197 participants were randomly assigned to either the 8-week Kuala Lumpur Qigong Trial or control groups in 2010-2011. Measurement taken at baseline and post-intervention included QoL, distress and fatigue. Analysis of covariance (ANCOVA) and Kruskal Wallis were used to examine for differences between groups in the measurements. Results : There were 95 consenting participants in this 8week …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Lrh1 As A Driving Factor For Cancer Development, Alissa M. Margraf

Senior Honors Projects

LRH1 as a driving factor for cancer development

Alissa Margraf, Qi Tang, Qiushi Lin, Xiaoqun Dong

Department of Biomedical and Pharmaceutical Science, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881 USA

Cancer is a major public health problem worldwide. Colon cancer ranks as the third most common causes of cancer mortality in the United States, with an estimated 96,830 new cases and 50,310 deaths in 2014. Colon cancer develops in the digestive tract where benign growths called polyps transform into malignant tumors. Colon cancer cells invade and destroy nearby tissue and can …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Stilbene Analogs And Methods Of Treating Cancer, David Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang

Molecular and Cellular Biochemistry Faculty Patents

Stilbene analogs and pharmaceutical compositions that are useful for the treatment of various cancers, including without limitation, colorectal cancer (CRC) and breast cancer are disclosed.

For the complete abstract, please download this patent.

Repair Of Oxidative Dna Damage And Cancer: Recent Progress In Dna Base Excision Repair, Timothy L. Scott, Suganya Rangaswamy, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

SIGNIFICANCE: Reactive oxygen species (ROS) are generated by exogenous and environmental genotoxins, but also arise from mitochondria as byproducts of respiration in the body. ROS generate DNA damage of which pathological consequence, including cancer is well established. Research efforts are intense to understand the mechanism of DNA base excision repair, the primary mechanism to protect cells from genotoxicity caused by ROS.

RECENT ADVANCES: In addition to the notion that oxidative DNA damage causes transformation of cells, recent studies have revealed how the mitochondrial deficiencies and ROS generation alter cell growth during the cancer transformation.

CRITICAL ISSUES: The emphasis of this …

Paracrine Apoptotic Effect Of P53 Mediated By Tumor Suppressor Par-4, Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53⁻/⁻ or Par-4⁻/⁻ mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 …

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …

Parp Inhibition: A Method Of Treating And Preventing Certain Cancers, Chana Tropper

The Science Journal of the Lander College of Arts and Sciences

Breast cancer is one of the largest causes of cancer related deaths in women. Less than 5% of breast cancer cases are genetically inherited and most often develop after menopause. The BRCA gene mutation is a genetic inheritance which increases ones chances of developing breast cancer at a young age tenfold. Recent research has proposed a method of treatment in genetically inherited breast cancers by taking advantage of the impaired DNA repair pathway caused by the BRCA mutation. The combination of a BRCA mutation, which leads to deficient double strand DNA repair, and PARP inhibition, which leads to deficient single …

Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

Attachment Style And Perceived Social Support As Predictors Of Biopsychosocial Adjustment To Cancer, Ayşe Gül Yilmaz Özpolat, Tuğba Ayaz, Özlem Konağ, Asi̇ye Özkan

Turkish Journal of Medical Sciences

Social support is associated with a decrease in psychological symptoms and a better quality of life in cancer patients. The aim of this study was to investigate the role of attachment dimensions on social and psychological adjustment to cancer and to explore the social and psychological adjustments, and medical adherence, among patients. Materials and methods: The study was conducted with 68 cancer patients, between 18 and 74 years of age. The measures taken were the Demographic Information Form, Multidimensional Scale of Perceived Social Support (MSPSS), Experiences in Close Relationships-Revised (ECR-R), and Psychosocial Adjustment to Illness Scale (PAIS-SR). Results: The results …

Identification And Characterization Of Downstream Effector Protein(S) Regulated By P53 And Prb, Miranda B. Carper

Theses, Dissertations and Capstones

A commonality among cancer types is the high frequency of mutations that inhibit or alter signaling of the p53 and pRb (Retinoblastoma) tumor suppressors. These genes regulate processes vital for cancer suppression such as apoptosis, senescence, and cell cycle arrest among others. Loss of both p53 and pRb promotes processes that support cancer progression and is associated with decreased patient survival and increased rates of tumor reoccurrence. Although data points to the ability of p53 and pRb to collaborate and to inhibit tumorigenesis, it remains unclear how p53 and pRb cooperate toward this task. Using RNA expression profiling, 179 p53 …

Metabolomic Analysis Of Liver Tissue From The Vx2 Rabbit Model Of Secondary Liver Tumors, Rafael A. Ibarra, J. E. Dazard, Y. Sandlers, F. Rehman, R. Abbas, R. Kombu, G. F. Zhang, H. Brunengraber, Juan R. Sanabria

Surgery

Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development.

Methods. We used the rabbitVX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using …

Oxaliplatin And Ototoxicity: Is It Really Safe For Hearing?, Sali̇m Yüce, Mehmet Meti̇n Şeker, Sema Koç, İsmai̇l Önder Uysal, Turgut Kaçan, Mehtap Doğan, Mansur Doğan, Nalan Akgül Babacan, Saadetti̇n Kiliçkap

Turkish Journal of Medical Sciences

Oxaliplatin is an effective and widely used chemotherapeutic agent in the treatment of many solid tumors. The most common side effects are peripheral neuropathy, gastrointestinal toxicity, and neutropenia. There have been some case reports about ototoxicity with oxaliplatin, but no clinical trials. In this trial, we explored whether or not oxaliplatin has ototoxic effects. Materials and methods: A total of 18 patients, 14 with colorectal cancer and 4 with pancreatic cancer, were included in this study. Four patients (22%) were treated with a capecitabine and oxaliplatin (CapeOx) regimen, and 14 patients (78%) were treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX-6). …

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

The Expression And Function Of Icam-2 In Neuroblastoma, Joseph Feduska

All ETDs from UAB

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 15% of all childhood cancer deaths. At the time of initial diagnosis, the majority of patients present with NB that has already metastasized. While initial remission is often achieved following treatment, roughly 50% of these patients will relapse and die from the development of intractable metastatic progression. Intercellular adhesion molecule-2 (ICAM-2) is a transmembrane glycoprotein, normally expressed only in endothelial cells and subsets of leukocytes. ICAM-2 expression in cancer cells had not been previously investigated, until our lab recently reported the novel finding of endogenous ICAM-2 expression …