Gene Set Analysis Of Post-Lactational Mammary Gland Involution Gene Signatures In Inflammatory And Triple Negative Breast Cancer, Arvind Bambhroliya

Dissertations and Theses (Open Access)

With each cycle of pregnancy and lactation, the mammary gland undergoes dramatic changes. Clarkson et al. (2004) and Stein et al. (2004) conducted a detailed analysis of these changes in the mouse mammary gland. Their results showed that tissue remodeling during post-lactational involution period mimics wound healing and tumorigenesis like pathological conditions. This indicates that post-lactational involution may create the microenvironment that initiates the development of precancerous mammary cells and promotes the progression of precancerous cells into cancer cells. Moreover, epidemiological studies have found that triple-negative (TN) breast cancer (BC) is associated with lower frequency and duration of breastfeeding compared …

Thermal Ablation Alters The Tumor Microenvironment Activating A Robust Immune Response., Matthew T. Campbell M.D.

Dissertations and Theses (Open Access)

THERMAL ABLATION ALTERS THE TUMOR MICROENVIRONMENT ACTIVATING A ROBUST IMMUNE RESPONSE.

Matthew T Campbell, M.D.

Advisor Professor: Padmanee Sharma, M.D Ph.D

Ablation techniques including radiofrequency ablation (RFA) and cryoablation have been shown to influence the immune system in animal models. Rare abscopal events, a distant metastatic response to a local procedure, have been observed in humans following both RFA and cryoablation. These rare observations have led to interest in further defining the impact of ablation procedures on the immune signature in the tumor microenvironment and in the systemic circulation.

Retrospectively 9 patients with nephrectomy alone (control) were compared to 16 …

Isoform Selective Regulation Of Adenylyl Cyclase By Small Molecule Inhibitors And Gbetagamma Protein, Cameron S. Brand

Dissertations and Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. All nine isoforms share a similar structural organization; thus, AC isoform differences in physiological function are due to different regulatory profiles. A physiological example is Gβγ, which can conditionally enhance stimulation of ACs 2, 4, 5, 6, and 7, but inhibit ACs 1, 3, and 8. There is also pharmacological control of AC isoforms through small molecule inhibitors.

Isoform specific AC functions could be explained by regulatory differences as subtle as single amino acid changes. …

Impact Of Differentiation Status Of Kidney Progenitors In Wilms Tumor Development, Le Huang

Dissertations and Theses (Open Access)

Wilms tumor is one of the most common solid tumors in children. It is an embryonic cancer of the kidney and is thought to arise from undifferentiated renal mesenchyme. However, the differentiation status of cells in the mesenchyme that can give rise to Wilms tumors is unknown. Gene expression analysis of a large panel of Wilms tumor patients has identified different subsets of Wilms tumors that are distinct in their clinical outcomes and gene expression signatures. These subsets express specific genes that correspond to different stages of differentiation during renal development, suggesting that Wilms tumors may arise from transformed cells …

Gsbs News, Spring 2015, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis, Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

Ms171: Interview With Elizabeth Travis, Elizabeth Travis Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Elizabeth Travis, PhD of MD Anderson Cancer Center. See more at Texas Medical Center-Women's History Project and its finding aid.

Ms171: Interview With Janet Butel, Janet Butel Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An Oral history interview with Janet Butel, PhD of Baylor College of Medicine. See more at Texas Medical Center-Women's History Project and its finding aid.

The Winnebago Educare Program: Be Strong And Educate My Children, Theresa K. Barron-Mckeagney, Marisa Miakonda Cummings

Journal of Family Strengths

Educare of Omaha began in 2002 as a private, non-profit collaborative effort of the Buffett Early Childhood Fund, the Omaha Public Schools, and the local Head Start grantee. Two sites are located in Omaha serving diverse communities in North and South Omaha. Educare differs from other early child care programs due to its prominent focus on children in poverty, and providing highest quality care by highly educated staff. “Students and families from low-income homes often face unique barriers in developing foundations for success and Educare’s program model is specifically designed to help at-risk students and their families overcome such barriers” …

Ms171: Interview With Kathryn Stream, Kathryn Stream Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Kathryn Sheaffer Stream. See more at Texas Medical Center-Women's History Project and its finding aid.

Ms171: Interview With Margaret Kripke, Margaret Kripke Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Margaret Kripke. See more at Texas Medical Center-Women's History Project and its finding aid.

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

Dissertations and Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms a heterotrimeric …

A Novel Tablet Based System To Measure The Effect Of Subconcussive Blows On Sensorimotor And Cognitive Functioning, Stuart D. Red

Dissertations and Theses (Open Access)

Concussions have become a major societal concern with studies showing detrimental short and long-term effects on cognitive and sensory functioning. More recently, research has begun to focus on “subconcussive” blows to the head. Subconcussive blows, which are common in many sports (soccer, boxing, football, etc), do not result in the more obvious symptoms of a concussion but have the potential to cause severe brain injury. In our lab and others, eye movements have been used as a sensitive marker of cognitive and sensory changes related to specific diseases and treatments. We have developed a novel measure based on eye movement …

The Role Of Mir-34a In Inhibition Of Prostate Tumor Growth In The Bone And Induction Of Autophagy, Sanchaika Gaur

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in the United States, with most deaths occurring from bone metastasis. Several new therapies have been FDA approved for bone-metastatic PCa, but patient survival has only marginally improved due to therapy resistance, which often arises from constitutive activation of compensatory signaling pathways. This dissertation work focused on a mechanistic understanding of how cross talk between tyrosine kinase receptors contributes to therapy resistance, and how this may be overcome by downregulating expression of these receptors. In PCa cell lines and xenograft models, I demonstrated that activation of IGF-1R …

Hypoxia Mediated Downregulation Of Mirna Biogenesis Leads To Increased Tumor Progression, Rajesha Rupaimoole

Dissertations and Theses (Open Access)

In recent years, there has been a growing recognition of the importance of tumor associated microenvironment in the initiation and progression of tumors. However, a mechanistic understanding of the complicated biological interplay between the stromal framework and malignant regions of the tumor remains incompletely understood. In this study, we address mechanisms by which hypoxia in the tumor microenvironment leads to attenuation of miRNA biogenesis by downregulation of two key enzymes, Drosha and Dicer in cancer cells. Previous data from our laboratory had shown the clinical relevance of downregulated Dicer and Drosha in ovarian and other cancer types, but a clear …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

Dissertations and Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser³³⁸ and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser³³⁸ phosphorylation …

Effects Of Oxytocin On Human Aggression, Joseph L. Alcorn Iii

Dissertations and Theses (Open Access)

EFFECTS OF OXYTOCIN ON HUMAN AGGRESSION

Joseph Louis Alcorn III, B.S.

Advisory Professor: Scott D. Lane, Ph.D.

Human interaction is comprised of common, yet complex, behaviors and the outcomes of these social behaviors can beneficially or detrimentally impact individual and public health. One social behavior that can have profound detrimental outcomes is aggression. Aggression is a class of social behavior that is particularly prevalent in individuals with antisocial personality disorder (ASPD) and comorbid substance use disorder (SUD). Aggression in these individuals can manifest at maladaptive levels that place considerable burdens on public health and communities. Therefore, understanding the neurobehavioral underpinnings …

Differential Pax5 Levels Promote Mcl Dispersal And Progression And Predict A Poor Prognosis In Advanced Mcl Patients, Albert Teo

Dissertations and Theses (Open Access)

Although PAX5 conditional silencing in mice models led to aggressive lymphoma formation, there has been a lack of understanding in the precise functions of PAX5 in human B cell cancers. PAX5 expression is used to diagnose different B cell lymphoma in the clinic including mantle cell lymphoma (MCL), which is one of the most aggressive B cell cancers. PAX5 levels in MCL patients were significantly repressed compared to normal B cells. Surprisingly, we found there were quantitative differences in PAX5 expression levels within MCL patient tissues, which prompted us to silence PAX5 in MCL cell lines to characterize PAX5 functions …

The Role Of Dual Specificity Phosphatase -11 In Innate And Adaptive Immune Responses, Kalyan Chakravarthy Nallaparaju

Dissertations and Theses (Open Access)

THE ROLE OF DUAL SPECIFICITY PHOSPHATASE -11 IN INNATE AND ADAPTIVE IMMUNE RESPONSES

Kalyan Chakravarthy Nallaparaju, M.S.

Supervisory Professor: Chen Dong, Ph.D.

Dual-specificity phosphatases (DUSPs) constitute a subfamily of protein tyrosine phosphatases characterized by their ability to dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within a substrate, typically among members of the MAP kinase family. DUSPs have been shown to play a critical role in the regulation of various cellular processes including signal transduction, cell cycle regulation and cellular proliferation via modulation of MAP kinase activities. Also, many members of this family have been demonstrated to be potent immune regulators. …

Nprl2/Tusc4 Functions As A Tumor Suppressor By Regulating Brca1’S Stability Via The E3 Ubiquitination Pathway, Yang Peng

Dissertations and Theses (Open Access)

Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrate through microarray analysis that cells with tumor suppressor candidate 4 (NPRL2/TUSC4) knockdown show critical changes to cell cycle, cell death pathways and a global impact on cancer development. More importantly, we observed a clear cluster pattern of NPRL2/TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, NPRL2/TUSC4 protein physically interacts with the E3 ligase HERC2 and prevents ubiquitin …

Change Detection In Rhesus Monkeys And Humans, Deepna T. Devkar, Deepna T. Devkar

Dissertations and Theses (Open Access)

Visual working memory (VWM) is the temporary retention of visual information and a key component of cognitive processing. The classical paradigm for studying VWM and its encoding limitations has been change detection. Early work focused on how many items could be stored in VWM, leading to the popular theory that humans could remember no more than 4±1 items. More recently, proposals have suggested that VWM is a noisy, continuous resource distributed across virtually all items in the visual field, resulting in diminished memory quality rather than limited quantity. This debate about the nature of VWM has predominantly been studied with …

Regulation Of Functional Expression Of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium And Sodium Intake, Nabila Boukelmoune

Dissertations and Theses (Open Access)

The Ca²⁺-permeable TRPV4 channel is predominantly expressed in the distal nephron (DN) and its activity is essential for [Ca²⁺]_i elevations in response to increased tubular flow. Here, I probed the physiological mechanisms controlling TRPV4 function and expression in the DN. I found that renal TRPV4 expression and mRNA levels were significantly increased by high K⁺ diet (5%) and decreased by dietary K⁺ restriction (0.003%). In contrast, variations in Na⁺ regimen had no apparent effect on TRPV4 expression and mRNA levels. Regulation of TRPV4 protein expression by K⁺ diet was independent of …

Dual Assembly Nanoparticles Achieve Sustained Silencing Of Znf304: A Novel Transcription Factor For Β1 Integrin, Burcu Aslan

Dissertations and Theses (Open Access)

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to this process currently are known. Here, an integrated computational analysis of The Cancer Genome Atlas ovarian cancer dataset coupled with experimental validation identified a novel zinc finger transcriptional factor 304 (ZNF304) as one of the key factors for ovarian cancer metastasis. High tumoral ZNF304 expression was associated with poor overall survival in ovarian cancer patients. Through reverse phase protein array analysis, we demonstrated that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration, and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase …

Gsbs News, Fall 2014, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster, Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty, Staff and Students Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

First Carpometacarpal Arthroplasty With Ligamentous Reconstruction: A Long-Term Follow-Up, Mark A Yaffe, Bennet Butler, James M Saucedo, Daniel J Nagle

Faculty, Staff and Student Publications

BACKGROUND: The purpose of the present study is to evaluate a single surgeon's short, intermediate, and long-term clinical, functional, and radiographic outcomes with a trapeziectomy with flexor carpi radialis (FCR) suspension arthroplasty without tendon interposition (LRSA).

METHODS: Twenty-one patients underwent 26 FCR suspension arthroplasties without tendon interposition by a single senior surgeon. All patients had Eaton stage III and IV carpometacarpal (CMC) osteoarthritis. The Patient-Rated Wrist and Hand Evaluation (PRWHE) and Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) were used to evaluate functional outcomes. A comprehensive strength and range of motion evaluation was performed to evaluate clinical outcomes. Plain …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations and Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …

Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady

Dissertations and Theses (Open Access)

Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α …

Characterization Of The Vascular Pathology In The Acta2 R258c Mouse Model And Cerebrovascular Characterization Of The Acta2 Null Mouse, Carlos A. Villamizar

Dissertations and Theses (Open Access)

Mutations in ACTA2, the gene encoding for smooth muscle α-actin, predispose patients to a wide range of vascular diseases and is most commonly associated with thoracic aortic aneurysms (TAAD) and dissections (TAAD) and strokes. TAAD in patients is characterized by aortic media degeneration and loss in contractile force generation followed by aortic enlargement and subsequent rupture. Most stroke cases associated with ACTA2 are described as moyamoya-like cerebrovascular incidents characterized by distal occlusion of the internal carotid artery, stenosis of arteries in the Circle of Willis, and straightening of cerebral arteries. Patient samples are scarcely available for analysis, and the few …