Medical Specialties Commons^™

Developing A Model System To Study The Mechanisms Of Resveratrol Inhibition Of Ar-V7 Transcriptional Activity, Sarah R. Wilson

PCOM Biomedical Studies Student Scholarship

Prostate cancer is one of the biggest threats to men’s health in the western world and it accounts for the second largest number of male cancer-related deaths in the United States. It is well established that prostate cancer cells depend on the androgen/androgen receptor pathway. Therefore, androgen deprivation therapy (ADT) has become the primary treatment option for prostate cancer. Patients with metastatic prostate cancer who receive (ADT) have shown increased quality of life. However, survival benefit with ADT is reduced dramatically in castration-resistant prostate cancer (CRPC). Androgen receptor (AR) continues to be functional in CRPC through various mechanisms. It is …

Oncolog, Volume 61, Number 08, August 2016, Joe Munch, Bryan Tutt, E Nielsen

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Finding a Way Forward in Parathyroid Carcinoma: Among the rarest of the rare malignancies, parathyroid carcinoma poses myriad diagnostic and treatment challenges. Owing to its extreme rarity, very little is known about the mechanisms driving parathyroid carcinoma, let alone how to target them; and survival rates have not budged in decades. However researchers at The University of Texas MD Anderson Cancer Center are working to change this.
• Studies Explore Screening for HPV-related Anal and Oropharyngeal Cancers: No consensus screening guidelines exist for human papillomavirus (HPV)-related cancers other than cervical cancer. As a step toward establishing such guidelines, studies under way …

Repetitive, Pre-Anesthetic Fasting And Malnutrition In A Pediatric Oncology Population Undergoing Radiation Therapy, Laura P. Santibáñez

Dissertations and Theses (Open Access)

Background: Pediatric oncology patients often experience nutritional status changes, particularly malnutrition, which may adversely affect their outcomes. Although the consequences of malnutrition are elucidated, its causes remain unclear. A possible cause of malnutrition in pediatric oncology patients is repetitive, pre-anesthetic fasting prior to non-invasive procedures and treatments, such as anesthesia-assisted radiation therapy (AART). This exploratory study investigated the association between repetitive, pre-anesthetic fasting and non-fasting days and malnutrition in pediatric oncology patients receiving AART.

Procedure: A retrospective cohort of 138 pediatric oncology patients (£ 10 years of age) who received any type of radiation therapy (RT) with or without anesthesia …

Geographical Location And Stage Of Breast Cancer Diagnosis: A Systematic Review Of The Literature, Faustine Williams, Aimee S. James, Stephen Jeanetta

ETSU Faculty Works

Objective: To examine systematically the literature on the effect of geographical location variation on breast cancer stage at diagnosis, race/ethnicity, and socioeconomic status.

Methods. Eight electronic databases were searched using combination of key words. Of the 312 articles retrieved from the search, 36 studies from 12 countries were considered eligible for inclusion.

Results. This review identified 17 (47%) of 36 studies in which breast cancer patients residing in geographically remote/rural areas had more late-stage diagnosis than urban women. Ten (28%) studies reported higher proportions of women diagnosed with breast cancer resided in urban than rural counties. Nine …

Reduction In Squamous Cell Carcinomas In Mouse Skin By Dietary Zinc Supplementation., Jin Sun, Rulong Shen, Morgan S. Schrock, James Liu, Xueliang Pan, Donald Quimby, Nicola Zanesi, Teresa Druck, Louise Y. Fong, Kay Huebner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12-dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression …

A Phase I Dose-Escalation Study Of The Braf Inhibitor Vemurafenib In Combination With The Mtor Inhibitor Everolimus In Subjects With Advanced Cancer, Javier Munoz

Dissertations and Theses (Open Access)

Vemurafenib has been approved in the United States for the treatment of relapsed or refractory BRAF mutation positive malignant melanoma and is being investigated in various other malignancies. The RAS/RAF/MEK/ERK (MAPK) pathway is critical to cell proliferation in many human cancers. The mTOR inhibitors are well known to exert profound anticancer effects across malignancies through inhibition of the PTEN/PI3K/AKT/mTOR (mTOR) pathway. We hypothesize that the toxicity profile of the combination of vemurafenib and everolimus will be well tolerated. The primary objective is to find the maximum tolerated dose (MTD) and the toxicity of the combination of vemurafenib and everolimus following …

Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu

Dissertations and Theses (Open Access)

Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …

Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi

Dissertations and Theses (Open Access)

Our objective was to determine predictors of potentially inappropriate medication (PIM) use and its impact on outcomes (including ER visits, hospitalization, all cause death, and composite of three) in breast and colorectal cancer patients receiving chemotherapy. We used data from the SEER database linked to Medicare claims. Our cohort included patients ≥ 66 years diagnosed with of Stage II/III breast or colorectal cancer between 7/1/2007-12/31/2009. Baseline PIM was defined using the Drugs to Avoid in the Elderly list (DAE) or Beers criteria. Univariate and multivariable logistic regression were used to determine the associations of baseline PIMs with different covariates. Event-free …

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations and Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …

The Immune Microenvironment Of Microsatellite Instable Endometrial Cancer, Janelle B. Pakish

Dissertations and Theses (Open Access)

Limited treatment options are available for patients with advanced and recurrent endometrial cancer (EC) should standard chemotherapy fail. Recent studies in other tumor types have shown that tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy treatments compared to microsatellite stable (MSS) tumors. Patients with MSI-H EC may also benefit from these therapies; however, the tumor immune microenvironment in MSI-H EC has not yet been well described.

In order to evaluate the immune microenvironment of MSI-H EC, multiple approaches were used, including analysis of large publically available datasets and detailed characterization of patient tumor samples. Uterine …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Marshall Journal of Medicine

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K₂ (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation …

Samarium-153-Edtmp (Quadramet®) With Or Without Vaccine In Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial, Christopher R. Heery, Ravi A. Madan, Mark N. Stein, Walter M. Stadler, Robert S. Dipaola, Myrna Rauckhorst, Seth M. Steinberg, Jennifer L. Marté, Clara C. Chen, Italia Grenga, Renee N. Donahue, Caroline Jochems, William L. Dahut, Jeffrey Schlom, James L. Gulley

Internal Medicine Faculty Publications

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet^®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. …

Cell Therapy Must Be Regulated As Medicine, Zihai Li, Delong Liu

NYMC Faculty Publications

Background

The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy.

Case presentation

We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens.

Conclusion This highly refractory pre-B Ph− ALL was induced to complete remission after one course of single agent blinatumomab.

Complete Remission After Single Agent Blinatumomab In A Patient With Pre-B Acute Lymphoid Leukemia Relapsed And Refractory To Three Prior Regimens: Hypercvad, High Dose Cytarabine Mitoxantrone And Clag, Katherine Linder, Deepthi Gandhiraj, Madhura Hanmantgad, Karen Seiter, Delong Liu

NYMC Faculty Publications

BACKGROUND: The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy.

CASE PRESENTATION: We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens.

CONCLUSION: This highly refractory pre-B Ph(-) ALL was induced to complete remission after one course of single agent blinatumomab.

Case Report: Pthrp Related Hypercalcemia In Diffuse Large B-Cell Lymphoma, Ankita Mehta, Md, Evan Caruso, Md

The Medicine Forum

INTRODUCTION

Hypercalcemia is commonly associated with solid tumor malignancies, but less often with hematologic malignancies. When present in hematologic malignancies, hypercalcemia is often secondary to overproduction of Vitamin D from the tumor cells. Very few cases with parathyroid hormone related peptide (PTHrP) induced hypercalcemia in B-cell lymphomas have been reported. Here we present a 44 year old male with a history of chronic lymphoctic leukemia who presented with hypercalcemia and an elevated PTHrP, found to have a transformation to Diffuse Large B-cell Lymphoma (DLBCL).

Anorectal Melanomas: Case Series, Jinyu Zhang, Md, Matthew Sochat, Md, Edward R. Feller, Md

The Medicine Forum

INTRODUCTION

Melanoma is the most common tumor to metastasize to the gastrointestinal (GI) tract. 60% of patients who die with malignant melanoma have GI involvement at autopsy1. Symptomatic disease presenting during life is unusual. Anorectal melanoma, a rare tumor that represents 1% of all melanomas and less than 4% of all anal malignancies, manifests with a range of non-specific symptoms and physical exam findings2. In fact, about one-third of lesions may be amelanotic3,4. Initial misdiagnosis as a benign lesion such as hemorrhoid is common.

We report 3 cases of anorectal melanoma presenting as primary GI complaints all without known cutaneous …

Case Report: Uncontrolled Anasarca: Capillary Leak Syndrome, Ankita Mehta, Md, Mansi Shah, Md

The Medicine Forum

INTRODUCTION

Capillary leak syndrome (CLS) is a rare clinical disease that causes edema, hypoproteinemia, episodic hypotension, dyspnea, hyponatremia, and weight gain that can be life threatening1. Although the underlying pathology is currently unknown, CLS is thought to be secondary to a systemic process associated with hyperpermeability of the body's microcirculation, resulting from a diffuse and severe disruption of the endothelium and causing generalized edema and often acute respiratory distress2.

Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan

Publications and Research

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and …

Erbb2 And P38Γ Mapk Mediate Alcohol-Induced Increase In Breast Cancer Stem Cells And Metastasis, Mei Xu, Zhenhua Ren, Xin Wang, Ashley Comer, Jacqueline A. Frank, Zun-Ji Ke, Yi Huang, Zhuo Zhang, Xianglin Shi, Siying Wang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Background: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence.

Methods: We evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in …

Exposure Of Human Lung Cells To Tobacco Smoke Condensate Inhibits The Nucleotide Excision Repair Pathway, Nathaniel C. Holcomb, Mamta Goswami, Sung Gu Han, Samuel Clark, David K. Orren, C. Gary Gairola, Isabel Mellon

Toxicology and Cancer Biology Faculty Publications

Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, …

High Crlf2 Expression Associates With Ikzf1 Dysfunction In Adult Acute Lymphoblastic Leukemia Without Crlf2 Rearrangement., Zheng Ge, Yan Gu, Gang Zhao, Jianyong Li, Baoan Chen, Qi Han, Xing Guo, Juan Liu, Hui Li, Michael D. Yu, Justin Olson, Sadie Steffens, Kimberly J. Payne, Chunhua Song, Sinisa Dovat

Student Papers, Posters & Projects

Overexpression of cytokine receptor-like factor 2 (CRLF2) due to chromosomal rearrangement has been observed in acute lymphoblastic leukemia (ALL) and reported to contribute to oncogenesis and unfavorable outcome in ALL. We studied B-ALL and T-ALL patients without CRLF2 rearrangement and observed that CRLF2 is significantly increased in a subset of these patients. Our study shows that high CRLF2expression correlates with high-risk ALL markers, as well as poor survival. We found that the IKZF1-encoded protein, Ikaros, directly binds to the CRLF2 promoter and regulates CRLF2 expression in leukemia cells. CK2 inhibitor, which can increase Ikaros activity, significantly increases Ikaros binding in …

Dasatinib-Loaded Albumin Nanoparticles Possess Diminished Endothelial Cell Barrier Disruption And Retain Potent Anti-Leukemia Cell Activity, Chunling Dong, Bo Li, Zhenyu Li, Sreerama Shetty, Jian Fu

Internal Medicine Faculty Publications

Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly …

Successful Treatment Of Ibrutinib-Associated Central Nervous System Hemorrhage With Platelet Transfusion Support, Karen Seiter, Michael Stiefel, Azfar Shaikh, Nasir Ahmed, Paul Baskind, Delong Liu

NYMC Faculty Publications

Ibrutinib is a novel targeted therapy for B-cell malignancies. Hemorrhagic events were reported in the original trials, however the mechanism of bleeding is just being elucidated. Recent studies have demonstrated platelet dysfunction as a mechanism of bleeding. Currently we report two patients who developed life-threatening central nervous system hemorrhage while receiving ibrutinib for chronic lymphoid leukemia (CLL) and mantle cell lymphoma, respectively. Both patients improved rapidly after platelet transfusions even though their platelet counts were normal or only mildly reduced at the time of hemorrhage. We suggest that platelet transfusions can ameliorate the platelet dysfunction defect of ibrutinib and can …

Three-Dimensional Printing And Nanotechnology For Enhanced Implantable Materials, Karthik Kumar Tappa

Doctoral Dissertations

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order …

Oncolog, Volume 61, Number 07, July 2016, Bryan Tutt, Sarah Bronson, Laura Russell

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Improving Rates of Vaccination after Hematopoietic Stem Cell Transplant: Patients who have undergone a hematopoietic stem cell transplant (HSCT) for a hematological cancer usually lose the immunity they had acquired through vaccination. Although guidelines exist for vaccinating immunocompromised transplant recipients, many patients go unvaccinated or do not complete the series of vaccinations. An ongoing initiative at The University of Texas MD Anderson Cancer Center is using a multipronged approach to improve rates of vaccination after HSCT.
• Bone Loss Prevention in Patients with Cancer: Patients undergoing cancer treatment are at an increased risk of fractures because many cancer therapies tend to …

Immunoglobulin G4-Related Disease: A Rare Disease With An Unusual Presentation, Muhammad Waqas Khan, Terrance Hadley, Melissa Kesler, Zartash Gul

Internal Medicine Faculty Publications

IgG4-RD can also present in the skeletal muscle, mimicking several other diseases. It is unusual for this relatively new classification of diseases to present in the muscles and can be mistakenly diagnosed as other autoimmune diseases rendering a delay in the appropriate management and progression of the disease.

The Write Stuff - Summer 2016 (Vol. 13, No. 3), Research Medical Library

Write Stuff 2016

• Tips for writing a journal submission cover letter
• New biosketch instructions and samples provided by the NIH
• Tips for shortening grant proposals through document and text formatting
• Fall schedule for the Research Medical Library webinar program
• Unusual terms used in scientific writing and publishing: Structured and unstructured abstracts

Predictive Biomarkers Of Cellular Radiosensitivity For Clinical Radiotherapy Treatment, Lisa White

Doctoral

Radiotherapy is prescribed to more than 50% of cancer patients during their treatment schedule. Due to intrinsic factors, individual variation in response exists, which will result in side effects or toxicity in a number of patients. Therefore, development of an assay or biomarker for the prediction and assessment of radiosensitivity among cancer patients undergoing radiotherapy would be beneficial. Such an assay would limit toxicities and facilitate dose-escalation for those patients who require it. Assays for predicting intrinsic cellular radiosensitivity remains as the established G2 chromosomal radiosensitivity and most promising, γH2AX foci assay. They can be applied to blood samples from …

Snpredict: A Machine Learning Approach For Detecting Low Frequency Variants In Cancer, Vatsal Mehra

Master's Theses (2009 -)

Cancer is a genetic disease caused by the accumulation of DNA variants such as single nucleotide changes or insertions/deletions in DNA. DNA variants can cause silencing of tumor suppressor genes or increase the activity of oncogenes. In order to come up with successful therapies for cancer patients, these DNA variants need to be identified accurately. DNA variants can be identified by comparing DNA sequence of tumor tissue to a non-tumor tissue by using Next Generation Sequencing (NGS) technology. But the problem of detecting variants in cancer is hard because many of these variant occurs only in a small subpopulation of …

Rna-Seq Analysis Of Localized Mst1/Stk4 Expression In Prostate Cancer, Damien Ready

Master's Theses (2009 -)

The SKT4-encoded MST1 is a serine-threonine protein kinase and has known associations with many diseases and cancer.MST1 plays a critical component of the Hippo tumor suppressor pathway responsible for limiting cell division and promoting apoptosis.Loss of MST1 function is associated with poor prognostic outcomes for cancers, though the mechanism is not well understood.There is increasing evidence that dysregulation of MST1 can lead to castration-resistant prostate cancer (CRPCa), an aggressive cancer with limited treatment options.To better understand the mechanistic underpinnings of CRPCa progression, C4-2 prostate cancer cells were engineered toexpress MST1 protein directed to a particular subcellular region: membrane, nucleus, or …