Diseases Commons^™

Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai

Graduate Theses, Dissertations, and Problem Reports (ETD)

With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …

Rates Of Benign Heart Tumors Diagnosed In Florida Hospitals: 1988-2012, Robert B. Hood, Elliott Smith, Richard B. Early, Zachary Weber, Sharona B. Ross, Alexander S. Rosemurgy Ii, Randall E. Harris

Florida Public Health Review

No abstract provided.

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

Targeted Inhibition Of Histone Deacetyltransferases For Pancreatic Cancer Therapy, Richard Laschanzky

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a dismal five-year survival rate of less than 10%. One major obstacle in PDAC treatment is acquired drug resistance. Pan-histone deacetylase inhibitors (pan-HDACi) are a relatively new class of anti-cancer drugs, with demonstrated ability to overcome drug resistance and re-sensitize PDAC tumors to Gemcitabine (Gem). These agents target HDACs, a family of 18 enzymes (divided into four classes, I-IV) that catalyze the deacetylation of histones and other cellular proteins and have multiple effects on cell growth, differentiation, survival, and tumorigenesis. Although pan-HDACi have shown significant efficacy in preclinical analysis, and some …

Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor

Capstone Experience: Master of Public Health

Background: Cancer is the second leading cause of death in the United States and remains a major public health problem worldwide. Epidemiological studies have demonstrated that insulin like growth factor-1 (IGF-1) is linked to ulcers and most cancers. Although studies have investigated the role of IGF1 in ulcer healing and cancer pathogenesis, the link between ulcer and cancer remains unclear. Hence, we assessed the relationship between ulcers and cancers.

Methods: This study consists of a sample of 180 cancer patients obtain by convenience sampling who were seen at Nebraska Medicine and were enrolled in the integrated cancer repository for cancer …

Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu

School of Medicine Faculty Publications

34th Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer - Part 1, November 6 - 10, 2019, National Harbor, MD

Bone Metastasis In Appendicular Skeleton: Rare Occurrence In Colorectal Cancer, Pratikkumar Vekaria Md, Chandrika Raiyani Md, Ravis Patel Md, Devin Vaishnani Md, Tejas Raiyani Md

Gastroenterology

Colorectal cancer (CRC) is considered as preventable cancer if diagnosed in the early stage. It is also second leading cause of death from cancer in US. Bone metastases (BM) is uncommon presentation with CRC and if it occurs, it involves axial skeletal more than extremities. Many case studies also reports that survival after BM is considerably poor than without BM. Cancer type and genetic mutations also play an important role in such metastasis.

Not Just A Cyst: A Rare Presentation Of Luq Pain, Richard Henriquez, Isin Y. Comba Md, Sundeep Kumar Md, Khawaja Arsalan Bashir, Maria Wallis-Crespo Md, Lakhinder Bhatia Md

Gastroenterology

Lymphangioma is a benign congenital malformation of the lymphatic system that is relatively common in juvenile population. Rarely, it can be seen in adults and majority of the cases are reported in the head and neck region (70-75%). Typically, these malformations are asymptomatic. In this report, we present a rare case of splenic lymphangioma presenting with severe, intractable abdominal pain.

Rare Malignant Peritoneum Mesothelioma Masquerading With Respiratory Manifestation, Ravish Patel, Pratikkumar Vekaria, Devin Vaishnani, Johnnie Mao, Chandrika Raiyani, Marvin Vaishnani, Tejas Raiyani

Internal Medicine

Mesothelioma is a rare and aggressive cancer that affects the linings of the pleura, peritoneum and pericardium. Pleural involvement is however most common. Malignant Peritoneal mesothelioma (MPM) is a cancer developing in the lining of the peritoneum, which is extremely rare. Most MPM cases are caused by asbestos exposure. Common symptoms of MPM include abdominal distension, abdominal pain, swelling or tenderness and constipation or diarrhea, with most common being abdominal swelling. MPM is difficult to diagnose due to its vague, nonspecific symptoms.

Choking On Adenocarcinoma, Andre Sahakian Md, Rajesh Gulati Md

Internal Medicine

No abstract provided.

Prediction Of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial (18)F-Fdg Pet/Ct, Michael Chuong

All Publications

No abstract provided.

1,25-Dihydroxyvitamin D Mediated Hypercalcemia As An Initial Presentation In A Patient With Undiagnosed B-Cell Non-Hodgkin’S Lymphoma, Ranjit Banwait Md, Jawad Noor Md, Jing He Md, Xiaolong Liu Md, Liang Sun Md

Internal Medicine

In non-Hodgkin's lymphoma the findings of hypercalcemia as an initial presentation is extremely rare (<3% of cases). Here we report a 67 year-old man who presented with ST changes secondary to hypercalcemia in the setting of B-cell lymphoma.

Blue Rubber Bleb Nevus Syndrome, Danielle Kocsis, Anthony Dupuy, Stacey Wice, Aftab Ahmad, Tehmina Yaquibi

Internal Medicine

No abstract provided.

Nivolumab Induced Myasthenia Gravis, Elizabeth Henderson Md, Imad Ikhawn Md, Dharti R. Patel Md, Monicka Felix

Internal Medicine

No abstract provided.

Effect Of Aquatic Exercise On Fatigue, Fitness, Arm Edema, Levels Of Distress, And Quality Of Life Among Breast Cancer Survivors, Ellen Broach, Phillip Norrell

International Journal of Aquatic Research and Education

The purpose of this study was to evaluate the effect of a recreational therapy aquatic intervention on physical and psychosocial performance of breast cancer survivors. Eligible participants were assigned to either a water exercise group or a control group who received standard care treatment for breast cancer. The intervention group attended aquatic exercise sessions three times per week for eight weeks in a heated outdoor pool. Sessions lasted 50 minutes in duration. The aquatic exercise group significantly improved their endurance, body mass, level of distress, and total score for fatigue. No significant differences occurred in the control group. Social validity …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

A High Throughput Assay For The Detection Of Stimulator Of Interferon Genes (Sting) Agonists, Michael J. Ingling

Graduate School of Biomedical Sciences Theses and Dissertations

The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. …

Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle

School of Medicine Faculty Publications

American Association for Cancer Research Annual Meeting 2019, March 29 - April 3, 2019, Atlanta, GA

Chemically Modified Variants Of Fenofibrate With Antiglioblastoma Potential, J Stalinska, E Zimolag, N. A. Pianovich, A Zapata, A Lassak, M Rak, M Dean, D Ucar-Bilyeu, D Wyczechowska, F Culicchia, L Marrero, Luis Del Valle, J Sarkaria, F Peruzzi, B. S. Jursic, K. Reiss

School of Medicine Faculty Publications

Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have …

Role Of Rac1-Pak Pathway In Aggressive B-Cell Lymphoma, Tian Tian

Theses & Dissertations

Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. Aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL) and B lymphoblastic lymphoma. The treatment of patients with aggressive B-cell lymphomas remains a clinical challenge. Conventional chemotherapeutic regimens, mainly based on the CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) combination, obtain a relatively high number of complete or partial clinical responses (20-80%), but the tumor relapses in most patients, who will die of the disease. …

Referral Patterns, Procedures, And Outcomes Of A Large Community- Based Urology Group: A Retrospective Chart Review, Hassan A. Al Saleh, Gregory C. Mcmahon, Michael Douglas, Michael Console, Mihir Thaker, Gordon A. Brown

Rowan-Virtua Research Day

In 2012 The United States Preventive Services Task Force (USPSTF) recommended against prostate cancer (Pca) screening. The purpose of our study is to assess the effects of the USPSTF grade D recommendation for PSA based screening on new PCa diagnoses within a large-community based private practice setting. We completed a retrospective chart review of men with an elevated PSA seen in our clinic between May 2009–May 2015 who had undergone a prostate biopsy and were diagnosed with PCa. We observed that following the 2012 USPSTF recommendations, there was a significant increase in patients with clinically significant prostate cancer GG ≥ …

Atypical Presentation Of Stemi With Cardiac Tamponade Related To Malignancy, Matthew J. Johnson, Rohan Penmetcha

Rowan-Virtua Research Day

Cardiac tamponade and myocardial infarction are rare as the initial presentation of a malignancy. Here, we describe a case with an atypical presentation of a myocardial infarction due to a thrombus in the right coronary artery occurring in the setting of a pericardial effusion causing tamponade physiology related to malignancy. We present this unique case of myocardial infarction and cardiac tamponade as this was not caused by a type-A aortic dissection. In conclusion, we suggest that malignancy be considered in the differential diagnosis when these findings present together.

Occult Renal Cell Carcinoma Presenting As A Palpable Supraclavicular Virchow's Node, Luke Perry, Jandie Schwartz, Gus Slotman, Omar Al Ustwani, Nandini Kulkarni

Rowan-Virtua Research Day

Occult papillary renal cell carcinoma (RCC) is a rare disease process in which there is evidence of metastatic kidney cancer, but no primary kidney tumor can be found on physical exam or imaging. The papillary subtype of RCC accounts for 10-15% of RCC’s. These lesions infrequently present as occult disease. A Virchow’s node can be positive for multiple cancer types, most notably gastric cancer, but also gallbladder, pancreas, kidneys, testicular, and prostate cancer. We describe a case of occult papillary renal cell carcinoma diagnosed by biopsy of a Virchow’s node.

Recurrent Renal Cell Carcinoma Post Radical Nephrectomy: A Case Report, Amarnath Polepalle, Neethi Dasu, Adam Freilich, Jayram Krishnan

Rowan-Virtua Research Day

This is a case of a 73-year-old Caucasian male presenting with an asymptomatic right adrenal mass.

Renal Cell Carcinoma (RCC) constitutes 80 to 85% of primary renal neoplasms. At presentation, up to 25% of patients with RCC will have evidence of metastases or locally advanced disease. [1] Patients will rarely present with any symptoms since the majority of patients are incidentally diagnosed due to radiologic procedures performed for other indications. RCC is considered the most lethal of urologic cancers because a patient without intervention who has stage IV metastatic disease has a 5-year survival rate of 23% in comparison to …

Long Term Functional And Esthetic Outcomes After Fibula Free Flap Reconstruction Of The Mandible, I. Petrovic, R. Blaser, Timothy Blackwell, C. Mccarthy, I. Ganley, S. Patel, P. Cordeiro, J.P. Shah

Rowan-Virtua Research Day

Objectives: To report functional and esthetic outcomes, after fibula free flap (FFF) reconstruction of the mandible for oral cancer, assessed by physicians, non-clinicians and patients.

Materials and Methods: Twenty-five long term survivors from oral cancer after FFF reconstruction were recalled for head and neck examination by surgeons and patient reported outcomes, using EORTC, QLQ C-30, H&N-35 and FACE-Q questionnaires.

Results: Physicians reported 64% restoration of functionality compared to normal. Patients reported high scores on QLQ-C30, but lower scores on H&N-35. Esthetic scores were reported higher by clinicians than non-clinicians. The decline in function and appearance was attributed to loss of …