Diseases Commons^™

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen

Jefferson Institute of Molecular Medicine Papers and Presentations

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANK_F377del mutation (Ank^KI/KI) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in Ank^KI/KI mice. PPi is a potent inhibitor of …

Sedation For Gi Endoscopy In The Morbidly Obese: Challenges And Possible Solutions, Lalitha Sundararaman, Basavana Goudra

Department of Anesthesiology Faculty Papers

With the increasing prevalence of obesity and morbid obesity, this subgroup's contribution to patients presenting for elective procedures requiring sedation is significant. Gastrointestinal (GI) procedures clearly form the largest group of such procedures. These procedures may be intended to treat obesity such as the insertion of an intragastric balloon or one or more unrelated procedures such as a screening colonoscopy and (or) diagnostic/therapeutic endoscopy. Regardless of the procedure, these patients pose significant challenges in terms of choice of sedatives, dosing, airway management, ventilation, and oxygenation. An understanding of dissimilarity in the handling of different groups of medications used by an …

Syphilitic Gumma Presenting As Squamous Cell Carcinoma Of Vulva: A Case Report, R.M. Nuss, A.J. Lazenby, Holly C. Provost, Tara Castellano

School of Medicine Faculty Publications

Introduction: Tertiary syphilis, a late form of the disease with neurologic, cutaneous, and cardiovascular manifestations, is rarely seen in the United States in modern times. Also called the “great imitator,” syphilis tends to mimic other disease processes, which can lead to a delay in proper diagnosis and treatment. Case: We present the case of a 59-year-old woman who presented for evaluation of possible squamous cell carcinoma of the vulva. After multiple inconclusive biopsies and extensive workup with multiple providers, she was instead found to have cutaneous and neurologic tertiary syphilis. A correct diagnosis was delayed in this patient due to …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

Antibody Therapies For Alzheimer's Disease, Alexandra Zerr

University Honors Theses

Alzheimer's Disease (AD) is the leading cause of dementia worldwide. Patients with this condition first experience mild cognitive impairment, followed by the loss of memory, cognitive skills, identity, and the ability to perform daily tasks unassisted, eventually culminating in death.

The dominant hypothesis for the mechanism of Alzheimer's, the amyloid cascade hypothesis, based on early-onset AD, suggests that amyloid plaques formed by Aβ peptides cause a cascading effect involving an increase in toxic tau protein, which is correlated with the disease progression of Alzheimer's patients. While the mechanism of late sporadic AD is not fully understood, this has been used …

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …

Clinical Implementation Of Tissue-Sparing Posterior Cervical Fusion: Addressing Market Access Challenges, Morgan Lorio, Pierce Nunley, Joshua Heller, Bruce Mccormack, Kai-Uwe Lewandrowski, Jon Block

Department of Neurosurgery Faculty Papers

Background: The traditional open midline posterior cervical spine fusion procedure has several shortcomings. It can cause soft tissue damage, muscle atrophy, compromise of the lateral masses and painful prominent posterior cervical instrumentation or spinous process if there is dehiscence of the fascia. Additionally, patients frequently experience the rapid development of adjacent segment disease, which can result in the reemergence of debilitating pain and functional impairment. Clinical relevance: Tissue-sparing posterior cervical fusion is an alternative method for treating patients with symptomatic cervical degenerative disc disease. However, widespread clinical adoption has been challenged by ambiguity, misunderstandings and misinterpretations regarding appropriate procedural reimbursement …

Comparative Plan Analysis: Helical Tomotherapy Vs. Linac Vmat For Lower Extremity Sarcomas, Marie E. Dibona

Masters Projects

Abstract

Introduction

Soft tissue sarcomas (STS) affect about 13,500 people annually in the United States, and those in the lower extremities present unique challenges in radiation therapy due to the wide variability in tumor sizes, sometimes exceeding 30cm. Traditional treatment involves C-Arm linear accelerators using Volumetric Modulated Radiation Therapy (VMAT), which provides precise targeting while sparing nearby organs. Helical Tomotherapy (HT) is another option, delivering radiation in a helical pattern with a binary MLC for a uniform dose distribution. However, no studies have compared VMAT and HT for lower extremity sarcomas of different sizes. This study aims to compare these …

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …

Effects Of E-Cigarettes On The Lung And Systemic Metabolome In People With Hiv, Aline Zaparte, Courtney J. Christopher, Connie Arnold, Lauren Richey, Adairre Castille, Kyle Mistretta, Christopher M. Taylor, Huiyi Lin, Steve Nelson, John P. Kirwan, John W. Apolzan, Shawn R. Campagna, David A. Welsh

School of Medicine Faculty Publications

The popularity of e-cigarettes (vaping) has soared, creating a public health crisis among teens and young adults. Chronic vaping can induce gut inflammation and reduce intestinal barrier function through the production of the proinflammatory molecule hydrogen sulfide (H2S). This is particularly concerning for people with HIV (PWH) as they already face impaired immune function and are at a higher risk for metabolic dysregulation, diabetes, and chronic liver disease. Furthermore, PWH experience unhealthy behaviors, making it crucial to understand the systemic metabolic dysregulation and pathophysiological mechanisms associated with vaping in this population. Here, we employed liquid chromatography–mass spectrometry (LC-MS)-based metabolomics to …

Stanniocalcin 2 Governs Cancer Cell Adaptation To Nutrient Insufficiency Through Alleviation Of Oxidative Stress, Shuo Qie, Haijuan Xiong, Yaqi Liu, Chenhui Yan, Yalei Wang, Lifeng Tian, Chenguang Wang, Nianli Sang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by …

Novel Case Of Staphylococcal Scalded Skin Syndrome In A 26-Year-Old With A History Of Ichthyosis, Gunja S. Shah, Sarah Snyder, Kayvan Mirhadi

Advances in Clinical Medical Research and Healthcare Delivery

Staphylococcal scalded skin syndrome (SSSS) is a bacterial toxin-mediated skin disorder that primarily affects neonates but rarely also presents in adults with underlying kidney disease. We present a case of a 26-year-old male with SSSS which was challenging to identify due to an underlying diagnosis of congenital epidermolytic ichthyosis. This case is novel as it is the first documented case of SSSS in an adult with ichthyosis. It highlights the unique challenge of recognizing cutaneous infections in patients with underlying skin disorders especially in the setting of a rural hospital without in-person dermatology coverage.

An Interesting Case Of Wunderlich Syndrome And Page Kidney, Megan Worthington, Nicholaus Monsma, Raj Pyne

Advances in Clinical Medical Research and Healthcare Delivery

We present a case of Wunderlich Syndrome and Page Kidney, a rarely reported combination. Wunderlich Syndrome, characterized by spontaneous renal hemorrhage without a history of trauma, is typically associated with Lenk’s triad of flank pain, mass, and hypovolemia. Page Kidney induced hypertension, a rare condition resulting from external renal compression associated with renin-mediated mechanisms. Our case demonstrates the importance in quick recognition and treatment as blood pressure changes can be fast and dramatic. Our case also has the added dimension of renin measurements. After the patients hypertension developed, his initial renin levels were within normal range, but they later showed …

Missing The Overlap, Rutwik Pradeep Sharma, Mohamed Mohamed Ahmed, Ryan Tam, Alexander T. Kusnik, Ali Jaan, Ari Chodos, Krishna Tangirala

Advances in Clinical Medical Research and Healthcare Delivery

A 43-year-old female presented with painful obstructive jaundice, a mixed pattern of elevation of liver injury markers and neutrophilic leukocytosis. Evaluation with endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. The antimitochondrial antibody (AMA) titers were elevated. She was discharged on ursodeoxycholic acid (UDCA) for Primary Biliary Cirrhosis (PBC) but was readmitted for worsening symptoms. The patient's liver biopsy results suggested Overlap syndrome (Primary Biliary Cirrhosis-Autoimmune hepatitis). She was then given corticosteroid therapy concurrently with UDCA after which she improved and remained asymptomatic. In conclusion, we would like to report this atypical presentation of overlap syndrome and hope the medical community learns …

Intrathecal Bupivacaine And Clonidine For Refractory Hyperhidrosis In Spinal Cord Injury, Soun Sheen, Hemant Kalia

Advances in Clinical Medical Research and Healthcare Delivery

Introduction: Autonomic dysreflexia (AD) in spinal cord injury (SCI) can present as hyperhidrosis due to sudomotor dysfunction. There are no standard treatment guidelines for refractory hyperhidrosis due to persistent noxious stimulation.

Case: A 58-year-old female with C7 ASIA-A quadriplegia was admitted to the hospital in 2018 for T7-8 discitis. Discitis acted as a noxious stimulus manifesting clinically as autonomic dysreflexia. On average, she experienced 50-60 sweating episodes every day. She underwent serial stellate ganglion blocks with >75% improvement which provided 9 months of continued relief. Patient transitioned to intrathecal bupivacaine 2.5mg/ml + Clonidine 200mcg/ml with the catheter tip located at …

Analyzing Hiv/Aids Trends And Disparities In The Bronx: A Comparative Study With Nyc Boroughs, Caleb Adjei

CUNY Mexican Studies Institute

This study analyzes changes in reported HIV/AIDS cases over time in the Bronx, identifying the racial/ethnic groups and neighborhoods most affected by the disease. The Bronx consistently exhibits the highest rate of new HIV diagnoses among New York City’s boroughs, with Latino/Hispanic and Black populations being disproportionately impacted. Key neighborhoods like High Bridge-Morrisania, Crotona-Tremont, and Fordham-Bronx Park have the highest case concentrations. Despite advancements in healthcare and treatments like antiretroviral therapy, disparities persist. The findings highlight the need for targeted interventions to support the most affected communities and address the underlying social determinants contributing to the disparities in HIV/AIDS diagnoses.

The Role Of Southern Red-Backed Voles, Myodes Gapperi, And Peromyscus Mice In The Enzootic Maintenance Of Lyme Disease Spirochetes In North Dakota, Usa, Michael W. Dougherty, Nathan M. Russart, Robert A. Gaultney, Emily Marie Gisi, Haley M. Cooper, Lindsey R. Kallis, Catherine A. Brissette, Jefferson A. Vaughan

Biology Faculty Publications

Lyme disease has expanded into the Great Plains of the USA. To investigate local enzootic transmission, small mammals were trapped in two forested tracts in northeastern North Dakota during 2012 and 2013. Peromyscus mice and southern red-backed voles, Myodes gapperi, comprised over 90% of all mammals captured. One site was dominated by Peromyscus (79% of 100 mammals captured). At the other site, M. gapperi (59% of 107 mammals captured) was more abundant than Peromyscus (36%). Immature stages of two tick species parasitized small mammals: Dermacentor variabilis and Ixodes scapularis. Larval I. scapularis ectoparasitism was significantly higher on Peromyscus (81% …

Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer

Faculty, Staff and Student Publications

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.

METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …

Comparing Virtual Reality Vs. Augmented Reality In Promoting Covid-19 Self-Testing, Vaccination, And Preventive Behaviors, Zhan Xu, Lisa Dam

Hank Greenspun School of Journalism and Media Studies Faculty Research

Objective: Virtual Reality (VR) and Augmented Reality (AR) are innovative technologies that can serve as effective tools for creating health interventions by altering psychological distance. Based on construal level theory and the reality-virtuality continuum, we designed, tested, and compared VR and AR campaigns to encourage proactive measures against COVID-19. Methods: 143 participants were randomly assigned to one of three messages: VR, AR, and a CDC video, and completed surveys before, immediately, and one week following message exposure. Results: VR and AR increased preventive intentions and behaviors against COVID-19 both in the short and long run. VR was particularly effective as …

Cardiac Mass In A 78-Year-Old Patient With A History Of Cancer: Diagnostic And Treatment Challenges, Bihong Zhao, Ayah Zaqqa, Michelle M Mcdonald, Ismael A Salas De Armas, Igor D Gregoric, L Maximilian Buja

The Texas Heart Institute Journal

Primary cardiac angiosarcoma is a rare, aggressive malignancy that commonly metastasizes to various organs. The presenting symptoms are typically nonspecific, so a comprehensive examination is required to confirm the diagnosis promptly. This case report describes the presentation of an older patient with a history of neoplasms. Echocardiography and biopsy were performed, but despite surgical intervention to resect a large right atrial mass, the patient died. A final diagnosis of primary angiosarcoma was made based on the resected specimen.

G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott

Department of Biochemistry and Molecular Biology Faculty Papers

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E Quiring, Raeann M Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H Parikh, Benjamin A Fink, Thomas Mueller, Gordon Brown

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

Safety And Feasibility Of Third-Party Cytotoxic T Lymphocytes For High-Risk Patients With Covid-19, Dolores Grosso, John L. Wagner, Allyson O'Connor, Kaitlyn Keck, Yanping Huang, Zi-Xuan Wang, Hilary Mehler, Benjamin Leiby, Phyllis Flomenberg, Usama Gergis, Neda Nikbakht, Michael Morris, Julie Karp, Alexis R. Peedin, Neal Flomenberg

COVID-19 Papers, Posters, and Presentations

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received …

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …

The Athero-Af Study: A Need To Optimize Af Management In An Environment Of Medical Advancement, Michael D. Ezekowitz, Ibrahim Alameh, Mohammed Kamareddine

Department of Medicine Faculty Papers

No abstract provided.

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …