Medicine and Health Sciences Commons^™

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects On Neuroinflammation And Synaptic Function Markers In A Mouse Model Of Doxorubicin-Based Chemotherapy, Tonya S. Orchard, Monica M. Gaudier-Diaz, Panchita Phuwamongkolwiwat-Chu, Rebecca Andridge, Maryam B. Lustberg, Joshua Bomser, Rachel M. Cole, Martha A. Belury, A. Courtney Devries

Clinical and Translational Science Institute

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six …

Permeability Changes And Effect Of Chemotherapy In Brain Adjacent To Tumor In An Experimental Model Of Metastatic Brain Tumor From Breast Cancer, Afroz S. Mohammad, Chris E. Adkins, Neal Shah, Rawaa Aljammal, Jessica I. G. Griffith, Rachel M. Tallman, Katherine L. Jarrell, Paul R. Lockman

Clinical and Translational Science Institute

Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of …

Updated Efficacy Of First Or Second-Line Pembrolizumab Plus In Metastatic Triple Negative Breast Cancer And Correlations With Baseline Lymphocyte And Naïve Cd4+ T-Cell Count, David Page, Joanna Pucilowska, Laura Bennetts, I Kim, Katherine Sanchez, Maritza Martel, Alison Conlin, Nikki Moxon, Staci Mellinger, Anupama Acheson, K Kemmer, Z Mitri, J Vuky, J Ahn, C Abaya, T Manigault, R Basho, Walter Urba, Hl Mcarthur

Books, Presentations, Posters, Etc.

Background: In mTNBC, anti-PD-1/L1 monotherapy is most effective when administered early in the course of disease, with recent trials demonstrating overall response rates (ORR) of 23-26% in the first-line setting and 5-6% in later lines. This may reflect iatrogenic lymphopenia from preceding cytotoxic chemotherapy. Furthermore, curative-intent chemotherapy is associated with prolonged suppression of naïve CD4+ cells, a T-cell subset that may play a critical role in the generation of de novo anti-tumor immune responses. We present the final clinical results of a pilot study evaluating the safety and efficacy of combining pembrolizumab plus standard-of-care capecitabine in the first/second-line mTNBC …

Actinomycin D And Telmisartan Combination Therapy Targets Lung Cancer Stem Cells, Ryan Green

USF Tampa Graduate Theses and Dissertations

The failure of lung cancer treatments has been attributed partly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. It has been suggested that a very small group of specific cells within the heterogeneous tumors, cancer initiating stem cells (CSC), develop resistance to treatment, survive and later initiate the growth of new tumors. Due to their pivotal role in maintenance and relapse of tumors following the acquisition of drug resistance, we reasoned that novel drugs targeting cancer cells and CSC might provide the most effective treatments, if not a cure. To this end, …

Clinical Audit To Assess Delays In Chemotherapy Administration At Daycare Oncology Center At A Tertiary Care Hospital In Karachi, Pakistan, Arifa Arifa Aziz, Zarka Samoon, Afsheen Feroz, Nadia Ayoub, Safia Awan, Madhia Beg

Department of Radiation Oncology

Aim: There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays. Materials and Methods: The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

The Impact Of Serum Glucose, Anti-Diabetic Agents, And Statin Usage In Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation, Nick A. Iarrobino, Beant S. Gill, Mark E. Bernard, Rainer J. Klement, Maria Werner-Wasik, Colin E. Champ

Radiation Medicine Faculty Publications

Introduction: Epidemiologic data indicate diabetes confers an augmented risk of lung cancer development, yet the relationship between hyperglycemia, metabolic agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti-diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC) patients undergoing chemoradiation.

Method and Materials: In total, data from 170 patients with stage III NSCLC treated at the University of Pittsburgh Medical Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival analysis was used to estimate time-to-event for overall survival (OS), disease-free survival, distant metastasis (DM), and loco-regional control (LRC). Blood glucose values (n …

Febrile Neutropenia, Tonja Plew

Nursing Student Class Projects (Formerly MSN)

Febrile Neutropenia (FN) is a common, yet potentially life-threatening, complication in cancer patients receiving myelosuppressive chemotherapy. FN occurs when a patient has a temperature of greater than 100.4℉ with an absolute neutrophil count of less than 500cells/mm³, which places the patient at a high risk for infection. Fever may be the only sign of FN. FN is an oncologic emergency, requiring immediate, aggressive treatment with broad-spectrum antibiotics. FN is associated with high morbidity and mortality in cancer patients.

Protection From Chemotherapy- And Antibiotic-Mediated Dysbiosis Of The Gut Microbiota By A Probiotic With Digestive Enzymes Supplement., Thomas E Ichim, Santosh Kesari, Kim Shafer

Articles, Abstracts, and Reports

There are numerous downstream consequences of marketed drugs like antineoplastic agents on the gut microbiome, an effect that is suggested to contribute to adverse event profiles and may also influence drug responses. In cancer, progress is needed toward modulation of the host microbiome to prevent off-target side effects of drugs such as gastrointestinal mucositis that result from gut dysbiosis. The objective of this study was evaluation of the bioactivity of a supplement consisting of capsules with a blend of 9 probiotic organisms of the genera

Implementation Of National Pediatric Guidelines To Prevent Chemotherapy Induced Nausea And Vomiting In Children With Cancer, Taryn Sandheinrich

Dissertations

Purpose: The purpose of this study was to assess the use of supplemental, as needed (prn) pharmacologic interventions for uncontrolled acute chemotherapy induced nausea and vomiting (CINV) in children with cancer after implementation of new pediatric CINV prophylaxis guidelines. Description of Project: A retrospective chart review was completed on forty-three children admitted to the hospital for chemotherapy during a 3 month period in 2017 to document the use of medications given for acute breakthrough CINV. The pre-implementation group received anti-emetics based on the institutional standard of care. A second retrospective chart review was completed on thirty-three children admitted to …

Metachronous Renal Ewing Sarcoma/Primitive Neuroectodermal Tumour In A Survivor Of Burkitt Lymphoma, Kumail Khandwala, Kiran Hilal, Zehra Fadoo, Khurram Minhas

Department of Radiology

We present a case of a 14-year-old girl who was diagnosed with Burkitt lymphoma in 2014. She was managed with chemotherapy and remained in remission for 3 years. On her surveillance imaging in 2017, a left-sided renal neoplastic mass was incidentally discovered. She underwent nephrectomy and pathology of the resected specimen revealed small cell tumour of the kidney with features favouring renal Ewing sarcoma/primitive neuroectodermal tumour. Molecular genetic analysis by fluorescence in situ hybridisation was performed which showed translocation of 22q12, thereby confirming the diagnosis. This is a rare secondary malignancy and an unusual association. This case highlights the importance …

Hazardous Drug Administration In The Home Setting: Reducing Exposure Risks, Cynthia D. Huff Msn, Rn, Ocn, Crni, Cnl

Master's Projects and Capstones

Hazardous drug (HD) administration used to be contained in controlled-healthcare settings, however, the introduction of HDs for home administration has become a growing area of concern for home health agencies. The objectives of the Clinical Nurse Leader (CNL) project aims to improve homecare nurses' knowledge of HDs and improve competency with personal protective equipment (PPE). The microsystem provides short-term homecare services for acute and chronically-ill patients. One team leader, two home infusion coordinators, and twelve registered infusion nurses participated in learning about exposure risks and PPE use with HD administration. Kotter's 8-step change theory was used to develop behavior change …

Olanzapine For Chemotherapy-Induced Nausea And Vomiting, John B. Bossaer

John B. Bossaer

Excerpt: Navari and colleagues (July 14 issue)1 report on the use of olanzapine for the prevention of chemotherapy-induced nausea and vomiting.

Circadian Regulation Of Temozolomide Sensitivity In Glioblastoma, Emily A. Slat

Arts & Sciences Electronic Theses and Dissertations

The safety and efficacy of multiple cancer chemotherapeutics can vary as a function of when during the day they are delivered. This study aimed to improve the treatment of glioblastoma multiforme (GBM), the most common brain cancer, by testing the efficacy of the DNA alkylator Temozolomide (TMZ) on GBM in vitro and in vivo as a function of time of day. We found cell-intrinsic, daily rhythms in susceptibility of GBM tumor cells (mouse astrocytes deficient in NF1 and p53 signaling) to TMZ in vitro. The greatest TMZ-induced DNA damage response, activation of apoptosis and growth inhibition, occurred near the peak …

Capecitabine And Temozolomide In Neuroendocrine Tumor Of Unknown Primary, Aman Chauhan, Zainab Farooqui, Leaundra Murray, Heidi L. Weiss, Zin W. Myint, Arun Kumar A. Raajasekar, B. Mark Evers, Susanne M. Arnold, Lowell B. Anthony

Internal Medicine Faculty Publications

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. Methods. Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012–2016). …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

Symptom Clusters And Quality Of Life Trajectories In Breast Cancer Patients Before And After Chemotherapy, Gaurav Kumar

Capstone Experience

Context. Breast cancer patients experience multiple concurrent symptoms before and after chemotherapy (CTX). Physical and psychological symptoms may persist after treatment and reduce the quality of life (QOL) of survivors.

Objectives. Identify differences in prevalence and severity of symptoms at three times within 1- year of starting CTX; and identify symptom cluster and QOL trajectories over these times in breast cancer patients.

Methods. Symptoms were identified in breast cancer patients (N=219) before the start of CTX (baseline), 30 days after the last CTX, and 1-year after the first CTX. Hospital Anxiety and Depression Scale and Symptom Experience Scale …

Translesion Synthesis Inhibitors As Anti-Cancer Adjuvant Agents, Kelly Allison Chan

University Scholar Projects

The translesion synthesis (TLS) pathway is a major mechanism through which cancer cells replicate past DNA lesions and promote chemoresistance. TLS allows cancers to survive genotoxic chemotherapy and increases the rate of mutation in tumors leading to drug-resistant cells. Cancer cells use a set of specialized low-fidelity TLS DNA polymerases to copy over lesions with Rev1 serving as a key scaffolding protein. Suppressing Rev1 activity sensitizes cancers to genotoxic chemotherapy and reduces the onset of chemoresistance by decreasing tumor mutation rate. Disruption of the Rev1/polζ-dependent TLS selective inhibitors has demonstrated the ability to sensitize cancer cells to platinating agents and …

Evaluating Itraconazole Analogues And Translesion Synthesis Inhibitors As Anti-Cancer Agents, Kelly Allison Chan

Honors Scholar Theses

My projects were to evaluate itraconazole (ITZ) analogues as anti-cancer hedgehog (Hh) and angiogenesis inhibitors, and translesion synthesis (TLS) inhibitors as anti-cancer agents. Itraconazole (ITZ) is a clinically effective triazole antifungal agent that has also been identified for its anti-cancer properties. As reported in the current literature, ITZ inhibits Gli1 transcription of the Hedgehog (Hh) signaling pathway and angiogenesis. However, the triazole moiety of ITZ has a detrimental side effect of inhibiting cytochrome P450 3A4 enzymes (CYP3A4). Thus, we have removed the triazole from the ITZ scaffold and develop a new series of ITZ analogues called des-triazole ITZ analogues. The …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Unusual Association Of Testicular Yolk Sac Tumor With Pectus Excavatum In An 18-Month-Old Child: A Case Report, Aditya P. Singh, Arvind K. Shukla, Dinesh K. Barolia, Pramila Sharma

Menoufia Medical Journal

Testicular tumors are rare in children, but highly treatable and usually curable. In children, testicular tumor accounts for ~ 1–2% of all tumors. Among testicular tumors, germ cell tumors have a bimodal age distribution. One peak occurs in the first 2 years of life and the second peak occurs in young adults 15–35 years of age. Germ cell tumors in children are distinct from that in adults in term of their behavior, histological nature, metastasis, and the treatment needed. Here, we present a case of testicular tumor with a chest wall deformity in an 18-month-old male child. This is the …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

Sab Concentration Determines The Chemotherapeutic Efficacy In Gynecological Cancer, Iru Paudel

FIU Electronic Theses and Dissertations

The American Cancer Society predicts there will be 110,070 new cases and 32,120 deaths due to gynecological malignancies in 2018. A major contributing factor to the high mortality associated with gynecological cancers is the recurrence of treatment-resistant tumors. Ovarian cancer (OC) remains the most lethal gynecological malignancy, yet the mechanisms responsible for regulating tumor resistance and vulnerability are largely unknown or undruggable. Therefore, the goal of this research is to identify mechanisms responsible for therapeutic resistance in gynecological cancers and discover innovative approaches to circumvent these molecular alterations. Our efforts began in OC where secondary analysis of gene expression data …

Treatment Options For Primary Cns Lymphoma, Abid Laghari, Syed Ijlal Ahmed, Adnan Jabbar, Muhammad Shahzad Shamim

Section of Haematology/Oncology

Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

Clinical Audit To Assess Delays In Chemotherapy Administration At Daycare Oncology Center At A Tertiary Care Hospital In Karachi, Pakistan, Arifa Aziz, Zarka Samoon, Mohammad Khurshid, Afsheen Feroz, Nadia Ayoub, Safia Awan, Madhia Beg

Section of Haematology/Oncology

Aim: There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays.

Materials and Methods: The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the …

Liposomal Irinotecan Accumulates In Metastatic Lesions, Crosses The Blood-Tumor Barrier (Btb), And Prolongs Survival In An Experimental Model Of Brain Metastases Of Triple Negative Breast Cancer, Afroz S. Mohammad, Jessica I. Griffith, Chris E. Adkins, Neal Shah, Emily Sechrest, Emma L. Dolan, Tori B. Terrell-Hall, Bart S. Hendriks, Helen Lee, Paul R. Lockman

Clinical and Translational Science Institute

Purpose—The blood-tumor barrier (BTB) limits irinotecan distribution in tumors of the central nervous system. However, given that the BTB has increased passive permeability we hypothesize that liposomal irinotecan would improve local exposure of irinotecan and its active metabolite SN-38 in brain metastases relative to conventional irinotecan due to enhanced-permeation and retention (EPR) effect. Methods—Female nude mice were intracardially or intracranially implanted with human brain seeking breast cancer cells (brain metastases of breast cancer model). Mice were administered vehicle, non-liposomal irinotecan (50 mg/kg), liposomal irinotecan (10 mg/kg and 50 mg/kg) intravenously starting on day 21. Drug accumulation, tumor burden, and survival …

Biodegradable Nanoparticles In The Treatment Of Cutaneous Malignancy, Emily Sara Yin

Yale Medicine Thesis Digital Library

Keratinocyte-derived carcinomas represent the most common type of malignancy worldwide, and while surgical removal is a first-line therapy, surgery may be impractical for certain patients and does not completely eliminate risk of recurrence. Previous studies have demonstrated the advantages of biodegradable poly(lactic acid)-hyperbranched polyglycerol non-bioadhesive nanoparticles (NNPs) and bioadhesive nanoparticles (BNPs) as chemotherapeutic drug delivery vehicles for the treatment of internal solid tumors. We are now investigating the use of this delivery system for the treatment of cutaneous malignancies, with the goal of maximizing drug efficacy while minimizing systemic effects and treatment-associated morbidity. After topical application of fluorescent dye-loaded NNPs …

Improved Therapy For Medulloblastoma: Targeting Hedgehog And Pi3k-Mtor Signaling Pathways In Combination With Chemotherapy, Nagendra K. Chaturvedi, Matthew J. Kling, Don W. Coulter, Timothy R. Mcguire, Sutapa Ray, Varun Kesherwani, Shantaram S. Joshi, J. Graham Sharp

Journal Articles: Radiation Oncology

Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated. Results showed that combined treatment of Vismodegib and BEZ235 …

Activity Of Pazopanib And Trabectedin In Advanced Alveolar Soft Part Sarcoma, S. Stacchiotti, O. Mir, A. Le Cesne, B. Vincenzi, A. Fedenko, R. G. Maki, N. Somaiah, S. Patel, M. Brahmi, A. Kawai, +13 Additional Authors

Journal Articles

No abstract provided.