Medicine and Health Sciences Commons^™

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 …

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 …

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

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 …

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.

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 …

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 …

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 …

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 …

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.

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, Courtney A. Devries

Faculty & Staff Scholarship

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 …

Prognostic Value Of 1p/19q Chromosomal Codeletion In Patients With Oligodendroglioma, Altaf Ali Laghari, Muhammad Usman Khalid, Namra Qadeer, Muhammad Shahzad Shamim

Section of Neurosurgery

Oligodendrogliomas are common intra-axial primary brain tumours, and carry special significance due to several key features, which when present provide better prognosis compared to other intra-axial tumours. One of these features is presence of 1p/19q chromosomal codeletion that seems to not only be a marker of better prognosis but also signifies better response to chemotherapy. Herein the authors review the literature for evidence of the prognostic value of 1p/19q codeletion in OD.

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …