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Full-Text Articles in Medicine and Health Sciences

Photon Irradation And Cisplatin Enrich Cancer Stem Cells In Ovarian Cancer, Ashley Antonissen May 2024

Photon Irradation And Cisplatin Enrich Cancer Stem Cells In Ovarian Cancer, Ashley Antonissen

Electronic Theses, Projects, and Dissertations

High Grade Serous Ovarian Cancer (HGSOC) has a 5-year survival rate of less than 50%. Ovarian cancer is one of the deadliest gynecological diseases and the 7th most common female cancer worldwide. Ovarian cancer patients generally have a poor prognosis despite the relatively successful treatments. When conventional cancer treatments, such as cisplatin chemotherapy and photon irradiation, are administered, residual cancer stem-like cells (CSCs) can survive, leading to CSC enrichment. CSCs are a small population of cancer cells that exhibit stem-like characteristics: quiescence (slowing of the cell cycle), differentiation, proliferation, and self-renewal to regenerate new CSCs. We hypothesized that providing cancer …


Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru Jan 2024

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …


Management And Prognosis Of Patients With Cancer Of Unknown Primary: 20 Years Of Experience, Murat Bardakçi, Efnan Algin, Büşra Dügeroğlu, Öznur Bal, Fahri̇ye Tuğba Köş, Doğan Uncu Dec 2023

Management And Prognosis Of Patients With Cancer Of Unknown Primary: 20 Years Of Experience, Murat Bardakçi, Efnan Algin, Büşra Dügeroğlu, Öznur Bal, Fahri̇ye Tuğba Köş, Doğan Uncu

Turkish Journal of Medical Sciences

Background/aim: Cancer of unknown primary (CUP) is a difficult clinical entity to manage. The aim of the study was to investigate the sociodemographic and pathological characteristics, treatment options, and factors affecting overall survival (OS) in CUP patients whose primary tumor was not detected during follow-up. Materials and methods: A total of 243 CUP patients whose primary tumors could not be detected during follow-up were included in the study. Their demographic characteristics, survival outcomes, and prognostic factors were investigated. Results: Of the 243 patients included in this study, 61.7% were male and 38.3% were female, and the median age was 61 …


Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang Oct 2023

Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA+), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …


Acute Esophageal Necrosis And Duodenal Disease In The Setting Of Recently Initiated Chemotherapy, Kulveer Dabb, Ryan Jansen Van Rensburg, Heba Yusuf, Daniel Klein, Alexander D. Lake, Mohamed Kaif Aug 2023

Acute Esophageal Necrosis And Duodenal Disease In The Setting Of Recently Initiated Chemotherapy, Kulveer Dabb, Ryan Jansen Van Rensburg, Heba Yusuf, Daniel Klein, Alexander D. Lake, Mohamed Kaif

HCA Healthcare Journal of Medicine

Introduction

Acute esophageal necrosis (AEN), commonly referred to as “black esophagus” or Gurvits syndrome, is a rare condition characterized by diffuse black mucosa in the distal esophagus. Most often, the patient is an older male with multiple comorbidities, presenting with upper gastrointestinal bleeding. The exact pathogenesis is unclear, but it is often thought to be secondary to acute vascular hypo-perfusion or ischemia of the esophageal mucosa in critically ill patients with certain secondary comorbid conditions such as renal insufficiency, diabetes mellitus, dyslipidemia, coronary artery disease, malnourishment, alcohol abuse, or association with an underlying malignancy.

Case Presentation

We present a case …


Radial Arterial Waves For Chemotherapy- And Radiotherapy-Related Myocardial Damage Identification In Patients With Breast Cancer, Chia-Ying Lee, Daniela Yunchin Yen, Mark C. Hou, Ying-Ling Chen, Rong-Jen Shiau May 2023

Radial Arterial Waves For Chemotherapy- And Radiotherapy-Related Myocardial Damage Identification In Patients With Breast Cancer, Chia-Ying Lee, Daniela Yunchin Yen, Mark C. Hou, Ying-Ling Chen, Rong-Jen Shiau

BioMedicine

Introduction

Chemotherapy and radiation therapy for breast cancer cause side effects, such as cardiovascular changes, which can be monitored with echocardiography. However, more convenient methods are always encouraged. Radial arterial waves that are used to detect cardiovascular changes can be used to assist in confirming cardiovascular changes.

Aim

This retrospective study aimed to analyze the frequency and time domains of the radial artery pulse wave in patients with breast cancer to understand its effectiveness in identifying cardiovascular changes.

Methods

Patients with breast cancer were screened from the pulse examination records in

Changhua Christian Hospital and divided into the treatment and …


Comparison Of The Inhibition Of An Oct3 Transporter Inhibitor, Nilotinib, On Doxorubicin’S Effects On Cardiac And Cancer Cell Lines, Zachary G. Tan, Juliet Melnik, Aakash Belsare, James Huang, Meagan Lyons, Kimberly Dowes, Gurpreet Kaur, Lindon H. Young, Robert J. Barsotti, Qian Chen May 2023

Comparison Of The Inhibition Of An Oct3 Transporter Inhibitor, Nilotinib, On Doxorubicin’S Effects On Cardiac And Cancer Cell Lines, Zachary G. Tan, Juliet Melnik, Aakash Belsare, James Huang, Meagan Lyons, Kimberly Dowes, Gurpreet Kaur, Lindon H. Young, Robert J. Barsotti, Qian Chen

Research Day

Introduction

Doxorubicin (DOX)-induced cardiotoxicity remains a significant barrier limiting its clinical application due to a lack of effective resolution. Targeting how DOX enters cardiac and cancer cells is a promising new strategy. Research suggests that an OCT3 transporter significantly contributes to DOX entry into the heart tissue. By contrast, it expresses much lower on breast cancer cell lines. Moreover, Nilotinib (NIB) can suppress OCT3 transporter function by 80%. Therefore, exploring the impact of NIB on the DOX’s effects on cardiac and cancer cell lines by altering DOX intracellular accumulation is intriguing.

Objective

First, we would establish a dose-response curve of …


Accidental Extravasation Of Mitomycin C Into The Subcutaneous Tissue, Johnathon Chung, Brooke Walterscheid, Jose Lopez-Vera, Hytham Rashid, Mike K. Liang Apr 2023

Accidental Extravasation Of Mitomycin C Into The Subcutaneous Tissue, Johnathon Chung, Brooke Walterscheid, Jose Lopez-Vera, Hytham Rashid, Mike K. Liang

HCA Healthcare Journal of Medicine

Introduction

Mitomycin C (MMC) is a common chemotherapeutic agent used to treat a variety of solid tumors. Cutaneous adverse events are rare, but MMC is a known vesicant reported to cause tissue necrosis and sloughing, erythema, and ulceration if incorrectly infused into the subcutaneous tissue. Definitive treatment of extravasation injuries due to MMC depends on the severity of the cutaneous manifestation, which includes stopping the infusion, removing the catheter, or possible debridement.

Case Presentation

We present the case of a 70-year-old female with extensive soft-tissue injury secondary to extravasation of MMC that required hospital admission and surgical intervention to remove …


Patterns Of Postmastectomy Radiation Therapy In Clinically Node-Positive Breast Cancerpatients With Pathologically Negative Lymph Nodes After Neoadjuvant Chemotherapy, Mutlay Sayan, Irina Vergalasova, Mridula George, Maria Kowzun, Lindsay Potdevin, Shicha Kumar, Bruce Haffty, Nisha Ohri Jan 2022

Patterns Of Postmastectomy Radiation Therapy In Clinically Node-Positive Breast Cancerpatients With Pathologically Negative Lymph Nodes After Neoadjuvant Chemotherapy, Mutlay Sayan, Irina Vergalasova, Mridula George, Maria Kowzun, Lindsay Potdevin, Shicha Kumar, Bruce Haffty, Nisha Ohri

Turkish Journal of Medical Sciences

Background/aim: To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node-positive breast cancer who are pathologically node-negative (ypN0) after neoadjuvant chemotherapy (NAC). Materials and methods: Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive nonmetastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. Results: The study included 8766 clinically node-positive patients who met the …


Predictors Of Lymphovascular Invasion In Estrogen Receptor Positive/Her-2 Negative Breast Cancer Patients Treated With Neoadjuvant Chemotherapy, Eyyüp Çavdar, Yakup İri̇ağaç Jan 2022

Predictors Of Lymphovascular Invasion In Estrogen Receptor Positive/Her-2 Negative Breast Cancer Patients Treated With Neoadjuvant Chemotherapy, Eyyüp Çavdar, Yakup İri̇ağaç

Turkish Journal of Medical Sciences

Background/aim: Lymphovascular invasion (LVI) is considered a high-risk factor for recurrence in early-stage breast cancer, hence examination of LVI in pathological samples is an absolute recommendation. We aim to investigate predictive factors of LVI in preneoadjuvant chemotherapy (NAC) patients with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) molecular subtypes of breast cancer. Materials and methods: One hundred and thirty-four patients treated with NAC were included in this study who were ER+/HER2-. The clinical characteristics of the patients, the data obtained from the core needle biopsy before NAC and the LVI status in the pathology …


Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta Sep 2021

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in


Generating Cisplatin Resistant Hpv-Positive Hnscc Cell Lines, Temitope Akintola Aug 2021

Generating Cisplatin Resistant Hpv-Positive Hnscc Cell Lines, Temitope Akintola

Undergraduate Student Research Internships Conference

Acquired or innate resistance to chemotherapy poses a significant challenge in the treatment of head and neck squamous cell carcinomas (HNSCC). HNSCCs are often treated with a combination of surgery, radiation and chemotherapy, with cisplatin being a standard-of-care chemotherapy drug. Human Papillomavirus (HPV) associated HNSCCs have better treatment outcomes and prognosis when compared to HPV- HNSCCs. However, a subset (15-20%) of HPV+ patients develop treatment resistant diseases. The purpose of this study is to generate in-vitro models of cisplatin resistance in five HNSCC cell lines. We aim to characterize the generated cells in order to identify target genes that may …


Polθ Promotes The Repair Of 5'-Dna-Protein Crosslinks By Microhomology-Mediated End-Joining, Gurushankar Chandramouly, Shuren Liao, Timur Rusanov, Nikita Borisonnik, Marissa L Calbert, Tatiana Kent, Katherine Sullivan-Reed, Umeshkumar Vekariya, Ekaterina Kashkina, Tomasz Skorski, Hong Yan, Richard T Pomerantz Mar 2021

Polθ Promotes The Repair Of 5'-Dna-Protein Crosslinks By Microhomology-Mediated End-Joining, Gurushankar Chandramouly, Shuren Liao, Timur Rusanov, Nikita Borisonnik, Marissa L Calbert, Tatiana Kent, Katherine Sullivan-Reed, Umeshkumar Vekariya, Ekaterina Kashkina, Tomasz Skorski, Hong Yan, Richard T Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5' terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5' terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to …


Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls Jan 2021

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …


The Prognostic Value Of Serum Levels Of A Proliferation-Inducing Ligand (April) Intreatment-Naïve Patients With Chronic Lymphocytic Leukemia, Si̇nem Ni̇hal Esatoğlu, Di̇lek Keski̇n, Ahmet Emre Eşkazan, Tuğrul Elverdi̇, Ayşe Sali̇hoğlu, Muhli̇s Cem Ar, Şeni̇z Öngören, Zafer Başlar, Yildiz Aydin, Hafi̇ze Uzun, Teoman Soysal Jan 2021

The Prognostic Value Of Serum Levels Of A Proliferation-Inducing Ligand (April) Intreatment-Naïve Patients With Chronic Lymphocytic Leukemia, Si̇nem Ni̇hal Esatoğlu, Di̇lek Keski̇n, Ahmet Emre Eşkazan, Tuğrul Elverdi̇, Ayşe Sali̇hoğlu, Muhli̇s Cem Ar, Şeni̇z Öngören, Zafer Başlar, Yildiz Aydin, Hafi̇ze Uzun, Teoman Soysal

Turkish Journal of Medical Sciences

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), …


Lycopene Sensitizes The Cervical Cancer Cells To Cisplatin Via Targeting Nuclear Factorkappab (Nf-��B) Pathway, Oktay Hali̇t Aktepe, Taha Koray Şahi̇n, Gürkan Güner, Zafer Arik, Şuayi̇b Yalçin Jan 2021

Lycopene Sensitizes The Cervical Cancer Cells To Cisplatin Via Targeting Nuclear Factorkappab (Nf-��B) Pathway, Oktay Hali̇t Aktepe, Taha Koray Şahi̇n, Gürkan Güner, Zafer Arik, Şuayi̇b Yalçin

Turkish Journal of Medical Sciences

Background/aim: Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. Materials and methods: HeLa cells were treated with cisplatin (1 μM) alone, lycopene (10 μM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-ΚB), B-cell-associated X protein (Bax), nuclear factor erythroid …


The Acute Effects Of 5 Fluorouracil On Skeletal Muscle Resident And Infiltrating Immune Cells In Mice, Brandon N. Vanderveen, Alexander T. Sougiannis, Kandy T. Velazquez, James A. Carson, Daping Fan, E. Angela Murphy Dec 2020

The Acute Effects Of 5 Fluorouracil On Skeletal Muscle Resident And Infiltrating Immune Cells In Mice, Brandon N. Vanderveen, Alexander T. Sougiannis, Kandy T. Velazquez, James A. Carson, Daping Fan, E. Angela Murphy

Faculty Publications

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis …


Dna Aptamer-Drug Targeting Chemotherapy: Investigation Of Cell Cycle Inhibition Via S15 Aptamer – Norcantharidin Complex, Shannon Fehr Nov 2020

Dna Aptamer-Drug Targeting Chemotherapy: Investigation Of Cell Cycle Inhibition Via S15 Aptamer – Norcantharidin Complex, Shannon Fehr

Senior Honors Theses

Lung Cancer is the leading cause of cancer related death in both men and women in the United States (Bray et al., 2018). Cancer treatments are often non-specific and kill many dividing cells within a patient causing unwanted side effects. Norcantharidin (NCTD) is a synthetic FDA approved treatment for cancers including non-small cell lung cancers (NSCLC). NCTD suppresses cell proliferation by inhibiting cells from exiting the G2 phase of the cell cycle. Aptamers are short single-stranded DNA or RNA molecules with ligand directed self-annealing capabilities allowing selective binding to specific targets. This paper will discuss the hypothesized effects of using …


Allogeneic Mesenchymal Cell Therapy In Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The Cctrn Seneca Trial., Roberto Bolli, Emerson C Perin, James T Willerson, Phillip C Yang, Jay H Traverse, Timothy D Henry, Carl J Pepine, Raul D Mitrani, Joshua M Hare, Michael P Murphy, Keith L March, Sohail Ikram, David P Lee, Connor O'Brien, Jean-Bernard Durand, Kathy Miller, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Adrian P Gee, Sara Richman, Doris A Taylor, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara M Simpson, Dejian Lai, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari Nov 2020

Allogeneic Mesenchymal Cell Therapy In Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The Cctrn Seneca Trial., Roberto Bolli, Emerson C Perin, James T Willerson, Phillip C Yang, Jay H Traverse, Timothy D Henry, Carl J Pepine, Raul D Mitrani, Joshua M Hare, Michael P Murphy, Keith L March, Sohail Ikram, David P Lee, Connor O'Brien, Jean-Bernard Durand, Kathy Miller, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Adrian P Gee, Sara Richman, Doris A Taylor, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara M Simpson, Dejian Lai, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Journal Articles

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.

OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.

METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10

RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the …


Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt May 2020

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …


How Can We Stop Cancer?, Joseph R. Current May 2020

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …


Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang Apr 2020

Adverse Aftereffects Of Methotrexate As Chemotherapy On Cognitive Deficits In Rat Models, Jubin Kang

Senior Honors Theses

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed …


Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson Jan 2020

Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson

Theses and Dissertations--Toxicology and Cancer Biology

Triple negative breast cancer (TNBC) comprises 15-20% of breast cancers, affects a younger patient population than other subtypes, and is very aggressive. TNBC is comprised of a diverse group of tumors that have proven refractory to targeted therapy and can be difficult to treat. Patients generally receive neoadjuvant chemotherapy (NAC), surgery, and radiotherapy. The standard of care for NAC includes a taxane, an anthracycline, and/or cyclophosphamide, and administration of NAC has resulted in pathological complete response (pCR) in 30-40% of patients. However, a majority of TNBC patients will not reach pCR and instead have residual disease (RD), which is associated …


The Generation Of Novel Metal-Folate- Phenanthroline Complexes And Phenanthroline-Folate Conjugates With Potential As Chemotherapeutic Agents, Aisling Crowley Jun 2019

The Generation Of Novel Metal-Folate- Phenanthroline Complexes And Phenanthroline-Folate Conjugates With Potential As Chemotherapeutic Agents, Aisling Crowley

Doctoral

The folate receptor (FR) was identified in 1986 and has been established as a ‘molecular Trojan Horse’ target for the uptake of folate-conjugated organic molecules into cells. The FR is overexpressed in many malignancies, including those of the ovary, uterus, breast, cervix, and prostate, yet it is reportedly under-expressed in normal healthy cells. This difference in expression and the high affinity/specificity of folate towards the folate receptor presents a promising drug delivery system. The aim of this research was to utilise folic acid as a targeting moiety and generate simple metal folate and novel folate-phenanthroline complexes with cytotoxic properties. A …


Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler Apr 2019

Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler

Selected Honors Theses

Leukemia is the number one cancer affecting children in the nation, with acute lymphoblastic leukemia being the most prevalent classification.1 While new and innovative treatment protocols have greatly increased the success rate of primary cancer patients, those who face relapse receive a much more dismal prognosis. Recent studies have shown that patients who relapse quite frequently have developed drug-resistant clones of the original cancer cells, leading to a need for various secondary treatment options. The drug-resistance is due to clonal mutations that take place within the cancer cell, most often because of an outside pressure or stress within the environment …


Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey Jan 2019

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …


Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson May 2018

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 …


A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo Apr 2018

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 Apr 2018

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 Mar 2018

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 …