Medical Specialties Commons^™

Myocarditis Concurrent With Sweet Syndrome: A Presentation Of Acute Myeloid Leukemia, Christopher G. Burkeen, David Pottinger, Chaitanya Iragavarapu, Reshma Ramlal, Gerhard C. Hildebrandt

Markey Cancer Center Faculty Publications

Acute myeloid leukemia (AML) is the most common acute leukemia in American adults and portends a poor prognosis if untreated. Commonly, AML presents with symptoms related to concurrent leukopenia, anemia, or thrombocytopenia; however, due to its ability to affect many organ systems in the body, AML can have a highly varied clinical presentation. One such presentation is myocarditis, which is a rarely reported manifestation of AML. Myocarditis can have a varied clinical picture and often requires exclusion of other causes of cardiac dysfunction. Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is another presentation of AML; however, it is …

The Immune Microenvironment And Relation To Outcome In Patients With Advanced Breast Cancer Treated With Docetaxel With Or Without Gemcitabine, Elisabeth S. Stovgaard, Karama Asleh, Nazia Riaz, Samuel Leung, Dongxia Gao, Lise B. Nielsen, Anne-Vibeke Lænkholm, Eva Balslev, Maj-Britt Jensen, Dorte Nielsen, Torsten O. Nielsen

Centre for Regenerative Medicine & Stem Cell Research

Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used. Immunohistochemical staining for CD8, FOXP3, LAG3, PD-1, PD-L1 and CD163 was performed. Tumor infiltrating lymphocytes (TILs) and tumor associated macrophages were evaluated. Prespecified …

Disruption Of Foxo3a-Mirna Feedback Inhibition Of Igf2/Igf-1r/Irs1 Signaling Confers Herceptin Resistance In Her2-Positive Breast Cancer, Liyun Luo, Zhijie Zhang, Ni Qiu, Li Ling, Xiaoting Jia, Ying Song, Hongsheng Li, Jiansheng Li, Hui Lyu, Hao Liu, Zhimin He, Bolin Liu, Guopei Zheng

School of Medicine Faculty Publications

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 …

Increased Diagnosis Of Hepatocellular Carcinoma In Hospitalized Patients With Alcohol Related Hepatitis After The Covid-19 Outbreak: A Global Multi-Center Propensity Matched Analysis., Abhilash Perisetti Md, Randeep Kaur, Ragesh Thandassery

PCI Publications and Projects

No abstract provided.

Standardization Of Fertility Preservation Discussion Amongst Pediatric Oncology And Bone Marrow Transplant Patients: A Single Institution Experience, Chandni Dargan, Sarah E. Mc Dermott, Shelby Chesbro

Research Days

Background/Project Intent (Aim Statement): As treatment for pediatric malignancies improves long term survival, physicians are shifting focus to late effects of therapy such as infertility. Currently, options for fertility preservation include cryopreservation of mature oocytes, sperm, and gonadal tissue, although barriers remain present. Within our division, we lacked a standard approach to discussing fertility preservation options prior to initiation of treatment.

Methods (include PDSA cycles): Records from 474 pediatric patients with new oncologic diagnoses at CMH from 2014- 2020 were retrospectively reviewed. We evaluated the frequency that reproductive health discussions were documented in pubertal males and females requiring chemotherapy or …

The Role Of Vgll4 And Mark2-Hdac Axis In Mitosis And Cancer, Yongji Zeng

Theses & Dissertations

The Hippo pathway is an evolutionarily conserved signaling pathway that plays important roles in stem cell biology, tissue homeostasis, and cancer development. The Hippo core signaling pathway features a kinase cascade consisting of mammalian sterile-20 like protein 1/2 (Mst1/2) and large tumor suppressor 1/2 (Lats1/2). Inactivation of the Hippo pathway is correlated with the promotion of proliferation and anti-apoptosis through activation of the transcriptional co-activator Yes-associated protein (YAP). YAP functions through binding with TEA-domain transcription factors (TEAD1–4) to activate target genes.

Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo-Yes associated protein (YAP) pathway. Vgll4 inhibits cell proliferation …

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Secreted Mucin 5ac-Mediated Epithelial And Stromal Modulations Augment Pancreatic Cancer Aggressiveness, Koelina Ganguly

Theses & Dissertations

The mucosal layer that shields the epithelium of the body cavities is made up of high molecular weight, heavily glycosylated proteins called mucins that are broadly categorized into transmembrane and secreted members. Aberrant expression of secreted mucin MUC5AC has been implicated in lung, stomach, and colon cancer pathologies. MUC5AC is expressed de novo in the pancreas upon oncogenic insult, and its abundance in pancreatic tumor and circulation correlates to disease progression. However, few studies have explored beyond the diagnostic and prognostic significance of MUC5AC in pancreatic cancer (PC).

In this dissertation, we sought to investigate the mechanistic contribution of MUC5AC …

A Phase I Trial Of The Met/Alk/Ros1 Inhibitor Crizotinib Combined With The Vegf Inhibitor Pazopanib In Patients With Advanced Solid Malignancies, Sarina A Piha-Paul, Ecaterina E Dumbrava, Binoj C Nair, Wendy Xiong, Li Xu, Rosa Mostorino, Vivek Subbiah, Nizar Tannir, Siqing Fu, Aung Naing, Filip Janku, Daniel D Karp, Shreyaskumar Patel, Najat C Daw, David Hong, Funda Meric-Bernstam, Ralph G. Zinner

Department of Medical Oncology Faculty Papers

Background: Crizotinib inhibits ALK, MET and ROS1 tyrosine kinases but the development of resistance to monotherapy is an issue. The anti-angiogenic properties of pazopanib could overcome crizotinib drug resistance. Additionally, the anti-angiogenic properties of crizotinib could augment the clinical efficacy of pazopanib.

Methods: We evaluated the safety and responses in patients with advanced solid tumors treated with crizotinib and pazopanib.

Results: Eighty-two patients (median age 53 years, range 18-78 years) were enrolled. The median number of prior systemic therapies was 3 (range, 0-8). We were able to dose escalate to dose level 8 (crizotinib 250 mg twice daily and pazopanib …

The Effect Of Carfilzomib And Bortezomib Based Regimes On Cardiotoxicity In Multiple Myeloma Patients At Cooper University Hospital, Ami Patel, Tulin Budak-Alpdogan, Stalam Tapati

Rowan-Virtua Research Day

Introduction

• Multiple myeloma (MM) is a cancer of plasma cells, which is a white blood cell that normally produces antibodies
• Treatment in patients younger than 65 years old is typically high dose chemotherapy, usually with bortezomib based regimens or lenalidomide dexamethasone, followed by a stem cell transplant
• For patients with relapsed myeloma, carfilzomib is usually the treatment of choice
• Carfilzomib is a highly selective, irreversible proteasome inhibitor that binds to the 20 S proteasome. Several studies have illustrated that carfilzomib has been associated with cardiovascular adverse events (CVAE).
• Current literature on the role and effect of bortezomib on cardiotoxicity is …

Phyllodes Tumor Containing Invasive Ductal Carcinoma: A Rare Case Description & Review Of Literature, Kathryn Eckert, John Ground, Alyssa Imperatore, Victoria Tiedemann, Linda Szczurek

Rowan-Virtua Research Day

Phyllodes tumors are uncommon, often benign, malignancies of the breast and account for approximately 0.5% of all breast malignancies. These tumors were first described in 1838 by Johannes Muller as cystosarcoma phyllodes and were later more aptly renamed phyllodes tumors (as they were neither cystic nor sarcomatous).(1) As a mixed connective tissue and epithelial tumor, these behave similar to benign fibroadenomas, though their growth is much more rapid and they tend to occur in older patients.(2) Hallmarked by their large size at presentation, these tumors average between 4 and 7 cm at the time of diagnosis. The only known risk …

Assessment Of Factors Preventing Adequate Decline In Cervical Cancer Rates Amongst Minority Women In New Jersey, Rosie Wenrich, Jillian Baker

Rowan-Virtua Research Day

Background

• Nationally declining cervical cancer rates are still high amongst minority women in NJ, with Hispanic women being affected the most.

• The Human Papilloma Virus (HPV) is the most common sexually transmitted infection and can lead to cervical cancer

• Administration of the 9-valent HPV vaccine can prevent infection and progression to cancer

• Regular cervical cancer screenings allow for better outcomes

• Various barriers prevent people with a cervix receiving the vaccine

• Various barriers prevent people with a cervix aged >/= 30 from receiving regular cervical cancer screenings

Conclusions

• Improved physician recommendation is required for the …

Barriers To Lung Cancer Screening Among African American Males Aged 50-70 In The United States, Edward Marines

Rowan-Virtua Research Day

Objectives:

• Identify the different barriers to lung cancer screening among African American males
• Examine potential methods of increasing access and participation within this population

Metastatic Adenocarcinoma Of The Prostate To The Brain Initially Diagnosed As Meningioma By Craniotomy: A Case Report, Julia T. Scali, Young Son, Paul Chialastri, Thomas Mueller

Rowan-Virtua Research Day

Prostate cancer is the second leading cause of cancer death in men after lung cancer. The most common site of prostate metastasis is bone (84%), lymph node (10.6%), liver (10.2%), and thorax (9.1%), with 18.4% to multiple metastatic sites [1]. Prostate metastasis to the brain is rare, with less than 1% documented cases from M.D. Anderson Cancer Center [2]. It is estimated that 1%-6% of prostate cancer metastasis is found in post mortem examination [3]. Parenchymal brain metastasis has a mean survival of 9.2 months after discovery of brain metastasis [4]. Acute neurological symptoms of metastatic prostate cancer are observed …

Multiple Myeloma With Dual Expression Of Kappa And Lambda Light Chains, Monica Patel, Akash Patel, Yvette Wang

Rowan-Virtua Research Day

Multiple myeloma (MM) is a malignancy of plasma cells that accounts for approximately 1 to 2 percent of all cancers and about 17% of all hematologic malignancies.

Plasma cells normally produce antibodies and provide a defense mechanism for the body to fight infections.

Antibodies typically consist of two heavy chains (IgG, IgA, IgM, IgD and IgE) and two light chains (kappa and lambda).

Most cases of MM have malignant plasma cells producing monoclonal (M) proteins, most common being IgG about 52% of the time (1).

Only about 2% of these myeloma cases were also found to secrete more than one …

Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with a poor prognosis. While chemotherapeutics are potent, these agents lack specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment could lead to more safe and efficacious drugs. We previously engineered a breast cancer cell targeting peptide 18-4 that specifically binds cell surface receptor keratin 1 (K1) on breast cancer cells. A conjugate of peptide 18-4 and doxorubicin (Dox) containing an acid-sensitive hydrazone linker showed specific toxicity toward TNBC cells. Here, we report the …

Survival Benefit For Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance, Carol Durno, Ayse Bahar Ercan, Vanessa Bianchi, Melissa Edwards, Melyssa Aronson, Melissa Galati, Eshetu G. Atenafu, Gadi Abebe-Campino, Abeer Al-Battashi, Naureen Mushtaq

Section of Haematology/Oncology

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.
Patients and methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.
Results: A total of 193 malignant tumors in 110 patients were identified. Median …

Guided Imagery And Sentinel Lymph Node Biopsy Pain, Brandy Alicia Kirk

Evidence-Based Practice Project Reports

The standard of care in the treatment for women diagnosed with breast cancer includes identification and biopsy of the sentinel lymph nodes (SLN) of the breast (Chaterjee et al., 2017; Kneece, 2017). The process of identifying the SLNs involves radioisotope injections into or near the areola. Because this area is highly sensitive, women report this procedure to be considerably painful. The purpose of this evidence-based practice (EBP) project was to determine if the provision of a 5-minute session of guided imagery (GI), as a complementary alternative medicine, prior to SLN injections was effective in mitigating reports of procedural pain. A …

Keeping Primary Care Providers Informed About Detecting Skin Cancer In Young Adults, Riley J. Spears

Evidence-Based Practice Project Reports

Skin cancer is a common, life-threatening disease that affects anyone, regardless of age or skin color (American Cancer Society [ACS], 2020). The incidence of melanoma is on the rise for young adults, with an estimated 2,400 new cases for individuals aged 15 to 29 (ACS, 2020). Although skin cancer is highly preventable, clinical guidelines are inconsistent regarding skin cancer screening. The purpose of this evidence-based practice (EBP) project was to determine if the implementation of the INternet curriculum FOR Melanoma Early Detection (INFORMED) program would improve primary care providers’ (PCPs’) confidence about skin cancer and the number of completed and …

Role Of Intra-Operative Ultrasound In Brain Tumour Surgeries, Mohammad Hamza Bajwa, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

The use of intra-operative ultrasound remains a largely underutilized option in brain tumour surgeries. The widespread availability of neuronavigation may be the reason why such a useful modality has become less popular even though recent advances in ultrasound technology have greatly improved its utility. The available literature also clearly shows that it offers additional advantages especially when used with neuronavigation. Herein the authors have briefly touched upon the available literature on the role of intraoperative ultrasound in brain tumour surgeries.

Novel Mouse Model For Analysis Of Macrophage Function In Neuroblastoma, Gabrielle L. Brumfield, Shelby M. Knoche, Alaina C. Larson, Brittany Poelaert, Benjamin T. Goetz, Poomy Pandey, Don W. Coulter, Joyce C. Solheim

Child Health Research Institute Pediatric Research Forum

Background: Neuroblastoma is the third most common childhood cancer and accounts for 12% of cancer-associated deaths in children under the age of 15. Patients with high risk neuroblastoma have a poor 5-year survival rate of less than 50%. Neuroblastoma tumors treated with the histone deacetylase inhibitor (HDACi) vorinostat have increased infiltration of macrophages with upregulated immune cell-surface receptors. Neuroblastoma cells release VEGF and M-CSF, which may alter intratumoral macrophage populations. VEGF has also been implicated in alteration of amyloid precursor protein family processing. Our lab demonstrated that amyloid precursor protein 2 (APLP2), a member of the amyloid precursor protein …

Hypercalcemia Of Malignancy Attributed To Cosecretion Of Pth And Pthrp In Lung Adenocarcinoma, Jeffrey Kroopnick, Ubaldo E. Martinez-Outshoorn, Madalina Tuluc, Caroline S Kim

Department of Medical Oncology Faculty Papers

Introduction: Hypercalcemia of malignancy (HCM) portends a very poor prognosis, and no established guidelines exist regarding its management. Most instances of HCM are due to local osteolysis or secretion of parathyroid hormone related-peptide, while less than 1% of all cases are due to ectopic secretion of parathyroid hormone.

Case report: We present an unusual case of HCM due to proposed cosecretion of both parathyroid hormone and parathyroid hormone-related protein in a 36-year-old man with a poorly differentiated lung adenocarcinoma. The patient's hypercalcemia was refractory to conventional measures, including intravenous bisphosphonate therapy (zoledronic acid), and was improved with administration of denosumab. …

Double The Battle: Two Cases Of Irreversible Endocrinopathies In Patients Already Fighting Metastatic Cancer., Olesya Petrenko, Nicholas L Stucky

Providence Portland Medical Center Internal Medicine 2021

INTRODUCTION: Emergence of cancer immunotherapy has instigated a new era in field of oncology and revolutionized treatment of cancer. In 2011, Immune Checkpoint Inhibitors (ICI) gained approval for treatment of advanced solid and hematological malignancies and have had remarkable results. Since being released, new cases of irreversible endocrine adverse events are increasingly becoming reported and leave patients with a new life-long diagnosis after battling metastatic cancer.

Discussion • 6 Immune Checkpoint Inhibitors (ICIs) approved: •CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor Ipilimumab •PD-1 (programmed cell death protein 1) inhibitors nivolumab, pembrolizumab •PD-L1 (programmed cell death ligand 1) inhibitors atezolizumab, avelumab, durvalumab …

The Effects Of Chemotherapeutic Agents On Cognitive Function: A Literature Review, Corinne Menz

The Eleanor Mann School of Nursing Undergraduate Honors Theses

With increasing cancer diagnoses and an increase of chemotherapy treatment, many patients complain of cognitive decline during the duration of treatment as well as once treatment has been completed. The purpose of this review is to compile relevant research regarding chemotherapy-related cognitive impairment and its implications for the care of cancer patients. Peer-reviewed articles and studies focusing on the impact of chemotherapy on cognitive function were evaluated, resulting in a total of 12 studies utilized in this review. Overall, it has been found that a large percentage of patients undergoing chemotherapy treatment report a subjective decline in cognitive functioning, but …

Breast Cancer Treatment Causing Cardiovascular Complications: How Can We Prevent It?, Abigail L. Reese

Honors Theses

Breast cancer has the highest incidence rate of any cancer in the United States, and it is the second most deadly. It comprises 30% of all diagnosed cancers in women, and it is predicted that the incidence of breast cancer will continue to rise. Most common chemotherapeutic agents utilized in the treatment of breast cancer are known to be cardiotoxic, each with differing mechanisms and possible damage done to the patient. In turn, cardiovascular diseases are the number one killer of women in the United States, and their prevalence is continually growing. It is unknown exactly how many women who …

Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller

Electronic Theses and Dissertations

Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

Breast Cancer Risk For Female Relatives Of Male Breast Cancer Patients With Negative Brca1/2 Testing, Emily Martin

Dissertations and Theses (Open Access)

Risk models exist to estimate a female’s lifetime risk of breast cancer in the absence of a hereditary predisposition to cancer, namely Hereditary Breast and Ovarian Cancer syndrome. These risk models consider various factors such as reproductive history and family history, but few models take a family history of male breast cancer into account. This study aims to evaluate if prevalence of breast cancer among female relatives is higher when there is a family history of male breast cancer in the context of uninformative BRCA1 and BRCA2 testing. This information may aid in the process of risk assessments for patients …

Combination Of Resveratrol And Green Tea Epigallocatechin Gallate Induces Synergistic Apoptosis And Inhibits Tumor Growth In Vivo In Head And Neck Cancer Models, Arm R. Amin, Dongsheng Wang, Sreenivas Nannapaneni, Rajan Lamichhane, Zhuo Georgia Chen, Dong M. Shin

Pharmaceutical Science and Research

Despite widespread interest in chemoprevention and therapy due to the high margin of safety of dietary natural compounds, clinical intervention with single agents has failed to yield the expected outcomes, mostly due to poor bioavailability and low potency. Combinations of natural agents with synergistic effects are gaining increasing attention. In the present study, in vitro and in vivo antitumor effects of a combination of two natural dietary agents, green tea epigallocatechin gallate (EGCG) and resveratrol were investigated. It was revealed that their combination at low doses (at which single agents induce minimal apoptosis) synergistically increased apoptosis (combination index < 1) in head and neck cancer cell lines. Synergistic apoptosis was also supported by caspase‑3 and PARP cleavage. The combination also significantly inhibited growth of xenografted head and neck tumors in nude mice as supported by significant inhibition of tumor volume, tumor weight and Ki67 expression, and increase in TUNEL‑positive cells. Mechanistic studies revealed that the combination inhibited AKT‑mTOR signaling both in vitro …