Neoplasms Commons^™

First-In-Human Study Of An Ox40 (Ivuxolimab) And 4-1bb (Utomilumab) Agonistic Antibody Combination In Patients With Advanced Solid Tumors, Omid Hamid, Alberto A Chiappori, John A Thompson, Toshihiko Doi, Siwen Hu-Lieskovan, Ferry A L M Eskens, Willeke Ros, Adi Diab, Jean-Philippe Spano, Naiyer A Rizvi, Jeffrey S Wasser, Eric Angevin, Patrick A Ott, Alison Forgie, Wenjing Yang, Cen Guo, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.

Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every …

Long-Term Follow-Up For The Development Of Subsequent Malignancies In Patients Treated With Genetically Modified Iecs, David H M Steffin, Ibrahim N Muhsen, Laquisa C Hill, Carlos A Ramos, Nabil Ahmed, Meenakshi Hegde, Tao Wang, Mengfen Wu, Stephen Gottschalk, Sarah B Whittle, Premal D Lulla, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Andras Heczey, Leonid S Metelitsa, Bambi J Grilley, Catherine Robertson, Virginia Torrano, Natalia Lapteva, Adrian P Gee, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop

Faculty, Staff and Students Publications

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, …

Dual-Mode Tumor Imaging Using Probes That Are Responsive To Hypoxia-Induced Pathological Conditions, S A Amali S Subasinghe, Robia G Pautler, Md Abul Hassan Samee, Jason T Yustein, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used …

Extragonadal Perirectal Mature Cystic Teratoma In The Adult Male, Pranamaya Mahankali, Liam Trimble, Diana Panciera, Hui Li, Thaer Obaid

Rowan-Virtua Research Day

A teratoma is a mass that originates from the germ cells of the three primitive embryonic layers and commonly arises from the ovaries or testicles, thereby characterized as gonadal in origin. These masses comprise different types of tissues such as fat, hair, muscle, and bone. Extragonadal teratomas are uncommon and arise from anatomical locations other than the gonads, such as the pineal gland, anterior mediastinum, retroperitoneum, and sacrococcygeal regions. The most common is the presacral region, as it contains tissue derived from all germ layers. Tumors in this specific location are far more common in neonates, infants, and children rather …

Case Report: Glioblastoma Tumor Presenting With Mild Changes In Memory, Samuel Thalathoti, Nicholas Palladino, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 66-year-old female who presented to the ED with generalized headache and mild confusion, who was diagnosed with high-grade glial neoplasm. The differential diagnosis of headache is vast, but without red flags or symptoms is generally from a benign cause and easily treatable. However, even in the context of a normal neurologic physical exam, symptoms such as confusion, forgetfulness, and behavioral changes should merit imaging in the workup. Glioblastoma is the most common brain tumor, accounting for 47.7% of all cases, with an incidence of 3.21 per 100,000 population. Median age of diagnosis is 64 …

Factors And Outcomes Contributing To Pelvic Lymph Node Dissection In Non-Muscle Invasive Bladder Cancer, Young Son, Brian Thomas, Lance Earnshaw, Mark Quiring, Erica Martel, Benjamin Fink, Raeann Dalton, Thomas Mueller, Philip Dorsey

Rowan-Virtua Research Day

Bladder cancer represents the 6th most common for men and is classified into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). NMIBC (T1, Ta, Tis), accounting for approximately 75% of new bladder cancer diagnoses, is limited to the mucosa, submucosa, and lamina propria. Studies have approximated the rate of recurrence in NMIBC between 50 - 70%, which sometimes progresses to muscle invasive disease. Management of NMIBC ranges from surveillance, intravesical chemotherapy to radical cystectomy (RC) and is dependent upon the TNM staging and grading of the tumor. Clinically, staging is determined via imaging, physical exam, and histology on transurethral …

Substrate-Specific Effect On Sirtuin Conformation And Oligomerization, Jie Yang, Shannon L. Dwyer, Nathan I. Nicely, Brian P. Weiser

Rowan-Virtua Research Day

Human sirtuins are a family of nicotinamide adenine dinucleotide (NAD +)-dependent enzymes that are responsible for removing acyl modifications from lysine residues. Sirtuins are involved in the formation and proliferation of cancers and are thought to regulate the progression of neurodegenerative diseases. Although sirtuins can be pharmacologically targeted by small molecules, it is not easy to modulate the substrate selectivity of sirtuins despite the chemical diversity of their substrates. Here, we report substrate-specific effects on sirtuin conformation and oligomerization that regulate enzyme deacylase activity. We used fluorescent acyl peptide probes to study substrate interactions with two sirtuin isoforms: SIRT2 and …

The Utilization Of Osteoarticular Transfer System In The Treatment Of Distal Femur Osteoid Osteoma: A Case Report, Nikki A. Doerr, Efstratios A. Papadelis, Alec S. Kellish, Matthew T. Kleiner, Christina Gutowski

Rowan-Virtua Research Day

We describe a technique for excision of subchondral epiphyseal bone lesions in the distal femur in skeletally immature patients that mitigates risk of complications associated with physeal injury, incomplete tumor resection, and iatrogenic injury to the overlying cartilage.

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …

Intrapulmonary Teratoma: A Rare Presentation Of Bronchiectasis, Beren Chandler, Garret Duron, Jason Mcclune, Lindsey Goldberg

South Atlantic Division GME Research Day 2022

No abstract provided.

Not Just An Accident: A Case Of Insulinoma, Asanka Ekanayake, Harrison Stubbs, Dominique Broutin, Olga Karasik, Mustafa Kinaan

North Florida Division GME Research Day 2022

No abstract available.

Induction Of Hypopituitarism Following Ipilimumab/ Nivolumab Therapy Followed By Radiation In The Treatment Of Metastatic Scalp Melanoma, Joshua K. Salabei, Dhaval Upadhyay, Sripal A. Padam

HCA Healthcare Journal of Medicine

Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to …

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 …

A Case Of Spinal Epidural Lipomatosis Presenting As A Stroke Mimic, Jonas Salna Iv, James Lee, Eric Maddock, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Spinal Epidural Lipomatosis (SEL) an excess of normal adipose tissue in the epidural space of the spinal canal, typically becoming symptomatic when cord compression results. First described in 1975 by Lee et al (Lee M, 1975), it is a relatively rare disease. Unfortunately, it is often diagnosed once patients have developed marked symptoms and can have dire complications. Oftentimes SEL is completely asymptomatic, and symptoms on initial presentation are vague. Mostly commonly it presents as worsening chronic back pain (Daniel R. Fassett M.D. M.B.A., 2004) with progressive lower extremity weakness and occasional cauda equina syndrome (Wells AJ, 2014), but this …

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

Pancoast Syndrome Due To High Grade Anaplastic Tumor, Christian Almanzar, Seth Maxwell, Mauricio Gomez, Omar Ansari, Luis Silva

HCA Healthcare Journal of Medicine

The Pancoast tumor is an uncommon type of lung cancer that arises from within the superior sulcus. With most clinical manifestations occurring due to mass effect, Pancoast syndrome is a known complication that includes shoulder and arm musculoskeletal pain, Horner’s syndrome and neurological complications of the upper extremities, including weakness and atrophy. Even though adenocarcinoma is the most common cause of Pancoast syndrome among lung cancers, other malignancies can be responsible as well. Treatment is similar to that of other standard NSCLC treatments that include chemotherapy, radiation, immunotherapy and surgery. Here we report a patient with Pancoast syndrome secondary to …

The Cancer Patient And Cardiology, José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A M Feijen, Péter Ferdinandy, Teresa López-Fernández, Chris P Gale, John H Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M Suter, Giorgio Minotti

Faculty, Staff and Students Publications

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and …

Investigation Of A Peculiar Case Of Childhood Lymphadenopathy, Chade Aribo, Alonso Al, Allison Woodall, Tommy Y. Kim

HCA Healthcare Journal of Medicine

Introduction: Lymphadenopathy is a common physical finding often associated with an infectious etiology. We present a case of a patient with generalized cervical and supraclavicular lymphadenopathy diagnosed with a rare malignancy. Health care providers should be aware of some uncommon historical or physical examination findings that warrant further investigation.

Clinical Findings: A 16-year-old female presented to the emergency department with 3 days of a fever, congestion and sore throat with swelling around the jaw. Her physical examination findings included bilateral mandibular swelling and generalized cervical lymphadenopathy with palpable supraclavicular lymph nodes.

Outcomes: Complete blood count showed pancytopenia with a white …

A Rare Case Of Primary Cutaneous Mucoepidermoid Carcinoma, Hassie Cooper, Maheera Farsi, Richard Miller, Pay Kamrani, Dudith Pierre Victor

West Florida Division GME Research Day 2020

Mucoepidermoid carcinoma (MEC) is a well-documented malignant tumor commonly found in the salivary glands. Cutaneous involvement is very rare, especially when presenting as a primary cutaneous neoplasm. Gallagher first described primary cutaneous MEC in 1959 and since then, to the best of our knowledge, there have been approximately 20 reports published in the literature. Here we present a very rare case of primary cutaneous mucoepidermoid carcinoma.

A Unique Schwannoma Of The Distal Hallux: A Case Study, Rebecca D. Stack Dpm, Brett Sachs Dpm Facfas, Dustin Kruse Dpm, Paul A. Stone Dpm, Facfas

Podiatry

No abstract provided.

A Rare Case Of Trichilemmal Carcinoma: Histology And Management, Lisa F. Fronek, Allyson Brahs, Maheera Farsi, Richard Miller

West Florida Division GME Research Day 2020

Trichilemmal carcinoma (TC) is a rare, malignant, adnexal neoplasm that is derived from the outer root sheath (ORS) of the hair follicle. These tumors predominantly occur in elderly patients on sun-exposed areas, specifically on the head and neck with the face defined as the most common location. The mean age of diagnosis is 70 years old with a slight male predominance. These lesions are commonly identified as a papular, nodular, and sometimes, exophytic. They generally arise de-novo, but may also derivate from an underlying proliferating trichilemmal cyst with a loss of p53, a seborrheic keratosis, a nevus sebaceous, or a …

Bone Metastasis In Appendicular Skeleton: Rare Occurrence In Colorectal Cancer, Pratikkumar Vekaria Md, Chandrika Raiyani Md, Ravis Patel Md, Devin Vaishnani Md, Tejas Raiyani Md

Gastroenterology

Colorectal cancer (CRC) is considered as preventable cancer if diagnosed in the early stage. It is also second leading cause of death from cancer in US. Bone metastases (BM) is uncommon presentation with CRC and if it occurs, it involves axial skeletal more than extremities. Many case studies also reports that survival after BM is considerably poor than without BM. Cancer type and genetic mutations also play an important role in such metastasis.

Choking On Adenocarcinoma, Andre Sahakian Md, Rajesh Gulati Md

Internal Medicine

No abstract provided.

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboobi Qureshi

Rowan-Virtua Research Day

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction …

Precision Medicine In Pediatric Cancer: Current Applications And Future Prospects., Atif Ahmed, Divya S. Vundamati, Midhat S. Farooqi, Erin M. Guest

Manuscripts, Articles, Book Chapters and Other Papers

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the …

A Rare But Life Threatening Case Of Labile Blood Pressures In Pregnancy, Kelsey Carrio, Aarti Aggarwal, Susan Mcgroarty

Rowan-Virtua Research Day

Pheochromocytoma is a rare but life threatening adrenal secreting tumor. The infrequency with which it is encountered makes pheochromocytoma, especially in pregnancy, a formidable diagnostic challenge.

Although a pheochromocytoma is rare, it is good to keep it in differential diagnosis as a possible cause of labile BP with headaches and significant orthostatic BP. It is critical to recognize this condition to institute an appropriate therapy & surgical intervention to prevent mortality.

Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder

Graduate School of Biomedical Sciences Theses and Dissertations

Leukemia is the most common childhood cancer, with a combined 40,000 predicted new cases in the United States in 2016 [8]. The two most common subtypes are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) [9-11]. The commercially available inhibitor of Bruton’s tyrosine kinase (BTK) has shown promising results in clinical trials for CLL because of the importance of BCR signaling in CLL [12-15]. Recent studies suggest that the outgrowth of BTK inhibitor resistant clonal cells in some CLL patients results in a treatment-refractory phenotype [16-18]. MALT1, a protein involved in BCR activation of the NF-κB pathway that functions …

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …