Medicine and Health Sciences Commons^™

Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

Repurposing The Fda-Approved Anthelmintic Pyrvinium Pamoate For Pancreatic Cancer Treatment: Study Protocol For A Phase I Clinical Trial In Early-Stage Pancreatic Ductal Adenocarcinoma, Francesca M. Ponzini, Christopher W. Schultz, Benjamin E. Leiby, Shawnna Cannaday, T. Yeo, James Posey, Wilbur B. Bowne, Charles Yeo, Jonathan R. Brody, Harish Lavu, Avinoam Nevler

Department of Surgery Faculty Papers

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.

METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will …

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

Nivolumab Plus Ipilimumab Versus Extreme Regimen As First-Line Treatment For Recurrent/Metastatic Squamous Cell Carcinoma Of The Head And Neck: The Final Results Of Checkmate 651., Robert I. Haddad, Kevin Harrington, Makoto Tahara, Robert L. Ferris, Maura Gillison, Jerome Fayette, Amaury Daste, Piotr Koralewski, Bogdan Zurawski, Miren Taberna, Nabil F. Saba, Milena Mak, Andrzej Kawecki, Gustavo Girotto, Miguel Angel Alvarez Avitia, Caroline Even, Joaquin Gabriel Reinoso Toledo, Alexander Guminski, Urs Müller-Richter, Naomi Kiyota, Mustimbo Roberts, Tariq Aziz Khan, Karen Miller-Moslin, Li Wei, Athanassios Argiris

Department of Medical Oncology Faculty Papers

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and …

An Unusual Case Of Hemophagocytic Lymphohistiocytosis Associated With Mycobacterium Chimaera Or Large-Cell Neuroendocrine Carcinoma, Tejaswi Venigalla, Sheila Kalathil, Meena Bansal, Mark Morginstin, Vinicius Jorge, Patricia Perosio

Einstein Health Papers

Hemophagocytic lymphohistiocytosis (HLH) is a rare and very dangerous condition characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections, malignancies, and rheumatologic disorders. Most current information on diagnosis and treatment is based on pediatric populations. HLH is a disease that should be diagnosed and treated promptly, otherwise it is fatal. Treatment is directed at treating the triggering disorder, along with symptomatic treatment with dexamethasone and etoposide. We present a 56-year-old …

The V8-10 Variant Isoform Of Cd44 Is Selectively Expressed In The Normal Human Colonic Stem Cell Niche And Frequently Is Overexpressed In Colon Carcinomas During Tumor Development, Bruce M. Boman, Vignesh Viswanathan, Caroline O B Facey, Jeremy Z Fields, James W Stave

Kimmel Cancer Center Faculty Papers

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development. We created a unique panel of anti-CD44 rabbit genomic antibodies to 16 specific epitopes that span the entire length of the CD44 molecule. Our panel was used to comprehensively investigate the expression of …

Real-World Maintenance Therapy And Survival Outcomes For Pembrolizumab Plus Pemetrexed And Platinum For Non-Small-Cell Lung Cancer In Usa, Himani Aggarwal, Kayonda Bayo, Yimei Han, Catherine Elizabeth Muehlenbein, Yajun Emily Zhu, Jong Seok Kim

Student Papers, Posters & Projects

Aim: To evaluate treatment patterns and overall survival (OS) in real world metastatic non-squamous non-small-cell lung cancer (NSQ-NSCLC) patients that received pembrolizumab plus pemetrexed-platinum (pembro+pem+plat) aligned with KEYNOTE-189.

Materials & methods: OS was evaluated for the overall cohort and maintenance therapy (MT) subgroups and analyzed using Kaplan-Meier estimates and Cox proportional hazards model.

Results: Of 2488 patients that received first-line treatment, 45.1% received less than four cycles of pembro+pem+plat, 43.9% received four cycles plus MT with pembro and/or pem, and 11.1% received four cycles without continuing on MT. The median OS was 21.0 months and 9.1 months in patients that …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Atrayee Basu Mallick, Nora K Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A Morse, Muhammad Shaalan Beg, Janet E Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L Schlechter, Hanna Sanoff, Christopher Manz, Brian M Wolpin, Philip Arlen, Jill Lacy, James M Cleary

Department of Medical Oncology Faculty Papers

Importance: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

Objective: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

Design, setting, and participants: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Adjuvant Nab-Paclitaxel + Gemcitabine In Resected Pancreatic Ductal Adenocarcinoma: Results From A Randomized, Open-Label, Phase Iii Trial, Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni

Department of Surgery Faculty Papers

PURPOSE

This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS

We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS

Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

Metformin Increases Natural Killer Cell Functions In Head And Neck Squamous Cell Carcinoma Through Cxcl1 Inhibition, Mckenzie Crist, Benyamin Yaniv, Sarah Palackdharry, Maria A. Lehn, Mario Medvedovic, Timothy Stone, Shuchi Gulati, Vidhya Karivedu, Michael Borchers, Bethany Fuhrman, Audrey Crago, Joseph Curry, Ubaldo Martinez-Outschoorn, Vinita Takiar, Trisha M. Wise-Draper

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Metformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in our phase 1 clinical trial (NCT02325401). Metformin is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) and natural killer T cells, including results from two phase I open-label studies in patients with HNSCC treated with metformin (NCT02325401, NCT02083692).

METHODS: Peripheral blood was collected before and after metformin treatment or from newly diagnosed patients with HNSCC. Peripheral immune cell …

Libretto-531: A Phase Iii Study Of Selpercatinib In Multikinase Inhibitor-Naïve, Lori J Wirth, Marcia S Brose, Rossella Elisei, Jaume Capdevila, Ana O Hoff, Mimi I Hu, Makoto Tahara, Bruce Robinson, Ming Gao, Meng Xia, Patricia Maeda, Eric Sherman

Department of Medicine Faculty Papers

Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. …

Interleukin-8 Produced From Cancer-Associated Fibroblasts Suppresses Proliferation Of The Ocuch-Lm1 Cancer Cell Line, Ryota Tanaka, Kenjiro Kimura, Shimpei Eguchi, Go Ohira, Shogo Tanaka, Ryosuke Amano, Hiroaki Tanaka, Masakazu Yashiro, Masaichi Ohira, Shoji Kubo

Department of Medical Oncology Faculty Papers

Background: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort.

Methods: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines …

Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are …

The Hispanic Paradox In Non-Small Cell Lung Cancer, Rohit Kumar, Franklin Castillero, Shruti Bhandari, Sindhu Malapati, Goetz Kloecker

Hematology/Oncology and Stem Cell Therapy

Objective/Background: According to the U.S. Census Bureau, 18% of the total population in the United States identified themselves as Hispanic in 2016 making it the largest minority group. This study aimed to evaluate the effect of Hispanic ethnicity on the overall survival of patients with non-small cell lung cancer (NSCLC) using a large national cancer database. Methods: We used the National Cancer Database to identify patients diagnosed with NSCLC between 2010 and 2015. The two comparative groups for this study were non-Hispanic Whites (NHWs) and Hispanics. The primary outcome was overall survival. Results: Of the 555,475 patients included in the …

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, …

18 Fdg Pet/Ct Imaging In Carcinoma Cesophagus, Maseeh Uz Zaman, Nosheen Fatima

Department of Radiology

No abstract provided.

Machine Learning Analyses Of Highly-Multiplexed Immunofluorescence Identifies Distinct Tumor And Stromal Cell Populations In Primary Pancreatic Tumors, Krysten Vance, Alphan Alitinok, Seth Winfree, Heather Jensen Smith, Benjamin Swanson Md, Phd, Paul M. Grandgenett, Kelsey Klute, Daniel J Crichton, Michael A. Hollingsworth

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

OBJECTIVE: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

METHODS: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples. Image registration and machine learning algorithms were developed to largely automate an imaging analysis pipeline identifying distinct cell …

High-Dose-Rate Brachytherapy For The Treatment Of Basal And Squamous Cell Carcinomas On Sensitive Areas Of The Face: A Report Of Clinical Outcomes And Acute And Subacute Toxicities, James M. Taylor, Bahar Dasgeb, Spencer Liem, Ayesha Ali, Amy Harrison, Mitchell Finkelstein, Jisun Cha, Rani Anne, Steven Greenbaum, William Sherwin, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Purpose Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face.

Methods and Materials Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos …

Bone In The Breast: A Case Report Of A Metaplastic Breast Cancer With Osseous Differentiation, Kyle Luo, Xiaoqin Wang

Radiology Faculty Publications

Metaplastic breast carcinoma is an uncommon malignant tumor with various pathologic subtypes. Diagnosis is often challenging due to the wide spectrum of clinical and imaging presentations. Here, we present the case of a very rare subtype of metaplastic breast carcinoma-a mixed-type metaplastic breast cancer with osseous differentiation in a 55-year-old female patient. The clinical presentation, imaging-pathology diagnosis, and treatment options are reviewed. Knowing this rarely reported but aggressive breast cancer is very important for clinicians to establish a timely diagnosis for effective management.

Management And Treatment Of Hepatocellular Carcinoma With Immunotherapy: A Review Of Current And Future Options, Shima Ghavimi, Tehila Apfel, Hamed Azimi, Alana Persaud

Internal Medicine

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

Recent Updates In The Management Of Merkel Cell Carcinoma, Ahmed Nadeem Abbasi, Syed Mustajab Ahmed, Bilal Mazhar Qureshi

Department of Radiation Oncology

Merkel cell carcinoma is an aggressive non-melanomatous cutaneous tumour of neuroendocrine origin with an increasing incidence in the recent years. It is a tumour of the elderly and immunosuppressed, which most often appears on sun-exposed areas of the body. The clinical features of the cutaneous or subcutaneous lesions hardly contribute to the diagnosis, and, hence, histopathology and immunohistochemistry play a vital role in diagnosis. The latest staging system by the American Joint Committee on Cancer includes non-nodal invasion to adjacent structures i.e. bone, muscle, fascia, or cartilage into the criteria, in additionto size and depth of invasion. The management reliesheavily …

Treatment Of Basal Cell Carcinoma With Vismodegib, Sunitha Johns, Katlyn Brown, Emily Loudermilk, Crystal Zheng, Anh Dao Le, Sophocles Chrissobolis

Pharmacy and Wellness Review

The most prevalent nonmelanoma skin cancers are basal cell carcinoma (BCC) and locally advanced basal cell carcinoma (aBCC). Current, effective first-line treatments for BCC aim to remove and destroy cancerous skin cells through excision surgery, Mohs surgery, radiation therapy and cryotherapy, while treatment of aBCC remains limited. An emerging treatment option for aBCC that promotes tumor size reduction is vismodegib, a pharmaceutical product approved in 2012 by the U.S. Food and Drug Administration (FDA). Vismodegib was approved for the treatment of aBCC, metastasized HCC (mBCC) or recurrent BCC after surgery as well as for use in adults who are not …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …