Medicine and Health Sciences Commons^™

Keratin 1 As A Cell-Surface Receptor In Cancer, Oluseye Ogunnigbagbe, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Keratins are fibrous proteins that take part in several important cellular functions, including the formation of intermediate filaments. In addition, keratins serve as epithelial cell markers, which has made their role in cancer progression, diagnosis, and treatment an important focus of research. Keratin 1 (K1) is a type II keratin whose structure is comprised of a coiled-coil central domain flanked by flexible, glycine-rich loops in the N- and C-termini. While the structure of cytoplasmic K1 is established, the structure of cell-surface K1 is not known. Several transformed cells, such as cancerous cells and cells that have undergone oxidative stress, display …

Ivermectin Induces Apoptosis Of Esophageal Squamous Cell Carcinoma Via Mitochondrial Pathway, Nana Xu, Mengmeng Lu, Jiaxin Wang, Yujia Li, Xiaotian Yang, Xiajie Wei, Jiaoyang Si, Jingru Han, Xiaojuan Yao, Juanmei Zhang, Junqi Liu, Yanming Li, Hushan Yang, Dengke Bao

Department of Medical Oncology Faculty Papers

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.

Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels.

Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, …

Metabolic Pathways And Targets In Chondrosarcoma, Ida Micaily, Megan E Roche, Mohammad Y Ibrahim, Ubaldo E. Martinez-Outshoorn, Atrayee Basu Mallick

Department of Medical Oncology Faculty Papers

Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and …

Association Between Sex And Immune Checkpoint Inhibitor Outcomes For Patients With Melanoma., Se Ryeong Jang, Nikita Nikita, Joshua Banks, Scott W. Keith, Jennifer M. Johnson, Melissa Wilson, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

Importance: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment and are now standard of care. Although sex is associated with immune function and immune-related diseases, the interaction between sex and ICIs is understudied.

Objective: To examine whether cancer immunotherapy effectiveness varies between female and male patients with advanced melanoma treated with either nivolumab plus ipilimumab combination therapy or anti-programmed cell death protein 1 (PD-1) therapy (namely, pembrolizumab or nivolumab).

Design, Setting, and Participants: The study population consisted of 1369 older adults (aged ≥65 years) with a record of melanoma diagnosis from January 1, 1991, to December 31, 2015, in the …

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Steviol Represses Glucose Metabolism And Translation Initiation In Pancreatic Cancer Cells, Sonam Kumari, Mohammed Sikander, Shabnam Malik, Manish Tripathi, Bilal B. Hafeez, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan, Meena Jaggi

School of Medicine Publications

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we …

Thrombosis With Thrombocytopenia Syndrome After Administration Of Azd1222 Or Ad26.Cov2.S Vaccine For Covid-19: A Systematic Review, Usama Waqar, Shaheer Ahmed, Syed M H Ali Gardezi, Muhammad Sarmad Tahir, Zain Ul Abidin, Ali Hussain, Natasha Bahadur Ali, Syed Faisal Mahmood

Medical College Documents

Background: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS.
Methods: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes.
Findings: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered …

Laparoscopic Assisted Robotic Radical Prostatectomy With Pelvic Lymph Node Dissection Using Viable Cryopreserved Umbilical Tissue To Improve Cavernosal Nerve Function., Joshua Volin, Brett Watson, Lior Kopel, Samantha Kraemer, Jason Hafron

Conference Presentation Abstracts

Radical prostatectomy is the preferred treatment for patients with clinically localized prostate cancer and is typically performed using a robotic approach. Surgical techniques that preserve the neurovascular bundle minimize the risk of incontinence and erectile dysfunction post-operatively. Umbilical cord tissue is a relatively new technique, which has been shown to reduce inflammation and promote regenerative healing. In this video we show a robotic radical prostatectomy with bilateral nerve sparing technique utilizing a cryopreserved umbilical cord allograft nerve wrap.

Modeling Recurrence In Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow, Kyle Kimura, Liping Du, Lynn D Berry, Li-Ching Huang, Sheau-Chiann Chen, David O Francis, Alexander Gelbard

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS

RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year, prospective study comparing surgical treatment efficacy and 385 had appropriate PEF …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …

Predicted Vitamin D Status And Colorectal Cancer Incidence In The Black Women's Health Study, Lauren E Barber, Kimberly A Bertrand, Jessica L Petrick, Hanna Gerlovin, Laura F White, Lucile L Adams-Campbell, Lynn Rosenberg, Hemant K Roy, Julie R Palmer

Faculty, Staff and Students Publications

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of …

Radioresistance In Prostate Cancer: Focus On The Interplay Between Nf-Κb And Sod, Sameera Kumar, Daret St. Clair

Toxicology and Cancer Biology Faculty Publications

Prostate cancer occurs frequently in men and can often lead to death. Many cancers, including prostate cancer, can be initiated by oxidative insult caused by free radicals and reactive oxygen species. The superoxide dismutase family removes the oxygen-derived reactive oxygen species, and increased superoxide dismutase activity can often be protective against prostate cancer. Prostate cancer can be treated in a variety of ways, including surgery, androgen deprivation therapy, radiation therapy, and chemotherapy. The clinical trajectory of prostate cancer varies from patient to patient, but more aggressive tumors often tend to be radioresistant. This is often due to the free-radical and …

Bay Leaf Extract‐Based Near‐Infrared Fluorescent Probe For Tissue And Cellular Imaging, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Vinitha Karumuru, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

The development of fluorescence dyes for near‐infrared (NIR) fluorescence imaging has been a significant interest for deep tissue imaging. Among many imaging fluoroprobes, indocyanine green (ICG) and its analogues have been used in oncology and other medical applications. However, these imaging agents still experience poor imaging capabilities due to low tumor targetability, photostability, and sensitivity in the biological milieu. Thus, developing a biocompatible NIR imaging dye from natural resources holds the potential of facilitating cancer cell/tissue imaging. Chlorophyll (Chl) has been demonstrated to be a potential candidate for imaging purposes due to its natural NIR absorption qualities and its wide …

Outcomes Of Patients With Double/Triple Expressor Diffuse Large B-Cell Lymphoma (Dlbcl) Treated With R-Da-Epoch/R-Chop: A Single-Center Experience, Kanta Devi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly …

Case Report: Molecular Diagnosis Of Cystoisospora Belli In A Severely Immunocompromised Patient With Hiv And Kaposi Sarcoma, Roumen Borilov Iordanov, Lauren M Leining, Meng Wu, Galant Chan, Andrew R Dinardo, Rojelio Mejia

Faculty, Staff and Students Publications

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting …

Case Report: Molecular Diagnosis Of Cystoisospora Belli In A Severely Immunocompromised Patient With Hiv And Kaposi Sarcoma, Roumen Borilov Iordanov, Lauren M Leining, Meng Wu, Galant Chan, Andrew R Dinardo, Rojelio Mejia

Faculty, Staff and Students Publications

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting …

Rare Case Of Mediastinal Myeloid Sarcoma, Kanta Devi, Salman Adil, Natasha Bahadur Ali, Nasir Ali, Hammad Khan

Section of Haematology/Oncology

Myeloid sarcoma is a rare tumor mass with extra medullary growth pattern, composed of myeloblast or immature myeloid cells. Myeloid sarcoma (MS) is a distinct clinical presentation of acute myeloid leukemia (AML) where less than 1% of patients present with prominent extra medullary disease which most commonly involves the bone, skin, lymph node, soft tissues, gastrointestinal tract or testes. The recommended treatment regimen in isolated myeloid sarcoma or with bone marrow involvement is upfront systemic chemotherapy. We report a case of a young female with anterior mediastinal mass diagnosed as myeloid sarcoma which was refractory to chemotherapy.

Multi-Institutional Study Validates Safety Of Intraoperative Cesium-131 Brachytherapy For Treatment Of Recurrent Head And Neck Cancer, Adam J. Luginbuhl, Alyssa Calder, David Kutler, Chad Zender, Trisha Wise-Draper, Jena Patel, Michael Cheng, Vidhya Karivedu, Tingting Zhan, Bhupesh Parashar, Shuchi Gulati, Min Yao, Pierre Lavertu, Vinita Takiar, Alice Tang, Jennifer Johnson, William M. Keane, Joseph Curry, David Cognetti, Voichita Bar-Ad

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Introduction: Surgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.

Methods and materials: Findings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts-surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)-were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.

Results: Forty-nine patients were enrolled in …

Intracranial Mesenchymal Tumors With Fet-Creb Fusion Are Composed Of At Least Two Epigenetic Subgroups Distinct From Meningioma And Extracranial Sarcomas, Emily A. Sloan, Rohit Gupta, Christian Koelsche, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer E. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of …

Large-Scale Dna Demethylation Occurs In Proliferating Ovarian Granulosa Cells During Mouse Follicular Development, Tomoko Kawai, Joanne S Richards, Masayuki Shimada

Faculty, Staff and Students Publications

During ovarian follicular development, granulosa cells proliferate and progressively differentiate to support oocyte maturation and ovulation. To determine the underlying links between proliferation and differentiation in granulosa cells, we determined changes in 1) the expression of genes regulating DNA methylation and 2) DNA methylation patterns, histone acetylation levels and genomic DNA structure. In response to equine chorionic gonadotropin (eCG), granulosa cell proliferation increased, DNA methyltransferase (DNMT1) significantly decreased and Tet methylcytosine dioxygenase 2 (TET2) significantly increased in S-phase granulosa cells. Comprehensive MeDIP-seq analyses documented that eCG treatment decreased methylation of promoter regions in approximately 40% of the genes in granulosa …

Enhancing Cancer Care Of Rural Dwellers Through Telehealth And Engagement (Encore): Protocol To Evaluate Effectiveness Of A Multi-Level Telehealth-Based Intervention To Improve Rural Cancer Care Delivery, Tuya Pal, Pamela C. Hull, Tatsuki Koyama, Phillip Lammers, Denise Martinez, Jacob Mcarthy, Emma Schremp, Ann Tezak, Anne Washburn, Jennifer G. Whisenant, Debra L. Friedman

Markey Cancer Center Faculty Publications

BACKGROUND: Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care …

Nitrous Oxide Adaptation On Gene Expression In Breast Cancer Cells, Harsh Chheda, Estevan Ruiz Limón López, Zainab Mahmood, Ankit Sharma, Tina Tran, Uzma Abdulbaseer, Farouk Alshatti, James A. Radosevich

Chemistry and Physics Faculty Proceedings, Presentations, Speeches, Lectures

Hypothesis and Objective: Genes participating in the notch signaling pathway are influenced by exposure to high nitrous oxide (HNO) levels. Notch signaling pathway genes are responsible for regulating cell fate, differentiation, and apoptosis. Dysregulation of these genes can contribute to tumorigenesis. Alterations in the expression of these genes in MCF7 breast cancer cells could help determine the effects of the notch signaling pathway on tumorigenesis as a result of exposure to nitrous oxide.

Methods: Samples of cDNA from MCF7 and MCF7-HNO cells were used in DNA microarray analysis. Qualifying genes of interest provided a p value < .05. Differentially expressed genes (DEGs) were defined and categorized using the Gene Oncology Uniprot (GO) Molecular Function database. These cells were further analyzed using a proprietary bioinformatics analysis created by our laboratory.

Results: Exposure to HNO …

Class Imbalance In Out-Of-Distribution Datasets: Improving The Robustness Of The Textcnn For The Classification Of Rare Cancer Types, Kevin De Angeli, Shang Gao, Ioana Danciu, Eric B. Durbin, Xiao Cheng Wu, Antoinette Stroup, Jennifer Doherty, Stephen Schwartz, Charles Wiggins, Mark Damesyn, Linda Coyle, Lynne Penberthy, Georgia D. Tourassi, Hong Jun Yoon

School of Public Health Faculty Publications

In the last decade, the widespread adoption of electronic health record documentation has created huge opportunities for information mining. Natural language processing (NLP) techniques using machine and deep learning are becoming increasingly widespread for information extraction tasks from unstructured clinical notes. Disparities in performance when deploying machine learning models in the real world have recently received considerable attention. In the clinical NLP domain, the robustness of convolutional neural networks (CNNs) for classifying cancer pathology reports under natural distribution shifts remains understudied. In this research, we aim to quantify and improve the performance of the CNN for text classification on out-of-distribution …

Nrf1 Association With Auts2-Polycomb Mediates Specific Gene Activation In The Brain, Sanxiong Liu, Kimberly A Aldinger, Chi Vicky Cheng, Takae Kiyama, Mitali Dave, Hanna K Mcnamara, Wukui Zhao, James M Stafford, Nicolas Descostes, Pedro Lee, Stefano G Caraffi, Ivan Ivanovski, Edoardo Errichiello, Christiane Zweier, Orsetta Zuffardi, Michael Schneider, Antigone S Papavasiliou, M Scott Perry, Jennifer Humberson, Megan T Cho, Astrid Weber, Andrew Swale, Tudor C Badea, Chai-An Mao, Livia Garavelli, William B Dobyns, Danny Reinberg

Faculty, Staff and Student Publications

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its …

Prognostic Values Of G-Protein Mutations In Metastatic Uveal Melanoma, Mizue Terai, Ayako Shimada, I Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B Wedegaertner, Jeffrey L Benovic, A E Aplin, Takami Sato

Department of Medical Oncology Faculty Papers

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and …

Posttranslational Modifications In Pd-L1 Turnover And Function: From Cradle To Grave, Xinfang Yu, Wei Li, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells' cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is …

16th Annual Pancreatic Cancer And Related Diseases Patient Symposium, Charles Yeo, Md, Facs, Adam C. Mueller, Md, Phd, Harish Lavu, Md, Facs, Theresa Yeo, Phd, Aochp, Acnp-Bc, Faanp, Avinoam Nevler, Md, Daniel Lin, Md, Msc, Wilbur Bowne, Md, Ira Sharp, Md

Pancreatic Cancer & Related Diseases Patient Symposium

On November 13, 2021, Charles J. Yeo, MD, FACS, and the multidisciplinary team of clinicians and scientists hosted the 16th Annual Pancreatic Cancer & Related Diseases Symposium.

The video of the event is available here: vimeo.com/646517712/36786afe68.

View our Pancreatic Cancer Program 2021 Update to learn more about Dr. Yeo and the team’s great work!

PROGRAM

Welcome and Program Overview
Charles J. Yeo, MD, FACS
Samuel D. Gross Professor and Chair of Surgery

Advances in FT in Treating Pancreatic Cancer
Adam Mueller, MD, PhD
Instructor, Radiation Oncology

KRAS Mutation Allele Frequency Impacts Prognosis in Pancreatic Ductal Adenocarcinoma Using Next-Generation Sequencing …

Mapk6-Akt Signaling Promotes Tumor Growth And Resistance To Mtor Kinase Blockade, Qinbo Cai, Wolong Zhou, Wei Wang, Bingning Dong, Dong Han, Tao Shen, Chad J Creighton, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK. Its function in regulating cancer growth remains elusive. Here, we reported that MAPK6 directly activated AKT and induced oncogenic outcomes. MAPK6 interacted with AKT through its C34 region and the C-terminal tail and phosphorylated AKT at S473 independent of mTORC2, the major S473 kinase. mTOR kinase inhibitors have not made notable progress in the clinic. Our identified MAPK6-AKT axis may provide a major resistance pathway. Besides repressing growth, inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. MAPK6 overexpression is associated with decreased overall survival and the survival of patients with …

Verrucous Carcinoma Of The Vulva: Patterns Of Care And Treatment Outcomes., Sara M. Dryden, Leonid B. Reshko, Jeremy T. Gaskins, Scott R. Silva

Faculty and Staff Scholarship

Background: Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. Aims: The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. Methods and results: Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. …