Medical Sciences Commons^™

Frailty In Children And Adolescents With Acute Lymphoblastic Leukemia Or Lymphoblastic Lymphoma Receiving Maintenance Chemotherapy – A Pilot Study, Thomas R. Cochran, Joy M. Fulbright, Samantha Butrous, Brian R. Lee, Keith J. August, David A. White

Research Days

The submitted study aims to identify children with acute lymphoblastic leukemia or lymphoblastic lymphoma that meet frailty criteria early to allow for prevention of chronic health conditions that lead to increased mortality as survivors age into adulthood. Prevention and/or reversal of frailty has the potential to improve quality of life, decrease burden of disease, and extend the lifespan of the growing population of childhood cancer survivors. Given that frailty has been accepted as a tool to identify elderly and chronically sick adults highly vulnerable to adverse health outcomes, better understanding of the relevance and applicability of frailty in pediatrics may …

Evaluation Of An End-To-End Radiotherapy Treatment Planning Pipeline For Prostate Cancer, Mohammad Daniel El Basha, Court Laurence, Carlos Eduardo Cardenas, Julianne Pollard-Larkin, Steven Frank, David T. Fuentes, Falk Poenisch, Zhiqian H. Yu

Dissertations & Theses (Open Access)

Radiation treatment planning is a crucial and time-intensive process in radiation therapy. This planning involves carefully designing a treatment regimen tailored to a patient’s specific condition, including the type, location, and size of the tumor with reference to surrounding healthy tissues. For prostate cancer, this tumor may be either local, locally advanced with extracapsular involvement, or extend into the pelvic lymph node chain. Automating essential parts of this process would allow for the rapid development of effective treatment plans and better plan optimization to enhance tumor control for better outcomes.

The first objective of this work, to automate the treatment …

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

Electronic Theses, Projects, and Dissertations

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

Genetic And Serological Markers In Colorectal Cancer Surgery, Adrian Silaghi, Vlad Denis Constantin, Dragos Serban, Dragos Epistatu, Ioana Paunica, Daniela Gabriela Bălan, Laura Florentina Rebegea

Journal of Mind and Medical Sciences

Colon cancer is relatively asymptomatic in the early stages, the manifestations appearing and intensifying with the evolution of the disease, especially when associated with local and/or systemic complications. In such cases, surgical interventions are often emergency and involve more extensive operations (on metabolically and immune-stressed organisms), so that an early diagnosis (endoscopy, tumor markers, etc.) remains not only desirable but even a priority, especially in predisposed patients (genetic factors, lifestyle, etc.). As a consequence, the involvement of tumor markers in colon neoplasms has become more and more investigated in recent times. This review investigates the roles of serological and genetic …

Typhlitis In A Neutropenic Patient, Alice He Bs, Wern Lynn Ng Md, Lay She Ng Md, Si Yuan Khor Md, Chandi Garg Md

Tower Health Research Day

No abstract provided.

Li-Fraumeni Syndrome And The Benefits Of Annual Comprehensive Screening: A Pancreatic Adenocarcinoma Case, Alice He Bs, Wern Lynn Ng Md, Faith Seltun Do, Lay She Ng Md, Si Yuan Khor Md, Elham Nasrollahi Md, Chandi Garg Md, Rong Rong Ge Md

Tower Health Research Day

No abstract provided.

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi

Research Symposium

Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated …

Spontaneous Tumor Lysis Syndrome In A Patient With Recent Diagnosis Of Multiple Myeloma — An Unusual Presentation, Taha Al Hassan, Olga G. Cantu-Rodriguez, Eunbee Cho, Edgar G. Dorsey Trevino

Research Symposium

Background: Tumor lysis syndrome (TLS) is an oncologic emergency that surfaces as a constellation of metabolic imbalances due to the rapid destruction of cancer cells and subsequent dissemination of their contents. However, a markedly rare subtype of TLS, known as spontaneous TLS (STLS), occurs without an evident trigger, such as cytotoxic therapy, and carries a similar mortality risk. It is paramount to recognize high-risk cases early and implement therapeutic measures to prevent complications of STLS.

Case Presentation: We present the case of a 74-year-old gentleman with a recent diagnosis of Kappa-restricted multiple myeloma who presented with worsening weakness, tremors, ataxia, …

Lncrna Impact On Regorafenib Resistance In Colorectal Cancer, Ricardo Pequeno Bracho, Kyle Doxtater, Dennis Kwabiah, Yamile Abuchard Anaya, Sophia Leslie, Mohammad Shabir Hussain, Manish Tripathi

Research Symposium

Cancer metastasis is one of the deadliest aspects of the disease, with about 90% of all cancer-related deaths due to its development at different sites within the body. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States, with 40-50% of all patients developing metastasis at some point during their fight with the disease. With the approval of Regorafenib for treating metastatic colorectal cancer, steps have been taken to combat metastasis in colorectal cancer. A vital aspect of the development of metastasis is the development of resistance to first-line chemotherapy. Regorafenib is an oral small-molecule …

Development Of Solitary Keratoacanthoma From A Cutaneous Wart, Joshua M. Ninan, Veronica Salazar

Research Symposium

Background: Common cutaneous warts, referred to in medicine as verrucae vulgaris, are proliferative lesions caused by human papillomavirus. These lesions are mostly benign and usually resolve without incident, except in the case of the patient mentioned in this report. Our patient developed a solitary keratoacanthoma, currently accepted as a clinical variant of squamous cell carcinoma, as a result of several risk factors and traumatic exposure. The current literature does not have an established association of HPV with solitary keratoacanthomas. This case report explores the presentation and pathogenesis of solitary keratoacanthomas within the setting of HPV.

Case Presentation: 48-year-old Caucasian female …

Single-Cell Transcriptomics Reveals Pre-Existing Covid-19 Vulnerability Factors In Lung Cancer Patients, Wendao Liu, Wenbo Li, Zhongming Zhao

Journal Articles

UNLABELLED: Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory …

Angiofibroma Of Soft Tissue: A Case Report, Mehruba Alam, Jake Robins

Annual Research Symposium

Differentiation between benign angiofibromas of soft tissue and malignant sarcomas.

The accurate diagnosis of this tumor is essential to prevent additional unnecessary treatments and/or surgeries. This can be achieved by proper genetic testing for the presence of markers including the NCOA2 fusion gene, CD34, α-SMA, and epithelial membrane antigen. Genetic testing is an essential component of accurate diagnosis as the appearance of these lesions can mimic other, more harmful neoplasms. Immunohistochemical analysis frequently shows the AHRR-NCOA2 driver mutation which is thought to be associated with t(5;8)(p15;q13), also commonly found in AFSTs. In combination, these immunohistochemical findings allow for accurate diagnosis …

Challenges In Diagnosing Hepatic Epithelioid Hemangioendothelioma: A Case Series, Aratara Nutcharoen, Elliott Beard, Anupa Thirmiya, Omar Taher, Jacob Adams, Mark Mortensen, John Pelham

Annual Research Symposium

Challenges in Diagnosing Hepatic Epithelioid Hemangioendothelioma

Effects Of Extraction Methods On The Structural Characteristics And Functional Properties Of Dietary Fiber Extracted From Papaya Peel And Seed, Xiaoyu Feng, Kashif Ameer, Guihun Jiang, Karna Ramachandraiah

School of Medicine Faculty Publications

This study aimed to characterize dietary fibers (DF) produced from papaya peel (PP) and seed (PS) using three different extraction methods (acidic: AC, enzymatic: EN and alkaline: AL). The scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermal and rheological properties, X-ray diffraction (XRD), monosaccharide composition were adopted for characterizing DF samples. All the DF samples showed representative infrared spectral features and crystalline structure, whereas DF derived from PP and PS extracted by AC had looser and more complicated structures. DF derived from PP and PS extracted by EN displayed greater thermal stability among DFs. DF extracted by PP-AC …

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Nutritional Support For Oncology Patients: Role For The Pcp, Annabelle S. Feist

Family Medicine Clerkship Student Projects

Adequate nutrition is a key prognostic factor in the treatment outcomes of patients with cancer diagnoses. Despite the increased morbidity and mortality of malnutrition, the importance of nutrition for oncology patients is often not well communicated and not well understood by patients. Part of this issue stems from the limited information most patient can absorb at any given doctors appointment, especially regarding their cancer. Primary care providers hold a unique position to fill this gap and have the information be heard and retained given their usual role in addressing overall health. This project compiles resources in an easily accessible and …

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

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

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

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Atm Deficiency Confers Specific Therapeutic Vulnerabilities In Bladder Cancer, Yuzhen Zhou, Judit Börcsök, Elio Adib, Sophia C. Kamran, Alexander J. Neil, Konrad Stawiski, Dory Freeman, Dag Rune Stormoen, Zsofia Sztupinszki, Amruta Samant, Amin Nassar, Raie T. Bekele, Timothy Hanlon, Henkel Valentine, Ilana Epstein, Bijaya Sharma, Kristen Felt, Philip Abbosh, Chin-Lee Wu, Jason A. Efstathiou, David T. Miyamoto, William Anderson, Zoltan Szallasi, Kent W. Mouw

Einstein Health Papers

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

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

School of Medicine

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

Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass …

Liposome Synthesis And Evaluation In The Hek-293 Cell Line, Christine Skibinski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Liposomes were synthesized using the thin film method. A lyophilized power of egg-derived phosphatidylcholine, stearylamine, and cholesterol were added to ethanol and dried under argon to form a lipid cake. The lipid cake was rehydrated with dPBS and sonicated at 60°C forming a heterogenous batch of liposomes. Our results revealed the average size of the liposomes, determined by Dynamic Light Scattering, was approximately 223.1nm, while demonstrating a weakly positive zeta-potential of 1.9± 8.07mv. Next, we tested the antitumor action of the liposomes in the HEK-293 cell line via an MTT assay. We observed that the liposomes were able to inhibit …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Recent advances in the understanding of the molecular mechanisms underlying cancer progression have led to the development of novel therapeutic targeting strategies. Aberrant glycosylation patterns and their implication in cancer have gained increasing attention as potential targets due to the critical role of glycosylation in regulating tumor-specific pathways that contribute to cancer cell survival, proliferation, and progression. A special type of glycosylation that has been gaining momentum in cancer research is the modification of nuclear, cytoplasmic, and mitochondrial proteins, termed O-GlcNAcylation. This protein modification is catalyzed by an enzyme called O-GlcNAc transferase (OGT), which uses the final product of the …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Variant Characterization Of A Representative Large Pedigree Suggests “Variant Risk Clusters” Convey Varying Predisposition Of Risk To Lynch Syndrome, Mouadh Barbirou, Amanda A. Miller, Amel Mezlini, Balkiss Bouhaouala-Zahar, Peter J. Tonellato

Department of Medical Oncology Faculty Papers

Recently, worldwide incidences of young adult aggressive colorectal cancer (CRC) have rapidly increased. Of these incidences diagnosed as familial Lynch syndrome (LS) CRC, outcomes are extremely poor. In this study, we seek novel familial germline variants from a large pedigree Tunisian family with 12 LS-affected individuals to identify putative germline variants associated with varying risk of LS. Whole-genome sequencing analysis was performed to identify known and novel germline variants shared between affected and non-affected pedigree members. SNPs, indels, and structural variants (SVs) were computationally identified, and their oncological influence was predicted using the Genetic Association of Complex Diseases and Disorders, …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …