Open Access. Powered by Scholars. Published by Universities.®
- Institution
- Keyword
-
- Apoptosis (4)
- Cancer (4)
- Humans (4)
- Oxidative stress (4)
- Cancer stem cells (3)
-
- Case report (3)
- Cell line (3)
- Female (3)
- Biomarker (2)
- Breast neoplasms (2)
- Carcinoma (2)
- Circulating tumor cells (2)
- Colorectal cancer (2)
- Fluid shear stress (2)
- Inflammation (2)
- Ionizing radiation (2)
- Neoplasm (2)
- Sensitivity (2)
- Triple negative breast cancer (2)
- Tumor (2)
- Ubiquitination (2)
- (BMPs) (1)
- 4T1 (1)
- 5-Fluorouracil (1)
- Ablation (1)
- Abscopal effect (1)
- Acetylglucosamine (1)
- Acquired-Resistence (1)
- Activation (1)
- Activin A (1)
- Publication Year
- Publication
-
- Department of Pathology and Laboratory Medicine (5)
- Markey Cancer Center Faculty Publications (5)
- Bioelectrics Publications (4)
- Department of Biomedical and Translational Sciences Faculty Publications (4)
- School of Medicine Faculty Publications (4)
-
- Department of Biological & Biomedical Sciences (2)
- Department of Surgery Docs (2)
- Journal of Patient-Centered Research and Reviews (2)
- Biological Sciences Faculty Publications (1)
- Biology, Chemistry, and Environmental Sciences Faculty Articles and Research (1)
- Chemistry & Biochemistry Faculty Publications (1)
- Computer Science Faculty Publications (1)
- Department of Medicine Faculty Publications (1)
- Departmental Honors & Graduate Capstone Projects (1)
- Honors Theses (1)
- Honors Undergraduate Theses (1)
- Internal Medicine Faculty Publications (1)
- Kimmel Cancer Center Faculty Papers (1)
- Manuscripts, Articles, Book Chapters and Other Papers (1)
- Marshall Journal of Medicine (1)
- Medical College Documents (1)
- School of Public Health Faculty Publications (1)
- Section of Diabetes, Endocrinology and Metabolism (1)
- Section of General Surgery (1)
- Section of Haematology/Oncology (1)
- Section of Internal Medicine (1)
- Student Publications & Research (1)
- Theses & Dissertations (1)
- Theses and Dissertations--Toxicology and Cancer Biology (1)
- Publication Type
Articles 1 - 30 of 49
Full-Text Articles in Cells
Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton
Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton
Honors Theses
Tumor innervation has emerged as a critical feature of cancer progression, with increased nerve density correlating with enhanced aggressiveness, metastatic dissemination, and poor clinical outcome. However, the functional contribution of neurons to tumor biology remains incompletely defined. We recently identified the intercellular transfer of mitochondria from neurons to cancer cells as a mechanism that promotes tumor progression. We therefore hypothesized that disruption of this transfer could attenuate tumor aggressivity. To directly investigate this process, we developed an approach to isolate mitochondria from donor cells and transplant them into recipient cancer cells independently of canonical cell-cell interactions. Transferred mitochondria were tracked …
Metabolic Reprogramming Following Mitochondrial Transfer Between Idh2-Mutant Chondrosarcoma Cells And A Normal B-Cell Line, Caleb Wyckoff, Christopher Osgood, Ellen Jing, Michael Stacey
Metabolic Reprogramming Following Mitochondrial Transfer Between Idh2-Mutant Chondrosarcoma Cells And A Normal B-Cell Line, Caleb Wyckoff, Christopher Osgood, Ellen Jing, Michael Stacey
Bioelectrics Publications
Background/Objectives: Chondrosarcoma, glioblastoma, acute myeloid leukemia, chronic lymphocytic leukemia, and cholangiocarcinoma cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme metabolizes alpha-ketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers, leading to altered cellular metabolism. Emerging evidence suggests that mitochondrial transfer between cancer and recipient cells represents an important form of intercellular communication that may influence cellular metabolism. The presence of intercellular TNTs between IDH2-mutant chondrosarcoma cells motivated an investigation into mitochondria-associated physiological changes occurring during an intercellular exchange with immune cells. A mitochondrial transfer is a two-way …
Establishment And Histopathological Characterization Of A Kyse-30 Subcutaneous Xenograft Model Of Esophageal Squamous Cell Carcinoma, Pavel A. Solopov, Alayna Enos, Mantas Silkunas, Giedre Silkuniene, Eleni Zivla, Andrei G. Pakhomov, Olga N. Pakhomova
Establishment And Histopathological Characterization Of A Kyse-30 Subcutaneous Xenograft Model Of Esophageal Squamous Cell Carcinoma, Pavel A. Solopov, Alayna Enos, Mantas Silkunas, Giedre Silkuniene, Eleni Zivla, Andrei G. Pakhomov, Olga N. Pakhomova
Bioelectrics Publications
Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis and limited treatment options, highlighting the need for reliable preclinical models for translational research. Although xenograft models are widely used in cancer biology, systematic characterization of subcutaneous ESCC models under defined implantation conditions remains limited. The objective of this study was to systematically compare implantation conditions and define histopathological and growth-related parameters that enable reproducible tumor establishment while maintaining a practical experimental window for therapeutic studies. Methods: We established and characterized a subcutaneous ESCC xenograft model using human ESCC cell line KYSE-30 implanted into immunodeficient J:NU mice. …
Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo
Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo
Bioelectrics Publications
Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase …
Nanosecond Electric Pulses As A Novel In Situ Vaccination Strategy For Cancer Treatment: Mechanisms, Challenges And Prospects, Siqi Guo
Bioelectrics Publications
Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can …
Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry
Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry
Department of Biomedical and Translational Sciences Faculty Publications
Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …
Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang
Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang
Computer Science Faculty Publications
The 3D organization of chromatin plays a fundamental role in gene regulation, cellular function, and disease mechanisms. However, current experimental techniques, such as Hi-C, remain costly and labor-intensive, limiting their application in large-scale and disease-related studies. To address this challenge, ChromNet is presented, a multi-task learning framework that integrates epigenetic signals across diverse cell types to enable high-precision prediction of chromatin architecture. By incorporating noise perturbation and auxiliary classification tasks, ChromNet improves the identification of topologically associating domains (TADs) and cell-type-specific chromatin structures, demonstrating superior generalization performance. Notably, ChromNet accurately predicts chromatin interactions in acute myeloid leukemia (AML) samples by …
Oncogenic Effects Of Ecm Remodeling In Obesity And Breast Cancer, Mackenzie L. Hawes, Marcus A. Moody, Caroline R. Mccauley, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin
Oncogenic Effects Of Ecm Remodeling In Obesity And Breast Cancer, Mackenzie L. Hawes, Marcus A. Moody, Caroline R. Mccauley, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin
School of Medicine Faculty Publications
Extracellular matrix (ECM) components are key regulators in breast cancer progression, as ECM remodeling is essential for breast cancer cells to invade into surrounding tissue. This process is characterized by the alignment of fibrillar collagens, breakdown of basement membrane components, and increased interstitial collagen stiffness. In patients with obesity, pre-existing ECM changes, including excessive collagen deposition and heightened matrix stiffness, mimic alterations detected in breast cancer. Given that obesity is a predictor of poor prognosis and resistance to treatment in breast cancer, it is crucial to understand how ECM conditioned by obesity affects disease outcomes. In this review, we highlight …
Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato
Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato
Kimmel Cancer Center Faculty Papers
The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …
Atypical Presentation Of Non-Small Cell Lung Carcinoma With Metastasis To Breast Tissue, Tylar P. Seckman, Diane Krutzler-Berry, Mohamed Ashal, Waqas Mahmud, Krista L. Denning, Logan M. Lawrence
Atypical Presentation Of Non-Small Cell Lung Carcinoma With Metastasis To Breast Tissue, Tylar P. Seckman, Diane Krutzler-Berry, Mohamed Ashal, Waqas Mahmud, Krista L. Denning, Logan M. Lawrence
Marshall Journal of Medicine
Malignant neoplasms of the lung commonly metastasize to lymph nodes, bone, brain, and liver via hematogenous and lymphatic routes. Much less commonly, metastasis occurs in the breast. Secondary metastatic disease of the breast is very rare, with a reported incidence ranging from 0.4-1.3%—with primary lung cancer being one of the most anomalous sources. This case details non-small cell lung cancer metastasis to the breast with proven primary contralateral lung origination. This atypical finding prompts medical professionals to consider these malignant cells' immunologic, histologic, and pathologic makeup to understand further and treat the neoplasm.
Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen
Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen
Department of Medicine Faculty Publications
Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to …
The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou
The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou
Biological Sciences Faculty Publications
[Introduction] The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2, 3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed …
Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu
Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu
Department of Biomedical and Translational Sciences Faculty Publications
Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …
5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker
5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker
Departmental Honors & Graduate Capstone Projects
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …
Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin
Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin
School of Medicine Faculty Publications
Following metastatic spread, many hormone receptor positive (HR(+)) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR(+) breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure …
Overexpression Of Fatty Acid Synthase Upregulates Glutamine–Fructose-6-Phosphate Transaminase 1 And O-Linked N-Acetylglucosamine Transferase To Increase O-Glcnac Protein Glycosylation And Promote Colorectal Cancer Growth, James Drury, Mariah E. Geisen, Josiane Weber Tessmann, Piotr G. Rychahou, Courtney O. Kelson
Overexpression Of Fatty Acid Synthase Upregulates Glutamine–Fructose-6-Phosphate Transaminase 1 And O-Linked N-Acetylglucosamine Transferase To Increase O-Glcnac Protein Glycosylation And Promote Colorectal Cancer Growth, James Drury, Mariah E. Geisen, Josiane Weber Tessmann, Piotr G. Rychahou, Courtney O. Kelson
Markey Cancer Center Faculty Publications
Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently being tested in multiple clinical trials. However, the mechanisms behind the pro- oncogenic action of FASN are still not completely understood. Here, for the first time, we show that overexpression of FASN increases the expression of glutamine–fructose-6-phosphate transaminase 1 (GFPT1) and O-linked N-acetylglucosamine transferase (OGT), enzymes involved in hexosamine metabolism, and the level of O-GlcNAcylation in vitro …
Diagnostic Accuracy Of Intraoperative Frozen Section For Margin Evaluation Of Oral Cavity Squamous Cell Carcinoma, Javaria P. Ali, Bakhtawar Allauddin Mallick, Khushbakht Rashid, Umair Arshad Malik, Atif Ali Hashmi, Shamail Zia, Muhammad Irfan, Amir Khan, Naveen Faridi
Diagnostic Accuracy Of Intraoperative Frozen Section For Margin Evaluation Of Oral Cavity Squamous Cell Carcinoma, Javaria P. Ali, Bakhtawar Allauddin Mallick, Khushbakht Rashid, Umair Arshad Malik, Atif Ali Hashmi, Shamail Zia, Muhammad Irfan, Amir Khan, Naveen Faridi
Section of Internal Medicine
Objectives: Intraoperative frozen-section evaluation is a valuable technique for detecting positive margins intraoperatively for oral squamous cell carcinoma. We conducted this study to determine the diagnostic accuracy of frozen section in detecting margin status and the effect of tumor grade and stage on diagnostic accuracy.
Results: A total of 251 biopsy-proven cases of oral squamous cell carcinoma were included in this study. The tissue specimen resected during surgery was sent to the laboratory for frozen section evaluation. The frozen section results were then compared with the permanent section results to determine the sensitivity, specificity, positive predictive value, negative predictive value, …
Elucidating The Role Of Fatty Acid Synthase In Apc-Driven Colorectal Cancer, Courtney O. Kelson
Elucidating The Role Of Fatty Acid Synthase In Apc-Driven Colorectal Cancer, Courtney O. Kelson
Theses and Dissertations--Toxicology and Cancer Biology
Globally, colorectal cancer (CRC) is the second leading cause of cancer related deaths. Currently, there is a growing incidence rate for individuals aged 20-49 years. Genetic and environmental factors contribute to the risk of this cancer. Early detection of CRC allows for the most effective treatment option in which surgical resection of the primary tumor occurs along with adjuvant chemotherapy. This therapeutic approach contributes to 5-year survival rate of 91%. However, surgical procedures and chemotherapy struggles against metastatic and relapsed CRC resulting in 5-year survival rate of 14%. Inefficacious treatments for relapsed and metastatic diseases emphasizes the need for more …
Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn
Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn
Markey Cancer Center Faculty Publications
The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …
Synthesis And Structure-Activity Relationship Of Boronic Acid Bioisosteres Of Combretastatin A-4 As Anticancer Agents, Yali Kong, Michael C. Edler, Ernest Hamel, Asa R. Britton-Jenkins, Omar Gillan, Susan L. Mooberry, David Mu, Milton L. Brown
Synthesis And Structure-Activity Relationship Of Boronic Acid Bioisosteres Of Combretastatin A-4 As Anticancer Agents, Yali Kong, Michael C. Edler, Ernest Hamel, Asa R. Britton-Jenkins, Omar Gillan, Susan L. Mooberry, David Mu, Milton L. Brown
Department of Biomedical and Translational Sciences Faculty Publications
The boronic acid group plays an important role in drug discovery. Following our discovery of a boronic acid analog of combretastatin A-4 (CA-4), a series of analogs featuring a boronic acid group on the C phenyl ring of CA-4 was synthesized and evaluated for cytotoxicity, as well as for their ability to inhibit tubulin polymerization, inhibit the binding of [³H]colchicine to tubulin and cause depolymerization of cellular microtubules. Modifications on the C ring of CA-4, either eliminating the methoxy group or replacing the C phenyl ring with a pyridine ring, resulted in a reduced potency for inhibiting tubulin polymerization, colchicine …
Enhancement Of Antitumor Effects Of Berberine Chloride With A Copper(Ii) Complex Against Human Triple Negative Breast Cancer: In Vitro Studies, Duaa R. Alajroush, Brittney F. Anderson, Janae A. Bruce, Christian I. Lartey, Dazonte A. Mathurin, Sean T. Washington, Tanaya S. Washington, Sidy Diawara, Sakariyau A. Waheed, Kaylin L. Thomas, Stephen J. Beebe, Alvin A. Holder
Enhancement Of Antitumor Effects Of Berberine Chloride With A Copper(Ii) Complex Against Human Triple Negative Breast Cancer: In Vitro Studies, Duaa R. Alajroush, Brittney F. Anderson, Janae A. Bruce, Christian I. Lartey, Dazonte A. Mathurin, Sean T. Washington, Tanaya S. Washington, Sidy Diawara, Sakariyau A. Waheed, Kaylin L. Thomas, Stephen J. Beebe, Alvin A. Holder
Chemistry & Biochemistry Faculty Publications
In this study, the copper(II) complex [Cu(chromoneTSC)Cl₂]•0.5H₂O•0.0625C₂H₅OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamide) was synthesized and characterized; then used to carry out in vitro studies in combination with berberine chloride (BBC). The ligand and complex were characterized by elemental analysis, FTIR and NMR (¹H and ¹³C) spectroscopy, and conductivity measurements. The cytotoxic effect was analyzed by using the CCK-8 viability assay in cancer MDA-MB-231 VIM RFP and non-cancer MCF-10A cell lines. The IC₅₀ values for the complex and BBC were 21.2 ± 1.6 and 48.3 ± 2.4 μM, respectively at 24 h incubation, while the IC₅₀ value of the combination treatment …
Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar
Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar
Honors Undergraduate Theses
Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …
Exploring Angiotensin Ii And Oxidative Stress In Radiation-Induced Cataract Formation: Potential For Therapeutic Intervention, Vidya P. Kumar, Yali Kong, Riana Dolland, Sandra R. Brown, Kan Wang, Damian Dolland, David Mu, Milton L. Brown
Exploring Angiotensin Ii And Oxidative Stress In Radiation-Induced Cataract Formation: Potential For Therapeutic Intervention, Vidya P. Kumar, Yali Kong, Riana Dolland, Sandra R. Brown, Kan Wang, Damian Dolland, David Mu, Milton L. Brown
Department of Biomedical and Translational Sciences Faculty Publications
Radiation-induced cataracts (RICs) represent a significant public health challenge, particularly impacting individuals exposed to ionizing radiation (IR) through medical treatments, occupational settings, and environmental factors. Effective therapeutic strategies require a deep understanding of the mechanisms underlying RIC formation (RICF). This study investigates the roles of angiotensin II (Ang II) and oxidative stress in RIC development, with a focus on their combined effects on lens transparency and cellular function. Key mechanisms include the generation of reactive oxygen species (ROS) and oxidative damage to lens proteins and lipids, as well as the impact of Ang II on inflammatory responses and cellular apoptosis. …
Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe
Dpp8 Selective Inhibitor Tominostat As A Novel And Broad-Spectrum Anticancer Agent Against Hematological Malignancies, Shohei Kikuchi, Akinori Wada, Yusuke Kamihara, Kosuke Okazaki, Paras Jawaid, Mati Ur Rehman, Eiji Kobayashi, Takeshi Susukida, Tomoki Minemura, Yoshimi Nabe
Department of Biological & Biomedical Sciences
DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for …
Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee
Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee
School of Medicine Faculty Publications
Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
School of Public Health Faculty Publications
Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.
Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava
Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava
School of Medicine Faculty Publications
Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …
Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim
Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim
Department of Biological & Biomedical Sciences
Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line.
Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked …
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Department of Pathology and Laboratory Medicine
Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …
Chronic Diarrhea: A Rare Presentation Of Hodgkin's Lymphoma, Saira Furqan, Sajjad Ali Khan, Dania Ali, Kaleemullah Badini
Chronic Diarrhea: A Rare Presentation Of Hodgkin's Lymphoma, Saira Furqan, Sajjad Ali Khan, Dania Ali, Kaleemullah Badini
Section of Diabetes, Endocrinology and Metabolism
Hodgkin's Lymphoma is a cancer affecting the lymphatic system. There are two subtypes of Hodgkin's Lymphoma: Nodular lymphocyte predominant (NLPHL) and classical Hodgkin's Lymphoma which has further four types. It has a bimodal distribution and is more common among males. The most common presentation is painless swelling in the neck, armpit or groin region. Associated Symptoms include night sweats, unintentional weight loss, fever, persistent cough or dyspnea. Involvement of the gastrointestinal tract is a rare occurrence. Diagnosis is based on hematological, radiological and histochemical studies. Here we report a rare presentation of a 47-year-old male who presented with symptoms of …