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Articles 1 - 30 of 160
Full-Text Articles in Chemicals and Drugs
Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary
Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary
Pharmacy Faculty Articles and Research
Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …
Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru
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. …
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
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 …
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
School of Graduate Studies Faculty Publications
Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
School of Graduate Studies Faculty Publications
Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
School of Medicine Faculty Publications
Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …
Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño
Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño
Health Sciences and Kinesiology Faculty Articles
Context
One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed …
Tebentafusp In Combination With Durvalumab And/Or Tremelimumab In Patients With Metastatic Cutaneous Melanoma: A Phase 1 Study, Omid Hamid, Jessica C. Hassel, Alexander N. Shoushtari, Friedegund Meier, Todd M. Bauer, April K.S. Salama, John M. Kirkwood, Paolo A. Ascierto, Paul C. Lorigan, Cornelia Mauch, Marlana Orloff, Thomas R. Jeffry Evans, Chris Holland, Ramakrishna Edukulla, Shaad E. Abedin, Mark R. Middleton
Tebentafusp In Combination With Durvalumab And/Or Tremelimumab In Patients With Metastatic Cutaneous Melanoma: A Phase 1 Study, Omid Hamid, Jessica C. Hassel, Alexander N. Shoushtari, Friedegund Meier, Todd M. Bauer, April K.S. Salama, John M. Kirkwood, Paolo A. Ascierto, Paul C. Lorigan, Cornelia Mauch, Marlana Orloff, Thomas R. Jeffry Evans, Chris Holland, Ramakrishna Edukulla, Shaad E. Abedin, Mark R. Middleton
Department of Medical Oncology Faculty Papers
BACKGROUND: Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority …
Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari
Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari
Pharmacy Faculty Articles and Research
The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a–d …
Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin
Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin
School of Medicine Faculty Publications
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …
Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville
Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville
Rowan-Virtua Research Day
PMPS is defined as chronic neuropathic pain following breast cancer procedures in the ipsilateral arm, chest wall, axilla or shoulder.1-3 Approximately 20 to 50% of post mastectomy patients suffer from Post Mastectomy Pain Syndrome (PMPS).1 With more than 3.8 million breast cancer survivors, due to advances in treatment, there is increased importance in findings ways to better manage the quality of life of breast cancer survivors.1,4 Ketamine induces analgesic effects through its non-competitive antagonism of NDMA receptors.5 Low doses of ketamine infusion (20–30 mg x h−1) have been shown to produce analgesia in neuropathic pain states with benefits lasting up …
Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey
Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey
Rowan-Virtua Research Day
Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, …
Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif
Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif
Student Research Submissions
Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H+ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …
Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West
Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West
School of Medicine Faculty Publications
HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …
Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia
Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia
Pharmacy Faculty Articles and Research
Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.
Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.
Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …
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 …
Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md
Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md
Theses and Dissertations--Clinical and Translational Science
Despite clinical advances, pancreatic neuroendocrine neoplasms (pNEN) remain a difficult clinical entity to treat and can carry a poor prognosis. Systemic therapy is used to treat pNENs which are not amenable to surgical resection. Peptide receptor radionuclide therapy, a form of radiation therapy (RT) and cisplatin are two different forms of DNA-damaging therapy in current use to treat pNENs. However, their efficacy remains poor as single agents. This study aimed to increase the sensitivity of pNENs to the DNA-damaging agents, RT and cisplatin, by inhibiting deoxynucleotide triphosphate (dNTP) synthesis. Triapine, a ribonucleotide reductase inhibitor (RNRi), and ataxia telangiectasia and Rad3-related …
Testing The Efficacy And Synergistic Components Of Sesamol And Black Rice Extract On Human Colon Cancer Cells, Sera Lim, Philip M. Gerk
Testing The Efficacy And Synergistic Components Of Sesamol And Black Rice Extract On Human Colon Cancer Cells, Sera Lim, Philip M. Gerk
Undergraduate Research Posters
Purpose: Systemic treatment of colorectal cancer involves chemotherapeutic agents which elicit serious and negative side effects from the toxicity of the drug. To address this issue, we are testing dietary supplements for their efficacy against human colon cancer cell lines and also their potential synergistic effects when combined with conventional chemotherapy. Dietary supplements (specifically sesamol and black rice extract) exhibit anticancer, anti-inflammatory, and chemo-preventive properties. Meanwhile, one of the cancer resistance mechanisms is the upregulation of drug elimination mechanisms, leading to multi-drug resistance. We hypothesize that dietary compounds will act as chemo-enhancers, thus enhancing potency of the chemotherapy drug(s) on …
Nurse-Led Education On Oral Chemotherapy Medications, Carmen Lucia Glick Alonso
Nurse-Led Education On Oral Chemotherapy Medications, Carmen Lucia Glick Alonso
Master's Projects and Capstones
Problem: Breast cancer is one of the leading causes of cancer death among women in the United States. Annually, around 264,000 breast cancer cases are diagnosed in women and 2,400 in men (Centers for Disease Control and Prevention, 2022). According to the American Cancer Society, the risk of a woman in the United States being diagnosed with breast cancer in their life is around 13% (2022).
Context: Along with a cancer diagnosis comes the need to introduce patient education about new oral chemotherapy treatments. As a treatment team member, the oncology nurse plays a vital role in this …
Reducing The Risk Of Chemotherapy Exposure, Miranda Susman
Reducing The Risk Of Chemotherapy Exposure, Miranda Susman
Symposium of Student Scholars
Concerns about antineoplastic drugs (ANPDs), also known as chemotherapy, began in the early 1970s by the National Institute for Occupational Safety and Health. Although ANPDs are used as a standard treatment for cancer, these drugs are considered hazardous due to their adverse health effects. About eight million healthcare workers are exposed to ANPDs and therefore essential that we continue to educate on ways to reduce the risk of exposure to occupational and home health hazards. The overall purpose of this study is to determine if additional education and use of surface wipe samplings reduce the risk of exposure. A literature …
Is There A Role For Allogeneic Hematopoietic Stem Cell Transplantation For Refractory Follicular Lymphoma?, Yang Yang, Xia Bi, Mia Gergis, Usama Gergis
Is There A Role For Allogeneic Hematopoietic Stem Cell Transplantation For Refractory Follicular Lymphoma?, Yang Yang, Xia Bi, Mia Gergis, Usama Gergis
Kimmel Cancer Center Papers, Presentations, and Grand Rounds
No abstract provided.
Metabolic Pathways Enriched According To Erg Status Are Associated With Biochemical Recurrence In Hispanic/Latino Patients With Prostate Cancer, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Melody C. Baddoo, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Marcela Nuñez Lemus, Martha Lucía Serrano, Jovanny Zabaleta, Alba L. Combita, María Carolina Sanabria-Salas
Metabolic Pathways Enriched According To Erg Status Are Associated With Biochemical Recurrence In Hispanic/Latino Patients With Prostate Cancer, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Melody C. Baddoo, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Marcela Nuñez Lemus, Martha Lucía Serrano, Jovanny Zabaleta, Alba L. Combita, María Carolina Sanabria-Salas
School of Medicine Faculty Publications
Background: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed …
A Machine Learning Model Of Response To Hypomethylating Agents In Myelodysplastic Syndromes, Nathan Radakovich, David A. Sallman, Rena Buckstein, Andrew Brunner, Amy Dezern, Sudipto Mukerjee, Rami Komrokji, Najla Al-Ali, Jacob Shreve, Yazan Rouphail, Anne Parmentier, Alexandre Mamedov, Mohammed Siddiqui, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha
A Machine Learning Model Of Response To Hypomethylating Agents In Myelodysplastic Syndromes, Nathan Radakovich, David A. Sallman, Rena Buckstein, Andrew Brunner, Amy Dezern, Sudipto Mukerjee, Rami Komrokji, Najla Al-Ali, Jacob Shreve, Yazan Rouphail, Anne Parmentier, Alexandre Mamedov, Mohammed Siddiqui, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha
Department of Medical Oncology Faculty Papers
Hypomethylating agents (HMA) prolong survival and improve cytopenias in individuals with higher-risk myelodysplastic syndrome (MDS). Only 30-40% of patients, however, respond to HMAs, and responses may not occur for more than 6 months after HMA initiation. We developed a model to more rapidly assess HMA response by analyzing early changes in patients’ blood counts. Three institutions’ data were used to develop a model that assessed patients’ response to therapy 90 days after the initiation using serial blood counts. The model was developed with a training cohort of 424 patients from2 institutions and validated on an independent cohort of 90 patients. …
Multidrug Resistance In Cancer: Understanding Molecular Mechanisms, Immunoprevention And Therapeutic Approaches, Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud, Tanjilur Rahman, Mehedy Hasan Abir, Mohd Faijanur-Rob Siddiquee, Hossain Ahmed, Nova Rahman, Firzan Nainu, Elly Wahyudin
Multidrug Resistance In Cancer: Understanding Molecular Mechanisms, Immunoprevention And Therapeutic Approaches, Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud, Tanjilur Rahman, Mehedy Hasan Abir, Mohd Faijanur-Rob Siddiquee, Hossain Ahmed, Nova Rahman, Firzan Nainu, Elly Wahyudin
School of Medicine Publications and Presentations
Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as …
Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin
Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin
Dissertations & Theses (Open Access)
One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …
Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu
Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu
Undergraduate Honors Theses
RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …
Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami
Chemistry & Biochemistry Undergraduate Honors Theses
The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …
Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari
Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari
Pharmacy Faculty Articles and Research
Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) …
Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse
Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse
Research outputs 2022 to 2026
Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001–2017. Drug exposures taken from the National Survey of Drug Use and Health 2003–2017, response rate 74.1%. Federal seizure data provided …
Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 3 – Spatiotemporal, Multivariable And Causal Inferential Pathfinding And Exploratory Analyses Of Prostate And Ovarian Cancers, Albert Stuart Reece, Gary Kenneth Hulse
Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 3 – Spatiotemporal, Multivariable And Causal Inferential Pathfinding And Exploratory Analyses Of Prostate And Ovarian Cancers, Albert Stuart Reece, Gary Kenneth Hulse
Research outputs 2022 to 2026
Background: The epidemiology of cannabinoid-related cancerogenesis has not been studied with cutting edge epidemiological techniques. Building on earlier bivariate papers in this series we aimed to conduct pathfinding studies to address this gap in two tumours of the reproductive tract, prostate and ovarian cancer. Methods: Age-standardized cancer incidence data for 28 tumour types (including “All (non-skin) Cancer”) was sourced from Centres for Disease Control and National Cancer Institute using SEER*Stat software across US states 2001–2017. Drug exposure was sourced from the nationally representative household survey National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental …