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Full-Text Articles in Medicine and Health Sciences

The Development Of A New Water-Soluble Zinc Porphyrin, Zntpp-2mp, As A Photodynamic Therapy Agent, Emily Payne Apr 2024

The Development Of A New Water-Soluble Zinc Porphyrin, Zntpp-2mp, As A Photodynamic Therapy Agent, Emily Payne

Scholars Day Conference

Photodynamic therapy is a new technique used in cancer treatment involving the use of a photosensitizer and light exposure to kill malignant cells. This research tested the use of ZnTPP-2MP as a photosensitizer using white light as a source of possible treatment of the A549 cancer cell line, with preliminary testing on MYC-22 and other G- quadruplex DNA samples. ZnTPP-2MP was synthesized by the reaction of the porphyrin, ZnTPPC, with 2-amino-2- methyl-1-propanol. Following synthesis, the new porphyrin was purified by column chromatography using Sephadex LH-20 and G-50. To confirm the identity and structure of the product, ZnTPP-2MP was analyzed through …


Targeting Tgf-Β During Epithelial-To-Mesenchymal Progression As An Effective Therapy Against Colorectal Cancer, Joyce Fan Apr 2024

Targeting Tgf-Β During Epithelial-To-Mesenchymal Progression As An Effective Therapy Against Colorectal Cancer, Joyce Fan

Undergraduate Research

Colorectal cancer is one of the most common cancers worldwide. Understanding the mechanisms of colorectal cancer progression is crucial for the development of effective therapeutics. Epithelial-to-mesenchymal transition is a hallmark feature of cancer and is defined as the loss of epithelial cell features, such as apical-basal polarity and high expression of cell adhesion molecules, and the development of mesenchymal features, such as lack of polarity and increased cell mobility. Epithelial-to-mesenchymal is essential for cell migration, proliferation, and tumor growth. Both the TGF-β and SMAD pathway are associated with colorectal cancer progression. TGF-β is crucial to the cellular mechanism of cell …


Mcl-1 Mediates Intrinsic Resistance To Raf Inhibitors In Mutant Braf Papillary Thyroid Carcinoma, Maria Cavallo, Jacob Yo, Kayla Gallant, Camille Cunanan, Amirali Amirfallah, Marzieh Daniali, Alyssa Sanders, Andrew Aplin, Edmund Pribitkin, Edward Hartsough Apr 2024

Mcl-1 Mediates Intrinsic Resistance To Raf Inhibitors In Mutant Braf Papillary Thyroid Carcinoma, Maria Cavallo, Jacob Yo, Kayla Gallant, Camille Cunanan, Amirali Amirfallah, Marzieh Daniali, Alyssa Sanders, Andrew Aplin, Edmund Pribitkin, Edward Hartsough

Kimmel Cancer Center Faculty Papers

Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response …


Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi Apr 2024

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: John Heinrichs Scholarly and Creative Activity Days

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …


Sickle Cell Disease Phenotypes And Obstructive Sleep Apnea; Are They Related?, Suhail Alsaleh, Norah Alshehri, Sara Alsiddiqi, Mohmmed Rayis, Safa Eltahir, Khaled Aldajjam, Mohammed Alzaid, Wadha Alotaibi Mar 2024

Sickle Cell Disease Phenotypes And Obstructive Sleep Apnea; Are They Related?, Suhail Alsaleh, Norah Alshehri, Sara Alsiddiqi, Mohmmed Rayis, Safa Eltahir, Khaled Aldajjam, Mohammed Alzaid, Wadha Alotaibi

Hematology/Oncology and Stem Cell Therapy

ABSTRACT: OBJECTIVE: This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD). MATERIALS AND METHODS: This prospective cross-sectional study was conducted in the Children’s Hospital at King Fahad Medical City, in Riyadh where children were recruited from the pediatric hematology clinic and pediatric sleep medicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study. RESULTS: Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their …


Outcomes And Long-Term Survival Of Adolescent And Young Adult Patients Admitted To The Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Centre Experience Of 152 Patients, Othman M. Solaiman, Tusneem Elhassan, Riad El Fakih, Abdul Mannan, Zainab Alduhailib, Ashwaq A. Mahdali, Hazzaa Alzahrani, Mouhamad Jamil, Naeem Chaudhri, Alyaa Elhazmi, Mohammad Kolko, Fahad Z. Al-Sharif, Abdullah Alrbiaan, Mohammed Shaban, Marwan Shaheen, Nawal Salahuddin, Feras A. Alfraih, Ashraf S. Altarifi, Mona Hassanein, Sulaiman Hosaini, Noura Alhashim, Alaa Abdelhafiz Mohamed, Amr Hanbali, Ali Hussein Aljanoubi, Nadia R. Al-Obaidi, Walid Rasheed, Khalid Maghrabi, Fahad Almohareb, Ayman Soubani, Mahmoud Aljurf, Syed Osman Ahmed Mar 2024

Outcomes And Long-Term Survival Of Adolescent And Young Adult Patients Admitted To The Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Centre Experience Of 152 Patients, Othman M. Solaiman, Tusneem Elhassan, Riad El Fakih, Abdul Mannan, Zainab Alduhailib, Ashwaq A. Mahdali, Hazzaa Alzahrani, Mouhamad Jamil, Naeem Chaudhri, Alyaa Elhazmi, Mohammad Kolko, Fahad Z. Al-Sharif, Abdullah Alrbiaan, Mohammed Shaban, Marwan Shaheen, Nawal Salahuddin, Feras A. Alfraih, Ashraf S. Altarifi, Mona Hassanein, Sulaiman Hosaini, Noura Alhashim, Alaa Abdelhafiz Mohamed, Amr Hanbali, Ali Hussein Aljanoubi, Nadia R. Al-Obaidi, Walid Rasheed, Khalid Maghrabi, Fahad Almohareb, Ayman Soubani, Mahmoud Aljurf, Syed Osman Ahmed

Hematology/Oncology and Stem Cell Therapy

Objective: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. Design: Retrospective review Setting: Tertiary care Centre, during the period of 2003-2013 Patients: AYA patients who underwent allo-HSCT and required ICU admission. Interventions: This was a non-interventional study. Only outcomes after first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. Measurements and Main Results: Overall, 152 patients were included (males, 60.5%); median …


Use Of Endpoints In Phase Iii Randomized Controlled Trials For Hematopoietic Stem Cell Transplantation Over The Last 15 Years: A Systematic Review, Moazzam Shahzad, Muhammad Fareed Khalid, Muhammad Kashif Amin, Mohammad Ammad-Ud-Din, Usman Ilyas, Ali H. Mushtaq, Atif Butt, Iqra Anwar, Sibgha Gull Chaudhary, Nausheen Ahmed, Leyla Shune, Anurag K. Singh, Sunil H. Abhyankar, Joseph P. Mcguirk, Muhammad Umair Mushtaq Mar 2024

Use Of Endpoints In Phase Iii Randomized Controlled Trials For Hematopoietic Stem Cell Transplantation Over The Last 15 Years: A Systematic Review, Moazzam Shahzad, Muhammad Fareed Khalid, Muhammad Kashif Amin, Mohammad Ammad-Ud-Din, Usman Ilyas, Ali H. Mushtaq, Atif Butt, Iqra Anwar, Sibgha Gull Chaudhary, Nausheen Ahmed, Leyla Shune, Anurag K. Singh, Sunil H. Abhyankar, Joseph P. Mcguirk, Muhammad Umair Mushtaq

Hematology/Oncology and Stem Cell Therapy

This systematic review aimed at evaluating the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and their trends over time and by study sponsorship status. Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006-2021 that reported 197 primary and 600 secondary endpoints were included for the analysis. Overall survival (OS, 17%), progression-free survival (PFS, 15%), graft-versus-host disease (GVHD, 8%), event-free survival (EFS, 8%), and organ function (8%) were the most common primary endpoints. GVHD (12.3%, n=74), safety/toxicity/adverse …


Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal B. B. Hafeez Mar 2024

Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal B. B. Hafeez

Research Symposium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and is expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. Existing therapeutic regimens against PanCa are not that effective and show unacceptable toxicities. Therefore, developing highly effective new agents with less toxicity is urgently required, which could be used as a monotherapy or as an adjuvant to treat PanCa patients. Honey is known for its tremendous health benefits …


A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard Mar 2024

A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. …


Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications. A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer., Chowdhury Arif Jahangir, David B. Page, Glenn Broeckx, Claudia A. Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S. Reis-Filho, Amy Ly, Paul Harms, Shahin Sayed Mar 2024

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications. A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer., Chowdhury Arif Jahangir, David B. Page, Glenn Broeckx, Claudia A. Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S. Reis-Filho, Amy Ly, Paul Harms, Shahin Sayed

Pathology, East Africa

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour …


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 Feb 2024

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 …


Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir Feb 2024

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …


The Transmission Of Oropharyngeal Squamous Cell Carcinoma, Kunjal Patel, Aleesha Thomas Feb 2024

The Transmission Of Oropharyngeal Squamous Cell Carcinoma, Kunjal Patel, Aleesha Thomas

Mako: NSU Undergraduate Student Journal

The existence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has recently been found to have correlations with the Human Papillomavirus. HPV-associated OPSCC exhibits a unique method of infection and transmission and has made this branch an emerging disease in the recent decade. This systematic review of the literature was conducted to further explore research into Oropharyngeal Squamous Cell Cancer (OPSCC). Commonly referred to as “throat cancer”, this growth originates in the oropharynx. Symptoms of this condition include sore throat, lumps in the neck, and difficulty with swallowing. OPSCC has many variants but has shown a strong association with Human Papillomavirus (HPV), …


Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad Feb 2024

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …


Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam Jan 2024

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …


Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando Jan 2024

Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando

Community & Environmental Health Faculty Publications

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, …


Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang Jan 2024

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …


Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal Jan 2024

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …


27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland Dec 2023

27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …


Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka Dec 2023

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE2/EP2 feedforward loop, …


Predicting Stage Progression In Binet Stage A Chronic Lymphocytic Leukemia, Salem H. Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M. Isaac, Andy Kaempf Dec 2023

Predicting Stage Progression In Binet Stage A Chronic Lymphocytic Leukemia, Salem H. Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M. Isaac, Andy Kaempf

Hematology/Oncology and Stem Cell Therapy

Introduction: the variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. Methods: this study involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E). We evaluated the applicability of these prognostic indices in our young, Middle Eastern cohort (median age 59 at diagnosis). Results: during a study period …


Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto Dec 2023

Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto

Kimmel Cancer Center Faculty Papers

Raf-1, a multifunctional kinase, regulates various cellular processes, including cell proliferation, apoptosis, and migration, by phosphorylating MAPK/ERK kinase and interacting with specific kinases. Cellular Raf-1 activity is intricately regulated through pathways involving the binding of regulatory proteins, direct phosphorylation, and the ubiquitin-proteasome axis. In this study, we demonstrate that PHI-1, an endogenous inhibitor of protein phosphatase-1 (PP1), plays a pivotal role in modulating Raf-1 proteostasis within cells. Knocking down endogenous PHI-1 in HEK293 cells using siRNA resulted in increased cell proliferation and reduced apoptosis. This heightened cell proliferation was accompanied by a 15-fold increase in ERK1/2 phosphorylation. Importantly, the observed …


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 Oct 2023

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 …


Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu Oct 2023

Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu

Research Colloquium

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …


Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser Oct 2023

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …


Tc-Ptp Overexpression Attenuates Skin Cancer Formation During Environmental Skin Carcinogenesis, Zahidur Rahmann, Carson Bogatto, Serena Olivarez, Dae Joon Kim Sep 2023

Tc-Ptp Overexpression Attenuates Skin Cancer Formation During Environmental Skin Carcinogenesis, Zahidur Rahmann, Carson Bogatto, Serena Olivarez, Dae Joon Kim

Research Symposium

Background: T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis.

Methods: we generated a novel epidermal specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling.

Results: We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5 or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in …


Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel Sep 2023

Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel

Research Symposium

Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.

Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.

Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …


Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Sheema Khan, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan Sep 2023

Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Sheema Khan, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan

Research Symposium

Pancreatic cancer (PanCa) is a third leading cause of cancer related deaths in US. Unlike other cancers, PanCa is highly resistant to TNF-related apoptosis-inducing ligand (TRAIL) that emerges as one of the most-promising therapy in clinical trials. Our group has previously identified microRNA-145 (miR-145) is downregulated in PanCa, the restoration of which inhibits tumor growth and enhances gemcitabine sensitivity. In this study, we have observed that miR-145 restoration in PanCa cells renders them sensitive to TRAIL treatment. Therefore, we have engineered unique superparamagnetic nanoparticles (SPs) for co-delivering miR-145 and TRAIL in PanCa for improving their therapeutic response to TRAIL. The …


International Conference On Cancer Health Disparities, Juhi Rais, Asif Jafri, Neelam Shivnath, Habiba Khan, Md Arshad Sep 2023

International Conference On Cancer Health Disparities, Juhi Rais, Asif Jafri, Neelam Shivnath, Habiba Khan, Md Arshad

Research Symposium

Background: Biochanin A, an isoflavone that is mainly present in red clover, has potent chemopreventive properties against many cancers. Ovarian carcinoma is fifth most common and deadliest gynaecological malignancy that causes the highest mortality in females worldwide. Hence a substantial need for new therapies for combating this gynaecological malignancy arises.

Methods: The present study aimed to investigate anti-cancerous potentials of biochanin A on cultured human ovarian carcinoma PA-1 cells through the cell viability assay, cellular apoptosis, disruption of mitochondrial membrane potential (MMP), involvement of ROS, cell cycle kinetics, and expression of apoptosis-related genes namely, p53, Bax, Bcl-2, Noxa and Puma. …


Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla Sep 2023

Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla

Research Symposium

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with …