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Cell and Developmental Biology

2023

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Articles 31 - 60 of 233

Full-Text Articles in Medicine and Health Sciences

Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan Sep 2023

Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan

Research Symposium

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 cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but …


Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, 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, 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 …


Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul Sep 2023

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …


Tmem27 Suppresses Tumor Development By Promoting Ret Ubiquitination, Positioning, And Degradation, Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, Matthew Rotondi, Gabriela Huelgas-Morales, Purushoth Ethiraj, Zhijun Qiu, Jonathan Lefkowitz, Wan Song, Bethany N Landry, Hector Lopez, Cynthia M Estrada-Zuniga, Shivi Goyal, Mohammad Aasif Khan, Timothy J Walker, Exing Wang, Faqian Li, Yanli Ding, Lois M Mulligan, Ricardo C T Aguiar, Patricia L M Dahia Sep 2023

Tmem27 Suppresses Tumor Development By Promoting Ret Ubiquitination, Positioning, And Degradation, Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, Matthew Rotondi, Gabriela Huelgas-Morales, Purushoth Ethiraj, Zhijun Qiu, Jonathan Lefkowitz, Wan Song, Bethany N Landry, Hector Lopez, Cynthia M Estrada-Zuniga, Shivi Goyal, Mohammad Aasif Khan, Timothy J Walker, Exing Wang, Faqian Li, Yanli Ding, Lois M Mulligan, Ricardo C T Aguiar, Patricia L M Dahia

Journal Articles

The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell …


Cell-Based Screening Of Antistress Activity Of Some Phytochemicals: Identification, Validation, And Relevance To Old-Age Related Pathologies, Huayue Zhang, Sunil Kaul, Renu Wadhwa Sep 2023

Cell-Based Screening Of Antistress Activity Of Some Phytochemicals: Identification, Validation, And Relevance To Old-Age Related Pathologies, Huayue Zhang, Sunil Kaul, Renu Wadhwa

Research Symposium

Background: A variety of environmental stresses have been shown to contribute to poor quality of life, tissue dysfunctions and ailments including metabolic disorders, cognitive impairment, and accelerated aging. Oxidative stress (an imbalance between the production and processing of highly reactive oxygen species) is largely associated with these phenotypes. Whereas drug development and disease therapeutics have advanced remarkably in last three decades, there are still limited options for stress management. Since the later can effectively decrease the disease burden, we aimed to screen phytochemicals with anti-oxidative stress activity using cell-based assays.

Methods: Brain-derived cells were subjected to chemical models of oxidative …


Transgenic Mice Expressing Functional Tcrs Specific To Cardiac Myhc-Α 334–352 On Both Cd4 And Cd8 T Cells Are Resistant To The Development Of Myocarditis On C57bl/6 Genetic Background, Meghna Sur, Mahima T. Rasquinha, Rajkumar Arumugam, Chandirasegaran Massilamany, Arunkumar Gangaplara, Kiruthiga Mone, Ninaad Lasrado, Bharathi Yalaka, Aakash Doiphode, Channabasavaiah Gurumurthy, David J. Steffen, Jay Reddy Sep 2023

Transgenic Mice Expressing Functional Tcrs Specific To Cardiac Myhc-Α 334–352 On Both Cd4 And Cd8 T Cells Are Resistant To The Development Of Myocarditis On C57bl/6 Genetic Background, Meghna Sur, Mahima T. Rasquinha, Rajkumar Arumugam, Chandirasegaran Massilamany, Arunkumar Gangaplara, Kiruthiga Mone, Ninaad Lasrado, Bharathi Yalaka, Aakash Doiphode, Channabasavaiah Gurumurthy, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis is a predominant cause of congestive heart failure and sudden death in children and young adolescents that can lead to dilated cardiomyopathy. Lymphocytic myocarditis mediated by T cells can result from the recognition of cardiac antigens that may involve CD4 or CD8 T cells or both. In this report, we describe the generation of T cell receptor (TCR) transgenic mice on a C57BL/6 genetic background specific to cardiac myosin heavy chain (Myhc)-α 334–352 and make the following observations: First, we verified that Myhc-α 334–352 was immunogenic in wild-type C57BL/6 mice and induced antigen-specific CD4 T cell responses despite being …


A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Sep 2023

A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and …


Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko Sep 2023

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).


The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle Sep 2023

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

International Undergraduate Journal of Health Sciences

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


Color Stability, Physical Properties And Antifungal Effects Of Zro2 Additions To Experimental Maxillofacial Silicones: Comparisons With Tio2, Mazen Alkahtany, Mark W. Beatty, Fahd Alsalleeh, Thomas M. Petro, Bobby Simetich, You Zhou, Dennis Feely, Grigoris Polyzois Sep 2023

Color Stability, Physical Properties And Antifungal Effects Of Zro2 Additions To Experimental Maxillofacial Silicones: Comparisons With Tio2, Mazen Alkahtany, Mark W. Beatty, Fahd Alsalleeh, Thomas M. Petro, Bobby Simetich, You Zhou, Dennis Feely, Grigoris Polyzois

School of Veterinary and Biomedical Sciences: Faculty Publications

(1) Background: Color changes, physical degradation, and fungal infections are challenges to the longevity of maxillofacial polydimethylsiloxane (PDMS) elastomers. This study aimed to evaluate color changes, physical properties, and antifungal properties of PDMS loaded with ZrO2 and TiO2 submicron- and nano-sized particles. (2) Methods: A 1% weight of 40 nm or 200 nm diameter ZrO2 or TiO2 nanoparticles was mixed into PDMS with 2% functional intrinsic yellow pigment and polymerized. Control materials contained 13% weight 200 nm silica. Samples were exposed to 3000 h of UVB radiation (200 μW/cm2) or darkness. Color parameters L*a*b* …


Age-Related Morphofunctional Changes In Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells, Felipe Augusto Rós, Péricles Natan Mendes Da Costa, Jonathan Milhomens, Débora Glenda Lima De La-Roque, Fernanda Ursoli Ferreira, Juliana De Matos Maçonetto, Camila Cristina De Oliveira Menezes Bonaldo, Julianne Vargas De Carvalho, Patrícia Vianna Bonini Palmaa Palma, Wassim El Nemer, Dimas Tadeu Covas, Simone Kashima Sep 2023

Age-Related Morphofunctional Changes In Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells, Felipe Augusto Rós, Péricles Natan Mendes Da Costa, Jonathan Milhomens, Débora Glenda Lima De La-Roque, Fernanda Ursoli Ferreira, Juliana De Matos Maçonetto, Camila Cristina De Oliveira Menezes Bonaldo, Julianne Vargas De Carvalho, Patrícia Vianna Bonini Palmaa Palma, Wassim El Nemer, Dimas Tadeu Covas, Simone Kashima

Hematology/Oncology and Stem Cell Therapy

Bone marrow mesenchymal stromal cells (BM-MSC) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSC). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSC and their relationship with age using sickle cell mice (Townes-SS). BM-MSC were isolated from Townes-SS, and control groups Townes-AA and C57BL/6J at 30- and 60-day-old. The BM-MSCs showed no morphological differences in culture and demonstrated the murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45- and CD117-). Subsequently, …


Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung Aug 2023

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …


A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy Aug 2023

A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy

Electronic Theses and Dissertations

Breast cancer is the second most occurring cancer type and is ranked fifth in terms of mortality. X-ray mammography is the most common methodology of breast imaging and can show radiographic signs of cancer, such as masses and calcifcations. From these mammograms, radiologists can also assess breast density, which is a known cancer risk factor. However, since not all dense tissue is cancer-prone, we hypothesize that dense tissue can be segregated into healthy vs. risky subtypes. We propose that risky dense tissue is associated with tissue microenvironment disorganization, which can be quantified via a computational characterization of the whole breast …


Muscle Defects Lead To Skeletal Deformities In A Zebrafish Model Of Distal Arthrogryposis, Emily A. Tomak Aug 2023

Muscle Defects Lead To Skeletal Deformities In A Zebrafish Model Of Distal Arthrogryposis, Emily A. Tomak

Electronic Theses and Dissertations

Distal Arthrogryposis Type 1 (DA1) involves mild muscle weakness and limb skeletal abnormalities thought to be caused by paralysis in utero. Why the limbs are particularly affected in DA1 and the degree of paralysis that leads to these skeletal deformities in utero remains unclear. Several muscle genes are known to cause DA1, including MYLPF (myosin light chain phosphorylatable), which encodes a myosin light chain protein that binds close to the force-generating head of myosin heavy chains. The zebrafish mylpfa-/- mutant displays a phenotype consistent with DA1, including impaired myosin activity, reduced muscle force overall, and complete fin paralysis. I …


Profiling And Verifying The Substrates Of E3 Ubiquitin Ligase Rsp5 In Yeast Cells, Shuai Fang, Geng Chen, Yiyang Wang, Rakhee Ganti, Tatiana A Chernova, Li Zhou, Savannah E Jacobs, Duc Duong, Hiroaki Kiyokawa, Yury O Chernoff, Ming Li, Natalia Shcherbik, Bo Zhao, Jun Yin Aug 2023

Profiling And Verifying The Substrates Of E3 Ubiquitin Ligase Rsp5 In Yeast Cells, Shuai Fang, Geng Chen, Yiyang Wang, Rakhee Ganti, Tatiana A Chernova, Li Zhou, Savannah E Jacobs, Duc Duong, Hiroaki Kiyokawa, Yury O Chernoff, Ming Li, Natalia Shcherbik, Bo Zhao, Jun Yin

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Yeast is an essential model organism for studying protein ubiquitination pathways; however, identifying the direct substrates of E3 in the cell presents a challenge. Here, we present a protocol for using the orthogonal ubiquitin transfer (OUT) cascade to profile the substrate specificity of yeast E3 Rsp5. We describe steps for OUT profiling, proteomics analysis, in vitro and in cell ubiquitination, and stability assay. The protocol can be adapted for identifying and verifying the ubiquitination targets of other E3s in yeast. For complete details on the use and execution of this protocol, please refer to Wang et al.


To Compare The Safety And Efficacy Of Intraluminal Brachytherapy Vs Isolated Percutaneous Transhepatic Biliary Drainage For Unresectable Malignant Biliary Obstruction - A Prospective Observational Study, Shikha Sood, John V Alexander, Manish Gupta, Ashish Chauhan Aug 2023

To Compare The Safety And Efficacy Of Intraluminal Brachytherapy Vs Isolated Percutaneous Transhepatic Biliary Drainage For Unresectable Malignant Biliary Obstruction - A Prospective Observational Study, Shikha Sood, John V Alexander, Manish Gupta, Ashish Chauhan

Hematology/Oncology and Stem Cell Therapy

BACKGROUND: Intraluminal therapies like brachytherapy can locally destroy the obstructing tumour and thus increase the duration of catheter/stent patency in patients with unresectable malignant biliary obstruction (MBO). OBJECTIVES: Evaluate the safety and efficacy of percutaneous transhepatic biliary drainage (PTBD) followed by HDR Intraluminal Brachytherapy (ILBT) in the palliative treatment of malignant biliary obstruction. DESIGN: Prospective observational study SETTING: An academic tertiary care hospital in Himachal Pradesh PATIENT AND METHODS: All consenting consecutive patients of MBO from January 2021 to March 2022, who were unfit for alternate treatment modalities were enrolled in our study and underwent percutaneous transhepatic biliary drainage (PTBD) …


Assessing The Efficacy Of Mitoxantrone And Doxorubicin As Frontline Anthracyclines During Induction Therapy Of Newly Diagnosed Acute Promyelocytic Leukemia, José Carlos Jaime-Pérez, Eugenia M. Ramos-Dávila, Jesús D. Meléndez-Flores, Mariana González-Treviño, David Gómez-Almaguer Aug 2023

Assessing The Efficacy Of Mitoxantrone And Doxorubicin As Frontline Anthracyclines During Induction Therapy Of Newly Diagnosed Acute Promyelocytic Leukemia, José Carlos Jaime-Pérez, Eugenia M. Ramos-Dávila, Jesús D. Meléndez-Flores, Mariana González-Treviño, David Gómez-Almaguer

Hematology/Oncology and Stem Cell Therapy

Background: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today’s most curable form of leukemia. However, recommended agents such as arsenic trioxide, idarubicin or daunorubicin are not easily available in low-middle-income countries, in which outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines. Materials: We conducted a retrospective cohort including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25mg/m2) with mitoxantrone or doxorubicin as induction to remission therapy. Groups were compared using the χ2 and Student’s T-tests. Kaplan–Meier analysis was used for survival …


Role Of Anti-Cd38 Monoclonal Antibodies In The Treatment Of Adult Immune Hematological Diseases., Erin Huilin Yang, Ibrahim N. Muhsen, Hadeel Samarkandi, Riad El Fakih, Mahmoud Aljurf, Amr Hanbali Aug 2023

Role Of Anti-Cd38 Monoclonal Antibodies In The Treatment Of Adult Immune Hematological Diseases., Erin Huilin Yang, Ibrahim N. Muhsen, Hadeel Samarkandi, Riad El Fakih, Mahmoud Aljurf, Amr Hanbali

Hematology/Oncology and Stem Cell Therapy

Daratumumab is a first-in-class human anti-CD38 IgG1 monoclonal antibody approved for the treatment of newly diagnosed as well as relapsed refractory multiple myeloma. Preclinical data supported dararumumab ability in depleting autoantibodies producing-plasma cells, B-cells as well as NK cells. Those reports showed promising results on the use of daratumumab in autoimmune disorders refractory to multiple lines of therapies, which encouraged the use of daratumumab in various autoimmune conditions that are refractory to standard therapies. The aim of this review is to summarize the literature reporting experience using anti-CD38 antibodies in hematological autoimmune diseases, focusing on the most common autoimmune hematological …


Invasive Pulmonary Aspergillosis In Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based On The United States National Readmission Database, Amir Khalil, Paramveer Singh, Tanveer Mir, Mohammed Uddin, Ayman O. Soubani Aug 2023

Invasive Pulmonary Aspergillosis In Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based On The United States National Readmission Database, Amir Khalil, Paramveer Singh, Tanveer Mir, Mohammed Uddin, Ayman O. Soubani

Hematology/Oncology and Stem Cell Therapy

Background and Objective: Hematopoietic Stem Cell Transplant (HSCT) is well established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. Our primary objective was to assess whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among patients undergoing HSCT. A secondary objective was to examine potential differences in complications between HSCT with IPA and HSCT without IPA. Materials and Methods: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and …


A Single Centre, Real-World Experience Of Chronic Gvhd Treatment Using Ibrutinib, Imatinib And Ruxolitinib And Its Treatment Outcomes, Swe Mar Linn, Igor Novitzky-Basso, Omar Abduljalil, Ivan Pasic, Wilson Lam, Arjun Law, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Dennis Dong Hwan Kim Aug 2023

A Single Centre, Real-World Experience Of Chronic Gvhd Treatment Using Ibrutinib, Imatinib And Ruxolitinib And Its Treatment Outcomes, Swe Mar Linn, Igor Novitzky-Basso, Omar Abduljalil, Ivan Pasic, Wilson Lam, Arjun Law, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Dennis Dong Hwan Kim

Hematology/Oncology and Stem Cell Therapy

Background: Chronic graft-versus-host-disease (cGVHD) is a common cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT). Tyrosine kinase inhibitors (TKIs), including Ruxolitinib, Imatinib and Ibrutinib, have shown promising efficacy in cGVHD treatment. Method: A total of 43 patients who developed cGVHD and received at least one line of TKI therapy for cGVHD treatment were evaluated retrospectively. Overall response, clinical benefit (CB), corticosteroid dose reduction, failure-free (FFS) and overall survival (OS) were assessed. Result: A total 62 lines of TKI therapy were evaluated, including Ruxolitinib (n=18), Ibrutinib (n=13), and Imatinib (n=31). With a median follow-up duration of 12 …


Is Mixed Chimerism Post Allogeneic Hematopoietic Stem Cell Transplantation In Pediatric Acute Lymphoid Leukemia A Prognostic Factor For Relapse ?, Saadiya Khan, Zainab Alsaif, Khawar Siddiqui, Hawazen Alsaedi, Ali Al-Ahmari, Abdullah Al-Jefri, Ibrahim Ghemlas, Awatif Alanazi, Mouhab Ayas Aug 2023

Is Mixed Chimerism Post Allogeneic Hematopoietic Stem Cell Transplantation In Pediatric Acute Lymphoid Leukemia A Prognostic Factor For Relapse ?, Saadiya Khan, Zainab Alsaif, Khawar Siddiqui, Hawazen Alsaedi, Ali Al-Ahmari, Abdullah Al-Jefri, Ibrahim Ghemlas, Awatif Alanazi, Mouhab Ayas

Hematology/Oncology and Stem Cell Therapy

Hematopoietic Stem Cell Transplantation (HSCT) has been considered curative for children with high-risk acute leukemia (ALL) offering better survival. Short tandem repeat (STR) has been used as a marker of chimerism status after HSCT. The appearance of recipient cells >1% post allogenic stem cell transplant was defined as mixed chimerism (MC). Chimeric studies post HSCT are dynamic. The aim of this study was to study the significance of recipients cells in post-HSCT pediatric ALL patients as a predictor of relapse of their primary disease. Rate of MC was 51.4% (19 out of 37 recipients). It was 48.6% (n=18) during Day+100 …


Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke Aug 2023

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …


A Comparison Of Pm-Nato3’S Influence On Neural Progenitors And Mature Dopamine Neurons, Mary E. West Aug 2023

A Comparison Of Pm-Nato3’S Influence On Neural Progenitors And Mature Dopamine Neurons, Mary E. West

Masters Theses

This thesis presents significant findings regarding the role of PM-Nato3 in its interaction with developing neurons in the context of Parkinson's disease (PD) and regenerative medicine. We investigated the effects of PM-Nato3 on dopamine (DA) neurogenesis under different culture conditions, both in vitro and in vivo. In the standard dopaminergic culture condition, PM-Nato3 potentially increased the speed of DA neuron production but did not significantly increase the yield of DA neurons. In a minimal culture condition, there was no notable difference between the control and PM-Nato3 conditions, suggesting minimal impact on DA neurogenesis. In vivo studies using a mouse model …


Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren Aug 2023

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …


Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser Aug 2023

Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Biphasic, non-sigmoidal dose-response relationships are frequently observed in biochemistry and pharmacology, but they are not always analyzed with appropriate statistical methods. Here, we examine curve fitting methods for “hormetic” dose-response relationships where low and high doses of an effector produce opposite responses. We provide the full dataset used for modeling, and we provide the code for analyzing the dataset in SAS using two established mathematical models of hormesis, the Brain-Cousens model and the Cedergreen model. We show how to obtain and interpret curve parameters such as the ED50 that arise from modeling, and we discuss how curve parameters might change …


Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino Aug 2023

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …


Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni Aug 2023

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations & Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …


Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry Jul 2023

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …


Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman Jul 2023

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …


Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura Jul 2023

Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura

School of Veterinary and Biomedical Sciences: Faculty Publications

Sensitization to self-peptides induces various immunological responses, from autoimmunity to tumor immunity, depending on the peptide sequence; however, the underlying mechanisms remain unclear, and thus, curative therapeutic options considering immunity balance are limited. Herein, two overlapping dominant peptides of myelin proteolipid protein, PLP136-150 and PLP139-151, which induce different forms of experimental autoimmune encephalomyelitis (EAE), monophasic and relapsing EAE, respectively, were investigated. Mice with monophasic EAE exhibited highly resistant to EAE re-induction with any encephalitogenic peptides, whereas mice with relapsing EAE were susceptible, and progressed, to EAE re-induction. This resistance to relapse and reinduction in monophasic EAE mice was associated with …