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Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal 2021 Old Dominion University

Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal

College of Sciences Posters

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. We have shown that this 38 kDa full-length Par-4 (Fl-Par-4) protein is predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate a 24 kDa functionally active cleaved Par-4 (cl-Par-4) fragment. The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells. Our laboratory is interested in how the disorder-order balance within Fl-Par-4 and cl-Par-4 may be related to the balance between cell survival and cell death. Currently, we are using biophysical techniques such as circular dichroism ...


A Mathematical Model Of Pancreatic Cancer Growth And Response To Treatment, Allison Cruikshank 2021 University of Nebraska - Lincoln

A Mathematical Model Of Pancreatic Cancer Growth And Response To Treatment, Allison Cruikshank

Honors Theses, University of Nebraska-Lincoln

Pancreatic cancer is one of the leading causes of death due to cancer in the United States. Analyzing the effects of radiation is extremely valuable in determining when a patient is allowed surgical resection, which is, presently, the only potentially curative treatment for pancreatic cancer. This study examines pancreatic tumor growth and shrinkage to predict tumor response and change of resectability for pancreatic cancer patients undergoing radiation therapy. This is done using ordinary differential equations as a mathematical model. Mathematical models have increasingly been applied to various biological systems/processes to analyze the principles involved. In our project, a population ...


A Qualitative Review On Mammography Interventions Among Asian American Women, Sayeda Tazim Zaidi, Raisa Kabir, Chia-Liang Dai 2021 University of Nevada, Las Vegas

A Qualitative Review On Mammography Interventions Among Asian American Women, Sayeda Tazim Zaidi, Raisa Kabir, Chia-Liang Dai

Undergraduate Research Symposium Posters

Breast cancer (BC) is a leading type of malignancy and the second most common cause of cancer-related death among women around the world. The occurrence of BC has been increasing in Asian American (AA) women. Early detection through mammography is an effective means to reduce mortality associated with BC. However, there is a paucity of data and interventions regarding mammography promotion interventions among AA women. The purpose of this study was to evaluate current interventions for promoting mammography among AA women and suggest recommendations for designing successful interventions. A review for peer-reviewed journal articles in PubMed Central, MEDLINE, CINAHL, ERIC ...


Identifying Determinants Of Breast Cancer Screening Through Mammography Among Asian American Women, Sayeda Tazim Zaidi, Raisa Kabir, Chia-Liang Dai 2021 University of Nevada, Las Vegas

Identifying Determinants Of Breast Cancer Screening Through Mammography Among Asian American Women, Sayeda Tazim Zaidi, Raisa Kabir, Chia-Liang Dai

Undergraduate Research Symposium Posters

Breast cancer is the most common malignancy affecting women around the world. In the US, approximately 1 in 8 women will develop breast cancer over the course of their lifetime. There is a growing incidence of breast cancer among Asian American (AA) women. Breast cancer screening by mammography is the most effective early detection method to reduce mortality but AA women have the lowest utilization rates. This study aims to identify the determinants affecting mammography among AA women. A literature search in PubMed Central, MEDLINE, and CINAHL was undertaken to include all peer-reviewed studies published within the past 20 years ...


Association Of Dietary Total Antioxidant Capacity With Bone Mass And Osteoporosis Risk In Korean Women: Analysis Of The Korea National Health And Nutrition Examination Survey 2008-2011, Donghyun Kim, Anna Han, Yongsoon Park 2021 Hanyang University

Association Of Dietary Total Antioxidant Capacity With Bone Mass And Osteoporosis Risk In Korean Women: Analysis Of The Korea National Health And Nutrition Examination Survey 2008-2011, Donghyun Kim, Anna Han, Yongsoon Park

Department of Cancer Biology Faculty Papers

Antioxidant intake has been suggested to be associated with a reduced osteoporosis risk, but the effect of dietary total antioxidant capacity (TAC) on bone health and the risk of osteoporosis remains unclear. We aimed to assess the hypothesis that dietary TAC is positively associated with bone mass and negatively related to the risk of osteoporosis in Korean women. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. Dietary TAC was estimated using task automation and an algorithm with 24-h recall data. In total, 8230 pre-and postmenopausal women were divided into four groups according ...


Synthesis Of Novel Temozolomide-Fatty Acid Imide Hybrid Compounds For The Chemotherapeutic Treatment Of Glioblastoma Multiforme, Janice Pakkianathan 2021 Andrews University

Synthesis Of Novel Temozolomide-Fatty Acid Imide Hybrid Compounds For The Chemotherapeutic Treatment Of Glioblastoma Multiforme, Janice Pakkianathan

Honors Scholars & Undergraduate Research Poster Symposium Programs

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that originates from glial cells, which make up the supportive tissue surrounding neurons. Temozolomide (TMZ) is the current chemotherapeutic drug administered to treat GBM as it works to inhibit the growth of the cancer cells. This research study focuses on developing a method for synthesizing novel hybrid compounds that combines TMZ with various fatty acids known to have anticancer properties, forming a series of imide compounds with potential chemotherapeutic effects. Once the novel hybrid compounds are successfully synthesized, they will be tested for their anticancer properties on glioblastoma cells.


Modulation Of Apoptosis In Breast Cancer Cells Mda-Mb-157, 93a And 93b By Aqueous Extract Of Chinese Medical Herb Scutel, Nathaly Manrique 2021 Andrews University

Modulation Of Apoptosis In Breast Cancer Cells Mda-Mb-157, 93a And 93b By Aqueous Extract Of Chinese Medical Herb Scutel, Nathaly Manrique

Honors Scholars & Undergraduate Research Poster Symposium Programs

Scutellaria barbata (SB), a Chinese medical herb, has been known to contain anti-cancer properties. In this study, the effectiveness of SB in apoptotic modulation of APC-mutant breast cancer cell lines MDA-MB-157, 93A, and 93B were investigated. Assessments were performed using the green/red/blue fluorescent Apoptosis/Necrosis Detection Kit and the Human Apoptosis Antibody Array -Membrane (43 Targets) test by
the Abcam cooperation. Our data demonstrated that 1-hour and 3-hour incubation treatments with aqueous extract of SB induced apoptosis in all cell lines. Additionally, modulation of pro-apoptotic markers (Bad,
Bax, BID, BIM, C3, C8, p53, p27), and anti-apoptotic markers (BcL-2 ...


Tea Polyphenol Epigallocatechin-3-Gallate Inhibits Cell Proliferation In A Patient-Derived Triple-Negative Breast Cancer Xenograft Mouse Model Via Inhibition Of Proline-Dehydrogenase-Induced Effects, Wen-Jui Lee, Tzu-Chun Cheng, Yun Yen, Chia-Lang Fang, You-Cheng Liao, Ching-Chuan Kuo, Shih-Hsin Tu, Li-Cheng Lin, Hui-Wen Chang, Li-Ching Chen, Yuan-Soon Ho 2021 The Ph.D. Program for Neural Regenerative Medicine, TMU

Tea Polyphenol Epigallocatechin-3-Gallate Inhibits Cell Proliferation In A Patient-Derived Triple-Negative Breast Cancer Xenograft Mouse Model Via Inhibition Of Proline-Dehydrogenase-Induced Effects, Wen-Jui Lee, Tzu-Chun Cheng, Yun Yen, Chia-Lang Fang, You-Cheng Liao, Ching-Chuan Kuo, Shih-Hsin Tu, Li-Cheng Lin, Hui-Wen Chang, Li-Ching Chen, Yuan-Soon Ho

Journal of Food and Drug Analysis

Triple-negative breast cancers (TNBCs) lack specific targeted therapy options and have evolved into highly chemo-resistant tumors that metastasize to multiple organs. The present study demonstrated that the proline dehydrogenase (PRODH) mRNA level in paired (tumor vs. normal) human breast tissue samples (n=234) was 6.6-fold greater than normal cells (*p=0.021). We established stable PRODH-overexpressing TNBC (HS578T) cells, and the malignant phenotypes were evaluated using soft agar colony formation and Transwell migration assays. The results demonstrated that PRODH induced epithelial-mesenchymal transition in cancer cells and increased cell proliferation. The present study found that the tea polyphenol epigallocatechin-3-gallate (EGCG ...


The Age-Dependent Characterization Of The Er-Alpha Positive Breast Cancer Tumor Microenvironment, Katie Marie Hamel 2021 Louisiana State University and Agricultural and Mechanical College

The Age-Dependent Characterization Of The Er-Alpha Positive Breast Cancer Tumor Microenvironment, Katie Marie Hamel

LSU Doctoral Dissertations

In disease states such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression and drug resistance. Young individuals diagnosed with estrogen receptor-alpha positive (ER-a+) breast cancer have an observed increase in resistance to endocrine therapies. This suggests that an alternative estrogen signaling pathway is active within these tumors. Despite this, the effects of stromal age on the endocrine response in breast cancer is not well known. Here, we review and highlight the involvement of the stromal age in both tumorigenesis and physiological wound healing. To identify specific differences between young and aged ER-a+ breast tumors, RNA ...


Cancer Immune Evasion Through Loss Of Mhc Class I Antigen Presentation, Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock 2021 University of Massachusetts Medical School

Cancer Immune Evasion Through Loss Of Mhc Class I Antigen Presentation, Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock

Open Access Publications by UMMS Authors

Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers that are expressing mutated proteins. In order for many cancers to arise and progress, they need to evolve mechanisms to avoid elimination by CD8 T cells. MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM ...


Xct-Driven Expression Of Gpx4 Determines Sensitivity Of Breast Cancer Cells To Ferroptosis Inducers, Namgyu Lee, Anne E. Carlisle, Austin Peppers, Sung Jin Park, Mihir B. Doshi, Meghan E. Spears, Dohoon Kim 2021 University of Massachusetts Medical School

Xct-Driven Expression Of Gpx4 Determines Sensitivity Of Breast Cancer Cells To Ferroptosis Inducers, Namgyu Lee, Anne E. Carlisle, Austin Peppers, Sung Jin Park, Mihir B. Doshi, Meghan E. Spears, Dohoon Kim

Open Access Publications by UMMS Authors

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal ...


Yap And Taz Are Transcriptional Co-Activators Of Ap-1 Proteins And Stat3 During Breast Cellular Transformation [Preprint], Lizhi He, Henry E. Pratt, Fengxiang Wei, Mingshi Gao, Zhiping Weng, Kevin Struhl 2021 Harvard Medical School

Yap And Taz Are Transcriptional Co-Activators Of Ap-1 Proteins And Stat3 During Breast Cellular Transformation [Preprint], Lizhi He, Henry E. Pratt, Fengxiang Wei, Mingshi Gao, Zhiping Weng, Kevin Struhl

University of Massachusetts Medical School Faculty Publications

The YAP and TAZ paralogues are transcriptional co-activators recruited to target sites, primarily by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB and STAT3, key factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, co-occupy many target sites in vivo via AP-1 and (to a lesser extent) STAT3 sequence motifs, and stimulate transcriptional activation by AP-1 proteins. A few target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes ...


Down-Regulation Of The Tumor Suppressor Mir-34a Contributes To Head And Neck Cancer By Up-Regulating The Met Oncogene And Modulating Tumor Immune Evasion, Xun Wu, Yi-Shing Lisa Cheng, Mathew Matthen, Angela Yoon, Gary K. Schwartz, Shashi Bala, Alison M. Taylor, Fatemeh Momen-Heravi 2021 Columbia University

Down-Regulation Of The Tumor Suppressor Mir-34a Contributes To Head And Neck Cancer By Up-Regulating The Met Oncogene And Modulating Tumor Immune Evasion, Xun Wu, Yi-Shing Lisa Cheng, Mathew Matthen, Angela Yoon, Gary K. Schwartz, Shashi Bala, Alison M. Taylor, Fatemeh Momen-Heravi

Open Access Publications by UMMS Authors

BACKGROUND: MicroRNAs (miRs) have been shown to play an important role in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). The miR-34 family is thought to play a role in tumor suppression, but the exact mechanism of their action in HNSCC is not well understood. Moreover, the impact of chromosomal changes and mutation status on miR-34a expression remains unknown.

METHODS: Differential expression of miR-34a, MET, and genomic alterations were assessed in the Cancer Genome Atlas (TCGA) datasets as well as in primary HNSCC and adjacent normal tissue. The biological functions of miR-34a in HNSCC were investigated in samples ...


Cohesin Mutations Alter Dna Damage Repair And Chromatin Structure And Create Therapeutic Vulnerabilities In Mds/Aml, Zuzana Tothova, Anne-Laure Valton, Sergey V. Venev, Job Dekker, Benjamin L. Ebert 2021 Dana-Farber Cancer Institute

Cohesin Mutations Alter Dna Damage Repair And Chromatin Structure And Create Therapeutic Vulnerabilities In Mds/Aml, Zuzana Tothova, Anne-Laure Valton, Sergey V. Venev, Job Dekker, Benjamin L. Ebert

Open Access Publications by UMMS Authors

The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells. We demonstrated increased levels of DNA damage and sensitivity of cohesin-mutant cells to poly(ADP-ribose) polymerase (PARP) inhibition. We developed a mouse model of MDS in which Stag2 mutations arose as clonal secondary lesions in the background of clonal hematopoiesis driven ...


Dna Repair Pathways In Cancer Therapy And Resistance, Lan-ya Li, Yi-di Guan, Xi-sha Chen, Jin-ming Yang, Yan Cheng 2021 Central South University, China

Dna Repair Pathways In Cancer Therapy And Resistance, Lan-Ya Li, Yi-Di Guan, Xi-Sha Chen, Jin-Ming Yang, Yan Cheng

Toxicology and Cancer Biology Faculty Publications

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for ...


Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin 2021 Thomas Jefferson University

Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin

Kimmel Cancer Center Faculty Papers

In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose ...


Flick: An Optimized Plate Reader-Based Assay To Infer Cell Death Kinetics, Ryan Richards, Megan E. Honeywell, Michael J. Lee 2021 University of Massachusetts Medical School

Flick: An Optimized Plate Reader-Based Assay To Infer Cell Death Kinetics, Ryan Richards, Megan E. Honeywell, Michael J. Lee

Open Access Publications by UMMS Authors

Evaluating drug sensitivity is improved by directly quantifying death kinetics, rather than correlates of viability, such as metabolic activity. This is challenging, requiring time-lapse microscopy and genetically encoded labels to distinguish live and dead cells. Here, we describe fluorescence-based and lysis-dependent inference of cell death kinetics (FLICK). This method requires only a standard fluorescence plate reader, retaining the high-throughput nature and broad accessibility of common viability assays. However, FLICK specifically quantifies death, including an accurate inference of death kinetics. For complete details on the use and execution of this protocol, please refer to Richards et al. (2020).


Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin 2021 The Graduate Center, City University of New York

Cell Cycle Progression Effects Of Albumin, Sharmeen Uddin

Dissertations, Theses, and Capstone Projects

Progression through G1 phase of the cell cycle is controlled largely by growth factors in early G1 and by nutrients in late G1 indicating sufficient raw material for cell division. We previously mapped a late G1 cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G1 checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G1 into S-phase. Quiescent BJ-hTERT human fibroblasts primed back into G1 with FBS treatment, were treated with a mixture ...


Anti-Cancer Effects By Interleukin 24, Xuelin Zhong 2021 The Graduate Center, City University of New York

Anti-Cancer Effects By Interleukin 24, Xuelin Zhong

Dissertations, Theses, and Capstone Projects

Cancers develop as some cells acquire the ability, either by exogenous stimulation or by spontaneous mutation, to keep growing despite normal restraints. Up-regulating translation of oncogenes involved in cell proliferation and tumor development and down-regulating translation of tumor-suppressors that normally suppress tumor development are two most common mechanisms by which cancers develop. Therefore, it is crucial to study how these proteins get either up-regulated or down-regulated at translational level.

The eukaryotic translation initiation factor, which is composed of subunits such as eIF4A, eIF4G and eIF4E, is one of the key factors that contribute to efficient translation initiation. Interleukin 24 (IL-24 ...


Cyld Mutation Characterizes A Subset Of Hpv-Positive Head And Neck Squamous Cell Carcinomas With Distinctive Genomics And Frequent Cylindroma-Like Histologic Features, Erik A. Williams, Meagan Montesion, Brian M. Alexander, Shakti H. Ramkissoon, Julia A. Elvin, Jeffrey S. Ross, Kevin Jon. Williams, Krzysztof Glomski, Jacob R. Bledsoe, Julie Y. Tse, Mark C. Mochel 2021 Foundation Medicine, Inc.

Cyld Mutation Characterizes A Subset Of Hpv-Positive Head And Neck Squamous Cell Carcinomas With Distinctive Genomics And Frequent Cylindroma-Like Histologic Features, Erik A. Williams, Meagan Montesion, Brian M. Alexander, Shakti H. Ramkissoon, Julia A. Elvin, Jeffrey S. Ross, Kevin Jon. Williams, Krzysztof Glomski, Jacob R. Bledsoe, Julie Y. Tse, Mark C. Mochel

Open Access Publications by UMMS Authors

Mutations in the tumor suppressor CYLD, known to be causative of cylindromas, were recently described in a subset of high-risk (hr) HPV-positive head and neck squamous cell carcinomas (HNSCC). Pathologic and genetic characterization of these CYLD-mutant carcinomas, however, remains limited. Here, we investigated whether CYLD mutations characterize a histopathologically and genomically distinct subset of hrHPV-positive HNSCC. Comprehensive genomic profiling via hybrid capture-based DNA sequencing was performed on 703 consecutive head and neck carcinomas with hrHPV sequences, identifying 148 unique cases (21%) harboring CYLD mutations. Clinical data, pathology reports, and histopathology were reviewed. CYLD mutations included homozygous deletions (n = 61/148 ...


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