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Full-Text Articles in Medical Molecular Biology

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari Jul 2023

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …


A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser Jul 2022

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …


Therapeutic Approaches To Alter Mineral Formation And Growth In Vascular Calcification, Amirala Bakhshiannik Feb 2022

Therapeutic Approaches To Alter Mineral Formation And Growth In Vascular Calcification, Amirala Bakhshiannik

FIU Electronic Theses and Dissertations

Cardiovascular diseases represent the global leading cause of morbidity and mortality. Cardiovascular calcification is the most significant predictor of cardiovascular events, but no therapeutic options exist to prevent or treat mineral formation in the vasculature. The presence of bone-like mineral increases cardiac work required to move blood through systemic circulation and can lead to mechanical stress in atherosclerotic plaques, promoting plaque rupture events that cause heart attacks. Clinical trials correlated bisphosphonates (BiPs), common anti-osteoporosis pharmaceuticals, with contradicting cardiovascular outcomes. Here, we demonstrated the importance of treatment timing in BiP-induced mineral disruption or promotion. We showed that BiPs can alter morphological …


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast Dec 2019

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …


Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel Sep 2018

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …


Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake May 2018

Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake

Honors Scholar Theses

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …


Sab Concentration Determines The Chemotherapeutic Efficacy In Gynecological Cancer, Iru Paudel Mar 2018

Sab Concentration Determines The Chemotherapeutic Efficacy In Gynecological Cancer, Iru Paudel

FIU Electronic Theses and Dissertations

The American Cancer Society predicts there will be 110,070 new cases and 32,120 deaths due to gynecological malignancies in 2018. A major contributing factor to the high mortality associated with gynecological cancers is the recurrence of treatment-resistant tumors. Ovarian cancer (OC) remains the most lethal gynecological malignancy, yet the mechanisms responsible for regulating tumor resistance and vulnerability are largely unknown or undruggable. Therefore, the goal of this research is to identify mechanisms responsible for therapeutic resistance in gynecological cancers and discover innovative approaches to circumvent these molecular alterations. Our efforts began in OC where secondary analysis of gene expression data …


A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang Feb 2018

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …


Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi May 2017

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …


Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori May 2017

Kinetic Studies Of Dna Repair Enzyme Alkbh2, Michael R. Vittori

Senior Honors Projects

The genomes of living organisms are under constant bombardment from various sources, including chemical modification stemming from processes within the organisms themselves or from exogenous agents, and from radiation. These sources of genomic damage may induce structural changes in the genome’s most basic functional units, the nucleotides that comprise DNA. Damage to an organism’s DNA may result in the production of dysfunctional or nonfunctional proteins. Failure to repair such damage may result in the compounding of successive mutations within the organism’s genome, the pathogenesis of cancer and various genetic disorders in humans. To ensure their viability, organisms have developed unique …


Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang Jul 2012

Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang

Department of Cancer Biology Faculty Papers

Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …


Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr Nov 2009

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.


Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell Jan 2006

Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful selective AR modulators. To this end, we used combinatorial peptide phage display coupled with molecular dynamic structure analysis to identify the surfaces on AR that are exposed specifically in the presence of selected AR ligands. Subsequently, we …


Expression Of G-Protein Inwardly Rectifying Potassium Channels (Girks) In Lung Cancer Cell Lines, Howard Plummer 3rd, Madhu Dhar, Maria Cekanova Ms, Rndr, Phd, Hildegard Schuller Aug 2005

Expression Of G-Protein Inwardly Rectifying Potassium Channels (Girks) In Lung Cancer Cell Lines, Howard Plummer 3rd, Madhu Dhar, Maria Cekanova Ms, Rndr, Phd, Hildegard Schuller

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

BACKGROUND: Previous data from our laboratory has indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. METHODS: GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay. RESULTS: GIRK1 mRNA was expressed in three of six small …


Expression And Localization Of Estrogen Receptor-Alpha Protein In Normal And Abnormal Term Placentae And Stimulation Of Trophoblast Differentiation By Estradiol, A Bukovsky, Maria Cekanova Ms, Rndr, Phd, Mr Caudle, J Wimalasena, Js Foster, Dc Henley, Rf Elder Feb 2003

Expression And Localization Of Estrogen Receptor-Alpha Protein In Normal And Abnormal Term Placentae And Stimulation Of Trophoblast Differentiation By Estradiol, A Bukovsky, Maria Cekanova Ms, Rndr, Phd, Mr Caudle, J Wimalasena, Js Foster, Dc Henley, Rf Elder

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

Estrogens play an important role in the regulation of placental function, and 17-beta-estradiol (E2) production rises eighty fold during human pregnancy. Although term placenta has been found to specifically bind estrogens, cellular localization of estrogen receptor alpha (ER-alpha) in trophoblast remains unclear. We used western blot analysis and immunohistochemistry with h-151 and ID5 monoclonal antibodies to determine the expression and cellular localization of ER-alpha protein in human placentae and cultured trophoblast cells. Western blot analysis revealed a ~65 kDa ER-alpha band in MCF-7 breast carcinoma cells (positive control). A similar band was detected in five normal term placentae exhibiting strong …


Placental Expression Of Estrogen Receptor Beta And Its Hormone Binding Variant – Comparison With Estrogen Receptor Alpha And A Role For Estrogen Receptors In Asymmetric Division And Differentiation Of Estrogen-Dependent Cells, Antonin Bukovsky, Michael R. Caudle, Maria Cekanova Ms, Rndr, Phd, Romaine I. Fernando, Jay Wimalasena, James S. Foster, Donald C. Henley, Robert F. Elder Jan 2003

Placental Expression Of Estrogen Receptor Beta And Its Hormone Binding Variant – Comparison With Estrogen Receptor Alpha And A Role For Estrogen Receptors In Asymmetric Division And Differentiation Of Estrogen-Dependent Cells, Antonin Bukovsky, Michael R. Caudle, Maria Cekanova Ms, Rndr, Phd, Romaine I. Fernando, Jay Wimalasena, James S. Foster, Donald C. Henley, Robert F. Elder

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

During human pregnancy, the production of 17-beta-estradiol (E2) rises steadily to eighty fold at term, and placenta has been found to specifically bind estrogens. We have recently demonstrated the expression of estrogen receptor alpha (ER-alpha) protein in human placenta and its localization in villous cytotrophoblast (CT), vascular pericytes, and amniotic fibroblasts. In vitro, E2 stimulated development of large syncytiotrophoblast (ST) aggregates. In the present study we utilized ER-beta affinity purified polyclonal (N19:sc6820) and ER-alpha monoclonal (clone h-151) antibodies. Western blot analysis revealed a single ~52 kDa ER-beta band in chorionic villi (CV) protein extracts. In CV, strong cytoplasmic ER-beta immunoreactivity …


Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova Ms, Rndr, Phd, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder Jan 2002

Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova Ms, Rndr, Phd, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.