Cancer Biology Commons^™

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

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

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

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

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

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 …

Selective Activation Of Thrombin Activatable Fibrinolysis Inhibitor (Tafi) Attenuates Metastatic And Angiogenic Capabilities Of Melanoma And Lung Carcinoma In Vitro, Jacklyn Krizsan

Electronic Thesis and Dissertation Repository

Metastasis and angiogenesis are hallmarks of aggressive cancers, both depending on degradation of extracellular matrix by proteases such as plasmin. Plasmin activation is inhibited by thrombin-activatable fibrinolysis inhibitor (TAFI)-mediated cleavage of terminal lysine residues on plasminogen receptors. Activation of TAFI is most effectively done in complex with thrombomodulin (TM). TM is known to have anti-cancer properties, but it is not known if this is due to TAFI activation or an alternative substrate protein C (PC). We hypothesize that specific promotion of TAFI activation with TM treatment will attenuate metastatic and angiogenic capabilities of tumour cells.

Melanoma and lung carcinoma cells …

Biomarkers In Borrelia Burgdorferi Infected Triple-Negative Breast Cancer Cells, Sambuddha Paul

Master's Theses

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Although some studies have attempted to identify new biomarkers and therapies, only a few have shown promise in clinical trials. In the context of cancer development, infectious agents rank as the third major risk factor, contributing to approximately 15-20% of cancer cases, according to the American Cancer Society. Hence, the identification of biomarkers associated with infection-originated cancer is crucial for enhancing cancer prevention, early detection, diagnosis, and treatment. Borrelia burgdorferi, the causative agent of Lyme disease, has been linked to TNBC …

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 …

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 …

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

Preclinical Evaluation Of Anti-Cd38 Therapy In Mature T-Cell Neoplasms, Colleen Isabelle, William Johnson, Kathleen Mcconnell, Ashley Vogel, Jonathan Brammer, Amy Boles, Robyn Keller, Paola Sindaco, Liam Nisenfeld, Guldeep Uppal, Neda Nikbakht, Bruno Calabretta, Patrizia Porazzi, Jerald Gong, Nitin Chakravarti, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

No abstract provided.

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi-Yang Peng, Rui Wang, Xiang Li, Ning Du, Da-Peng Liu, Jia Zhang, Yun-Feng Zhang, Lei Ma, Ye Sun, Shou-Ching Tang, Hong Ren, Yi-Ping Yang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem.

METHODS: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Regulation Of The Wnt/Wingless Receptor Lrp6/Arrow By The Deubiquitylating Complex Usp46, Zachary T. Spencer

Dartmouth College Ph.D Dissertations

The evolutionarily conserved Wnt/Wingless signal transduction pathway is critical for the proper development of all animals and implicated in numerous diseases in adulthood. Upon binding of the Wnt/Wingless ligand, a cascade of events culminates in inactivation of the destruction complex, a negative regulator of the pathway, and the subsequent formation of singalosomes which mediate pathway activation. A critical component of signalosome formation is the Wnt/Wingless receptor LRP6/Arrow. Upon canonical pathway activation, LRP6/Arrow undergoes activation via phosphorylation by several kinases and complexes with another Wnt/Wingless receptor Frizzled, along with several cytoplasmic components. While many studies have investigated the regulatory mechanisms of …

Cytotoxic Activity Of Salvia Officinalis Extract Mediated By The Inhibition Of Jak2 In Breast Cancer, Salma Alawadi Dawood

Theses and Dissertations

Background: Breast cancer is the most common type of invasive cancer in women in their forties and fifties. Recent evidence suggests that JAK2/STAT3 signaling is constitutively active in breast cancer. Previous studies suggest that plant extracts, including Salvia Officinalis, have strong cytotoxic effects on breast cancer cells. The differential expression of miRNAs is also strongly linked to cancer development.

Aim: In the current study, we hypothesize that S. Officinalis extract suppresses JAK2 expression and has strong anticancer potential in MCF7 breast cancer cell lines.

Methods: GC-MS analysis showed the presence of flavonoids in dried leaf of …

Side Effects After Use Of Bedside Thaw Method In An Umbilical Cord Blood Stem Cells For Allogeneic Transplantation In A Children Cohort: A Single-Center Experience., Natalia Builes, Laura Niño-Serna, Juan Felipe Combariza

Hematology/Oncology and Stem Cell Therapy

Background: Several strategies and procedures have been described for thawing umbilical cord blood (UCB) products. The ideal method for each center depends on the resources, staff training and access to each of them. Method: We retrospectively evaluated the incidence of side effects using the bedside thaw method after unrelated UCB transplantation in 34 children. Patient, donor, graft characteristics and side effects were identified. In addition, we attempt to identify the risk factors that could be associated with side effects. Result: Sixty-eight percent of patients experienced any adverse reaction. All the reactions were mild and transient events. The most frequent side …

Analysis Of Macrophage Migration Inhibitory Factor Genotype In Hemophilia A Patients, Murtadha Ali Hadi, Wijdan Nazar Ibrahim, Meaad Kadhum Hassan

Hematology/Oncology and Stem Cell Therapy

Background Hemophilia A, an X-linked bleeding disorder, is caused by a complete or partial deficiency in Factor VIII. Multiple factors play a role in the development and progression of bleeding episodes, especially arthropathy, in hemophilia patients. Objectives Detection of macrophage migration inhibitory factor (MIF)-173 G/C polymorphism in people with hemophilia A (PWH) and the possible associations between the type of MIF gene polymorphism and selected disease-related variables. Subjects and Methods This case–control study included 95 male patients aged 2 months to 63 years with hemophilia A and 95 nonhemophiliac subjects matched for age and sex. Allele-specific polymerase chain reaction (AS-PCR) …

Oncotypedx Testing Does Not Benefit Patients With Grade 1, Estrogen And Progesterone Receptor Positive Breast Cancers: A Tailorx Validated Study, Udai S. Sibia, W. Charles Mylander, Tasha Martin, Martin Rosman, Thomas J. Sanders, Young Lee, Lorraine Tafra, Rubie S. Jackson

Hematology/Oncology and Stem Cell Therapy

Background & Objectives We previously described a predictive AAMC model that identifies patients (grade 1, hormone positive) who would not benefit from OncotypeDX testing. The purpose of this study was to validate the AAMC model by assessing distant recurrence-free interval (DRFI) and invasive disease-free survival (IDFS) using TAILORx clinical trial data. Materials & Methods We retrospectively analyzed TAILORx trial data and categorized patients based on the AAMC model. AAMC low-risk patients are those with grade 1 and hormone positive tumors. Kaplan-Meier curves examined DRFI and IDFS. Results Of the total 9195 cases, 2246 (24.4%) were identified as AAMC low-risk. Among …

Post Autologous Hematopoietic Cell Transplant Care In The “Home Sweet Home” Setting: A Treatment Paradigm Shift, Mohamed A. Kharfan-Dabaja, Vivek Roy, Hemant Murthy, Deborah Fischer, Razan Mohty, Ashley Greathouse, Alethea Brown, Kathryn Moreno, Emily Godsey, Jennifer M. Higginbotham, Ashley Bartholomew, Alexis Jackson, Ricardo A. Torres-Guzman, Antonio J. Forte, Sikander Ailawadhi, Roxana Dronca, Michael Maniaci

Hematology/Oncology and Stem Cell Therapy

Multiple myeloma (MM) is the second most common hematologic malignancy with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) is a standard treatment for MM even in the era of novel therapies. This is usually done in hospital-based setting, whether in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with vendor-mediated supply chain capable of delivering high-acuity care in the comfort of patient’s own homes. In our program, we leveraged the existing ACH platform to deliver post-HCT care …

Cytogenetically Normal Acute Myeloid Leukaemia At A Single Centre In South Africa, Nicholas Jenkins, Lee-Ann Phillips, Marian Stone, Estelle Verburgh, Jenna Oosthuizen, Karen Shires

Hematology/Oncology and Stem Cell Therapy

Background: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge. The European Leukaemia Net 2017 guidelines attempted to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. Objectives: This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple-mutation testing approach for risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin (NPM1), fms-like tyrosine kinase internal …

Peritoneal And Pleural Drains In Pediatric Hematopoietic Cell Transplant Recipients With Veno-Occlusive Disease Are Safe And Do Not Adversely Impact Clinical Outcomes, Hemalatha G. Rangarajan, Vinita B Pai Pharm, Joseph R. Stanek, Cassandra Rush Pharm, Jeffrey Naples, Misti Drope, Veronika Polishchuk, Rolla Abu Arja, Rajinder Ps Bajwa

Hematology/Oncology and Stem Cell Therapy

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study we compared the clinical outcomes and health resource utilization (HRU) in 32 patients with VOD who had a PD placed (PD+) post HCT with 27 patients who did not (PD-). Nine patients had a CT (7 PD+ and 2 PD-). PD+ patients were more likely than PD- patients to have received myeloablative conditioning (100% vs 85.2%; p=0.04) and have severe or very …

Post-Transplantation Cyclophosphamide Based Graft-Versus-Host-Disease Prophylaxis Compared To Methotrexate-Cyclosporine A In Matched Related Allogeneic Hematopoietic Stem Cell Transplantation, Mohamed Shouman, Osman Mansour, Mosaad M. El Gammal, Raafat Abdel-Fattah, Mohamed A. Samra, Alaa El Haddad, Mohamed Maher, Hossam K. Mahmoud

Hematology/Oncology and Stem Cell Therapy

Background: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce.

Objective: The study aimed to evaluate the rates of GVHD and survival outcomes in patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA matched related donors (MRD) receiving PTCy based GVHD prophylaxis and to compare it with the outcomes of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis.

Patients and Methods: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic …

Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño

Health Sciences and Kinesiology Faculty Articles

Context

One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed …

Determining The Existence And Regulation Of Microlipophagy In Primary Brown And White Adipocytes, Sara C. Arenas De Leon

Biomedical Sciences ETDs

Lipids are one of life’s four main macromolecules and provide essential functions to cells, as they serve as building blocks of cellular membranes, mediate cell signaling, and are a critical energy source. Within cells, esterified fatty acids aggregate into lipid droplets in the form of triglycerides, consisting of a neutral lipid core surrounded by a phospholipid monolayer decorated with various proteins.

The degradation of lipid droplets and mobilization of lipids occurs through lipolysis, a process that hydrolyzes a molecule of triglyceride into a glycerol and three fatty acids. Emerging evidence demonstrates the involvement of a selective form of autophagy in …

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Identifying The Temporal N-Linked Glycosylation Changes During Liver Disease Progression: From Liver Injury To End-Stage Liver Disease, Shaaron Ochoa-Rios

MUSC Theses and Dissertations

The high mortality rates of liver diseases and primary liver cancers can be attributed to the lack of screening and diagnostic strategies currently available for early detection. Non-alcoholic fatty liver disease (NAFLD) is an early stage of liver disease known to progress to a variety of pre-malignant and malignant conditions, like advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Based on the wide variety of diseases that NAFLD can progress to, strategies to understand and detect the progression of NAFLD are of great value. Core fucosylation of N-linked glycans has been demonstrated to be useful for the clinical diagnosis …

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …

Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression, Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M Cecilia Caino, Dario C. Altieri

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson's disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and β1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does …

Regulation Of De Novo And Maintenance Dna Methylation By Dnmt3a And Dnmt3b, Yang Zeng

Dissertations & Theses (Open Access)

DNA methylation (5-methylcytosine, 5mC) is essential for the regulation of gene expression and integrity of the mammalian genome. It occurs predominantly in the context of CpG dinucleotides to form a symmetrical pattern on both DNA strands, which allows DNA methylation patterns to be semi-conservatively maintained during DNA replication. There are two classes of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B function primarily as de novo methyltransferases that establish DNA methylation patterns, whereas DNMT1 is the major enzyme responsible for maintaining DNA methylation patterns by converting hemi-methylated CpGs to fully methylated CpGs during DNA replication. Two accessory factors also play critical regulatory …