Medicine and Health Sciences Commons^™

Targeting Cancer Hallmarks With Epigallocatechin Gallate (Egcg): Mechanistic Basis And Therapeutic Targets, Wamidh H. Talib, Dima Awajan, Abdelrahim Alqudah, Razan Alsawwaf, Raha Althunibat, Mahmoud Abu Alroos, Ala’A Al Safadi, Sharif Abu Asab, Rawan W. Hadi, Lina T. Al Kury

All Works

Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of …

Allicin And Cancer Hallmarks, Wamidh H. Talib, Media Mohammed Baban, Aya O. Azzam, Jenan J. Issa, Alaa Y. Ali, Alia Kh Alsuwais, Sana Allala, Lina T. Al Kury

All Works

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, …

Effects Of 5% Astaxanthin Gel On Angiogenesis And Granulation Tissue In Second-Degree Burn Animal Model, Aunur Rofiq, Anggun Putri Yuniaswan, Rizki Hapsari Nugraha

Journal of General - Procedural Dermatology & Venereology Indonesia

Background: Burn injuries generate more free radicals and lead to complex immune dysfunction, which can delay wound healing compared to other wound types. Angiogenesis, essential for wound healing, requires granulation tissue as a marker for successful wound healing. Low concentrations of reactive oxygen species (ROS) are necessary to initiate this process. Astaxanthin is a potent antioxidant with anti-inflammatory properties, known to activate angiogenesis and modulate ROS signaling during wound healing.

Methods: This experimental study aimed to evaluate 5% astaxanthin gel on second-degree burns using 30 male Wistar rats. Simple random sampling was utilized. A total of 6 groups …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Biomedical Engineering: Graduate Reports and Projects

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Abcb5+ Mesenchymal Stromal Cells Therapy Protects From Hypoxia By Restoring Ca2+ Homeostasis In Vitro And In Vivo, Kaixuan Yan, Jiaxing Zheng, Mark Andreas Kluth, Lin Li, Christoph Ganss, Benito Yard, Richard Magdeburg, Markus H. Frank, Prama Pallavi, Michael Keese

Research outputs 2022 to 2026

Background:

Hypoxia in ischemic disease impairs Ca²⁺ homeostasis and may promote angiogenesis. The therapeutic efficacy of mesenchymal stromal cells (MSCs) in peripheral arterial occlusive disease is well established, yet its influence on cellular Ca²⁺ homeostasis remains to be elucidated. We addressed the influence of ATP-binding cassette subfamily B member 5 positive mesenchymal stromal cells (ABCB5⁺ MSCs) on Ca²⁺ homeostasis in hypoxic human umbilical vein endothelial cells (HUVECs) in vitro and in vivo.

Methods:

Hypoxia was induced in HUVECs by Cobalt (II) chloride (CoCl₂) or Deferoxamine (DFO). Dynamic changes in the cytosolic- and endoplasmic reticulum …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T. Batchelor, Minhee Won, Arnab Chakravarti, Costas G. Hadjipanayis, Wenyin Shi, Lynn S. Ashby, Volker W. Stieber, H. Ian Robins, Heidi J. Gray, Alfredo Voloschin, John B. Fiveash, Clifford G. Robinson, Ushasree Chamarthy, Young Kwok, Terrence P. Cescon, Anand K. Sharma, Rekha Chaudhary, Mei-Yin Polley, Minesh P. Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Poornima Devi Shaji, Swathi Holla, Nirnoy Dan, Shabnam Malik, Murali M. Yallapu, Meena Jaggi, Stephen W. Behrman, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Introduction: In pancreatic ductal adenocarcinoma (PDAC), low patient survival rate remains a problem. The activating point mutation of KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRAS^G12D regulates cell proliferation, differentiation, apoptosis; recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both PDAC and stromal cells, which modulate tumor microenvironment and metastasis. Therefore, we have developed a novel combination therapy for PDAC by targeting mutated KRAS^G12D and Gal-1 to target both proliferation and metastasis in PDAC. This includes the delivery of KRAS^{G12D …}

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan

School of Graduate Studies Faculty Publications

Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression …

Cellular Heterogeneity And Stem Cells Of Vascular Endothelial Cells In Blood Vessel Formation And Homeostasis: Insights From Single-Cell Rna Sequencing, Taku Wakabayashi, Hisamichi Naito

Wills Eye Hospital Papers

Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed …

Exploring The Past, Present, And Future Of Anti-Angiogenic Therapy In Glioblastoma., Ashley B. Zhang, Khashayar Mozaffari, Brian Aguirre, Victor Li, Rohan Kubba, Nilay C Desai, Darren Wei, Isaac Yang, Madhuri Wadehra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the …

Hypoxia Regulates Vessel-Modifying Macrophages And Vice Versa In Tumors, Kayla Jo Steinberger

Graduate Theses, Dissertations, and Problem Reports

Hypoxia, or low oxygen, is a common feature of solid tumors correlating with poor survival in cancer patients. Growing tumors need a blood supply to deliver oxygen. Tumors attempt to re-acquire oxygen by forming new blood vessels from nearby, pre-existing vessels, a process known as angiogenesis. Past treatments aimed at preventing this process yielded not only disappointing results in the clinic but sometimes worsened the patient’s prognosis making the tumor more hypoxic, emphasizing the urgent need for novel targets. In tumors, angiogenesis is notoriously dysfunctional resulting in leaky, under-perfused blood vessels which cannot adequately deliver oxygen and exacerbates hypoxia. Emerging …

Determination Of The Effects Of Advanced Glycation End Products Receptor Polymorphisms And Its Activation On Structural Cell Responses And Inflammation In Asthma, Esra Bi̇rben, Ümi̇t Murat Şahi̇ner, Can Ömer Kalayci

Turkish Journal of Medical Sciences

Background/aim: Advanced glycation end products receptor (RAGE) is a pattern recognition receptor which attracted attention in chronic airway diseases recently. This study aimed to determine the association of RAGE with asthma and the cellular responses resulting from RAGE signaling pathway activation. Materials and methods: Asthmatic (n = 362) and healthy (n = 134) children were genotyped by PCR-RFLP. Plasma sRAGE levels were determined by ELISA. Lung structural cells were stimulated with AGEs (advanced glycation end products) and control BSA. Expressions of cytokines and protein levels were determined by real-time PCR and ELISA. Results: Gly82Ser and -374 T/A polymorphisms in RAGE …

Skin-Derived Abcb5+ Mesenchymal Stem Cells For High-Medical-Need Inflammatory Diseases: From Discovery To Entering Clinical Routine, Elke Niebergall-Roth, Natasha Y. Frank, Christoph Ganss, Markus H. Frank, Mark A. Kluth

Research outputs 2022 to 2026

The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential …

Epigenetic Regulation In Chromium-, Nickel- And Cadmium-Induced Carcinogenesis, Lei Zhao, Ranakul Islam, Yifang Wang, Xiujuan Zhang, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; …

Percussive Massage Increases Capillary Density In Type I And Ii Skeletal Muscle Fibers, Thane Thomas, Mohadeseh Ahmadi, Robert D. Hyldahl

International Journal of Exercise Science: Conference Proceedings

Capillaries play a critical role in delivering oxygen and nutrients to cells. Skeletal muscle adapts to increased demand by increasing capillary density through a process known as angiogenesis. The effects of alternative therapies such as massage on angiogenic adaptation in skeletal muscle are inconclusive, particularly for newer techniques such as percussive massage. PURPOSE: To investigate the effect of 6 weeks of percussive massage on skeletal muscle myofiber area and angiogenesis. METHODS: 11 healthy young (22±4 yr.) men (n=5) and women (n=6) received 18 sessions of 30-min-percussive massage on their right thigh over the course of 6 weeks. Muscle samples were …

Epigenetic Dysregulations In Arsenic-Induced Carcinogenesis, Ranakul Islam, Lei Zhao, Yifang Wang, Grace Lu-Yao, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced …

Translational Development Of Abcb5+ Dermal Mesenchymal Stem Cells For Therapeutic Induction Of Angiogenesis In Non-Healing Diabetic Foot Ulcers, Andreas Kerstan, Kathrin Dieter, Elke Niebergall-Roth, Sabrina Klingele, Michael Jünger, Christoph Hasslacher, Georg Daeschlein, Lutz Stemler, Ulrich Meyer-Pannwitt, Kristin Schubert, Gerhard Klausmann, Titus Raab, Matthias Goebeler, Korinna Kraft, Jasmina Esterlechner, Hannes M. Schröder, Samar Sadeghi, Seda Ballikaya, Martin Gasser, Ana M. Waaga-Gasser, George F. Murphy, Dennis P. Orgill, Natasha Y. Frank, Christoph Ganss, Karin Scharffetter-Kochanek, Markus H. Frank, Mark A. Kluth

Research outputs 2022 to 2026

Background

While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly to standard treatment. GMP-manufactured skin-derived ABCB5⁺ mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing and engraftment potential, their ability to adaptively respond to inflammatory signals, and their wound healing-promoting efficacy in mouse wound models and human chronic venous ulcers.

Methods

The angiogenic potential of ABCB5⁺ MSCs was characterized with respect to angiogenic factor expression at the mRNA and protein level, in vitro endothelial trans-differentiation and …

The Study Of Immunohistochemical Expression Of Vascular Endothelial Growth Factor In Renal-Cell Carcinoma, Alyaa Abou El-Maged Moselhy, Dalia R. Al-Sharaky, Marwa M. Dawoud, Mona Abd El-Halim Kandil

Menoufia Medical Journal

Objective To study immunohistochemical expression of vascular endothelial growth factor (VEGF) renal-cell carcinoma (RCC) and correlate its expression with the studied clinicopathologic parameters. Background RCC is the sixth diagnosed cancer in males and the tenth in females accounting for 5 and 3% of cancer incidence, respectively. VEGF is a peptide with angiogenic properties. It is thought to have an important role in RCC development and progression. Patients and methods This retrospective study was performed on 58 cases of RCC and 31 cases of nonneoplastic kidney tissue. The slides were subjected to VEGF immunohistochemical staining using a streptavidin–biotin–peroxidase technique. The relationships …

Pulsatility Is A Predictive Marker Of Improved Cardiac Function In Patients With Liquid Matrix-Treated Left Ventricular Assist Devices, Philemon Mikail, Rinku Skaria, Marvin Slepian, Janny Garcia, Richard Smith, Zain Khalpey

The VAD Journal

Objective: Left ventricular assist devices (LVADs) are utilized as a bridge to transplant or as destination therapy for patients with end-stage heart failure. Although cardiac offloading from these devices rarely leads to complete remodeling and functional recovery, the use of mesenchymal cells to modulate heart failure has been explored in recent years due to its intrinsic regenerative properties. Current methods of evaluating cardiac function have too much variability, difficulty of access, or require too frequent follow up to create universal weaning protocols. We hypothesized that the administration of amniotic allograft liquid matrix (LM) containing amnion-derived mesenchymal stem cells (aMSCs) in …

Tannic Acid Exhibits Antiangiogenesis Activity In Nonsmall-Cell Lung Cancer Cells, Elham Hatami, Prashanth K.B. Nagesh, Mohammed Sikander, Anupam Dhasmana, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications and Presentations

Nonsmall-cell lung cancer (NSCLC) is the most common type of lung cancer, with a dismal prognosis. NSCLC is a highly vascularized tumor, and chemotherapy is often hampered by the development of angiogenesis. Therefore, suppression of angiogenesis is considered a potential treatment approach. Tannic acid (TA), a natural polyphenol, has been demonstrated to have anticancer properties in a variety of cancers; however, its angiogenic properties have yet to be studied. Hence, in the current study, we investigated the antiproliferative and antiangiogenic effects of TA on NSCLC cells. The (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay revealed that TA induced a dose- and time-dependent …

The Phenomenon Of Multidrug Resistance In Glioblastomas, Alexandr N. Chernov, Diana A. Alaverdian, Elvira S. Galimova, Alessandra Renieri, Elisa Frullanti, Ilaria Meloni, Olga V. Shamova

Hematology/Oncology and Stem Cell Therapy

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms.

The Tca Cycle As A Nexus Of Metabolic Vulnerabilities In Cancer, Sunada Khadka

Dissertations & Theses (Open Access)

Uncontrolled proliferation of cancer cells necessitates rewiring of metabolic pathways to meet biosynthetic and bioenergetic demands of proliferation and fortify redox homeostasis. An increasing body of literature suggests that mitochondrial metabolism (tricarboxylic acid cycle (TCA) and oxidative phosphorylation) is imperative for cancer cell growth and proliferation. The scope of the works presented in this dissertation is to explore the importance of mitochondrial metabolism, and primarily the TCA cycle—the anabolic factory of cancer cells and leverage it as a targetable vulnerability in cancer. Cancer cells consume anabolic nutrients that are used to generate biosynthetic precursors in the TCA cycle. Continuous efflux …

Mechanistic Insights On The Role Of Ambrisentan, An Endothelin Type-A Receptor Antagonist, In Breast Cancer, Ruba Saleem Lutfi Amer

Theses

The activation of the endothelin receptor type A (ETAR) by its ligand endothelin-1 (ET-1) is well known for its role in vasoconstriction. Interestingly, ET-1 and ETAR are over-expressed in various human tumours, including breast cancer. Several studies described the important role of ETAR in cancer progression and metastasis. The extensive network of interactions that exist between the ET-1 axis and other signalling pathways can trigger autocrine and paracrine signalling that modulates different tumorigenesis processes, such as cellular proliferation and survival, epithelial-to-mesenchymal transition (EMT) and chemoresistance. The main objective of this study was to investigate the antitumor effects of Ambrisentan, a …

Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown

Electronic Theses and Dissertations

The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …

Human Endothelial Cells Promote Arsenic-Transformed Lung Epithelial Cells To Induce Tumor Growth And Angiogenesis Through Interleukin-8 Induction, Lei Zhao, Yi-Fang Wang, Jie Liu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B …

Targeting Angiogenesis In Squamous Cell Carcinoma Of The Head And Neck: Opportunities In The Immunotherapy Era, Nabil Saba, Pooja Vijayvargiya, Jan Vermorken, Juan Rodrigo, Stefan Willems, Nina Zidar, Remco De Bree, Antti Mäkitie, Greg Wolf, Athanassios Argiris, Yong Teng, Alfio Ferlito

Department of Medical Oncology Faculty Papers

Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has …

Extracellular Matrix Guidance Of Autophagy: A Mechanism Regulating Cancer Growth, Carolyn Chen, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The extracellular matrix (ECM) exists as a dynamic network of biophysical and biochemical factors that maintain tissue homeostasis. Given its sensitivity to changes in the intra- and extracellular space, the plasticity of the ECM can be pathological in driving disease through aberrant matrix remodelling. In particular, cancer uses the matrix for its proliferation, angiogenesis, cellular reprogramming and metastatic spread. An emerging field of matrix biology focuses on proteoglycans that regulate autophagy, an intracellular process that plays both critical and contextual roles in cancer. Here, we review the most prominent autophagic modulators from the matrix and the current understanding of the …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Gene Electrotransfer Of Fgf2 Enhances Collagen Scaffold Biocompatibility, Carly Boye, Kyle Cristensen, Kamal Asadipour, Scott Declemente, Michael Francis, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Tendon injuries are a common athletic injury that have been increasing in prevalence. While there are current clinical treatments for tendon injuries, they have relatively long recovery times and often do not restore native function of the tendon. In the current study, gene electrotransfer (GET) parameters for delivery to the skin were optimized with monophasic and biphasic pulses with reporter and effector genes towards optimizing underlying tendon healing. Tissue twitching and damage, as well as gene expression and distribution were evaluated. Bioprinted collagen scaffolds, mimicking healthy tendon structure were then implanted subcutaneously for biocompatibility and angiogenesis analyses when combined with …