scholarly journals Adrenergic-Angiogenic Crosstalk in Head and Neck Cancer: Mechanisms and Therapeutic Implications

2021 ◽  
Vol 2 ◽  
Author(s):  
Vui King Vincent-Chong ◽  
Mukund Seshadri
Keyword(s):  
Head And Neck ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Implications ◽  
Multiple Components ◽  
Aggressive Tumors ◽  
Approved Drugs ◽  
Neural Signaling ◽  
Fda Approved Drugs

Head and neck squamous cell carcinomas (HNSCC) are loco-regionally aggressive tumors that often lead to debilitating changes in appearance, speech, swallowing and respiratory function in patients. It is therefore critical to develop novel targeted treatment strategies that can effectively target multiple components within the tumor microenvironment. In this regard, there has been an increased recognition of the role of neural signaling networks as mediators of disease progression in HNSCC. Here, we summarize the current knowledge on the mechanisms of adrenergic signaling in HNSCC specifically focusing on neurovascular crosstalk and the potential of targeting the adrenergic-angiogenic axis through repurposing of FDA-approved drugs against HNSCC.

166 TLR-4-Regulated Cerebrospinal Fluid Hypersecretion in Post-Hemorrhagic Hydrocephalus

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 242-242 ◽  
Author(s):  
Jason K Karimy ◽  
Jinwei Zhang ◽  
David B Kurland ◽  
Brianna Carusillo Theriault ◽  
Daniel Duran ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fold Increase ◽  
Pharmacological Intervention ◽  
Antisense Oligodeoxynucleotide ◽  
Genetic Ablation ◽  
Csf Shunting ◽  
Approved Drugs ◽  
Molecular Patterns ◽  
Fda Approved Drugs

Abstract INTRODUCTION Intraventricular hemorrhage (IVH) frequently causes post-hemorrhagic hydrocephalus (PHH) as a result of impaired cerebrospinal fluid (CSF) homeostasis. The most common treatment for PHH is surgical CSF shunting, a procedure fraught with complications. Historically, it is thought that PHH results from impaired reabsorption of CSF, however, little consideration has been given to the role of CSF hypersecretion. Recently, toll-like receptor-4 (TLR-4) has been implicated in the CNS by detecting “alarmins”, including IVH-derived metabolites, via recognition of damage-associated molecular patterns. We speculate that IVH triggers TLR-4-dependent inflammation at the choroid plexus epithelia (CPE), leading to CSF hypersecretion contributing to the development of PHH. METHODS In an established rat model of IVH, we assessed the rate of CSF secretion, CPE inflammation and the effect of genetic and pharmacological intervention on the development of PHH. We developed and implemented a novel surgical method in rats to measure the rate of CSF secretion. TLR-4 knockout rats, antisense oligodeoxynucleotide-mediated gene knockdown, and intracerebroventricular delivery of FDA-approved drugs were used to assess the role of specific inflammatory and ion transport targets on CSF secretion rate and ventriculomegaly following IVH. Immunoblot and immunohistochemistry were used to detect and quantify inflammatory markers. RESULTS >We show IVH triggers TLR4-NFkB-mediated inflammation at the CPE that is associated with a striking ∼3-fold increase in CSF secretion sufficient to cause PHH. CSF hypersecretion is dependent on the NFkB-regulated kinase SPAK, which interacts with and phosphorylates the bumetanide-sensitive NKCC1 at the CPE apical membrane. Genetic ablation of TLR-4 or SPAK, and pharmacology antagonizing TLR-4-NFkB signaling or the SPAK-NKCC1 complex normalizes CSF secretion rates and ventriculomegaly after IVH. CONCLUSION These data uncover a previously unrecognized role for CSF hypersecretion in the pathogenesis of PHH, and reveal a novel TLR-4-dependent regulatory pathway of CSF secretion that can be targeted with repurposed, FDA-approved drugs for the non-surgical treatment of PHH.

scholarly journals The Role of MRI in Prostate Cancer Active Surveillance

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Linda M. Johnson ◽  
Peter L. Choyke ◽  
William D. Figg ◽  
Baris Turkbey
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Treatment Strategies ◽  
Low Grade ◽  
Common Cancer ◽  
High Incidence ◽  
Aggressive Tumors ◽  
Slow Growing

Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance.

scholarly journals The Role of microRNA in Head and Neck Cancer: Current Knowledge and Perspectives

Molecules ◽  
2014 ◽  
Vol 19 (5) ◽  
pp. 5704-5716 ◽  
Author(s):  
Giulia Courthod ◽  
Pierfrancesco Franco ◽  
Loredana Palermo ◽  
Salvatore Pisconti ◽  
Gianmauro Numico
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Current Knowledge

scholarly journals The Role of Molecular Modeling and Bioinformatics in Treating a Pandemic Disease: The Case of COVID-19

2021 ◽  
Vol 1 (1) ◽  
pp. 216-234
Author(s):  
Abdallah S. Abdelsattar ◽  
Zahraa M. El-Awadly ◽  
Mai Abdelgawad ◽  
Fayrouz Mahmoud ◽  
Sahar A. Allam ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Treatment Strategies ◽  
Docking Studies ◽  
Current Treatment ◽  
Minor Role ◽  
Biologic Drugs ◽  
N Protein ◽  
Approved Drugs

The COVID-19 pandemic first appeared in Wuhan, China, in December 2019 in a cluster of pneumonia patients. The causative agent was found to be SARS-CoV-2. Here, we are summarizing current treatment strategies and highlighting the role of bioinformatics, molecular modeling, and structural biology during the COVID-19 pandemic. There are different pharmacological treatments, mostly repurposed drugs, employed for the treatment of COVID-19, including antiviral drugs, corticosteroids, biologic drugs, antibiotics, antifungal agents, and anticoagulants. Some immune-based therapies are also under evaluation, including convalescent plasma, IL-1, IL-6 inhibitors, and interferons. Different bioinformatics networks are established to provide information about the structure, transcriptome, and pathogenicity of the virus. The genotyping analysis for SARS-CoV-2 is also useful in identifying different mutations, SNPs, and conservative domains along the viral genome. Cryo-EM and X-ray diffraction had a crucial role in determining the structure of viral proteins such as spike (S) protein, main protease, and RdRp. NMR had a minor role and determining the structure of nucleocapsid (N) protein only. Several docking studies were performed to predict the interaction of certain FDA-approved drugs with known efficacy and toxicity, while others used natural products. Among different study types, in silico drug prediction and repurposing have the lowest risk with less off-target results. Therefore, bioinformatics and in silico studies have an important role during pandemics in providing information about viral structure and function and predicting potential treatments.

scholarly journals The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1667
Author(s):  
Mansoureh Barzegar ◽  
Karen Y. Stokes ◽  
Oleg Chernyshev ◽  
Roger E. Kelley ◽  
Jonathan S. Alexander
Keyword(s):  
Ischemic Stroke ◽  
Time Window ◽  
Renin Angiotensin System ◽  
Experimental Stroke ◽  
Stroke Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Thrombolytic Agents ◽  
Approved Drugs ◽  
Fda Approved Drugs

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1–7. In this review, we extensively discuss the protective functions of ACE2-Ang (1–7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.

scholarly journals Releasing the Brake: Targeting Cbl-b to Enhance Lymphocyte Effector Functions

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Stephanie Wallner ◽  
Thomas Gruber ◽  
Gottfried Baier ◽  
Dominik Wolf
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Negative Regulator ◽  
Therapeutic Concept ◽  
Therapeutic Implications

The E3 ubiquitin ligase Cbl-b is an established nonredundant negative regulator of T-cell activation. Cbl-b fine-tunes the activation threshold of T cells and uncouples T cells from their vital need of a costimulatory signal to mount a productive immune response. Accordingly, mice deficient incblbare prone to autoimmunity and reject tumors. The latter has been described to be mediatedviaCD8+T cells, which are hyperactive and more abundant in shrinking tumors ofcblb-deficient animals. This might at least also in part be mediated by resistance ofcblb-deficient T cells to negative cues exerted by tumor-associated immuno-suppressive factors, such as TGF-βand regulatory T cells (Treg). Experiments usingcblb-deficient T cells either alone or in combination with vaccines validate the therapeutic concept of enhancing the efficacy of adoptively transferred lymphocytes to treat malignant tumors. This paper summarizes the current knowledge about the negative regulatory role of Cbl-b in T-cell activation and its potential therapeutic implications for cancer immunotherapy.

scholarly journals Role of chemotherapy in nasopharyngeal carcinoma

2012 ◽  
Vol 6 (1) ◽  
pp. 1 ◽  
Author(s):  
Fabiola Paiar ◽  
Vanessa Di Cataldo ◽  
Giacomo Zei ◽  
Eleonora Monteleone Pasquetti ◽  
Sara Cecchini ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Head And Neck ◽  
Locally Advanced ◽  
Survival Rates ◽  
Treatment Strategies ◽  
High Sensitivity ◽  
Chemotherapeutic Agents ◽  
High Response Rate ◽  
Poorly Differentiated

Nasopharyngeal carcinoma (NPC) is a unique malignant head and neck cancer with clinical, demographic, and geographic features distinct from other head and neck epithelial malignancies. Non-keratinizing, poorly differentiated, and undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is also characterized by its relatively high sensitivity to radiation, so that in the last decades radiotherapy (RT) has been the cornerstone of treatment. However, in the majority of cases NPC is discovered at locally advanced stage. The results are disappointing when RT alone is offered. The 5-year survival rates have been reported to be about 34-52%. The poor prognosis for advanced NPC led to increasing interests in exploring the use of chemotherapy (CT). NPC has been considered to be not only radiosensitive but also chemo-sensitive and has shown high response rate to various chemotherapeutic agents. Certainly, the treatment strategies for NPC will continue to change and evolve as a better understanding is gained of the molecular and immune mechanisms that drive this disease. We reviewed the current literature focusing on the role of CT and new-targeted agents.

scholarly journals Role of microRNAs in Hemophilia and Thrombosis in Humans

2020 ◽  
Vol 21 (10) ◽  
pp. 3598 ◽  
Author(s):  
Katarzyna I. Jankowska ◽  
Zuben E. Sauna ◽  
Chintamani D. Atreya
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Current Knowledge ◽  
Genetic Defect ◽  
Treatment Strategies ◽  
Basic Research ◽  
Coagulation Cascade ◽  
Small Subset ◽  
Missense Mutations

MicroRNAs (miRNA) play an important role in gene expression at the posttranscriptional level by targeting the untranslated regions of messenger RNA (mRNAs). These small RNAs have been shown to control cellular physiological processes including cell differentiation and proliferation. Dysregulation of miRNAs have been associated with numerous diseases. In the past few years miRNAs have emerged as potential biopharmaceuticals and the first miRNA-based therapies have entered clinical trials. Our recent studies suggest that miRNAs may also play an important role in the pathology of genetic diseases that are currently considered to be solely due to mutations in the coding sequence. For instance, among hemophilia A patients there exist a small subset, with normal wildtype genes; i.e., lacking in mutations in the coding and non-coding regions of the F8 gene. Similarly, in many patients with missense mutations in the F8 gene, the genetic defect does not fully explain the severity of the disease. Dysregulation of miRNAs that target mRNAs encoding coagulation factors have been shown to disturb gene expression. Alterations in protein levels involved in the coagulation cascade mediated by miRNAs could lead to bleeding disorders or thrombosis. This review summarizes current knowledge on the role of miRNAs in hemophilia and thrombosis. Recognizing and understanding the functions of miRNAs by identifying their targets is important in identifying their roles in health and diseases. Successful basic research may result in the development and improvement of tools for diagnosis, risk evaluation or even new treatment strategies.

scholarly journals Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Marcus M. Monroe ◽  
Eric C. Anderson ◽  
Daniel R. Clayburgh ◽  
Melissa H. Wong
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Implications

Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs), whereas the remaining tumor cell population lacks the ability to initiate tumor development or support continued tumor growth. In head and neck squamous cell carcinoma (HNSCC), as with other malignancies, cancer stem cells have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In this paper we summarize the current knowledge of the role of CSCs in HNSCC and discuss the therapeutic implications and future directions of this field.

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