Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In normal physiological condition, the maintenance of cellular proteostasis is a prerequisite for cell growth, functioning, adapting to changing micro-environments, and responding to extracellular stress. Cellular proteostasis is maintained by specific proteostasis networks (PNs) to prevent protein misfolding, aggregating, and accumulating in subcellular compartments. Commonly, the PNs are composed of protein synthesis, molecular chaperones, endoplasmic reticulum (ER), unfolded protein response (UPR), stress response pathways (SRPs), secretions, ubiquitin proteasome system (UPS), and autophagy-lysosomal pathways (ALPs). Although great efforts have been made to explore the underlying detailed mechanisms of proteostasis, there are many questions remain to explore, especially in proteostasis regulated by the ALPs. Proteostasis out-off-balance is correlated with various human diseases such as diabetes, stroke, inflammation, hypertension, pulmonary fibrosis, and Alzheimer's disease. , enhanced regulation of PNs is observed in tumors, thereby indicating that proteostasis may play a pivotal role in tumorigenesis and cancer development. Recently, inhibitors targeting the UPS have shown to be failed in solid tumor treatment. However, there is growing evidence showing that the ALPs play important roles in regulation of proteostasis alone or with a crosstalk with other PNs in tumors. In this review, we provide insights into the proteostatic process and how it is regulated by the ALPs, such as macroautophagy, aggrephagy, chaperone-mediated autophagy, microautophagy, as well as mitophagy during tumor development.
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PMID:The Autophagy-Lysosomal Pathways and Their Emerging Roles in Modulating Proteostasis in Tumors. 3057 55

The search for efficient chemotherapy drugs and other anti-cancer treatments would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME and in vitro models often do not include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we present a new fully-coupled, agent-based, multi-scale mathematical model of tumor growth, angiogenesis and metabolism that includes important aspects of the TME spanning subcellular-, cellular- and tissue-level scales. The mathematical model is computationally implemented for a three-dimensional TME, and a double hybrid continuous-discrete (DHCD) method is applied to solve the governing equations. The model recapitulates the distinct morphological and metabolic stages of a solid tumor, starting with an avascular tumor and progressing through angiogenesis and vascularized tumor growth. To examine the robustness of the model, we simulated normal and abnormal blood conditions, including hyperglycemia/hypoglycemia, hyperoxemia/hypoxemia, and hypercarbia/hypocarbia - conditions common in cancer patients. The results demonstrate that tumor progression is accelerated by hyperoxemia, hyperglycemia and hypercarbia but inhibited by hypoxemia and hypoglycemia; hypocarbia had no appreciable effect. Because of the importance of interstitial fluid flow in tumor physiology, we also examined the effects of hypo- or hypertension, and the impact of decreased hydraulic conductivity common in desmoplastic tumors. The simulations show that chemotherapy-increased blood pressure, or reduction of interstitial hydraulic conductivity increase tumor growth rate and contribute to tumor malignancy.
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PMID:A multi-scale model for determining the effects of pathophysiology and metabolic disorders on tumor growth. 3208 Feb 50

Coronavirus disease 19 (Covid-19) is a new emerging virus responsible for pandemic and death. High blood pressure, diabetes, obesity have been described as poor prognosis factors. Few data have been reported in patient with immunocompromised status (solid tumor, hematological malignancy, rheumatoid conditions or organ transplant). We evaluated the characteristics of patients, including the outcome, with immunodepression hospitalized in Besancon University hospital (East of France). We wanted to identify if a type of immunosupression influences the course of Covid-19. In a cohort of 80 patients with immunosupression (42 solid tumors, 20 hematological malignancy and 18 non neoplastic immunosupression), poor outcomes (Intensive care unit hospitalization and or deaths) was frequent (38%) and tended to be more frequent in patients with hematological malignancy.
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PMID:Does type of immunosupression influence the course of Covid-19 infection? 3241 9

Neuroendocrine tumors (NETs) are rare in childhood. Neuroblastoma is the most common pediatric extracranial solid tumor, occurring >90% in children younger than 5 years of age. Pheochromocytoma and paraganglioma are rare NETs, causing hypertension in 0.5-2% of hypertensive children. Gastroenteropancreatic NETs can occur in children and are classified into carcinoids and pancreatic tumors. Nuclear medicine procedures have an essential role both in the diagnosis and treatment of NETs. Metaiodobenzylguanidine (MIBG) labeled with radioiodine has a well-established role in diagnosis as well as therapeutic management of the neuroblastoma group of diseases. During recent decades, establishing the abundant expression of somatostatin receptors by NETs first led to scintigraphy with somatostatin analogs (i.e. Tc/In-octreotide) and, later, with the emergence of positron-emitting labeled agents (i.e. Ga-DOTATATE/DOTATOC/DOTANOC) PET scans with significantly higher detection efficiency became available. Therapy with somatostatin analogs labeled with beta emitters such as Lu-177 and Y-90, known as peptide receptor radionuclide therapy, is a promising new option in the management of patients with inoperable or metastasized NETs. In this article, pediatric NETs are briefly reviewed and the role of radioactive agents in the detection and treatment of these tumors is discussed.
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PMID:A review of pediatric neuroendocrine tumors, their detection, and treatment by radioisotopes. 3304


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