Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases.
...
PMID:Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. 2407 69

This study (N = 102 women) evaluated the time course of posttraumatic stress symptomatology (PTSS) at different stages of nonmetastastic cancer diagnosis and treatment: during treatment, at the end of treatment, and at a 6-12 months follow-up. We also assessed the contribution of demographic, trait, and state predictors to PTSS, and coping processes as proximal mediators of the relation between Type C personality and PTSS. Results indicated that PTSS remained constant across all phases. There were significant correlations (range = .28 to .81) between PTSS and psychosocial variables and age, but not with other sociodemographic or medical factors. A linear growth curve model showed that hopelessness/helplessness (B = 1.45) and Type C personality (B = 1.40) were the best predictors of PTSD symptomatology, followed by trait dissociation (B = 0.55), and the coping strategies of anxious preoccupation (B = 1.20), cognitive avoidance (B = 0.91), and symptoms of acute stress disorder (B = 0.19). A mediation model showed that the coping strategies of anxious preoccupation, cognitive avoidance, and helplessness/hopelessness mediated the relationship between Type C personality and PTSS during treatment, posttreatment, and follow-up. These results clarify the contribution of different predictors of PTSS and can help develop prevention programs.
...
PMID:Posttraumatic stress symptoms in breast cancer patients: temporal evolution, predictors, and mediation. 2465 62

Under conditions of acute stress, rapid adaptation is crucial for maximizing biological survival. The responses to environmental stress are often complex, involving numerous genes and integrating events at the cellular and organismal levels. The heat shock proteins (HSPs) are a family of highly conserved proteins that play critical roles in maintaining cell homeostasis and protecting cells under chronic and acute stress conditions. The genes for these stress-responding proteins are widely distributed in organisms, tissues and cells. HSPs participate in a variety of physiological processes and are associated with various types of disease. In this review, we focused on family with sequence similarity 107 (FAM107), a novel unique protein family that exhibits functional similarity with HSPs during the cellular stress response. This review aimed to summarize the biological properties of FAM107 in cancer and the nervous system.
 ...
PMID:Family with sequence similarity 107: A family of stress responsive small proteins with diverse functions in cancer and the nervous system (Review). 2474 67

Alterations of the dynamics of DNA replication cause genome instability. These alterations known as "replication stress" have emerged as a major source of genomic instability in pre-neoplasic lesions, contributing to cancer development. The concept of replication stress covers a wide variety of events that distort the temporal and spatial DNA replication program. These events have endogenous or exogenous origins and impact globally or locally on the dynamics of DNA replication. They may arise within a short window of time (acute stress) or during each S phase (chronic stress). Here, we review the known situations in which the dynamics of DNA replication is distorted. We have united them in four main categories: (i) inadequate firing of replication origins (deficiency or excess), (ii) obstacles to fork progression, (iii) conflicts between replication and transcription and (iv) DNA replication under inappropriate metabolic conditions (unbalanced DNA replication). Because the DNA replication program is a process tightly regulated by many factors, replication stress often appears as a cascade of events. A local stress may prevent the completion of DNA replication at a single locus and subsequently compromise chromosome segregation in mitosis and therefore have a global effect on genome integrity. Finally, we discuss how replication stress drives genome instability and to what extent it is relevant to cancer biology.
...
PMID:The causes of replication stress and their consequences on genome stability and cell fate. 2481 79

Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.
 ...
PMID:Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. 2549 9

The unfolded protein response (UPR) remediates endoplasmic reticulum (ER) stress. IRE1, a component of the UPR, senses misfolded protein and cleaves XBP1 mRNA, which is ligated to code for the prosurvival transcription factor. IRE1 also cleaves other mRNAs preceding their degradation, termed regulated IRE1-dependent mRNA decay (RIDD). It has been reported that RIDD may be involved in cell viability under stress and therefore may contribute to cancer cell viability. To investigate RIDD targets that may have functional relevance in cell survival, we identified conserved RIDD targets containing stringent IRE1 RNase target sequences. Using a systematic bioinformatics approach with quantitative-PCR (qPCR) validation, we show that only BLOC1S1 is consistently a RIDD target in all systems tested. Using cancer cell lines, we show that BLOC1S1 is specifically cleaved by IRE1 at guanine 444, but only under conditions of IRE1 hyperactivation. BLOC1S1 cleavage is temporally separate from XBP1 splicing, occurring after depletion of unspliced XBP1. Expression of an uncleavable BLOC1S1 mutant or inhibition of RIDD using an IRE1 RNase inhibitor did not affect cellular recovery from acute ER stress. These data demonstrate that although hyperactivated IRE1 specifically cleaves BLOC1S1, this cleavage event and RIDD as a whole are dispensable for cell viability under acute stress.
...
PMID:Cleavage of BLOC1S1 mRNA by IRE1 Is Sequence Specific, Temporally Separate from XBP1 Splicing, and Dispensable for Cell Viability under Acute Endoplasmic Reticulum Stress. 2587 Jan 7

Malfunction of the trabecular meshwork (TM)/schlemm's canal (SC) conventional outflow pathway is associated with elevated intraocular pressure (IOP) and, therefore, increased risk of developing glaucoma, a potentially blinding disease affecting more than 70 million people worldwide. This TM/SC tissue is subjected to different types of stress, including mechanical, oxidative, and phagocytic stress. Long-term exposure to these stresses is believed to lead to a progressive accumulation of damaged cellular and tissue structures causing permanent alterations in the tissue physiology, and contribute to the pathologic increase in aqueous humor (AH) outflow resistance. Autophagy is emerging as an essential cellular survival mechanism against a variety of stressors. In addition to performing basal functions, autophagy acts as a cellular survival pathway and represents an essential mechanism by which organisms can adapt to acute stress conditions and repair stress-induced damage. A decline in autophagy has been observed in most tissues with aging and has been considered responsible, at least in part, for the accumulation of damaged cellular components in almost all tissues of aging organisms. Dysfunction in the autophagy pathway is associated with several human diseases, from infectious diseases to cancer and neurodegeneration. In this review, we will summarize our current knowledge of the emerging roles of autophagy in outflow tissue physiology and pathophysiology, including novel evidence suggesting compromised autophagy in the glaucomatous outflow pathway.
...
PMID:The autophagic lysosomal system in outflow pathway physiology and pathophysiology. 2622 31

A systematic review of the literature investigating the early traumatic stress responses in parents of children diagnosed with a serious illness/injury. A literature review was conducted (September 2013) using Medline, PsycINFO, and CINAHL databases. Twenty-four studies related to parents of children hospitalized due to diagnosis of cancer, type 1 diabetes, meningococcal disease, trauma or serious injury, preterm birth and other serious illnesses requiring admission to intensive care were included. Parents were assessed for early traumatic stress symptoms within 3 months of their child's diagnosis/hospitalization. Prevalence rates of acute stress disorder in parents ranged from 12 to 63%. Prevalence of posttraumatic stress disorder ranged from 8 to 68%. Variability was related to methodological factors including differences in study design, timing of assessments, measurement tools, and scoring protocols. Psychosocial factors rather than medical factors predicted parent distress. This review integrates and compares early traumatic reactions in parents with children suffering a range of serious illnesses. Findings suggest a high prevalence of acute and posttraumatic stress symptoms in parents. Methodological inconsistencies made comparison of early traumatic stress prevalence rates difficult. Risk factors associated with traumatic stress symptoms were identified.
 ...
PMID:Early Traumatic Stress Responses in Parents Following a Serious Illness in Their Child: A Systematic Review. 2629 14

Tumors perturb various physiological systems beyond their local microenvironment, including the immune, nervous, and metabolic systems. Given the involvement of these systems in physiological stress responses, the goal of this review is to compile evidence regarding whether or not cancer alters acute stress responses. Here, we focus on stress responses that are endocrine, immune, or behavioral. This question is clinically relevant as cancer patients are exposed to many stressors throughout diagnosis and treatment, and then later as survivors. Alterations in their stress responses may specifically affect how they respond to advice, treatments, and surgery under duress. To determine whether tumors alone alter stress responses, the relevant literature using rodent cancer models is first reviewed. Next, the more complicated clinical literature in cancer patients is integrated into the discussion. Based on the results of this analysis, goals for future basic and clinical research are proposed. This work aims to advance our understanding of the most effective methods for treating cancer patients and supporting their long-term survival.
 ...
PMID:The influence of cancer on endocrine, immune, and behavioral stress responses. 2643 87

The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of cancer metastases-the major cause of cancer related death. However, immune-stimulatory approach has not been used perioperatively given several contraindications to surgery. To overcome these obstacles, in this study, we used the newly introduced, fully synthetic TLR-4 agonist, Glucopyranosyl Lipid-A (GLA-SE), in various models of cancer metastases, and in the context of acute stress or surgery. Without exerting evident adverse effects, a single systemic administration of GLA-SE rapidly and dose dependently elevated both innate and adaptive immunity in the circulation, lungs and the lymphatic system. Importantly, GLA-SE treatment led to reduced metastatic development of a mammary adenocarcinoma and a colon carcinoma by approximately 40-75% in F344 rats and BALB/c mice, respectively, at least partly through elevating marginating-pulmonary NK cell cytotoxicity. GLA-SE is safe and well tolerated in humans, and currently is used as an adjuvant in phase-II clinical trials. Given that the TLR-4 receptor and its signaling cascade is highly conserved throughout evolution, our current results suggest that GLA-SE may be a promising immune stimulatory agent in the context of oncological surgeries, aiming to reduce long-term cancer recurrence.
Int J Cancer 2016 Apr 01
PMID:Perioperative treatment with the new synthetic TLR-4 agonist GLA-SE reduces cancer metastasis without adverse effects. 2645 48


<< Previous 1 2 3 4 5 6 7 8 Next >>