scholarly journals The Role of Morphine in Animal Models of Human Cancer: Does Morphine Promote or Inhibit the Tumor Growth?

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Giuseppe Palma ◽  
Claudio Arra
Keyword(s):  
Tumor Growth ◽  
Human Cancer ◽  
Primary Tumour ◽  
Cancer Cell Growth ◽  
Peripheral Tissues ◽  
Patients With Cancer ◽  
Relieve Pain ◽  
Pain And Suffering ◽  
The Central Nervous System

Morphine, a highly potent analgesic agent, is widely used to relieve pain and suffering of patients with cancer. Additionally, it has been reported that morphine is important in the regulation of cancerous tissue. Morphine relieves pain by acting directly on the central nervous system, although its activities on peripheral tissues are responsible for many adverse side effects. For these reasons, it is very important also to understand the role of morphine in cancer treatment. The published literature reporting the effect of morphine on tumor growth presents some discrepancies, with reports suggesting that morphine may either promote or inhibit the tumor growth. It has been also demonstrated that morphine modulates angiogenesis which is important for primary tumour growth, invasiveness, and the development of metastasis. This review will focus on the latest findings on the role of morphine in the regulation of cancer cell growth and angiogenesis.

scholarly journals Hypermethylation of DHRS3 as a Novel Tumor Suppressor Involved in Tumor Growth and Prognosis in Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Sha Sumei ◽  
Kong Xiangyun ◽  
Chen Fenrong ◽  
Sun Xueguang ◽  
Hu Sijun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Human Cancer ◽  
Methylation Status ◽  
Ectopic Expression ◽  
Survival Times

Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

scholarly journals α7 Nicotinic Receptor Promotes the Neuroprotective Functions of Astrocytes against Oxaliplatin Neurotoxicity

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lorenzo Di Cesare Mannelli ◽  
Barbara Tenci ◽  
Matteo Zanardelli ◽  
Paola Failli ◽  
Carla Ghelardini
Keyword(s):  
Nicotinic Receptor ◽  
Caspase 3 ◽  
Cell Metabolism ◽  
Strong Increase ◽  
Neuronal Homeostasis ◽  
Relieve Pain ◽  
The Central Nervous System ◽  
Detoxifying Enzyme ◽  
Anti Inflammatory Cytokine

Neuropathies are characterized by a complex response of the central nervous system to injuries. Glial cells are recruited to maintain neuronal homeostasis but dysregulated activation leads to pain signaling amplification and reduces the glial neuroprotective power. Recently, we highlighted the property ofα7 nicotinic-acetylcholine-receptor (nAChR) agonists to relieve pain and induce neuroprotection simultaneously with a strong increase in astrocyte density. Aimed to study the role ofα7 nAChR in the neuron-glia cross-talk, we treated primary rat neurons and astrocytes with the neurotoxic anticancer drug oxaliplatin evaluating the effect of theα7 nAChR agonist PNU-282987 (PNU). Oxaliplatin (1 μM, 48 h) reduced cell viability and increased caspase-3 activity of neuron monocultures without damaging astrocytes. In cocultures, astrocytes were not able to protect neurons by oxaliplatin even if glial cell metabolism was stimulated (pyruvate increase). On the contrary, the coculture incubation with 10 μM PNU improved neuron viability and inhibited apoptosis. In the absence of astrocytes, the protection disappeared. Furthermore, PNU promoted the release of the anti-inflammatory cytokine TGF-β1 and the expression of the glutamate-detoxifying enzyme glutamine synthetase. Theα7 nAChR stimulation protects neurons from oxaliplatin toxicity through an astrocyte-mediated mechanism.α7 nAChR is suggested for recovering the homeostatic role of astrocytes.

scholarly journals The Inhibitory Role of B7-H4 in Antitumor Immunity: Association with Cancer Progression and Survival

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Changjun He ◽  
Haiquan Qiao ◽  
Hongchi Jiang ◽  
Xueying Sun
Keyword(s):  
Cancer Progression ◽  
Antitumor Immunity ◽  
Human Cancer ◽  
Physiological Role ◽  
T Cell Response ◽  
Soluble Form ◽  
Peripheral Tissues ◽  
Inhibitory Role ◽  
Pertinent Data

B7-H4 is one of the most recently identified members of B7 superfamily of costimulatory molecules serving as an inhibitory modulator of T-cell response. B7-H4 is broadly expressed in human peripheral tissues and inducibly expressed in immune cells. The expression of B7-H4 has been observed in various types of human cancer tissues, and its soluble form has been detected in blood samples from cancer patients. However, its precise physiological role is still elusive, as its receptor has not been identified and the expression levels are not consistent. This paper summarizes the pertinent data on the inhibitory role of B7-H4 in antitumor immunity and its association with cancer progression and survival in human patients. The paper also discusses the clinical significance of investigating B7-H4 as potential markers for cancer diagnosis and prognosis, and as therapeutic targets.

scholarly journals The PI3K Pathway As Drug Target in Human Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 1075-1083 ◽  
Author(s):  
Kevin D. Courtney ◽  
Ryan B. Corcoran ◽  
Jeffrey A. Engelman
Keyword(s):  
Human Cancer ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Cancer Cell Growth ◽  
Growth And Survival ◽  
Genes Encoding ◽  
Signaling Axis ◽  
Rapid Pace

The phosphatidylinositol 3-kinase (PI3K) signaling axis impacts on cancer cell growth, survival, motility, and metabolism. This pathway is activated by several different mechanisms in cancers, including somatic mutation and amplification of genes encoding key components. In addition, PI3K signaling may serve integral functions for noncancerous cells in the tumor microenvironment. Consequently, therapeutics targeting the PI3K pathway are being developed at a rapid pace, and preclinical and early clinical studies are beginning to suggest specific strategies to effectively use them. However, the central role of PI3K signaling in a large array of diverse biologic processes raises concerns about its use in therapeutics and increases the need to develop sophisticated strategies for its use. In this review, we will discuss how PI3K signaling affects the growth and survival of tumor cells. From this vantage, we will consider how inhibitors of the PI3K signaling cascade, either alone or in combination with other therapeutics, can most effectively be used for the treatment of cancer.

scholarly journals Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology

2021 ◽  
Vol 8 ◽  
Author(s):  
Saeideh Aghayari Sheikh Neshin ◽  
Shima Shahjouei ◽  
Eric Koza ◽  
Isabel Friedenberg ◽  
Faezeh Khodadadi ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Renin Angiotensin System ◽  
Cardiovascular Complications ◽  
Elevated Risk ◽  
Peripheral Tissues ◽  
Angiotensin System ◽  
Cerebrovascular Complications ◽  
The Central Nervous System ◽  
Personalized Approach

Since the early days of the pandemic, there have been several reports of cerebrovascular complications during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Numerous studies proposed a role for SARS-CoV-2 in igniting stroke. In this review, we focused on the pathoetiology of stroke among the infected patients. We pictured the results of the SARS-CoV-2 invasion to the central nervous system (CNS) via neuronal and hematogenous routes, in addition to viral infection in peripheral tissues with extensive crosstalk with the CNS. SARS-CoV-2 infection results in pro-inflammatory cytokine and chemokine release and activation of the immune system, COVID-19-associated coagulopathy, endotheliitis and vasculitis, hypoxia, imbalance in the renin-angiotensin system, and cardiovascular complications that all may lead to the incidence of stroke. Critically ill patients, those with pre-existing comorbidities and patients taking certain medications, such as drugs with elevated risk for arrhythmia or thrombophilia, are more susceptible to a stroke after SARS-CoV-2 infection. By providing a pictorial narrative review, we illustrated these associations in detail to broaden the scope of our understanding of stroke in SARS-CoV-2-infected patients. We also discussed the role of antiplatelets and anticoagulants for stroke prevention and the need for a personalized approach among patients with SARS-CoV-2 infection.

scholarly journals Broadening the role of osteocalcin in hypothalamic-pituitary-gonadal axis

2021 ◽  
Author(s):  
Chang Shan ◽  
Jiang Yue ◽  
Wei Liu
Keyword(s):  
Developmental Disorders ◽  
Active Form ◽  
Peripheral Tissues ◽  
Glucose And Lipid Metabolism ◽  
Reproductive Endocrine ◽  
The Central Nervous System ◽  
Testosterone Biosynthesis ◽  
Increase Insulin Secretion ◽  
Functional Mechanisms

Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide hormone secreted by osteoblasts, has been found to exert multiple endocrine functions through its metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence has shown that following its binding to G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic β cells to increase insulin secretion, and on muscle and white adipose tissue to promote glucose and lipid metabolism. More strikingly, researchers have found a surprising role of uOCN in testicular function to facilitating testosterone biosynthesis and regulating male fertility via a pancreas-bone-gonadal axis. However, the detailed functional mechanisms of uOCN on the hypothalamic-pituitary-gonadal axis or the pancreas-bone-gonadal axis are not fully understood. Besides highlighting the regulatory mechanisms of uOCN in the central nervous system, hypothalamus and pituitary, we also discuss its role in male as well as female fertility and its potential clinical implications in some reproductive endocrine diseases and pubertal developmental disorders.

scholarly journals Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Adrian Sturza ◽  
Călin M. Popoiu ◽  
Mihaela Ionică ◽  
Oana M. Duicu ◽  
Sorin Olariu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Diseases ◽  
Noncommunicable Diseases ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Available Information ◽  
New Generation ◽  
Vascular Oxidative Stress ◽  
Inflammatory Burden

Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies. Indeed, oxidative stress and chronic inflammation are the most common pathomechanisms of the main noncommunicable diseases of our century. MAO inhibition with the new generation of reversible and selective drugs has recently emerged as a pharmacological strategy aimed at mitigating both processes. The aim of this minireview is to summarize available information regarding the contribution of MAO to the vascular oxidative stress and endothelial dysfunction in hypertension, metabolic disorders, and chronic kidney disease, all conditions associated with increased inflammatory burden.

scholarly journals Peripheral Spexin Inhibited Food Intake in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shuangyu Lv ◽  
Yuchen Zhou ◽  
Yu Feng ◽  
Xiaomei Zhang ◽  
Xinyue Wang ◽  
...  
Keyword(s):  
Food Intake ◽  
Dark Period ◽  
Mrna Level ◽  
Inhibitory Effect ◽  
Appetite Regulation ◽  
Peripheral Tissues ◽  
Anorectic Effect ◽  
The Central Nervous System ◽  
Cumulative Food Intake

Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0–6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.

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