Abstract:
:Metastatic cancers account for more than 90% of cancer mortality. The metastasis of all cancers is critically mediated by enzymes that degrade extracellular matrix. Aggressive tumors are characterized by an imbalance between enzymes that degrade ECM and endogenous inhibitors of the enzymes. Matrix metalloproteinases (MMPs) make up the majority of ECM degrading enzymes implicated in cancer metastasis. The potent MMP inhibitory activities of tetracyclines, especially their chemically modified analogs, combined with their relatively well tolerated pharmacological profile, led several researchers to investigate their anticancer potential in a variety of cancers, including melanoma, lung, breast and prostate cancers. Chemically modified non-antibiotic tetracyclines (CMTs or COL) were tested using tumors of prostate, breast and melanomas. Some of these CMTs, notably, CMT-3 and CMT-308 significantly inhibited not only invasive potential and MMP activity, but also inhibited cell proliferation by inducing cell cycle arrest and apoptosis. CMT-3 and CMT-308 were significantly more potent than doxycycline or minocycline in inhibiting tumor cell-derived MMPs and inducing apoptosis in vitro and in vivo. CMT-3 (COL-3) showed potent inhibition of tumor growth in xenografts and in bone metastatic models of prostate cancer. Similar results were also reported in melanoma and breast cancer models. The mechanism by which CMTs kill tumor cells is via generation of hydroxyl free radicals ([OH](-)) which permeate and depolarize mitochondria, which in turn activates caspase mediated apoptosis. Analysis of tumor tissues from CMT-3 treated rats demonstrated reduction in angiogenesis and increase in apoptosis; both emerged as mechanisms of CMT action. These observations led to testing the efficacy of CMT-3 in human clinical trials against several types of cancer with significant outcomes, which are described in the next chapter of this issue.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Lokeshwar BLdoi
10.1016/j.phrs.2010.11.003subject
Has Abstractpub_date
2011-02-01 00:00:00pages
146-50issue
2eissn
1043-6618issn
1096-1186pii
S1043-6618(10)00216-1journal_volume
63pub_type
杂志文章,评审abstract::Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. This study aimed to investigate potential protective effects of angiotensin II type-2 receptor (AT2R) activation in cigarette smoke (...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105223
更新日期:2020-11-01 00:00:00
abstract::The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decreas...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1993.1031
更新日期:1993-05-01 00:00:00
abstract::Oxidative stress is related to the progression of renal diseases and modulation of oxidative stress can lead to a reduction in vascular events in patients with chronic renal insufficiency (CRI). Indoxyl sulfate (IS) and xanthine oxidase (XO) are related to impaired neovasculogenesis in CRI. Hydralazine is suggested fo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104509
更新日期:2020-01-01 00:00:00
abstract::Cosmetics are largely diffused substances topically applied to wash, to perfume or to improve the look, nevertheless the number of reported adverse reactions is very low, probably because of underreporting. This could be due to self-diagnosis and self-medication that is common in the presence of not severe reactions. ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.08.003
更新日期:2006-01-01 00:00:00
abstract::The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.01.006
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abstract::In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.04.002
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abstract::The vascular endothelial growth factor receptor-1 (VEGFR-1) is a membrane receptor for VEGF-A, placenta growth factor (PlGF) and VEGF-B that plays a crucial role in melanoma invasiveness, vasculogenic mimicry and tumor-associated angiogenesis. Furthermore, activation of VEGFR-1 is involved in the mobilization of myelo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104957
更新日期:2020-09-01 00:00:00
abstract::Though the AMPA receptor has been implicated in several neurodegenerative processes (epilepsy, ischemia, spasticity), its role in cognition is yet to be clarified. The aim of this study was to assess in the rat the effects of the AMPA receptor antagonist NBQX (3.5, 7, 10, 20 and 30 mgkg(-1), i.p.) on learning and memo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0898
更新日期:2002-01-01 00:00:00
abstract::A novel alkynylthiophene series of cannabinoid CB1 receptor antagonists has been described to exhibit distinct intrinsic activities with minimal substructure modifications. The three representatives, BPR0432, BPR0568 and BPR0569, functioning as a neutral antagonist, an inverse agonist and a partial agonist, respective...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2010.06.001
更新日期:2010-10-01 00:00:00
abstract::Biochemical evaluations of the effects of the sulfhydryl-containing angiotensin-converting enzyme inhibitor (captopril) on the nephrotoxicity induced by doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg kg-1) which caused nephrotoxicity was manifested biochemically by the elevation of se...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1998.0432
更新日期:1999-03-01 00:00:00
abstract::The herbal formulation Sinpo-Tang (SPT) has long been used for various allergic diseases. We investigated the effect of SPT on the mast cell-mediated anaphylactic reactions in vivo and in vitro murine models. SPT dose dependently inhibited compound 48/80-induced ear swelling response and histamine release. SPT (0.001-...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043661802002037
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abstract::Cardiovascular diseases (CVD) are among the main causes of death globally and in this context hypertension represents one of the key risk factors for developing a CVD. It is well established that the peripheral renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). All components of ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.06.016
更新日期:2017-11-01 00:00:00
abstract::Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of cancer cells is one of the major directions of anti-metastatic drug development. Calumenin and fibulin-1 are two extracellular proteins that synergistically inhibit cell migration and tumor metastasis, and could potentially be served as t...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.05.001
更新日期:2015-09-01 00:00:00
abstract::Results presented in this study demonstrate an association between the L-Histidine-mediated enhancement of H2O2-induced cytotoxicity and the formation of DNA double strand breakage (DSB), whereas no relationship exists between the increased cytotoxic response and DNA single strand breakage (SSB). Indeed, the higher le...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/1043-6618(94)80041-3
更新日期:1994-02-01 00:00:00
abstract::Diabetic nephropathy (DN) is a common and serious complication of diabetes and causes kidney failure. Ginsenoside Rg5 (Rg5) is an important monomer in the main protopanaxadiol component of black ginseng. Rg5 has exhibited some beneficial biological effects, such as anti-cancer, neuroprotection, and anti-depression, bu...
journal_title:Pharmacological research
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doi:10.1016/j.phrs.2020.104746
更新日期:2020-05-01 00:00:00
abstract::We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolid...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.09.010
更新日期:2016-11-01 00:00:00
abstract::Several factors such as proteinuria and renal fibrosis may be important in the progression of many forms of chronic renal diseases. The purposes of the current study were to investigate the progressive renal failure of the rats with surgical renal mass reduction (RMR) and the effect of the angiotensin-converting enzym...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(02)00321-3
更新日期:2003-03-01 00:00:00
abstract::The review emphasizes the role of NGF, the most representative member of the neurotrophins family, in cardiac physiopathology with a particular focus on healing and sprouting processes occurring after tissue damage. Cardiac and circulating NGF levels dramatically increase following myocardial injury (MI). A very early...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2010.12.017
更新日期:2011-04-01 00:00:00
abstract::Mitochondria are best known for their role in ATP generation. However, studies over the past two decades have shown that mitochondria do much more than that. Mitochondria regulate both necrotic and apoptotic cell death pathways, they store and therefore coordinate cellular Ca2+ signaling, they generate and metabolize ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.08.010
更新日期:2018-12-01 00:00:00
abstract::The polyphenol resveratrol is considered to exert many beneficial actions, such as antioxidant, anti-inflammatory, insulin-sensitizer and anticancer effects. Its benefits in patients with type 2 diabetes mellitus (T2DM) are controversial. Our aims were to determine whether resveratrol supplementation at two different ...
journal_title:Pharmacological research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.phrs.2016.08.010
更新日期:2016-09-01 00:00:00
abstract::There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both,...
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doi:10.1016/j.phrs.2016.06.012
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journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.08.034
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abstract::The antipsychotic drug olanzapine is widely used in the treatment of schizophrenia, bipolar and other mental disorders; however, it causes serious metabolic disorders, including dyslipidemia. Our previous studies have identified that olanzapine activated expression of the sterol regulatory element binding transcriptio...
journal_title:Pharmacological research
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abstract::Alzheimer's disease (AD) is regarded as a progressive and devastating neurodegenerative disorder. In aged individuals, it is the most prevalent cause of dementia and is characterized by gradual loss of cognitive functions. In the last decade, numerous research works were undertaken to investigate the pathogenesis of A...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.11.028
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abstract::This study aimed to elucidate whether the effect of cilostazol to suppress apoptotic cell death is directly coupled to cAMP-dependent protein kinase activation in human umbilical vein endothelial cells (HUVECs). After exposure of HUVECs to LPS (1 microgml(-1)) for 18 h, the endothelial cells irregularly aggregated wit...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2006.05.006
更新日期:2006-10-01 00:00:00
abstract::Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate t...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104887
更新日期:2020-09-01 00:00:00
abstract::Local microcirculatory dysfunction within the pancreatic gland might be an important factor in the conversion of oedematous to necrotizing pancreatitis. Therapeutic agents, improving the pancreatic blood flow, might be valuable in acute pancreatitis treatment. An influence of nitric oxide, heparin and procaine treatme...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0200
更新日期:1997-08-01 00:00:00
abstract::The cytokine thymic stromal lymphopoietin (TSLP) is involved in the development and the progression of allergic diseases. It is mainly released by epithelial cells at barriers such as skin and gut in response to danger signals. Overexpression of TSLP in keratinocytes (KC) can provoke the development of a type 2 inflam...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.08.001
更新日期:2016-11-01 00:00:00
abstract:AIM:Acute myocardial infarction and subsequent post-infarction heart failure are among the leading causes of mortality worldwide. The endocannabinoid system has emerged as an important modulator of cardiovascular disease, however the role of endocannabinoid metabolic enzymes in heart failure is still elusive. Herein, w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104578
更新日期:2020-01-01 00:00:00
abstract::The objective of the study was to investigate possible changes in vancomycin serum levels induced by cardio-pulmonary bypass (CPB). Ten cardiac patients (seven males, three females, aged between 56 and 81), who underwent cardiac surgery requiring CPB, took part in the study. Vancomycin (15 mg kg-1) was intravenously i...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1006/phrs.1998.0370
更新日期:1998-10-01 00:00:00