RESUMEN
BACKGROUND: Cardiomyocytes form, transport, and metabolize the omnipresent metabolite adenosine. Depending upon the adenosine concentrations and the pharmacological properties of receptor subtypes, adenosine exerts (patho)physiological responses in the cardiovascular system. The objective of this review is to present different protective mechanisms of A1-adenosine receptor inhibitors in cardiovascular diseases. METHODS AND RESULTS: Literature references were collected and sorted using relevant keywords and key phrases as search terms in scientific databases such as Web of Science, PubMed and Google Scholar. A1 adenosine receptor regulates free fatty acid metabolism, lipolysis, heart rate, blood pressure, and cardiovascular toxicity. The evidence clearly supporting the therapeutic potency of pharmacological A1 adenosine receptors agonists and antagonists in modulating cardiovascular risk factor parameters and treatment of cardiovascular diseases. CONCLUSION: This review summarizes the protective role of pharmacological A1-adenosine receptor regulators in the pathogenesis of cardiovascular diseases for a better management of cardiovascular diseases.
Asunto(s)
Enfermedades Cardiovasculares , Antagonistas de Receptores Purinérgicos P1 , Humanos , Antagonistas de Receptores Purinérgicos P1/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Presión Sanguínea , Adenosina , Receptores Purinérgicos P1RESUMEN
Hepatocellular carcinoma (HCC) is one of the common malignant human tumors with high morbidity worldwide. Aberrant activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is related to clinicopathological features of HCC. Emerging data revealed that microRNAs (miRNAs) have prominent implications for regulating cellular proliferation, differentiation, apoptosis, and metabolism through targeting the PI3K/AKT/mTOR signaling axis. The recognition of the crucial role of miRNAs in hepatocarcinogenesis represents a promising area to identify novel anticancer therapeutics for HCC. The present study summarizes the major findings about the regulatory role of miRNAs in the PI3K/AKT/mTOR pathway in the pathogenesis of HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-ß type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients.
Asunto(s)
Compuestos de Anilina/farmacología , Adherencias Tisulares/prevención & control , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Triazoles/farmacología , Células 3T3 , Animales , Apoptosis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/metabolismo , Inflamación/prevención & control , Ratones , Estrés Oxidativo , Distribución AleatoriaRESUMEN
microRNA-21 (miR-21) is a small noncoding RNA that regulates gene expression in different types of human malignancies. The potential prognostic value of miR-21 in cancer progression is controversial. This meta-analysis includes 76 studies of 10,213 cancer patients to test miR-21 prognostic value in various human cancers. We obtain hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS) to assess association strength. In the pooled analysis, high miR-21 expression is associated with poor OS, with a combined HR of 1.59 (95% CI, 1.49-1.70; p < 0.001; random-effects model). Furthermore, subgroup analysis demonstrates that high miR-21 expression is related to shorter OS in patients with digestive system cancers (HR = 1.02; 95% CI, 1.002 to 1.04; p = 0.026), respiratory system cancers (HR = 1.93; 95% CI, 1.48 to 2.51; p < 0.001), and breast cancer (HR = 2.20; 95% CI, 1.78 to 2.73; p = 0.001). These results indicate that miR-21 may be a clinically useful prognostic biomarker for cancer progression.
Asunto(s)
Biomarcadores de Tumor/genética , MicroARNs/genética , Neoplasias/genética , Neoplasias/mortalidad , Supervivientes de Cáncer , Intervalos de Confianza , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Angiotensin II receptor blockers (ARBs) have a potential role in reducing inflammation and fibrosis. We have integrated systems and molecular biology approaches to investigate the therapeutic potential of ARBs in preventing postsurgical adhesion band formation. MATERIAL AND METHODS: we have followed the ARRIVE guidelines point by point during experimental studies. Telmisartan (1 and 9 mg/kg), valsartan (1 and 9 mg/kg), and losartan (1 and 10 mg/kg) were administered intraperitoneally in different groups of male albino Wistar rat. After 7 d of treatment, macroscopic evidence and score of fibrotic bands based on scaling methods was performed. Moreover, the anti-inflammatory and antifibrosis effects of telmisartan on reduction of fibrotic bands were investigated by using histopathology, ELISA, and real-time polymerase chain reaction methods. RESULTS: Telmisartan, but not losartan or valsartan, prevented the frequency as well as the stability of adhesion bands. Telmisartan appears to elicit anti-inflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that telmisartan prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic genes expression at the peritoneum adhesion tissues. CONCLUSIONS: These results support the potential application of telmisartan in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in postsurgery patients.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Telmisartán/administración & dosificación , Adherencias Tisulares/prevención & control , Animales , Evaluación Preclínica de Medicamentos , Inyecciones Intraperitoneales , Masculino , Distribución Aleatoria , Ratas WistarRESUMEN
Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n»6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.
Asunto(s)
Carotenoides/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Animales , Carotenoides/efectos adversos , Carotenoides/farmacología , Colitis Ulcerosa/inducido químicamente , Colon/efectos de los fármacos , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Transforming growth factor ß (TGF-ß) modulates tumor progression by regulating cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance. Biological and pharmacological agonists/antagonists, the interplay between intracellular signaling pathways, and microRNAs (miRNAs) control the initiation and activation of the TGF-ß signaling pathway. It has been proposed that the expression profiles of tumor suppressor and oncogenic TGF-ß miRNAs may be used for the classification, diagnosis, and prognosis of human malignancies. Deregulated miRNAs and aberrant activation of TGF-ß signaling are frequently found in human colorectal cancers (CRCs), but a little is known about their mechanisms of action in the development and progression of colorectal carcinoma. This review summarizes the current knowledge of the role of TGF-ß signaling regulatory miRNAs in the pathogenesis of CRC for a better understanding and hence better management of this disease.
RESUMEN
Crocin is the major component of saffron, which is used in phytomedicine for the treatment of several diseases including diabetes, fatty liver, depression, menstruation disorders, and, of special interest in this review, inflammatory diseases. Promising selective anti-inflammatory properties of this pharmacological active component have been observed in several studies. Saffron has been shown to exert anti-inflammatory properties against several inflammatory diseases and can be used as a novel therapeutic agent for the treatment of inflammatory diseases either alone or in combination with other standard anti-inflammatory agents. This review summarizes the protective role of saffron and its pharmacologically active constituents in the pathogenesis of inflammatory diseases including digestive diseases, dermatitis, asthma, atherosclerosis, and neurodegenerative diseases for a better understanding and hence a better management of these diseases.
RESUMEN
Adenosine and its analogs are of particular interest as potential therapeutic agents for treatment of cardiovascular diseases (CVDs). A2 adenosine receptor subtypes (A2a and A2b) are extensively expressed in cardiovascular system, and modulation of these receptors using A2 adenosine receptor agonists or antagonists regulates heart rate, blood pressure, heart rate variability, and cardiovascular toxicity during both normoxia and hypoxia conditions. Regulation of A2 adenosine receptor signaling via specific and novel pharmacological regulators is a potentially novel therapeutic approach for a better understanding and hence a better management of CVDs. This review summarizes the role of pharmacological A2 adenosine receptor regulators in the pathogenesis of CVDs.
Asunto(s)
Agonistas del Receptor de Adenosina A2/uso terapéutico , Antagonistas del Receptor de Adenosina A2/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Sistema Cardiovascular/efectos de los fármacos , Receptores de Adenosina A2/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Agonistas del Receptor de Adenosina A2/efectos adversos , Antagonistas del Receptor de Adenosina A2/efectos adversos , Animales , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Humanos , Terapia Molecular Dirigida , Receptores de Adenosina A2/metabolismo , Resultado del TratamientoRESUMEN
Aberrant microRNA (miR) expression is implicated in multiple human malignancies. miR-21, acting as a proto-oncogene, is involved in a variety of cellular processes and tumorigenesis and is frequently overexpressed in some cancer types. Several tumor suppressors, metastatic, and apoptotic genes have been identified as miR-21 targets, including Ras homolog gene family member B, PTEN, Sprouty2, programmed cell death 4, Integrin-ß4, and E-cadherin thereby regulating tumor growth, invasion, and metastasis. There is a growing evidence that miR-21 expression is associated with clinical outcomes in patients with colorectal cancer (CRC). In this review, we summarize the potential diagnostic, prognostic, and therapeutic values of miR-21 in CRC progression for a better understanding and hence a better management of this disease.
Asunto(s)
Proliferación Celular/genética , Neoplasias del Colon/genética , MicroARNs/genética , Pronóstico , Apoptosis/genética , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Fosfohidrolasa PTEN/genética , Proto-Oncogenes Mas , Proteína de Unión al GTP rhoB/genéticaRESUMEN
Prostate cancer is a major cause of cancer-related death in males. Wnt/ß-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Wnt/antagonistas & inhibidores , Vía de Señalización Wnt/efectos de los fármacos , Animales , Humanos , Masculino , Terapia Molecular Dirigida , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Wnt/metabolismoRESUMEN
Homeobox transcript antisense intergenic RNA (HOTAIR), one of the well-known long noncoding RNAs (lncRNAs), plays an important role in initiation and development of various tumors. Elevated level of HOTAIR is associated with metastatic behavior of primary tumor and poor outcome in several cancers. Therefore, we conducted a meta-analysis to clearly measure the prognostic impact of HOTAIR in patients with digestive system carcinomas. Fourteen studies including 2,666 patients with five different type of digestive system cancers were selected to be entered in meta-analysis. Finding demonstrated that HOTAIR overexpression could predict unfavorable outcome in digestive system carcinomas (hazard ratio [HR] = 2.4, 95% confidence interval [CI]: 2.0-2.9; p < 0.001; fixed-effect model). In stratified analysis, increased level of HOTAIR predicted poor overall survival in gastric cancer (HR = 2.1, 95% CI: 1.6-2.9; p < 0.001), colorectal cancer (HR = 4.1, 95% CI: 1.6-10.2; p = 0.002), esophageal squamous cell carcinoma (HR = 2.3, 95% CI: 1.7-3.0; p < 0.001), and hepatocellular carcinoma (HR = 3.4, 95% CI: 1.9-6.1; p < 0.001). Our meta-analysis results clearly support the prognostic value of HOTAIR to predict unfavorable prognostic outcomes in diverse digestive system carcinomas.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Neoplasias del Sistema Digestivo/genética , ARN Largo no Codificante/genética , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/terapia , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/patología , Neoplasias del Sistema Digestivo/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
EW-7197 is a transforming growth factor-ß type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.
Asunto(s)
Compuestos de Anilina/uso terapéutico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Colon/patología , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Triazoles/uso terapéutico , Compuestos de Anilina/farmacología , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Colon/efectos de los fármacos , Fibrosis , Inflamación/patología , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Triazoles/farmacologíaRESUMEN
The hypoxic niche of tumor leads to a tremendous increase in the extracellular adenosine concentration through alteration of adenosine metabolism in the tumor microenvironment (TME). This consequently affects cancer progression, local immune responses, and apoptosis of tumor cells. Regulatory effect of adenosine on apoptosis in TME depends on the cancer cell type, pharmacological characteristics of adenosine receptor subtypes, and the adenosine concentration in the tumor niche. Exploiting specific pharmacological adenosine receptor agonist and antagonist inducing apoptosis in cancer cells can be considered as a proper procedure to control cancer progression. This review summarizes the regulatory role of adenosine in cancer cell apoptosis for a better understanding, and hence better management of the disease.
Asunto(s)
Neoplasias/tratamiento farmacológico , Agonistas del Receptor Purinérgico P1/uso terapéutico , Antagonistas de Receptores Purinérgicos P1/uso terapéutico , Receptores Purinérgicos P1/genética , Adenosina Trifosfato/genética , Apoptosis/efectos de los fármacos , Neoplasias/genética , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacosRESUMEN
Breast cancer is the most common cause of cancer death in women and presents a serious therapeutic challenge worldwide. Traditional treatments are less successful at targeting cancer tumors, leading to recurrent treatment-resistant secondary malignancies. Oncolytic virotherapy (OV) is a novel anticancer strategy with therapeutic implications at targeting cancer cells by using mechanisms that differ from conventional therapies. Administration of OVs either alone or in combination with standard therapies provide new insights regarding the effectiveness and improvement of treatment responses for breast cancer patients. This review summarizes cellular, animal and clinical studies investigating therapeutic potency of oncolytic virotherapy in breast cancer treatment for a better understanding and hence a better management of this disease.
Asunto(s)
Neoplasias de la Mama/terapia , Viroterapia Oncolítica/tendencias , Animales , Neoplasias de la Mama/patología , Femenino , Humanos , Células Madre Neoplásicas/patología , Virus Oncolíticos/genética , Virus Oncolíticos/fisiología , Receptores Virales/metabolismo , TransgenesRESUMEN
Brain tumors are the most common form of solid tumors in children and is presently a serious therapeutic challenge worldwide. Traditional treatment with chemotherapy and radiotherapy was shown to be unsuccessful in targeting brain tumor cancer stem cells (CSCs), leading to recurrent, treatment-resistant secondary malignancies. Oncolytic virotherapy (OV) is an effective antitumor therapeutic strategy which offers a novel, targeted approach for eradicating pediatric brain tumor CSCs by utilizing mechanisms of cell killing that differ from conventional therapies. A number of studies and some clinical trials have therefore investigated the effects of combined therapy of radiations or chemotherapies with oncolytic viruses which provide new insights regarding the effectiveness and improvement of treatment responses for brain cancer patients. This review summarizes the current knowledge of the therapeutic potency of OVs-induced CSCs targeting in the treatment of brain tumors for a better understanding and hence a better management of this disease.
Asunto(s)
Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Terapia Molecular Dirigida , Células Madre Neoplásicas/patología , Viroterapia Oncolítica/tendencias , Humanos , Virus OncolíticosRESUMEN
Gastrointestinal (GI) cancers are major causes of cancer-related mortality worldwide and include malignancies of the GI tract such as the stomach, liver, pancreas, small intestine, colon, and rectum. Promising and selective anticancer effects of pharmacologically active components of saffron (Crocus sativus L.) have been shown in preclinical in vitro and in vivo studies. Saffron and its active components including crocin, crocetin, and safranal exert their anticancer effects through different mechanisms, including induction of apoptosis, influence on the cell cycle, and regulation of host immune response and anti-inflammatory activities. This review summarizes the recent literature on the chemopreventive properties of saffron in GI cancers to have a better understanding of the potential underlying mechanisms and hence the appropriate management of these malignancies.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Crocus , Neoplasias Gastrointestinales/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , HumanosRESUMEN
The angiotensin-converting enzyme (ACE) is the major regulator of the renin-angiotensin system, and it has been reported that genetic polymorphisms at this locus are associated with risk in numerous types of human cancers. In the current meta-analysis, we aimed to evaluate the association between the ACE Gene insertion/deletion (I/D) polymorphism (DD vs II) and digestive system cancer susceptibility. A total of 19 case-control studies among 3722 patients with seven different types of cancer were included in this meta-analysis. In the pooled analysis, the relationship between the ACE I/D polymorphism and digestive system cancer risk was not statistically significant (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.68-1.29; P = 0.65; random model). Furthermore, subgroup analyses by cancer type also did not reveal an association between ACE polymorphisms and colorectal cancer (OR, 1.14; 95% CI, 0.823-1.58; P = 0.43; random effect model) and gastric cancer (OR, 0.79; 95% CI, 0.51-1.22; P = 0.28; random effect model). These findings indicate that ACE polymorphisms in the digestive tract may still affect the survival of cancer patients, and future studies into the topic of effect of ACE on cancer prognosis are warranted.
Asunto(s)
Neoplasias del Sistema Digestivo/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , MasculinoRESUMEN
The Wnt signaling pathway plays a critical role in initiation, progression, invasion and metastasis of cancer. Wnt3a as a canonical Wnt ligand is strongly implicated in the etiology and pathology of a number of diseases including cancer. Depending on cancer type, Wnt3a enhances or suppresses metastasis, cell proliferation and apoptosis of cancer cells. This review summarizes the role of Wnt3a in the pathogenesis of different cancers including colorectal, prostate, hepatocellular, lung and leukemia, for promoting greater understanding and clinical management of these diseases.
Asunto(s)
Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , Proteína Wnt3A/fisiología , Apoptosis , Proliferación Celular , Humanos , Metástasis de la Neoplasia , Neoplasias/genética , Neoplasias/metabolismo , Vía de Señalización Wnt/genética , Vía de Señalización Wnt/fisiologíaRESUMEN
Increasing evidence suggests that adenosine is dysregulated in ulcerative colitis (UC), potentially affecting UC pathogenesis, diagnosis, and therapy. Dysregulation of the activity of adenosine generating enzymes including adenosine deaminase in serum of patients with acute colitis supports the role of this omnipresent metabolite in the pathogenesis of colitis. Adenosine regulates inflammatory responses including epithelial barrier hyper-permeability, myeloperoxidase activity, and neuromuscular motility in colitis, supporting the therapeutic potency of adenosine receptors agonists and antagonists in this disease. Depending upon the adenosine receptor subtype, activation or suppression of the receptor with pharmacological agonists or antagonists attenuates colitis pathological symptoms in colitis model. This review summarizes the role of adenosine receptors agonists and antagonists in the pathogenesis of colitis for a better understanding and hence a better management of this disease.