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Cancers Sep 2020This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We... (Review)
Review
This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We searched MEDLINE for articles on BRAF inhibitor resistance in patients with melanoma published since January 2010 in the following areas: (1) genetic basis of resistance; (2) epigenetic and transcriptomic mechanisms; (3) influence of the immune system on resistance development; and (4) combination therapy to overcome resistance. Common resistance mutations in melanoma are BRAF splice variants, amplification, neuroblastoma RAS viral oncogene homolog (NRAS) mutations and mitogen-activated protein kinase kinase 1/2 (MEK1/2) mutations. Genetic and epigenetic changes reactivate previously blocked mitogen-activated protein kinase (MAPK) pathways, activate alternative signaling pathways, and cause epithelial-to-mesenchymal transition. Once BRAF inhibitor resistance develops, the tumor microenvironment reverts to a low immunogenic state secondary to the induction of programmed cell death ligand-1. Combining a BRAF inhibitor with a MEK inhibitor delays resistance development and increases duration of response. Multiple other combinations based on known mechanisms of resistance are being investigated. BRAF inhibitor-resistant cells develop a range of 'escape routes', so multiple different treatment targets will probably be required to overcome resistance. In the future, it may be possible to personalize combination therapy towards the specific resistance pathway in individual patients.
PubMed: 33003483
DOI: 10.3390/cancers12102801 -
Oxidative Medicine and Cellular... 2016Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia... (Review)
Review
Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Reactive Oxygen Species; Salvia miltiorrhiza
PubMed: 27579153
DOI: 10.1155/2016/5293284 -
Cureus Jun 2022Myocardial infarction (MI) is a global cause of morbidity and mortality. MI is the outcome of a chronic process termed atherosclerosis, a buildup of fatty and other... (Review)
Review
Myocardial infarction (MI) is a global cause of morbidity and mortality. MI is the outcome of a chronic process termed atherosclerosis, a buildup of fatty and other substances called plaques inside the coronary vessels, causing hardening and thickening of the arterial wall. Erythropoietin (EPO) is a pleiotropic cytokine released mainly by the kidneys in adults. Besides its well-known erythropoietic functions, EPO possesses anti-apoptotic, mitogenic, and angiogenic effects. This review aims to analyze the strength of any therapeutic or protective value of EPO on the heart and safety concerns regarding its administration in MI individuals. This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four databases (PubMed, PubMed Central, Google Scholar, and Sciences Direct) were employed to search for articles published in the last 10 years. Focused studies were relevant articles in the English language, trials, reviews, meta-analyses, and studies with a control group. Following the quality assessment process, nine studies were eligible and hence were included in the review consisting of six randomized controlled trials and three systematic reviews and meta-analyses. Contrary to preclinical studies, EPO administration did not significantly have notable effects on mortality, major adverse cardiovascular events, or infarction size reduction. Significant left ventricle ejection fraction amelioration was not appreciated either. However, EPO seems to reduce the incidence of post-MI arrhythmias.
PubMed: 35812547
DOI: 10.7759/cureus.25671 -
Cancer Treatment Reviews Nov 2022Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status.
METHODS
In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis.
RESULTS
A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 - 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I = 85 %; P = 0.009).
CONCLUSIONS
Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.
Topics: Female; Humans; Mitogen-Activated Protein Kinase Kinases; Ovary; Peritoneal Neoplasms; Protein Kinase Inhibitors
PubMed: 36063572
DOI: 10.1016/j.ctrv.2022.102458 -
Chinese Medical Journal Jul 2017Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and... (Review)
Review
BACKGROUND
Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and reduced T-cell mitogen proliferative responses. GS is difficult to diagnose preoperatively due to its rarity and lack of typical symptoms, the characteristics of Chinese GS patients are still lacking. This study aimed to systematically review all the clinical, laboratory, and immunologic findings of reported cases of Chinese patients with GS.
METHODS
We searched for case reports and articles up to January 2017 using PubMed, China National Knowledge Infrastructure, Wangfang database and China Science and Technology Journal Database with the following words in combinations as key words: "thymoma," "hypogammaglobulinemia," and "Good's syndrome." The text words and MeSH terms were entered depending on the databases characteristics. The reference lists from retrieved articles were also screened for additional applicable studies. The authors were restricted to Chinese. There was no language restriction.
RESULTS
Forty-seven patients were reported in 27 studies. We found that GS has a nationwide distribution and that most cases (83%) have been described on the mainland of China. The initial clinical presentation is varied, ranging from symptoms related to the thymoma to infections resulting from immunodeficiency. Type AB (50%) is the most common histologic type of thymomas in Chinese GS patients according to the World Health Organization classification of thymomas. With respect to infection, sinopulmonary infection (74%) is the most common type, followed by skin infection (10%) and intestinal tract infection (10%). Diarrhea was presented in 36% of patients, and autoimmune manifestations were presented in 36% of patients.
CONCLUSIONS
GS is a rare association of thymoma and immunodeficiency with a poor prognosis. Astute clinical acumen and increased awareness of the clinical and immunological profile of GS are needed to increase early diagnosis, that would benefit improved therapeutic effects.
Topics: Agammaglobulinemia; Animals; China; Humans; Immunologic Deficiency Syndromes; Rare Diseases; Thymoma; Thymus Neoplasms
PubMed: 28639577
DOI: 10.4103/0366-6999.208234 -
Molecular Syndromology Feb 2022Noonan syndrome spectrum disorders are a group of phenotypically related conditions, resembling Noonan syndrome, caused by germline pathogenic variants in genes within... (Review)
Review
Noonan syndrome spectrum disorders are a group of phenotypically related conditions, resembling Noonan syndrome, caused by germline pathogenic variants in genes within the Ras/mitogen-activated protein kinase (Ras/MAPK) signalling pathway. Lymphatic dysplasia with a clinical lymphatic abnormality is one of the major features. We performed a systematic review to get more insight in (1) the prevalence of clinically lymphatic abnormalities in patients with a genetically proven Noonan syndrome spectrum disorder, (2) if a genotype-lymphatic phenotype relation can be found and describe the clinical presentation and course of the lymphatic abnormality. Most studies report patients with Noonan syndrome. Prenatally, the prevalence of increased nuchal translucency differs from 7% in patients with pathogenic variant to 38% in patients with pathogenic variants, and the prevalence of pleural effusions differed from 7% in patients with pathogenic to 29% in patients with pathogenic variants. Postnatally, the prevalence of lymphedema differs from 16% in patients with pathogenic variants to 44% in patients with pathogenic variants, and the prevalence of acquired chylothorax is 4% in patients with pathogenic variants. Lymphatic abnormalities do occur in patients with cardiofaciocutaneous syndrome and Costello syndrome. In conclusion, Noonan syndrome spectrum disorders, Noonan syndrome in particular, are associated with lymphatic abnormalities. Combining the available published literature about genetically proven Noonan syndrome spectrum disorders, it appears likely that the lifetime prevalence of these abnormalities in Noonan syndrome is higher than the 20% that were generally accepted so far. This is increasingly important, because the activation of the RAS/MAPK pathway can be inhibited by RAS/MAPK inhibitors, and clinically severe lymphatic abnormalities may improve.
PubMed: 35221870
DOI: 10.1159/000517605 -
Journal of Ethnopharmacology Jan 2023Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt,... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt, Arabia, Greece, and China, PEOs were traditional used in aromatherapy for various health disorders, including pain and inflammation.
AIM OF THE STUDY
In this review, we provide an overview of the anti-inflammatory effects of PEOs and the underlying mechanisms associated with anti-inflammatory effects using in vitro and in vivo models. Further, clinical trials associated with PEOs were explored.
MATERIALS AND METHODS
The literature search was performed using various web-based tools and databases like Google Scholar, Web of Science, PubMed, CNKI and SCOPUS. The keywords used for conducting the literature review were general terms like "essential oils" followed by (AND) the subject of interest like "in vitro and/or in vivo anti-inflammatory models," "inflammatory response," "inflammatory indicators," "pro-inflammatory cytokines," "signaling pathway," "anti-inflammatory mechanism," "toxicology and side effects" and "clinical trials." The articles selected were published between 2017 and 2022. The articles prior to 2017 were only considered if they were associated with molecular mechanisms or signaling pathways involved in the inflammatory responses.
RESULTS
In vitro and in vivo inflammation models have been used to study the anti-inflammatory effects of 48 PEOs. Studies have reported that PEOs targets and inhibit multiple dysregulated signaling pathways associated with inflammation, including Toll-like receptors, nuclear transcription factor-κ B, mitogen-activated protein kinases, Nod-like receptor family pyrin domain containing 3, and auxiliary pathways like the nuclear factor erythroid 2-related factor 2/antioxidant response element and Janus kinase/signal transducers and activators of transcription) signaling pathways.
CONCLUSION
PEOs extracted from different plant materials had varied qualitative and quantitative compositions of biologically active compounds. Different anti-inflammatory potentials and different molecular signal transduction have been attributed to PEOs-derived bioactive compounds with different chemical structures. The data on therapeutic efficacy and the long-term side effects of PEOs as an anti-inflammatory drug are still unknown due to the lack of clinical trials on PEOs. There is still insufficient evidence to draw conclusions on anti-inflammatory properties of PEOs without promising outcomes from clinical trials.
Topics: Humans; Oils, Volatile; Plant Oils; Anti-Inflammatory Agents; Cytokines; Inflammation; NF-kappa B; Plant Extracts
PubMed: 36252876
DOI: 10.1016/j.jep.2022.115829 -
Pharmaceuticals (Basel, Switzerland) Oct 2022(C.) belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. berries have been used for... (Review)
Review
(C.) belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. berries have been used for centuries in traditional medicine. Recent studies have revealed that not only the berries but also the leaves have relevant antioxidant, antiproliferative, and anti-inflammatory properties, bringing this plant to the forefront of discussion. A systematic review of the literature was carried out to summarize the phenolic compounds and bioactive properties identified in berries and leaves and to search for research gaps on this topic. The search was conducted in three electronic databases (PubMed, SCOPUS, and Web of Science) using PRISMA methodology. The inclusion criteria were the chemical compositions of the berries, leaves, or their extracts and their bioactive properties. The exclusion criteria were agronomic and archaeological research. The number of studies concerning phenolic compounds' composition and the bioactive properties of berries and leaves is still limited (11 articles). However, the variety of polyphenolic compounds identified make it possible to infer new insights into their putative mechanism of action towards the suppression of NF-kB transcription factor activation, the modulation of inflammatory mediators/enzymes, the induction of apoptosis, the modulation of mitogen activated protein kinase, cell cycle arrest, and the reduction of oxidative stress. These factors can be of major relevance concerning the future use of as nutraceuticals, food supplements, or medicines. Nevertheless, more scientific evidence concerning bioactivity is required.
PubMed: 36297345
DOI: 10.3390/ph15101231 -
Current Pharmaceutical Biotechnology Jan 2024Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
BACKGROUND
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
OBJECTIVES
This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs.
METHODS
This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel.
RESULTS
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs.
CONCLUSION
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.
PubMed: 38310454
DOI: 10.2174/0113892010281821240102105415 -
Pharmacology, Biochemistry, and Behavior Feb 2023Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are... (Review)
Review
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Topics: Humans; Ketamine; Depression; Depressive Disorder, Major; Systems Biology; Antidepressive Agents; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 36731751
DOI: 10.1016/j.pbb.2023.173523