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Osteoarthritis and Cartilage Mar 2023To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes. (Review)
Review
OBJECTIVE
To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes.
METHOD
PubMed, EMBASE and Web of Science databases were searched up to 19 September 2021 to identify in vitro studies exploring ultrasound to stimulate chondrocytes for osteoarthritis (OA) treatment. Study characteristics, ultrasound parameters, in vitro setup, and mechanotransduction pathways were collected. Risk of bias was judged using the Risk of Bias Assessment for Non-randomized Studies (RoBANS) tool.
RESULTS
Thirty-one studies were included comprising healthy and OA chondrocytes and explants. Most studies had high risk of performance, detection and pseudoreplication bias due to lack of temperature control, setup calibration, inadequate semi-quantitatively analyzes and independent experiments. Ultrasound was applied to the culture plate via acoustic gel, water bath or culture media. Regardless of the setup used, ultrasound stimulated the cartilage production and suppressed its degradation, although the effect size was nonsignificant. Ultrasound inhibited p38, c-Jun N-terminal kinases (JNK) and factor nuclear kappa B (NFκB) pathways in OA chondrocytes to reduce apoptosis, inflammation and matrix degradation, while triggered phosphoinositide-3-kinase/akt (PI3K/Akt), extracellular signal-regulated kinase (ERK), p38 and JNK pathways in healthy chondrocytes to promote matrix synthesis.
CONCLUSION
The included studies suggest that ultrasound application induces therapeutic effects on chondrocytes. However, these results should be interpreted with caution because high risk of performance, detection and pseudoreplication bias were identified. Future studies should explore the application of ultrasound on human OA chondrocytes cultures to potentiate the applicability of ultrasound towards cartilage regeneration of knee with OA.
Topics: Humans; Chondrocytes; Mechanotransduction, Cellular; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Cartilage, Articular; Osteoarthritis; Ultrasonic Therapy
PubMed: 36481451
DOI: 10.1016/j.joca.2022.07.014 -
Cancers Nov 2022The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence... (Review)
Review
The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence regarding this mutation occurrence and its association with clinical information. This systematic review and meta-analysis aim to pool the overall mutation prevalence of V600E in reported ameloblastoma cases and to determine its association with patient demographic and clinicopathological features. Following the PRISMA guidelines, a comprehensive article search was conducted through four databases (Scopus, Google Scholar, PubMed, and Web of Science). Seventeen articles between 2014 and 2022 met the inclusion criteria with 833 ameloblastoma cases. For each included study, the significance of V600E on the outcome parameters was determined using odd ratios and 95% confidence intervals. Meta-analysis prevalence of V600E in ameloblastoma was 70.49%, and a significant meta-analysis association was reported for those younger than 54 years old and in the mandible. On the contrary, other factors, such as sex, histological variants, and recurrence, were insignificant. As a result of the significant outcome of V600E mutation in ameloblastoma pathogenesis, targeted therapy formulation can be developed with this handful of evidence.
PubMed: 36428683
DOI: 10.3390/cancers14225593 -
Endocrine Journal Feb 2023Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the...
Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the rarity of rectal NETs in rectal cancer, the molecular features and the correlation with patient therapeutic response and prognosis have not been investigated in detail. In this review, we focused on the molecular features, potential therapeutic targets and prognosis of rectal NETs. By summarizing the relevant studies, we established the mutational landscape of rectal NETs and identified a series of large fragment variations. Driver genes including TP53, APC, KRAS, BRAF, RB1, CDKN2A and PTEN were found as the top mutated genes. Large fragment alterations mainly involved known driver genes, including APC, TP53, CCNE1, MYC, TERT, RB1 and ATM. Germline mutations of APC, MUTYH, MSH6, MLH1 and MSH2 associated with Lynch syndrome or FAP were also found in rectal NETs. The BRAF-V600E mutation was reported as an actionable target in rectal NETs, and the combined BRAF/MEK inhibitors were found to be effective targeting BRAF-V600E in advanced or metastatic NETs. The known prognostic risk factors of rectal adenocarcinoma, including a series of demographic and clinicopathological factors were also prognostic factors for rectal NETs. Furthermore, three types of markers, including genetic alterations, protein expression levels and methylation, were also suggested as prognostic factors for rectal NETs. In summary, we established the landscape of mutations and large-fragment alterations of rectal NETs, and identified potential therapeutic targets and a series of prognostic factors. Future studies may focus on the optimization of therapeutic strategies based on potential actionable biomarkers.
Topics: Humans; Proto-Oncogene Proteins B-raf; Neuroendocrine Tumors; Rectal Neoplasms; Mutation; Prognosis; Biomarkers, Tumor
PubMed: 36403965
DOI: 10.1507/endocrj.EJ22-0262 -
Frontiers in Endocrinology 2022The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some recent epidemiological studies have described the relationship between urinary iodine concentration (UIC) and PTC.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science for case-control studies about UIC and PTC published before September 2022. Results are presented as the overall odds ratio (OR) and 95% confidence intervals (CI).
RESULTS
According to the analysis of the included studies, excessive iodine intake (UIC≥300ug/L) was positively associated with the occurrence of PTC patients compared with healthy controls (OR4.05, 95%CI 1.64-10.02, P=0.002). Meanwhile, adequate iodine exposure (100≤UIC<200ug/L) may play a protective role in the occurrence of PTC compared with healthy individuals (OR 0.36, 95%CI 0.14-0.91, P=0.03) while the difference in the prevalence of insufficient iodine intake (UIC<100ug/L) and iodine above requirements (200≤UIC<300ug/L) among the two groups were not significant (deficiency: OR 0.38, 95%CI 0.13-1.16, P=0.09; above requirements: OR 0.92, 95%CI 0.40-2.10, P=0.84). After comparing the UIC levels of PTC patients with those of other thyroid diseases, we found that there was also no significant difference in the incidence of different levels of UIC in the two groups (excessive: OR 1.25, 95%CI 0.87-1.80, P=0.22; above requirements: OR 0.93, 95%CI 0.77-1.14, P=0.49; adequate: OR 0.96, 95%CI 0.78-1.17, P=0.67; deficiency: OR 1.02, 95%CI 0.86-1.22, P=0.80). The result of this meta-analysis also did not support the relationship between UIC and the BRAF mutation and lymph node metastasis (LNM) of PTC patients. Besides, we also found that studies on the relationship between urinary iodine and PTC may be influenced by the way UIC was measured.
CONCLUSION
The 10 case-control included studies involved a total of 6,544 participants. The results of this meta-analysis showed excessive iodine intake, that is, UIC≥300ug/L was associated with the occurrence of PTC but not with BRAF mutation and LNM while adequate iodine intake (100≤UIC<200ug/L) may be one of the protective factors for PTC.
Topics: Humans; Thyroid Cancer, Papillary; Iodine; Proto-Oncogene Proteins B-raf; Thyroid Diseases; Lymphatic Metastasis; Thyroid Neoplasms
PubMed: 36387866
DOI: 10.3389/fendo.2022.1049423 -
BMC Complementary Medicine and Therapies Sep 2022Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction,...
BACKGROUND AND OBJECTIVE
Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS.
METHODS
First, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes.
RESULTS
Twelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets.
CONCLUSIONS
ICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS.
Topics: Animals; Female; Flavonoids; Humans; Ischemic Stroke; Male; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PubMed: 36180911
DOI: 10.1186/s12906-022-03732-9 -
World Journal of Gastroenterology Sep 2022Chronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear.
AIM
To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG.
METHODS
We systematically searched 3 English (PubMed, Embase, Medline) and 4 Chinese databases (Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG.
RESULTS
Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that: (1) SLBZS was superior to conventional therapies [risk ratio (RR): 1.29, 95% confidence interval (CI): 1.21 to 1.37, < 0.00001]; (2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval (95%CI): 0.11 to 0.55, = 0.0007] in terms of recurrence rate and reversal of positivity (RR: 1.20, 95%CI: 1.11 to 1.30, < 0.00001); and (3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others.
CONCLUSION
SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.
Topics: Drugs, Chinese Herbal; ErbB Receptors; Gastritis; Humans; Language; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt
PubMed: 36156925
DOI: 10.3748/wjg.v28.i33.4890 -
Cancer Treatment Reviews Nov 2022The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis.
BACKGROUND
The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA).
METHODS
A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted.
RESULTS
A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints.
CONCLUSIONS
This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Benzimidazoles; Carbamates; Humans; Melanoma; Mutation; Neoplasms, Second Primary; Network Meta-Analysis; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Sulfonamides; Vemurafenib
PubMed: 36099854
DOI: 10.1016/j.ctrv.2022.102463 -
Genetics Research 2022Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study is a meta-analysis undertaken to estimate the prognosis and survival associated with , , , , , and genes among CRC patients.
METHODS
The authors searched PubMed, EMBASE, and Science Direct for relevant reports published between 2000 and 2020 and analyzed them to determine any relationship between the (immunohistochemically/sequencing-detected) gene expression and variants of the selected genes and the survival of CRC patients.
RESULTS
The analysis included 34,074 patients from 64 studies. To evaluate association, hazard ratios (HRs) were estimated for overall survival (OS) or disease-free survival (DFS), with a 95% confidence interval (CIs). Pooled results showed that overexpression, mutation, or 4 loss of expression, mutations, and expression were associated with shorter OS. overexpression (HR: 0.137 (95% CI: 0.131-0.406)), loss of expression of or 4 (HR: 0.449 (95% CI: 0.146-0.753)), the mutations of (HR: 0.179 (95% CI: 0.126-0.485)), and expression (HR: 0.485 (95% CI: 0.772-0.198)) also presented risk for shorter DFS.
CONCLUSIONS
The present meta-analysis indicates that overexpression or underexpression and variants of , , 4, , and genes potentially acted as unfavorable biomarkers for the prognosis of CRC. The gene was not associated with prognosis.
Topics: Colorectal Neoplasms; Cyclin D1; Genes, bcl-1; Humans; Prognosis; Smad3 Protein; Tumor Suppressor Protein p53; beta Catenin
PubMed: 36072013
DOI: 10.1155/2022/5338956 -
JCO Precision Oncology Aug 2022Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.
METHODS
We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival.
RESULTS
A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors.
CONCLUSION
This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Topics: Humans; Lung Neoplasms; Melanoma; Mitogen-Activated Protein Kinases; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; United States
PubMed: 35977349
DOI: 10.1200/PO.22.00107 -
Medicina (Kaunas, Lithuania) Jun 2022Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic... (Meta-Analysis)
Meta-Analysis Review
Background: Signet ring cell carcinoma (SC) accounts for 1% of total colorectal cancer (CRC) cases and is associated with aggressive behaviors, such as lymphatic invasion and distant metastases, resulting in poor prognosis. To date, there is still a lack of consensus on the genetic etiology underpinning this cancer subtype. This study aimed to clarify the molecular associations of SC by using meta-analysis and a systematic review. Methods: PubMed, Embase, and Cochrane Library were searched for studies evaluating the KRAS, BRAF, P53 statuses, and microsatellite instability (MSI) in CRC patients with different histological subtypes, including SC. The diagnosis of SC is defined as the signet ring cells comprising ≥50 percent of the tumor mass. By dividing the studies into subgroups based on the composition of control groups, such as classic adenocarcinoma (AC; no SC components) and non-SC (including those with SC components < 50%), the relative risk (RR) of molecular alterations for SC in each study were pooled using a random-effects model. Two reviewers identified trials for inclusion, assessed quality, and extracted data independently. Results: Data from 29 studies consisting of 9366 patients were included in this analysis. SC was associated positively with MSI (RR 1.78, 95% CI 1.34 to 2.37; 95% CI 0.77 to 4.15; p = 0.0005), BRAF mutation (RR 1.99, 95% CI 1.21 to 3.26; 95%CI 0.68 to 5.82; p = 0.0146), and negatively with KRAS mutation (RR 0.48, 95% CI 0.29 to 0.78; 95% CI 0.09 to 2.49; p = 0.0062). No association was found between SC and P53 expression (RR 0.92, 95% CI 0.76 to 1.13; 95%CI 0.61 to 1.39; p = 0.3790). Moreover, it was associated negatively with P53 gene mutations (RR 0.92, 95% CI 0.77 to 1.09; 95% CI 0.46 to 1.82; p = 0.1568), and P53 protein (RR 0.93, 95% CI 0.58 to 1.49; 95% CI 0.40 to 2.17; p = 0.6885). Conclusions: The molecular etiology of SC may be associated with the BRAF and MSI pathways. Its features, such as the high frequency of BRAF mutation, could partly explain its less favorable outcomes and limited effects of traditional chemotherapy.
Topics: Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Humans; Microsatellite Instability; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Tumor Suppressor Protein p53
PubMed: 35888555
DOI: 10.3390/medicina58070836