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The International Journal of Biological... May 2016PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers.
AIMS
In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis.
METHODS
First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTS
Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = -0.271*; p<0.02) and grade (r = -0.228*; p<0.02) of HNC tissues. Furthermore, the expression variations of PTEN were correlated with the expression pattern of the proliferation marker Ki-67. Significantly (p<0.008) upregulated expression of Ki-67 was observed in HNC patients compared with adjacent normal-tissue controls This upregulation of Ki-67 was confirmed at the protein level by immunohistochemistry in HNC patients. When Spearman's correlation was carried out a significant negative correlation was observed between PTEN and Ki-67 (r = -0.230*; p<0.03).
CONCLUSIONS
Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.
Topics: Biomarkers, Tumor; Carcinogenesis; Cell Proliferation; Female; Head and Neck Neoplasms; Humans; Ki-67 Antigen; Male; Middle Aged; PTEN Phosphohydrolase
PubMed: 26916897
DOI: 10.5301/jbm.5000196 -
Journal of Diabetes Research 2020The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM.
METHODS
We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0.
RESULTS
Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD = -1.20, 95% CI -1.91 to -0.49, = 0.0009) and increase fasting C-peptide levels (MD = 0.25, 95% CI 0.04 to 0.45, = 0.02) and AUCC (SMD = 0.66, 95% CI 0.13 to 1.18, = 0.01). Stem cell therapy could also reduce insulin dosages (SMD = -2.65, 95% CI -4.86 to -0.45, = 0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, = 0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, = 0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, < 0.00001).
CONCLUSION
Stem cell therapy for T1DM may improve glycemic control and cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.
Topics: Area Under Curve; C-Peptide; Diabetes Mellitus, Type 1; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Risk; Stem Cell Transplantation; Treatment Outcome
PubMed: 33102605
DOI: 10.1155/2020/5740923 -
International Journal of Molecular... Jun 2016Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next... (Review)
Review
Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs.
Topics: Amino Acids; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteria; Gramicidin; Lipid Bilayers; Peptides; Protein Structure, Secondary
PubMed: 27376281
DOI: 10.3390/ijms17071023 -
BMC Cancer Nov 2017Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected... (Review)
Review
BACKGROUND
Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected to be involved in this type of tumorigenesis, as supported by an accumulating body of research evidence. However, little is known about how mitochondrial alterations contribute to tumorigenesis. Mitochondrial biogenesis is a fundamental cellular process required to maintain functional mitochondria and as an adaptive mechanism in response to changing energy requirements. Mitochondrial biogenesis is regulated by peroxisome proliferator-activated receptor gamma coactivator 1-α (PPARGC1A or PGC1α). In this paper, we report a systematic review to summarize current evidence on the role of PGC1α in the initiation and progression of CRC. The aim is to provide a basis for more comprehensive research.
METHODS
The literature search, data extraction and quality assessment were performed according to the document Guidance on the Conduct of Narrative Synthesis in Systematic Reviews and the PRISMA declaration.
RESULTS
The studies included in this review aimed to evaluate whether increased or decreased PGC1α expression affects the development of CRC. Each article proposes a possible molecular mechanism of action and we create two concept maps.
CONCLUSION
Our systematic review indicates that altered expression of PGC1α modifies CRC risk. Most studies showed that overexpression of this gene increases CRC risk, while some studies indicated that lower than normal expression levels could increase CRC risk. Thus, various authors propose PGC1α as a good candidate molecular target for cancer therapy. Reducing expression of this gene could help to reduce risk or progression of CRC.
Topics: Animals; Carcinogenesis; Colorectal Neoplasms; Evaluation Studies as Topic; Gene Expression Regulation, Neoplastic; Humans; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Risk Factors
PubMed: 29121859
DOI: 10.1186/s12885-017-3725-3 -
PloS One 2015The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers.
METHODS
We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated.
RESULTS
A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001) and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) = 1.895, 95% CI: 1.364-2.632, P < 0.001) and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis.
CONCLUSION
Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.
Topics: Digestive System Neoplasms; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Phosphoproteins; STAT3 Transcription Factor; Survival Rate
PubMed: 26024373
DOI: 10.1371/journal.pone.0127356 -
Cancer Control : Journal of the Moffitt... 2021Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features.
METHODS
Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle-Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data.
RESULTS
A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, =.008; = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, < .001; = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, < .001; = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer.
CONCLUSION
For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.
Topics: Humans; Neoplasm Staging; Neoplasms; Protein-Arginine N-Methyltransferases; Survival Analysis
PubMed: 34758643
DOI: 10.1177/10732748211050583 -
Acta Ophthalmologica Nov 2021To assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations.
PURPOSE
To assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations.
METHODS
We reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in general population using gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of the variants in gnomAD, including its subpopulations.
RESULTS
We found 13 missense and 5 loss-of-function (LOF) reported variants in MYOC that were both probable pathogenic or risk variants and listed in gnomAD. Six likely pathogenic missense variants were p.(Cys25Arg), p.(Gln48His), p.(Gly326Ser), p.(Thr353Ile), p.(Thr377Met) and p.(Gly399Val). They were most prevalent in East and South Asia (frequency, 0.92% and 0.81%, respectively). The most common missense variants were p.(Thr353Ile) (0.91% in East Asia) and p.(Gln48His) (0.79% in South Asia). Five LOF variants were p.(Arg46Ter), p.(Arg91Ter), p.(Arg272Ter), p.(Gln368Ter) and p.(Tyr453MetfsTer11). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.93% and 0.33%, respectively).
CONCLUSION
Pathogenic MYOC variants appear to be population-associated. Our results highlight allelic heterogeneity of MYOC variants in open-angle glaucoma. Many of the probable pathogenic variants are over-represented in some of the populations causing doubt of their status as monogenic disease-causing variants.
Topics: Cytoskeletal Proteins; DNA; Eye Proteins; Gene Expression Regulation; Glaucoma; Global Health; Glycoproteins; Humans; Population Surveillance; Prevalence
PubMed: 33421356
DOI: 10.1111/aos.14738 -
Cells Feb 2020Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is...
Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell-cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.
Topics: Animals; Disease Progression; Glycosylation; Humans; Neoplasm Metastasis; Neoplasms; Polysaccharides; Protein Processing, Post-Translational
PubMed: 32075174
DOI: 10.3390/cells9020446 -
Cancer Treatment Reviews Sep 2021Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.
METHODS
Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.
RESULTS
Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).
CONCLUSION
The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
Topics: B7-H1 Antigen; Breast Neoplasms; Female; Humans; Neoplasm Metastasis
PubMed: 34237488
DOI: 10.1016/j.ctrv.2021.102257 -
Frontiers in Endocrinology 2021To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes.
METHODS
All literature from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Clinical Trials was searched, and the language was limited to English. Two reviewers independently assessed study eligibility, continuous data extraction, and independent assessment of bias risk. Our primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels, while our secondary outcomes were high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, body weight, BMI, and fasting glucose and glycosylated hemoglobin (HbA1c) levels.
RESULTS
The review identified 20 eligible trials that met the inclusion criteria. We found that, compared to other drugs, thiazolidinediones, especially pioglitazone, had a greater effect on the levels of ALT (-8.01 (95% CI -14.3 to 2.02)) and AST (-5.0 (95% CI -9.21 to -1,22)) and other biological indicators, but they were also associated with an increased risk of weight gain (3.62 (95% CI 2.25 to 4.99) and increased BMI (0.59 (95% Cl -0.13 to 1.29). GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.
CONCLUSION
Despite the significant risk of weight gain, thiazolidinediones, especially pioglitazone, are beneficial in normalizing liver and glucose metabolism in NAFLD patients. In clinical practice, we believe that GLP1 RAs such as liraglutide and exenatide or metformin can be used in combination to offset the risk of weight gain associated with thiazolidinediones. However, long-term studies are still needed to verify the efficacy and safety of individual hypoglycemic agents.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42020212025].
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bayes Theorem; Blood Glucose; Body Mass Index; Body Weight; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Glycated Hemoglobin; Glycosylation; Humans; Hypoglycemic Agents; Lipoproteins, HDL; Lipoproteins, LDL; Metformin; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Reproducibility of Results; Risk; Treatment Outcome
PubMed: 33841337
DOI: 10.3389/fendo.2021.649018