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Indian Journal of Dental Research :... 2017The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic... (Review)
Review
BACKGROUND
The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic cells. A better understanding of this contrasting behavior was provided in the early 1990s with the discovery of a relationship between telomeres, telomerase, aging, and cancer. Telomeres (tandem repeat DNA sequence TTAGGG) are protective caps at the ends of human chromosomes. Normal human cells experience telomere shortening with each successive cell division. However, in tumor cells, an overexpression of telomerase confers limitless replicative potential to tumor cells by continuous elongation of telomeres. The objective of this review was to systematically assess the data available on telomerase expression in oral cancer, with special reference to its role in diagnosis, prognosis, and treatment.
MATERIALS AND METHODS
A systematic review of studies that investigated the telomerase expression in oral squamous cell carcinoma (OSCC) was registered with PROSPERO. Subsequent to registration, a predetermined search strategy in accordance with PRISMA guidelines was formulated, and a literature search was conducted using online databases along with hand searching.
RESULTS
Eighty-nine articles from PubMed, 83 from Scopus, 5 from BioMed Central, 43 from Google Scholar, and 2 from hand search were identified. A total of 21 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for the markers under study, type of sample used, study design/methodology, and statistical analysis. The studies were then grouped into three subheads depending on their implications in the diagnosis, prognosis, and treatment of OSCC.
CONCLUSION
This review explains the basic biology and the clinical implications of telomerase-based diagnosis and prognosis, the prospects for its use in anticancer therapy, in the context of oral cancer.
Topics: Carcinoma, Squamous Cell; Cell Proliferation; Humans; Mouth Neoplasms; Prognosis; Telomerase; Telomere
PubMed: 29072223
DOI: 10.4103/ijdr.IJDR_690_16 -
Molecular Medicine Reports May 2022The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in...
The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in and studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were and/or studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full‑text published studies, 11 were full‑text reviews, 10 structure‑based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age‑related diseases. However, further and studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.
Topics: Aging; Enzyme Inhibitors; Humans; Neoplasms; Telomerase; Telomere
PubMed: 35266017
DOI: 10.3892/mmr.2022.12674 -
European Journal of Cancer (Oxford,... Sep 2023The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and ii) whether anthracyclines could be excluded.
METHODS
A systematic literature search in Medline, Embase and Web of Science databases was performed. Studies had to satisfy the following criteria: i) randomised controlled trials (RCTs), ii) enroled patients treated preoperatively for HER2-positive BC (breast cancer), iii) at least one treatment group received an anti-HER2 agent, iv) available information of any efficacy end-point and v) published in English. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR), event-free survival (EFS) and overall survival (OS) were the efficacy end-points of interest, and selected safety end-points were also analysed.
RESULTS
A total of 11,049 patients with HER2-positive BC (46 RCTs) were included in the network meta-analysis, and 32 different regimens were evaluated. Dual anti-HER2-therapy, with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab and chemotherapy in terms of pCR, EFS and OS. However, a higher risk of cardiotoxicity was observed with dual anti-HER2-therapy. Anthracycline-based chemotherapy was not associated with better efficacy outcomes in comparison with non-anthracycline-based chemotherapy. In anthracycline-free regimens, the addition of carboplatin presented numerically better efficacy outcomes.
CONCLUSION
Dual HER2 blockade with chemotherapy is the recommended choice as neoadjuvant therapy for HER2-positive breast cancer, preferably by omitting anthracyclines in favour of carboplatin.
Topics: Humans; Female; Neoadjuvant Therapy; Carboplatin; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Antibiotics, Antineoplastic; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37142539
DOI: 10.1016/j.ejca.2023.03.042 -
Nutrients Nov 2022Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal... (Review)
Review
BACKGROUND
Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal remodelling process favouring bone resorption. Various natural compounds can positively influence the skeletal remodelling process, of which naringenin is a candidate. Naringenin is an anti-inflammatory and antioxidant compound found in citrus fruits and grapefruit. This systematic review aims to present an overview of the available evidence on the skeletal protective effects of naringenin.
METHOD
A systematic literature search was conducted using the PubMed and Scopus databases in August 2022. Original research articles using cells, animals, or humans to investigate the bone protective effects of naringenin were included.
RESULTS
Sixteen eligible articles were included in this review. The existing evidence suggested that naringenin enhanced osteoblastogenesis and bone formation through BMP-2/p38MAPK/Runx2/Osx, SDF-1/CXCR4, and PI3K/Akt/-Fos/-Jun/AP-1 signalling pathways. Naringenin also inhibited osteoclastogenesis and bone resorption by inhibiting inflammation and the RANKL pathway.
CONCLUSIONS
Naringenin enhances bone formation while suppressing bone resorption, thus achieving its skeletal protective effects. It could be incorporated into the diet through fruit intake or supplements to prevent bone loss.
Topics: Humans; Animals; Phosphatidylinositol 3-Kinases; Flavanones; Osteogenesis; Bone Resorption
PubMed: 36432535
DOI: 10.3390/nu14224851 -
Critical Reviews in Oncology/hematology Jun 2023The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no... (Review)
Review
BACKGROUND AND AIMS
The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no response to this neoadjuvant chemoradiotherapy. This systematic review aimed to identify biomarkers of innate radioresistant rectal cancer.
METHOD
Through a systematic literature search, 125 papers were included and analyzed using ROBINS-I, a Cochrane risk of bias tool for non-randomized studies of interventions. Both statistically significant and nonsignificant biomarkers were identified. Biomarkers mentioned more than once in the results or biomarkers with a low or moderate risk of bias were included as the final results.
RESULTS
Thirteen unique biomarkers, three genetic signatures, one specific pathway, and two combinations of two or four biomarkers were identified. In particular, the connection between HMGCS2, COASY, and PI3K-pathway seems promising. Future scientific research should focus on further validating these genetic resistance markers.
Topics: Humans; Phosphatidylinositol 3-Kinases; Chemoradiotherapy; Rectal Neoplasms; Neoadjuvant Therapy; Biomarkers, Tumor; Treatment Outcome; Neoplasm Staging
PubMed: 37059272
DOI: 10.1016/j.critrevonc.2023.103991 -
PloS One 2017Phosphorylated mammalian target of rapamycin (p-mTOR) is a promising prognostic marker in many types of cancer. However, its survival benefit in patients with breast... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Phosphorylated mammalian target of rapamycin (p-mTOR) is a promising prognostic marker in many types of cancer. However, its survival benefit in patients with breast carcinoma remains unknown. The aim of the present study was to assess the relationship between p-mTOR expression and prognosis in breast carcinoma based on a systematic review and meta-analysis.
MATERIALS AND METHODS
Electronic databases (including Pubmed, Embase, ISI web of science, and Cochrane Library) were searched up to November 24, 2015. The outcome measures were hazard ratios (HRs) with 95% confidence interval (CI) for the association between the prognosis of breast carcinoma patients and p-mTOR expression. Primary end points were disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS). Statistical analysis was performed with STATA 12.0.
RESULTS
Nine cohort studies including 3051 patients met full eligibility criteria. The pooled HRs (95% CI) for OS, DFS, and RFS were 0.84 (0.27-2.63), 0.71 (0.40-1.23), and 0.48 (0.20-1.18), respectively.
CONCLUSIONS
Our findings suggested that p-mTOR overexpression was not significantly related to prognosis in breast carcinoma regarding OS and disease recurrence. Prospective studies are warranted to examine the association between p-mTOR expression and survival outcomes in breast carcinoma.
Topics: Breast Neoplasms; Female; Humans; Survival Analysis; TOR Serine-Threonine Kinases
PubMed: 28114374
DOI: 10.1371/journal.pone.0170302 -
Nephrology, Dialysis, Transplantation :... Jun 2023Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects.
METHODS
We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible.
RESULTS
There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91-1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70-1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49-40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04-2.46)].
CONCLUSION
In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.
Topics: Humans; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Receptors, Vascular Endothelial Growth Factor; Diabetic Retinopathy; Hypertension; Proteinuria
PubMed: 36318455
DOI: 10.1093/ndt/gfac305 -
Oncotarget Aug 2016mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to... (Meta-Analysis)
Meta-Analysis Review
mTOR regulates several cellular processes that are critical for tumorigenesis. However, previous studies on the association of mTOR polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed a systematic review and updated meta-analysis of the available evidence regarding the relationship between mTOR single nucleotide polymorphisms (SNPs) and cancer risk. Up to November 2015, 23 original publications were identified covering 20 mTOR SNPs, of which seven SNPs (rs2536, rs2295080, rs1883965, rs1034528, rs17036508, rs3806317 and rs1064261) were included in the final meta-analysis. We estimated the summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for mTOR polymorphisms and cancer risk, and used the model-free approach to investigate the biological effect of each polymorphism. Our meta-analysis found that rs1883965, rs1034528, and rs17036508 were correlated with increased cancer risk in the complete over-dominant model (rs1883965 GA versus GG/AA: fixed-effects OR=1.15, 95% CI 1.02-1.29; rs1034528 GC versus GG/CC: fixed-effects OR=1.30, 95% CI 1.13-1.48; rs17036508 TC versus CC/TT: fixed-effects OR=1.23, 95% CI 1.06-1.43). Stratifying analyses by cancer type, we found that the rs2295080 G allele was associated with a significantly higher risk of acute leukemia in the recessive model (GG versus GT/TT: fixed-effects OR=2.08, 95% CI 1.34-3.22) and a lower risk of genitourinary cancers in the dominant model (TG/GG versus TT: fixed-effects OR=0.77, 95% CI 0.68-0.86). Interestingly, further expression analysis showed that homozygous variant genotype carriers of rs1883965, rs1034528 and rs17036508 had lower mTOR transcript levels, based on HapMap data.
Topics: Alleles; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genotype; Humans; Neoplasms; Odds Ratio; Polymorphism, Single Nucleotide; TOR Serine-Threonine Kinases
PubMed: 27462867
DOI: 10.18632/oncotarget.10805 -
Eye (London, England) Jan 2023This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related... (Meta-Analysis)
Meta-Analysis Review
This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections.
Topics: Humans; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Clinical Protocols; Intravitreal Injections; Treatment Outcome; Recombinant Fusion Proteins; Wet Macular Degeneration; Randomized Controlled Trials as Topic
PubMed: 35396574
DOI: 10.1038/s41433-022-02020-7 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692