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Archives of Gerontology and Geriatrics Oct 2023Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound... (Review)
Review
Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound healing, tissue regeneration, and prevention of tissue fibrosis. Despite the short-term benefits of CS, accumulation of senescent cells has deleterious effects and is associated with several pathological age-related phenotypes. As Heat Shock Proteins (HSP) are associated with cyto-protection, their role in longevity and CS became a research interest. However, an overview of the relationship between HSP and CS in humans still lacks in the literature. To provide an overview of the current state of the literature, this systematic review focused on the role of HSP in the development of CS in humans. PubMed, Web of Science and Embase were systematically screened for studies on the relationship between HSP and CS in humans. A total of 14 articles were eligible for inclusion. The heterogeneity and lack of numerical reporting of outcomes obstructed the conduction of a meta-analysis. The results consistently show that HSP depletion results in increased CS, while overexpression of HSP decreases CS, whether in cancer, fibroblasts, or stem cell lines. This systematic review summarized the literature on the prospective role of HSP in the development of CS in humans.
Topics: Humans; Cellular Senescence; Heat-Shock Proteins; Longevity; Neoplasms
PubMed: 37207540
DOI: 10.1016/j.archger.2023.105057 -
Tumour Biology : the Journal of the... 2022Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies.
MATERIALS AND METHODS
PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study.
RESULTS
Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features.
CONCLUSION
APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.
Topics: Breast Neoplasms; Cytidine Deaminase; Disease-Free Survival; Female; Humans; Lung Neoplasms; Minor Histocompatibility Antigens; Proportional Hazards Models
PubMed: 36093650
DOI: 10.3233/TUB-211577 -
Head & Neck Jan 2021The goal of this review was to present an overview of the currently identified molecular parameters in head and neck squamous cell carcinoma (HNSCC) of nonsmokers and... (Meta-Analysis)
Meta-Analysis Review
Evidence for different molecular parameters in head and neck squamous cell carcinoma of nonsmokers and nondrinkers: Systematic review and meta-analysis on HPV, p16, and TP53.
BACKGROUND
The goal of this review was to present an overview of the currently identified molecular parameters in head and neck squamous cell carcinoma (HNSCC) of nonsmokers and nondrinkers (NSND).
METHODS
Following the PRISMA guidelines, a systematic search was performed using the electronic databases PubMed, Embase, and Google Scholar.
RESULTS
Of the 902 analyzed unique studies, 74 were included in a quantitative synthesis and 24 in a meta-analysis. Human papillomavirus (HPV) was reported as a molecular parameter in 38 studies, followed by p16 and TP53 (23 and 14 studies, respectively). The variety of other molecular parameters concerned sporadic findings in small numbers of NSND.
CONCLUSIONS
HNSCC in NSND is more often related to HPV and p16 overexpression compared to tumors of smokers-drinkers. In a third of virus-negative tumors, TP53 mutations were detected with a mutational profile associated with aging and ultraviolet light exposure rather than to tobacco consumption.
Topics: Alphapapillomavirus; Cyclin-Dependent Kinase Inhibitor p16; Head and Neck Neoplasms; Humans; Non-Smokers; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Tumor Suppressor Protein p53
PubMed: 33098216
DOI: 10.1002/hed.26513 -
Critical Reviews in Oncology/hematology Mar 2021Hypoxia is a characteristic of many solid tumours and results in an increase in expression of HIF-1α. Many studies have investigated the prognostic value of HIF-1α... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hypoxia is a characteristic of many solid tumours and results in an increase in expression of HIF-1α. Many studies have investigated the prognostic value of HIF-1α expression in breast cancer (BC), however, the prognostic value remains unclear. Therefore, a systematic review and meta-analysis was undertaken to determine the prognostic value of HIF-1α in BC patients.
METHODS
The electronic databases PubMed and Web of science were systematically searched to identify relevant papers. The clinical outcomes included disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) in BC patients. Review Manager version 5.4 was employed to analysis data from 30 eligible studies (containing 6201patients).
RESULTS
High expression of HIF-1α was associated with poorer DFS and OS. There was an effect of survival analysis, study region, antibodies used, scoring and threshold methods on HIF-1α expression.
CONCLUSION
HIF-1α overexpression was significantly associated with poorer DFS and OS in breast cancer patients.
Topics: Biomarkers, Tumor; Breast Neoplasms; Disease-Free Survival; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Prognosis; Survival Analysis
PubMed: 33482350
DOI: 10.1016/j.critrevonc.2021.103231 -
Journal of Cellular Physiology Sep 2019Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays a pivotal part in the formation of spindles. There is... (Review)
Review
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays a pivotal part in the formation of spindles. There is accumulating evidence that the expression of TPX2 is upregulated in many kinds of human cancers and that this protein is involved in the occurrence and progression of tumors. The purpose of this meta-analysis was to investigate the relationship between the overexpression of TPX2 and poor prognosis in cancer patients. A total of 18 eligible studies encompassing 3115 patients were included by searching relevant databases. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled under random-/fixed-effect models. After calculation, the results showed that patients with increased TPX2 expression had a significantly shorter overall survival (HR = 2.21; 95% CI: 1.70-2.86), and disease-free survival (HR = 2.10; 95% CI: 1.67-2.64). In addition, it was found that increased TPX2 expression was significantly associated with TNM stage (OR = 2.17; 95% CI:1.42-3.32), lymph node metastasis (OR = 2.98; 95% CI: 2.28-3.89), distant metastasis (OR = 2.25; 95% CI:1.03-4.92), and vascular invasion (OR = 2.22; 95% CI:1.26-3.91). Nevertheless, there was no significant correlation between increased expression of TPX2 and either gender, tumor differentiation, or tumor size. Thus, we can come to the conclusion that the overexpression of TPX2 is related to poor clinical outcomes and can be used as a biomarker for the prognosis of patients with cancer.
PubMed: 30779127
DOI: 10.1002/jcp.28343 -
Journal of Medicine and Life May 2022This study is a systematic review and meta-analysis to assess the overexpression rate of HER2 in patients with salivary gland tumors. We included peer-reviewed... (Meta-Analysis)
Meta-Analysis Review
This study is a systematic review and meta-analysis to assess the overexpression rate of HER2 in patients with salivary gland tumors. We included peer-reviewed publications from 1995 to 2020, indexed in medical databases, using search terms such as "human epidermal growth factor receptor 2 (HER2)" and "salivary gland tumors", and extracted relevant data. The extracted data were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t-tests, and the rates of HER2 positivity among studies were evaluated. 80 studies were included in the analysis. The positive rates of HER2 ranged from 3.3% to 84.0% and 1% to 9% in malignant and benign subtypes, respectively. The highest HER2 overexpression rate among malignant tumors was in salivary ductal carcinomas (SDC), with a 45% positive rate (CI 95%: 21.9-70.3%). Mucoepidermoid carcinoma (MEC) had the highest positive rate of 84% (CI 95%: 74.1-90.0%). Among benign salivary gland tumors, the highest rate was found in myoepithelioma, with a positive rate of 9% (CI 95%: 1.7-33.6%). The highest rate of HER2 overexpression is present in malignant subtypes of salivary gland tumors, more specifically in salivary ductal carcinoma, mucoepidermoid carcinomas, salivary duct carcinoma in situ, and carcinoma ex pleomorphic adenoma.
Topics: Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Humans; Receptor, ErbB-2; Salivary Gland Neoplasms; Salivary Glands
PubMed: 35815077
DOI: 10.25122/jml-2021-0394 -
Critical Reviews in Oncology/hematology May 2021Accurate data on HER2 positivity in esophageal squamous cell carcinoma patients (ESCC) is lacking. We conducted a systematic review and meta-analysis (Single Incidence... (Meta-Analysis)
Meta-Analysis Review
Accurate data on HER2 positivity in esophageal squamous cell carcinoma patients (ESCC) is lacking. We conducted a systematic review and meta-analysis (Single Incidence Rates; metarate package, R) to examine the prevalence of HER2 in ESCC. Data on in situ hybridization (ISH) and immunohistochemistry (IHC) were extracted to derive pooled prevalence estimates, characteristics of the studies were extracted for subgroup analysis. Eighteen studies with 1505 patients were identified. HER2 gene amplification by ISH were prevalent in 10 % (95 % CI 6.9 %-15 %). Prevalence of HER2 overexpression (IHC3+) and borderline HER2 expression (IHC2+) were 6 % (95 % CI: 3.5 %-8.7 %) and 10 % (95 % CI: 6.0 %-17 %), respectively. An estimated 8.6 % (95 % CI: 5.5 %-13 %) of ESCC were HER2 positive using initial IHC followed by reflex ISH confirmation of borderline HER2 expression. In conclusion: Estimated prevalence of HER 2 positivity in ESCC were 10 % assessed by ISH and 8.6 % assessed by initial IHC followed by ISH.
Topics: Biomarkers, Tumor; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Prevalence; Receptor, ErbB-2
PubMed: 33865993
DOI: 10.1016/j.critrevonc.2021.103339 -
Expert Review of Anticancer Therapy Jun 2023Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and...
INTRODUCTION
Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and efforts to target this receptor have lagged. Despite recent FDA approval for the first directed therapy combination for HER2 amplified metastatic CRC, the EMA has not yet authorized any such treatment and this represents a persistent unmet need in Europe and beyond. Here, we review data from trials targeting HER2 amplification, the latest target for CRC therapy.
AREAS COVERED
PubMed, Cochrane Library, EMBASE, and clinicaltrials.gov were reviewed systematically for possible manuscripts from inception to 1 July 2022. Results: A total of seven studies comprised of 284 locally advanced/mCRC patients receiving HER2 targeting agents were included in this systematic review. Most of the studies (n = 5) were non-randomized phase 2 trials, one phase 2/3 randomized controlled trial, and one phase 2a multiple-basket study. The outcomes consisted in the analysis of HER2 targeting agents and ORR, PFS, OS benefit, and toxicities of the therapy.
EXPERT OPINION
Anti-HER2 therapy exhibits a favorable toxicity profile compared with other targeted approaches; however, there is work to be done on optimizing patient selection and understanding resistance mechanisms.
Topics: Female; Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Receptor, ErbB-2; Rectal Neoplasms; Clinical Trials as Topic
PubMed: 37127555
DOI: 10.1080/14737140.2023.2207830 -
Frontiers in Oncology 2022Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous... (Review)
Review
BACKGROUND
Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous clinical trials are currently investigating several therapies based on modulation of the MET pathway.
OBJECTIVES
This study aimed to systematically evaluate the activity and safety of MET inhibitors in patients with NSCLC.
METHODS
We searched PubMed, Embase, and the Cochrane Library from inception to June 02, 2022. The objective response rate (ORR) and disease control rate (DCR) were extracted as the main outcomes and pooled using the weighted mean proportion with fixed- or random-effects models in cases of significant heterogeneity ( >50%). Safety analysis was performed based on adverse events reported in all studies.
RESULTS
Eleven studies (882 patients) were included in the meta-analysis. The pooled ORR was 28.1% (95% confidence interval [CI], 0.223-0.354), while the pooled DCR was 69.1% (95% CI, 0.631-0.756). ORRs were higher for tepotinib (44.7% [95% CI, 0.365-0.530]) and savolitinib (42.9% [95% CI, 0.311-0.553]) than for other types of MET inhibitors. Patients with NSCLC with exon 14 skipping exhibited higher ORRs (39.3% (95% CI, 0.296-0.522)) and DCRs (77.8% (95% CI, 0.714-0.847)) than those with MET protein overexpression or amplification. Intracranial response rate and intracranial disease control rates were 40.1% (95% CI, 0.289-0.556) and 95.4% (95% CI, 0.892-0.100), respectively. Adverse events were mild (grade 1 to 2) in 87.2% of patients. Common adverse events above grade 3 included lower extremity edema (3.5% [95% CI, 0.027-0.044]), alanine aminotransferase (ALT) elevation (2.4% [95% CI, 0.014-0.033]), and lipase elevation (2.2% [95% CI, 0.016-0.031]).
CONCLUSION
MET inhibitors, which exhibited a satisfactory safety profile in the current study, may become a new standard of care for addressing MET dysregulation in patients with advanced or metastatic NSCLC, and even in those with brain metastases, particularly tepotinib, savolitinib and capmatinib. Further randomized trials are required to establish standard predictive biomarkers for MET therapies and to compare the effects of different MET inhibitors in NSCLC with MET dysregulation.
PubMed: 36387098
DOI: 10.3389/fonc.2022.1013299 -
Head & Neck Oct 2020The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial... (Meta-Analysis)
Meta-Analysis Review
The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16 overexpression in relation to HPV-status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16 overexpression in relation to HPV-status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6-38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16 . This meta-analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.
Topics: Alphapapillomavirus; Carcinoma in Situ; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence
PubMed: 32573035
DOI: 10.1002/hed.26330