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Diagnostics (Basel, Switzerland) Mar 2023Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD is clinical, neuroimaging plays a key role in the evaluation of patients who present symptoms related to neurodegenerative disorders. MRI, DAT-SPECT, and PET with [F]-FDG are routinely used in the diagnosis and focus on the investigation of morphological changes, nigrostriatal degeneration or shifts in glucose metabolism in patients with parkinsonian syndromes. The aim of this study is to review the current PET radiotracers targeting TSPO, a transmembrane protein that is overexpressed by microglia in another pathophysiological process associated with neurodegenerative disorders known as neuroinflammation. To the best of our knowledge, neuroinflammation is present not only in PD but in many other neurodegenerative disorders, including AD, DLB, and MSA, as well as atypical parkinsonian syndromes. Therefore, in this study, specific patterns of microglial activation in PD and the differences in distribution volumes of these radiotracers in patients with PD as compared to other neurodegenerative disorders are reviewed.
PubMed: 36980337
DOI: 10.3390/diagnostics13061029 -
International Journal of Molecular... Mar 2022Wound healing is a complex process that is mediated and influenced by several cytokines, chemokines, and growth factors. Interleukin-22 (IL-22) is a cytokine that plays... (Review)
Review
Wound healing is a complex process that is mediated and influenced by several cytokines, chemokines, and growth factors. Interleukin-22 (IL-22) is a cytokine that plays a critical role in tissue regeneration. Our study is a systematic review that addressed the implications of IL-22 in the healing of wounds caused by external factors. Thirteen studies were included in our review, most of them being experimental studies. Three clinical studies underlined the potential role of IL-22 in day-to-day clinical practice. IL-22 plays a central role in wound healing, stimulating the proliferation, migration, and differentiation of the cells involved in tissue repair. However, overexpression of IL-22 can cause negative effects, such as keloid scars or peritoneal adhesions. The results of the presented studies are promising, but further research that validates the roles of IL-22 in clinical practice and analyzes its potential implication in surgical healing is welcomed.
Topics: Chemokines; Cytokines; Interleukins; Wound Healing; Interleukin-22
PubMed: 35409053
DOI: 10.3390/ijms23073693 -
Frontiers in Endocrinology 2022Up to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Up to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of amplification on estrogen receptor positive patients' disease outcomes, is vital. This review aims to evaluate amplification as a prognostic and predictive biomarker in BCa.
MATERIALS AND METHODS
Publications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].
RESULTS
amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.
CONCLUSION
While a lack of standardised approach for the detection of amplification is to be considered as a limitation, amplification was found to be prognostic of shorter RFS and OS in BCa. amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of amplification, amplification would have potential as a predictive biomarker in breast cancer patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.
Topics: Breast Neoplasms; Cyclin D1; Gene Amplification; Humans; Postmenopause; Prognosis; Receptors, Estrogen
PubMed: 35784572
DOI: 10.3389/fendo.2022.895729 -
Cancers Jul 2022Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and... (Review)
Review
Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the prognostic, diagnostic and clinicopathological value of NRP1 in liver cancer and CRC patients. We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for articles evaluating the NRP1 correlation with survival parameters, tumor development or clinicopathological features. Hazard ratios and odds ratios with 95% confidence intervals were extracted or estimated by Parmar method and pooled to evaluate the overall effect size with STATA 16 software. Heterogeneity was analyzed by chi-square-based Q test and I statistic, along with meta-regression and subgroup analysis, and publication bias was assessed by funnel plot asymmetry and Egger's test. The study protocol was registered in PROSPERO (CRD42022307062). NRP1 overexpression was significantly correlated with lower survival in liver cancer patients and with tumor development in hepatocarcinoma patients, and was strongly correlated with an increased risk of vascular invasion in liver cancer and metastasis in CRC and liver tumors. These results support the role of NRP1 as a potential and useful biomarker in both types of cancer.
PubMed: 35884516
DOI: 10.3390/cancers14143455 -
Oncotarget Apr 2016Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and... (Meta-Analysis)
Meta-Analysis Review
Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 63 studies identified from PubMed, Medline and EBSCO. We found STAT3 overexpression was significantly associated with worse 3-year overall survival (OS) (OR = 2.06, 95% CI = 1.57 to 2.71, P < 0.00001) and 5-year OS (OR = 2.00, 95% CI = 1.53 to 2.63, P < 0.00001) of human solid tumors. Similar results were observed when disease free survival (DFS) were analyzed. Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer. The correlation between STAT3 and survival of solid tumors was related to its phosphorylated state. High expression level of STAT3 was also associated with advanced tumor stage. In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; STAT3 Transcription Factor; Sensitivity and Specificity; Survival Analysis
PubMed: 26959884
DOI: 10.18632/oncotarget.7887 -
Cancers Jul 2020Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer...
Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of AQP expression and survival rates for patients were evaluated by systematic review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange. AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.
PubMed: 32679804
DOI: 10.3390/cancers12071911 -
British Journal of Cancer Jun 2017The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer.
METHODS
A systematic review of published studies reporting BAG-1 (mRNA and/or protein) expression and clinical outcome in early breast cancer. The REporting Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were used as a template against which data were assessed. Meta-analyses were performed for studies that provided a hazard ratio and 95% confidence intervals for clinical outcomes including disease-free survival or breast cancer-specific survival from univariate analysis.
RESULTS
Eighteen studies used differing methodologies and reported on differing outcomes. Meta-analyses were only possible on results from a subset of reported studies. Meta-analyses suggested improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by immunohistochemisty.
CONCLUSIONS
Increased levels of BAG-1 are associated with better breast cancer outcomes.
Topics: Biomarkers, Tumor; Breast Neoplasms; DNA-Binding Proteins; Disease-Free Survival; Female; Humans; RNA, Messenger; Survival Rate; Transcription Factors
PubMed: 28510570
DOI: 10.1038/bjc.2017.130 -
Frontiers in Physiology 2019The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich...
The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich PPR-motif-containing protein (LRPPRC), a member of the PPR family, is a known gene mutation that causes Leigh syndrome French-Canadian. Recently, growing evidence has pointed out that LRPPRC dysregulation is related to various diseases ranging from tumors to viral infections. This review presents available published data on the LRPPRC protein function and its role in tumors and other diseases. As a multi-functional protein, LRPPRC regulates a myriad of biological processes, including energy metabolism and maturation and the export of nuclear mRNA. Overexpression of LRPPRC has been observed in various human tumors and is associated with poor prognosis. Downregulation of LRPPRC inhibits growth and invasion, induces apoptosis, and overcomes drug resistance in tumor cells. In addition, LRPPRC plays a potential role in Parkinson's disease, neurofibromatosis 1, viral infections, and venous thromboembolism. Further investigating these new functions of LRPPRC should provide novel opportunities for a better understanding of its pathological role in diseases from tumors to viral infections and as a potential biomarker and molecular target for disease treatment.
PubMed: 31178748
DOI: 10.3389/fphys.2019.00595 -
Scientific Reports Sep 2016Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the... (Meta-Analysis)
Meta-Analysis Review
Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS). In this meta-analysis, 16 studies involving 2,569 participants were included, and we drew the conclusion that TROP2 overexpression was significantly associated with poor OS (pooled HR = 1.896, 95% CI = 1.599-2.247, P < 0.001) and short DFS (pooled HR = 2.336, 95% CI = 1.596-3.419, P < 0.001). Furthermore, the subgroup analysis revealed that the associations between TROP2 overexpression and the outcome endpoints (OS or DFS) were significant in in patients with female genital system neoplasms, as well in gastrointestine neoplasms. In addition, subgroup analysis found no difference HR across populations of different descent.Taken together, TROP2 overexpression was associated with poor survival in human solid tumors. TROP2 may be a valuable prognosis predictive biomarker and a potential therapeutic target in human solid tumors.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cell Adhesion Molecules; Gene Expression; Humans; Neoplasms; Prognosis; Publication Bias; Survival Analysis
PubMed: 27645103
DOI: 10.1038/srep33658 -
PloS One 2016Human epidermal growth factor receptor (HER) family plays an important role in gastric cancer (GC), especially HER2. Too much attention has been paid to HER2; however,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Human epidermal growth factor receptor (HER) family plays an important role in gastric cancer (GC), especially HER2. Too much attention has been paid to HER2; however, the functions of HER3 and HER4 overexpression in GC are always ignored. The clinicopathological and prognostic roles of HER3 and HER4 in GC are controversial. In this study, a systematic review and meta-analysis was conducted to evaluate the use of HER3 or HER4 as a predictor of clinicopathology and survival time in GC patients.
METHODS
Eligible studies were searched on PubMed, Ovid, Web of Science, and Cochrane databases through multiple search strategies. Data collection and statistical analysis were carried out by the Revman 5.3 software. The Newcastle-Ottawa scale was used to assess the quality of included studies.
RESULTS
A total of 448 studies about HER3 overexpression and GC, and 398 studies about HER4 overexpression and GC were searched. Of these, 5 eligible studies about HER3 including 1016 GC patients and 3 eligible studies about HER4 including 793 GC patients met the inclusion criteria. The results showed that HER3 and HER4 overexpression were significantly associated with depth of tumor invasion (OR = 0.44, 95%CI 0.29-0.67, P = 0.0002 and OR = 0.50, 95%CI 0.38-0.86, P = 0.007) and lymph node metastasis (OR = 0.40, 95%CI 0.20-0.77, P = 0.007 and OR = 0.57, 95%CI 0.38-0.86, P = 0.007), and HER3 overexpression reveals a tendency of later tumor node metastases (TNM) stage (OR = 0.50, 95%CI 0.22-1.15, P = 0.10) and predicts a worse survival time (RR = 0.71, 95%CI 0.61-0.84, P<0.00001), while HER4 overexpression had no correlation with TNM stage (OR = 0.60, 95%CI 0.20-1.78) and survival time (RR = 1.09, 95%CI 0.91-1.30).
CONCLUSIONS
This meta-analysis indicated that HER3 plays an essential role in the clinicopathology and prognosis of GC. However, HER4 may not be an ideal prognostic factor for GC.
Topics: Biomarkers, Tumor; Humans; Prognosis; Receptor, ErbB-3; Receptor, ErbB-4; Stomach Neoplasms
PubMed: 27536774
DOI: 10.1371/journal.pone.0161219