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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 -
European Review For Medical and... Aug 2017Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported. The current study was, therefore, designed to systematically review and appraise current knowledge and conduct a meta-analysis on phase I, II, and III clinical trials in which ALK-inhibitors were used to treat NSCLC.
MATERIALS AND METHODS
The PubMed online database was thoroughly searched. A total of 26 articles were included in a qualitative systematic review, and four of them were used to conduct the quantitative meta-analysis.
RESULTS
We found that ALK inhibitors significantly improved the overall survival (OS) and progress free survival (PFS) of NSCLC patients, especially of ALK or ROS1 gene fusion-positive cases. ALK inhibitors contributed to better therapeutic outcomes regarding increased one-year and two-year OS, PFS, and ORR (Odds ratio: 4.393, 95% CI: 3.302-5.845, p < 0.001). Visual disturbance was the most common side effect observed in the patients treated with crizotinib, whereas mild gastrointestinal reactions, such as diarrhea and nausea, were most frequent in the patients treated with the 2nd generation of ALK inhibitors.
CONCLUSIONS
ALK inhibitors are safe and effective in the treatment of NSCLC patients, especially those with positive ALK-EML4 gene fusion or rearrangement.
Topics: Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lung Neoplasms; Pyrazoles; Pyridines; Randomized Controlled Trials as Topic; Receptor Protein-Tyrosine Kinases
PubMed: 28829490
DOI: No ID Found -
Acta Pharmaceutica Sinica. B Nov 2015Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for... (Review)
Review
Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
PubMed: 26713267
DOI: 10.1016/j.apsb.2015.08.001 -
CNS Neuroscience & Therapeutics Feb 2019Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy...
AIMS
Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction.
DISCUSSION
Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia.
CONCLUSION
A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.
Topics: Adult; Aged; Antiparkinson Agents; Child; Humans; Parkinsonian Disorders
PubMed: 30294976
DOI: 10.1111/cns.13068 -
Medicine Oct 2018The prognostic role of targeting protein for Xklp2 (TPX2) in solid tumors has been investigated in several researches, but the results remain controversial. Here we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognostic role of targeting protein for Xklp2 (TPX2) in solid tumors has been investigated in several researches, but the results remain controversial. Here we present a meta-analysis to systematically review the association between TPX2 expression levels and prognosis of human solid tumors.
METHODS
Studies published until December 2017 were searched in PubMed, Web of Science, and EBSCO, 13 studies (2134 patients) were collected for analysis. Odds ratios (ORs) for overall survival (OS) and disease-free survival (DFS) from individual studies were calculated by the application of Mantel-Haenszel random effect model. Pooled ORs were estimated by Z test. Publication bias and interstudy heterogeneity analyses were also performed.
RESULTS
TPX2 overexpression was associated with poor OS at 3 and 5 years [OR = 4.63, 95% confidence interval (CI): 3.27-6.56, P < .00001; OR = 4.05, 95% CI: 2.32-7.07, P < .00001, respectively] of solid tumors. Similar results were observed with DFS at 3 and 5 years (OR = 3.35, 95% CI: 1.83-6.14, P < .0001; OR = 2.94, 95% CI: 1.74-4.98, P < .0001, respectively). Subgroup analysis revealed that increased TPX2 expression was related to worse prognosis of gastric cancer and hepatocellular cancer, while irrelevant to esophageal squamous cell cancer at 5-year survival rate.
CONCLUSIONS
Overexpression of TPX2 is related to poor survival rate in most solid tumors, which indicates that the expression level of TPX2 is a significant prognostic parameter and potential therapeutic target in various solid tumors.
Topics: Biomarkers, Tumor; Cell Cycle Proteins; Humans; Microtubule-Associated Proteins; Neoplasms; Nuclear Proteins; Prognosis
PubMed: 30412141
DOI: 10.1097/MD.0000000000013018 -
Mathematical Biosciences and... Jul 2019p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer.... (Meta-Analysis)
Meta-Analysis
p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer. Moreover, p62 can easily promote tumor metastasis. However, studies have not reached a consensus on the relationship of p62 expression with the diagnosis and prognosis of lung cancer. We conducted a systematic review and meta-analysis of studies on p62 expression in the prognosis and clinical-pathological parameters of lung cancer patients. Literature search was performed with PubMed, Web of Science, EMBASE, Cochrane Library, and SpringerLink databases. Fixed-effects and random-effects models were used to study the relationship of p62 expression with patients' overall survival (OS) and clinical-pathological parameters. I2 was used to test for heterogeneity. Egger's test was used to assess publication bias. The meta-analysis collected and considered 13 articles, which included 1393 lung cancer patients. The studies show that the high expression of p62 is associated with poor OS in lung cancer patients. The clinical-pathological parameters of patients show that p62 is more highly expressed in high TNM stage (II + III + IV VS. I), Lymph node metastasis (N1 VS. N0), and distant metastases (D1 VS. D0). However, there is no correlation between the p62 expression and the Beclin 1 and LC3B in lung cancer patients. In conclusion, the over-expression of p62 is associated with poor OS in lung cancer patients and can be used as a biomarker for lung cancer diagnosis and prognosis.
Topics: Autophagy; Beclin-1; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Microtubule-Associated Proteins; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Sequestosome-1 Protein; Treatment Outcome
PubMed: 31698589
DOI: 10.3934/mbe.2019340 -
OncoTargets and Therapy 2018Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and... (Review)
Review
Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer.
PubMed: 29551902
DOI: 10.2147/OTT.S150829 -
Photomedicine and Laser Surgery Jun 2011The objective of this review was to systematically identify experimental studies of non-ablative laser irradiation (LI) on peripheral nerve morphology, physiology, and... (Review)
Review
OBJECTIVE
The objective of this review was to systematically identify experimental studies of non-ablative laser irradiation (LI) on peripheral nerve morphology, physiology, and function. The findings were then evaluated with special reference to the neurophysiology of pain and implications for the analgesic effects of low-level laser therapy (LLLT).
BACKGROUND
LLLT is used in the treatment of pain, and laser-induced neural inhibition has been proposed as a mechanism. To date, no study has systematically evaluated the effects of LI on peripheral nerve, other than those related to nerve repair, despite the fact that experimental studies of LI on nerves have been conducted over the past 25 years.
METHODS
We searched computerized databases and reference lists for studies of LI effects on animal and human nerves using a priori inclusion and exclusion criteria.
RESULTS
We identified 44 studies suitable for inclusion. In 13 of 18 human studies, pulsed or continuous wave visible and continuous wave infrared (IR) LI slowed conduction velocity (CV) and/or reduced the amplitude of compound action potentials (CAPs). In 26 animal experiments, IR LI suppressed electrically and noxiously evoked action potentials including pro-inflammatory mediators. Disruption of microtubule arrays and fast axonal flow may underpin neural inhibition.
CONCLUSIONS
This review has identified a range of laser-induced inhibitory effects in diverse peripheral nerve models, which may reduce acute pain by direct inhibition of peripheral nociceptors. In chronic pain, spinal cord changes induced by LI may result in long-term depression of pain. Incomplete reporting of parameters limited aggregation of data.
Topics: Action Potentials; Analgesia; Animals; Evoked Potentials; Humans; Low-Level Light Therapy; Neural Conduction; Pain; Peripheral Nerves
PubMed: 21456946
DOI: 10.1089/pho.2010.2928 -
ESMO Open Mar 2024The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC.
MATERIALS AND METHODS
A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed.
RESULTS
Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months).
CONCLUSIONS
ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.
Topics: Humans; Female; Circulating Tumor DNA; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis; Disease-Free Survival
PubMed: 38460249
DOI: 10.1016/j.esmoop.2024.102390 -
Acta Oncologica (Stockholm, Sweden) Feb 2018advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the... (Review)
Review
BACKGROUND
advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes.
METHOD
this systematic literature review was conducted by reviewing all relevant literature in PubMed. Six separate searches were performed: Three searches where controlled entry terms were used and three free text searches. Furthermore, other relevant publications were included manually. A total of seventy-two studies met the search criteria and were thus further analyzed and evaluated.
RESULTS
In the included studies, various TAs and their effect on different molecular targets have been evaluated. Clinical responses vary considerably among the different genetic aberrations. The majority of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1) rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2), Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal-epithelial transition factor (MET) were included as well. In general, studies comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK) rearranged patients after use of either TA or standard chemotherapy, present significant better results after TA.
CONCLUSIONS
This systematic review provides an overview of available literature in PubMed regarding NSCLC and TA. Included studies point toward that TA appears to be a promising therapeutic tool in treating NSCLC patients and use of TA is expected to result in improved treatment outcomes.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Molecular Targeted Therapy; Proto-Oncogene Mas
PubMed: 29172833
DOI: 10.1080/0284186X.2017.1404634