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Biomarkers in Medicine Aug 2019To investigate the prevalence of variants in non-small-cell lung cancer (NSCLC) patients. Database of Pubmed, Embase, Medline and Cochrane Library were searched... (Meta-Analysis)
Meta-Analysis
To investigate the prevalence of variants in non-small-cell lung cancer (NSCLC) patients. Database of Pubmed, Embase, Medline and Cochrane Library were searched systematically to April 2018. A total of 39 articles including 1903 NSCLC patients with positive were recruited. The overall pooled prevalence for variant 1 to 3 was 81.84% (95% CI: 76.68-86.99%), ranging from 86.64% tested by RT-PCR to 70.85% tested by other methods (p = 0.00). Subgroup analysis showed that the pooled prevalences of variant 1, 2 and 3 were 40.38% (95% CI: 34.83-45.93%), 6.59% (95% CI: 4.27-8.91%) and 26.54% (95% CI: 20.89-32.2%), respectively. This present study provides the exact prevalence of rearrangement in different variants for NSCLC patients with positive.
Topics: Aged; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Female; Gene Rearrangement; Humans; Lung Neoplasms; Male; Middle Aged; Oncogene Proteins, Fusion
PubMed: 31432686
DOI: 10.2217/bmm-2018-0277 -
Andrology Sep 2019The primary cilium is a microtubule-based organelle that extends transiently from the apical cell surface to act as a sensory antenna. Initially viewed as a cellular...
BACKGROUND
The primary cilium is a microtubule-based organelle that extends transiently from the apical cell surface to act as a sensory antenna. Initially viewed as a cellular appendage of obscure significance, the primary cilium is now acknowledged as a key coordinator of signaling pathways during development and in tissue homeostasis.
OBJECTIVES
The aim of this review was to present the structure and function of this overlooked organelle,with an emphasis on its epididymal context and contribution to male infertility issues.
MATERIALS AND METHODS
A systematic review has been performed in order to include main references relevant to the aforementioned topic.
RESULTS
Increasing evidence demonstrates that primary cilia dysfunctions are associated with impaired male reproductive system development and male infertility issues.
DISCUSSION
While a large amount of data exists regarding the role of primary cilia in most organs and tissues, few studies investigated the contribution of these organelles to male reproductive tract development and homeostasis.
CONCLUSION
Functional studies of primary cilia constitute an emergent and exciting new area in reproductive biology research.
Topics: Animals; Cellular Microenvironment; Cilia; Ciliopathies; Epididymis; Humans; Infertility, Male; Male; Mechanotransduction, Cellular; Mice; Microtubules; Rete Testis; Signal Transduction; Sperm Tail
PubMed: 31131532
DOI: 10.1111/andr.12650 -
Topics in Current Chemistry (Cham) May 2019As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer...
Systematic Review on Cytotoxic and Anticancer Potential of N-Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis.
As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer agents which have the ability to overcome multidrug resistance (MDR) mechanisms. The search for the development of novel isatin-based antitumor agents accelerated after the approval by the Food and Drug Administration (FDA) of sunitinib malate, a C-3 isatin derivative, as a multitargeted receptor tyrosine kinase inhibitor. However, it is interesting to note that, over the last decade, various N-substituted analogs of isatin with intact carbonyl functionalities have been found to show more promising anticancer potential than its C-3 derivatives. Microtubule-targeting agents are a class of anticancer drugs which affect mitosis by targeting microtubules and suppressing their dynamic behavior. This review presents a systematic compilation of the in vitro cytotoxic and anticancer properties of various N-substituted isatins and illustrates their mechanism of action to overcome MDR by acting as microtubule-destabilizing agents. Predictions of the biological activities and cytotoxic effects of potential N-substituted isatins against various cancer cell lines have also been performed using the PASS computer-aided drug discovery program. Findings from such in vitro and in silico studies will act as a guide for the development of structure-activity relationship and will facilitate the design and exploration of more potent analogs of isatin with high potency and lower side effects for treatment of drug-resistant cancer. Mechanism of action of N-substituted isatin as microtubule-destabilizing agent on tumor cells. N-Substituted isatins bind to colchicine binding site on β-tubulin, which inhibits microtubule polymerization and thereby destabilizes microtubule dynamics, resulting in mitotic arrest leading to tumor cell growth suppression.
Topics: Antineoplastic Agents; Cell Proliferation; Computer Simulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Isatin; Microtubules; Quantitative Structure-Activity Relationship
PubMed: 31073777
DOI: 10.1007/s41061-019-0240-9 -
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 Journal of Dermatology : EJD Oct 2018In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with...
In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with particular emphasis on genetic alterations underlying aetiopathogenesis. When appropriate, diagnostic and/or prognostic biomarkers for cSCC are also considered. This review is intended to aid future investigation into the molecular characterization of cSCC.
Topics: Carcinogenesis; Carcinoma, Squamous Cell; Cell Cycle Proteins; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Microtubule-Associated Proteins; Mutation; Prevalence; Retinoblastoma Binding Proteins; Risk Assessment; Skin Neoplasms; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 30530431
DOI: 10.1684/ejd.2018.3403 -
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 -
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 -
Expert Review of Anticancer Therapy Nov 2018Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with...
Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). Cisplatin may be combined with etoposide, vinorelbine or other vinca alkaloids, which act also as radiation sensitizers. Initially administered intravenously, vinorelbine is also available as oral formulation and is the only orally available microtubule-targeting agent. In addition, the oral formulation avoids the risk of extravasation and phlebitis. Areas covered: A literature search has been performed for articles reporting phase II-III trials aimed to evaluate efficacy and safety of oral vinorelbine-based chemoradiotherapy in unresectable locally advanced NSCLC. Expert commentary: In a series of trials with various protocols published from 2008 to 2018, mostly phase II studies, oral vinorelbine demonstrated a significant activity in concomitant chemoradiotherapy for unresectable locally advanced NSCLC typically as part of combination schedules with cisplatin. Main toxicities were hematologic (neutropenia and anemia); non-hematological toxicities included esophagitis and gastro-duodenal adverse events. Large prospective phase III trials are needed to confirm the role of vinorelbine-based chemotherapy associated to thoracic radiotherapy in unresectable stage III NSCLC and more particularly trials with metronomic oral vinorelbine.
Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Humans; Lung Neoplasms; Neoplasm Staging; Vinorelbine
PubMed: 30173589
DOI: 10.1080/14737140.2018.1518714 -
Der Nervenarzt Oct 2018The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
BACKGROUND
The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
OBJECTIVE
Provide a timely state of the art review on recent scientific advances in the field of tauopathies.
MATERIAL AND METHODS
Systematic review of the literature from the past 10 years.
RESULTS
Tau proteins are increasingly being recognized as a highly variable protein, underlying and defining a spectrum of molecularly defined diseases, with a clinical spectrum ranging from dementia to hypokinetic movement disorders. Genetic variation at the tau locus can trigger disease or modify disease risk. Tau protein alterations can damage nerve cells and propagate pathologies through the brain. Thus, tau proteins may serve both as a serological and imaging biomarker. Tau proteins also provide a broad spectrum of rational therapeutic interventions to prevent disease progression. This knowledge has led to modern clinical trials.
CONCLUSION
The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.
Topics: Brain; Genetic Variation; Humans; Tauopathies; tau Proteins
PubMed: 30120488
DOI: 10.1007/s00115-018-0584-3 -
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