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Evidence-based Complementary and... 2020At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have... (Review)
Review
OBJECTIVE
At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it.
METHODS
PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC.
RESULTS
A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), =0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), =0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), =0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), < 0.05), stages (HR = 0.51, 95% CI (0.35-0.74), < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), < 0.05).
CONCLUSIONS
Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.
PubMed: 32280357
DOI: 10.1155/2020/8475840 -
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 -
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 -
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 -
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 -
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 -
Critical Reviews in Oncology/hematology Jan 2017Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease... (Review)
Review
BACKGROUND
Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL.
OBJECTIVE
Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30 malignancies in humans.
DATA SOURCES
We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015).
ELIGIBILITY CRITERIA
Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered.
INCLUDED STUDIES
A total of 28 articles met these criteria and are summarized in this manuscript.
CONCLUSION
Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30 malignancies.
Topics: Antineoplastic Agents; Brentuximab Vedotin; Clinical Trials, Phase II as Topic; Humans; Immunoconjugates; Lymphoma, Non-Hodgkin; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 28010897
DOI: 10.1016/j.critrevonc.2016.11.009 -
Oxidative Medicine and Cellular... 2016Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia... (Review)
Review
Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Reactive Oxygen Species; Salvia miltiorrhiza
PubMed: 27579153
DOI: 10.1155/2016/5293284 -
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