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Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557 -
The Journal of Clinical Psychiatry Mar 2011To look at (1) the association between antipsychotics and cell stress, (2) whether first-generation antipsychotics may show different effects than second-generation... (Review)
Review
OBJECTIVE
To look at (1) the association between antipsychotics and cell stress, (2) whether first-generation antipsychotics may show different effects than second-generation antipsychotics, and (3) whether recommendations can be made regarding medication.
DATA SOURCES
We conducted a systematic review of 5 databases for all articles published until December 31, 2007: PubMed, Ovid MEDLINE, EMBASE, PsycINFO, and EBM Reviews. Under specific headings (eg, "heat shock proteins" and "oxidative stress"), a systematic search of these databases included such terms as HSP70 and homocysteine, and specific search strings were constructed. No limits were placed on the year or language of publication. References from pertinent articles or books were retrieved.
STUDY SELECTION
We included 42 articles of human studies from 2,387 references originally retrieved. We included only articles that (1) were quantitative; (2) referred only to human tissue, in vivo, or in vitro; (3) stated what tissue was examined; (4) identified what metabolites were measured; and (5) had references.
DATA EXTRACTION
All articles were assessed by 2 authors, which ensured that the inclusion criteria were met. The selected studies were too heterogeneous to be combined for any useful meta-analysis. Three authors, therefore, independently interpreted the data, using specified criteria to judge whether each study showed a beneficial, detrimental, or no effect on the markers measured.
DATA SYNTHESIS
The analysis revealed no conclusive association with direct or indirect markers of oxidative cell stress and antipsychotics. For every reviewed antipsychotic, we revealed differing research results showing a beneficial, detrimental, or no effect. This was true for in vivo as well as in vitro studies.
CONCLUSIONS
It remains unclear whether antipsychotics increase or reduce cell stress. Claims of neuroprotective properties of antipsychotics seem premature.
Topics: Antipsychotic Agents; Haloperidol; Heat-Shock Proteins; Humans; Oxidative Stress
PubMed: 20673558
DOI: 10.4088/JCP.09r05268yel -
Medicine Jul 2022The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell...
BACKGROUND
The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.
METHODS
This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.
RESULTS
In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.
LIMITATIONS
The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Topics: Adult; DNA-Binding Proteins; Hematologic Neoplasms; Histone Chaperones; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Transcription Factors
PubMed: 35905214
DOI: 10.1097/MD.0000000000029294 -
Biomedical Papers of the Medical... Sep 2015Environmental and patho-physiologic stresses stimulate synthesis of heat shock proteins (HSPs) which enable the cell to survive and recover from stressful conditions, by... (Review)
Review
BACKGROUND
Environmental and patho-physiologic stresses stimulate synthesis of heat shock proteins (HSPs) which enable the cell to survive and recover from stressful conditions, by as yet incompletely understood mechanisms. Heat shock proteins show an increased expression in a wide range of human cancers and have been associated with tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. Yet the role of heat shock proteins in oral cancer is ambiguous. The objective of this review was to systematically assess the data available on the role of HSP expression in oral cancer with special reference to its role in diagnosis, prognosis and treatment.
METHODS AND RESULTS
A systematic review of studies that investigated the HSP expression in oral squamous cell carcinoma using Scopus, Medline, Embase and Google scholar databases from their inceptions to 2013, without language restrictions was conducted. We selected 24 studies from which data extraction and validations were performed.
CONCLUSION
The literature search revealed differential expression of HSPs during oral tumorigenesis with implications for the specific role of HSPs in the pathogenesis of oral cancer. HSP expression has been regarded as an independent prognostic factor for oral squamous cell carcinoma patients and HSPs are being explored as potent vehicles for delivery of preventive and treatment vaccines in cancer and other diseases.
Topics: Carcinoma, Squamous Cell; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; Humans; Molecular Chaperones; Mouth Neoplasms
PubMed: 25703280
DOI: 10.5507/bp.2015.004 -
Croatian Medical Journal Apr 2019To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine...
AIM
To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF.
METHODS
We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment.
RESULTS
The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration.
CONCLUSION
The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Calcium; Cells, Cultured; Cytokines; Electromagnetic Fields; Heat-Shock Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Magnetic Field Therapy; Microglia; Neurodegenerative Diseases; Receptor Cross-Talk; Tumor Necrosis Factor-alpha
PubMed: 31044584
DOI: 10.3325/cmj.2019.60.127 -
Medicine Jan 2021Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer.
MATERIALS AND METHODS
We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX).
RESULTS
A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression.
CONCLUSION
HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.
Topics: HSP70 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Mouth Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 33546049
DOI: 10.1097/MD.0000000000024274 -
International Journal of Molecular... Aug 2018Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.
Topics: Activating Transcription Factor 6; Animals; Antibodies; Carcinoma, Pancreatic Ductal; Communicable Diseases; Deoxycytidine; Diabetes Complications; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoribonucleases; Gene Expression Regulation; Heat-Shock Proteins; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic; Protein Serine-Threonine Kinases; RNA, Small Interfering; Risk Factors; Sulfones; eIF-2 Kinase; Gemcitabine
PubMed: 30134550
DOI: 10.3390/ijms19092468 -
Current Oncology (Toronto, Ont.) Nov 2022The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in... (Meta-Analysis)
Meta-Analysis
The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP's association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP's clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.
Topics: Humans; Female; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis
PubMed: 36547124
DOI: 10.3390/curroncol29120710 -
Current Alzheimer Research 2019Plasma clusterin has been reported to be associated with the pathology, prevalence, severity, and rapid clinical progress of Alzheimer's Disease (AD). However, whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plasma clusterin has been reported to be associated with the pathology, prevalence, severity, and rapid clinical progress of Alzheimer's Disease (AD). However, whether plasma clusterin can be used as a biomarker of AD is inconsistent and even conflicting.
OBJECTIVE
We conducted this study to evaluate the potential of plasma clusterin as the biomarker of AD.
METHOD
PubMed, Embase, and Cochrane databases were systematically searched for studies on the relationship between plasma clusterin levels and AD diagnosis, risk and disease severity. We also compared the difference in Cerebrospinal Fluid (CSF) clusterin levels between AD and control groups. We converted and pooled data using standardized mean difference, Pearson linear regression model and the Cox regression model.
RESULTS
A total of 17 articles and 7228 individuals, including 1936 AD were included. The quality ranged from moderate to high. There was no difference in plasma clusterin between AD and control groups (SMD= 0.19 [-0.10, 0.48], p=0.20). Plasma clusterin levels were not correlated with the risk (RR=1.03 [0.97-1.09], p=0.31), the MMSE scores (R=0.33 [-0.06, 0.71], p= 0.09), and the integrated neuropsychological measurements (R=0.21 [-0.20, 0.63], p=0.31) of AD. Additionally, there was no difference in CSF clusterin between AD and control groups (SMD=1.94 [ -0.49, 4.37], p=0.12).
CONCLUSION
Our meta-analysis suggested no relationship between plasma clusterin levels and the diagnosis, risk, and disease severity of AD and no difference in the CSF clusterin between AD and the control groups. Overall, there is no evidence to support plasma clusterin as a biomarker of AD based on the pooled results.
Topics: Alzheimer Disease; Biomarkers; Clusterin; Humans
PubMed: 31647395
DOI: 10.2174/1567205016666191024141757 -
Journal of the Formosan Medical... Jan 2022A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia...
BACKGROUND/PURPOSE
A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort.
METHODS
We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020.
RESULTS
Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04).
CONCLUSION
Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.
Topics: Adult; Child; Dystonic Disorders; Genetic Diseases, X-Linked; Humans; Male; Molecular Chaperones; Taiwan
PubMed: 34092466
DOI: 10.1016/j.jfma.2021.05.017