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1.
Clin Radiol ; 76(1): 78.e19-78.e25, 2021 01.
Article in English | MEDLINE | ID: mdl-32948315

ABSTRACT

AIM: To examine the prognostic value of global peak diastolic strain rate (PDSR) derived from cardiac magnetic resonance (CMR) tissue tracking (CMR-TT) in predicting adverse outcomes in hypertrophic cardiomyopathy (HCM) patients. MATERIALS AND METHODS: A total of 98 patients diagnosed with HCM (44 patients had left ventricle [LV] outflow tract obstruction [LVOTO] and 54 patients did not) were enrolled and followed for the specified endpoint. LV global myocardial mechanics was assessed in all participants using CMR-TT at study entry. RESULTS: Compared with the non-obstructive subgroup, the obstructive subgroup demonstrated deteriorated magnitude of LV global radial, circumferential, and longitudinal PDSR (all p<0.05). After a mean follow-up period of 4.5 years, 24 patients reached an endpoint before the end of the study. Furthermore, when using the specified cut-off value (0.33 1/s) of longitudinal PDSR, the Kaplan-Meier curve demonstrated that patients with lower longitudinal PDSR had a significantly lower freedom from major adverse cardiovascular events (MACE) compared with their counterparts in the non-obstructive, obstructive, and overall cohorts (all log-rank p<0.05). Multivariable analysis showed that longitudinal PDSR remained the strongest predictor of outcome after adjusting for baseline and CMR variables (hazard ratio, 2.65; 95% confidence interval, 2.21-11.44; p<0.05). CONCLUSION: CMR-TT-derived longitudinal PDSR is probably considered a novel and easy-to-perform marker for predicting adverse outcomes in HCM patients, which is beneficial to risk stratification. Further confirmatory studies are needed.


Subject(s)
Cardiomyopathy, Hypertrophic/diagnostic imaging , Magnetic Resonance Imaging, Cine , Cardiomyopathy, Hypertrophic/physiopathology , Diastole , Disease Progression , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Predictive Value of Tests , Prognosis
2.
Int J Oral Maxillofac Surg ; 48(9): 1153-1155, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30876796

ABSTRACT

The lingual lymph nodes (LLNs) can only be detected with difficulty in early-stage tongue squamous cell carcinomas owing to the small size. Recurrence or metastasis could occur in the floor of the mouth as a result of neglecting the LLNs. The injection of carbon nanoparticles to track occult LLNs in early-stage tongue squamous cell carcinoma is presented and discussed. This technique is simple and easy to use intraoperatively. If LLNs were stained black during the operation, the sublingual gland along with the fatty tissue of the floor of the mouth were removed simultaneously. The LLNs in early-stage tongue squamous cell carcinoma deserve more attention.


Subject(s)
Carcinoma, Squamous Cell , Nanoparticles , Tongue Neoplasms , Carbon , Humans , Lymph Nodes , Lymphatic Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging
3.
Osteoporos Int ; 29(12): 2645-2658, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30306226

ABSTRACT

By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal metabolism. INTRODUCTION: Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes. METHODS: BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the P values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples. RESULTS: Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants. CONCLUSIONS: Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.


Subject(s)
Bone Density/genetics , Osteoporosis/genetics , Polymorphism, Single Nucleotide , Databases, Genetic , Gene Expression Profiling/methods , Gene Expression Regulation/physiology , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Humans
4.
Clin. transl. oncol. (Print) ; 20(7): 889-898, jul. 2018. tab
Article in English | IBECS | ID: ibc-173640

ABSTRACT

Background: The effect of postoperative chemoradiotherapy (CRT) for esophageal carcinoma (EC) was investigated. Patients who can obtain benefit from this treatment modality have not yet been well identified. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies published from January 1993 to July 2016. Research comparing surgery alone (SA) with postoperative CRT in patients with resectable EC was procured; collected articles were written in English. Results: Nine studies comparing of postoperative CRT versus SA (n = 1650) in patients with resectable EC met the inclusion criteria. No survival benefit was achieved for postoperative CRT compared with SA. Subgroup analysis was conducted for patients under resection with positive lymph node carcinoma; there was a significant survival benefit at 1 year [risk ratio (RR) = 0.55 95% CI: 0.37-0.82; P = 0.003], 3 years (RR = 0.71 95% CI: 0.61-0.83; P<0.0001), as well as 5 years (RR = 0.86 95% CI: 0.78-0.94; P = 0.0007). Subgroup analysis by tumor histology of squamous cell carcinoma (SCC) was also performed, but there was no significant survival benefit when postoperative CRT was compared with SA. Fail models after surgery were performed; the RR for local control rate and distant metastasis rate were 0.64 (95% CI 0.49-0.85; P = 0.002) and 0.87 (95% CI 0.67-1.15; P = 0.34), which indicates lower local recurrence rates of post-CRT than that of SA. Conclusion: This meta-analysis demonstrated a survival benefit of postoperative CRT over SA in resectable EC patients with positive lymph nodes. Improvements of local control rates with postoperative CRT were also detected


No disponible


Subject(s)
Humans , Esophageal Neoplasms/therapy , Chemoradiotherapy/statistics & numerical data , Lymphatic Metastasis/pathology , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/epidemiology , Treatment Outcome , Local Lymph Node Assay , Lymph Node Excision/statistics & numerical data , Postoperative Care/statistics & numerical data
5.
Clin Radiol ; 73(7): 676.e1-676.e7, 2018 07.
Article in English | MEDLINE | ID: mdl-29573787

ABSTRACT

AIM: To evaluate the association between oesophageal tumour motion and tumour location using cine magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-three consecutive patients with oesophageal squamous cell carcinoma were enrolled, and underwent cine MRI of oesophageal tumours. The maximum displacements in the anterior-posterior (A-P), superior-inferior (S-I), and left-right (L-R) directions of the tumours were assessed statistically to show their associations with tumour location. RESULTS: Tumour motion in A-P and S-I directions increased from upper to lower oesophagus (r=0.505, p=0.003; and r=0.600, p<0.001, respectively). In A-P and S-I directions, tumours showed larger motion in the lower oesophagus than in the upper or middle oesophagus (all p<0.05). Motion of middle and lower oesophageal tumours in the S-I direction was larger than in L-R or A-P direction (all p<0.05). To provide 95% geometric coverage for the motion of upper oesophageal tumours, statistical analysis showed margins of 3.75 mm in L-R direction, 3.72 mm in A-P direction, and 5.38 mm in S-I direction. For the motion of tumours of the middle oesophagus, 95% coverage required margins of 8.50, 6.62, and 11.96 mm in L-R, A-P, and S-I directions, respectively, and for lower oesophageal tumours, 95% coverage required margins of 9.17, 9.68, and 12.98 mm in L-R, A-P, and S-I direction, respectively. CONCLUSION: Oesophageal tumour motion in different directions can be associated with tumour location as shown on cine MRI, suggesting that the present findings could be helpful for better understanding oesophageal tumour motion and gating individualised radiation delivery strategies.


Subject(s)
Esophageal Neoplasms/diagnostic imaging , Esophageal Squamous Cell Carcinoma/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Aged , Esophagus/diagnostic imaging , Female , Humans , Male , Middle Aged , Motion , Reproducibility of Results
6.
J Viral Hepat ; 25(8): 904-910, 2018 08.
Article in English | MEDLINE | ID: mdl-29582521

ABSTRACT

The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.


Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , Genetic Variation , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/pathology , Adult , Asian People , Ethnicity , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Sequence Analysis, DNA
7.
Int J Oral Maxillofac Surg ; 47(5): 561-567, 2018 May.
Article in English | MEDLINE | ID: mdl-28966067

ABSTRACT

This study aimed to evaluate the efficacy of iodine-125 (125I) brachytherapy alone for the treatment of advanced parotid gland carcinoma and to identify predictors of tumour control and patient survival. Primary parotid gland carcinoma patients (n=23) treated with 125I brachytherapy alone between 1 October 2005 and 31 July 2013 at Peking University Stomatology Hospital were enrolled in this retrospective study. All had clinical stage IV disease. The prescribed dose was 60-160Gy. The local control rate, survival rate, and predictors of the prognosis were evaluated. Adverse events related to treatment were also noted. The average follow-up time was 29 months (range 9-74 months). Among the 23 patients, six had local failure and 11 died during the follow-up period. The 1-, 3-, and 5-year overall survival rates were 87.0%, 55.4%, and 47.5%, respectively. The 1-, 3-, and 5-year progression-free survival rates were 73.9%, 47.0%, and 39.2%, respectively. The 1-, 3-, and 5-year local control rates were 82.1%, 73.9%, and 73.9%, respectively. Age and distant metastasis were independent predictors of survival, while the preoperative duration of the disease was an independent predictor of local control. The use of 125I seed brachytherapy alone for the treatment of primary parotid gland carcinoma can provide good short-term results without causing any severe side effects.


Subject(s)
Brachytherapy/methods , Parotid Neoplasms/radiotherapy , Adolescent , Adult , Aged , Biopsy , Child , Child, Preschool , Female , Humans , Infant , Iodine Radioisotopes , Male , Middle Aged , Neoplasm Staging , Parotid Neoplasms/pathology , Prognosis , Radiotherapy Dosage , Retrospective Studies , Survival Rate , Treatment Outcome
8.
Int J Obes (Lond) ; 41(12): 1782-1789, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28769120

ABSTRACT

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.


Subject(s)
Adiponectin/metabolism , Insulin Resistance/physiology , Insulin/metabolism , Interferon-gamma/metabolism , Omentum/cytology , Subcutaneous Fat, Abdominal/metabolism , Adaptive Immunity/physiology , Body Mass Index , Cells, Cultured , Humans , Immunity, Innate/physiology , Immunohistochemistry , Phenotype , Subcutaneous Fat, Abdominal/physiopathology
10.
Osteoporos Int ; 28(3): 1035-1046, 2017 03.
Article in English | MEDLINE | ID: mdl-27844135

ABSTRACT

In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. INTRODUCTION: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis. METHODS: Here, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes. RESULTS: Of the total of 3796 detected cytosolic proteins, we identified 16 significant (P < 0.05) and an additional 22 suggestive (P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration. CONCLUSIONS: The combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis.


Subject(s)
Cytosol/metabolism , Monocytes/metabolism , Osteoporosis/blood , Proteome/metabolism , Absorptiometry, Photon , Adult , Bone Density/genetics , Bone Density/physiology , Fructose-Bisphosphate Aldolase/biosynthesis , Fructose-Bisphosphate Aldolase/genetics , Gene Expression Profiling/methods , Gene Expression Regulation/physiology , Gene Ontology , Gene Regulatory Networks/physiology , Humans , Male , Middle Aged , Myosin Heavy Chains/biosynthesis , Myosin Heavy Chains/genetics , Myosin Type II/biosynthesis , Myosin Type II/genetics , Osteoporosis/genetics , Osteoporosis/physiopathology , Proteome/genetics , Proteomics/methods , rap GTP-Binding Proteins/biosynthesis , rap GTP-Binding Proteins/genetics
11.
Herz ; 41(8): 732-740, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27220978

ABSTRACT

AIM: Primary percutaneous coronary intervention is the most effective treatment for patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to investigate whether the combination of aspiration thrombectomy with intracoronary tirofiban treatment can result in smaller infarcts and better patient prognosis compared with aspiration thrombectomy alone. PATIENTS AND METHODS: In all, 150 patients with STEMI underwent primary percutaneous coronary intervention. Group A received aspiration thrombectomy and group B received a combination treatment of aspiration thrombectomy with intracoronary tirofiban. The endpoint was major adverse cardiovascular events, including myocardial (re)infarction, cardiovascular death, and target vessel revascularization. RESULTS: The clinical characteristics of the groups were not significantly different (p > 0.05). The percentage of patients whose thrombolysis in myocardial infarction (TIMI) myocardial perfusion grades were less than 3 was significantly higher for group B than for group A (13.9 vs. 3.8 %, p = 0.029). The infarct size on cardiac magnetic resonance imaging was significantly different between groups (p = 0.036). At 6 months after the operation, the echocardiography results were better for patients in group B than for those in group A (p = 0.024 and p = 0.016, respectively). The frequency of bleeding complications and major adverse cardiac events of the groups were not significantly different (p > 0.05). CONCLUSION: Aspiration thrombectomy with intracoronary tirofiban in patients with STEMI is safe and effective. For cases with a large angiographic thrombus burden, tirofiban did not increase the rate of bleeding complications or major adverse cardiovascular events.


Subject(s)
Percutaneous Coronary Intervention/mortality , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Thrombectomy/mortality , Tyrosine/analogs & derivatives , China/epidemiology , Combined Modality Therapy/mortality , Combined Modality Therapy/statistics & numerical data , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/statistics & numerical data , Prevalence , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , Survival Rate , Thrombectomy/statistics & numerical data , Tirofiban , Treatment Outcome , Tyrosine/administration & dosage
12.
Cell Death Dis ; 7: e2051, 2016 Jan 14.
Article in English | MEDLINE | ID: mdl-26775703

ABSTRACT

Necroptosis is a caspase-independent form of regulated cell death that has been implicated in the development of a range of inflammatory, autoimmune and neurodegenerative diseases. The pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), is the most terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by Receptor Interacting Protein Kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. However, the molecular interactions governing the processes downstream of RIPK3 activation remain poorly defined. Using a phenotypic screen, we identified seven heat-shock protein 90 (HSP90) inhibitors that inhibited necroptosis in both wild-type fibroblasts and fibroblasts expressing an activated mutant of MLKL. We observed a modest reduction in MLKL protein levels in human and murine cells following HSP90 inhibition, which was only apparent after 15 h of treatment. The delayed reduction in MLKL protein abundance was unlikely to completely account for defective necroptosis, and, consistent with this, we also found inhibition of HSP90 blocked membrane translocation of activated MLKL. Together, these findings implicate HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3.


Subject(s)
HSP90 Heat-Shock Proteins/genetics , Protein Kinases/genetics , Animals , Apoptosis , Cell Death , HSP90 Heat-Shock Proteins/metabolism , Humans , Mice , Necrosis , Phosphorylation , Protein Kinases/metabolism , Translocation, Genetic
13.
Gene Ther ; 22(9): 729-38, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25965392

ABSTRACT

Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.


Subject(s)
Cell Proliferation , Drug Resistance, Neoplasm , Ectopic Gene Expression , MicroRNAs/metabolism , Pancreatic Neoplasms/diagnosis , Aged , Animals , Cell Line, Tumor , Female , Heterografts , Humans , Male , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Pancreatic Neoplasms/metabolism , Prognosis , Proto-Oncogene Proteins c-myc/metabolism , Sirtuin 1/metabolism
14.
Nano Lett ; 15(3): 2168-73, 2015 Mar 11.
Article in English | MEDLINE | ID: mdl-25705928

ABSTRACT

An operando electrochemical stage for the transmission electron microscope has been configured to form a "Li battery" that is used to quantify the electrochemical processes that occur at the anode during charge/discharge cycling. Of particular importance for these observations is the identification of an image contrast reversal that originates from solid Li being less dense than the surrounding liquid electrolyte and electrode surface. This contrast allows Li to be identified from Li-containing compounds that make up the solid-electrolyte interphase (SEI) layer. By correlating images showing the sequence of Li electrodeposition and the evolution of the SEI layer with simultaneously acquired and calibrated cyclic voltammograms, electrodeposition, and electrolyte breakdown processes can be quantified directly on the nanoscale. This approach opens up intriguing new possibilities to rapidly visualize and test the electrochemical performance of a wide range of electrode/electrolyte combinations for next generation battery systems.

15.
Br J Oral Maxillofac Surg ; 53(1): 58-62, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25445387

ABSTRACT

To find out if brachytherapy with radioactive seeds was effective in patients with recurrent malignant tumours of the parotid gland we retrospectively studied 64 such patients, 24 of whom were treated with implantation of radioactive seeds alone, and 40 of whom had their recurrent tumours resected followed by implantation of radioactive seeds. Patients were followed up for a mean of 50 months (range 4 months to 12 years). The local control rate was 76.6%, and overall survival 79.7%. Of the 24 patients treated with brachytherapy alone, 22 achieved a complete response (91.7%). At 1, 3, and 5 years the local control rates were 81.5%, 67.2%, and 53.8%, respectively, and the overall survival 82.7%, 70%, and 61.2%, respectively. In the 40 patients whose tumours were resected before brachytherapy, the local control rates at 1, 3, and 5 years were 87.5%, 82.4%, and 78.6%, respectively, and the overall survival was 97.5%, 86.5%, and 86.5%, respectively. Sex, age, histopathological grade, size of tumour, history of radiotherapy, time of recurrence and method of treatment were not shown to have a significant effect on local control, but method of treatment had a significant impact on overall survival (p=0.008). We conclude that treatment of recurrent malignant tumours of the parotid efficacy can be successfully treated with brachytherapy with radioactive seeds, either alone or combined with resection.


Subject(s)
Brachytherapy/methods , Neoplasm Recurrence, Local/radiotherapy , Parotid Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Adenoid Cystic/radiotherapy , Carcinoma, Adenoid Cystic/surgery , Carcinoma, Mucoepidermoid/radiotherapy , Carcinoma, Mucoepidermoid/surgery , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Recurrence, Local/surgery , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , Remission Induction , Retrospective Studies , Survival Rate , Treatment Outcome , Young Adult
17.
Neuroscience ; 256: 370-8, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24200923

ABSTRACT

Kainic acid (KA) administration is known to cause seizures and neuronal death in the hippocampus. High-frequency stimulation (HFS) of the hippocampus can be a promising method in the treatment of epilepsy while the mechanism of action is unknown yet. It remains unknown whether HFS is neuroprotective for hippocampal neurons following KA-induced seizures in macaques, although HFS has neuroprotective effects in animal models of Parkinson's disease. We therefore examined the effects of HFS on KA-induced seizures and neuronal survival in macaque's hippocampus. Seizure frequency following KA that led to seizures in macaques was strongly reduced by HFS of the hippocampus. In addition, administration of KA led to marked neuronal apoptosis in the hippocampus, accompanied by increased levels of Bax, activated caspase-3 and decreased levels of Bcl-2. HFS was found to attenuate changes in apoptosis-related proteins and robustly decreased neuronal loss following KA administration. These data indicate that hippocampal HFS can protect hippocampal neurons against KA neurotoxicity, and that HFS neuroprotection is likely to operate with inhibition of apoptosis.


Subject(s)
Electric Stimulation/methods , Hippocampus/physiology , Neurons/drug effects , Seizures/therapy , Analysis of Variance , Animals , Apoptosis/drug effects , Apoptosis/physiology , Biophysics , Caspase 3/metabolism , Disease Models, Animal , Electroencephalography , Excitatory Amino Acid Agonists/toxicity , Hippocampus/pathology , In Situ Nick-End Labeling , Kainic Acid/toxicity , Macaca , Magnetic Resonance Imaging , Male , Seizures/chemically induced , bcl-2-Associated X Protein/metabolism
18.
Placenta ; 34(11): 1014-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24074901

ABSTRACT

INTRODUCTION: Ectopic pregnancy is unique to humans and a leading cause of maternal morbidity and mortality. The etiology remains unknown however factors regulating embryo implantation likely contribute. Leukemia inhibitory factor (LIF) has roles in extravillous trophoblast adhesion and invasion and is present in ectopic implantation sites. We hypothesised that LIF facilitates blastocyst adhesion/invasion in the Fallopian tube, contributing to ectopic pregnancy. METHODS: We immunolocalised LIF receptor (R) in tubal ectopic pregnancy (N = 5). We used an oviduct cell line (OE-E6/E7) to model Fallopian tube epithelial cells and a trophoblast spheroid co-culture model (HTR-8/SVneo cell line formed spheroids) to model blastocyst attachment to the Fallopian tube. We examined LIF signaling pathways in OE-E6/E7 cells by Western blot. The effect of LIF and LIF inhibition (using a novel LIF inhibitor, PEGLA) on first-trimester placental outgrowth was determined. RESULTS: LIFR localised to villous and extravillous trophoblast and Fallopian tube epithelium in ectopic pregnancy. LIF activated STAT3 but not the ERK pathway in OE-E6/E7 cells. LIF stimulated HTR-8/SVneo spheroid adhesion to OE-E6/E7 cells which was significantly reduced after PEGLA treatment. LIF promoted placental explants outgrowth, while co-treatment with PEGLA blocked outgrowth. DISCUSSION: Our data suggests LIF facilitates the development of ectopic pregnancy by stimulating blastocyst adhesion and trophoblast outgrowth from placental explants. Ectopic pregnancy is usually diagnosed after 6 weeks of pregnancy, therefore PEGLA may be useful in targeting trophoblast growth/invasion. CONCLUSION: LIF may contribute to the development of ectopic pregnancies and that pharmacologically targeting LIF-mediated trophoblast outgrowth may be useful as a treatment for ectopic pregnancy.


Subject(s)
Blastocyst/metabolism , Fallopian Tubes/metabolism , Leukemia Inhibitory Factor Receptor alpha Subunit/metabolism , Leukemia Inhibitory Factor/metabolism , Placenta/metabolism , Pregnancy, Tubal/metabolism , Signal Transduction , Adolescent , Adult , Blastocyst/drug effects , Blastocyst/pathology , Cell Adhesion/drug effects , Cell Line , Cell Proliferation/drug effects , Coculture Techniques , Embryo Implantation/drug effects , Epithelium/drug effects , Epithelium/metabolism , Epithelium/pathology , Fallopian Tubes/drug effects , Fallopian Tubes/pathology , Fallopian Tubes/surgery , Female , Humans , Leukemia Inhibitory Factor/antagonists & inhibitors , Leukemia Inhibitory Factor/genetics , Leukemia Inhibitory Factor/pharmacology , Leukemia Inhibitory Factor Receptor alpha Subunit/agonists , Leukemia Inhibitory Factor Receptor alpha Subunit/antagonists & inhibitors , Leukemia Inhibitory Factor Receptor alpha Subunit/genetics , Middle Aged , Placenta/drug effects , Placenta/pathology , Polyethylene Glycols/pharmacology , Pregnancy , Pregnancy, Tubal/pathology , Pregnancy, Tubal/surgery , STAT3 Transcription Factor/agonists , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Spheroids, Cellular , Tissue Culture Techniques , Young Adult
19.
Eur Rev Med Pharmacol Sci ; 17(6): 752-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23609358

ABSTRACT

AIM: The aim of this study was to clarify the clinico-pathological outcome and prognostic significance of phospholipase A2 group IIA (PLA2G2A) in esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Immunohistochemical staining for PLA2G2A was performed on surgical specimens obtained from 132 patients with ESCC, and 43 from matched adjacent non-malignant sites. Differences in PLA2G2A expression and clinical characteristics were compared by χ2 test. Correlations between prognostic outcomes and with PLA2G2A expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Immunoreactivity of PLA2G2A was observed in 32% (42 of 132) of ESCC tissues compared with negative staining in matched adjacent non-malignant sites. In addition, PLA2G2A expression inversely correlated with pathological classification (p < 0.05 for T, N, and M classifications) and clinical staging (p = 0.03). Furthermore, patients with positive PLA2G2A had prolonged overall survival (p < 0.01). CONCLUSIONS: Reduced PLA2G2A expression may be a risk factor for advanced clinicopathological classification and poor patient survival. These findings suggest that PLA2G2A may serve as a useful marker for the prognostic evaluation of ESCC patients.


Subject(s)
Carcinoma, Squamous Cell/enzymology , Esophageal Neoplasms/enzymology , Group II Phospholipases A2/biosynthesis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma , Female , Humans , Male , Middle Aged
20.
Strahlenther Onkol ; 189(6): 502-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23625361

ABSTRACT

BACKGROUND AND PURPOSE: This retrospective study was to evaluate the local control and survival of (125)I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. PATIENTS AND METHODS: A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received (125)I brachytherapy alone from 2001-2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100-160 Gy. RESULTS: Patients were followed for 12-122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5 %, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1 %, respectively. Tumors > 6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up. CONCLUSION: (125)I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.


Subject(s)
Brachytherapy/methods , Carcinoma, Adenoid Cystic/radiotherapy , Facial Neoplasms/radiotherapy , Iodine Radioisotopes/therapeutic use , Mouth Neoplasms/radiotherapy , Nose Neoplasms/radiotherapy , Salivary Gland Neoplasms/radiotherapy , Skull Base Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Adenoid Cystic/pathology , Child , Disease Progression , Facial Neoplasms/pathology , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mouth Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Nose Neoplasms/pathology , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Adjuvant , Retrospective Studies , Salivary Gland Neoplasms/pathology , Skull Base Neoplasms/pathology , Young Adult
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