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1.
J Cell Mol Med ; 26(5): 1466-1472, 2022 03.
Article in English | MEDLINE | ID: mdl-35166019

ABSTRACT

Phospholipases A2 (PLA2) are a superfamily of enzymes, playing a critical role in the development of various human cancers. However, the mechanism of PLA2 as an oncogene in glioblastoma remains largely unknown. In this study, we explored the effects of PLA2 on glioblastoma and investigated the underlying mechanism. The results showed that PLA2 was highly expressed in glioblastoma. Patients with a high PLA2 level have low overall survival than those with low PLA2 expression. PLA2 overexpression promoted glioblastoma cell proliferation and viability and inhibited cell apoptosis by inducing cell cycle transition from G1 to S stage. Knockdown of PLA2 inhibited tumor growth in the xenograft mice model. In addition, PLA2 knockdown decreased the protein level of MCM2 and MCM5. These findings identify PLA2 as an oncogene in glioblastoma progression and provide a promising strategy to treat glioblastoma in the future.


Subject(s)
Glioblastoma , Animals , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation , DNA Replication/genetics , Glioblastoma/pathology , Humans , Mice , Oncogenes , Phospholipases A2/genetics , Phospholipases A2/metabolism , Phospholipases A2/pharmacology
2.
Ann Hematol ; 100(5): 1251-1260, 2021 May.
Article in English | MEDLINE | ID: mdl-33686491

ABSTRACT

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochemistry. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A positive correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 months, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 months, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-molecule Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.


Subject(s)
Multiple Myeloma/genetics , Proto-Oncogene Proteins c-myc/genetics , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Chromosome Aberrations , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/pathology , Prognosis , RNA, Messenger/genetics
5.
Atten Percept Psychophys ; 77(8): 2728-39, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26337611

ABSTRACT

In this paper, we explore the rules followed by the auditory system in grouping temporal patterns. Imagine the following cyclical pattern (which we call an "auditory necklace"-AN for short-because those patterns are best visualized as beads arranged on a circle) consisting of notes (1s) and rests (0s): … 1110011011100110 …. It is perceived either as repeating 11100110 or as repeating 11011100. We devised a method to explore the temporal segmentation of ANs. In two experiments, while an AN was played, a circular array of icons appeared on the screen. At the time of each event (i.e., note or rest), one icon was highlighted; the highlight moved cyclically around the circular array. The participants were asked to click on the icon that corresponded to the note they perceived as the starting point, or clasp, of the AN. The best account of the segmentation of our ANs is based on Garner's (1974) run and gap principles. An important feature of our probabilistic model is the way in which it combines the effects of run length and gap length: additively. This result is an auditory analogue of Kubovy and van den Berg's (2008) discovery of the additivity of the effects of two visual grouping principles (proximity and similarity) conjointly applied to the same stimulus.


Subject(s)
Auditory Perception/physiology , Acoustic Stimulation , Algorithms , Female , Humans , Male , Models, Statistical , Psychomotor Performance/physiology , Young Adult
6.
Q J Exp Psychol (Hove) ; 68(11): 2243-54, 2015.
Article in English | MEDLINE | ID: mdl-25747914

ABSTRACT

We provide a test of Patel's [( 2003 ). Language, music, syntax and the brain. Nature Neuroscience, 6, 674-681] shared syntactic integration resources hypothesis by investigating the competition between determinants of rhythmic parsing and linguistic parsing using a sentence-rhythm Stroop task. We played five-note rhythm patterns in which each note is replaced with a spoken word of a five-word sentence and asked participants to indicate the starting point of the rhythm while they disregarded which word would normally be heard as the first word of the sentence. In Study 1, listeners completed the task in their native language. In Study 2, we investigated whether this competition is weakened if the sentences were in a listener's non-native language. In Study 3, we investigated how much language mastery is necessary to obtain the effects seen in Studies 1 and 2. We demonstrate that processing resources for rhythmic parsing and linguistic parsing overlap with one another, particularly when the task is demanding. We also show that the tendency for language to bias processing does not require deep knowledge of the language.


Subject(s)
Psycholinguistics , Speech , Stroop Test , Acoustic Stimulation , Auditory Perception , Conflict, Psychological , Form Perception , Humans , Learning , Photic Stimulation
7.
Brain Tumor Pathol ; 30(2): 117-21, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22899540

ABSTRACT

We describe a case of dural angioleiomyoma (ALM) of the middle cranial fossa. A 62-year-old man was referred to our center for fracture of the left clavicle because of a fall, and he had a sudden seizure during admission. The mass was completely resected. The tumor base was located at the bottom of the temporal lobe in the front of the petrous apex and near the cavernous sinus. After 7 months, the postoperative course demonstrated no tumor recurrence. The lesion had the typical appearance of ALM. Mitoses and necrosis were not identified. The lesion contained multifocality of fat in some areas of spindle-shaped cells, and markedly myxoid change was present. The spindle cells were positive for SMA and DES and negative for EMA, HMB-45, p53 and p16. A small focus of fat was positive for S-100. Less than 1% of the tumor cells showed immunoreactivity for Ki-67. EBV-encoded RNA was negative for tumor cells. Stainings for p53, p16, Ki-67 and EBV infection need to be carried out in cases of intracranial ALM because they are correlated with the biological behavior and prognosis of the tumor.


Subject(s)
Angiomyoma/pathology , Skull Base Neoplasms/pathology , Angiomyoma/diagnosis , Angiomyoma/surgery , Biomarkers, Tumor/metabolism , Cranial Fossa, Middle , Cyclin-Dependent Kinase Inhibitor p16 , Herpesvirus 4, Human/genetics , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Middle Aged , Neoplasm Proteins/metabolism , Prognosis , RNA, Viral/metabolism , Skull Base Neoplasms/diagnosis , Skull Base Neoplasms/surgery , Tumor Suppressor Protein p53/metabolism
8.
Neuropsychologia ; 51(2): 267-74, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23084982

ABSTRACT

Studies in motor timing have shown that the basal ganglia and cerebellum play an important role in temporal processing. Timing studies in Cerebellar/ataxic Disorders (CD) and Parkinson's disease (PD) patients contrast the roles of the cerebellum and basal ganglia in motor timing. Here, we used a synchronization-continuation task to compare accuracy and variability of motor timing during repetitive tapping. We compared data collected for the present study - from patients with CD and healthy controls - to data from a previous study with patients with PD. We asked participants to tap at Inter-stimulus Intervals (ISIs) of 250, 500, 1000, and 2000 ms. Using Linear Mixed Models (LMMs), we explored how ISI, Task Phase, and Diagnosis interacted to determine the (i) the accuracy and (ii) the variability of tapping. In our analysis of accuracy, we found evidence that during the synchronization phase, at ISI=250 ms, CD patients lagged 'behind the beat'; whereas our previous work has suggested that medicated PD patients hasten 'ahead of the beat'. In our analysis of variability, we observed that at ISIs below 1000 ms, CD patients showed greater variability in motor timing than the healthy controls, while PD patients showed less variability than CD patients and healthy controls during the synchronization phase at the 1000 ms ISI. These results highlight the differential performance on explicit motor timing between patients with disorders of the cerebellum and basal ganglia. Our results illustrate a novel approach to discerning cognitive control of motor timing.


Subject(s)
Cerebellar Diseases/complications , Cerebellum/pathology , Parkinson Disease/complications , Perceptual Disorders/etiology , Time Perception/physiology , Aged , Aged, 80 and over , Basal Ganglia/pathology , Female , Humans , Linear Models , Magnetic Resonance Imaging , Male , Middle Aged
9.
Med Oncol ; 30(1): 445, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23307254

ABSTRACT

Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Transitional Cell/metabolism , SOXB1 Transcription Factors/biosynthesis , Urinary Bladder Neoplasms/metabolism , Aged , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Disease-Free Survival , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Proportional Hazards Models , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SOXB1 Transcription Factors/analysis , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
10.
Philos Trans R Soc Lond B Biol Sci ; 367(1591): 954-64, 2012 Apr 05.
Article in English | MEDLINE | ID: mdl-22371617

ABSTRACT

We present a sceptical view of multimodal multistability--drawing most of our examples from the relation between audition and vision. We begin by summarizing some of the principal ways in which audio-visual binding takes place. We review the evidence that unambiguous stimulation in one modality may affect the perception of a multistable stimulus in another modality. Cross-modal influences of one multistable stimulus on the multistability of another are different: they have occurred only in speech perception. We then argue that the strongest relation between perceptual organization in vision and perceptual organization in audition is likely to be by way of analogous Gestalt laws. We conclude with some general observations about multimodality.


Subject(s)
Auditory Perception/physiology , Visual Perception/physiology , Acoustic Stimulation , Models, Neurological , Models, Psychological , Photic Stimulation , Psychoacoustics , Psychophysics
11.
J Chin Med Assoc ; 75(6): 269-74, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22721621

ABSTRACT

BACKGROUND: TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be up-regulated or be down-regulated in many cancer types, suggesting the oncogenic function of TRIM29 may be depend on different molecular signaling pathway. It was found that ß-catenin function (a key molecule in the Wnt signaling pathway) was required for TRIM29's oncogenic effects. TRIM29 gene expression was also found to be heterogeneous in non-small-cell lung cancer (NSCLC) subtypes. In this study, the possible associations of TRIM29 expression with clinicopathological factors, prognosis, and ß-catenin in human NSCLC were analyzed. METHODS: TRIM29 and ß-catenin expression of tumor and adjacent normal tissues in 251 cases of NSCLC treated by surgery was detected by the Immunohistochemical method. The relationship between clinical pathological data, ß-catenin, and TRIM29 expression was analyzed. RESULTS: TRIM29 expression of tumor tissues was significantly higher than adjacent normal tissues. Expression of TRIM29 in squamous cell carcinoma (SC) tissues was positively correlated with abnormal expression of ß-catenin, histological grade, tumor-node-metastasis (TNM) stage, and lymph node metastasis and that was positively correlated with tumor size, histological grading, TNM stage and lymph node metastasis in adenocarcinoma (AC). TRIM29 expression in SC and AC was significantly different and the intensity of poorly differentiated SC was significantly higher than that of AC. High-expression of TRIM29, poorly differentiated grade, and high clinical stage were independent prognostic indicators. CONCLUSION: We considered that TRIM29 may play a reference role in distinguish poorly differentiated AC and SC of NSCLC, combining with CK5/6 and CK7, and it could improve postoperative assessment and have the reference value for clinical treatment. The interaction between TRIM29 and ß-catenin may participate in the development of lung SC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , DNA-Binding Proteins/physiology , Lung Neoplasms/pathology , Transcription Factors/physiology , beta Catenin/physiology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Small Cell/etiology , Carcinoma, Small Cell/pathology , DNA-Binding Proteins/genetics , Female , Humans , Lung Neoplasms/etiology , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , Transcription Factors/genetics , beta Catenin/genetics
12.
Chin Med J (Engl) ; 124(23): 4002-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22340332

ABSTRACT

BACKGROUND: Blood culture contamination is a significant adverse event. The aim of this project was to evaluate the efficacy of a strict blood collection procedure in reducing the blood culture contamination rate. METHODS: A prospectively controlled study was performed in two different medical areas in Peking Union Medical College Hospital (PUMCH) for 16 months (from May 2006 to September 2007). In test group, a strict blood collection procedure was carried out by trained nurses with the veinpuncture sites were scrupulously disinfected with 2.5% tincture of iodine plus 70% alcohol. In control group, commonly used procedure in PUMCH was performed with 0.45% chlorhexidine acetate plus 0.2% iodine. Blood culture positive results for 4 target organisms (Coagulase-negative staphylococci, Propionibacterium acnes, Corynebacterium species and Bacillus species) were further assessed by physicians from infectious department to determine whether a sample was true positive (pathogen) or false positive (contamination). RESULTS: Total 9321 blood culture collections were analyzed. The blood culture contamination rate in test group was significantly lower than that in control group (5/3177 (0.16%) vs. 77/6144 (1.25%); χ(2) = 13.382, P < 0.001). The most common contaminant was Coagulase-negative staphylococcus (76.83%). The average cultural time during which contaminated samples became positive was longer than that for true pathogen samples (42.0 hours vs. 13.9 hours, P = 0.041). CONCLUSION: Using a strict blood collection procedure can significantly reduce blood culture contamination rate.


Subject(s)
Blood Specimen Collection/adverse effects , Blood Specimen Collection/methods , Blood/microbiology , Disinfection/methods , Anti-Infective Agents, Local/pharmacology , Bacillus/drug effects , Chlorhexidine/pharmacokinetics , Corynebacterium/drug effects , Humans , Iodine/pharmacology , Propionibacterium/drug effects , Prospective Studies , Staphylococcus/drug effects
13.
Article in English | MEDLINE | ID: mdl-22207839

ABSTRACT

Parkinson's disease (PD) is characterized by difficulty with the timing of movements. Data collected using the synchronization-continuation paradigm, an established motor timing paradigm, have produced varying results but with most studies finding impairment. Some of this inconsistency comes from variation in the medication state tested, in the inter-stimulus intervals (ISI) selected, and in changeable focus on either the synchronization (tapping in time with a tone) or continuation (maintaining the rhythm in the absence of the tone) phase. We sought to re-visit the paradigm by testing across four groups of participants: healthy controls, medication naïve de novo PD patients, and treated PD patients both "on" and "off" dopaminergic medication. Four finger tapping intervals (ISI) were used: 250, 500, 1000, and 2000 ms. Categorical predictors (group, ISI, and phase) were used to predict accuracy and variability using a linear mixed model. Accuracy was defined as the relative error of a tap, and variability as the deviation of the participant's tap from group predicted relative error. Our primary finding is that the treated PD group (PD patients "on" and "off" dopaminergic therapy) showed a significantly different pattern of accuracy compared to the de novo group and the healthy controls at the 250-ms interval. At this interval, the treated PD patients performed "ahead" of the beat whilst the other groups performed "behind" the beat. We speculate that this "hastening" relates to the clinical phenomenon of motor festination. Across all groups, variability was smallest for both phases at the 500-ms interval, suggesting an innate preference for finger tapping within this range. Tapping variability for the two phases became increasingly divergent at the longer intervals, with worse performance in the continuation phase. The data suggest that patients with PD can be best discriminated from healthy controls on measures of motor timing accuracy, rather than variability.

14.
Int J Surg Pathol ; 18(5): 363-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20667924

ABSTRACT

Here, the authors describe a case of giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity-which could be a distinctive form of thymic carcinoma-which expressed CD5 and CD45. To the authors' knowledge, there has been no previous report on this subject. A 62-year-old woman presented with continuous pain in the left back associated with coughing and shortness of breath for more than 2 months prior to referral to the hospital. Palliative resection of a mediastinal tumor was performed. During the operation, it was found that the mass occupied most of the chest invading the chest wall, aorta, vena cava, and lung tissue. The patient soon died from diabetic complications in spite of anti-infection treatment. The tumor was composed of large areas of necrosis and anaplastic neoplastic giant cells with high mitotic activity, and osteoclast-like cells; there was marked inflammatory cell infiltration. The anaplastic neoplastic giant cells were immunoreactive for CKpan, CD5, CD45, VIM, and p53. Approximately 50% to 60% of the tumor cells showed immunoreactivity for Ki-67. In situ hybridization for Epstein-Barr virus-encoded RNA was negative for tumor cells and nonneoplastic osteoclastic giant cells. Because this tumor is very rare, extensive clinical, radiological, and morphological examinations as well as immunohistochemical studies are essential to make the diagnosis.


Subject(s)
Carcinoma/pathology , Osteoclasts/pathology , Thoracic Cavity/pathology , Thoracic Neoplasms/pathology , Thymus Neoplasms/pathology , Biomarkers, Tumor/metabolism , CD5 Antigens/metabolism , Carcinoma/metabolism , Carcinoma/surgery , Fatal Outcome , Female , Humans , Leukocyte Common Antigens/metabolism , Middle Aged , Palliative Care , Thoracic Neoplasms/metabolism , Thoracic Neoplasms/surgery , Thymus Neoplasms/metabolism , Thymus Neoplasms/surgery
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