PTK7 regulates Id1 expression in CD44-high glioma cells

Background

CD44 is a molecular marker associated with molecular subtype and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting the CD44-high gliomas.

Methods

Protein tyrosine kinase 7 (PTK7) mRNA expression was analyzed based on The Cancer Genome Atlas glioblastoma dataset. PTK7 expression was depleted through lentivirus-mediated short hairpin RNA knockdown. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to evaluate cell apoptosis following PTK7 knockdown. Gene expression analysis was performed on Affymetrix microarray. A nude mice orthotopic tumor model was used to evaluate the in vivo effect of PTK7 depletion.

Results

PTK7 is highly expressed in CD44-high glioblastoma and predicts unfavorable prognosis. PTK7 knockdown attenuated cell proliferation, impaired tumorigenic potential, and induced apoptosis in CD44-high glioma cell lines. Gene expression analysis identified inhibitor of DNA Binding 1 (Id1) gene as a potential downstream effector for PTK7. Overexpression of Id1 mostly restored the cell proliferation and colony formation attenuated by PTK7 depletion. PTK7 enhanced anchorage-independent growth in normal human astrocytes, which was attenuated by Id1 knockdown. Furthermore, PTK7 regulated Id1 expression through modulating TGF-β/Smad signaling, while pharmacological inhibition on TGF-β/Smad signaling or PTK7/Id1 depletion attenuated TGF-β–stimulated cell proliferation. PTK7 depletion consistently reduced Id1 expression, suppressed tumor growth, and induced apoptosis in a murine orthotopic tumor model, which could be translated into prolonged survival in tumor-bearing mice.

Conclusions

PTK7 regulates Id1 expression in CD44-high glioma cell lines. Targeting PTK7 could be an effective strategy for treating glioma with high CD44 expression.     

MR imaging features of clear-cell meningioma with diffuse leptomeningeal seeding

Clear-cell meningioma is a rare disease entity showing a more aggressive nature, clinically, than those of other subtypes of meningioma. It occurs in younger persons and commonly in the spinal canal. The recurrence rate has been reported to be as high as 60%. We present a case of clear-cell meningioma in a 17-year-old man in whom initial MR imaging showed localized leptomeningeal enhancement that had progressed into the entire subarachnoid space after surgical resection of the primary tumor.     

Impact of left ventricular epicardial and biventricular pacing on ventricular repolarization in normal-heart individuals and patients with congestive heart failure.

AIMS: Malignant ventricular arrhythmias can arise in a subset of congestive heart failure (CHF) patients after they undergo cardiac resynchronization therapy (CRT), thus counteracting the haemodynamic benefits typically associated with biventricular pacing. This study seeks to assess whether alteration of the ventricular transmural repolarization and conduction due to reversal of the depolarization sequence during epicardial or biventricular pacing facilitate the development of ventricular arrhythmias. METHODS AND RESULTS: ECGs and monophasic action potential (MAP) were recorded during programmed stimulation from right ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or both (biventricular, Bi-V) in 15 individuals without structural heart diseases. In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo, LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT, and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and compared. In subjects with or without structural heart disease, compared with RV-Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV-Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal-heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition to prolonged myocardial repolarization time and delayed endocardial activation. During follow-up, sudden death and arrhythmia storm occurred in two CHF patients after CRT. CONCLUSION: Epicardial and biventricular pacing prolong the time and increase the dispersion of myocardial repolarization and delay the transmural conduction. All of these should be considered as potential arrhythmogenic factors in CHF patients who receive CRT.     

茶多酚与茶色素对大鼠肝癌前病变组织细胞周期调节因子的影响

目的 利用大鼠肝癌前病变模型探讨茶多酚和茶色素对细胞周期因子的影响。方法 采用改良的Solt-Farber大鼠肝癌癌前病变模型,分别饮用0．1％和0．1％茶多酚,喂养56d。采用Westernblot方法观察细胞周期素D1、D21^WAF1/CIPI、GADD45和PCNA蛋白的表达;用RT－PCR在mRNA水平观察Ckd4的表达。结果 茶多酚和茶色素显著抑制细胞周期素D1、Ckd4和PCNA表达,诱导P21^WAF1／CIP1和GAD45蛋白表达。结论 茶多酚和茶色素通过调节细胞周期调节因子而诱导细胞周期阻滞,抑制细胞过度增值。     

脑络通胶囊中维生素B6的含量测定

目的：采用高效液相色谱法测定脑络通胶囊中维生素B6的含量。方法：以十八烷基硅烷键合硅胶为填充剂，以0．5％磷酸二氢钾．甲醇．三乙胺（85：14．5：0．5）为流动相，流速1．0mL·min^-1，检测波长290nm。结果：进样量在0．646—2．582μg范围内与峰面积呈良好的线性关系，相关系数0．9999，回收率100．16％。结论：本方法操作简便，精密度好，结果准确可靠，可以作为该药品的质量检测标准。     

Head and neck sarcomas: the UCLA experience

Purpose

To profile the clinical presentation, subtype distribution, and treatment results of sarcomas of the head and neck at a single tertiary academic center over an 11-year period.

Materials and methods

A retrospective review was performed by examining the records and reviewing the pathology of 186 patients with head and neck sarcomas treated at UCLA Medical Center from 2000 to 2011.

Results

The mean age of the study population was 49 ± 22 years. 58% of the patients were male and 42% were female. Median duration of follow-up for the entire group was 18.5 months. The most common presenting symptom was a mass lesion in 59.9% of patients. The nasal cavity/sinus was the most common presenting site seen in 22% of patients. Solitary fibrous tumor/hemangiopericytoma was the most common subtype. 15% of patients had evidence of prior radiation exposure. 26.3% of tumors were greater than 5 cm and 35.5% were high-grade. Margins were positive in 31.2% of patients. Lymph node metastasis was rare at 6.5%. Perineural invasion was identified in 6.5%. Among all subtypes, 5-year recurrence-free survival and overall survival were 50% and 49%, respectively. Multivariate analysis demonstrated that grade and margin status were predictors of recurrence-free survival while grade and age affected overall survival.

Conclusions

Head and neck sarcomas are a rare entity frequently presenting as a mass lesion. In our series, lesions tended to be high-grade with a significant portion of surgical specimens having positive margins. Grade and margin status were the most important predictors of survival.     

Damage accrual in southern Chinese patients with systemic lupus erythematosus

OBJECTIVE: To study the predictive factors of damage accrual in a large cohort of southern Chinese patients with systemic lupus erythematosus (SLE). METHODS: A cohort of consecutive Chinese patients with SLE was recruited in 1998 and prospectively followed for 3 years. Demographic data, disease manifestations and activity, medication use, and damage scores were recorded. Organ damage was assessed using the SLE International Collaborating Clinics Damage Index (SDI), which was scored at study entry and then annually. Disease flares and new damage were recorded during followup visits. Predictive factors of new damage were studied by statistical analysis. RESULTS: The cohort consisted of 242 consecutive patients with SLE (221 women, 21 men; F:M = 10.5:1). All fulfilled at least 4 American College of Rheumatology criteria for the classification of SLE. At entry, mean age was 35.7 +/- 10.7 years and mean disease duration was 75.3 +/- 79 months. Ninety (38%) patients had damage. The mean SDI score at year 0 was 0.76 +/- 1.3 (range 0-8), and this increased significantly to 1.33 +/- 1.7 (range 0-9) at year 3 (p < 0.001). The most frequent organ damage at entry was musculoskeletal (26.5%), followed by damage in central nervous system (18.4%), renal (15.1%), and cardiovascular (12.4%) systems. The increase in SDI scores over the 3 year period was primarily caused by the increase in renal, musculoskeletal, and gonadal damage. Twelve patients died. Multiple regression revealed that the number of major disease flares and the use of cyclophosphamide were independent factors predictive of damage accrual. An increase in SDI scores was associated with mortality risk (OR 1.47 per 1 point, 95% CI 1.03-2.11, p = 0.04). CONCLUSION: The damage scores of our SLE cohort increased significantly over 3 years. Severe disease flares and the use of cyclophosphamide predicted new damage. Increase in damage was associated with mortality risk. Judicious use of immunosuppressive agents to achieve prompt control of disease activity was essential in minimizing damage and improving survival of our patients with SLE.     

鼻内镜辅助支撑喉镜下新生儿咽喉部肿物的手术治疗

目的 探讨新生儿咽喉部肿物患者的临床表现及手术方式。方法 通过回顾2020—2022年就诊于兰州大学第二医院的3例新生儿咽喉部肿物患者的临床资料,总结分析3例新生儿咽喉部肿物患者的临床表现及治疗方法。3例患者中,咽喉部囊肿1例,咽部毛息肉1例,咽部畸胎瘤1例。结果 3例患儿均表现为呼吸或吸吮困难,均在鼻内镜辅助下顺利进行支撑喉镜咽喉部肿物切除手术。随访10个月以上,均无复发。结论 鼻内镜的运用可以帮助明确肿物基底部及其与周围组织的关系,确定手术切除范围,在鼻内镜辅助的支撑喉镜下行咽喉部肿物切除,可以完整切除肿瘤,充分止血,并发症少,应用于新生儿患者具有一定的优势。     

人流感病毒H1N1与禽流感病毒H5N1感染人神经胶质细胞的实验研究

目的：研究人流感病毒（H1N1）及禽流感病毒（H5N1）感染人神经胶质细胞后,促炎症因子的分泌特点。方法：分离培养人胶质细胞,用H1N1及H5N1分别感染刺激人胶质细胞;用RT-PCR技术探求白细胞介素（IL）-1β、-6和肿瘤坏死因子（TNF）-α变化。结果：与阴性对照比,H1N1和H5N1感染人神经胶质细胞IL-1β、-6和TNF-α的表达量均增高,且H5N1的表达量多于H1N1。结论：H1N1与H5N1可体外感染人神经胶质细胞,并诱导其分泌大量促炎症因子,提示此与流感病毒感染中枢神经系统所致的功能紊乱及免疫病理损伤有关。