Tspan8 and CD151 promote metastasis by distinct mechanisms

AimCD151 and Tspan8 are metastasis-promoting tetraspanins. To define whether Tspan8 and CD151 fulfil redundant or additive activities, Tspan8 and CD151 were stably knocked-down in highly metastatic rat pancreatic adenocarcinoma BSp73ASML cells (ASML^wt, ASML-Tspan8^kd, ASML-CD151^kd).ResultsASML-CD151^kd and ASML-Tspan8^kd cells metastasise via the lymphatics to the lung with delay and a 2–3-fold increased survival time compared to ASML^wt cells. Yet, CD151 and Tspan8 distinctly contribute to metastasis. Pronounced adhesion of ASML-Tspan8^kd cells is due to CD151 associating with the alpha3 integrin chain, whereas strikingly increased ASML-CD151^kd cell motility is efficiently inhibited by anti-beta4. These opposing Tspan8 and CD151 activities are due to distinct beta4 recruitment into Tspan8 complexes, accompanied by beta4 phosporylation, src recruitment, focal adhesion kinase (FAK) and Ras activation. On the other hand, CD151 associates more readily with proteases, particularly matrix metalloproteinase (MMP)13 and MMP9, than Tspan8. The stronger CD151–MMP association is accompanied by pronounced collagen I and IV and laminin111 degradation, also seen in metastatic tissue, and strengthens invasiveness.ConclusionCD151 and Tspan8 coordinately promote metastasis, where Tspan8 overrides the adhesive features of CD151 by recruiting integrins out of adhesion into motility promoting complexes. CD151 more efficiently than Tspan8 recruiting and activating MMP9 and MMP13 creates a path for migrating tumour cells.     

Is it possible to predict para-aortic lymph node metastasis in endometrial cancer?

Objective

The purpose of this study was to determine the histopathologic risk factors for pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastasis in endometrial cancer (EC) and to identify in which patients PALN dissection should be performed.

Study design

A total of 204 consecutive patients, with EC and underwent systematic pelvic and para-aortic lymphadenectomy extending to the renal vessels, were studied retrospectively. Statistical significance between risk factors was examined using multivariant logistic regression analysis.

Results

Cell type, depth of myometrial invasion and tumor size were found to be independently related to PLN metastasis. PLN metastasis in any site and lymphovascular invasion (LVSI) were independent prognostic factors for predicting PALN metastasis. The sensitivity, specificity and the NPV of PLN metastasis for detecting PALN metastasis were 80.8%, 89.3% and 97%, respectively. Furthermore, the 204 patients were divided into two groups according to the presence of one of these following factors: (1) non-endometrioid cell type, (2) PLN metastasis, (3) LVSI, (4) adnexal metastasis and (5) serosal involvement. Among these 204 patients, 104 had one or more of these factors (group A), and 100 patients had none of these factors (group B). PALN metastasis was significantly greater in group A, compared to group B. The sensitivity and the NPV of these combined prognostic factors for predicting PALN metastasis were 96.2% and 99%, respectively.

Conclusions

Presence of non-endometrioid cell type, PLN metastasis, LVSI, adnexal metastasis or serosal involvement diagnosed by frozen section (FS) seem to be poor prognostic factor for PALN metastasis in EC. Also, PALN dissection should be extended to the level of the renal vessels in all patients who will undergo PALN dissection, due to frequent involvement of the supramesenterial region.     

Cytokeratin 19 expression in primary thoracic tumors and lymph node metastases

BackgroundThe use of one-step nucleic acid amplification (OSNA), which allows for the rapid intraoperative detection of lymph node (LN) metastasis, is becoming more widely accepted in breast cancer. To provide basic data for the development of this method for lung tumors, we conducted a large-scale investigation of cytokeratin (CK) 19 expression in thoracic tumors.Patients and methodsWe examined CK19 expression in specimens from a total of 801 surgically resected samples of primary lung adenocarcinoma (ADC), squamous cell carcinoma (SQC), large-cell carcinoma (LCC), pleomorphic carcinoma (PC), large cell neuroendocrine carcinoma (LCNEC), small cell carcinoma (SCC), and carcinoid tumor (CT) as well as pleural malignant mesothelioma and lung metastatic deposits from breast cancer using tissue microarrays (TMAs) and whole sections. We also compared the CK19 expression status between primary sites and LN metastatic deposits.ResultsThe overall rate of CK19 expression as observed on TMAs and whole sections in the 801 analyzed cases was 88.0%. CK19 expression was detected in 94.6% of ADCs, 93.6% of SQCs, 54.5% of LCCs, 54.8% of PCs, 77.4% of LCNECs, 31.8% of SCCs, 34.0% of CTs, and 92.9% of malignant mesotheliomas. Expression of CK19 was also detected in 90.9% of lung metastatic deposits from breast carcinomas. CK19 expression was maintained between CK19-positive primary sites and the corresponding LN metastatic deposits. Of note, a portion of CK19-negative primary tumors showed upregulation of CK19 protein expression in LN metastases.ConclusionsMost thoracic tumors, except for PCs, CTs, and SCCs, were positive for CK19. We also found that CK19 expression was maintained between CK19-positive primary tumors and the corresponding LN metastatic deposits. These results may be useful in the development of the OSNA method for the intraoperative detection of LN metastasis in non-small cell lung cancer (NSCLC).     

肝癌患者血清中透明质酸、层粘蛋白、Ⅵ型胶原的测定及临床意义

目的探讨透明质酸（HA）、层粘蛋白（LN）和Ⅳ型胶原（Ⅳ-C）三项肝纤维化指标在原发性肝癌和转移性肝癌血清中的变化,阐明肝纤维化和肝功能指标两者之间的相关关系。方法正常对照组30例、原发性肝癌组23例和转移性肝癌组20例。采用半自动化学发光法测定23例原发性和20例转移性肝癌病人血清中的HA、LN、Ⅳ-C三项肝纤维化指标。同时检测天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、谷氨酰转肽酶（γ-GT）三项肝功能指标。结果 43例原发性肝癌和转移性肝癌病人HA、LN、Ⅳ-C水平均明显高于正常对照组（P〈0.01）。HA、LN、Ⅳ-C原发性肝癌组与转移性肝癌组比较,有统计学差异（P〈0.05）,原发性肝癌组明显升高。肝功能指标在原发性肝癌组明显升高,与转移性肝癌组比较,有统计学差异（P〈0.01）,HA、LN、Ⅳ-C与肝功能指标之间有相关性。结论 HA、LN和Ⅳ-C是判断肝纤维化、肝硬变的程度的良好检测指标,重复性好,无创伤,便于掌握病变进展,临床应用效果好。     

lncRNA FAM95B1在胶质瘤中的表达及其影响LN382细胞增殖和迁移的可能机制

目的:探讨lncRNA FAM95B1对胶质瘤细胞增殖和迁移能力的影响并探究其相关作用机制.方法:选取2018年1月至2020年8月于合肥市第三人民医院行手术治疗的38例胶质瘤患者的胶质瘤组织及癌旁组织标本,利用qPCR检测胶质瘤组织与4种细胞系中FAM95B1的表达水平,以表达最低的胶质瘤LN382细胞为研究对象,转...     

抗嗜中性粒细胞胞浆抗体与狼疮性肾炎的关系

目的探讨抗嗜中性粒细胞胞浆抗体（ANCA）与狼疮性肾炎（LN）临床相关表现和发病机制的关系。方法分别应用间接免疫荧光法和酶联免疫吸附分析的方法,检测81例LN患者血清中的ANCA,并分析ANCA与LN临床表现和其它实验室检查结果之间的关系。结果单用间接免疫荧光法检测时,ANCA在LN中的阳性率是30.9％（25／81）。对间接免疫荧光法检测为阳性的血清,用酶联免疫吸附分析法进行验证,结果仅有72.0％（18／25）仍为阳性,全部是核周型ANCA（p-ANCA）,未见中央型ANCA（c-ANCA）出现。ANCA阳性组LN患者合并浆膜炎、神经系统累及、贫血、抗ds-DNA抗体阳性和低补体的频率均显著高于ANCA阴性组LN患者。结论ANCA在LN中的阳性率为30.9％,并与LN特定的临床表现相关,提示ANCA可能参与了LN的发病过程。     

Lithium normalizes elevated intracellular sodium

BACKGROUND: Both mania and bipolar depression are characterized by elevations of intracellular sodium concentrations. This observation has been purported to be central to the pathophysiology of abnormal moods in bipolar illness. Reduction of sodium influx is a proposed shared mechanism of action of effective mood stabilizers, but direct documentation of this effect for lithium has never been demonstrated. METHODS: Flame spectroscopic determinations of intracellular sodium concentration were performed in the human glioma cell line, LN292, after treatment with the sodium pump inhibitor, ouabain, and co-treatment with ouabain and lithium. RESULTS: Ouabain 0.1 microM doubles the intracellular sodium concentration after 3 days. Pretreatment with lithium 1 mM for 1 week normalizes intracellular sodium. CONCLUSION: This is the first demonstration that lithium can normalize abnormally elevated intracellular sodium levels. This may be an important mechanism of lithium action.     

发热 贫血 血小板减少 神经系统异常

患儿男,13岁7个月。2010-11-04以发热伴面色苍白1周为主诉入住中国医科大学附属第一医院儿科病房。患儿1周前开始无诱因发热伴颈部包块,无触痛,咳嗽无痰,体温最高达39℃,同时伴有面色苍白、乏力,无皮肤黄染,尿色略黄。曾于当地医院就诊,静滴抗炎类药物3d(具体药物不详),病情无好转,化验发现贫血严重。患儿病来时有烦躁,无水肿,睡眠可,精神差,进食差,鼻衄2次,黑便1次,无明显腹痛及尿量减少。     

红花注射液对慢性肾疾病血清纤维化指标表达的临床观察

目的：研究红花注射液对慢性肾脏病患者肾功能、肾纤维化的作用。方法：60例患者随机分为治疗组40例和对照组20例,对照组予以一般治疗和对症治疗,治疗组在对照组治疗的基础上予红花注射液20 mL静滴,日1次,2周为1疗程,1-3疗程后观察红花注射液对慢性肾脏病患者肾功能指标即血清肌酐（Scr）、尿素氮（BUN）、内生肌酐清除率（Ccr）和纤维化指标即血清层粘连蛋白（LN）、Ⅲ型前胶原（PC-Ⅲ）、Ⅳ型胶原（CⅣ）、透明质酸（HA）的影响。结果：与对照组患者比较,治疗组能明显降低慢性肾脏病患者的Scr、BUN、LN、PC-Ⅲ、CⅣ、HA水平。两者比较有统计学意义（P〈0.05）。结论：红花注射液能改善肾纤维化,延缓慢性肾脏病的进程。