层粘连蛋白受体与胆管癌细胞不同转移性亚群的关系研究

探讨胆管癌细胞不同转移性亚群层粘连蛋白受体的表达差异。以腹膜浸润筛选模型筛选胆管癌细胞高、低转移性亚群 ,体外侵袭实验验证筛选结果 ,流式细胞仪比较两亚群间层粘连蛋白受体的表达差异。结果显示 ,本研究成功地以腹膜浸润筛选模型筛选出胆管癌细胞高、低转移性亚群 ,体外侵袭实验进一步验证了两亚群间存在着侵袭能力上的显著差异。高、低转移性亚群层粘连蛋白受体的阳性细胞百分数分别为 (36 36± 9 2 2 ) %和 (13 17±3 4 3) % ,两者间差异显著 (P <0 0 5 )。提示层粘连蛋白受体的表达与体外胆管癌细胞的不同转移倾向密切相关。     

不同浓度葡萄糖对大鼠间皮细胞增殖及细胞外基质产生的影响

观察了不同浓度葡萄糖对膜腹间皮细胞增殖和产生细胞外基质的作用，发现：①不同浓度的高渗葡萄糖可以抑制大鼠腹膜间皮细胞的增殖，引起间皮细胞的死亡，增强层粘连蛋白和Ⅳ型胶原的产生；②葡萄糖浓度与在此环境下培养的活细胞百分比呈负相关，但与层粘连蛋白的产生呈正相关，且活细胞百分比与层粘连蛋白的产生呈负相关。提示：培养液中葡萄糖的浓度在大鼠腹膜间皮细胞的增殖和细胞外基质的产生中起重要作用。     

层粘素受体显像

层粘素(亦称层粘连蛋白)在恶性肿瘤的浸润和转移中起着重要的作用,恶性细胞表面有大量的层粘素受体,而且能更多、更快地与层粘素结合。人工合成的层粘素五肽酪氨酰-异亮氨酰-甘氨酰-丝氨酰-精氨酸(YIGSR)肽能够与肿瘤相关的高亲和性层粘素受体结合放射性核素标记YIGSR是一种很有发展潜力的、能够估计活体内肿瘤细胞转移潜能的、具有受体特异性的放射性药物。     

层粘连蛋白受体Ⅰ与hPeriod1相互作用的研究

目的寻找与节律蛋白hPeriod1（hPer1）相互作用的蛋白，并对筛选出的层粘连蛋白受体Ⅰ（Lamr1）在节律系统中的功能作初步研究。方法分别构建pGAD rec／脑cDNA文库和pGBKT7／hPer1bHLH—PAS重组诱饵蛋白质粒，酵母双杂交筛选下丘脑里与hPer1相互作用的蛋白。利用RT—PCR技术检测新蛋白在脑、肺、心、肝、肾组织中的表达及在SH—SY5Y细胞中的节律性质。通过RNA干扰技术研究新蛋白与hPer1的关系。结果通过酵母双杂交筛选，证明Lamr1能与hPer1蛋白发生相互作用。该蛋白在脑、肺、心、肝、肾组织广泛表达，灰度比较显示经马血清诱导后的SH～SY5Y细胞的hPer1表达呈现近日节律，而Lamr1表达无节律变化。RNA干扰显示hPer1表达下调不影响Lamr1的表达。结论Lamr1能与hPer1蛋白发生相互作用，但其表达在RNA水平无节律变化。Lamr1参与细胞的黏附、转移和侵袭。其前体蛋白作为核蛋白参与细胞蛋白的合成。Lamr1可能参与hPer1相关的生物节律系统的信号传出。     

G蛋白偶联受体与辐射关系的研究进展

G蛋白偶联受体(GPCR)是一类细胞表面受体大家族,通过G蛋白介导其细胞作用,在介导细胞间信号转导的过程中起着十分重要的作用。研究发现,G蛋白和GPCR与辐射损伤关系密切,这些研究为充分认识辐射损伤机制及提高防治水平提供了新的观点。     

CCR5受体促进Jurkat细胞穿过人脑微血管内皮细胞单层

目的探讨高表达巨噬细胞炎性蛋白-1α(MIP-1α)的人淋巴细胞系Jurkat作为模式细胞对穿过人脑微血管内皮细胞单层机制。方法通过蛋白免疫印迹技术、真核表达载体的构建与细胞转染技术,同时进行跨内皮迁移和抗体封闭实验,集中探讨了HBMEC膜受体CCR5在Jurkat细胞穿过HBMEC单层过程中的作用。结果在Jurkat细胞与HBMEC单层单独孵育过程中,引起HBMEC膜受体CCR5表达变化;HBMEC膜受体CCR5的高表达使Jurkat细胞穿过HBMEC单层能力增强。结论 HBMEC膜受体CCR5参与了Jurkat细胞穿过HBMEC单层过程。     

大鼠坐骨神经损伤后雪旺细胞、层粘连蛋白动态变化研究

目的 研究大鼠坐骨神经损伤后的变性以及其再生过程中雪旺细胞（Schwann cell,SC)、层粘连蛋白（laminin,LN)变化规律。方法 用硅胶管桥接大鼠（60只）左侧坐骨神经缺损（缺损长6mm)，分别于伤后3、7、15、30、60、90天用免疫组化方法检测损伤神经近、远端和新生神经中段雪旺细胞，层粘连蛋白的表达。结果 损伤神经近、远SC和LN均于伤后30天达增殖高峰，新生神经中段LN的增殖于伤后60天达高峰，近端SC和LN的数量多于远端，LN在神经损伤区存在明显的浓度梯度。结论 LN的表达依赖于SC的增殖，LN的浓度梯度引导神经生长和雪旺细胞迁移的方向。     

胆管癌细胞层粘连蛋白受体表达下调对蛋白水解酶MMP-2、MMP-9 mRNA表达的影响

研究层粘连蛋白受体（laminin receptor,LNR)反义寡核苷酸硫代修饰片段（AS－OD）对人胆管癌QBC939细胞MMP－2，MMP－9基因表达的调节，应用逆转录聚合酶链反应（RT－PCR）方法分析12μmol/L浓度的LNR AS－OD在作用72h后对QBC939细胞MMP－2，MMP－9，mRNA表达水平的影响，结果显示，LNR AS－OD能明显抑制人胆管癌细胞表达MMP－2，MMP－9的作用，与正常对照组相比，其MMP－2，MMP－9 mRNA相对丰度分别下降了33．2％，和23．9％（P＜0．05），研究表明，LNR AS－OD是胆管癌细胞表达MMP－2和MMP－9基因的调节剂，能抑制胆管癌细胞MMP－2，MMP－9基因的表达，本研究为预防和治疗胆管癌的侵袭和转移提供了新的途径和方法。     

透明质酸、层粘连蛋白作为早期放射性肺损伤标志物的实验研究

目的 :探索透明质酸和层粘连蛋白对早期放射性肺损伤的诊断价值以及氟伐他汀对放射性肺损伤的治疗作用。方法 :将SD大鼠随机分为正常对照组 (C组 )、单纯照射组 (R组 )和氟伐他汀防治组 (TG组 )。TG组于照射前一周开始服氟伐他汀2 0mg·kg- 1·d- 1,直至活杀。其他组灌服等容量生理盐水。R组和TG组以直线加速器全胸部照射 ,单次剂量 2 0Gy ,于照射后5、15、3 0、60d以硫喷妥钠 40mg·kg- 1腹腔内注射。麻醉后固定 ,抽取心脏血 3ml ,分离血清。用放射免疫法测透明质酸、层粘连蛋白含量 ,统计分析用重复测量多因素方差分析和t检验。结果 :透明质酸在R组于照射后 60d较C组显著升高 (P <0 .0 1) ,TG组较R组减低 (P <0 .0 5)。层粘连蛋白在R组 3 0、60d较C组升高 (P <0 .0 5) ,TG组在相应时间减低 (P <0 .0 5)。结论 :透明质酸可作为放射性肺炎治疗情况的监测指标 ,层粘连蛋白可以作为预测纤维组织增生的一个早期指标 ;氟伐他汀对放射性肺损伤有一定的防治作用 ,用药后透明质酸、层粘连蛋白增高均受抑制     

坏死性凋亡在肿瘤放化疗中的研究进展与思考

肿瘤具有对程序性细胞死亡的抵抗作用,这是肿瘤细胞会产生放化疗耐受的原因之一。细胞程序性死亡不仅包括依赖含半胱氨酸的天冬氨酸蛋白水解酶（caspase）的细胞凋亡,也包括一种最近研究热门的非依赖caspase的死亡形式——坏死性凋亡。目前研究发现坏死性凋亡是由受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）以及混合谱系激酶结构域蛋白（MLKL）进行调控。笔者简要地总结了目前国内外坏死性凋亡相关的研究进展,为坏死性凋亡作为一种肿瘤放化疗新靶点的深入研究提供新思路。     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.     

A preliminary study for exploring the luminance ratio of liquid-crystal displays required for display of radiographs

Medical-grade liquid-crystal displays (LCDs) with high contrast ratio (CR) values have recently been developed and become available for soft-copy reading. When the LCD is used under ambient light conditions, the luminance ratio (LR) is a more appropriate indicator than the CR. Our aim was to explore the LR required for LCDs for soft-copy reading by comparing the effective LR values with the LR of the LCD. We defined “the luminance ratio in an image (LR_img)”, the ratio of the maximum to minimum luminance in a radiograph displayed on the LCD, as the effective LR values required for the LCD. The maximum LR_img values in chest radiographs and those in mammograms ranged from 109 to 143 and 372 to 431, respectively. The LR of the LCD was higher than the LR_img values of the radiographs. Our results indicate that currently available medical-grade LCDs have enough LR for display of radiographs.     

Cirrhotic liver: What's that nodule? The LI‐RADS approach

The Liver Imaging Reporting and Data System (LI‐RADS) is an American College of Radiology (ACR)‐endorsed diagnostic system of standardized terminology, interpretation, and reporting for imaging examinations of the liver in patients at high risk for hepatocellular carcinoma (HCC). LI‐RADS assigns a category to observations in the liver indicating the likelihood of benignity or HCC. LI‐RADS categories include LR‐1: Definitely Benign, LR‐2: Probably Benign, LR‐3: Intermediate Probability for HCC, LR‐4: Probably HCC, LR‐5: Definite HCC, LR‐5V: Definite HCC with Tumor in Vein, LR‐Treated: Treated HCC, LR‐M Probable Malignancy, not specific for HCC. This article reviews the types of nodules seen in the cirrhotic liver, examines core LI‐RADS concepts and definitions, and utilizes the LI‐RADS v2014 algorithm to categorize representative observations depicted at magnetic resonance imaging in a case‐based approach. J. Magn. Reson. Imaging 2016;43:281–294.     

Sibling assessment based on likelihood ratio and total number of shared alleles using 21 short tandem repeat loci included in the GlobalFiler™ kit

Sibling assessment using the 15 autosomal short tandem repeat (STR) loci included in the Identifiler® kit can be difficult when comparing an unidentified party to an alleged sibling. Therefore, we investigated the likelihood ratio (LR) and the total number of shared alleles (TNSA) for sibship determination using the 21 autosomal STR loci included in the GlobalFiler™ kit.We computationally generated the genotypes of 10,000 sibling pairs and 10,000 unrelated pairs based on previously reported allele frequencies of the 15 Identifiler loci and the remaining 6 GlobalFiler loci. The LR and the TNSA were then calculated in each pair using the 15 and 21 loci. Next, these calculations were applied to 22 actual sibling pairs.LR values ⩾10,000 were observed in 48% of the sibling pairs using the 15 loci and in 80% of the sibling pairs using the 21 loci. The TNSA distribution between siblings and unrelated pairs was more divergent in GlobalFiler than in Identifiler. TNSA values ⩾20 were found only in true siblings in Identifiler, while TNSA values ⩾24 in GlobalFiler. In Identifiler, all pairs with TNSA ⩾24 had LR values ⩾10,000 and the same was true in GlobalFiler for TNSA ⩾29. Therefore, increasing the number of loci is very efficient for sibship determination.The LR is most reliable for determining sibship. However, TNSA values may be useful for the preliminary method of LR values because LR value demonstrated a significantly positive correlation with TNSA value in both Identifiler and GlobalFiler.     

Added value of CEA scintigraphy in the detection of recurrence of rectal carcinoma

PURPOSE: To explore the diagnostic value of immunoscintigraphy compared to CT and/or MR imaging in the diagnosis of local recurrence (LR) of rectal cancer. MATERIAL AND METHODS: Forty-six patients suspected of having LR of rectal cancer were retrospectively studied. Carcinoembryonic antigen (CEA) scintigraphy findings were compared to CT and/or MR in all patients, and with data from surgery and morphology (31 patients), biopsy (7 cases) and follow-up (8 patients). RESULTS: CEA scintigraphy was not complementary to CT and/or MR in the detection of LR. Two false-positive and 14 false-negative diagnoses of LR occurred with CEA scintigraphy. Distant metastases including metastatic lymph nodes were found by this method in only 7 of 27 patients with proven metastases. CT/MR were able to demonstrate these metastases in 21 of 27 patients. CONCLUSION: Accuracy and sensitivity of CEA scintigraphy in the detection of LR and distant metastases is lower than that of CT and/or MR. However, CEA scintigraphy seems to have a high specificity and could therefore be used in patients with a strong clinical suspicion of LR but negative CT/MR investigations. Available diagnostic methods have limitations in differentiating between benign, post-treatment changes and LR of rectal cancer and in staging of malignant disease.     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (¹⁸F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of ¹⁸F-DOPA, 11 patients with medullary thyroid carcinoma were examined using ¹⁸F-DOPA PET. Results of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. ¹⁸F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), ¹⁸F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: ¹⁸F-DOPA PET 63%, ¹⁸F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with ¹⁸F-DOPA PET. ¹⁸F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and ¹⁸F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, ¹⁸F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.     

Clinical test for diagnosis of patellofemoral pain syndrome: Systematic review with meta-analysis

The high incidence and diversity of factors attributed to the etiology of patellofemoral pain syndrome (PFPS) makes the diagnosis of this problem somewhat complex and susceptible to misinterpretation. Currently, there is not a defined set of procedures considered as ideal to diagnose PFPS. To investigate the diagnostic accuracy of clinical and functional tests used to diagnose PFPS through a systematic review. We searched relevant studies in the databases Medline, CINAHL, SPORTDiscus and Embase. The QUADAS score was used to assess the methodological quality of the eligible studies. We analyzed data that indicated the diagnostic properties of tests, such as sensibility, specificity, positive (LR+) and negative (LR?) likelihood ratio, and predictive values. The search identified 16,169 potential studies and five studies met the eligibility criteria. The 5 studies analyzed 25 tests intending to accurately diagnose PFPS. Two tests were analyzed in two studies and were possible to perform a meta-analysis. Within the five studies included, one study had high methodological quality, two studies had good methodological quality and two studies had low methodological quality. Two tests, the patellar tilt (LR+ = 5.4 and LR? = 0.6) and squatting (LR+ = 1.8 and LR? = 0.2), had values that show a trend for the diagnosis of PFPS (LR+ >5.0 and LR? <0.2), however their values do not represent clear evidence regarding diagnostic properties as suggested in the literature (LR+ >10 and LR? <0.1). Future diagnostic studies should focus on the sample homogeneity and standardization of tests analyzed so future systematic reviews can determine with more certainty the accuracy of the tests for diagnosis of PFPS.     

Therapy monitoring using dynamic MRI: Analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy

A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2±0.9 cm if the tumor was located in the lower LR (middle LR: 5.5±0.8 cm; upper LR: 6.0±0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P<0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5±0.6 vs. 2.0±0.3 cm (middle LR; P<0.05) vs. 0.7±0.2 cm (upper LR; P<0.01). After RT, tumor mobility was significantly reduced in the lower LR (P<0.01) and in T2 tumor patients (P<0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter.     

ProbRank: An efficient DNA database search method for complex mixtures per a quantitative likelihood ratio model

Searching a DNA Database with a DNA profile from an evidentiary trace can provide investigative leads in a forensic case. Various searching approaches exist such as conventional methods based on matching alleles or more advanced methods computing likelihood ratios (LR) while considering drop-in and drop-out. Here we examine the potential of using a quantitative LR model (EuroForMix model incorporated in ProbRank method) that takes peak heights into account in comparison to a qualitative LR model (LRmix model implemented in SmartRank method). Both methods present DNA database candidates in order of decreasing LR. Especially regarding minor contributors in complex mixtures, the method using the quantitative model outperforms the method using the qualitative model in terms of sensitivity and specificity as more true donors and less adventitious matches are retrieved. ProbRank is to be implemented in DNAStatistX and is sufficiently fast for daily use.