肺腺癌细胞微环境及转移与黏附分子表达的关系

目的研究肺腺癌细胞生长环境及转移性与黏附分子CD44v6和CD29的表达关系。方法将起源相同、转移性不同的两个肺腺癌细胞系AGZY和Anip分别用简便肿瘤多细胞球体(MTS)培养法培养，并设常规单层贴壁细胞培养对照。通过倒置显微镜、扫描及透射电镜观察MTS形成情况，并用免疫组化法分别对MTS及贴壁细胞上CD44v6和CD29表达进行检测。结果MTS培养成功，贴壁细胞与MTS在细胞结构及细胞连接结构上相似，两种MTS在形态及结构上差异无显著性。免疫组化结果显示，CD29在高转移性的Anip细胞及其MTS上呈阳性表达；在低转移性的AGZY细胞及其MTS上阴性表达。CD44v6在Anip和AGZY细胞及MTS上均呈阳性表达，差异无显著性。贴壁细胞与MTS上两种黏附分子表达均无差异。结论成功建立了一种简易制备MTS的方法。细胞生长方式(单层贴壁与MTS)可能不影响CD44v6和CD29的表达。CD29表达可能与肺腺痛转移性相关；CD44v6表达可能与肺腺癌转移无关。     

Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.     

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.     

Alteration of the p53 gene of lung carcinomas with sarcomatous transformation (spindle cell carcinoma): analysis of four cases

Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene.     

Non-invasive evaluation of abdominal aortic properties: lumped circuit model and estimation of its parameters

To non-invasively determine abdominal aortic properties, a five-element lumped circuit model was adopted. The model consists of resistance due to blood viscosity (R1), inertia of blood flow, compliances of the vessel (C1, C2), resistance of the peripheral arteries (R2) and the impedance of the femoral arteries (termination). Patterns of the central velocity of the upper abdominal aorta and the femoral artery are measured by pulsed Doppler echocardiography, and confours of flow volume rates are calculated. The pressure pattern of the lower limb is recorded by a pulse wave rransducer and corrected according to sphygmomanometer values. Contours are transformed into respective Fourier transform components. The current transfer function is described theoretically and calculated from the acquired Fourier components. Values of every element are evaluated by the nonlinear least squares method. In 94 subjects (17–92 years), the values of each element are estimated. R2 values are greater in the elderly group, than in the young group and r₁ (R1/cm) increased with age. This model demonstrates that vessel compliance (c₁+c₂ (C1+C2/cm)) decreases with age, and it is suggested that this may be a useful marker of arteriosclerosis.     

Development of patient derived organoids for cancer drug screening applications

Cancer is a disease characterised by abnormal cell growth that can invade or spread to other regions of the body. Organoids are three-dimensional ex vivo tissue cultures made from embryonic stem cells, induced pluripotent stem cells, progenitor cells or tissue that serve as a physiological model for cancer research. These are designed to recapitulate the in vivo properties of tumours. Importantly, effective recapitulation of the structure of tissues and function is believed to predict patient response, allowing for the creation of personalised therapy in a timely manner that may be used in the clinic. This Review discusses the pre-clinical model and different types of human organoids as models for the development of high throughput drug screening and also aims to highlight how organoids are shaping the future of cancer research.     

超声多普勒检测糖尿病患者心功能的研究

目的检测糖尿病患者心功能。方法采用脉冲多普勒彩色超声心动图检测糖尿病、糖尿病合并冠心病患者各33例的心室结构和功能，并与健康组对照。结果糖尿病组的左心室舒张功能较健康组减退，而合并症组较糖尿病组减退更显著。结论糖尿病组的收缩功能与健康组间无统计学意义（P〉0．05），而三组问舒张功能有统计学意义（P〈0．01）。提示心室舒张功能较收缩功能变化更早、更显著。糖尿病组及合并症组左右心室均存在舒张功能障碍，表现为舒张早期心室充盈减低及房缩充盈代偿增强等（E峰流速减慢，A峰流速增快）。糖尿病的心室舒张功能减退与糖尿病的心脏病变和代谢紊乱均有关系，纠正代谢紊乱可避免心功能进一步恶化。     

Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma

Vascular endothelial growth factor receptor 3 (VEGFR-3) has been proposed as a marker for lymphatic endothelial cells. This study investigated the expression of VEGFR-3 in the tumour vessels of lung adenocarcinoma and evaluated whether VEGFR-3 staining was useful for identifying lymphatic vessels within the tumour stroma. It also explored whether active growth of lymphatic vessels occurred in lung adenocarcinoma. Formalin-fixed, paraffin-embedded specimens obtained from 60 cases of lung adenocarcinoma, including five cases of pure bronchiolo-alveolar carcinoma (BAC) without stromal, vascular, and pleural invasion, were examined. No VEGFR-3-positive vessels were observed in pure BAC, but varying numbers of VEGFR-3-positive vessels were found in 39 of 55 (70.9%) invasive adenocarcinomas. A comparison of serial sections stained for VEGFR-3, CD31, and laminin-1 showed that most of the VEGFR-3-positive vessels appeared to be blood vessels (CD31-positive, laminin-1-positive), but some had the characteristics of lymphatic vessels (variable staining for CD31, little or no staining for laminin-1). VEGFR-3 staining highlighted lymphatic invasion by cancer cells; this invasion could not be detected by CD31 or haematoxylin and eosin (H&E) staining. Active growth of lymphatic vessels (as indicated by nuclear Ki-67 labelling of the endothelium) was observed in five tumours, four of which showed a high level of lymphatic invasion by cancer cells. It was concluded that VEGFR-3 immunostaining did not discriminate clearly between vascular and lymphatic endothelial cells, since expression of VEGFR-3 can be up-regulated in tumour blood vessels. However, VEGFR-3 staining combined with laminin-1 and CD31 staining would be useful for identifying lymphatic vessels and their invasion by tumour cells in a more objective way. Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells.     

肺癌患者化疗前后血清Hcy、IGF-Ⅱ和TSGF检测的临床意义

目的：探讨肺癌患者化疗前后血清Hcy、IGF-Ⅱ和TSGF水平的变化及临床意义。方法：应用免疫法和放射免疫分析对35例肺癌患者进行了血清Hcy、IGF-Ⅱ和TSGF含量检测,并与30名正常健康人作比较。结果：肺癌患者在化疗前血清Hcy、IGF-Ⅱ和TSGF水平均非常显著地高于正常人组（P〈0.01）,化疗后6个月在未复发的27例中明显下降接近于正常人组,而复发的8例,其数值又回升至化疗前水平（P〈0.05）。结论：检测肺癌患者血清Hcy、IGF-Ⅱ和TSGF水平的变化可作为诊断和疗效观察的参考。