Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR–based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.     

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.     

肺腺癌CT影像分子分型研究进展

研究表明在明确驱动基因后进行特异性靶向治疗,肺癌患者的中位生存期显著延长。而除高通量测序技术和荧光原位杂交等分子生物学技术外,影像基因组学的出现,也为肺腺癌分子分型预测提供了一种无创的新方法。本文对肺腺癌计算机断层扫描（computed tomography,CT）影像分子分型的研究进展进行综述。首先,介绍肺腺癌分子分型的研究背景及肺腺癌主要的基因突变类型;然后,重点介绍两种主要的研究方法,即CT语义特征与肺腺癌分子亚型的相关性分析和基于机器学习的肺腺癌分子分型预测模型;最后,总结了该领域现阶段面临的主要问题,并对未来的研究方向做出展望。肺腺癌CT影像分子分型研究已经取得了一定成果,但仍存在很多问题。相关性分析与基于影像组学的预测模型研究由于样本各异且受过多人为干预,导致研究结果差异大,甚至有部分文献得到的结论截然相反。而基于深度学习的预测模型研究采用端到端的神经网络模型,人为参与极少,降低了研究难度,但尚处于起步阶段,构建的模型大多相对简单,远不能达到临床应用标准。今后的研究应聚焦于结合多种医学图像构建肺腺癌分子分型的大样本深度学习预测模型,同时结合临床信息、语义特征及影像组学特征,实现肺腺癌分子分型的无创、精准预测。     

Incidence of adenoviruses in raw and treated water

Adenoviruses are of major public health importance and are associated with a variety of clinical manifestations, i.e. gastroenteritis, eye infections and respiratory infections. The importance of water in the epidemiology of adenoviruses and the potential health risks constituted by adenoviruses in water sources and supplies are widely recognised. This study was conducted to assess the incidence of human adenoviruses in raw and treated water systems. Various raw and treated water were routinely monitored for the presence of adenoviruses, over a 1-year period (July 2000-June 2001). The supplies were derived from acceptable quality surface water sources using treatment processes, which conform to international standards for the production of safe drinking water. Adenoviruses were detected by firstly amplifying the viruses in cell cultures and then amplifying the extracted nucleic acids of these viruses using molecular techniques (nested PCR). The results indicated human adenoviruses present in 13 (12.75%) of the raw and 9 (4.41%) of the treated water samples tested. The combination of cell culture and nested PCR has proved to be a quick and reliable method for the detection of adenoviruses in water environments.     

当归挥发油对人肺腺癌GLC-82细胞增殖及凋亡的影响

目的: 探讨当归挥发油对人肺腺癌GLC-82细胞增殖及凋亡的作用。方法: MTT比色法检测当归挥发油对GLC-82细胞的细胞毒作用;流式细胞术检测GLC-82细胞凋亡;吖啶橙/溴化乙锭（AO/BE）双荧光染色法观察GLC 82细胞凋亡。结果: 当归挥发油在浓度6.25～200 μg/mL范围内对GLC-82细胞的增殖具有浓度依赖性抑制作用,对GLC-82细胞的IC50为113.03 μg/mL。流式细胞术检测结果表明,当归挥发油可诱导GLC-82细胞凋亡、坏死,且细胞凋亡、坏死率随药物浓度增高而升高。AO/BE双荧光染色法结果显示,用药组随着药物浓度的升高,细胞结构固缩加重,凋亡、坏死细胞增多。结论: 当归挥发油具有诱导GLC-82细胞凋亡的作用。     

Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted.     

胃肝样腺癌:1例报告

Objective:We reported a case with AFP produced gastric hepatoid adenocarcinoma. Methods:A male patient,77 year-old, was admitted to our hospital due to an unreasonable elevation of serum AFP. The tumors were revealed by PETCT,but until the tumors were removed during the surgery, we did not recognize the primary lesion was the gastric cancer.Results:Radical distal gastrectomy was performed. The gastric lesion was confirmed by histology as a hepatic adenocarcinoma in its early stage. Conclusion:The rare etiology of the AFP elevation should be kept in mind in clinic, extrahepatic lesions should be excluded.     

去甲苔藓葸噻吩抑制血管生成作用的体外实验研究

Objective:The aim of the study was to investigate the effect of Demethyl bryoanthrathiophene (DBT) on pro-liferations of human umbilical vein endothelial cells (HUVECs) and human lung adenocarcinoma cell line A549, and antian-giogenic effect of DBT on HUVECs in vitro. Methods: MTT assay was used to observe the effect of DBT on proliferations of HUVECs and A549 cells, fiat plate scarification assay and tube formation in vitro test were used to observe the impact of DBT on migration and vaso-formed ability of HUVECs. The effects of DBT on apoptosis and cell cycle of HUVECs were calculated by flow cytometry. Results: MTT assay showed that treatment with DBT resulted in strong inhibition to the growth of HUVECs and A549 cells. The inhibition effects of DBT on HUVECs and A549 cells were related to dosage and times of dependency.In different doses of DBT (0.16, 0.32 and 0.48 μmol/L) of fiat plate scarification for 24 h, inhibition rates of DBT to migration of HUVECs were 14.70%, 38.23% and 58.82%, respectively. In dose of DBT from 0.04, 0.20 to 0.40 μmol/L for 24 h in tube formation, there were significance differences (P < 0.01) in the decreasing number of angiogenesis and incomplete blood vessel compared with control groups. All results showed that DBT promoted the apoptosis rate of HUVECs, and the increase of concentration of DBT accompanied the acceleration of apoptosis rate. Conclusion: DBT could inhibit the proliferations of HUVECs and A549 cells, and effectively suppress angiogenesis in vitro.     

The pinhole SPECT for animal model of bone metastasis with SPC-A-1BM human pulmonary adenocarcinoma bone metastasis cell line

The study was to investigate the role of pinhole single photon emission computed tomography （SPECT）, the human pulmonary adenocarcinoma bone-seeking metastasis cell line SPC-A-1BM was used. These cells form typical osteolytic bone metastases when inoculated into the arterial circulation of NIH-Beige-Nude-XD （BNX） mice v/a the left ventricle. In order to evaluate the irradiation impact of ^99mTc-MDP versus X-ray on cells growth, we used six groups of SPC-A-IBM cells in our imaging scheme and irradiated by various doses of ^99mTc-MDP （37, 74, 111, 370, 740 MBq） and X-ray（40 kV, 2 mA, 6 s） respectively. The cell＇s number of each group was well recorded in different exposure time（ 4, 8, 12, 24, 48, 72, 96 hours ）. After that, SPC-A-1BM cells （1×106） were inoculated into the mice via left ventricle. We compared the results obtained with those different doses of ^99mTc-MDP using pinhole SPECT and conventional X-ray skeletal surveys. The data show that the cell-survival number of 111 MBq group has insignificant difference with that of X-ray and the dose is adequate to have an ideal image. Besides, it is important that the chromosome of the cells in the group of 111 MBq showed no irradiation-related damages in our test. These results implied that ^99mTc-MDP pinhole SPECT may provide another way other than conventional X-ray skeletal surveys in detecting bone metastasis of pulmonary adenocarcinoma in BNX mice.