Current Status on Stem Cells and Cancers of the Gastric Epithelium

Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.     

YAG：Nd激光照射犬气管粘膜的实验研究

An experimental study for the pathologic changes of the canine tracheal mucosa under YAG:Nd laser ablation was performed in order to master the appropriate parameters for the clinical treatment of YAG:Nd laser. 6 male and female Mongolia dogs weighing 13-18 kg were received 20W YAG:Nd laser treatment and their pathologic changes were examined instantly and 3, 7, 14 and 28 days after ablation.     

胃动力信息采集与分析系统设计

本文设计了一套提取胃电和胃阻抗信号的胃动力信息采集与分析系统，该系统由采集系统和分析系统两部分构成。前者以单片机（ADuC834）为核心部件，实现了胃电和生物阻抗信号的同步采集和数据传输。后者对提取的阻抗信号和胃电信号运用小波多分辨分析处理，利用小波变换将胃阻抗信号从呼吸和血流信号中分离。系统可以应用于分析功能性消化不良患者胃动力的电过程和机械过程。     

Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells

We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.     

Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.     

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.     

Optimized Identification with Severity Factors of Gastric Cancer for Internet of Medical Things

The Internet of Medical Things (IoMT) emerges with the vision of the Wireless Body Sensor Network (WBSN) to improve the health monitoring systems and has an enormous impact on the healthcare system for recognizing the levels of risk/severity factors (premature diagnosis, treatment, and supervision of chronic disease i.e., cancer) via wearable/electronic health sensor i.e., wireless endoscopic capsule. However, AI-assisted endoscopy plays a very significant role in the detection of gastric cancer. Convolutional Neural Network (CNN) has been widely used to diagnose gastric cancer based on various feature extraction models, consequently, limiting the identification and categorization performance in terms of cancerous stages and grades associated with each type of gastric cancer. This paper proposed an optimized AI-based approach to diagnose and assess the risk factor of gastric cancer based on its type, stage, and grade in the endoscopic images for smart healthcare applications. The proposed method is categorized into five phases such as image pre-processing, Four-Dimensional (4D) image conversion, image segmentation, K-Nearest Neighbour (K-NN) classification, and multi-grading and staging of image intensities. Moreover, the performance of the proposed method has experimented on two different datasets consisting of color and black and white endoscopic images. The simulation results verified that the proposed approach is capable of perceiving gastric cancer with 88.09% sensitivity, 95.77% specificity, and 96.55% overall accuracy respectively.     

99Tcm-PHY和113Inm-DTPA双核素胃排空显像检查

采用99Tcm-植酸钠(PHY)标记鸡肝(固相)和113Inm-DTPA(液相)混合餐作双核素显像检测受试者的胃半排空时间(T1/2),建立正常值;并对非胰岛素依赖性糖尿病、十二指肠溃疡、功能性消化不良、硬皮病等165例患者的胃排空时间进行检测与分析。结果表明:20例正常对照组液相食物T1/2为25.7～53.7min,平均41.2±9.1min;固相食物T1/2为50.5～100.3min,平均70.5±16.5min。正常上限:液相T1/2为60min,固相T1/2为104min。107例糖尿病患者中有固相食物排空延迟者达47例,占43.9%,并有液相食物延迟者19例,占17.8%。经西沙比利治疗后复查,均见有胃排空的明显改善。硬皮病患者的胃排空延迟最严重,且所占比率达82%。双核素胃排空显像检查尤其是固相食物检查为临床胃排空研究提供了灵敏可靠的检查方法。