Ruinuo Jia

Microarray Expression Profile Analysis of Long Non-Coding RNAs in Human Gastric Cardiac Adenocarcinoma

Background/Aims: Long noncoding RNAs (lncRNAs) are pervasively transcribed and have been shown to regulate key biological processes that maintain normal cellular functions. Abnormal regulation of these lncRNAs can promote tumorigenesis through resulting aberrant cellular essential functions. however, the roles of lncRNAs played in the development of gastric cardiac adenocarcinoma (GCA) remain unknown. With this work we aimed to show the expression profile of lncRNAs in GCA tissues compared with paired adjacent noncancerous tissue using microarray analysis in order to interrogate potential carcinogenesis molecular mechanisms of GCA from lncRNA level. Methods: In this study, total RNA was isolated from 15 pairs of GCA tissue, cancerous and non-cancerous, and hybridized to arraystar lncRNA V2.0 chips containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (PCR) was used to validate 6 up-regulated and 6 down-regulated lncRNAs. Bioinformatic analysis including gene ontology(GO) analysis, pathway analysis and network analysis was done for further investigation. Results: Pathway analysis indicated that 8 pathways corresponded to downregulated transcripts and that 20 pathways corresponded to up-regulated transcripts (p-value cut-off is 0.05). GO analysis showed that the highest enriched GOs targeted by up-regulated transcripts were tissue homeostasis and the highest esenriched GOs targeted by the downregulated transcripts were tissue homeostasis. Conclusion: Our study is the first to interrogate differentially expressed lncRNAs in human GCA tissues and indicates that lncRNAs may be used as novel candidate biomarkers for the clinical diagnosis of GCA and potential targets for further therapy.

Therapeutic effects of combined oxaliplatin and S-1 in older patients with advanced gastric cardiac adenocarcinoma

AIM To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m² po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m² iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. RESULTS The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ² = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ² = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ² = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). CONCLUSION The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.

KDM4C, a H3K9me3 Histone Demethylase, is Involved in the Maintenance of Human ESCC-Initiating Cells by Epigenetically Enhancing SOX2 Expression

Our studies investigating the existence of tumor-initiating cell (TIC) populations in human esophageal squamous cell carcinoma (ESCC) had identified a subpopulation of cells isolated from ESCC patient-derived tumor specimens marked by an ALDHbri+ phenotype bear stem cell-like features. Importantly, KDM4C, a histone demethylase was enhanced in ALDHbri+ subpopulation, suggesting that strategies interfering with KDM4C may be able to target these putative TICs. In the present study, by genetic and chemical means, we demonstrated that, KDM4C blockade selectively decreased the ESCC ALDHbri+ TICs population in vitro and specifically targeted the TICs in ALDHbri+-derived xenograft, retarding engraftment. Subsequent studies of the KDM4C functional network identified a subset of pluripotency-associated genes (PAGs) and aldehyde dehydrogenase family members to be preferentially down-regulated in KDM4C inhibited ALDHbri+ TICs. We further supported a model in which KDM4C maintains permissive histone modifications with a low level of H3K9 methylation at the promoters of several PAGs. Moreover, ectopic expression of SOX2 restored KDM4C inhibition-dependent ALDHbri+ TIC properties. We further confirmed these findings by showing that the cytoplasmic and nuclear KDM4C staining increased with adverse pathologic phenotypes and poor patient survival. Such staining pattern of intracellular KDM4C appeared to overlap with the expression of SOX2 and ALDH1. Collectively, our findings provided the insights into the development of novel therapeutic strategies based on the inhibition of KDM4C pathway for the eliminating of ESCC TIC compartment.

Corrigendum to “KDM4C, a H3K9me3 histone demethylase, is involved in the maintenance of human ESCC-initiating cells by epigenetically enhancing SOX2 expression” [Neoplasia 18 (2016) 594-609]

Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China; Barbara Ann Karmanos Cancer Institute and Department of Oncology, Wayne State University, 4100 John R, Detroit, MI 48201; State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking, China; Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan, China

Evaluation of Combined Argon Plasma Coagulation and Savary Bougienage for the Relief of Anastomotic-Stenosis after Esophageal Squamous Cancer Surgery

Background: Several endoscopic dilation techniques have been reported for treatment of anastomotic-stenosis of esophageal cancer, but the high incidence of dysphagia has remained unchanged. The aim of this study was to compare the effect of Argon Plasma Coagulation (APC) combined with Savary Bougienage (SB) compared to APC alone or SB alone for anastomotic-stenosis after radical operation for squamous cell carcinoma of the esophagus. Methods: Patients with anastomotic-stenosis that was diagnosed for the first time following esophageal squamous cell carcinoma resection surgery were randomly assigned to undergo APC combined with SB, APC alone, or SB alone. Primary endpoints were the dysphagia-free survival (DFS defined as the time from first dilatation of effectively relieved dysphagia to dysphagia relapse expressed in days) after 6 months of follow up. Results: A total of 90 patients from the Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology were entered into the study (APC group, n = 30, SB group, n = 30, combination group [APC combined with SB], n = 30). Primary endpoints: 6 months after treatment, DFS of combination group (115.63 days; 95% CI, 105.31-125.95) was significantly longer than the APC alone group (39.53 days; 95% CI, 35.95-43.11, p = 0.000) and the SB alone group (16.93 days; 95% CI, 15.01-18.84, p = 0.000). No severe complications occurred within the three treatment groups. Conclusions: APC combined with SB was a safe and well-tolerated method for relieving dysphagia of esophageal squamous cell cancer patients with anastomotic-stenosis. (Registered with randomized controlled trials, ChiCRT, registration number ChiCTR-TRC-13003757.)