• biomarkers
• cancer
• gastric cancer
• treatment

• carcinogenesis
• signaling pathways
• therapeutic targets
• tight junctions

• Tight Junction Proteins/metabolism
• Tight Junctions/metabolism
• Cell Differentiation
• Signal Transduction
• Biology
• Neoplasms/metabolism

• I01 BX002086 BLRD VA
• R01 CA250383 NCI NIH HHS

• Chemoresistance
• Metastasis
• Therapeutics
• Tight junctions
• Tumorigenesis

• Claudin 4
• Gastric adenocarcinomas
• histopathological parameters

Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma.

Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients.

Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001).

LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.

• ROC curve
• gastric adenocarcinoma
• ocular metastases
• risk factors
• serological indicators

Tight junctions (TJs) are an important component of cell connectivity; they maintain cell polarity, permeability and adhesion, and participate in the regulation of cell proliferation and differentiation. The claudin (CLDN) family is integral to TJs, and CLDN6 is an important member of this family. Abnormal expression of CLDN6 can destroy the integrity of TJs through various mechanisms and can serve multiple roles in the occurrence and development of tumours. CLDN6 is widely expressed in various tumours but rarely expressed in healthy adult tissues. The aim of this review is to critically examine the recent literature on CLDN6, including its structure, expression in different tumours, regulatory mechanisms and therapeutic prospects. Although some conclusions are controversial, in certain tumours, such as liver, ovarian, endometrial and oesophageal cancer, and atypical teratoid/rhabdoid tumours, research consistently shows that CLDN6 is expressed in tumour tissues but is not expressed or is expressed at low levels in surrounding tissues. In these tumours, CLDN6 has potential as a carcinoembryonic antigen and a therapeutic target.

• CLDN6
• cancer
• expression
• regulatory mechanisms
• review
• structure
• target
• therapeutic prospects

• Claudins
• cancer
• diagnosis
• prognosis
• targeted therapy

• biomarkers
• gastric cancer
• prognostic
• survival
• umbrella review

• SWI/SNF proteins
• claudin-4
• endometrial cancer
• endometrioid adenocarcinoma
• undifferentiated carcinoma
• uterine sarcomas

• Claudin-4
• Molecular imaging
• Pancreatic ductal adenocarcinoma
• SPECT

• Adenocarcinoma/diagnostic imaging
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Animals
• Antibodies, Monoclonal/chemistry
• Autoradiography
• Carcinoma, Pancreatic Ductal/diagnostic imaging
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/pathology
• Claudin-4/metabolism
• Humans
• Imaging, Three-Dimensional
• Indium Radioisotopes/chemistry
• Mice, Inbred BALB C
• Mice, Nude
• Pentetic Acid/chemistry
• Radiopharmaceuticals/chemistry
• Reproducibility of Results
• Tissue Distribution
• Xenograft Model Antitumor Assays

• 16466 Cancer Research UK
• 23970 Cancer Research UK
• RIF2014_02_CORNELISSEN Pancreatic Cancer UK
• Medical Research Council
• Pancreatic Cancer Research Fund

• Claudins
• ERK1/2
• Helicobacter pylori
• Lipopolysaccharide
• STAT3
• Toll-like receptors

To investigate the effects of Clostridium perfringens enterotoxin (CPE) on gastric cancer cells which highly expressed claudin-4 (CL4) protein.

In this study, we detected expression of CL4 protein in different gastric cancer cell lines. Then, we investigated the effects of CPE on SGC7901 cells which highly expressed CL4 protein and the effects of CPE on subcutaneous tumor in nude mice models.

CL4 are highly expressed in SGC7901 cells. CPE expressed significant cytotoxicity in SGC7901 cells. Suppression of CL4 expression significantly decreased CPE-mediated cytotoxicity. CPE also inhibited tumor growth in subcutaneous tumor xenograft models.

CPE showed CL4 mediated cytotoxicity on gastric cancer cells SGC7901 and inhibited tumor growth in nude mice models.

• Gastric cancer
• Clostridium perfringens enterotoxin
• Claudin-4 protein
• Cytotoxicity
• Tight junction

Oridonin, the major terpene found in Rabdosia rubescens (Henmsl.) Hara, is widely used as a dietary supplement and therapeutic drug. Oridonin has been proven to possess good anti-tumour activity, but little is known about its effect on angiogenesis. The aim of this study was to investigate the antiangiogenic effects of oridonin in vivo and in vitro and prove that oridonin anti-tumour activity is based on suppressing angiogenesis.

In vitro, the antiangiogenesis effect was studied by proliferation, apoptosis, migration, invasion, and tube formation experiments on human umbilical vascular endothelial cells (HUVECs). In vivo, using the Tg (fli1: GFP) zebrafish model, the embryonic vasculogenesis and postnatal regeneration were evaluated. The vascular endothelial growth factor (VEGF) signalling pathway gene expressions were assessed by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the inhibition effects on tumour growth and metastasis were observed using a xenograft zebrafish tumour model and xenograft nude mouse tumour model. Angiogenesis was assayed by immunostaining with cluster of differentiation 31. Importantly, the proteins were identified as being differentially expressed in an in vivo model by two-dimensional electrophoresis-mass spectrometry (2D–MS) and western blot (WB).

The results indicated that oridonin inhibited HUVEC proliferation, migration, invasion, and tube formation and induced cell apoptosis. Oridonin inhibited zebrafish angiogenesis during embryonic development and tail fin regeneration. RT-PCR showed that oridonin decreased the VEGFA, VEGFR2, and VEGFR3 expressions in zebrafish, while the TP53 expression increased. Moreover, oridonin had strong effects on tumour growth and metastasis in vivo. 2D–MS identified a total of 50 proteins differentially expressed (17 up-expressed, 28 down-expressed). Lastly, WB showed that Claudin 1, Claudin 4, and Claudin 7 were closely related to tumour growth and metastasis.

This study demonstrated that oridonin could inhibit tumour growth and metastasis, which mainly based on oridonin antiangiogenic effects. Claudin 1, Claudin 4, and Claudin 7 were the main contributors to the mechanism.

• Angiogenesis
• HUVECs
• Mouse
• Oridonin
• Zebrafish

• Animals
• Claudins/metabolism
• Humans
• Neoplasm Metastasis
• Neoplasms/metabolism
• Neoplasms/pathology

• MOP-136907 CIHR

The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4 expression and clinicopathological characteristics and assess the prognostic significance of CLDN4 in GC.

We searched the PubMed and Embase databases. We performed the meta-analysis with odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) as effect values.

Fourteen studies containing 2,106 patients with GC were analyzed. The overall analysis showed that CLDN4 expression was associated with increasing pT category, tumor size, and lymph node metastasis in patients with GC (pT3–T4 vs pT1–T2: OR =1.56, 95% CI =1.13–2.16; P<0.01; large tumor size vs small tumor size: OR =1.64, 95% CI =1.15–2.34; P<0.01; positive lymph node metastasis vs negative lymph node metastasis: OR =1.49, 95% CI =1.12–1.97; P<0.01). CLDN4 expression was associated with histological differentiation (differentiated type vs undifferentiated type: OR =2.90, 95% CI =1.32–6.37; P=0.01; Lauren intestinal type vs diffuse type: OR =3.51, 95% CI =1.48–8.28; P<0.01). CLDN4 expression was also strongly associated with sex and age. This meta-analysis found no significant association between CLDN4 expression and prognosis for overall survival in patients with GC (HR =0.74, 95% CI =0.43–1.27; P=0.28).

Present study indicates that aberrant CLDN4 expression plays an important role in the clinicopathological characteristics of GC.

• CLDN4
• biomarker
• gastric cancer
• meta-analysis
• metastasis
• prognosis
• stage