Nishiguchi Y(1)(2), Fujiwara-Tani R(1), Sasaki T(1), Luo Y(1)(3), Ohmori H(1), Kishi S(1), Mori S(1), Goto K(1), Yasui W(4), Sho M(2), Kuniyasu H(1). claudin-1 levels were downregulated in the tumor relative to. This study aimed to determine the prevalence of CLDN18.2 in primary tumors and lymph node (LN) metastases of Japanese patients with GC. Of particular interest, in the possible use of Clostridium perfringens enterotoxin (CPE) as a novel … Claudin-7 expression correlated with shorter overall survival in gastric cancer patients, while the overall survival was increased in patients with claudin-18 expression. Membranous claudin-4 expression is associated with gastric cancer progression and prognosis in gastric carcinoma [10]. As mentioned above, the loss of claudins and other tight junction proteins in cancer has been interpreted as a mechanism for the loss of cell adhesion and an important step in the progression of cancer to metastasis. The expression of claudin-3 and claudin-4 was highly increased in gastric cancer. Previous studies have demonstrated that overexpression of claudin may promote tumorigenesis and metastasis through increased invasion and survival of tumor cells. In this study, we conducted an immunohistochemical examination of cell adhesion molecule claudin-1 in mucosa A total of 122 patients with advanced gastric cancer [stage IIB‑IV, with … In a randomized clinical study (FAST; … Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. For patients with one of the types of cancer listed above, mFOLFOX6 (a combination of three chemotherapies known as Oxaliplatin, Leucovorin, and Fluorouracil) is a current treatment option. Frequently, patients are … There is evidence to suggest that expression of CLDN18.2, in normal tissue, is strictly confined to tight junctions of the gastric mucosa, buried within a supramolecular complex [14] . … Overall, our result revealed that β‐elemene inhibited peritoneal metastases from gastric cancer by modulating the FAK/Claudin‐1 pathway. Oncol Lett 2014; 8 : 1367–1371. Go to: Introduction. Consistent with this hypothesis, a recent study showed that expression of claudin-4 in pancreatic cancer cells reduces invasiveness of these cells ( 33). This … Claudin‑3 expression is associated with gastric cancer progression, but the role of epigenetic modifications remains unclear. Positive expression of claudin-3 protein was found in 56.5% (52/92) of gastric cancer tissues and in 23.9% (22/92) of adjacent tissues (Table 1).The expression rate of claudin-3 in gastric cancer tissues was higher than the rate in adjacent tissues (The Chi-square test/Chi-Square Goodness-of-Fit Test, P = 0.001 < 0.01) (Figure 1C, … Claudin-low gastric cancer was defined by low expression levels of tight-junction claudins, high levels of EMT, and enrichment for TIC signatures. CAR-CLDN18.2 (CARsgen Therapeutics) targets claudin 18.2, a stomach-specific isoform of claudin-18 that is highly expressed in gastric and pancreatic adenocarcinomas. 2003; 11:683–689. gastric cancer and adjacent non-neoplastic tissues revealed that. Gastric cancer (GC) ranks as the fourth most common cancer worldwide and is among the most aggressive types of cancer. Immunohistochemistry was performed to detect the in situ expression of … The need for identification of prognostic and early detection biomarkers is thus compulsory. However, the prognostic significance of claudin-4 in gastric cancer remains unclear. Despite the variability of GC incidence and mortality, an estimated 1,033,701 new stomach cancers and 782,685 deaths occurred in 2018 1. [Google Scholar] 33. Here, we adopted this approach to identify novel targets in gastric cancer and identified the tight junction molecule claudin-18 isoform 2 (CLDN18.2). Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide and the second cause of cancer-related death. In this study, we aimed to outline the expression of CLDN18.2 and its correlation with clinico-pathological patient characteristics in a large and well … In … Gastric cancer (GC) is the fifth most frequently diagnosed cancer and third leading cause of cancer death worldwide [].Despite important advances for clarification of the etiology and molecular basis, as well as development of treatment strategies, survival rates for affected patients remain poor [].Presently, two molecular targets, human epidermal growth factor receptor-2 (HER2) and vascular … The pooled hazard ratio (HR) … Cancer … Our results suggested that Claudin-18 plays an important role in the development of gastric cancer, however, the development of gastric cancer is a complex process of multi-step, stage, and gene collaborative changes. Li and colleagues conducted a first-in-human, open-label, single-arm, phase 1 clinical trial to evaluate autologous CAR-CLDN18.2 T cells in patients with advanced gastric or pancreatic cancer whose tumors expressed claudin 18.2. The incidence of gastric cancer varies … There was no … These genes interact, promote or inhibit each other, or regulate each … Keyword: Gastric cancer, Claudiximab, IMAB362, Targeted therapy, Anti-claudin antibody Background Gastric cancer is one of the most common cancers worldwide, the fourth (in males) and fifth (in females) most common causes of cancer-related deaths in the developed world. Claudin18.2 (CLDN 18.2) is a stomach-specific isoform of Claudin-18, and highly expressed in gastric and pancreatic adenocarcinoma, the advanced form of both of which have urgent unmet medical needs. Mechanistically, we demonstrated that the anti‐metastatic effects of β‐elemene were exerted by downregulating the expression of Claudin‐1. Citing Literature. Claudin (CLDN)18.2 has emerged as a promising targetable biomarker. CLDN18.2 has been regarded as a potential therapeutic target for gastrointestinal tumors, and global clinical trials have been in process. Claudin-4 is deregulated in various cancers, including breast, prostate, ovarian, and gastric cancer. Thus, we conducted a meta-analysis to assess the association of claudin-4 expression with the prognosis and clinical parameters more precisely. Cunningham SC, Kamangar F, Kim MP, Hammoud S, Haque R, et al. Methods. The invasion, metastasis, and development of gastric cancer all involve the changes of many related genes. The … 48. Impact of claudin 18.2 expression on survival of patients with metastatic solid cancer types. normal tissue. Furthermore, β‐elemene was found to … This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph … We investigated methylation of the claudin‑3 promoter and expression profiles in gastric adenocarcinoma and their associations with clinicopathological characteristics and prognosis of the patients. Claudin 18 (CLDN18) is a member of the claudin family of tetraspanin membrane proteins expressed at epithelial tight junctions; claudin 18.2 (CLDN18.2) is a splice variant of CLDN18 . We may be able to use a treatment that targets the proteins to kill the cancer cells. Immunohistochemistry was used to analyze the expression of claudin … Claudin-7 (CLDN7) has been found to be aberrantly expressed in some types of cancers. In addition, because claudins are surface proteins, they may represent useful target for various therapeutic strategies. Moreov er, we further explored whether overexpression of claudin-6 altered proliferation, apoptosis, migration, invasiveness, differentiation in BGC-823 cells and the potential mechanism. Recently, claudin-3 and -7 are also considered … Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and -9 expression. In gastric cancer (GC) there is a need for therapeutic targets/biomarkers beyond HER2 and PD-L1; Claudin 18.2 (CLDN18.2) is a promising target. Gastric cancer (GC) is frequently diagnosed and treated in advanced tumour stages with poor prognosis. Keywords: claudin 18.2, gastric cancer, TNM stages, HER2, Lauren classification. An estimated 951,600 new stomach cancer cases and 723,100 deaths occurred in 2012. Targeting claudin-4 enhances CDDP-chemosensitivity in gastric cancer. In order to verify the function of claudin-6 in the development of gastric cancer, we investigated claudin-6 expression in different gastric disease tissues. Furthermore, the claudin-low … However, 51.5% of gastric cancer tissues exhibited reduced expression of claudin-18. However, claudin 18.2 was more frequently positive in intestinal-type compared to diffuse-type by Lauren classification (p = 0.026). Roles of Claudin in Cancer. In addition, individual increased expression of CLDN6, CLDN7, or CLDN9 is sufficient to enhance migration, invasion and proliferation of gastric cancer cell [11]. TPS4648 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. In the FAST Phase 2 trial (NCT01630083), IMAB362, an anti-CLDN18.2 monoclonal antibody, administered in combination with EOX chemotherapy, prolonged survival compared to EOX alone in patients with advanced/recurrent gastric, gastroesophageal junction (GEJ), and … We show here for the first time that CLDN18.2 is activated in a wide range of human malignancies, including gastric, esophageal, pancreatic, lung, and ovarian cancers, and can be specifically targeted with mAbs. In addition, compared with GS subtype, claudin-low subtype had the lower expression of proliferation signature, significant activation in Rho family of GTPases signaling, and enrichment of cell motility and adhesion-associated pathways. Recent studies have identified isoform 2 of the tight junction protein claudin-18 (CLDN18.2) as a promising target in GC therapy. Background: The monoclonal antibody zolbetuximab (formerly IMAB362), which is being developed as a potential treatment for gastric cancer (GC), targets Claudin 18.2 (CLDN18.2), a GC biomarker. Among patients with metastatic solid cancer tumors, the influence of claudin 18.2 expression on survival was analyzed, based on the anatomic tumor type. Int J Mol Med. metastatic gastric or GEJ cancer These types of cancers have a unique set of proteins (called Claudin 18.2). Claudins are biomarkers that are currently evaluated in the literature in the frame of epithelial-mesenchymal transition. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Hence, the precise, efficient, and noninvasive detection of CLDN18.2 expression is important for the effective application of this … Twelve of 17 patients positive for claudin 18.2 had gastric cancers; this subgroup showed no statistical difference by gender, age, disease extent, primary tumor site, pathologic differentiation, HER2 status, or EBV status with or without claudin 18.2 expression. Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions. PURPOSE: Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors diagnosed at advanced stage. The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). In this study, we have performed the largest expression analysis study to date of CLDN7 in … The purpose of this investigation was to study the … Gastric cancer (GC) is a major global cancer burden, and only HER2-targeted therapies have been approved in first line clinical therapy. In healthy tissue, CLDN18.2 is confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to exposure of CLDN18.2 on the surface of GC cells. (2)Department of Surgery, Nara Medical University, Kashihara, Nara … Number of times cited according to CrossRef: 4. However, the expression and role of CLDN7 on gastric cancer (GC) remain largely unknown. 4038 Background: Claudin 18.2 (CLDN18.2), a gastric mucosa tight junction protein, is aberrantly expressed in various cancers. In our study, we found that β‐elemene significantly inhibited the migration and invasive capacity of gastric cells in vitro and inhibited the capacity of gastric cancer cells to peritoneally diffuse and metastasize in vivo. Systematic searches on PubMed, Embase, and Cochrane Library prior to December 2014 were performed. Katoh M. CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. Downregulation of CLDN18 expression, possibly regulated by PKC/MAPK/AP-1 pathway and DNA methylation, is … Mingming Deng, Bofang Liu, Zhe Zhang, Yang Chen, Yizhe Wang, Ximing Wang, Qingjie Lv, Xianghong Yang, Kezuo Hou, Xiaofang Che, Xiujuan Qu, Yunpeng Liu, Ye Zhang, Xuejun Hu, Loss of G … For example, claudin-1 expression has been shown to have prognostic value in colon cancer , claudin-18 in gastric cancer , and claudin-10 in hepatocellular carcinoma . Claudin-3 and claudin-7 were expressed in 25.4% and 29.9% of the gastric cancer tissues, respectively. Background: Cell adhesion molecule abnormalities are given as one reason for the occurrence of invasion and metastasis in various cancers. The current reports on the association of claudin-4 expression with gastric cancer outcome were inconsistent. We previously developed and demonstrated ability of CLDN 18.2-specific CAR (CAR-CLDN18.2) T cells to eradicate CLDN 18.2-positive gastric cancer xenografts without obvious on … A meta-analysis indicates that Claudin-4 over-expression is associated with progress of gastric cancer and poor survival in gastric cancer patients [57]. Author information: (1)Department of Molecular Pathology, Nara Medical University, Kashihara, Nara 634-8521, Japan. Aberrant expression of claudin proteins has been reported in a variety of cancers.