Objective: Gastric cancer (GC) is one of the most common human cancers. A useful method of gastric cancer stem cell (CSC) characterization is spheroid colony formation. Previously, we reported that KIF11 expression is >2-fold in spheroid-body-forming GC cells compared with parental cells. Here, we analyzed the expression and distribution of KIF11 in human GC by immunohistochemistry. Methods: Expression of KIF11 in 165 GC cases was determined using immunohistochemistry. For mucin phenotypic expression analysis of GC, immunostaining of MUC5AC, MUC6, MUC2 and CD10 was evaluated. RNA interference was used to inhibit KIF11 expression in GC cell lines. Results: In total, 119 of 165 GC cases (72%) were positive for KIF11. Expression of KIF11 was not associated with any clinicopathologic characteristics; however, it was observed frequently in GC exhibiting an intestinal phenotype. Both the number and size of spheres formed by MKN-74 cells were significantly reduced following transfection of KIF11-targeting siRNA compared with negative-control siRNA. Furthermore, levels of phosphorylated Erk1/2 were lower in KIF11 siRNA-transfected cells than with negative-control siRNA-transfected cells. Conclusion: These results indicate that KIF11 is involved in intestinal mucin phenotype GC.

Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, may be useful biomarkers for cancer diagnosis and therapeutics. In the present study, we focused on the PCDHB9 gene, which encodes the transmembrane protein protocadherin B9. Immunohistochemical analysis revealed that 62 (36%) of 173 GC cases were positive for protocadherin B9. Protocadherin B9 staining was mainly observed on the GC cell membrane. Expression of protocadherin B9 was frequently found in intestinal-type GC and correlated with poor prognosis in patients with intestinal-type GC. Although PCDHB9 knockdown or forced expression of PCDHB9 did not change cell growth or invasion activity in a GC cell line, cell adhesion to fibronectin was significantly reduced by PCDHB9 knockdown and significantly enhanced by overexpression of PCDHB9. Expression levels of ITGA3, ITGA4, ITGA5, and ITGB1 were significantly reduced by knockdown of PCDHB9 and significantly enhanced by overexpression of PCDHB9. Furthermore, both the number and the size of spheres in culture were significantly decreased by PCDHB9 knockdown and significantly increased by overexpression of PCDHB9. In a peritoneal dissemination mouse model, the weight of the total disseminated nodules of MKN-74 cells was significantly increased by forced expression of PCDHB9. These results indicate that protocadherin B9 plays an important role in the progression rather than the pathogenesis of intestinal-type GC. Specific inhibitors of protocadherin B9 may constitute promising anti-cancer drugs with fewer side-effects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Abstract. Background: Oesophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC) are common types of human cancer. Spheroid colony formation is used to characterize cancer stem cell (CSCsGastrointestinal (GI) cancer, including oesophageal squamous cell carcinoma (ESCC), gastric cancer (GC), and colorectal cancer (CRC), are common malignancies worldwide. A variety of genetic and epigenetic alterations are associated with GI cancer, and better knowledge of the changes in gene expression that occur during gastric carcinogenesis may lead to improvements in diagnosis, treatment, and prevention (1). Genes encoding transmembrane/secretory proteins that are specifically expressed in cancer are ideal diagnostic biomarkers. Moreover, if the gene product functions in the neoplastic process, the gene is not just a potential biomarker, but may also be a therapeutic target (2).In the past decade, cancer has been recognized as a stem cell disease (3). Cancer stem cells (CSCs) are defined as malignant cells that possess the ability to initiate tumour growth and sustain self-renewal (4). Moreover, CSCs play an important role in resistance to chemotherapy (4). Therefore, characterization of CSCs is important for establishing more effective cancer treatments. One useful method for characterizing CSCs is spheroid colony formation. We previously showed that KIF11 and kinesin family C1 (KIFC1) genes are more highly expressed, by more than two-fold, in spheroid-forming cells than in the parental cells of GC cell lines (5). We also showed that KIF11 protein expression is upregulated in GC tissue samples, and that both the number and size of spheres produced by GC cells are significantly reduced by inhibition of KIF11 (6). These results suggest that KIF11 likely plays an important role in gastric CSCs.KIF11 (also known as EG5) is a member of the kinesin superfamily. The kinesin superfamily proteins are classified as mitotic kinesins, which are involved in cell division, and non-mitotic kinesins, which are principally involved in intracellular transport (7). KIF11 is a mitotic kinesin and is required for the separation of duplicated centrosomes during spindle formation (8). Thus, a KIF11 inhibitor is thought to be useful to specifically target proliferating tumour tissue (9). Several small molecule KIF11 inhibitors have been reported (10). There is a possibility that KIF11 inhibitors 47

Gastric cancer (GC) is one of the most common human cancers. Spheroid colony formation is an effective model for characterization of cancer stem cells. However, gene expression profiles of spheroid colonies obtained from GC cells have not been examined. We performed microarray analyses by Human Genome U133 Plus 2.0 Array in spheroid body-forming and parental cells from MKN-45 and MKN-74 GC cell lines. Kinesin family member C1 (KIFC1) was expressed >2-fold higher in spheroid body-forming cells than in parental cells in both GC lines. Both the number and size of spheres from MKN-45 cells were significantly reduced upon KIFC1 siRNA-transfection compared with negative control siRNA-transfection. Immunohistochemical analysis of 114 GC tissue samples revealed that 42 (37%) of GC cases were positive for KIFC1 expression. GC cases positive for KIFC1 were found more frequently in stage III/IV cases than in stage I/II cases. GC cases positive for KIFC1 were found more frequently in intestinal type GC cases than in diffuse type GC cases. Furthermore, KIFC1-positive GC cases showed high Ki-67 labeling index. Kaplan-Meier analysis demonstrated that KIFC1 expression was not associated with survival. We found positive expression of KIFC1 in CD44‑positive GC and aldehyde dehydrogenase 1 (ALDH1)-positive GC cells. Our results showed that KIFC1 is overexpressed in GC. Since knockdown of KIFC1 inhibited sphere formation, KIFC1 likely plays an important role in cancer stem cells.

The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

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Background/Aim: Nivolumab is effective against advanced gastric cancer (AGC) refractory to or in patients intolerant of standard chemotherapy. This study was designed to clarify the impact of cancer cachexia in patients with AGC who received nivolumab. Patients and Methods: We recruited AGC patients who were treated with nivolumab from October 2017 to December 2019. Clinical outcomes were compared between patients with and without cancer cachexia at the start of nivolumab. Cancer cachexia was defined as weight loss >5%; weight loss >2% and body mass index (BMI) <20; or sarcopenia and BMI <20. Primary endpoints were median overall survival (OS) and median time to treatment failure (TTF), while secondary endpoints were overall response rate (ORR) and incidence of adverse events. Results: The study enrolled 44 patients. Median OS and TTF were significantly shorter in patients with cancer cachexia than in those without cancer cachexia

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Spheroid colony formation is a useful method to identify cancer stem cells (CSCs). The aim of this study was to identify a novel prognostic marker or therapeutic target for GC using a method to identify CSCs. We analyzed the microarray data in spheroid body-forming and parental cells and focused on the CLSPN gene because it is overexpressed in the spheroid body-forming cells in both the GC cell lines MKN-45 and MKN-74. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that CLSPN messenger RNA (mRNA) expression was upregulated in GC cell lines MKN-45, MKN-74, and TMK-1. Immunohistochemistry of claspin showed that 94 (47%) of 203 GC cases were positive. Claspin-positive GC cases were associated with higher T and N grades, tumor stage, lymphatic invasion and poor prognosis. In addition, claspin expression was co-expressed with CD44, human epidermal growth factor receptor type 2 (HER2) and p53. CLSPN small interfering RNA (siRNA) treatment decreased GC cell proliferation and invasion. These results indicate that the expression of claspin might be a key regulator in the progression of GC and might play an important role in CSCs of GC.