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Linear trends in Kuroshio transport during a recent global warming hiatus (1998–2013) were evaluated using long‐term ferryboat ADCP (acoustic Doppler current profiler) data and tidal gauge data in the Tokara Strait south of Japan. The Kuroshio exhibited a remarkable weakening trend of approximately 0.05 Sv year−1 (1 Sv = 106 m3 s−1). The pycnocline in the weakened Kuroshio was relaxed and displayed shoaling at the offshore edge, which was attributed to vertical thermocline displacement rather than to water mass modification. Importantly, Kuroshio transport trends in the Tokara Strait were affected by sea surface height anomalies, which were driven by the combined effects of the clockwise baroclinic‐mode coastal trapped wave propagation along the southern coast of Japan and downstream Kuroshio advection in the East China Sea. Both features were induced by wind stress curl changes related to the global warming hiatus over the North Pacific. Plain Language Summary: The Kuroshio is the western boundary current in the wind‐driven subtropical circulation of the North Pacific. It exits the East China Sea and flows into the North Pacific through the Tokara Strait between the Yakushima and Amami Oshima Islands to the south of Kyushu, Japan. This study revealed that the Kuroshio transport through the Tokara Strait showed a remarkable weakening trend along with a northward shift during 1998–2013. Changes in the wind stress curl in the high (low)‐latitude band over the North Pacific during the global warming hiatus exhibited negative (positive) tendencies, leading to anomalously high (low) sea surface heights. The high (low) sea surface height anomaly arrived at the onshore (offshore) side of Tokara Strait from the high (low)‐latitude band decreasing Kuroshio transport because of geostrophy. Key Points: Kuroshio transport in the Tokara Strait south of Japan decreased by ∼4% during 1998–2013, indicating a rate of about 0.05 Sv year−1Shoaling of the offshore pycnocline in the Kuroshio was due to vertical thermocline displacement rather than to modified water massDynamic‐topography propagation pathways from the northern and southern interior regions caused weakened Kuroshio transport in the hiatus [ABSTRACT FROM AUTHOR] more...

Here, we collected the information of 17304 and 2014 inpatients with colorectal cancer (CRC) from general hospitals of China and Japan respectively, and analyzed microscopic and macroscopic aspects, even stratified by the age and gender. It was found that Chinese CRC patients showed younger prone, more rectal and ascending cancers, less sigmoid and transverse cancers, larger size, less invasion into lymphatic system or metastasis into lymph node, and poorer differentiation than Japanese ones (p < 0.05). TNM staging was employed as an independent factor for the prognosis of the CRC patients regardless of the country (p < 0.05). Female patients showed larger tumor size, easier invasion and metastasis into lymphatic system, and worse differentiation than males (p < 0.05). The younger patients displayed frequent invasion and metastasis into lymphatic system, and poor differentiation in comparison to elder ones (p < 0.05). These findings demonstrated that Japanese patients seemed to have more invasion and metastasis due to standard and precise operation and pathological diagnosis accuracy. Actually, Chinese patients had more aggressive pathological characteristics and a poorer prognosis. Therefore, it is essential to establish a routine screening methodology, a standard treatment system and postoperative diagnosis protocol for the prevention and therapeutics of Chinese CRC patients, especially for female and young patients. more...

Here, we retrospectively compared the differences in clinicopathological behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1, n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka, n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and large cell carcinomas than Chinese patients (p<0.05). Survival analysis showed that tumor size was employed as a prognostic factor for the Japanese and Chinese cancer patients (p<0.05). In DMU and CMUS, the ratios of female patients or adenocarcinoma were higher than other hospitals (p<0.05), while the patients from CMUT and CMU1 were younger than the others (p<0.05). The ratios of squamous cell carcinoma from CMUT, CMU1 and JMU were higher than the others, while it was the same for the ratio of large and small cell carcinoma in Takaoka and CMU1 (p<0.05). TNM staging was higher in CMUT than JMU and Takaoka (p<0.05). The female patients of lung cancer showed young prone, large tumor size, a high ratio of adenocarcinoma and advanced TNM staging in comparison to the counterpart (p<0.05). The younger patients of lung cancer displayed smaller tumor size, higher ratio of adenocarcinoma, lower TNM staging than the elder in Takaoka (p<0.05). There were more aggressive behaviors and shorter survival time for Chinese than Japanese lung cancer patients. The prevention of lung cancer should be strengthened by establishing a systematic and effective screening strategy, especially for the young and female patients. more...

Background & Objectives: ING3 (inhibitor of growth protein 3) overexpression decreased S-phase cell population and colony-forming efficiency, and induced apoptosis at a p53-mediated manner. The aim of this study was to investigate the clinicopathological and prognostic significance of ING3 expression in colorectal carcinogenesis and subsequent progression., Methods: ING3 expression was examined by immunohistochemistry on tissue microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for ING3 expression by Western blot or RT-PCR., Results: ING3 mRNA was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells. Carcinomas showed significantly lower ING3 expression than matched NNM at mRNA level (P< 0.05), but not at protein level. Immunohistochemically, ING3 expression was significantly decreased from NNM, adenoma to adenocarcinoma (P< 0.05). ING3 expression was not correlated with age, sex, tumour size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumour- node- metastasis staging or differentiation. Kaplan-Meier analysis indicated that ING3 protein expression was not associated the prognosis of the patients with colorectal carcinoma (P< 0.05)., Interpretation & Conclusions: Our study showed that downregulated ING3 expression might play an important role in colorectal adenoma-adenocarcinoma sequence. Further studies are required to understand the mechanism. more...

Glycogen synthase kinase 3beta is reported to repress Wnt/beta-catenin pathway and regulate the balance between cellular proliferation and apoptosis. Its inactivation by ser(9) phosphorylation might play a critical role in the tumorigenesis and development of malignancies. Here, the expression of phosphorylated glycogen synthase kinase 3beta at ser(9) was examined in gastric carcinoma and adjacent non-neoplastic mucosa by immunohistochemistry and Western blot, and compared with the clinicopathological parameters of carcinomas, including the expression of vascular endothelial growth factor, extracellular matrix metalloproteinase inducer and beta-catenin, and microvessel density labeled by CD34, as well as survival data. Gastric carcinoma cell lines (MKN28, MKN45, AGS, GT-3 TKB, KATO-III and HGC-27) were studied for the phosphorylated kinase by Western blot and for its encoding mRNA by RT-PCR, followed by sequencing. All carcinoma cell lines showed strong expression of the phosphorylated kinase and its encoding mRNA.There were two isoforms of glycogen synthase kinase 3beta in all carcinoma cell lines and a synonymous mutation in HGC-27 carcinoma cell line at codon 65(GGA-->GGT: Gly). The phosphorylated kinase was localized in the cytoplasm of gastric carcinoma cell lines or carcinomas. It was more expressed in gastric carcinomas than that in non-neoplastic mucosa (P < .05) in line with the data of Western blot. There was a higher expression of the phosphorylated kinase in men carcinoma patients than that in women (P < .05). Its expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, Union Internationale le Contre Cancer staging, expression of vascular endothelial growth factor and extracellular matrix metalloproteinase inducer in gastric carcinoma (P < .05). Survival analysis indicated the phosphorylated kinase expression to be positively linked to poor prognosis (P< 05), but not independent (P>.05). Three independent prognostic factors, depth of invasion, lymphatic and venous invasion, concordantly influenced its relationship with prognosis (P < .05). Our study indicated that up-regulated expression of phosphorylated glycogen synthase kinase 3beta at ser(9) was closely linked to gastric carcinogenesis and subsequent progression, and could be employed as a good indicator of aggressive behaviors and prognosis of gastric carcinoma., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.) more...

Background & Objectives: Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths after lung carcinoma. The aim of this study was to understand the difference in clinicopathological behaviours and prognosis of gastric cancer in patients from China and Japan., Methods: Paraffin-fixed tissue samples of gastric cancer were collected retrospectively from two hospitals between 1993 to 2006 in Japan (n=2063) and during 1980-2003 in China (n=2496) respectively, and staging was done by TNM system and typing by Japanese Endoscopy Society criteria or Borrmann's classification. The histological architecture of the tumours was expressed according to Lauren's classification., Results: Compared to Japan, the occurrence of gastric cancer was more common in younger Chinese population and prone to invasion and metastasis in muscularis propia, lymphatic, lymph node, liver, peritoneal parts, and exhibited large tumour size and high TNM staging in both the sexes and in different age groups (P<0.05). Intestinal and mixed types of carcinomas were more frequently observed in Japanese patients compared to Chinese and the difference was significant (P<0.05). It was observed that the commonly reported types in early gastric cancers (EGC) in Japanese patients were IIc, IIa+IIc or IIa while those of Chinese patients were IIc, III or IIb. In the case of advanced gastric cancers (AGC), type II and III were most common in both the countries. The cumulative survival rate of Chinese patients was significantly (P<0.05) higher compared to Japanese in different stratified groups via depth of invasion, TNM staging or Lauren's classification., Interpretation & Conclusion: Gastric cancers in Chinese patients had more aggressive pathological characteristics and poorer prognosis than those from Japan. To reduce incidence and to improve treatment facilities, it is necessary to have a systematic screening system. more...

Japan is a high-risk region for gastric carcinoma with a comparatively early stage and favorable prognosis. To clarify the pathobiological behaviors and prognosis of Japanese gastric adenocarcinoma, we analyzed the clinicopathological characteristics of different WHO subtypes of carcinomas. The expression of ki-67, CPP32, p53, FHIT, maspin, parafibromin, GRP78, GRP94, EMMPRIN, VEGF, P-GSK3beta-ser9, fascin, cortactin, Arp2, Arp3 MUC-2, MUC-5AC and MUC-6 was examined using immunohistochemistry and tissue microarrays. The majority of cases were well-, poorly-, or moderately-differentiated subtype, whereas the minority were papillary or signet ring cell carcinoma (SRC). Patients with poorly-differentiated or SRC carcinoma were predominantly young and female. Poorly-differentiated and mucinous carcinomas were larger, with deeper invasion, more venous or lymphatic invasion, frequent lymph node involvement and peritoneal dissemination, or higher staging. The SRC group exhibited weaker expression of ki-67, CPP32, p53, parafibromin, GRP78, GRP94, P-GSK3beta-ser9, VEGF or cortactin. The moderately-differentiated subtype exhibited lower expression of FHIT and Arp3 positivity. The poorly-differentiated group showed weaker expression of CPP32, EMMPRIN, MUC-2, MUC-5AC, and MUC-6. Survival analysis indicated that the patients with poorly-differentiated or mucinous subtypes had a lower cumulative survival rate than those with papillary, well-, moderately-differentiated, or SRC carcinomas (P<0.05). The age, invasive depth, lymphatic invasion, peritoneal dissemination, and WHO classification were independent prognostic factors for carcinoma patients (P<0.05). It was suggested that poorly-differentiated and mucinous subtypes are more aggressive and of unfavorable prognosis among Japanese gastric carcinomas. Lower levels of proliferation and apoptosis, as well as alterations in tumor suppressor genes, mucin production and ER stress protein played important roles in the pathogenesis of poorly-differentiated and SRC carcinomas. more...

Glucose-related proteins (GRPs) are ubiquitously expressed in endoplasmic reticulum and able to assist in protein folding and assembly; consequently, they are considered as molecular chaperones. GRP78 and GRP94 expression was induced by glucose starvation and up-regulated in the malignancies. To clarify the roles of both molecules in tumorigenesis and progression of gastric carcinomas, immunohistochemistry was used on tissue microarray containing gastric carcinomas, adenomas, and nonneoplastic mucosa using the antibodies against GRP78 and GRP94, with a comparison of their expression with clinicopathological parameters of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III, and HGC-27) were studied for both proteins by immunohistochemistry and Western blot. There was more expression of both proteins in gastric carcinoma and adenoma than in nonneoplastic mucosas (P < .05). All gastric carcinoma cell lines showed their expression at different levels. They were positively correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis, and Union Internationale Contre le Cancer staging (P < .05), with positive relationship between both proteins (P < .05). Univariate analysis indicated the postsurgical cumulative survival rate of patients with positive GRP78 or GRP94 expression to be lower than that in those without GRP78 or GRP94 expression (P < .05), but the close link disappeared if stratified according to depth of invasion (P > .05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion, lymph node metastasis, Union Internationale Contre le Cancer staging, and Lauren classification (P < .05), but not GRP78 and GRP94 expression, were independent prognostic factors for carcinomas (P > .05). Up-regulated expression of GRP78 and GRP94 was possibly involved in pathogenesis, growth, invasion, and metastasis of gastric carcinomas. They were considered objective and effective markers for the aggressive behavior and poor prognosis in gastric carcinomas. more...

Background: MUC-1 is synthesized as a single polypeptide that then undergoes proteolytic cleavage, and is associated with the epidermal growth factor receptor tyrosine kinases. In malignancies, MUC-1 may function as an anti-adhesion molecule, but can also promote adhesion and presumably metastasis., Materials and Methods: Expression of MUC-1, -2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas (n = 237) and adjacent non-cancerous mucosa specimens (n = 89) by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients., Results: MUC-1 was found to be highly expressed in gastric carcinomas in comparison with noncancerous mucosa (p < 0.05) and positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, UICC staging and MUC-4 expression (p < 0.05), but not with age, tumor size, MUC-2 or MUC-5AC expression (p > 0.05). Intestinal-type carcinomas showed more MUC-1 expression than their diffuse-type counterparts (p < 0.05). Kaplan-Meier analysis indicated that the cumulative survival rate of patients with no MUC-1 expression was significantly higher than those with weak, moderate or strong expression in gastric carcinomas (p < 0.05), but no difference was observed when tumors were stratified according to the depth of invasion (p > 0.05). Cox's analysis showed three independent prognostic factors, depth of invasion, lymphatic invasion and venous invasion, to affect the relationship between MUC-1 expression and prognosis., Conclusion: Up-regulation of MUC-1 expression may be involved in pathogenesis, invasion, metastasis and differentiation of gastric carcinoma. Altered expression might therefore be employed as an indicator of pathobiological behavior of gastric carcinoma. MUC-1 expression was found to be a prognostic factor for gastric carcinoma patients, albeit not independent of parameters of invasion. more...