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A 54-year-old man underwent laparoscopic distal gastrectomy with D2 lymph node dissection and ante-colic Roux-en-Y reconstruction for gastric cancer. The histopathological diagnosis was pT2N3aM0, pStage ⅢA, HER2 negative. After 8 courses of S-1 plus oxaliplatin as adjuvant chemotherapy, he was diagnosed as peritoneal dissemination and treated with ramucirumab(RAM)plus paclitaxel(PTX). On the 12th day of course 10, he visited to our hospital with abdominal pain. CT showed free air and massive ascites. Emergent surgery was performed under the diagnosis of gastrointestinal perforation. A small intestinal perforation in front of the jejunal limb near gastric-jejunal anastomosis was identified and there was no peritoneal dissemination. We performed partial resection of remnant stomach and jejunal limb by linear stapler and reconstruction by end to side gastric-jejunal anastomosis. Because the gastric and intestinal wall were quite fragile and RAM impaired wound healing as adverse event, we feared about leakage, but he had no major postoperative complications and discharged on the 33th day after surgery. After 24 courses of nivolumab as third-line chemotherapy, the peritoneal dissemination disappeared. He has been alive without recurrence for about 1 year since then.

Soybean (Glycine max (L.) Merr.) plants form root nodules and fix atmospheric dinitrogen, while also utilizing the combined nitrogen absorbed from roots. In this study, nodulated soybean plants were supplied with 5 mM N nitrate, ammonium, or urea for 3 days, and the changes in metabolite concentrations in the xylem sap and each organ were analyzed. The ureide concentration in the xylem sap was the highest in the control plants that were supplied with an N-free nutrient solution, but nitrate and asparagine were the principal compounds in the xylem sap with nitrate treatment. The metabolite concentrations in both the xylem sap and each organ were similar between the ammonium and urea treatments. Considerable amounts of urea were present in the xylem sap and all the organs among all the treatments. Positive correlations were observed between the ureides and urea concentrations in the xylem sap as well as in the roots and leaves, although no correlations were observed between the urea and arginine concentrations, suggesting that urea may have originated from ureide degradation in soybean plants, possibly in the roots. This is the first finding of the possibility of ureide degradation to urea in the underground organs of soybean plants.

Leaf iron (Fe) contents in Fe-deficiency-tolerant plants are not necessarily higher than that in Fe-deficiency-susceptible ones, suggesting an unknown mechanism involved in saving and allowing the efficient use of minimal Fe. To quantitatively evaluate the difference in Fe economy for photosynthesis, we compared the ratio of CO2 assimilation rate to Fe content in newly developed leaves as a novel index of photosynthetic iron-use efficiency (PIUE) among 23 different barley (Hordeum vulgare L.) varieties. Notably, varieties originating from areas with alkaline soil increased PIUE in response to Fe-deficiency, suggesting that PIUE enhancement is a crucial and genetically inherent trait for acclimation to Fe-deficient environments. Multivariate analyses revealed that the ability to increase PIUE was correlated with photochemical quenching (qP), which is a coefficient of light energy used in photosynthesis. Nevertheless, the maximal quantum yield of photosystem II (PSII) photochemistry, non-photochemical quenching, and quantum yield of carbon assimilation showed a relatively low correlation with PIUE. This result suggests that the ability of Fe-deficiency-tolerant varieties of barley to increase PIUE is related to optimizing the electron flow downstream of PSII, including cytochrome b6f and photosystem I.

A 77-year-old man was given a diagnosis of pT4aN0M1a(PUL2), stage Ⅳ, RAS mutant type, after the operation for advanced ascending colon cancer. He was administered mFOLFOX6 plus Bmab as first-line chemotherapy. He showed consciousness disturbance on the 2nd day during the 6 cycles. Because of head computed tomography and magnetic resonance imaging showing no abnormal findings, we diagnosed convulsive seizure. His consciousness level gradually improved after intravenous infusion. He showed consciousness disturbance on the 2nd day during the 7 cycles again. Because blood ammonia level were high at 400μg/dL, he was diagnosed as hyperammonemic encephalopathy. His consciousness level rapidly recovered after branched chain amino acid(BCAA)infusion. SOX plus Bmab therapy was started as a post-treatment, he developed hyperammonemia(NH3 288μg/dL)again, on the 4th day during the 3 cycles. After taking of oral administration of BCAA and lactulose, the recurrence of hyperammonemic encephalopathy was not found. Therefore, 3 cycles of SOX plus Bmab therapy and 12 cycles of IRIS plus Bmab therapy were administered.

Iron (Fe) is an essential trace element in plants; however, the available Fe in soil solution do not always satisfy the demand of plants. Genetic diversity in the rate of Fe uptake by plants has not been broadly surveyed among plant species or genotypes, although plants have developed various Fe acquisition mechanisms. The “Live-autoradiography” technique with radioactive 59Fe was adopted to directly evaluate the uptake rate of Fe by barley cultivars from a nutrient solution containing a very low concentration of Fe. The uptake rate of Fe measured by live-autoradiography was consistent with the amount of accumulation of Fe-containing proteins on the thylakoid membrane. These data revealed that the ability to acquire Fe from the low Fe so-lution was not always the sole determinant of tolerance to Fe deficiency among the barley geno-types. The live-autoradiography system visualizes the distribution of β-ray emitting nuclides and has flexibility in the shape of the field of view. Such a technique will strongly support phenotyping with regard to the long-distance transport of nutrient elements in the plant body.

Many crops grow well on neutral or weakly acidic soils. The ability of roots to elongate under high-external pH would be advantageous for the survival of plants on alkaline soil. We found that root elongation was promoted in some plant species in alkaline-nutrient solution. Barley, but not tomato, root growth was maintained in pH 8 nutrient solution. Fe and Mn were absorbed well from the pH 8 nutrient solution by both barley and tomato plants, suggesting that the different growth responses of these two species may not be caused by insolubilization of transition metals. The ability of intact barley and tomato plants to acidify external solution was comparable; in both species, this ability decreased in plants exposed to pH 8 nutrient solution for 1 w. Conversely, cell proliferation and elongation in barley root apices were facilitated at pH 8 as shown by microscopy and cell-cycle-related gene-expression data; this was not observed in tomato. We propose that barley adapts to alkaline stress by increasing root development.

It has been reported that supply of nitrate to culture solution rapidly and reversibly inhibits nodule growth and nitrogen fixation activity of soybean. In this study, the effects of ammonium, urea, or glutamine on nodule growth and nitrogen fixation activity are compared with that for nitrate. Soybean plants were cultivated with a nitrogen-free nutrient solution, then 1 mM-N of nitrate, ammonium, glutamine, or urea were supplied from 12 DAP until 17 DAP. Repression of nodule growth and nitrogen fixation activity at 17 DAP were observed by ammonium, urea, and glutamine like nitrate, although the inhibitory effects were milder than nitrate. The removal of nitrogen from the culture solutions after nitrogen treatments resulted in a recovery of the nodule growth. It was found that the glutamine treatment followed by N-free cultivation gave highest nitrogen fixation activity about two times of the control. Tracer experiments with 15N and 13C were performed to evaluate the translocation of N and C to the different tissues. Culture solutions containing a 15N-labeled nitrogen source were supplied from 21 DAP, and the whole shoots were exposed to 13CO2 for 60 min on 23 DAP, and plants were harvested on 24 DAP. The percentage distribution of 15N in nodules was highest for ammonium (1.4%) followed by glutamine (0.78%), urea (0.32%) and nitrate (0.25%). The percentage distribution of 13C in the nodules was highest for the control (11.5%) followed by urea (5.8%), glutamine (2.6%), ammonium (2.3%), and nitrate (2.3%). The inhibitory effects of nitrogen compounds appeared to be related to a decrease in photoassimilate partitioning in the nodules, rather than 15N transport into the nodules. The free amino acid concentrations after nitrogen treatments were increased in the nodules and leaves by nitrate, in the roots by ammonium, in the stems by urea, and the roots, stems, and leaves by glutamine treatment. The concentrations of asparagine, aspartate, and glutamine were increased after nitrogen treatments. By the long-term supply of nitrogen for 2-weeks, nitrate significantly increased the lateral roots and leaf growth. The long-term supply of urea and glutamine also promoted the lateral roots and leaf growth, but ammonium suppressed them.

We previously found a novel Cd-associated molecule with an apparent molecular weight of 10–50 kDa in common reeds grown in the presence of Cd. The partial structure of this molecule was predicted by enzymatic digestion to release Cd from a trace amount that had been partially purified from the cell sap. The major component was branched α-glucan, whereas a peptide, β-1,4 glucan, and mannose were found as minor components. Uronic acids appeared to provide functional groups that bind Cd.

Aims Although expressed in tumour cells of various malignancies, cadherin 5 (CDH5), also known as vascular endothelial cadherin, plays an important role in homotypic cell–cell adhesion among epithelial cells. However, the clinical significance of CDH5 expression in gastric cancer has not been sufficiently demonstrated. In this study, CDH5 expression in gastric cancer was evaluated and the correlations between CDH5 expression and the clinicopathological features and outcomes of the disease were examined. Methods Differentiated-type gastric adenocarcinomas obtained from 102 patients who underwent gastrectomy were analysed. CDH5 expression was assessed by immunohistochemical staining of the membranes of the cancer cells. Results High CDH5 expression was significantly associated with the following clinicopathological variables related to tumour progression: depth of invasion (p=0.012), venous invasion (p=0.013), lymphatic invasion (p=0.001), metastatic lymph nodes (p=0.009), pathological stage (p=0.008) and distant metastasis or recurrent disease (p=0.009). Patients with high CDH5 expression had significantly poorer disease-specific survival (p=0.021), although CDH5 was not determined to be an independent prognostic factor by multivariate analysis. Conclusions CDH5 may play a key role in the progression or metastasis of differentiated-type gastric cancer and serve as a target for its treatment.

Gallbladder carcinoma producing alpha-fetoprotein(AFP)is rare.We report a case of AFP producing carcinoma of the gallbladder with huge metastatic hepatic tumor.A 81-year-old female with a hepatitis B virus(HBV)had a fever and right hypochondralgia.Abdominal CT showed an enlarged gallbladder with gallbladder stones, a huge tumor in the right lobe of liver, and swelling paraaortic lymph nodes.Acute cholecystitis was treated by percutaneous transhepatic gallbladder drainage (PTGBD).The hepatic tumor was diagnosed as hepatocellular carcinoma for HBV carrier and the high level of AFP and PIVKA- II .We performed right lobectomy, cholecystectomy and the resection of paraaortic lymph nodes.In the resected gallbladder, the papillary tumor was detected.Histopathological diagnosis was moderately to poorly differentiated adenocarcinoma of the gallbladder.The liver tumor and paraaortic lymph nodes were metastases of the gallbladder carcinoma.The both of gallbladder and liver tumor immunohistochemically stained positive to AFP.It was difficult to diagnose the hepatic tumor because of HBV carrier, the high level of AFP and the unnoticed gallbladder tumor.Gallbladder carcinoma with the high level of AFP might have relation to liver metastases.

Aimsp-21 activated kinase (PAK) 4, part of the six PAK families, plays an important role in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated. PAK4 expression was evaluated, and the correlations of PAK4 expression with clinicopathological features and outcomes in gastric cancer were examined.MethodsGastric adenocarcinomas obtained from 217 patients who underwent gastrectomy were analysed. PAK4 expression was evaluated using immunohistochemical staining.ResultsPAK4 overexpression was found in 95 (43.8%) of 217 tumours . High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival (DSS) (pConclusionsPAK4 may become a new prognostic factor in patients with gastric cancer.

AimsInsulin-like growth factor binding protein 7 (IGFBP7) is reported to have tumour suppressor function through an IGF-dependent pathway in various malignant tumours. However, the expression of IGFBP7 in adenocarcinoma and its relationship with tumour progression and survival differs among studies. Our aims were to investigate the relationship between the expression of IGFBP7 and clinicopathological variables and outcomes of patients with gastric cancer.MethodsTumour samples were obtained from 219 patients with gastric cancer who underwent gastrectomy. The expression of IGFBP7 protein was examined by immunohistochemical staining. IGFBP7 mRNA levels were analysed using real-time quantitative reverse-transcriptase PCR in 24 of the gastric cancer tumours and in adjacent non-tumour tissues. Correlation of IGFBP7 expression with clinicopathological features was analysed.ResultsThe protein expression of IGFBP7 was positively correlated with depth of invasion, lymph node metastasis, distant metastasis or recurrence and pathological stage. High expression of IGFBP7 protein was associated with a significantly worse disease-specific survival (pConclusionsOverexpression of IGFBP7 was associated with tumour progression and poor survival in gastric cancer. IGFBP7 may play a role in tumour progression in gastric cancer.

We analyzed the directions and rates of translocation of sodium ions (Na(+)) within tissues of a salt-tolerant plant, common reed [Phragmites australis (Cav.) Trin. ex Steud.], and a salt-sensitive plant, rice (Oryza sativa L.), under constant high-salt conditions using radioactive (22)Na tracer and a positron-emitting tracer imaging system (PETIS). First, the test plants were incubated in a nutrient solution containing 50 mM NaCl and a trace level of (22)Na for 24 h (feeding step). Then the original solution was replaced with a fresh solution containing 50 mM NaCl but no (22)Na, in which the test plants remained for >48 h (chase step). Non-invasive dynamic visualization of (22)Na distribution in the test plants was conducted during feeding and chase steps with PETIS. Our results revealed that (22)Na was absorbed in the roots of common reed, but not transported to the upper shoot beyond the shoot base. During the chase step, a basal to distal movement of (22)Na was detected within the root tissue over >5 cm with a velocity of approximately 0.5 cm h(-1). On the other hand, (22)Na that was absorbed in the roots of rice was continuously translocated to and accumulated in the whole shoot. We concluded that the basal roots and the shoot base of common reed have constitutive functions of Na(+) exclusion only in the direction of root tips, even under constant high-salt conditions. This function apparently may contribute to the low Na(+) concentration in the upper shoot and high salt tolerance of common reed.

BACKGROUND/AIM Cadherin 5 (CDH5) is important for adhesion in epithelial cells, and expressed in tumor cells in several malignancies. In the present study, we evaluated the clinical significance of CDH5 protein expression in locally advanced gastric cancer. MATERIALS AND METHODS Tumor tissues obtained from 113 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. RESULTS High CDH5 expression was significantly associated with recurrence (p=0.017), especially hematological recurrence (p=0.022). High CDH5 expression was a significant risk factor for hematogenous recurrence on multivariate analysis (odds ratio[OR]=3.9, confidential interval [CI] 1.0-15, p=0.043). Patients with high CDH5 expression had a significantly shorter progression-free interval (RFI, p=0.010) than patients with low CDH5 expression. High CDH5 expression was an independent prognostic factor on multivariate analysis of RFI (hazard ratio[HR]=2.2, 95% CI 1.1-4.3, p=0.021). CONCLUSION CDH5 may play a key role in hematogenous recurrence of advanced gastric cancer and may be a viable treatment target.

The introduction of an active Na+ excretion system from salt-tolerant plants in salt-sensitive crop plants might necessitate enhancement of the robustness of K+ homeostasis and lead to improved plant growth under salt stress. To address this issue, we compared the acquisition and retention of K+ under excess Na+ concentrations in the common reed, which possesses excellent Na+ excretion ability, and low-Na+ excreting rice. Under excess Na+ concentrations, common reed maintained constant K+ content in all plant parts, whereas K+ content in rice decreased with increasing Na+ concentration. Preferential uptake of K+ against high Na+/K+ ratio in nutrient solution was approximately 10 times higher in common reed than in rice. The impact of excess Na+ on net K+ absorption rate of common reed was small. On the other hand, the net K+ absorption rate of rice was decreased by excess Na+ concentration. However, after the Na+ concentration in the nutrient solution was decreased from 50 to 1 mM, K+ absorption in rice recovered immediately. Thus, selectivity of K+ transporters or channels for K+ over Na+ in roots could be involved in the differences in K+ accumulation in rice and common reed.

Barley (Hordeum vulgare), which tolerates iron (Fe) deficiency, secretes a large amount of phytosiderophores from its roots. However, how barley is able to allocate resources for phytosiderophore synthesis when the carbon assimilation rate is reduced by Fe deficiency is unknown. We previously suggested that the acceleration of senescence in older leaves triggered by Fe deficiency may allow the recycling of assimilates to contribute to phytosiderophore synthesis. In this work, we show the relationship between an increase in the C/N ratio in older leaves and Fe-deficiency tolerance among three barley cultivars. The increase in the C/N ratio suggests an enhanced capacity for the retranslocation of carbohydrates or amino acids from older leaves to the sink organs. An increase in the sucrose concentration in Fe-deficient barley also suggests active redistribution of assimilates. This metabolic modulation may be supported by accelerated senescence of older leaves, as Fe deficiency increased the expression of senescence-associated genes. The older leaves of Fe-deficient barley maintained CO2 assimilation under Fe deficiency. Barley that had been Fe-deficient for 3 days preferentially allocated newly assimilated (13) C to the roots and nutrient solution. Interestingly, the oldest leaf of Fe-deficient barley released more (13) C into the nutrient solution than the second oldest leaf. Thus, the balance between anabolism and catabolism in older leaves, supported by highly regulated senescence, plays a key role in metabolic adaptation in Fe-deficient barley.

Common reed (Phragmites australis) is a phytoremediator tolerant to heavy metals. In this study, we found that 70% of the cadmium (Cd) found in the stem of common reed exists in a soluble form, with more than half of the soluble Cd in the 10- to 50-kDa fraction. Based on an enzyme degradation assay, the major component of the Cd-associated molecule is assumed to be an amylopectin-like α-glucan. This molecule may associate with Cd via the carboxyl group, rather than the thiol group. The conditions required for the disengagement of Cd from the 10- to 50-kDa fraction indicated that disulfide bonds and other intramolecular interactions may contribute to maintaining the proper conformation of the molecule and to stabilizing its association with Cd. Accumulation of the Cd-associated molecule was induced by Cd stress, and the molecule was found to be also associated with Cu and Fe. Thus, we have identified a novel mechanism of Cd-pooling, namely, the association of Cd with an α-glucan-like molecule in reed stem.

Iron (Fe) deficiency primarily damages photosystems. A large proportion of the reducing equivalents in mesophyll cells are dependent on the photosynthetic apparatus in the chloroplasts; thus, Fe deficiency profoundly affects nitrogen (N) and sulfur (S) assimilation. Microarray data suggested that nutrient metabolisms concerning the assimilation and re-utilization of essential elements were modulated in barley under Fe-deficient condition. We compared the concentrations of the major essential elements between Fe-deficient barley leaves and Fe-deficient rice leaves. The Fe-deficient barley and rice plants had the same Fe and chlorophyll concentrations, but growth was reduced more in Fe-deficient rice than in Fe-deficient barley. The accumulation of ribulose-1,5-bisphosphate carboxylase/oxygenase protein and nitrite reductase, sulfite reductase, and ferredoxin-dependent glutamate synthase mRNAs was reasonably decreased in the chlorotic young leaves of Fe-deficient barley. , , , , and Ca2+ concentrations were...

It is well known that growth of Suaeda salsa (L.) Pall. is stimulated by NaCl application. However, the physiological role of sodium in the growth of Suaeda salsa has not been elucidated. We thus examined the physiological role of sodium in the growth of Suaeda salsa grown in nutrient solutions containing 5 mmol L ―1 Cl ― and graded concentrations of Na 2 SO 4 . Sodium concentrations in plant tissues increased as the growth medium salinity increased. The osmolality gradient between plant tissues and growth medium was maintained at constant levels despite the increase of osmolality in the growth medium. As a result, the amount of water absorbed by the plant tissues was not significantly affected by the salinity of the medium. The dry weight of the S. salsa plants did not increase significantly as sodium concentrations in plant tissues rose. As salinity of the medium increased, the contribution of water-soluble sodium to the osmolality in the leaves, stems, and roots also rose. There was a significant positive correlation between sodium concentration and osmolality in plant tissues. These results suggest that sodium is the major cation contributing to the maintenance of high osmolality in plant tissues of S. salsa grown under the high-salinity conditions. Therefore, under high-salinity conditions, the physiological role of sodium may be to maintain water absorption by maintaining osmolality in the plant tissues, which would help explain the normal growth of S. salsa under high NaCl conditions.

Potato dextrose broth (PDB), a well-known medium for cultivation of fungi, can be made from potato extract and glucose (handmade PDB) or bought as a commercial powder (commercial PDB). Previously, we reported that bud cell formation and fungal biomass of Fusarium oxysporum in handmade PDB are higher than in commercial PDB, and the presence of high molecular weight (>20 MDa) carbohydrates in PDB promoted bud cell formation by most strains of F. oxysporum. In this study, we report the effects of inorganic ions in PDB on bud cell formation and fungal biomass production by F. oxysporum. Concentrations of Mg, K, Fe, PO4 3− and SO4 2− were higher and of Na and Cl− were lower in handmade PDB than in commercial PDB. Adding each inorganic ion alone to commercial PDB showed that Mg is critical for enhancement of bud cell formation by some strains of F. oxysporum. The addition of Mg2+ with raw potato starch to commercial PDB promoted bud cell formation by some, but not all, of the seven F. oxysporum strains tested in this study.