Interaction between gastric cancer stem cells and the tumor microenvironment

Gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. Cancer stem cells (CSCs) are selectively capable of tumor initiation and are implicated in tumor relapse and metastasis, thus, governing the prognosis of GC patients. Stromal cells and extracellular matrix adjacent to cancer cells are known to form a supportive environment for cancer progression. CSC properties are also regulated by their microenvironment through cell signaling and related factors. This review presents the current findings regarding the influence of the tumor microenvironment on GC stem cells, which will support the development of novel therapeutic strategies for patients with GC.     

A case of solitary bone cyst in the skull increasing in size after trivial head injury

A 12-year-old boy had been known to have a small swelling in the left high vertex for several years. After a trivial head hit to the site of the swelling, the swelling enlarged gradually. A bone window CT scan showed a lesion having bubble-like lytic change in the left parietal bone. Similar changes, but small, were able to be pointed out in a CT scan taken seven years previously. In the following 13 months CT scans eventually revealed sequential increases to 3.5 cm in diameter. Surgical exploratory resection of the mass was performed. Intraoperatively, partial destruction of the outer skull table and a simple cyst with serous yellowish brown colored fluid were identified. There was no finding adherent to the diploic structure. The bone defect after excision was reconstructed by using a titanium plate. The patient was followed up for 2 years after the surgery. Bone window CT showed bony development of normal appearance. Histological examination showed the cyst wall consisted of fibrous connective tissue but there were neither epithelial nor endothelial cells. The histopathological diagnosis of SBC was most likely. SBC is relatively common in long bones, but rarely in flat bones. Only several cases of the SBC of cranial bone have been reported. Although a craniectomy for total excision followed by cranioplasty by resin was common, in cases of children, cyst removal with titanium plate application would be an alterative. SBC increasing in size after head injury is extremely rare, but clinicians may need to be aware of cystic skull bone tumors increasing in size after head injury.     

Clinicopathological features of gastric carcinoma in younger and middle-aged patients: A comparative study

Gastric carcinoma is relatively rare in patients under the age of 40. This study was undertaken to clarify the clinicopathological characteristics and surgical outcomes of gastric carcinoma in younger patients compared with those of middle-aged patients. The surgical results from 131 younger patients (aged ⩽40 years) and 918 middle-aged patients (aged 55–65 years) were compared retrospectively. Female gender, undifferentiated tumor type and lymphatic invasion were significantly more common in the younger patients. Survival time did not differ between the two groups. The depth of tumor invasion was the only prognostic factor in younger patients, whereas macroscopic appearance, tumor diameter, depth of invasion, lymph node metastasis, and venous invasion were all significant prognostic factors in middle-aged patients. Peritoneal recurrence was significantly more common in younger patients. A family history of gastric adenocarcinoma was observed in 25.9% of younger patients, but this did not affect survival outcomes. As depth of invasion affects prognosis independently, and peritoneal metastasis is the predominant pattern of recurrence, it is essential to establish an optimal prophylactic treatment for peritoneal metastasis to improve surgical outcomes in younger patients with advanced gastric cancer.     

Priority of Lymph Node Dissection for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction

Objective

The purpose of this study was to clarify the priority of nodal dissection in Siewert types II and III adenocarcinoma of the esophagogastric junction (AEG).

Methods

The priority of nodal dissection was evaluated based on the therapeutic value index calculated by multiplying of the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station.

Results

A total of 176 patients (95 type II and 81 type III) were examined. Among the lymph nodes that had a metastatic incidence exceeding 10 %, the stations showing the first to fourth highest index were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the node at the root of the left gastric artery (No. 7) in the total cohort, as well as in each type. The next station was the lower thoracic paraesophageal lymph node (No. 110), followed by the nodes along the proximal splenic artery (No. 11p) in type II, whereas it was the nodes along the proximal splenic artery (No. 11p) followed by the para-aortic nodes (No. 16a2), the nodes at the celiac artery (No. 9), and the nodes around the splenic hilum (No. 10) in type III.

Conclusions

These results suggest that the highest priority nodal stations to be dissected were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the nodes at the root of the left gastric artery (No. 7), regardless of the Siewert subtype, but the subsequent priority was different depending on the subtype.     

Oxidation-degree-dependent moisture-induced actuation of a graphene oxide film

Multilayered films prepared from graphene oxide (GO) subjected to a single oxidation process (1GO) can actuate in response to moisture, whereas those prepared from GO subjected to two oxidation processes (2GO) lose this ability. To elucidate the origin of this difference, the structures and properties of various multilayered films and their contents were analyzed. According to atomic force microscopy images, the lateral size of the GO monolayer in 2GO (2.0 ± 0.4 μm) was smaller than that in 1GO (3.2 ± 0.4 μm), although this size difference did not affect actuation. Scanning electron microscopy images of the cross sections of both films showed fine multilayered structures and X-ray diffraction measurements showed the moisture sensitive reversible change in the interlayer distances for both films. Both films adsorbed 30 wt% moisture in 60 s with different water contents at the bottom moist sides and top air sides of the films. Nanoindentation experiments showed hardness values (1GO: 156 ± 67 MPa; 2GO: 189 ± 97 MPa) and elastic modulus values (1GO: 4.7 ± 1.7 GPa; 2GO: 5.8 ± 3.2 GPa) typical of GO, with no substantial difference between the films. On the contrary, the 1GO film bent when subjected to a weight equal to its own weight, whereas the 2GO film did not. Such differences in the macroscopic hardness of GO films can affect their moisture-induced actuation ability.

The moisture-induced actuation behavior of graphene oxide (GO) thin films was found to depend on their extent of oxidation.     

Enzymatic kinetics regarding reversible metabolism of CS-0777, a sphingosine 1-phosphate receptor modulator,via phosphorylation and dephosphorylation in humans

1.?CS-0777, a candidate compound for autoimmune diseases, becomes phosphorylated active metabolite, M1, by fructosamine 3-kinase (FN3K), FN3K-related protein (FN3K-RP); and M1 is reverted back to CS-0777 by alkaline phosphatase (ALP) in the body. We performed enzyme kinetic analysis of phosphorylation of CS-0777 by FN3K, FN3K-RP, human erythrocytes and human platelets; and dephosphorylation of M1 by various ALP isozymes and human liver, kidney, lung and small intestine microsomes.

2.?The Michaelis constants of human FN3K, FN3K-RP and erythrocytes for CS-0777 phosphorylation were in the range from 498?μM to 1060?μM. FN3K inhibitor, 1-deoxy-1-morpholinofructose, suppressed only about 20% of CS-0777 phosphorylation activity in human erythrocyte lysate. Immunodepletion of FN3K and FN3K-RP decreased M1 formation activity by about 25% and 50%, respectively, in human erythrocyte lysate.

3.?The Michaelis constants of four human ALPs and microsomes were in the range from 10.9?μM to 32.1?μM. The ALP inhibitor, levamisole, suppressed over 50% of M1 dephosphorylation activity in liver, kidney and lung microsomes.

4.?FN3K-RP is expected to take a prominent role in the phosphorylation of CS-0777 in human erythrocytes; dephosphorylation of M1 was observed in all ALPs and human tissue microsomes examined, with a similar affinity towards M1 among them.     

Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: A multicenter,randomized, double‐blind,placebo‐controlled,parallel‐group,phase III study in Japan

Aims/IntroductionThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial has shown the effects of canagliflozin on preventing clinically important kidney outcomes in patients with type 2 diabetes mellitus and chronic kidney disease; however, not many Japanese patients were included in the trial. The present study evaluated the efficacy and safety of canagliflozin in Japanese chronic kidney disease patients with type 2 diabetes mellitus.Materials and MethodsIn this multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, chronic kidney disease patients with type 2 diabetes mellitus were randomly assigned to receive either 100 mg canagliflozin or a matching placebo once daily for 104 weeks. The primary efficacy end‐point was the incidence of a 30% decline in estimated glomerular filtration rate.ResultsOverall, 308 patients were randomized to the canagliflozin (n = 154) and placebo (n = 154) groups. The incidence of a 30% decline in estimated glomerular filtration rate at week 104 was 18.2% and 29.5%, respectively, and the point estimate of the intergroup difference (placebo − canagliflozin) was 11.3% (95% confidence interval 1.2–21.5, P = 0.029), which was significant. The overall incidence of adverse events was similar in the two groups.ConclusionsThis study suggests that canagliflozin safely reduces the risk of end‐stage renal disease in Japanese chronic kidney disease patients with type 2 diabetes mellitus.