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Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is the active treatment for peritoneal carcinomatosis of appendiceal origin. However, surgical management is sometimes difficult in patients with a high-tumor burden. A high-tumor burden was defined as a peritoneal cancer index (PCI) ≥ 28. Among 49 patients receiving CRS + HIPEC, 29 had a PCI ≥ 28. Complete cytoreduction (CC-0/1) was achieved in 20 of the 29 patients with a PCI ≥ 28 and in all 20 patients with a PCI

Rationale: Cystic lymphangiomas are uncommon congenital malformations that originate from lymphatic channels. Lymphangiomas frequently appear in the head, neck, and axillary regions of children. Abdominal cystic lymphangiomas are extremely rare, having a reported incidence of 1 in 20,000 to 250,000. Patient concerns: A 50-year-old female patient was admitted to our hospital with a cough that had persisted for several weeks. Abdominal ultrasonography incidentally revealed a multilocular cystic lesion in the lesser curvature of the stomach. Diagnosis: Preoperative findings indicated that the lesion was cystic lymphangioma. However, the possibility of a pancreatic tumor could not be completely excluded. Interventions: Laparoscopy revealed a multilocular cyst in the lesser curvature of the stomach. The gastrocolic ligament was divided, and the body and tail of the pancreas was exposed in the omental bursa, showing that the cystic lesion was not derived from the pancreas but from the lesser omentum. Although it was located directly beside the left gastric artery, the cyst was enucleated and totally resected laparoscopically without sacrificing the artery. Outcomes: The cystic lesion was histopathologically diagnosed as an abdominal cystic lymphangioma originating from the lesser omentum. The patient was discharged on the postoperative day 4 without complications. Lessons: Preoperative imaging cannot completely distinguish abdominal cystic lymphangiomas from other types of cystic tumors. Because cystic lymphangiomas have the potential to grow, invade vital structures, and develop life-threatening complications, laparoscopic assessment followed by total resection is considered a useful treatment strategy for peripancreatic cystic lesions.

Objective: To evaluate whether or not the liquid-based procedure (LBP) for endometrial cytology is as worthwhile for endometrial phasing as conventional slides. Materials and Methods: The subjects were 81 women who underwent endometrial cytology and were defined as negative. The specimens obtained by either Endocyte® or Masubuchi aspiration tube® were processed first with the conventional procedure and then with LBP using TACAS™. Results: (1) The number of subjects diagnosed by the conventional method as having proliferative, mid-, middle-secretory and late-secretory and atrophic phases was 40, 11, 10, 0 and 20, respectively. The rate of agreement with those using LBP was 87.7%. (2) Incidences of large clusters, ductal clusters, palisade arrangement, uneven staining and dirty mucous background detected were significantly higher with the conventional method, whereas with LBP clean background, inconspicuous bonding of cells, scattered solitary glandular cells, clear well-stained cytoplasm and cell compactness were higher. (3) Especially in the proliferative phase, clusters tended to be smaller and lose their architectural structures, and scattered solitary columnar cells were present. (4) Cells in the mid-phase tended to have loose contact and to mimic other phases. Conclusions: Cytodiagnosis of endometrial phasing prepared with LBP is feasible to perform when some modifications are implemented.

Amino acid analysis of Saccharomyces cerevisiae cells indicated that neutral amino acids such as glycine and alanine were probably excluded from the vacuoles, and that vacuolar H(+)-ATPase (V-ATPase) was involved in the vacuolar compartmentalization of these amino acids. We found that vacuolar membrane vesicles export neutral amino acids in an ATP-dependent manner. This is important in identifying vacuolar transporters for neutral amino acids.

Objective: To evaluate a fully automated processing system (TACAS™ Pro) for liquid-based procedures (LBPs). Methods and Materials: Materials were 3,483 and additionally 502 specimens that were taken at Kanagawa Health Service Association. Specimens obtained with a Cervex-Brush® were first smeared to glass slides using one side of the brush and then processed to TACAS Pro. Results: (1) The microscopy watching time per normal case was 3.65 ± 0.85 min in the conventional procedure, whereas in the LBP it was 1.95 ± 0.60 min, and the latter reduced workload to 53%. (2) The handling time of TACAS Pro per day was 2 h and 25.8 min. The workload at a laboratory offset it and revealed the work saving to be 63.8%. (3) Unsatisfactory rates were 0% in the conventional procedure, whereas in the LBP it was 1.88% at first. The latter rate decreased to 0.5% after system improvement. (4) Specimens which may disturb microscopy analysis were found in 1.06%, including 3 cases of possible carry-over of cells to the following slides. An additional study with the revised system confirmed no carry-over. (5) Incidences of abnormal cytology were consistent between the two methods. Conclusions: The revised automated processing system TACAS Pro is a feasible and useful LBP and reduces the workload of cytology laboratories.

Basic amino acids (lysine, histidine and arginine) accumulated in Saccharomyces cerevisiae vacuoles should be mobilized to cytosolic nitrogen metabolism under starvation. We found that the decrease of vacuolar basic amino acids in response to nitrogen starvation was impaired by the deletion of AVT4 gene encoding a vacuolar transporter. In addition, overexpression of AVT4 reduced the accumulation of basic amino acids in vacuoles under nutrient-rich condition. In contrast to AVT4, the deletion and overexpression of AVT3, which encodes the closest homologue of Avt4p, did not affect the contents of vacuolar basic amino acids. Consistent with these, arginine uptake into vacuolar membrane vesicles was decreased by Avt4p-, but not by Avt3p-overproduction, whereas various neutral amino acids were excreted from vacuolar membrane vesicles in a manner dependent on either Avt4p or Avt3p. These results suggest that Avt4p is a vacuolar amino acid exporter involving in the recycling of basic amino acids.

A vacuolar membrane protein, Vba2p of Schizosaccharomyces pombe, is involved in basic amino acid uptake by intact cells. Here we found evidence that Vba2p mediated ATP-dependent lysine uptake by vacuolar membrane vesicles of Saccharomyces cerevisiae. Vba2p was also responsible for quinidine sensitivity, and the addition of lysine improved cell growth on quinidine-containing media. These findings should be useful for further characterization of Vba2p.

Objective: To evaluate the usefulness of a new liquid-based cytological procedure in a population screening program for cervix cancer. Subjects and Methods: Subjects were 1,000 women who underwent primary screening at the Kanagawa Health Service Association. The cytological specimens obtained by either cotton stick and Cytobrush® or Cervex-Brush® were processed using the Thinlayer Advanced Cytology Assay System (TACAS™), following the manufacturer’s instructions. Results: (1) Cells were evenly distributed on specimens and stained evenly; (2) shrinkage of cells was 5% based on measurement of the nuclear diameters of granulocytes in comparison with those of the conventional procedure; (3) incidences of cells that occupied the whole area, 1/20≤, 1/4≤, 1/4> of the observation fields were 58.8, 26.2, 12.0 and 3.0%, respectively; (4) number of the squamous cells in cases with 1/4> was Conclusion: TACAS is a feasible and useful cytological procedure.

The fission yeast Schizosaccharomyces pombe has a homolog of the budding yeast Atg22p, which is involved in spore formation (Mukaiyama H. et al., Microbiology, 155, 3816–3826 (2009)). GFP-tagged Atg22p in the fission yeast was localized to the vacuolar membrane. Upon disruption of atg22, the amino acid levels of the cellular fraction as well as the vacuolar fraction decreased. The uptake of several amino acids, such as lysine, histidine, and arginine, was impaired in atg22Δ cells. S. pombe Atg22p plays an important role in the compartmentalization of amino acids.

A recent study filling the gap in the genome sequence in the left arm of chromosome 2 of Schizosaccharomyces pombe revealed a homolog of budding yeast Vba2p, a vacuolar transporter of basic amino acids. GFP-tagged Vba2p in fission yeast was localized to the vacuolar membrane. Upon disruption of vba2, the uptake of several amino acids, including lysine, histidine, and arginine, was impaired. A transient increase in lysine uptake under nitrogen starvation was lowered by this mutation. These findings suggest that Vba2p is involved in basic amino acid transport in S. pombe under diverse conditions.