A case of microscopic low-grade appendiceal mucinous neoplasm complicated with appendicitis resected by reduced-port laparoscopic surgery

Appendicitis is a benign disease for which surgical treatment is widely provided. The complication of neoplastic lesions may be discovered only after resection. However, in some cases, specimens are not submitted to histopathological examination in Japan because of an extreme deficiency of pathologists. We report our experience with one patient who experienced the complication of latent low-grade appendiceal mucinous neoplasm (LAMN) after surgery for appendicitis. Our patient was an 85-year-old woman. Conservative treatment failed to relieve fever and lower abdominal pain and it was decided to treat her surgically. Abdominal computed tomography (CT) showed appendicitis with severe inflammation and suspected adhesion. We decided to explore the abdominal cavity using a reduced-port laparoscopic approach. We found no mucous debouchment or clear tumors in the specimen. Histopathological findings indicated the coexistence of appendicitis and LAMN. At one year and a half after surgery, there was no evidence of the development of pseudomyxoma peritonei. In appendectomy, it is thought that careful perioperative treatment and a postoperative pathological search are important when there are no preoperative findings suggesting a neoplastic lesion

Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells.

Sept4, a subunit of the septin cytoskeleton specifically expressed in quiescent hepatic stellate cells (HSCs), is downregulated through transdifferentiation to fibrogenic and contractile myofibroblastic cells. Since Sept4(-/-)mice are prone to liver fibrosis, we aimed to identify the unknown molecular network underlying liver fibrosis by probing the association between loss of Sept4 and accelerated transdifferentiation of HSCs

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species

Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment.We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germlayer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stemcells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestockmammals, pluripotent stemcells related to the formative embryonic disc are reliably established using a common and defined signalling environment

Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma

We sought to identify a secreted biomarker for β-catenin activation commonly seen in hepatocellular carcinoma (HCC). By examination of our previously published genearray of hepatocyte-specific β-catenin knockout (KO) livers, we identified secreted factors whose expression may be β-catenin-dependent. We verified expression and secretion of the leading factor in HCC cells transfected with mutated (Hep3BS33Y)-β- catenin. Serum levels of biomarker were next investigated in a mouse model of HCC with β-catenin gene (Ctnnb1) mutations and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2) expression was decreased in KO livers. Hep3BS33Y expressed and secreted more LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations showed significantly higher serum LECT2 levels. However patients with CTNNB1 mutations showed LECT2 levels of 54.28±22.32 ng/mL (Mean ± SD; n = 8) that were insignificantly different from patients with non-neoplastic chronic liver disease (32.8±21.1 ng/mL; n = 15) or healthy volunteers (33.2±7.2 ng/mL; n = 11). Intriguingly, patients without β-catenin mutations showed significantly higher serum LECT2 levels (54.26 ± 22.25 ng/mL; n = 46). While β-catenin activation was evident in a subset of non-mutant β-catenin HCC group with high LECT2 expression, serum LECT2 was unequivocally similar between β-catenin-active and -normal group. Further analysis showed that LECT2 levels greater than 50 ng/ml diagnosed HCC in patients irrespective of β-catenin mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus, LECT2 is regulated by β-catenin in HCC in both mice and men, but serum LECT2 reflects β-catenin activity only in mice. Serum LECT2 could be a potential biomarker of HCC in patients. © 2014 Okabe et al

The Case Study of the Instructional Method to Develop Scientific Competencies in Junior High School Science : Focus on “the ability to using scientific evidence”

The purpose in this study was inventing an instructional method to develop “scientific competencies” through a unit for junior high school students. And the instructional method focus on “the ability to using scientific evidence” in “scientific competencies”. In this method, students will do the following four leaning activities in the unit of “Changes in biological and animal life”. First, they will lead conclusion which based on scientific evidence. Second, they will evaluate the conclusion of others and self. In order to investigate effectiveness of the method, we conducted a class which 41 junior high school students. Based on their writings on questionnaires and worksheets for class, we conclude that our method can improve their ability to evaluate the conclusion of others and self, which is a part of “the ability to using scientific evidence”

Advances in Allogeneic Cancer Cell Therapy and Future Perspectives on “Off-the-Shelf” T Cell Therapy Using iPSC Technology and Gene Editing

The concept of allogeneic cell therapy was first presented over 60 years ago with hematopoietic stem cell transplantation. However, complications such as graft versus host disease (GVHD) and regimen-related toxicities remained as major obstacles. To maximize the effect of graft versus leukemia, while minimizing the effect of GVHD, donor lymphocyte infusion was utilized. This idea, which was used against viral infections, postulated that adoptive transfer of virus-specific cytotoxic T lymphocytes could reconstitute specific immunity and eliminate virus infected cells and led to the idea of banking third party cytotoxic T cells (CTLs). T cell exhaustion sometimes became a problem and difficulty arose in creating robust CTLs. However, the introduction of induced pluripotent stem cells (iPSCs) lessens such problems, and by using iPSC technology, unlimited numbers of allogeneic rejuvenated CTLs with robust and proliferative cytotoxic activity can be created. Despite this revolutionary concept, several concerns still exist, such as immunorejection by recipient cells and safety issues of gene editing. In this review, we describe approaches to a feasible “off-the-shelf” therapy that can be distributed rapidly worldwide. We also offer perspectives on the future of allogeneic cell cancer immunotherapy