Donor mesenchymal stem cells trigger chronic graft-versus-host disease following minor antigen-mismatched bone marrow transplantation

Chronic graft-versus-host disease (cGVHD) is a complication after minor antigen mismatched bone marrow transplantation (BMT) characterized by an autoimmune-type reaction in various organs. Aberration in T cell regulation is involved, with donor mesenchymal stem cells (MSCs) playing a possible role in immunomodulation. In a minor-antigen mismatched mouse BMT model, transplantation of mismatched, but not syngeneic MSCs triggered the onset of cGVHD, and was associated with fibrosis, increased IL-6 secretion, decreased Foxp3+ regulatory T cells and increased Th17 in the peripheral blood. Mismatched MSCs alone were sufficient to induce cGVHD, while removal of donor MSCs rescued mice from cGVHD. RAG2 knockout recipient mice did not suffer cGVHD, indicating that host T cells were involved. Residual host-derived T cells were significantly higher in cGVHD patients compared to non-cGVHD patients. In conclusion, donor MSCs react with residual host T cells to trigger the progression of cGVHD

Remarks on the Gauss images of complete minimal surfaces in Euclidean four-space

We perform a systematic study of the image of the Gauss map for complete minimal surfaces in Euclidean four-space. In particular, we give a geometric interpretation of the maximal number of exceptional values of the Gauss map of a complete orientable minimal surface in Euclidean four-space. We also provide optimal results for the maximal number of exceptional values of the Gauss map of a complete minimal Lagrangian surface in the complex two-space and the generalized Gauss map of a complete nonorientable minimal surface in Euclidean four-space. © 2017 Fondazione Annali di Matematica Pura ed Applicata and Springer-Verlag Berlin HeidelbergEmbargo Period 12 month

Excited States of Calogero-Sutherland Model and Singular Vectors of the WNW_N Algebra

Using the collective field method, we find a relation between the Jack symmetric polynomials, which describe the excited states of the Calogero-Sutherland model, and the singular vectors of the $W_N$ algebra. Based on this relation, we obtain their integral representations. We also give a direct algebraic method which leads to the same result, and integral representations of the skew-Jack polynomials.Comment: LaTeX, 29 pages, 2 figures, New sections for skew-Jack polynomial and example of singular vectors adde

ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC

Deregulated GSK3β sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase

金沢大学がん研究所分子標的がん医療研究開発センターPurpose: Glycogen synthase kinase-3β (GSK3β) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3β in gastrointestinal, pancreatic, and liver cancers. Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3β expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3β activity by in vitro kinase assay. The effects of small-molecule GSK3β inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3β inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells. Results: Cancer cell lines and most cancer tissues showed increased GSK3β expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3β resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3β inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity. Conclusion: The results indicate that deregulated GSK3β sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. © 2009 American Association for Cancer Research

イガン サイハツゴ ノ テイアルブミン ケッショウ ト ナンジセイ オウト ニ ハロペリドール ガ ユウコウ デアッタ イチショウレイ

The patient was an 83-year-old woman who underwent laparoscopy-assisted distal gastrectomy for gastric cancer on February 25, 201X. S‐1 and UFT were performed, but metastatic liver cancer was seen on a CT scan on September 2. S‐1 was restarted on October 2６ but discontinued on January 18, 201X＋1 and best supportive care was adopted. She was hospitalized on April 15 for loss of appetite and anasarca. The patient had intractable vomiting and treatment resistance to metoclopramide and domperidone. ALB had decreased to 1．3 g/dl on April 22. A decrease in gastrointestinal motility from ascites retention was seen on a CT scan on April 25. Continuous subcutaneous infusion with haloperidol was started on April 25. The frequency of vomiting significantly decreased immediately afterward, and daily caloric intake significantly increased. Her ascites and anasarca were markedly improved on a CT scan on May 11. ALB had risen to 2．7 g/dlon June 14. Continuous subcutaneous infusion of haloperidol was effective for hypoalbuminemia and intractable vomiting after gastric cancer recurrence