大腸癌肝転移におけるCD200発現の臨床的意義

Background: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). Methods: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. Results: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy. Conclusions: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM.博士（医学）・乙第1497号・令和3年3月15日© 2021. Society of Surgical Oncology.© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Annals of Surgical Oncology. The final authenticated version is available online at: https://doi.org/10.1245/s10434-020-09471-w

Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

[Purpose] A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. [Methods] We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. [Results] Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS-defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. [Conclusion] Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions

p53 変異型ヒト口腔がん細胞における高LET 放射線によるp53 非依存Akt 生存シグナルの抑制

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.博士（医学）・甲第598号・平成25年3月15日Copyright © 2012 Elsevier Inc. All rights reserve

Variation in bradyrhizobial NopP effector determines symbiotic incompatibility with Rj2-soybeans via effector-triggered immunity

The soybean Rj2 gene encodes a TIR-NBS-LRR protein that confers resistance to nodulation by certain rhizobial strains. Here, the authors show that T3SS effector NopP is an avirulence protein that is necessary for Bradyrhizobium diazoefficiens USDA 122 to trigger Rj2-dependent incompatibility

根治切除後の結腸癌StageⅡ、StageⅢ、及び大腸癌肝転移における原発部位が与える影響

Purpose: Primary tumor location of colon cancer has been reported to affect the prognosis after curative resection. However, some reports suggested the impact was varied by tumor stage. This study analyzed the prognostic impact of the sidedness of colon cancer in stages II, III, and liver metastasis after curative resection using propensity-matched analysis. Methods: Right-sided colon cancer was defined as a tumor located from cecum to splenic flexure, while any more distal colon cancer was defined as left-sided colon cancer. Patients who underwent curative resection at Nara Medical University hospital between 2000 and 2016 were analyzed. Results: There were 110 patients with stage II, 100 patients with stage III, and 106 patients with liver metastasis. After propensity matching, 28 pairs with stage II and 32 pairs with stage III were identified. In the patients with stage II, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for right- and left-sided colon cancers. In the patients with stage III, OS and RFS were significantly worse in right-sided colon cancer. In those with liver metastasis, OS of right-sided colon cancer was significantly worse than left-sided disease, while RFS was similar. Regarding metachronous liver metastasis, the difference was observed only in the patients whose primary colon cancer was stage III. In each stage, significantly higher rate of peritoneal recurrence was found in those with right-sided colon cancer. Conclusion: Sidedness of colon cancer had a significant and varied prognostic impact in patients with stage II, III, and liver metastasis after curative resection.博士（医学）・乙第1495号・令和3年3月15日Copyright © 2021 The Korean Society of Coloproctology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn\u27s disease patients

Complementa esse poema o artigo “Shelley, poesia e liberdade” em verve dobras http://www.nu-sol.org/verve/verve1.php

LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn\u27s disease patients

BACKGROUND. Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn’s disease (CD) patients, and are associated with autophagy-associated ATG16L1 and NOD2 variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy. METHODS. We performed a hypothesis-driven analysis of 56 single nucleotide polymorphisms (SNPs) associated with CD susceptibility or known to affect Paneth cell function in 110 Japanese CD patients who underwent ileal resection. We subsequently performed a genome-wide association analysis. Paneth cell phenotype was determined by defensin-5 immunofluorescence. Selected genotype–Paneth cell defect correlations were compared to a Western CD cohort (n = 164). RESULTS. The average percentage of abnormal Paneth cells in Japanese CD was similar to Western CD (P = 0.87), and abnormal Paneth cell phenotype was also associated with early recurrence (P = 0.013). In contrast to Western CD, ATG16L1 T300A was not associated with Paneth cell defect in Japanese CD (P = 0.20). Among the 56 selected SNPs, only LRRK2 M2397T showed significant association with Paneth cell defect (P = 3.62 × 10(–4)), whereas in the Western CD cohort it was not (P = 0.76). Pathway analysis of LRRK2 and other candidate genes with P less than 5 × 10(–4) showed connections with known CD susceptibility genes and links to autophagy and TNF-α networks. CONCLUSIONS. We found dichotomous effects of ATG16L1 and LRRK2 on Paneth cell defect between Japanese and Western CD. Genes affecting Paneth cell phenotype in Japanese CD were also associated with autophagy. Paneth cell phenotype also predicted prognosis in Japanese CD. FUNDING. Helmsley Charitable Trust, Doris Duke Foundation (grant 2014103), Japan Society for the Promotion of Science (KAKENHI grants JP15H04805 and JP15K15284), Crohn’s and Colitis Foundation grant 274415, NIH (grants 1R56DK095820, K01DK109081, and UL1 TR000448)

Analysis of the Evidence-practice Gap to Facilitate Proper Medical Care for the Elderly: Investigation, using Databases, of Utilization Measures for National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB)

As Japan becomes a super-aging society, presentation of the best ways to provide medical care for the elderly, and the direction of that care, are important national issues. Elderly people have multi-morbidity with numerous medical conditions and use many medical resources for complex treatment patterns. This increases the likelihood of inappropriate medical practices and an evidence-practice gap. The present study aimed to: derive findings that are applicable to policy from an elucidation of the actual state of medical care for the elderly; establish a foundation for the utilization of National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), and present measures for the utilization of existing databases in parallel with NDB validation. Cross-sectional and retrospective cohort studies were conducted using the NDB built by the Ministry of Health, Labor and Welfare of Japan, private health insurance claims databases, and the Kyoto University Hospital database (including related hospitals). Medical practices (drug prescription, interventional procedures, testing) related to four issues—potential inappropriate medication, cancer therapy, chronic kidney disease treatment, and end-of-life care—will be described. The relationships between these issues and clinical outcomes (death, initiation of dialysis and other adverse events) will be evaluated, if possible