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991.
Takahiro Aoki Mariko Takami Tomozumi Takatani Kiwamu Motoyoshi Ayana Ishii Ayaka Hara Takahide Toyoda Reona Okada Moeko Hino Ryo Koyama‐Nasu Masahiro Kiuchi Kiyoshi Hirahara Motoko Y. Kimura Toshinori Nakayama Naoki Shimojo Shinichiro Motohashi 《Cancer science》2020,111(7):2223-2233
Invariant natural killer T (iNKT) cells are innate‐like CD1d‐restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vβ11 in humans. iNKT cells specifically recognize glycolipid antigens such as α‐galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d‐positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d‐negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d‐negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d‐independent manner, however still in a TCR‐mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d‐negative leukemia cells (K562, HL‐60, REH) as well as αGalCer‐loaded CD1d‐positive Jurkat cells. The CD1d‐independent cytotoxicity was enhanced by natural killer cell‐activating receptors such as NKG2D, 2B4, DNAM‐1, LFA‐1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d‐negative leukemia cells. In contrast, TCR was essential for CD1d‐independent recognition and cytotoxicity. iNKT cells degranulated toward patient‐derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti–tumor mechanism of iNKT cells in targeting CD1d‐negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d. 相似文献
992.
Yuma Wada Kazunori Tokuda Yuji Morine Shohei Okikawa Shoko Yamashita Tetsuya Ikemoto Satoru Imura Yu Saito Shinichiro Yamada Mitsuo Shimada 《Oncotarget》2020,11(49):4593
Introduction: The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation.Materials and Methods: The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 μg/ml). Activated HSCs (aHSCs) were detected by α-SMA and IL-6 mRNA expressions and cytokine arrays of HSC’s culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression.Results: Colon cancer-CM significantly increased α-SMA and IL-6 mRNA expressions of aHSC. α-SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death.Conclusions: TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells. 相似文献
993.
994.
Shinichiro Nanko M.D. Masaru Kobayashi Ph.D. Shinobu Gamou Ph.D. Jun Kudoh Ph.D. Nobuyoshi Shimizu Ph.D. Noboru Takazawa M.D. Hajime Kazamatsuri M.D. Toshiyuki Furusho M.D. Ph.D. 《Psychiatry and clinical neurosciences》1991,45(1):53-56
Abstract: We have investigated two pedigrees in an attempt to detect the putative linkages between affective disorder and c-Ha- ras -1 oncogene and the insulin gene on chromosome 11, or hypoxanthhte phosphoribosyltransferase (HPRT) on X chromosome. The linkage between affective disorders and the markers on chromosomes 11 and X was ruled out with the assumption of no recombination. 相似文献
995.
Suga S Kato K Ohgami T Yamayoshi A Adachi S Asanoma K Yamaguchi S Arima T Kinoshita K Wake N 《Gynecologic oncology》2007,105(2):341-350
OBJECTIVE: We previously demonstrated that that the Ras/ER/MDM2 pathway was critical for NIH3T3 cell transformation. In this study, we examined the effect of blocking this pathway on cell growth in gynecologic cancer cells. METHODS: (1) The levels of MDM2, ER, p53 and p21 in endometrial or ovarian cancer cell lines were investigated and compared with that in normal cells by Western blots. (2) The effects of MEK-inhibitor and/or anti-estrogen, and siRNA of MDM2 on cell growth, tumorigenicity in nude mice were examined. RESULTS: The MDM2 level was enhanced in cancer cells compared with normal cells. Treatment with MEK inhibitor(U0126) resulted in a reduced MDM2 level, enhanced p53 and p21 levels and inhibited cell growth by the induction of premature senescence. The effect of MEK inhibitor on cell growth was affected by ER levels and functions. Treatment with low-dose MEK inhibitor in combination with anti-estrogen (ICI182,780) had a more inhibitory effect on cell growth compared to treatment with MEK inhibitor or anti-estrogen alone in cancer cells. Down-regulation of the MDM2 level by siRNA resulted in the inhibition of growth in cancer cells. CONCLUSION: The blockage of the MAPK/ER/MDM2 pathway suppress cell proliferation and it is supposed as a new molecular target therapy in estrogen-dependent gynecologic cancers, such as endometrial or ovarian cancer. 相似文献
996.
Shinichiro Ikuta Kazuhiro Kobuke Yoshitaka Iwanaga Yoshifumi Nakauchi Kenji Yamaji Shunichi Miyazaki 《Heart and vessels》2014,29(3):320-327
Compared with the bare metal stent (BMS), suppression of neointimal growth in the sirolimus-eluting stent (SES) reduced restenosis at the cost of more exposed struts that could impose the risk of stent thrombosis. The present study was conducted to analyze neointimal coverage patterns of stents at a strut-level after implantation of BMS or SES with the use of optical coherence tomography (OCT). We enrolled 35 patients and analyzed neointimal coverage of every strut from 41 stents (BMS: n = 8, SES: n = 33) by using OCT at follow-up of the stent implantation. All of the 371 struts from eight BMSs were covered with ≥100 μm of neointima, while 19.8 and 3.5 % of 3,478 struts from 33 SESs were uncovered (neointimal thickness of <10 μm) and malapposed, respectively. The histogram of neointimal thickness showed basically normal distribution in BMS but skewed in SES. No regional difference in neointimal thickness was observed in BMS (proximal, 535.7 ± 25.2 μm; body, 532.4 ± 17.0 μm; distal, 485.8 ± 27.0 μm). In SES, however, the body segment showed thinner neointima [median 40 μm (interquartile range (IQR) 10–90 μm)] than proximal [60 μm (IQR 10–140 μm), p < 0.001] or distal [50 μm (IQR 10–110 μm), p < 0.001] segment, while uncovered and malapposed struts were more frequent in the proximal and body segments. In conclusion, SES, compared with BMS, showed more suppressed neointimal growth with regional variation: neointimal thickness was the least in the body part while the ratio of exposed and malapposed struts was minimal in the distal segment. OCT was useful for a strut-level analysis of neointimal coverage over the whole stent. 相似文献
997.
Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation 总被引:16,自引:0,他引:16
Ebara M Okabe S Kita K Sugiura N Fukuda H Yoshikawa M Kondo F Saisho H 《Journal of hepatology》2005,43(3):458-464
BACKGROUND/AIMS: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC). METHODS: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period. RESULTS: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients. CONCLUSIONS: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy. 相似文献
998.
Role of thrombospondin‐1 expression in colorectal liver metastasis and its molecular mechanism
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999.
Syusai Yamada Kazuya Fukuoka Mitsutomi Miyake Shigeru Miyata Taisuke Nakajima Kunihiro Tamura Chiharu Tabata Shinichiro Iida Kozo Kuribayashi Ayuko Uesaka Aki Murakami Akihiro Yasumitsu Takashi Nakano 《Nihon Kokyūki Gakkai zasshi》2007,45(9):720-725
A 66-year-old woman was admitted due to right cervical lymphadenopathy and an abnormal chest radiograph. Acid-fast bacilli smear of fine needle aspiration from a right cervical lymph node was positive. Histopathological examination of the specimen obtained by percutaneous right cervical lymph node biopsy showed necrotizing epithelioid granulomas and no malignant cells. Therefore, right cervical tuberculous lymphadenitis was diagnosed. Partial lung resection of the right S4 was carried out by video-assisted thoracoscopic surgery and primary lung cancer was diagnosed. To our knowledge, there has been no previous report of both primary lung cancer and cervical tuberculous lymphadenitis being present at the time of the first examination. We report this very rare case. 相似文献
1000.
Shinsuke Washizuka Kazuya Iwamoto An-A Kazuno Chihiro Kakiuchi Kanako Mori Mizue Kametani Kazuo Yamada Hiroshi Kunugi Osamu Tajima Tsuyoshi Akiyama Shinichiro Nanko Takeo Yoshikawa Tadafumi Kato 《Neuropsychopharmacology》2004,56(7):483-489
BACKGROUND: Linkage with 18p11 is one of the replicated findings in molecular genetics of bipolar disorder. Because mitochondrial dysfunction has been suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is a candidate gene for this disorder. We previously reported that a polymorphism in the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in Japanese subjects; however, functional significance of -602G> A was not known. METHODS: We screened the further upstream region of NDUFV2. We performed a case-control study in Japanese patients with bipolar disorder and control subjects and a transmission disequilibrium test in 104 parent and proband trios of the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also performed the promoter assay to examine functional consequence of the -602G> A polymorphism. RESULTS: The -602G> A polymorphism was found to alter the promoter activity. We found that the other haplotype block surrounding -3542G> A was associated with bipolar disorder. The association of the haplotypes consisting of -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in Japanese case-control samples and NIMH trios. CONCLUSION: Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic risk factor for bipolar disorder by affecting promoter activity. 相似文献