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61.
Junko?KishikawaEmail author Shinsuke?Kazama Koji?Oba Kiyoshi?Hasegawa Hiroyuki?Anzai Yuzo?Harada Hiroyuki?Abe Keisuke?Matsusaka Kumiko?Hongo Masaru?Oba Koji?Yasuda Kensuke?Otani Takeshi?Nishikawa Toshiaki?Tanaka Junichiro?Tanaka Tomomichi?Kiyomatsu Keisuke?Hata Kazushige?Kawai Hiroaki?Nozawa Hironori?Yamaguchi Soichiro?Ishihara Eiji?Sunami Tetsuo?Ushiku Joji?Kitayama Masashi?Fukayama Norihiro?Kokudo Toshiaki?Watanabe 《Annals of surgical oncology》2016,23(6):1916-1923
Background
CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.Methods
CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.Results
CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).Conclusions
Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.62.
Tsuyoshi Ozawa MD Shinsuke Kazama MD PhD Takashi Akiyoshi MD PhD Koji Murono MD Satomi Yoneyama MD PhD Toshiaki Tanaka MD PhD Junichiro Tanaka MD PhD Tomomichi Kiyomatsu MD PhD Kazushige Kawai MD PhD Hiroaki Nozawa MD PhD Takamitsu Kanazawa MD PhD Hironori Yamaguchi MD PhD Soichiro Ishihara MD PhD Eiji Sunami MD PhD Joji Kitayama MD PhD Teppei Morikawa MD PhD Masashi Fukayama MD PhD Toshiaki Watanabe MD PhD 《Annals of surgical oncology》2014,21(8):2650-2658
Background
The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.Methods
The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.Results
Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).Conclusions
Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC. 相似文献63.
Kuroda T Tanabe N Sakatsume M Nozawa S Mitsuka T Ishikawa H Tohyama CT Nakazono K Murasawa A Nakano M Gejyo F 《Clinical rheumatology》2002,21(1):23-27
In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone
marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis
(OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients
and cytokine levels measured. The serum levels of five cytokines (IL-1β, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA.
Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly
higher in all RA patients than in those with OA. Mean (tSD) IL-2 levels were significantly higher in patients with mutilans-type
RA (309.8t686.3 pg/ml) than in patients with other types of RA (66.5t173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of
RA (P<0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables
were no different between mutilans RA and other types of RA. No correlations were observed between IL-1β, IL-2, IL-3, IL-6
and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum
were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related
to systemic inflammation, as there was no correlation with other inflammatory factors.
Received: 9 October 2000 / Accepted: 16 July 2001 相似文献
64.
Rei Miyamoto Takashi Nozawa Koichi Shiozuka Kenji Tabata 《Journal of pharmaceutical sciences》2019,108(3):1085-1089
Lilly Laboratories cell porcine kidney 1 (LLC-PK1) cells transfected with human P-glycoprotein (LLC-PK1-P-gp) are widely used in transport assays to identify drug candidates that function as substrates of this efflux transporter. Endogenous transporters expressed in LLC-PK1 cells may complicate the interpretation of findings from P-gp-mediated transport assays. We investigated the impact of porcine breast cancer resistance protein (Bcrp) in P-gp-mediated transport assays in LLC-PK1 cells. Porcine Bcrp mRNA was detected in both LLC-PK1 wildtype (WT) and LLC-PK1-P-gp cells by quantitative RT-PCR. To investigate the activity and impact of porcine Bcrp, we conducted transport assays using 6 typical BCRP substrates in LLC-PK1 cells. Efflux ratios (ER) of the 6 BCRP substrates in LLC-PK1 WT cells were >2, and were reduced in the presence of the BCRP inhibitor Ko143. The efflux activities of the 6 BCRP substrates were confirmed using MDCKII cells transfected with human BCRP. Net ERs of prazosin and fluvastatin, dual substrates of P-gp and BCRP, determined by dividing ERs in LLC-PK1-P-gp cells by those in LLC-PK1 WT cells, were <2, but increased to >2 in the presence of Ko143. These results indicated that endogenous Bcrp in LLC-PK1 cells was involved in the transport of BCRP substrates and may interfere with the identification of P-gp substrates. 相似文献
65.
Tetsuhiko Okabe Noriko Aida Tetsu Niwa Kumiko Nozawa Jun Shibasaki Hitoshi Osaka 《Pediatric radiology》2014,44(5):597-604
Background
Knowledge of MRI findings in pediatric cerebral infarction is limited.Objective
To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen.Materials and methods
Images from 12 children (age range: 0–9 years; neonates [<1 month], n=5; infants [1 month–12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset.Results
Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete.Conclusion
In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one. 相似文献66.
Yosuke Osawa Yoshiko Banno Masahito Nagaki Yoshinori Nozawa Hisataka Moriwaki Shigeru Nakashima 《Liver international》2001,21(5):309-319
Abstract: Background/Aims: To clarify the mechanism of hepatocyte apoptosis induced by tumor necrosis factor‐α (TNF‐α), caspase cascade and ceramide formation were investigated in the liver of D‐galactosamine (GalN)‐sensitized mice treated with TNF‐α. Methods: Seven‐week‐old male BALB/c mice were intraperitoneally injected with 20 mg GalN 30 min prior to the intravenous injection of recombinant mouse TNF‐α (0.5 μg/mouse). Cytochrome c release and processing of procaspases in the liver were analyzed by Western blotting. Activities of caspases were measured using chromogenic peptides as substrates. Ceramide content was determined using Escherichia coli diacylglycerol kinase. Results: Apoptosis of hepatocytes was observed in mice treated with both GalN and TNF‐α (GalN/TNF‐α), but not GalN or TNF‐α alone. Activation of caspases‐9 and ‐3, and cytochrome c release were observed only in liver from mice treated with GalN/TNF‐α. In a cell‐free system, processing of procaspases‐9 and ‐3, and cytochrome c release were observed in the postnuclear fraction of liver obtained from GalN/TNF‐α‐treated mice, but not in that from control mice. Processing of procaspase‐3 was inhibited by a caspase‐9 inhibitor, but not by inhibitor for caspase‐8 or ‐2. In a reconstitution assay system, procaspase‐9 processing occurred, when both cytosol and membrane fractions were obtained from the liver of mice treated with GalN/TNF‐α. Ceramide accumulation was observed only in apoptotic liver and preceded cytochrome c release and caspase activation. Conclusion: Cytochrome c release and caspase‐9 activation are required for the activation of executor caspase‐3 in TNF‐α‐induced hepatocyte apoptosis, but caspases‐8 and ‐2 play, if any, a minimal role. Ceramide may be implicated in this apoptotic process. 相似文献
67.
Hiroshi Ninomiya Michio Ozeki Akifumi Nozawa Shiho Yasue Saori Endo Masayuki Inuzuka Natsuko Obara Kiyofumi Mochizuki Masaya Kawaguchi Yo Kaneko Naoyuki Ohe Yoko Aoki Masayuki Matsuo Toru Iwama Hidenori Ohnishi 《Medicine》2022,101(6)
Rationale:McCune–Albright syndrome (MAS) is a rare disorder characterized by clinical findings, which includes fibrous dysplasia (FD). FD is a benign tumor that leads to increased rates of bone fracture. In some MAS cases with FD, facial deformities, severe pain, and orbital neuropathies are complicated. Aneurysmal bone cyst (ABC) is a benign bone tumor and rare complication of FD.Patient concerns:A 9-year-old boy was admitted to our hospital because of acute visual disturbance.Diagnosis and interventions:The patient was clinically diagnosed as ABC complicated with MAS, and he underwent surgery.Outcomes:After the surgery, his sight became normal. Recurrence of ABC and visual disturbance was not observed in 3 years. Genetic analysis of a tissue sample from the ABC lesion by next-generation sequencing revealed a somatic activating GNAS mutation.Lessons:To the best of our knowledge, this is the first case report of MAS causing optic neuropathy complicated with ABC. ABC complicated with MAS is extremely rare, but it should be considered as a possible diagnosis in patients with acute visual loss and facial swelling. In addition, our case had OAS, which is an uncommon syndrome and a rare complication in ABC with MAS, and rapid decompression of the ABC was effective in improving the patient''s eyesight. 相似文献
68.
69.
Kae Kawachi Takeshi Sasaki Ayumi Murakami Takashi Ishikawa Ayako Kito Ikuko Ota Daisuke Shimizu Akinori Nozawa Yoji Nagashima Rikuo Machinami Ichiro Aoki 《Pathology, research and practice》2010
This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer. 相似文献
70.
Nakadate S Nozawa K Sato H Horie H Fujii Y Nagai M Hosoe T Kawai K Yaguchi T 《Journal of natural products》2008,71(9):1640-1642
In the course of searching for new antifungal agents, a new cyclic depsipeptide, eujavanicin A (1), was isolated from Eupenicillium javanicum as an antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established by spectroscopic and chemical investigations. The absolute stereochemistry was elucidated by Marfey's method and by chiral HPLC analysis. 相似文献