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991.
Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib
Kohji Noguchi Haruka Kawahara Airi Kaji Kazuhiro Katayama Junko Mitsuhashi Yoshikazu Sugimoto 《Cancer science》2009,100(9):1701-1707
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) inhibit the function of certain adenosine triphosphate (ATP)‐binding cassette transporters, including P‐glycoprotein/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2. We previously reported an antagonistic activity of gefitinib towards BCRP. We have now analyzed the effects of erlotinib, another EGFR‐TKI, on P‐glycoprotein and BCRP. As with gefitinib, erlotinib effectively reversed BCRP‐mediated resistance to SN‐38 (7‐ethyl‐10‐hydroxycamptothecin) and mitoxantrone. In contrast, we found that erlotinib effectively suppressed P‐glycoprotein‐mediated resistance to vincristine and paclitaxel, but did not suppress resistance to mitoxantrone and doxorubicin. Conversely, erlotinib appeared to enhance P‐glycoprotein‐mediated resistance to mitoxantrone in K562/MDR cells. This bidirectional activity of erlotinib was not observed with verapamil, a typical P‐glycoprotein inhibitor. Flow cytometric analysis showed that erlotinib co‐treatment restored intracellular accumulation of mitoxantrone in K562 cells expressing BCRP, but not in cells expressing P‐glycoprotein. Consistently, erlotinib did not inhibit mitoxantrone efflux in K562/MDR cells although it did vincristine efflux in K562/MDR cells and mitoxantrone efflux in K562/BCRP cells. Intravesicular transport assay showed that erlotinib inhibited both P‐glycoprotein‐mediated vincristine transport and BCRP‐mediated estrone 3‐sulfate transport. Intriguingly, Lineweaver‐Burk plot suggested that the inhibitory mode of erlotinib was a mixed type for P‐glycoprotein‐mediated vincristine transport whereas it was a competitive type for BCRP‐mediated estrone 3‐sulfate transport. Collectively, these observations indicate that the pharmacological activity of erlotinib on P‐glycoprotein‐mediated drug resistance is dependent upon the transporter substrate. These findings will be useful in understanding the pharmacological interactions of erlotinib used in combinational chemotherapy. (Cancer Sci 2009; 100: 1701–1707) 相似文献
992.
Shutaro Nakaaki Yoshie Murata Junko Sato Yoshihiro Shinagawa Jin Hongo Hiroshi Tatsumi Masaru Mimura Toshi A Furukawa 《Cognitive and behavioral neurology》2007,20(2):121-125
OBJECTIVE: The aim of this study was to use the Iowa Gambling Task (IGT) to examine decision-making cognition in a patient with mild frontal variant of frontotemporal dementia (fv-FTD). BACKGROUND: Although fv-FTD may present with bizarre and dramatic behavioral changes, traditional executive tasks are sometimes preserved in patients with mild fv-FTD. Some evidence suggests that tasks assessing decision-making cognition, such as the IGT, may be sensitive to detect cognitive dysfunction in patients with mild fv-FTD. Here, we report a patient with fv-FTD who presented with bizarre behavior including hoarding, pathologic gambling, and abnormal sexual behavior. METHODS: A 54-year-old man who had been diagnosed as having fv-FTD was examined using a behavioral assessment, a wide range of neuropsychologic tasks, and the IGT. Brain magnetic resonance imaging and brain 99mTc-ethylcysteinate dimer single-photon emission computed tomography examinations were also performed. RESULTS: Although the patient's cognitive abilities were almost fully preserved for a number of traditional neuropsychologic tasks (memory, executive function), the IGT suggested that his decision-making cognition was impaired. The 99mTc-ethylcysteinate dimer single-photon emission computed tomography examination revealed hypometabolism in bilateral medial frontal and orbitofrontal regions of the cerebral cortex, and also in the cingulate gyri. CONCLUSIONS: Our findings suggest that the IGT may be a sensitive tool for assessing patients with mild fv-FTD before the development of severe dementia. We speculate that the deficit in decision-making cognition observed in the present case was associated with hypometabolism in the neural networks of the frontal lobe and involving both the bilateral medial frontal and orbitofrontal regions of the cerebral cortex. 相似文献
993.
Yoshihiko Kanno Kazuhiro Kobayashi Hiroshi Takane Hiroshi Arima Naofumi Ikeda Junko Shoda Hiromichi Suzuki 《Nephrology, dialysis, transplantation》2007,22(4):1224-1227
BACKGROUND: A double-lumen catheter (DLC) is used as a temporary blood access in emergency haemodialysis and continuous haemodialysis. There are various reports concerning thrombosis related to use of DLC and other catheters. The objective of this study is to assess the incidence of venous thrombosis when using DLC in patients undergoing blood purification. Method. Forty-eight Japanese patients, hospitalized in the Saitama Medical University hospital from December 2004 to April 2005, who had DLC insertion as a temporary blood access for blood purification. The existence of a thrombus was determined using ultrasonography, before catheter insertion, and every 2 days after insertion up to 3 weeks. At the time of DLC insertion, general blood tests including plasma D-dimer, and serum C-reactive protein (CRP) were performed. When DLC was removed, plasma D-dimer and serum CRP were measured. RESULTS: In 30 of 48 (62.5%) patients with DLC insertion as a temporary blood access for haemodialysis, venous thrombi with diameters>1.1 mm were detected by venous ultrasonography. No predictive factors were recognized except an increase in plasma D-dimer that was significantly higher in the patients with venous thrombus. The changes in plasma D-dimer were 3.54 (SE 0.8) microg/dl in patient with thrombus, and 0.29 (0.30) microg/dl in patient without thrombus (P=0.004). CONCLUSIONS: The study suggests that changes in plasma D-dimer after the insertion of the catheter may be used to predict thrombus formation and is more accurate than baseline measurements, and easier than other new markers. 相似文献
994.
Kenzaburo Tani Yukoh Nakazaki Hidenori Hase Keisuke Takahashi Miyuki Azuma Junko Ohata Reiko Kitamura Fumihiko Komine Maki Oiwa Atsuko Masunaga 《Cancer chemotherapy and pharmacology》2000,46(7):S73-S76
There is no effective treatment for patients with stage IV renal cell cancer (RCC), although the introduction of new therapy is imminent. Cancer gene therapy is currently considered to be one of the most promising therapeutic modalities in the field of cancer treatment. Based on the results of animal studies, vaccination using autologous granulocyte-macrophage colony-stimulating factor-transduced renal cancer cells appears promising. Before initiating a clinical study using an ex vivo gene-transduced autologous cell vaccine-based immunogene therapy for RCC in Japan, in 1992 we initially planned a Japanese version of a clinical protocol in collaboration with a US group. In 1993, the original protocol was refined. We performed five preclinical qualification studies using RCC nephrectomy specimens from patients in 1997, and the results showed that preparation of RCC cells for autologous vaccines at the Clinical Cell Technology Facility, Research Hospital of the Institute of Medical Science, University of Tokyo, was feasible. Subsequently in August 1998, the Ministry of Health and Welfare and the Ministry of Education, Science, Culture, and Sport approved our clinical protocol. We have recruited two patients with stage IV RCC to our study so far. Here we report the background to the initiation of cancer gene therapy in Japan. 相似文献
995.
996.
997.
Mari Yamaguchi Shin Morizane Toshihisa Hamada Tomoko Miyake Makoto Sugaya Hiroaki Iwata Kazuyasu Fujii Rie Haramoto‐Shiratsuki Yuki Nakagawa Mayumi Miura Koichi Ohshima Kazuhiro Morishita Takahide Takahashi Masahide Imada Ken Okada Jiro Uehara Junko Sowa‐Osako Keiji Iwatsuki 《The Journal of dermatology》2019,46(11):967-977
998.
Shintaro Nagashima Chikako Yamamoto Ko Ko Channarena Chuon Aya Sugiyama Masayuki Ohisa Tomoyuki Akita Keiko Katayama Masaharu Yoshihara Junko Tanaka 《Vaccine》2019,37(1):145-151
Background
Health care workers (HCWs) are at high risk of contracting blood-borne infections including hepatitis B virus (HBV) infection. In Japan, all HCWs are required to receive HB vaccination before beginning work. This study aimed to investigate the dynamics of the HB surface antibody (anti-HBs) titer after a three-dose HB vaccination in HCWs and to determine effective scheduling of HB vaccination for non-responders.Methods
Subjects included 832 medical and dental students who had received a three-dose HB vaccination (Bimmugen® 0.5?ml/vial). Anti-HBs was measured three times (before the third dose and 1 and 5?months after the third dose) using the CLIA method. The cut-off value of anti-HBs acquisition was 10 mIU/mL. After booster doses (three maximum) were administered to non-responders, the anti-HBs titers were measured again.Results
Out of 832 students, 491 were analyzed, of which 58.9% (289) were male. Anti-HBs-positive rates before the third dose and 1 and 5?months later were 47.9%, 95.9%, and 89.0%, respectively. The relationship between the antibody titer at one month (x) and 5?months (y) was estimated by log10y?=?log10x???0.134 (P?<?0.0001). Twelve non-responders were followed-up, all of which acquired a protective anti-HBs titer after revaccination with a three-dose booster.Conclusion
Anti-HBs titer decreases by an average of 20% within 4?months between the 1st and 5th month after the third dose. Therefore, anti-HBs titer should be measured periodically after completing the three-dose vaccination. Additionally, results suggested that booster doses are effective if administered with the same schedule as primary vaccination. 相似文献999.
1000.
Hidetoshi Hayashi Masakazu Ogura Takashi Niwa Toshihide Yokoyama Junko Tanizaki Tomohiro Ozaki Hiroshige Yoshioka Takayasu Kurata Yosuke Tamura Yasuhito Fujisaka Kaoru Tanaka Yoshikazu Hasegawa Keita Kudo Yasutaka Chiba Kazuhiko Nakagawa 《The oncologist》2021,26(1):19-e52
Lessons Learned
- The combination of cisplatin plus nab‐paclitaxel with concurrent thoracic radiotherapy in unresectable stage III non‐small cell lung cancer is a promising therapeutic strategy.
- Further investigation is warranted.