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Takafumi Koyama Toshio Shimizu Satoru Iwasa Yutaka Fujiwara Shunsuke Kondo Shigehisa Kitano Kan Yonemori Akihiko Shimomura Sakura Iizumi Tatsuya Sasaki Junji Furuse Noboru Yamamoto 《Cancer science》2020,111(2):571-579
Fibroblast growth factor receptors (FGFR) are a family of transmembrane receptor tyrosine kinases involved in regulating cellular processes. FGFR mutations are implicated in oncogenesis, representing therapeutic potential in the form of FGFR inhibitors. This phase I, first‐in‐human study in Japan evaluated safety and tolerability of E7090, a potent selective FGFR1‐3 inhibitor, in patients with advanced solid tumors. Dose escalation (daily oral dose of 1‐180 mg) was carried out to assess dose‐limiting toxicity (DLT), maximum tolerated dose, and pharmacokinetics. Pharmacodynamic markers (serum phosphate, fibroblast growth factor 23, and 1,25‐(OH)2‐vitamin D) were also evaluated. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled. No DLT were observed up to the 140‐mg dose; one patient in the 180‐mg cohort experienced a DLT (increased aspartate aminotransferase/alanine aminotransferase, grade 3). The maximum tolerated dose was not reached. Dose‐dependent increases in the maximum concentration and area under the curve from time 0 to the last measurable concentration were observed up to 180 mg. Dose‐dependent increases were observed in all pharmacodynamic markers and plateaued at 100‐140 mg, indicating sufficient FGFR pathway inhibition at doses ≥100 mg. In conclusion, E7090 showed a manageable safety profile with no DLT at doses ≤140 mg. Maximum tolerated dose was not determined. The recommended dose for the follow‐up expansion part, restricted to patients with tumors harboring FGFR alterations, was determined as 140 mg, once daily. 相似文献
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Rika Yoshimatsu Takuji Yamagami Miki Nishimori Kenta Ogi Yoriko Murata Hitomi Iwasa Kenji Kajiwara Tomoaki Yamanishi Hiroki Minamiguchi Takashi Karashima Keiji Inoue 《Journal of vascular and interventional radiology : JVIR》2019,30(3):460-465
Purpose
To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney.Materials and Methods
Between June 2016 and September 2017 at our institution, 12 inoperable patients underwent 15 cryoablation sessions for 17 small renal tumors. Of these, 9 patients who underwent 11 sessions of cryoablation were the focus of this study. For those patients, time-dependent changes in postoperative renal function were investigated by a retrospective review of clinical records. Evaluated were the estimated glomerular filtration rate (eGFR) and scintigraphy using 99m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before and 1 week, 1–2 months, and more than 6 months after cryoablation.Results
Mean baseline eGFR was 76.88 ± 29.82 mL/min/1.73 m2 (mean ± standard deviation; range, 23.4–112.5). Mean eGFR 1 week, 1–2 months, and more than 6 months after cryoablation were 74.56 ± 26.68 mL/min/1.73 m2 (21.0–101.1), 69.5 ± 25.28 mL/min/1.73 m2 (24.1–105.6), and 75.08 ± 26.25 mL/min/1.73 m2 (29.0–107.3), respectively. Changes were statistically insignificant (P = .6044, P = .6699, and P = .9038, respectively). Regarding split renal function, the mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 47.27% ± 6.14 (38.8%–57.0%). Mean contributions of the affected kidney 1 week after, 1–2 months after, and more than 6 months after cryoablation were 44.40% ± 5.37 (38.3%–53.6%), 44.57% ± 6.52 (34.35%–55.0%), and 45.41% ± 7.77 (34.4%–56.5%), respectively. Differences from baseline were significant for the earliest 2 periods (P = .0473 and P = .0334, respectively) but not the later period (P = .2532).Conclusions
Results suggested that total renal function does not worsen after cryoablation; however, function of the affected kidney worsened after cryoablation but later partially recovered. 相似文献5.
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Aim: We report two patients with Panayiotopoulos syndrome (PS) who developed encephalopathy related to status epilepticus during slow sleep (ESES) at the peak of their clinical course. Methods: Clinical charts and EEG data were reviewed. Results: The patients exhibited nocturnal autonomic seizures and occipital EEG foci, the latter of which later evolved into multifocal EEG foci with synchronous frontopolar and occipital spikes (Fp‐O EEG foci), and finally into continuous spikes‐waves during sleep (CSWS; spike‐wave index >85% based on whole‐night sleep recording) at eight years and seven years of age, respectively. The occipital spikes always preceded frontopolar spikes by 30~50 mseconds based on the analysis of CSWS. Neuropsychological ability, including IQ, deteriorated during the CSWS period in both patients. The autonomic seizures and focal to bilateral tonic‐clonic seizures were initially resistant to antiepileptic drugs (AEDs), and occurred more than 10 times in both patients. However, the seizures and EEG findings gradually resolved, and AEDs were successfully terminated in both patients. Conclusion: PS can progress to ESES if the clinical course exhibits atypical evolution. The initial autonomic symptom of the seizures and interictal Fp‐O EEG foci should be carefully monitored in patients with CSWS or ESES. 相似文献
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This report describes a unique case of a 56-year-old female who suffered from recurrent stroke after double mechanical valve replacement. During the four years after the surgery, she remained in normal sinus rhythm, received adequate anticoagulation therapy, and no apparent left atrial thrombus was detected. She underwent redo surgery to prevent further stroke after fourth instance of cerebral infarction. Intraoperative findings revealed a ‘dome-shaped’ pannus formation covering the sewing ring of the mitral prosthesis circumferentially, probably leading to clot formation and repeated infarctions. She has been stroke free for three years after pannus resection. 相似文献
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