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排序方式: 共有5210条查询结果,搜索用时 62 毫秒
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Sanne C. F. A. Huijberts Robin M. J. M. van Geel Emilie M. J. van Brummelen Frans L. Opdam Serena Marchetti Neeltje Steeghs Saskia Pulleman Bas Thijssen Hilde Rosing Kim Monkhorst Alwin D. R. Huitema Jos H. Beijnen Ren Bernards Jan H. M. Schellens 《Cancer chemotherapy and pharmacology》2020,85(5):917-930
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated. 相似文献
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Ohne Zusammenfassung 相似文献
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Julli?tte E M van Eerd Huub J J M Rennen Wim J G Oyen Thomas D Harris D Scott Edwards Frans H M Corstens Otto C Boerman 《Journal of nuclear medicine》2004,45(10):1747-1753
Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate. 相似文献
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Pitfalls in diagnosis of aortic dissection by angiography: Algorithmic approach utilizing CT and MRI
Harold L. Mast David H. Gordon Alan M. Kantor 《Computerized medical imaging and graphics》1991,15(6):431-440
Dissection of the thoracic aorta is a life-threatening event requiring imaging studies to define the level of the tear and the intinmal flap. The “gold standard” has been angiography. This method may fail to demonstrate the dissection, however, due to overlap of the true and false lumens or a very thin flap that is imaged en face rather than tangentially. Computed tomography has a diagnostic accuracy of 95%, but can fail to image the dissection due to technical factors or a thrombosed false hunen. Magnetic resonance imaging requires a hemodynamically stable and cooperative patient. A diagnostic algorithm is proposed for diagnosis of aortic dissection based on renal function and the surgeon's imaging modality preference. 相似文献
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Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer 总被引:7,自引:3,他引:4
Bastiaan P. Geerdes M.D. Frans A. N. Zoetmulder M.D. Ph.D Erik Heineman M.D. Ph.D. Egbert J. Vos M.Sc. Mart -Jan Rongen M.D. Cor G. M. I. Baeten M.D. Ph.D. 《Diseases of the colon and rectum》1997,40(6):698-705
PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction
(APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity.
The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients
with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25–71) years and a rectal tumor at a mean
of 3 (range, 0–5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction
of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1–8.8)
years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean
follow-up of 24 (range, 1–60) months after APR, none of the patients developed local recurrence, whereas four patients developed
distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these
15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was
converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n=2) and incontinence (n=3). At
26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD,
46) mmHg at a mean of 35 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1–5). Of the
eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0–30) minutes. CONCLUSION:
In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional
outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So
far, the addition of a pouch has not resulted in improved outcome.
Supported by the Profileringsfonds of the Maastricht University Hospital, The Netherlands, and by the Stichting Fondsenwervingsactie
Volksgezondheid, Amsterdam, The Netherlands.
Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1995. 相似文献