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1.
Sarina A. Piha-Paul Do-Youn Oh Makoto Ueno David Malka Hyun Cheol Chung Adnan Nagrial Robin K. Kelley Willeke Ros Antoine Italiano Kazuhiko Nakagawa Hope S. Rugo Filippo de Braud Andrea Iolanda Varga Aaron Hansen Hui Wang Suba Krishnan Kevin G. Norwood Toshihiko Doi 《International journal of cancer. Journal international du cancer》2020,147(8):2190-2198
We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity. 相似文献
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The results of parenteral treatment with Etaretin in 40 patients (79 eyes) suffering from senile maculopathy are reported. In 84% of the cases there was a degeneration of the dry type and in 16% a disciform exudative maculopathy. The cases of dry maculopathy responded well within a floow-up period of 8 to 18 months. 相似文献
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W J Thompson P S Anderson S F Britcher T A Lyle J E Thies C A Magill S L Varga J E Schwering P A Lyle M E Christy 《Journal of medicinal chemistry》1990,33(2):789-808
A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested. 相似文献
6.
Dominic Varga Walther Vogel Ariane Bender Harald Surowy Christiane Maier Rolf Kreienberg Helmut Deissler Georg Sauer MD 《Strahlentherapie und Onkologie》2007,183(12):655-660
PURPOSE: This paper briefly summarizes the research on increased radiosensitivity in breast cancer patients measured by the micronucleus test (MNT) and its association to genetic variants in DNA repair genes. More preliminary data are presented on the distribution of chromosomes and chromosome fragments in micronuclei (MN) in order to gain more information on clastogenic and aneugenic effects and better understand the phenotype of increased radiosensitivity. MATERIAL AND METHODS: Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. In four patients with high MN frequency (three cancer patients, one control) and four probands with low MN frequency, the presence of chromosome fragments or whole chromosomes in MN was determined by fluorescence in situ hybridization analysis for chromosomes 1, 7, and 17. RESULTS: An increased MN frequency in breast cancer patients compared to controls has consistently been reported with high significance. Higher MN frequencies were observed in 20-50% of breast cancer patients. Chromosomal fragments of chromosome 17, but not of chromosomes 1 and 7 were more frequent in the probands with high MN frequency than in those with low frequency (p = 0.045). CONCLUSION: The MNT detects a cellular phenotype common to a portion of sporadic breast cancer patients. This phenotype is very likely to be genetically determined. For the genetic dissection of breast cancer susceptibility this phenotype may turn out to be more efficient than breast cancer itself. Additional parameters which can be measured simultaneously with the MN frequency may be able to further enhance its usefulness. 相似文献
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The acute phase of subarachnoid haemorrhage (SAH) is frequently associated with an impaired water metabolism and a disposition to cerebral oedema. For study of the pathogenesis of brain oedema following SAH, an experimental model of SAH was created in the rat The diuretic curves after water loading, the brain water and electrolyte contents and the plasma and cerebrospinal fluid arginine vasopressin (AVP) levels were examined in rats with SAH. Following a water load, a significant water retention and increases in brain water and sodium contents were observed after subarachnoid bleeding. Plasma and cerebrospinal fluid AVP levels were also elevated following SAH. It can be concluded that AVP plays important roles in the development of antidiuresis after water loading and in the disturbance of the brain water and electrolyte balance following experimental SAH. 相似文献
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László Bajnok Bertalan Kozlovszky József Varga Judit Antalffy Sándor Olvasztó Tamás Fülöp Jr. 《European journal of nuclear medicine and molecular imaging》1994,21(12):1326-1332
Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients
with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the
legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over
the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences
between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every
case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures.
The sensitivity and specificity of99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error
was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied
by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This
phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In
conclusion,99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral
vascular disease. 相似文献
10.
Thirty primary gastrointestinal non-Hodgkin's lymphoma treated between 1983-1990 were reviewed to reveal the efficacy of various treatment strategies. The average age at the diagnosis 53.6 (18-76) years. The histologic material were evaluated according to the Kiel classification: 22 patients had high grade malignant lymphoma (centroblastoma 8, immunoblastoma 6, lymphoblastoma 2, non classifiable 5, T-cell lymphoma 1) 8 patients low grade malignant lymphoma (lymphocytic 2, immunocytic 2, MALT lymphoma 1, centrocytoma 1, non-classifiable 1, pleomorph small cell lymphoma 1). 21 were primary gastric lymphoma, 5 involved the small intestine, 2 the ileocecal region, and 2 the large intestine. According to the Ann Arbor staging system 7 patients were stage I/E, 16 patients stage II/E, 5 patients stage III/E and 2 patients stage IV/E. Every patients underwent surgical resection. After surgical treatment high grade malignancies were treated with ProMACE-COPP (9) and CHOP-Bleo (10) polychemotherapy; low grade malignancies received VEP (5) and CVP (3) chemotherapy. 23 of 30 patients achived complete remission. The patients with low grade malignancy are in remission. All but one patients with high grade malignant gastric lymphoma achieved complete remission with a median of 37 (3-81) months relapse-free survival. Out of 5 cases in the small intestine only in 1 case was remission achieved. Histological type (Kiel) and surgical resection were the most important prognostic factors. 相似文献