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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
2.
Christian Holm Hansen Shelley Lees Saidi Kapiga Janet Seeley Tony Barnett 《Global public health》2020,15(3):402-413
ABSTRACTMeasuring hope reliably and accurately remains an important research objective, not least in less prosperous settings where ‘holding on to hope’ may be critically important in the struggle against adverse life conditions. The State Hope Scale was designed for use in the US. Despite reported application in diverse cultures and using translations the scale has not been extensively validated outside US populations. This study contributes to a larger project exploring the measurement of hope and provides a critique of Snyder’s scale as used in a Tanzanian female population of 1021 urban microfinance participants. We evaluate the scale’s validity through assessment of the empirical distribution of scores, item response profiles, internal consistency and discriminatory ability. Participants mostly scored very high and many reached very near the maximum attainable score. Hardly any endorsed the negative half of the response scale. Several problems are discussed including poor discrimination and strong evidence of acquiescence response bias. We also found little association of the scale scores with hypothesised correlates of hope. Future improvements on the measurement of hope are recommended, especially in studies outside the narrow Western context in which the scale was devised. 相似文献
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Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser473, increased inhibitory phosphorylation of proapoptotic BAD on Ser136, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death. 相似文献
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Katrina Hueniken MPH Catriona M. Douglas BSc MBChB MD Ashok R. Jethwa MD Maryam Mirshams MSc Lawson Eng MD Andrew Hope MD Douglas B. Chepeha MD David P. Goldstein MD MSc Jolie Ringash MD MSc Aaron Hansen BSc MBBS Rosemary Martino PhD Madeline Li MD PhD Geoffrey Liu MD Wei Xu MD John R. de Almeida MD MSc 《Cancer》2020,126(17):4042-4050
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Clinical versus ultrasonographic evaluation of scrotal disorders 总被引:1,自引:0,他引:1
B Kromann-Andersen L B Hansen P N Larsen K Lawetz P Lynge D Lysen S P Nielsen K H Stockholm P Foged 《British journal of urology》1988,61(4):350-353
Clinical and ultrasonographic examinations of scrotal disorders were compared in 166 patients in order to determine their ability to distinguish between those diseases requiring surgery and those requiring clinical follow-up only. Ultrasound examinations were efficient in discriminating between normal and pathological findings. Extra-testicular lesions were readily differentiated from testicular ones. Although both clinical and ultrasonographic examinations had high sensitivity (90%) in detecting testicular cancer, the number of false positive findings was smaller after ultrasound examination. This gave a predictive value of a positive test of 53% after ultrasound examination but only 33% after clinical examination. Ultrasound examination may, therefore, reduce the number of surgical explorations in the scrotum and should be performed in patients with suspected testicular pathology based on history and palpatory findings. 相似文献
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P.J. Hansen P. Soto . 《American journal of reproductive immunology (New York, N.Y. : 1989)》2002,48(3):150-150
Increased peripheral NK cells in aborting women are considered as a predictor of immunological miscarriages. Here, we investigated the diagnostic value of the NK count at the time of abortion. Peripheral NK cells were counted by flow cytometry in 44 women undergoing therapeutic termination of first trimester missed pregnancy (A = 24) or elective abortion (B = 20). Histology of the extracted material was performed and immunological lesions (villitis, intervillositis, vascular thrombosis, increased fibrinoid necrosis) were recorded. Twenty first trimester pregnant women (C1) and 20 nonpregnant women (C2) served as controls. In 20 women of groups A and B (A1 = 10, B2 = 10) count was repeated after 5 days. At abortion time, the NK percentage and number did not differ between groups A and B (18.18%, 360 versus 15.61%, 374), but there was a statistically significant difference between A and C1 (18.18% versus 13.6%, P < 0.03). When histology negative (11) and positive (8) cases were excluded from groups A and B, respectively, NKs were slightly higher in group A (18.18–19.76%) and significantly lower in B (15.61–13.07%, P < 0.05). At the time of second count, aborters' NKs decreased (A1 = 16.64 versus 13.6 and 10.6 in groups C1 and C2 –P = 0.01, respectively). In group B, NK percentage was equal to that of nonpregnant women (10.94 versus 10.6). At the time of abortions, NKs increase only in cases of immune‐mediated miscarriages. Their – in time – count may contribute to the diagnosis of immmunological abortions. 相似文献