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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.
Susanna Zanutto Chiara Maura Ciniselli Antonino Belfiore Mara Lecchi Enzo Masci Gabriele Delconte Massimo Primignani Giulia Tosetti Marco Dal Fante Linda Fazzini Aldo Airoldi Marcello Vangeli Francesca Turpini Giovanni Giuseppe Rubis Passoni Paolo Viaggi Monica Arena Roberta Ilaria Olimpia Motta Anna Maria Cantù Cristiano Crosta Giuseppe De Roberto Francesca Iannuzzi Andrea Cassinotti Valentina Dall'Olio Laura Tizzoni Gabriella Sozzi Emanuele Meroni Luigi Bisanti Marco Alessandro Pierotti Paolo Verderio Manuela Gariboldi 《International journal of cancer. Journal international du cancer》2020,146(4):1164-1173
Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most. 相似文献
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5.
MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment 下载免费PDF全文
Eliana Gianolio Francesca Arena Enza Di Gregorio Roberto Pagliarin Martina Delbianco Gabriella Baio Silvio Aime 《NMR in biomedicine》2015,28(9):1104-1110
The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn2+ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn2+ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn2+ ions, as the addition of Ca‐DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1‐weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
6.
Lucio Lucchin Amleto D’Amicis Maria Gabriella Gentile Nino Carlo Battistini Maria Antonia Fusco Augusta Palmo Maurizio Muscaritoli Franco Contaldo Emanuele Cereda 《Mediterranean journal of nutrition and metabolism》2009,2(3):171-179
Aim and methods Nutrition, unhealthy lifestyles and cancer appear to be strictly related, but few authors have analysed the interest in dietary
information of cancer patients and their families. This survey was conducted in the Veneto area (Italy) to investigate the
concern of cancer patients and their family members about diet as a health tool before and after diagnosis of cancer.
Results Seven hundred and four questionnaires were collected: 380 from cancer patients and 324 from family members of cancer subjects.
Breast cancer (BC) was the most frequent disease for patients (61.8%) as well as families (26.5%). Generally, the importance
of having precise diet information after diagnosis is recognised by 40.3% of patients, with significant differences between
the various types of cancer: gastric and colon/rectum cancer (GCC) patients were more concerned than BC women about precise
information concerning a diet to follow immediately after diagnosis (p = 0.000, ODs = 3.10, CI 1.68–5.71) or during treatments (p = 0.001, ODs = 2.67, CI 1.46–4.89). The nutritional information is supplied to patients in 34% of cases and to relatives
in 30.3%, often from non-medical sources. In total healthcare workers (family doctor, oncologist, surgeon, dietician) represented
the exclusive source of dietary information for 24.9% of patients and 22.9% of family members. Diet after diagnosis changes
in 69.1% of GCC patients and in 39.2% of BC women. Relatives, particularly women, report difficulties preparing patients’
meals in 30.7% of cases, changes in the eating habits of the entire family in 29.9% and discontent connected with patients
diet in 13.9%. The concern about proper nutrition after diagnosis increases more in GCC subjects (p < 0.025) when compared to BC subjects and in patients with more recent diagnosis (p < 0.041) when compared with patients with diagnosis >5 years ago, while in family members the interest in diet after diagnosis
increases more in women than in men (p < 0.030) without other differences regarding the degree of relationship, type of cancer or diagnosis time. Relatives (92.7%)
have more interest in nutritional education than patients (74.9%). Cancer patients <65 years were more interested in educational
initiatives concerning nutrition (p = 0.000, ODs = 4.46, CI 2.6–7.4) than older patients (>65 years) and female subjects were more concerned than male patients
(p = 0.008, ODs = 2.11, CI 1.2–3.6).
Conclusions The interest in the dietary knowledge and in educational initiatives concerning nutrition is high in cancer patients and their
relatives, although it decreases with the age. The poor attention paid to nutrition of cancer patients by various healthcare
workers deserves consideration, since the psychophysical wellbeing and perhaps also survival of cancer patients can be improved
by correct dietary management, as well as, naturally, by the principal treatments themselves. 相似文献
7.
Francesca Borrelli Nicola Borbone Raffaele Capasso Domenico Montesano Simona De Marino Gabriella Aviello Giovanni Aprea Stefania Masone Angelo A. Izzo 《Journal of ethnopharmacology》2009
Ethnopharmacological importance
Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms.Aim of the study
To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001–10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract.Materials and methods
The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum.Results
CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC50: 0.24 ± 0.02 μg/mL; Emax: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC50: 0.26 ± 0.02 μg/mL; Emax: 99.1 ± 0.46%).Conclusion
It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca2+-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms. 相似文献8.
9.
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
10.
Leandro Provinciali Mario Signorino Bruno Censori Gabriella Ceravolo Maria Del Pesce 《Epilepsia》1991,32(5):684-689
The occurrence of transitory cognitive impairment during diffuse subclinical electroencephalographic (EEG) discharges has been widely documented but the role of the parameters influencing the cognitive performance and the involvement of motor or verbal response in the tasks used is still under debate. Fifteen patients suffering from primary generalized epilepsy with frequent bisynchronous EEG epileptic bursts underwent a shape recognition task during EEG monitoring. The test sequence was as follows: memorandum, pause, and multiple choice set. After pressing the response button, the patient was asked to confirm the choice verbally. The following parameters were considered: geometrical complexity of the shape, chronological position of the burst occurring during the single test, and the duration of discharge ranging from 1 to 3 s. Results showed a significant increase in incorrect responses during the test when discharges occurred, with more errors occurring for difficult than for easy shapes. Neither the discharge position nor the duration of the epileptic burst influenced the performance. Diffuse epileptic activity of short duration produced selective effects on the cognitive process regardless of the motor component of the response. 相似文献