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排序方式: 共有5195条查询结果,搜索用时 15 毫秒
1.
Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs
Nicolò Mauro Giulia Di Prima Paola Varvarà Mariano Licciardi Gennara Cavallaro Gaetano Giammona 《Journal of pharmaceutical sciences》2019,108(2):960-969
Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C8) to design an amphiphilic copolymer, henceforth CAC8, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC8 MPs (CAC8-MPs) were studied, showing that CAC8-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC8-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity. 相似文献
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Stephen J Woolford Stefania D'Angelo Giulia Mancano Elizabeth M Curtis Shanze Ashai Nitin Shivappa James R Hébert Sarah R Crozier Catherine M Phillips Matthew Suderman Caroline L Relton Cyrus Cooper Nicholas C Harvey the ALPHABET Consortium Investigators 《Journal of bone and mineral research》2022,37(8):1511-1519
Systemic inflammation is associated with reduced bone mineral density and may be influenced by pro-inflammatory diets. We undertook an observational analysis of associations between late pregnancy energy-adjusted dietary inflammatory index (E-DII) scores and offspring bone outcomes in childhood. E-DII scores (higher scores indicating pro-inflammatory diets) were derived from food frequency questionnaires in late pregnancy in two prospective mother-offspring cohorts: the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) offspring age at dual-energy X-ray absorptiometry (DXA) scanning was 9.2 (0.2) years. Linear regression was used to assess associations between E-DII and bone outcomes, adjusting for offspring sex and age at DXA and maternal age at childbirth, educational level, pre-pregnancy body mass index (BMI), parity, physical activity level, and smoking in pregnancy. Associations were synthesized using fixed-effect meta-analysis. Beta coefficients represent the association per unit E-DII increment. In fully adjusted models (total n = 5910) late pregnancy E-DII was negatively associated with offspring whole body minus head bone area (BA: β = −3.68 [95% confidence interval −6.09, −1.27] cm2/unit), bone mineral content (BMC: β = −4.16 [95% CI −6.70, −1.62] g/unit), and areal bone mineral density (aBMD: β = −0.0012 [95% CI −0.0020, −0.0004] g.cm−2/unit), but there was only a weak association with BMC adjusted for BA (β = −0.48 [95% CI −1.11, 0.15] g/unit) at 9 years. Adjustment for child height partly or, for weight, fully attenuated the associations. Higher late pregnancy E-DII scores (representing a more pro-inflammatory diet) are negatively associated with offspring bone measures, supporting the importance of maternal and childhood diet on longitudinal offspring bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
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Riccardo Zuccarino Valeria Prada Isabella Moroni Emanuela Pagliano Maria Foscan Giulia Robbiano Chiara Pisciotta Kayla Cornett Rosemary Shy Angelo Schenone Davide Pareyson Michael Shy Joshua Burns 《Journal of the peripheral nervous system : JPNS》2020,25(2):138-142
The Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS) is a Rasch‐built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. The CMTPedS (Italian) was translated and culturally adapted from source into Italian by two experts in CMT with good English language proficiency. The two translations were reviewed by a panel of experts in CMT. The agreed provisional version was back translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the same panel. CMT patients were assessed with the final version of the outcome measure and a subset had a second assessment after 2 weeks to evaluate test‐retest reliability. Seventeen patients with CMT aged 5 to 20 years (eight female) were evaluated with the CMTPedS (Italian), and test‐retest was performed in three patients. The CMTPedS (Italian) showed a high test‐retest reliability. No patient had difficulty in completing the scale. The instructions for the different items were clearly understood by clinicians and therefore the administration of the outcome measure was straight forward and easily understood by the children assessed. The CMTPedS (Italian) will be used for clinical follow‐up and in clinical research studies in the Italian population. The data is fully comparable to that obtained from the English language version. 相似文献
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Sara Caratelli Roberto Arriga Tommaso Sconocchia Alessio Ottaviani Giulia Lanzilli Donatella Pastore Carlo Cenciarelli Adriano Venditti Maria Ilaria Del Principe Davide Lauro Elisa Landoni Hongwei Du Barbara Savoldo Soldano Ferrone Gianpietro Dotti Giuseppe Sconocchia 《International journal of cancer. Journal international du cancer》2020,146(1):236-247
Cetuximab and panitumumab bind the human epidermal growth factor receptor (EGFR). Although the chimeric cetuximab (IgG1) triggers antibody-dependent-cellular-cytotoxicity (ADCC) of EGFR positive target cells, panitumumab (a human IgG2) does not. The inability of panitumumab to trigger ADCC reflects the poor binding affinity of human IgG2 Fc for the FcγRIII (CD16) on natural killer (NK) cells. However, both human IgG1 and IgG2 bind the FcγRII (CD32A) to a similar extent. Our study compares the ability of T cells, engineered with a novel low-affinity CD32A131R-chimeric receptor (CR), and those engineered with the low-affinity CD16158F-CR T cells, in eliminating EGFR positive epithelial cancer cells (ECCs) in combination with cetuximab or panitumumab. After T-cell transduction, the percentage of CD32A131R-CR T cells was 74 ± 10%, whereas the percentage of CD16158F-CR T cells was 46 ± 15%. Only CD32A131R-CR T cells bound panitumumab. CD32A131R-CR T cells combined with the mAb 8.26 (anti-CD32) and CD16158F-CR T cells combined with the mAb 3g8 (anti-CD16) eliminated colorectal carcinoma (CRC), HCT116FcγR+ cells, in a reverse ADCC assay in vitro. Crosslinking of CD32A131R-CR on T cells by cetuximab or panitumumab and CD16158F-CR T cells by cetuximab induced elimination of triple negative breast cancer (TNBC) MDA-MB-468 cells, and the secretion of interferon gamma and tumor necrosis factor alpha. Neither cetuximab nor panitumumab induced Fcγ-CR T antitumor activity against Kirsten rat sarcoma (KRAS)-mutated HCT116, nonsmall-cell-lung-cancer, A549 and TNBC, MDA-MB-231 cells. The ADCC of Fcγ-CR T cells was associated with the overexpression of EGFR on ECCs. In conclusion, CD32A131R-CR T cells are efficiently redirected by cetuximab or panitumumab against breast cancer cells overexpressing EGFR. 相似文献
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Erika Borlenghi Chiara Cattaneo Elisa Cerqui Silvana Archetti Diego Bertoli Daniela Bellotti Doriana Gramegna Giulia Soverini Margherita Oberti Francesca Schieppati Chiara Pagani Angela Passi Margherita Sciumé Mirko Farina Cecilia Carbone Claudia Crippa Daniela Dalceggio Alessandra Tucci Giuseppe Rossi 《Hematological oncology》2020,38(5):754-762
Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19–75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis. 相似文献
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Rosa Della Monica Mariella Cuomo Roberta Visconti Annabella di Mauro Michela Buonaiuto Davide Costabile Giulia De Riso Teodolinda Di Risi Elia Guadagno Roberto Tafuto Sabrina Lamia Alessandro Ottaiano Paolo Cappabianca Maria Laura Del Basso de Caro Fabiana Tatangelo Juergen Hench Stephan Frank Salvatore Tafuto Lorenzo Chiariotti 《Oncology research》2020,28(9):837-845
Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches.
Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response
rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation
status of the MGMT gene, as its product, O6
-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we
have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two
different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma
management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing
and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT
methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results,
we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation
status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs. 相似文献
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