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排序方式: 共有10000条查询结果,搜索用时 156 毫秒
51.
Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
52.
Bhavana Pothuri Allison L. Brodsky Joseph A. Sparano Stephanie V. Blank Mimi Kim Dawn L. Hershman Amy Tiersten Brian F. Kiesel Jan H. Beumer Leonard Liebes Franco Muggia 《Cancer chemotherapy and pharmacology》2020,85(4):741-751
Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy. 相似文献
53.
Javad Sharifi‐Rad Shahira M. Ezzat Mahitab H. El Bishbishy Dima Mnayer Farukh Sharopov Ceyda S. Kl Monica Neagu Carolina Constantin Mehdi Sharifi‐Rad Maria Atanassova Silvana Nicola Giuseppe Pignata Bahare Salehi Patrick V. T. Fokou Natlia Martins 《Phytotherapy research : PTR》2020,34(7):1474-1518
Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications. 相似文献
54.
Imre W.K. Kouw Bart B.L. Groen Joey S.J. Smeets Irene Fleur Kramer Janneau M.X. van Kranenburg Rachél Nilwik Jan A.P. Geurts René H.M. ten Broeke Martijn Poeze Luc J.C. van Loon Lex B. Verdijk 《Journal of the American Medical Directors Association》2019,20(1):35-42
Objectives
Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.Design and participants
Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study.Measurements
On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type–specific CSA.Results
An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (?3.4% ± 1.0%) and thigh muscle CSA (?4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 μm2 vs 4075 ± 279 μm2, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10).Conclusions
Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization. 相似文献55.
Ellen Strijbos Martijn R. Tannemaat Iris Alleman Robert H.P. de Meel Jaap A. Bakker Ruud van Beek Frank P. Kroon Guus F. Rimmelzwaan Jan J.G.M. Verschuuren 《Vaccine》2019,37(7):919-925
Objective
To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).Methods
An influenza vaccination or placebo was administered to 47 AChR MG patients. Before and 4?weeks after administration blood samples and clinical outcome scores were obtained. Antibodies to the vaccine strains A/California/7/2009 (H1N1)pdm09, A/Hong Kong/4801/14 (H3N2) and B/Brisbane/060/08 were measured using the hemagglutination-inhibition (HI) assay and disease-specific AChR antibody titers were measured with a radio-immunoprecipitation assay. Forty-seven healthy controls (HC) were vaccinated with the same influenza vaccine to compare antibody titers.Results
A post-vaccination, seroprotective titer (HI?≥?1:40) was achieved in 89.4% of MG patients vs. 93.6% in healthy controls for the H3N2 strain, 95.7% vs 97.9% for the H1N1 strain and 46.8 vs 51% for the B-strain. A seroprotective titer for all three strains of the seasonal influenza vaccine was reached in 40.4% (19/47) of the MG group and in 51% (24/47) of the HC group. Immunosuppressive medication did not significantly influence post geomean titers (GMT). The titers of disease-specific AChR antibodies were unchanged 4?weeks after vaccination. The clinical outcome scores showed no exacerbation of MG symptoms.Conclusion
The antibody response to an influenza vaccination in patients with AChR MG was not different from that in healthy subjects, even in AChR MG patients using immunosuppressive medication. Influenza vaccination does not induce an immunological or clinical exacerbation of AChR MG.Clinical trial registry
The influenza trial is listed on clinicaltrialsregister.eu under 2016-003138-26. 相似文献56.
57.
Doreen A. Ezeife MD Francois Dionne PhD Aline Fusco Fares MD Ellen Laura Rose Cusano MD Rouhi Fazelzad BSc MISt Wenzie Ng BSc MPharm RPh Don Husereau BSc Pharm MSc Farzad Ali BPharm MSc Christina Sit MSc Barry Stein B.Com BCL LLB Jennifer H. Law MSc Lisa Le MSc Peter Michael Ellis MD MMed PhD Scott Berry MD Stuart Peacock PhD Craig Mitton PhD Craig C. Earle MD Kelvin K. W. Chan MD PhD Natasha B. Leighl MD MMSc 《Cancer》2020,126(7):1530-1540
58.
59.
L.M. Abbassi M. Laurans A. Gasnier A. Smulevici H. Tournat J.-E. Bibault A. Huertas E. Jouglar A. Suissa S. Kreps P. Giraud C. Durdux 《Cancer radiothérapie》2019,23(4):316-321
PurposeTo evaluate prospectively asthenia and the quality of life in patients treated by stereotactic body irradiation and to determine their predictive factors.Methods and materialsQuality of life was assessed by the EORTC QLQ-C30 and asthenia was evaluated with the Brief Fatigue Inventory (BFI), on the first day (T1), last day (T2) and 1–3 weeks after the end of treatment (T3).ResultsSixty-three patients were treated with stereotactic body irradiation from February 2017 to May 2017 and 41 were included in the analysis (22 patients excluded for lack of understanding, organization, psychologic disorders or refusal). The mean number of fractions was 5 (± 2). The compliance to quality of life assessment was 98%, 95% was 81% at T1, T2 and T3, respectively. An increase of asthenia and a worsened quality of life were found in 12 (29%) and 14 (34%) patients between T1 and T2. Univariate analysis demonstrated a correlation between asthenia and quality of life were correlated with performans status (P = 0.03 and 0.05 respectively), hemoglobin level (p = 0.01 and 0.004), albumin level (P = 0.01 and 0.06), distance between home and radiotherapy department (P = 0.05 and 0.02). Multivariate analysis demonstrated a correlation between female gender (P = 0.012), albumin level (P < 0.001), distance over 25 km (P < 0.001) with asthenia, and albumin level (P = 0.003), hemoglobin level (P = 0.004) and previous chemotherapy (P = 0.003) with quality of life. No influence of stereotactic body ratiotherapy parameters was seen.ConclusionDespite hypofractionation, stereotactic body radiotherapy induced asthenia and deterioration of quality of life. 相似文献
60.