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41.
Rafiye Ciftciler Haluk Demiroglu Yahya Buyukasık Elifcan Aladag Salih Aksu Ibrahim C. Haznedaroglu Nilgun Sayınalp Osman Ozcebe Umit Yavuz Malkan Hakan Goker 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):177-182
Background
Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.Patients and Methods
We retrospectively analyzed the clinical outcome of 91 patients who were diagnosed with treatment-refractory AML at Hacettepe University Hospital between January 2002 and June 2018. Patients' disease status included refractory AML, defined as failure to respond to standard induction chemotherapy and relapse within 6 months after first complete remission.Results
The median follow-up was 12 months (range, 0.5-184 months) for the entire group. Kaplan-Meier estimates of the 3-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 67% and 12%, respectively. Additionally, the Kaplan-Meier estimates of 5-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 44% and 4%, respectively (P < .001). Complete remission was obtained in 25 patients (83.3%) who underwent allo-HSCT; however, the disease of only 3 patients (3.8%) exhibited complete response after salvage chemotherapy.Conclusion
Allo-HSCT is still the best-known treatment option with curative potential in patients with treatment-refractory AML. Therefore, all efforts should be made in an attempt to find a suitable matched donor in order to perform allo-HSCT. 相似文献42.
《Vaccine》2020,38(50):7916-7927
Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially VH4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of VH4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs. 相似文献
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Rosario Gulias-Cañizo Anell Lagunes-Guillén Arturo González-Robles Erika Sánchez-Guzmán Federico Castro-Muñozledo 《Burns : journal of the International Society for Burn Injuries》2019,45(2):398-412
Background
Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.Materials and methods
Initially, EGCG was assayed on the rabbit corneal epithelial cell line RCE1(5T5) to establish the best testing conditions, and to avoid unwanted outcomes in the experimental animals. Then, we studied its effects on cell proliferation, cell cycle progression and cell differentiation. Afterwards, we instilled EGCG in experimental grade II corneal alkali burns in mice, three times a day up to 21 days, and evaluated by slit lamp examination and histological sections of corneal epithelial, corneal endothelial and stromal edema, as well as the presence of inflammatory cells and neovascularization.Results
EGCG reduced cell growth and led to a decline in the proportion of proliferative cells in a concentration dependent manner. At 10 μM, EGCG promoted cell differentiation, an effect not related with apoptosis or cytotoxicity. When 10 μM EGCG was instilled in corneal alkali burns in mice three times a day up to 21 days, EGCG significantly reduced corneal opacity and neovascularization. The improved clinical appearance of the cornea was associated to a controlled epithelial growth; epithelial morphology was similar to that observed in normal epithelium and contrasted with the hyperproliferative, desquamating epithelium observed in control burn wounds. EGCG reduced corneal, stromal and endothelial edema, and wound inflammation.Conclusion
This work constitutes the first evidence for the use of EGCG in the acute phase of a corneal alkali burn, representing a possible novel alternative to improve patient outcomes as an add-on therapy. 相似文献47.
《Mayo Clinic proceedings. Mayo Clinic》2019,94(7):1321-1329
Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase. 相似文献
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Using JEG-3 and BeWo cells, we examined the effect of “real life” mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal and hormone-stimulated matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) protein expression was evaluated. Under basal conditions, the PAH mixtures increased hCG and decreased hPLGF levels in both cell lines, while hPL expression was stimulated in JEG-3 and inhibited in BeWo. There was no effect on the MMP-2/MMP-9 ratio or VEGF expression. In hormone-stimulated cells, PAH mixtures changed the MMP-2/MMP-9 ratio in JEG-3 cells in favor of MMP-9, while in BeWo MMP-2 was favored. The effect on VEGF expression was cell specific and dependent on the mixture. In hCG-treated cells, only Mix II inhibited VEGF expression in JEG-3 cells. Neither PAH mixtures affected this protein in BeWo cells. In hPL-treated cells, Mix I had a stimulatory effect in JEG-3 cells, while Mix II exerted an inhibitory effect in BeWo cells. In hPLGF-treated cells, Mix II decreased in JEG-3 cells, but in BeWo cells, both mixtures increased VEGF expression. Considering that the evaluated protein hormones play crucial roles in angiogenesis and neovascularization in the placenta, “real life” PAH mixtures by disrupting protein hormones levels, the MMP-2/MMP-9 ratio and VEGF expression can lead to insufficiency and many pregnancy-related disorders. 相似文献
50.
Qianlai Luo Jonathan N. Hofmann Ruth M. Pfeiffer Cari M. Kitahara Minkyo Song Meredith S. Shiels 《International journal of cancer. Journal international du cancer》2023,153(1):64-72
In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend. 相似文献