Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factors can activate multiple signaling pathways in central nervous system microglia and can regulate their immune effects, but whether growth factors can affect the morphological characteristics and ultrastructure of microglia has not been reported. After microinjecting 300 nL of a growth factor cocktail, including 10 μg/mL epidermal growth factor, 10 μg/mL basic fibroblast growth factor, 10 μg/mL hepatocyte growth factor and 10 μg/mL insulin-like growth factor into adult rat cortex, we found that the number of IBA1-positive microglia around the injection area increased significantly, indicating local activation of microglia. All CD68-positive labeling co-localized with IBA1 in microglia. Cell bodies and protrusions of CD68-positive cells were strongly attached to or were engulfing neurons. Characteristic huge phagosomes were observed in activated phagocytes by electron microscopy. The phagosomes generally included non-degraded neuronal protrusions and mitochondria, yet they contained no myelin membrane or remnants, which might indicate selective phagocytosis by the phagocytes. The remnant myelin sheath after phagocytosis still had regenerative ability and formed "myelin-like" structures around phagocytes. These results show that microinjection of a growth factor cocktail into the cerebral cortex of rodents can locally activate microglia and induce selective phagocytosis of neural structures by phagocytes. The study was approved by the Institute of Laboratory Animal Science, Beijing Institute of Basic Medical Sciences(approval No. IACUC-AMMS-2014-501) on June 30, 2014. 相似文献
BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8+ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected. 相似文献
Purpose: Family psychosocial risk in pediatric oncology can be assessed using the Psychosocial Assessment Tool (PAT), a brief parent report screener based on the Pediatric Psychosocial Preventative Health Model (PPPHM; universal, targeted, and clinical). However, little is known about risk over the course of treatment and its association with medical and psychosocial healthcare utilization. Methods: Primary caregivers of children with cancer participated in this prospective multisite investigation, completing the PAT at diagnosis (T1; n = 396) and 6 months later (T2; n = 304). Healthcare utilization data were extracted from electronic health records. Results: The distribution of PPPHM risk levels at T1 and T2 was highly consistent for the samples. Two‐thirds of families remained at the same level of risk, 18% decreased and 16% increased risk level. Risk was not related to sociodemographic or treatment variables. The PAT risk score correlated with psychosocial contacts over the 6‐month period. Conclusions: Although the majority of families reported universal (low) risk on the PAT and were stable in their risk level over 6 months, reassessing risk is helpful in identifying those families who report higher level of risk during treatment than at diagnosis. PAT scores were related to psychosocial services that are provided to most but not all families and could be tailored more specifically to match risk and delivery of evidence‐based care. 相似文献
Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.
Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.
Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer. 相似文献
Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients. 相似文献
目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。 相似文献