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1.
Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications. 相似文献
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目的 建立蒙药绿松石的质量标准。方法 收集不同产地绿松石,共10批。观察绿松石样品和粉末的性状并进行理化鉴别;按2020年版《中国药典》(四部)通则方法测定绿松石样品中水分、浸出物含量;采用原子吸收光谱法测定绿松石样品铜元素含量。结果 绿松石为不规则、周围带有黑石的块状物,表面蓝绿色,体重,质硬脆,难砸碎,断面呈贝壳状,蜡样光泽,粉末呈灰绿色,无臭,味淡;理化鉴别结果显示,呈铜盐反应;10批次样品中水分含量为0.41%-3.94%(SD=1.37%),浸出物含量为0.21%-0.81%(SD=0.21%),铜元素含量为3.03%-4.63%(SD=0.63%)。结论 初步拟定绿松石中水分含量不得超多5.0%、浸出物含量不得低于0.10%,铜元素含量应为2.60%-4.84%,制定的标准可用于蒙药材绿松石的质量控制。 相似文献
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Wuteng Cao Huabin Hu Jiao Li Qianyu Wu Lishuo Shi Biao Li Jie Zhou Xinhua Wang Junhong Chen Chao Wang Huaiming Wang Weihao Deng Yan Huang Yanhong Deng 《International journal of cancer. Journal international du cancer》2023,153(11):1894-1903
Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy. 相似文献
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目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例,随机均分为3组:对照组(C组)、体温保护组(T组)和体温保护联合右美托咪定组(T-D组),每组30例。C组常规体温保护,T组和T-D组综合体温保护;T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时(T0)、手术开始30 min(T1)、60 min(T2)、90 min(T3)、120 min(T4)以及手术结束时(T5)的鼻咽温度;于T0、术后2 h(T6)、24 h(T7)和48 h(T8)时抽取静脉血标本,测定T淋巴细胞亚群(CD3+、CD4+和CD8+)和自然杀伤细胞(NK cell)水平;记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T0比较,C组T2~T5时点鼻咽温度均明显降低(P < 0.05);与C组比较,T组和T-D组T2~T5时点鼻咽温度明显升高(P < 0.05)。与T0时点比较,C组、T组和T-D组T6、T7和T8时点CD3+和NK cell活性均明显降低(P < 0.05);C组在T6、T7和T8时点,T组和T-D组在T6和T7时点,CD4+活性均明显降低(P < 0.05)。与C组比较,T组和T-D组T6和T7时点CD3+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6和T7时点,CD4+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6、T7和T8时点,NK cell活性均明显升高(P < 0.05)。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定,减少围手术期意外低体温(IPH)的发生,并有效提高患者苏醒期质量,减轻免疫抑制程度,加速患者早期恢复。 相似文献
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Qian Zhang Larry D. Mesner Gina M. Calabrese Naomi Dirckx Zhu Li Angela Verardo Qian Yang Robert J. Tower Marie-Claude Faugere Charles R. Farber Thomas L. Clemens 《The Journal of clinical investigation》2021,131(7)
Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass. 相似文献
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