87例骨髓增殖性肿瘤患者JAK2及MPL基因突变位点研究

目的:探讨JAK2V617F及MPLW515L/K点突变在骨髓增殖性肿瘤(MPN)患者中的发生情况及临床意义。方法:回顾性统计分析87例MPN患者的临床及实验室检查资料,应用等位基因特异性-聚合酶链反应(AS-PCR)及序列测定方法,检测MPN患者骨髓/外周血单个核细胞JAK2V617F及MPLW515L/K点突变的发生情况,结合JAK2V617F及MPLW515L/K点突变阳性与阴性2组患者的临床及实验室检查指标,探讨其在疾病诊断及分子发病机制中的意义。结果:87例MPN患者[真性红细胞增多症(PV)36例,原发性血小板增多症(ET)33例,原发性骨髓纤维化(PMF)18例]中共检出55例患者存在JAK2V617F突变,总突变率为63.2%(55/87),其中PV28例,突变率77.8%(28/36);ET17例,突变率51.5%(17/33);PMF10例,突变率55.6%(10/18)。JAK2V617F阳性PV和ET患者WBC及Hb水平高于阴性患者(P<0.05);JAK2V617F阳性PMF患者WBC及PLT高于阴性患者(P<0.05)。JAK2V617F阳性MPN患者血栓发生率高于阴性患者(P<0...     

类胰蛋白酶与代谢综合征

代谢综合征是心血管疾病的多种代谢危险因素在个体内集结的状态,主要包括肥胖、糖尿病或糖调节受损、血脂紊乱以及高血压.近来研究发现,代谢综合征的发病与机体慢性炎性反应状态相关.类胰蛋白酶是肥大细胞中含量最丰富的颗粒蛋白,也是一种重要的炎性介质,它可通过促进炎性反应细胞的聚集、细胞凋亡、新生血管形成、基质蛋白重塑等多种机制参与代谢综合征的发生与发展.     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

Quantitative light microscopic autoradiographic localization of binding sites labelled with [3H]vasopressin antagonist d(CH2)5Tyr(Me)VP in the rat brain, pituitary and kidney

Binding sites for the vasopressin (VP) antagonist d(CH2)5Tyr(Me)VP, were located in various brain areas (e.g. the lateral septum, amygdala, choroid plexus and nucleus of the solitary tract) using light microscopic autoradiography. A number of areas (e.g. suprachiasmatic and arcuate nucleus, pineal gland) which previously showed no VP binding were labelled in the present study. The olfactory nucleus and ventromedial hypothalamic nucleus were not labelled. It therefore appears that d(CH2)5Tyr(Me)VP is capable of discriminating between VP and oxytocin binding sites and a more sensitive means of detecting VP binding sites than VP alone.     

分泌粒细胞-巨噬细胞集落刺激因子的重组痘苗病毒转染的瘤苗裂解物抗肿瘤作用

将小鼠粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）基因经过同源重组得到表达ＧＭ－ＣＳＦ的重组痘苗病毒，用此痘苗病毒转染小鼠黑色素瘤细胞，制备黑色素瘤瘤苗裂解物（ＧＭ－ＣＳＦＶＭＯ），Ｃ５７ＢＬ／６小鼠皮下接种Ｂ１６－Ｆ１０细胞３天后在注射部位注射瘤苗裂解物，一周后再注射一次。结果发现ＧＭ－ＣＳＦＶＭＯ能够显著地抑制荷瘤小鼠肿瘤结节的生长并明显延长荷瘤小鼠的存活期。用此瘤苗裂解物免疫小鼠两次，间隔一周，免疫一周后给Ｃ５７ＢＬ／６小鼠皮下接种Ｂ１６－Ｆ１０细胞，结果肿瘤结节出现时间明显延长，部分小鼠肿瘤不再生长。经ＧＭ－ＣＳＦＶＭＯ治疗或免疫后小鼠的外周血和脾淋巴细胞对肿瘤细胞杀伤活性明显升高，ＮＫ活性变化不明显。本结果提示，诱导机体特异性细胞免疫可能是瘤苗裂解物的抗肿瘤作用机理之一。     

胎儿脐静脉壁组织结构增龄性变化的定量分析

目的 :探讨胎儿脐带静脉随胎龄变化的形态学改变 ,为临床挑选适当的血管代用品提供科学的理论依据。方法 :3 3例新鲜脐带 ,常规石蜡包埋、切片、HE染组织结构 ,Weigert,AnilineBlue及桔黄G分染弹性纤维 ,胶原纤维和平滑肌 ,光镜观察及计算机图像分析。结果 :随胎龄随长 ,脐静脉管径、中膜厚度、中膜弹性纤维含量逐渐增多 ;平滑肌含量及细胞核的数密度和面密度在 3 7～ 40周最大 (P <0 .0 5 ) ,胶原纤维则最小 ,因而此时段顺应性最好。结论 :脐静脉管壁中各成分的含量随胎龄变化呈不等比增长 ,3 7～ 40周时血管顺应性最好。建议选用此时段胎龄的脐静脉作为移植材料。     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Arginine-grafted bioreducible poly(disulfide amine) for gene delivery systems

Arginine-grafted bioreducible poly(disulfide amine) (ABP) polymer was synthesized for non-viral gene delivery systems. Its Mw was measured to be 4.45 × 10³ Da/mole by FPLC-SEC and its PDI value was 1.49. ABP was able to retard pDNA from a weight ratio of 2 but ABP could not retard pDNA even at a weight ratio of 10 in the presence of DTT, showing that it can be biodegraded in reducing environment such as cytoplasm. ABP was examined to form positively charged nano-sized particles (<200 nm) with pDNA. ABP showed no significant cytotoxicity and greatly enhanced transfection efficiency in comparison with unmodified poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH)) and PEI25k in mammalian cells. The transfection efficiency of ABP was not much reduced even in the serum condition. Chloroquine treatment was not found to improve the transfection efficiency of ABP. The cellular uptake pattern of ABP polyplexes was almost similar with poly(CBA-DAH), suggesting that greatly enhanced transfection efficiency of ABP is not induced by its high cellular penetrating ability but may be mediated by other factors such as good nuclear localization ability.