乳腺癌患者血清TK1、CA153、CEA的变化及临床意义

目的探讨胸苷激酶1(TK1)、糖类抗原(CA)153、癌胚抗原(CEA)在乳腺癌患者血清中的变化情况及临床意义。方法选择92例住院治疗的乳腺癌患者,66例乳腺良性疾病患者和50例健康体检者,分别检测各组血清TK1、CA153、CEA水平,用单因素分析法分析血清TK1、CA153、CEA水平与乳腺癌病理参数的关系。结果乳腺癌组血清TK1、CA153、CEA水平显著高于乳腺良性疾病组和对照组,差异均有统计学意义(P0.05)。血清TK1、CA153、CEA水平与乳腺癌病理分期、淋巴结转移等因素相关(P0.05)。结论 TK1、CA153、CEA水平升高对乳腺癌的诊断、浸润、转移及严重程度具有重要临床意义。     

血清胸苷激酶1水平在乳腺癌术后疗效评估中的作用

目的探讨血清胸苷激酶1(TK1)水平对乳腺癌的临床应用价值。方法采用CIS-1型印迹免疫-增强发光检测系统检测100例乳腺癌患者、30例乳腺良性疾病、30例正常对照者血清TK1水平。比较乳腺癌患者不同病理参数下血清TK1水平的差异。分析血清TK1水平与雌激素受体(ER)、孕激素受体(PR)的关系。结果乳腺癌患者血清TK1水平均明显高于乳腺良性疾病组和对照组(P<0.05),且血清TK1水平与乳腺癌分期密切相关。在有淋巴结转移或术后2年复发的乳腺癌患者中,TK1水平明显升高(P<0.05)。ER、PR双阳性的乳腺癌患者术后血清TK1水平高于术前(P<0.05),ER、PR双阴性的乳腺癌患者术前和术后1年的TK1水平无差异(P>0.05),ER、PR双阳性的乳腺癌患者术前血清TK1水平低于ER、PR双阴性患者(P<0.05)。结论血清TK1可为乳腺癌预后判断及病情监测提供重要价值。     

血清胸苷激酶1水平在乳腺癌术后疗效评估中的作用

目的探讨血清胸苷激酶1（TK1）水平对乳腺癌的临床应用价值。方法采用CIS-1型印迹免疫-增强发光检测系统检测100例乳腺癌患者、30例乳腺良性疾病、30例正常对照者血清TK1水平。比较乳腺癌患者不同病理参数下血清TK1水平的差异。分析血清TK1水平与雌激素受体（ER）、孕激素受体（PR）的关系。结果乳腺癌患者血清TK1水平均明显高于乳腺良性疾病组和对照组（P〈0.05）,且血清TK1水平与乳腺癌分期密切相关。在有淋巴结转移或术后2年复发的乳腺癌患者中,TK1水平明显升高（P〈0.05）。ER、PR双阳性的乳腺癌患者术后血清TK1水平高于术前（P〈0.05）,ER、PR双阴性的乳腺癌患者术前和术后1年的TK1水平无差异（P〉0.05）,ER、PR双阳性的乳腺癌患者术前血清TK1水平低于ER、PR双阴性患者（P〈0.05）。结论血清TK1可为乳腺癌预后判断及病情监测提供重要价值。     

血清同型半胱氨酸水平与乳腺肿瘤的关系分析

目的探讨乳腺癌及其术后和乳腺良性肿瘤患者与血清同型半胱氨酸(Hcy)关系。方法采用循环酶法检测90例乳腺癌、乳腺癌术后及乳腺良性肿瘤患者血清Hcy水平,并与50例健康体检者(健康对照组)检测结果比较。结果乳腺癌组与乳腺良性肿瘤组、健康对照组之间血清Hcy水平的差异无统计学意义(P>0.05)。乳腺癌术后组与健康对照组之间血清Hcy水平差异有统计学意义(P<0.05)。结论血清Hcy与乳腺肿瘤的发生、发展无相关性。     

乳腺良恶性肿瘤组织中CD44的表达及其与淋巴管生成的关系

目的 研究细胞黏附分子44(CD44)在乳腺良恶性肿瘤组织中的表达及其与淋巴管生成的关系,探讨其在鉴别诊断中的应用价值。方法 收集2005～2015年广州医科大学附属肿瘤医院乳腺肿瘤患者组织样品75例(均为女性)并分为良性肿瘤组、乳腺浸润性导管癌淋巴结转移组和未转移组,每组各25例。免疫组织化学法(IHC)检测CD44在各组患者肿瘤组织样品中的表达并以CD44作为淋巴管内皮细胞标记物比较各组样品中的淋巴管生成情况。生物信息分析验证研究结果。结果 在良性肿瘤组、乳腺浸润性导管癌淋巴结转移组和未转移组中,CD44的IHC评分结果分别为0.60±0.82,3.16±2.70和3.52±2.47,乳腺浸润性导管癌淋巴结转移组和未转移组的CD44表达水平均高于乳腺良性肿瘤组,差异具有统计学意义(F=13.52,P<0.000 1)。以CD44作为淋巴管内皮细胞特异性标记物可有效辅助三组样品的淋巴管生成计数。在乳腺良性肿瘤组、乳腺浸润性导管癌伴淋巴结转移组和未伴淋巴结转移组中,淋巴管生成数分别为4.08±2.43,13.80±13.54和12.72±13.69,乳腺浸润性导管癌淋巴结转移组和未转移组的淋巴管生成数均高于乳腺良性肿瘤组,差异具有统计学意义(F=4.94,P=0.009 7)。生物信息分析结果也显示CD44在乳腺癌中的表达较正常乳腺增加。结论 乳腺癌的发生与CD44表达以及淋巴管的生成有关。CD44有望成为乳腺良性肿瘤与乳腺癌的辅助鉴别诊断指标,同时其也可作为乳腺淋巴管内皮细胞的特异性标记物。     

能量多普勒超声检测乳腺癌血管生成活性及其与腋窝淋巴结转移的关系

目的　研究乳腺癌血管生成活性与腋窝淋巴结转移的关系。方法　采用能量多普勒 (PDI)检测80例乳腺癌内血流信号并通过图像分析技术定量测定肿瘤内血管阳性反应总面积 ,同时采用免疫组化技术以FVIII RA检测肿瘤内微血管密度 (MVD) ,分析两者与腋窝淋巴结转移的关系。结果　有腋窝淋巴结转移即LN( )组血流信号较无腋窝淋巴结转移即LN(-)组明显丰富 ,至少可见 1支以上穿入型血管束 ,LN( )组血管阳性反应总面积 (40 0 9± 2 6 8)明显高于LN(-)组 (2 116± 2 0 0 ) ,差异有显著性意义 (P <0 .0 1) ,LN ( )组MVD(5 7.14± 30 .98)较LN (-)组MVD(2 3 .96± 12 .96 )亦显著增高 (P <0 .0 1)。结论　乳腺癌血管生成活性与其腋窝淋巴结转移密切相关 ,血管生成活跃者 ,腋窝淋巴结转移可能性大。PDI对乳腺癌肿瘤组织内血流的定量检测可能为临床判断乳腺癌预后提供一较为简便的指标。     

TK1检测对常见恶性肿瘤诊断的临床应用

目的 探讨胸苷激酶1(TK1)对常见恶性肿瘤诊断的临床应用。方法 采用酶免疫点印迹化学发光法检测444例肿瘤患者和161例健康体检者(对照组)血清中TK1水平。结果 与对照组比较,肺癌、消化道肿瘤、乳腺癌患者血清TK1水平均显明显升高(P<0.05)。肺癌、食管癌、结肠癌、直肠癌、乳腺癌、宫颈癌、卵巢癌患者TK1检测阳性率,分别为52.0%、59.6%、62.9%、60.0%、62.1%、32.3%、21.4%、11.0%。与对照组(TK1检测阳性率为0.0%)比较,肺癌、消化道肿瘤、乳腺癌TK1检测阳性率明显升高(P<0.01)。结论 血清TK1检测在常见恶性肿瘤的辅助诊断上是一个有价值的指标。     

血清胸苷激酶1在乳腺癌诊治中的应用

目的:探讨血清胸苷激酶1(TK1)检测在乳腺癌辅助诊断及术后化疗效果评估中的作用。方法:应用免疫印迹-增强化学发光法(ECL)检测20例健康志愿者(健康对照组)和30例乳腺癌患者(乳腺癌组)术前、术后及化疗后血清TK1水平。比较不同疾病分期下TK1水平的差异。分析术前血清TK1水平与雌激素受体(ER)、孕激素受体(PR)的关系。结果:乳腺癌患者血清TK1水平均明显高于健康对照组(P<0.05);乳腺癌患者化疗后TK1水平明显低于术前(P<0.05),但术前术后TK1水平无明显差异(P>0.05),且TK1水平与乳腺癌分期也无明显相关性(P>0.05);同时ER、PR双阳性乳腺癌患者术前血清TK1水平低于ER、PR双阴性患者(P<0.05)。结论:血清TK1水平可反映肿瘤细胞增殖,有望成为乳腺癌预后判断及病情监测的重要指标,但其确切机制及与肿瘤进展间的关系还需深入研究。     

CA15-3、CEA在乳腺癌中应用价值探讨

目的　探讨CA15 3、CEA在乳腺癌中应用价值。方法　应用电化学发光技术对 6 2例乳腺癌患者、2 2例乳腺良性疾病及2 0例正常对照血清CA15 3、CEA水平进行了检测。结果　CA15 3、CEA水平在乳腺癌Ⅰ、Ⅱ、Ⅲ期与乳腺良性疾病组及正常对照组无显著性差异 (P >0 .0 5 ) ,但有逐渐升高趋势 ,在Ⅳ期乳腺癌中表达明显增高 (P <0 .0 5 ;P <0 .0 1) ,在远处转移患者表达明显高于单纯淋巴结转移患者 ,有淋巴结转移患者表达明显高于无淋巴结转移患者 (均P <0 .0 1) ,在不同组织来源乳腺癌患者中表达无明显差异 (P >0 .0 5 )。结论　CA15 3、CEA并非乳腺癌早期诊断的理想标志物 ,但其表达与肿瘤临床分期、淋巴结转移及远处转移密切相关 ,在预测乳腺癌转移、复发及监测疗效、判断预后等方面具有重要临床应用价值 ,其在乳腺癌中表达无组织细胞特异性。     

血清组织多肽特异性抗原表达水平在乳腺癌中的临床应用价值探讨

目的分析血清组织多肽特异性抗原(TPS)水平与乳腺癌生物学行为的相关性,探讨血清TPS表达在乳腺癌中的临床应用价值。方法回顾性选取2019年1月至2020年1月在首都医科大学附属北京天坛医院住院治疗的乳腺癌患者85例为乳腺癌组;选取同时期诊断为乳腺良性肿瘤的患者83例为良性疾病组;选取同时期健康体检者86例为健康对照组。应用酶联免疫吸附实验(ELISA)法检测所有入选对象的血清TPS表达水平,分析比较血清TPS的表达情况与是否发生淋巴结转移、TNM分期、病理学分化程度、雌、孕激素受体及Cer Bb-2基因等的关系,同时检测TPS与肿瘤标志物CEA、CA15-3、CA125联合检测在乳腺癌诊断中的灵敏度及特异度情况。结果乳腺癌组患者TPS表达水平及阳性率显著高于良性疾病组和健康对照组(P <0.05),乳腺癌患者经治疗后血清TPS表达水平明显降低,与治疗前比较差异有统计学意义(P <0.05);乳腺癌患者血清TPS表达与年龄、肿瘤直径无关(P> 0.05),与临床TNM分期、腋窝淋巴结转移、肿瘤分化程度密切相关(P <0.05)。TPS联合CEA、CA15-3和CA125检测可大幅度提高乳腺癌诊断的灵敏度和特异度,与单独使用TPS指标相比差异具有统计学意义(P <0.05)。结论血清TPS的表达水平与乳腺癌患者生物学行为存在相关性,其可作为乳腺癌早期诊断、治疗效果评价、复发转移及预后判断的临床指标,为乳腺癌患者的临床治疗及预后判断提供有力的依据和新思路。     

Shh、Ptch、Gli1与CyclinB1-CDK1在肝癌发生发展过程中的改变

目的观察大鼠诱发肝癌过程中Shh信号通路相关蛋白及细胞周期蛋白的表达变化,探讨其在肝癌发生发展过程中的作用。方法利用二乙基亚硝胺(DEN)制备诱发性大鼠肝癌模型,通过HE染色观察肝组织的形态学变化,应用免疫组织化学方法检测Shh、Ptch、Gli1、CyclinB1、CDK1蛋白在诱发性肝癌发生过程中的表达变化。结果根据HE染色结果将实验动物分为正常对照组、肝细胞损伤期、肝细胞增生-硬化期和肝细胞癌变期。Shh、Ptch、Gli1蛋白阳性表达细胞主要分布在增生结节、癌结节、小叶间胆管上皮细胞和癌周组织中,其阳性表达率均随肝癌发生发展过程逐渐增高的趋势;CyclinB1和CDK1阳性表达的细胞主要分布于门管区、肝小叶的周边及癌结节内,在肝细胞增生-硬化期和肝细胞癌变期大鼠肝组织中表达均高于正常对照组。结论 Shh信号通路被激活后,可通过影响CyclinB1和CDK1蛋白的表达促进细胞G2/M期转变,完成有丝分裂,导致细胞失控性增殖,促进肝癌的发生发展。     

Anti-Sc1 in pregnancy

Anti-Sc1 was detected in a gravida-2 patient at 12 weeks' gestation. At 29 weeks, the antibody was found to be of the IgG3 subclass with a titer of 16, score 36, by the indirect antiglobulin test, and it produced 7 percent lysis by antibody-dependent cellular cytotoxicity (ADCC) assay, a finding that suggested an unaffected fetus. The titer remained constant throughout the pregnancy, as did the IgG subclass and activity in the ADCC assay. At delivery of the full-term infant, the cord hemoglobin was 13.5 g per dL and the direct antiglobulin test was positive (3+) with anti-IgG. The infant did not require transfusion. A sample taken 9 weeks after delivery showed 44 percent lysis in the ADCC assay. The anti-Sc1 titer was 32, score 65.     

A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.Billions of anucleated platelets circulate in mammalian blood to prevent blood loss in case of tissue injury. The lifespan of platelets is short (4–6 d in mice and 5–9 d in humans; Leeksma and Cohen, 1955; Robinson et al., 2000); as a consequence, several million platelets have to be produced every hour to maintain their physiological blood counts and to avoid the risk of bleeding. In mammals, platelets are generated in BM from megakaryocytes (MKs), polyploid, terminally differentiated myeloid cells with a typical morphology and diameters of up to 100 µm.The production of platelets from MKs involves several sequential developmental and maturation steps. MKs develop from hematopoietic stem and progenitor cells, which give rise to an increasingly restricted lineage culminating in the formation of megakaryocytic precursors that generate MKs. During their differentiation and maturation, MKs localize to the perivascular niche, where they interact with sinusoidal BM endothelial cells (Avecilla et al., 2004; Patel et al., 2005a). Once they have settled in the perivascular microenvironment, mature MKs form dynamic transendothelial pseudopods, which extend into the lumen of BM sinusoids. These intravascular pseudopodial extensions, termed proplatelets (PPs), continue to elongate and become tapered into multiple platelet-size beads connected to each other and with their maternal MKs by thin cytoplasmic bridges (Italiano et al., 1999; Patel et al., 2005a). The release of platelets, the final step of platelet formation, then occurs within the blood, where new platelets are shed as fragments from the tips of intravascular PPs (Stenberg and Levin, 1989; Choi et al., 1995; Italiano et al., 1999; Junt et al., 2007).MKs are a rare cell population, constituting <0.01% of all BM cells. This contrasts with the high demand of platelet production, implying that the differentiation of MKs (termed megakaryocytopoiesis) and the subsequent assembly and release of platelets by MKs (termed thrombopoiesis) are highly efficient and tightly controlled processes. Among the factors that modulate megakaryocytopoiesis, thrombopoietin (TPO) is the major regulator of MK expansion from hematopoietic stem and progenitor cells, whereas chemokines, including stromal-derived factor-1 (SDF-1), primarily initiate the relocation of maturing MKs to the perivascular microenvironment (Avecilla et al., 2004). In contrast, the molecular pathways that control the final steps of thrombopoiesis, particularly the guidance signals that direct megakaryocytic pseudopodial extensions into the vascular lumen and trigger the intravascular release of new platelets, are entirely unknown.The bioactive sphingolipid sphingosine 1-phosphate (S1P) and the receptors responsive to this mediator regulate important biological functions of various hematopoietic cell types (Spiegel and Milstien, 2003, 2011; Schwab et al., 2005; Massberg et al., 2007), including cell migration in the BM compartment (Ishii et al., 2009; Allende et al., 2010). Here we report that S1P and the MK S1P receptor S1pr1 receptor are indispensable for normal BM thrombopoiesis. Using mouse mutants and by multiphoton intravital microscopy (MP-IVM), we demonstrate that a transendothelial S1P gradient navigates megakaryocytic PP extensions into the lumen of BM sinusoids. In the blood, PP extensions are exposed to high S1P concentrations, which initiate the subsequent shedding of platelets into the circulation. Both processes involve the S1P receptor S1pr1, triggering activation of the Gi/Rac GTPase signaling. Correspondingly, lack of S1pr1 on MKs, but not of other S1P receptors, results in severe thrombocytopenia. Thus, we have identified the S1P–S1pr1 pathway as a key nodal point integrating guidance cues that navigate directional PP elongation and enabling the final step of thrombopoiesis, the shedding of new platelets into the blood stream.     

骨髓增生异常综合征患者GSTT1、GSTM1基因分布频率和NQO1基因多态性分析

目的探讨谷胱甘肽S转移酶（GST）基因T1、M1（GSTY1、GSTM1）和苯醌氧化还原酶基因（NQO1C609T）多态性与骨髓增生异常综合征（MDS）易感性及MDS染色体核型异常的关系。方法用多重PCR方法检测52例MDS患者和241名与患者无血缘关系的正常人GSTF1和GSTM1基因型，用PCR-限制性片段长度多态性（RFLP）方法分析NQO1C609T基因型。结果与正常人对照组相比，MDS患者GSTT1和GSTM1无效型（nu11）比例明显增高（P值均〈0．01），其比值比（OR）分别为2．873（95％可信区间：1．491～5．537）和3．591（95％可信区间：1．717～7．508）。染色体核型正常的MDS患者GSTT1无效型比例较正常人对照组显著增高（OR=5．336，P〈0．01），而GSTM1无效型比例与正常人对照组比较差异无统计学意义染色体核型异常的MDS患者GSTM1无效型比例较正常人对照组显著增高（OR=3．740，P〈0．01），而GSTT1无效型比例与正常人对照组比较差异无统计学意义MDS患者的NQI1C609T各基因型与正常人对照组差异无统计学意义。结论GSTT1和GSTM1基因无效型可能与MDS发生相关，对判断MDS患者是否出现染色体核型异常有一定意义。