CD200 Expression in Diagnostic and Prognostic Assessment of Mature B Cell Lymphophoproliferative Neoplasms

Background: Multiparameter flow cytometry is a useful tool for diagnostic evaluation of mature B-cell neoplasms(MBN). Recently, it has been shown that assessment of CD200 expression may improve the distinction betweenchronic lymphocytic leukemia (CLL; CD200 positive) and mantle cell lymphoma (MCL; CD200 negative), but anypotential as a prognostic marker for CLL remains to be established. Materials and methods: This cross sectionalstudy was conducted on sixty-seven patients newly diagnosed as having mature B-cell lymphoproliferative disordersLevels of CD 200 in lymphoma cells were assessed. Results: CD200 was consistently expressed in CLL and hairycell leukemia B cells, but not in MCL cells. Heterogeneous expression was noted in other CD5 positive Non-Hodgkinlymphomas. High CD200 expression (≥50%) was associated with a higher CD5, 19 and CD23 expression, olderage, higher TLC and absolute lymphocyte count, hepatomegaly, splenomegaly and a higher Rai stage. There wereno significant correlations between CD200 expression and response to treatment. Conclusion: CD200 could be of highvalue in distinguishing CLL, MCL, and atypical CLL. CD200 expression can also be of prognostic and therapeuticvalue in CLL cases.     

神经节苷脂诱导胶质瘤细胞自噬性死亡

目的 探讨神经节苷脂(GM1)对恶性脑胶质瘤细胞U251自噬性死亡的影响.方法 GM1作用U251细胞后,应用MTT法检测细胞的存活率,流式法检测细胞凋亡的改变,荧光显微镜下观察MDC染色后细胞质内酸性自噬泡的形成情况及外源性LC3-Ⅱ的表达;Western blotting法检测细胞自噬相关蛋白LC3-Ⅱ/LC3-Ⅰ的比值、Lamp-2a、Beclin-1的表达.结果 与对照组相比,GM1作用48 h后,U251细胞存活率明显降低,且具有剂量依赖性,差异有统计学意义(P<0.05);与对照组相比,GM1作用48 h后,U251细胞凋亡率明显升高,且具有剂量依赖性,差异有统计学意义(P<0.05);GM1作用后细胞内LC3-Ⅱ/LC3-Ⅰ的比值、Lamp-2a及Beclin-1的表达水平明显上调,差异有统计学意义(P<0.05).结论 GM1可以诱导恶性脑胶质瘤细胞U251自噬性死亡,为恶性脑胶质瘤的治疗提供新的方向.     

神经节苷脂诱导U251细胞内质网应激相关凋亡

目的：探讨神经节苷脂（ GM1）对人脑星形胶质瘤细胞U251内质网应激（ ERS）相关凋亡的调控。方法用含不同浓度的GM1培养基培养U251细胞,MTT法检测细胞存活率,乳酸脱氢酶（ LDH）检测细胞损伤,流式细胞术检测细胞凋亡率,Western blotting检测ERS凋亡相关蛋白CHOP及caspase-12表达变化。结果与对照组比较,GM1孵育48 h后,U251细胞存活率明显降低,且具有剂量依赖性（ P＜0.05）;U251细胞培养基中LDH量明显增高,且具有剂量依赖性（P＜0.05）;GM1诱导U251细胞凋亡率明显增高,且具有剂量依赖性（P＜0.05）;GM1诱导细胞内CHOP及caspase-12的表达上调,且有剂量依赖性（P＜0.05）。结论 GM1可诱导U251细胞ERS相关凋亡,为恶性脑胶质瘤的治疗提供新的方向。     

EBER Gene Expression in Epstein-Barr Virus-Associated Hematopoietic Neoplasms

Epstein-Barr virus encoded RNA's (EBER) are small RNA species found in cells latently infected by the virus. The physiological function of these molecules is currently a matter of speculation. Nonetheless, their presence in extremely high copy number has made it possible to reliably detect the Epstein-Barr virus by in-situ hybridization, in human tissues routinely fixed with formalin and embedded in paraffin. Such studies have enhanced our understanding of a number of hematologic malignancies, particularly Hodgkin's disease, angiocentric im-munoproliferative lesions and angio-immunoblastic lymphadenopathy. In addition, sequential EBER in-situ hybridization studies on lymphoid tissues should enable oncologists to monitor the development of lymphoproliferative disorders occurring in the setting of organ transplantation, AIDS and hereditary immunodeficiencies.     

survivin和CK18在甲状腺肿瘤中的表达

目的 探讨甲状腺肿瘤中survivin基因和CK18的表达对病理诊断及淋巴结微转移的意义。方法 采用免疫组化SP法检测56例甲状腺癌、13例甲状腺腺瘤和10例正常甲状腺组织中CK18和survivin基因的表达。结果 （1）CK18在三种甲状腺组织中的阳性表达率均为100%,survivin在正常甲状腺、甲状腺腺瘤和甲状腺癌中的阳性表达率分别为0.00%、15.38%和60.71%。甲状腺癌与甲状腺腺瘤及正常甲状腺survivin表达差异有统计学意义（P<0.05）。（2）56例甲状腺癌患者的94枚淋巴结CK18阳性表达率为35.11%（33/94）。显著高于HE染色发现的淋巴转移阳性率20.21%（19/94）（P<0.05）。56例甲状腺癌中有7例14枚淋巴结属于微转移。（3）CK18标记有助于识别甲状腺高分化滤泡状癌侵犯被膜。结论 CK18是检测甲状腺癌淋巴结微转移及侵犯被膜的一个敏感指标,而survivin的表达与甲状腺癌的发生、发展以及转移有关,两者联合检测可作为临床病理诊断的客观依据。     

卵巢恶性生殖细胞肿瘤手术方式的探讨

目的　本文分析164例卵巢恶性生殖细胞肿瘤的手术疗效,探讨治疗该瘤更合理的手术方式。方法　回顾性分析164例卵巢恶性生殖细胞肿瘤患者的临床资料,其中5 7例采用保留生育功能的术式;10 7例采用不保留生育功能的传统术式。2组均根据个体状况辅以适当的化疗(和/或放疗)。结果　保留生育功能组和不保留生育功能组的5年生存率分别为69.0 1% (3 9/5 7)、5 4.94% (5 9/10 7) (P >0 .0 5 )。2组术后并发症发生率分别为3 .5 1% (2 /5 7)、3 .74% (4 /10 7) (P >0 .0 5 )。多因素分析显示临床分期、病理类型、残留肿瘤体积是影响预后的主要因素(P均<0 .0 5 )。结论　卵巢恶性生殖细胞肿瘤患者可根据需要采用保留生育功能的术式,并辅以适当的化疗和(或)放疗。     

Expression of Globo-series Gangliosides in Human Renal Cell Carcinoma

Gangliosides have been shown to be involved in development, differentiation, oncogenesis, and cancer progression. We investigated immunohistochemical expression of globo-series gangliosides in human renal cell carcinoma (RCC) and whether their expression is related to the clinical course. The expression of globo-series gangliosides was evaluated in fresh-frozen sections of 55 primary renal tumors and 8 metastatic deposits using monoclonal antibodies RM1 and RM2, which define mono-sialosyl and disialosyl galactosylgloboside, respectively. The immunorcaetivity of primary tumors to RM1 and/or RM2 was correlated with the clinicopathological data. Cumulative incidence of metastasis detected at initial diagnosis and during the follow-up period was significantly higher in the cases whose primary tumors were RMl/RM2-positive (RM1 and/or RM2-positive) than in the RM1/ RM2-negative (neither RM1 nor RM2-positive) cases ( P <0.05). During the follow-up period, metastasis developed in none of the RMl/RM2-negative cases which had not shown metastasis at initial diagnosis. High nuclear grade was observed only in the RMl/RM2-positive cases. The RM1/RM2-positive rate of the metastatic deposits was higher than that of the primary tumors. Furthermore, a metastatic deposit obtained from one of the cases whose primary tumors were equivocal for RM1/ RM2 was extensively stained by RM1 and RM2. These results indicate that globo-series gangliosides may be one of the biochemical indicators related to the metastatic potential of human RCC.     

细胞周期蛋白A在舌癌中的表达及意义

[目的]研究不同级别的舌鳞状细胞癌中细胞周期蛋白A（cyclinA）基因和蛋白的表达及其意义。［方法］应用微波内免疫组化ABC法检测cyclinA蛋白及原位杂交技术检测cyclinAmRNA的表达情况。［结果〕免疫组化cyclinA多克隆抗体标记60.0％（18／30）显示cyclinA蛋白过度表达;cyclinA探针随机引物标记,经原位杂交后显示,cyclinAmRNA的阳性表达率为70.0％（21／30）。（结论］cyclinA在舌癌中有高水平的表达,且临床分期越晚,恶性程度越高,其表达率也较高,提示cyclinA的过度表达与舌癌的特性密切相关,cyclinA阳性检出率有助于判断舌癌恶性程度及预测肿瘤的转移,在舌癌的发生、发展中起着重要作用。     

基因芯片在肾癌相关基因研究中的应用

目的：通过研究人肾癌组织和癌旁正常组织中差异表达的基因，寻找肾癌相关基因以用于诊断和治疗。方法：以包含8000个cDNA基因表达谱芯片研究1组肾癌组织样本的基因表达谱。按一步法抽提肾癌和对照组癌旁正常组织的总RNA并纯化mRNA；将等量的对照组织和肾癌组织mRNA分别逆转录合成荧光分子掺入的cDNA-链做探针，混合后杂交上述基因芯片。经严格洗片后用ScanArray3000扫描仪扫描芯片荧光信号图像，计算分析后比较2种组织中差异表达的基因。结果：共筛选出差异表达基因95条，其中未知基因44条。结论：基因芯片在筛选肾癌相关基因的改变具有快速、高通量、灵敏的特点，肾癌在细胞代谢、信号转录、蛋白合成的相关基因方面有异常表达。     

结肠腺瘤和腺癌肠血管活性多肽及胰泌素受体表达

目的了解结肠腺瘤和腺癌肠血管活性多肽vasoactiveintestinalpeptideVIP受体和胰泌素受体表达的变化。方法:采用储磷放射自显影技术测定并显示无肿瘤结肠、结肠腺瘤、结肠癌、结肠癌肝转移灶及无肿瘤肝脏的组织切片上的VIP和胰泌素受体。结果:无肿瘤结肠、结肠腺瘤、结肠癌、结肠癌肝转移灶组织均表达了VIP和胰泌素受体。结肠癌肝转移灶中的VIP受体亲和力Kd=3.30nmol显著低于无肿瘤结肠Kd=0.82nmolP<0.05。与之相反,结肠癌肝转移灶中的胰泌素受体亲和力Kd=1.9nmol显著高于无肿瘤结肠Kd=5.3nmolP<0.05。结论:在结肠癌发生发展过程中,属于同一家族的VIP和胰泌素两种受体亲和力的变化恰好相反,前者降低,后者增加。结肠癌肝转移灶中VIP受体结合量的显著降低可能有助于理解结肠癌细胞转移的现象。     

Ganglioside modulation of the PDGF receptor

Summary Gangliosides are a family of glycolipids that are present at the cell surface of all mammalian cells. Patterns of gangliosides are different in gliomas than normal brain, and exogenously added gangliosides affect the growth of cultured glioma cells. Gangliosides inhibit the activities of several kinases, including protein kinase C (PKC) and cAMP-kinase. U-1242 MG cells (derived from a human malignant glioma) have receptors for platelet-derived growth factor (PDGF) that become phosphorylated on tyrosine when exposed to PDGF. Exposure of these cells to PDGF also causes an increase in intracellular calcium concentration ([Ca²⁺]_i) and induces a translocation of PKC to the membrane. Preincubation of U-1242 MG cells with several species of gangliosides inhibits the increase in ([Ca²⁺]_i) and PKC translocation in response to PDGF, but GM3 is much less effective than other species tested. This is due to a lack of activation of the receptor tyrosine kinase as monitored by phosphorylation of the receptor on tyrosine residues, but is not due to an inhibition of binding of PDGF to its receptors. The lack of activation of the PDGF receptor tyrosine kinase is due to an inhibition of dimerization of the receptor monomers by gangliosides GM1, GM2, GD1a, GT1b, but not GM3. Therefore, gangliosides may be involved in coordinating the activities of multiple trophic factors simultaneously acting on a cell by regulating the dimerization of their respective receptor monomers.     

食管鳞癌形成中基因表达谱的研究

[目的]初步了解食管鳞癌形成中5个不同时期（正常、食管上皮不典型增生Ⅰ级、食管上皮不典型增生Ⅱ级、食管原位鳞癌和食管鳞癌）的基因表达谱,并探讨cDNA微点阵技术在肿瘤研究中的应用价值。[方法]收集上述5种不同病理类型的组织标本,提取总RNA,逆转录合成cDNA探针,分别与cDNA微点阵膜杂交,随机挑选8个EST片段,分别以杂交样品和配对组织标本总教育界模板完成RT-PCR以验证杂交结果的准确性,用专用软件分析得到各位点光密度值,将此数值标准化后进一步比较分析。[结果]对于杂交样品和配对组织标本,都是6个EST片段的RT-PCR结果与其杂交结果一致,数据分析显示,正常时期和其他各期相比分别有492,481,473和501个基因的表达改变了2倍及2倍以上,其中386个基因在4个异常时期均表达下调,而其他各期之间相比,大多数基因的表达无明显改变,还观察了一些已知的肿瘤相关基因在5个不同时期的表达状况。[结论]本实验再一次证实食管上皮不典型增生Ⅰ级是食管鳞癌形成的一个早期阶段。利用cDNA微点阵技术将有望发现导致食管鳞癌形成的关键基因,为临床早期诊断、治疗和预防提供新的线索。     

FasL表达在肝癌肿瘤免疫逃避中的意义

目的 :探讨肝癌中FasL表达在肿瘤免疫逃避中的意义。方法 :采用免疫组织化学法和脱氧核糖核酸末端转移酶介导的缺口末端标记 (TUNEL)技术 ,对 4 1例肝癌组织中FasL表达及其肿瘤浸润淋巴细胞凋亡的关系进行研究。结果 :肝癌FasL表达阳性率为 4 1 4 6% ,FasL阳性组肝癌肿瘤浸润淋巴细胞 (tumorinfiltratinglymphocytes ,TIL )凋亡指数约是FasL阴性组肝癌的 2倍 ,两组差异有显著意义。结论 :肝癌FasL表达在肿瘤免疫逃避中有重要意义     

非小细胞肺癌bax蛋白的表达及意义

目的 :探讨凋亡相关基因bax在人非小细胞肺癌 (non smallcelllungcarcinoma ,NSCLC)组织中的表达情况及其与肺癌临床病理特征和预后的关系。方法 :用免疫组织化学SABC法检测 6 8例NSCLC中bax蛋白的表达水平 ,用TUNEL法检测其中的细胞凋亡情况。研究对象 :鳞癌 38例 ,腺癌 30例 ,同时检测 11例正常肺组织作为对照。结果bax蛋白在肺癌组织中的阳性表达率为 5 4 4 1% ,正常肺组织为 10 0 % ,两者差异有极显著性 (P <0 .0 1) ;在鳞癌中的阳性表达率为 39 4 7% ,小于腺癌的73 33% (P <0 0 1) ;bax的表达与T和N情况、临床分期、年龄、性别和是否吸烟无关。NSCLC组织的凋亡指数 (AI)为 1 79± 0 5 1,小于正常肺组织的 14 33± 5 6 2 (P <0 0 5 )。在NSCLC中 ,bax蛋白表达阴性者生存时间长于阳性者 (P <0 0 5 )。结论 :bax蛋白的表达与非小细胞肺癌的组织类型和预后相关 ,并通过对细胞凋亡的调控参与了肺癌的发生、发展。     

Ganglioside GM3 inhibits proliferation and invasion of glioma

GM3, the simplest ganglioside, modulates cell adhesion, proliferation and differentiation in the central nervous system and exogenously added GM3 regulates cell–cell and cell–extracellular matrix adhesion and induces apoptosis. To assess the anti-tumor action of exogenous GM3, we examined its effect on the proliferation and invasion of glioma cells. Its inhibitory effect on cell proliferation was demonstrated in vitro by 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and in vitro in rats with meningeal gliomatosis whose survival was significantly prolonged by the intrathecal injection of GM3. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay revealed that GM3 induced glioma cell apoptosis in vitro and in vitro. In rat brain slice cultures, GM3 suppressed the invasion of glioma cells; this effect manifested earlier than the inhibition of cell proliferation and before apoptosis induction. Our results suggest exogenous GM3 as a potential therapeutic agent in patients with glioma requiring adjuvant therapy.     

B细胞淋巴瘤的Fas蛋白表达及意义

目的：探讨Fas蛋白在不同类型B细胞源性非霍奇金淋巴瘤（non-Hodgkon‘s Bcell lymphoma,B-NHL)中的分布及意义,为B－NHL诊治提供新的观察指标及实验依据。方法：对确诊为B－NHL的79例及良性淋巴组织20例的石蜡切片,用免疫组化方法进行Fas蛋白表达的检测。结果：发现B－NHL的Fas蛋白平均阳性表达率为65．8％,良性淋巴组织为60．0％,单从数量上,良恶两者之间差异无显著性（P＜0．05）,而从阳性细胞分布上良、恶性可见区别,良性分布有规律,主要集中在生发中心;恶性分布无规律性。淋巴瘤组内各亚组之间差异有显著性意义：弥漫大B细胞淋巴瘤（deffuse large B cell lymphoma,DLBL)组表达分别高于滤泡性淋巴瘤（follicular cell lymphoma,FCL)(P＜0．05）和小淋巴细胞性淋巴瘤（small lymphocytic lymphoma,SLL)组（P＜0．01）;FCL组表达高于SLL组（P＜0．05）。Fas蛋白的表达与性别、年龄及部位无相关性。结论：1、Fas的表达与B淋巴瘤的类型及恶性程度有关。2、Fas的表达半定量检测不能作为鉴别良恶性的指标,而分布规律不同可作参考。检测Fas蛋白的数量及注意阳性细胞分布规律,对病理确诊淋巴瘤疑难病例有一定应用价值,可为临床选择治疗方案提供参考。     

CD44V6在结直肠癌组织中的表达及临床意义

目的：探讨CD44V6表达与结直肠癌发生、发展及转移的关系。方法：采用S－P免疫组织化学方法，检测78例原发性结直肠腺癌、14例结直肠腺瘤癌变、57例结直肠腺瘤、30例结直肠增生性息肉和24例结直肠正常黏膜中CD44V6的表达情况。结果：腺瘤、腺瘤癌变和腺癌组织中CD44V6阳性表达率分别为78．95％、100．00％和56．41％，明显高于增生性息肉和正常黏膜组织的阳性表达率（14．81％）。CD44V6阳性表达与腺癌淋巴结转移、Dukes分期和病理分级无相关性。结论：CD44V6表达与结直肠癌的发生有关，可作为诊断结直肠癌前病变和早期癌的生物学指标。     

Ki-67抗原在原发性胆囊癌中的表达及其意义

目的探讨Ki-67抗原表达与原发性胆囊癌病理生物学行为的关系.方法采用免疫组化S-P法,检测胆囊良、恶性病变中Ki-67抗原的表达情况,以其表达阳性率评估胆囊癌组织的增生活性.结果Ki-67抗原在胆囊癌组织中的表达量显著高于胆囊良性病变(P＜0.01).但Ki-67抗原的表达强度与胆囊癌组织学类型、Nevin分期及病理分级无明显相关性(P＞0.05),与胆囊癌的突变型p53基因产物表达量呈明显正相关(P＜0.05).结论Ki-67抗原作为1个代表增殖活性的肿瘤标志,其过量表达是胆囊癌高度恶性的生物学行为的客观指标之一,对胆囊恶性肿瘤的病理诊断有较高的实用价值.p53基因可能通过基因突变增强胆囊癌细胞的增殖活性,从而使Ki-67抗原表达量明显增加.     

p16、p63蛋白在甲状腺肿瘤中的表达及其意义

目的　探讨抑癌基因蛋白p16和 p63在各型甲状腺肿瘤中的表达及其意义。 方法　采用免疫组织化学 (EnvisionTM)法检测 60例甲状腺肿瘤细胞中 p16和 p63蛋白的表达情况。 结果　甲状腺腺瘤中 p16及 p63蛋白阳性表达率分别为 60 .0 % ( 18/3 0 )和 46.7% ( 14 / 3 0 ) ,明显高于甲状腺癌 ( 3 3 .3 % ,10 / 3 0 ;2 0 .0 % ,6/ 3 0 ) ,有显著性差异 (P <0 .0 5 )。甲状腺乳头状腺瘤中 p16和p63蛋白阳性表达率分别为 80 .0 % ( 12 / 15 )和 60 .0 % ( 9/ 15 ) ,明显高于甲状腺乳头状腺癌中阳性率 ( 3 3 .3 % ,5 / 15 ;2 0 .0 % ,3 / 15 ) ,有显著性差异 (P <0 .0 5 )。甲状腺滤泡状腺瘤中 p16和p63蛋白阳性表达率分别为 40 .0 % ( 6/ 15 )和 3 3 .3 % ( 5 / 15 ) ,高于甲状腺滤泡状腺癌中其阳性表达率 ( 3 3 .3 % ,5 / 15 ;2 0 .0 % ,3 / 15 ) ,但无显著性差异 (P >0 .0 5 )。结论　检测甲状腺癌中p16和 p63蛋白表达水平 ,对甲状腺恶性肿瘤的诊断和预后评估有一定意义