滋养细胞肿瘤PP11,PP19,PP25和PP26的免疫组织化学研究

通过免疫组织化学方法研究了４种胎盘蛋白（ＰＰ１１、ＰＰ１９ＰＰ２５和ＰＰ２６）在滋养细胞肿瘤中的表达情况，发现ＰＰ１１在恶性葡萄胎中的表达明显低于葡萄胎（Ｐ＜０．０５）、ＰＰ２５和ＰＰ２６在绒癌中的表达低于葡萄胎（Ｐ＜０．０５）；ＰＰ１９在各种滋养细胞肿瘤中皆有强表达，提示联合检测４种胎盘蛋白有助于滋养细胞肿瘤间的鉴别诊断。ＰＰ１９还是中间型滋养细胞肿瘤的优良标志物。     

滋养细胞疾病中p27蛋白表达的研究

目的 探讨周期素依赖激酶抑制剂ｐ２７蛋白在滋养细胞中的表达及其与滋养细胞疾病发生、发展和预后的关系。方法 采用免疫组织化学ＳＰ（ＬＳＡＢ）法检测３５例滋养细胞中ｐ２７蛋白的表达情况。结果 ｐ２７蛋白在１０例正常早孕绒毛和１５例良性葡萄胎中的表达阳性率明显高于１１例侵蚀性葡萄胎和９例绒毛膜癌（Ｐ〈０．０５）。正常早孕绒毛和良性葡萄胎ｐ２７蛋白表达阳性率分别为８０．０％（８／１０）和７３．３％（１１／     

妊娠性滋养细胞肿瘤P185和雌孕激素受体的表达及意义

以ＡＢＣ法检测了４０例妊娠性滋养细胞肿瘤石蜡标本Ｐ１８５及ＥＲ、ＰＲ的表达。其中绒毛膜癌２４例。侵蚀性葡萄胎１６例，Ｐ１８５阳性率为４０％，ＥＲ、ＰＲ阳性率分别为４５％，７５％，Ｐ１８５在侵蚀性葡萄胎中的阳性率均明显高于绒瘤（Ｐ＜０．０１）。病程小于１年者，Ｐ１８５的阳性率高于病程大于１年者（Ｐ＜０．０５），ＥＲ、ＰＲ阳性者，Ｐ１８５的阳性率分别高于其阴性者（Ｐ＜０．０５、Ｐ＜０．０１），Ｐ１８５阳性与阴性的患者，分别有８１．３％、５０％的患者于３疗程内血ｈＣＧ转阴（Ｐ＜０．０５）。资料提示：Ｐ１８５倾向于在滋养细胞肿瘤恶性转化的早期表达，Ｐ１８Ｓ阳性者对化疗较为敏感。     

妊娠滋养细胞肿瘤nm23H1和PCNA的表达及其临床意义

目的 观察ｎｍ２３Ｈ１表达与妊娠滋养细胞肿瘤转移及细胞地殖状态的关系，并观察化疗对滋养细胞肿瘤细胞增殖状态的影响。方法 采用免疫组化方法检测４８例妊娠滋养细胞肿瘤手术标本、１０全恶性循环葡萄胎和１０例正常早孕绒毛组织刮宫标本中ｎｍ２３Ｈ１和ＰＣＮＡ的表达。结果 正常早孕绒毛或葡萄胎的ｎｍ２３Ｈ１，表达较妊娠滋养细胞肿瘤强（Ｐ〈０．０１），妊娠滋养细胞肿瘤中侵蚀性葡萄胎较绒癌强（Ｐ，０．０５），ＷＯ     

前列腺癌中p53和p16蛋白的表达及其临床病理学意义

目的探讨抑癌基因在前列腺癌组织中的表达及临床意义。方法应用免疫组织化学方法,检测２５例前列腺癌中ｐ５３和ｐ１６基因蛋白产物的表达。结果ｐ５３蛋白阳性率为３２％（８／２５）,明显高于良性前列腺增生（Ｐ＜０．０５）,并在低分化肿瘤中表达高（Ｐ＝０．０４０３）;在临床分期Ⅲ～Ⅳ期癌中表达升高（Ｐ＜０．０５）。ｐ１６的失活率４４％（１１／２５）,也是低分化组高于高分化组（Ｐ＜０．０５）。并发现４例低分化癌中有ｐ５３和ｐ１６共同异常。结论ｐ５３和ｐ１６基因的异常表达均与前列腺癌的形成和恶性程度有关,但两者之间是否具有协同作用尚待进一步证明。     

妊娠滋养细胞肿瘤（疾病）保留生育功能的治疗

妊娠滋养细胞疾病是一系列的疾病，包括葡萄胎、侵蚀性葡萄胎（简称侵葡）、绒毛膜癌（简称绒癌）和胎盘部位滋养细胞肿瘤（简称ＰＳＴＴ）。除葡萄胎外，后三者又统称妊娠滋养细胞肿瘤。葡萄胎约有１４．５％～２０％可恶变为滋养细胞肿瘤，这类疾病大多发生在生育年龄的...     

前列腺癌中p53和p16蛋白的表达及其临床病理学意义

目的 探讨抑癌基因在前列腺癌组织中的表达及临床意义。方法 应用免疫组织化学方法,检测２５例前列腺癌中ｐ５３和ｐ１６基因蛋白产物的表达。结果 ｐ５３蛋白阳性率为３２％（８／２５）,明显高于良性前列腺增生（Ｐ〈０．０５）,并在低分化肿瘤中表达高（Ｐ＝０．０４０３）;在临床分期Ⅲ￣Ⅳ期癌中表达升高（Ｐ〈０．０５）。ｐ１６的失活率４４％（１１／２５）,也是低分化组高于高分化组（Ｐ〈０．０５）。并发现４例低     

Src基因产物PP60~（C—Src）在食管癌中表达的研究

本实验用Ｃ—Ｓｒｃ基因表达产物ＰＰ６０Ｃ—Ｓｒｃ的特异性单克隆抗体ＭＡｂ３２７对３５例食管鳞癌及２２例癌旁组织进行了免疫组织化学研究。食管鳞癌、癌旁增生及正常鳞状上皮ＰＰ６Ｃ—Ｓｒｃ性率分别为６５．７％（２３／３５）、１００．０％（１５／１５）、５７．１％（４／７），具有显著差异（Ｐ＜０．０５），鳞癌细胞ＰＰ６０Ｃ—Ｓｒｃ表达量高于癌旁增生及癌旁正常鳞状上皮。不同分化程度（Ⅰ、Ⅱ、Ⅲ级）鳞癌ＰＰ６０Ｃ—Ｓｒｃ阳性率分别为８０％（８／１０）、６８．４％（１３／１９）、３３．３％（２／６），无显著性差异（Ｐ＞０．００５），分化程度越高，ＰＰ６０Ｃ—Ｓｒｃ表达量越高（Ｐ＜０．０５）。结果提示，Ｃ—Ｓｒｃ基因激活表达与食管鳞癌发生发展有关，在其癌变过程中ＰＰ６０Ｃ—Ｓｒｃ表达量升高，并与食管鳞癌分化有关。     

胸腺瘤p53蛋白表达与肿瘤临床病理学特征及预后关系的研究

应用免疫组织化学方法（Ｓ－Ｐ法）观察５４例胸腺瘤Ｐ５３蛋白表达及其与肿瘤临床病理学和预后关系。结果显示：１８例侵袭型胸腺瘤中１１例Ｐ５３蛋白阳性（６１．１％），３例非侵袭型胸腺瘤中７例Ｐ５３蛋白阳性（１９．４％）；单纯性胸腺瘤４８例（其中上皮细胞型９例，淋巴细胞型１７例、混合型２２例）中１２例Ｐ５３蛋白阳性（２５．０％）胸腺类癌２例及胸腺癌４例Ｐ５３蛋白均阳性（Ｐ〉０．０５）；有ＭＧ者１７例Ｐ５３     

Src基因产物PP60~（c－src）与大肠癌发生关系的研究

用Ｃ－Ｓｒｃ基因产物（ＰＰ６０ｃ－ｓｒｃ）的特异性单克隆抗体Ｍａｂ３２７对１２例胎儿大肠粘膜、１８例癌旁正常上皮、１８例癌旁增生上皮及３７例大肠癌进行免疫组化研究，其阳性率分别为１００．０％（１２／１２），０％（０／１８），６１．１％（１１／１８），５６．８％（２１／３７）。几者间阳性率有显著性差异（Ｐ＜０．００５），其表达量也有显著性差异（Ｐ＜０．０５）。不同分化程度（高、中、低）的管状腺癌ＰＰ６０ｃ－ｓｒｃ阳性率分别为１００．０％（８／８）、６６．７％（１０／１５）、３７．５％（３／８），分化程度越高，ＰＰ６０ｃ－ｓｒｃ阳性率越高（Ｐ＜０．０５），表达量越高（Ｐ＜０．０１）。３例乳头状腺癌中２例有ＰＰ６０ｃ－ｓｒｃ低表达，３例粘液腺癌未检出ＰＰ６０ｃ－ｓｒｃ。结果提示，ＰＰ６０ｃ－ｓｒｃ激活表达与大肠癌发生发展有关，可能是大肠癌变的早期改变，在其癌变过程中ＰＰ６０ｃ－ｓｒｃ表达量升高，并与大肠癌分化有关。     

细胞生长相关新基因PP3105的克隆及其初步功能研究

目的 新基因PP3105的克隆及其初步功能研究。方法 分离和克隆新基因PP3105的全长序列，在生物信息学分析的基础上，采用克隆形成、亚细胞定位、生长曲线等实验对该基因进行初步功能研究。结果 实验表明PP3105有两个不同的转录本，并表现出一定的组织特异性；染色体定位于4q22-24；蛋白定位于细胞膜和细胞浆中；克隆形成实验显示有明显的体外集落抑制作用；生长曲线实验表明PP3105在SMMC7721细胞中的表达对细胞增殖有抑制作用。结论 新基因PP3105可能是一个新的金属离子尤其是锌的转运蛋白，并且与肝癌细胞的生长、增殖相关。     

Role of PP2Cα in cell growth,in radio- and chemosensitivity,and in tumorigenicity

Background  

PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis.     

Phosphatase: PP2A structural importance,regulation and its aberrant expression in cancer

Protein Phosphatase 2A (PP2A) is an important and ubiquitously expressed serine threonine phosphatase and regulates the function by dephosphorylating many critical cellular molecules like Akt, p53, c-Myc and β-catenin. It plays a critical role in cellular processes, such as cell proliferation, signal transduction and apoptosis. Structurally, it is multifarious as it is composed of catalytic, scaffold and regulatory subunits. The catalytic and scaffold subunits have two isoforms and the regulatory subunit has four different families containing different isoforms. The regulatory subunit is the most diverse with temporal and spatial specificity. PP2A undergoes post-translational modifications (i.e. phosphorylation and methylation), which in turn, regulates its enzymatic activity. Aberrant expression, mutations and somatic alterations of the PP2A scaffold and regulatory subunits have been observed in various human malignancies, including lung, breast, skin and colon cancer, highlighting its role as a ‘tumor suppressor’. This review is focused on the structural complexity of serine/threonine phosphatase PP2A and summarizes its expression pattern in cancer. Additionally, the PP2A interacting and regulatory proteins and substrates are also discussed. Finally, the mouse models developed to understand the biological role of PP2A subunits in an in vivo model system are also reviewed in this article.     

Targeting PP2A for cancer therapeutic modulation

Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal organization. Protein phosphatase 2A (PP2A) is highly conserved and is the predominant serine/threonine phosphatase in the nervous system, constituting more than 70% of all neuronal phosphatases. PP2A is involved in diverse regulatory functions, including cell cycle progression, apoptosis, and DNA repair. Although PP2A has historically been identified as a tumor suppressor, inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various cancers. LB100, a water-soluble, small-molecule competitive inhibitor of PP2A, has shown particular promise as a chemo- and radio-sensitizing agent. Preclinical success has led to a profusion of clinical trials on LB100 adjuvant therapies, including a phase I trial in extensive-stage small-cell lung cancer, a phase I/II trial in myelodysplastic syndrome, a phase II trial in recurrent glioblastoma, and a completed phase I trial assessing the safety of LB100 and docetaxel in various relapsed solid tumors. Herein, we review the development of LB100, the role of PP2A in cancer biology, and recent advances in targeting PP2A inhibition in immunotherapy.     

三丁基锡对小鼠脾、肝和脑组织蛋白磷酸酶2A活性的影响

目的： 研究三丁基锡 (tributyltin，TBT)对小鼠脾、肝和脑组织蛋白磷酸酶2A (protein phosphatase 2A，PP2A)活性的影响。方法：将不同浓度TBT (0、10、20、60 mg/kg)，分别以灌胃的方式对小鼠染毒24和96 h，检测脾、肝和脑组织PP2A酶活性的改变。结果：TBT染毒24和96 h，小鼠脾脏PP2A酶活性在20和60 mg/kg剂量组明显下降，与对照组相比差异均具有统计学意义 (P < 0.01)；肝脏PP2A酶活性仅在60 mg/kg时，较对照组明显被抑制 (P < 0.05)；而脑PP2A酶活性在各浓度组与对照组相比均未发生明显改变 (P>0.05)。结论：PP2A酶活性的降低可能是TBT产生免疫和肝毒性效应的重要分子机制。     

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases,inhibits anaplastic thyroid carcinoma cell proliferation and migration

The tyrosine and phosphoinositide kinases play crucial roles in the regulation of many cancer cell processes including cell survival and cell motility. Anaplastic thyroid carcinoma (ATC) is a rare and deadly type of thyroid cancer, and so far, there are no effective therapeutic compounds for ATC. Herein, we investigate the anticancer activities of PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, in ATC therapy. We found that PP121 is effective at suppressing cell viability, inducing cell apoptosis, and inhibiting cell migration and invasion. The potential anticancer mechanism for PP121 might be its inhibitory effects on phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in ATC cells. Furthermore, PP121 is effective at suppressing ATC tumor growth in vivo. In summary, our studies suggest that PP121 might be a promising therapeutic compound for ATC treatment, which might shed new light on ATC therapy.     

PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers

The chromosome region 11q is frequently deleted in colorectal cancers. The PPP2R1B tumor suppressor gene, encoding the beta isoform of the A subunit of serine/threonine-specific protein phosphatase 2A (PP2A-Abeta), located at 11q22-23, is inactivated in patients with cancer. The present study investigated whether or not PP2A-Abeta is altered in colorectal cancers. We searched for alterations of the PPP2R1B gene and interactions between PP2A-Abeta and PP2A-C proteins in 50 surgically resected colorectal cancer tissues. Missense mutations and homozygous deletions of the PPP2R1B gene were found in 4 of 50 patients (8%) and in 1 of 50 patients, respectively, with colorectal cancers. Deletions and/or point mutations within 412-601 amino acid sequences (binding regions of PP2A-C protein) of the PPP2R1B gene derived from colorectal cancer tissues inhibited co-immunoprecipitation of PP2A-Abeta and PP2A-C proteins. These finding suggested that the PPP2R1B gene functions as a tumor suppressor gene and acts as a molecular switch that becomes active in response to specific up-stream signals. Upon activation, the gene alters the activities of specific downstream target proteins for the cell cycle regulations and/or metabolism in some colorectal cancers.     

Structural-functional damage to cellular membranes in deficiency of vitamins A,E, B2, B6, PP in children with calculous pyelonephritis

Lipids were studied in 150 patients with nephrolithiasis, calculous pyelonephritis; enzymes, LPO products, phospholipase in 111 patients; vitamins A and E in 136 patients, vitamins B2, B6 and PP in 146 patients in the course of the disease, at admission and after treatment. In acute purulent and aggravated chronic calculous pyelonephritis lysophospholipids levels rose manifolds. Activation of LPO products, phospholipase, organ-specific enzymes is closely associated with low provision of vitamins A, E, B2, B6, PP. Deficiency of these vitamins ranged from 76.8 to 94.6% in acute purulent calculous pyelonephritis in all the patients.