依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Ureteral carcinoid tumor

Most ureteral tumors are transitional cell neoplasms. Neuroendocrine tumors of the genitourinary tract are extremely rare. To our knowledge, only one ureteral carcinoid tumor has been reported before. We report a second case of ureteral carcinoid tumor found in a 70-year-old female.     

中原地区遗传性非息肉病性大肠癌表型特征的临床研究

目的探讨中原地区遗传性非息肉病性大肠癌(HNPCC)的表型特征,为制订适合我国国情的HNPCC遴选标准提供依据。方法对符合Am sterdam标准的8个家系37例患者的临床资料(A组),与随机抽调我院40例确切无家族史的大肠癌患者的临床资料(B组)进行对比分析。结果①发病年龄:A组平均46岁,B组62.6岁,平均提前16.6年;<50岁者:A组73%(27/37),B组30%(12/40),两组比较P<0.01;第1、2、3代平均发病年龄分别为69.2、46.9、34.6岁,逐代比较差异有统计学意义(P<0.05或P<0.01)。②发病部位:右半结肠A组73.2%(30/41),B组39.0%(16/41),两组比较P<0.05。③同时、异时多发大肠癌:A组8.1%(3/37),B组2.5%(1/40)。④大肠外癌:A组17.1%(7/41),B组0,两组比较P<0.05。⑤合并腺瘤:A组0,B组22.5%(9/40),两组比较P<0.05。⑥组织学类型:低分化腺癌A组69.7%(23/33),B组40%(16/40),两组比较P<0.05。结论中原地区HNPCC有其独特的临床特征,国际遴选标准不能完全适用于中国人,制定适合我国国情的HNPCC遴选标准确有必要。     

Primary malignant melanoma of the bladder

Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder. There was no history of previous or regressed cutaneous malignant melanoma. Margins of the bladder lesion contained atypical melanocytes similar to those commonly seen in the periphery of primary mucous membrane lesions. Clinical studies and radiological examinations were negative for other primary site of melanoma. The patient had a bladder recurrence that was consistent with primary tumor and died of widespread disease 9 months after diagnosis.     

乳腺癌HSV—1,HSV—2与c—erbB—2关系的免疫组化研究

采用免疫组织化学Ｓ－Ｐ法检测５２例手术切除乳腺癌组织ｃ－ｅｒｂＢ－２蛋白和ＨＳＶ－１、ＨＳＶ－２表达情况。结果发现癌组织中ｃ－ｅｒｂＢ－２阳性３４例（６５．４％）；ＨＳＶ－１阳性３８例（７３．１％）；ＨＳＶ－２阳性１５例（２８．８％）。癌旁组织３２例，阳性分别为３例（９．４％）；１２例（３７．５％）；２例（６．３％）。乳腺癌中ｃ－ｅｒｂＢ－２阳性率明显高于癌旁组织。乳腺癌及癌旁的ＨＳＶ－１阳性率明     

Wortmannin-mediated inhibition of phosphatidylinositol 3-kinase activity triggers apoptosis in normal and neoplastic B lymphocytes which are in cell cycle

The B cell functional response following ligation of surface(s) lgM is dependent upon the differentiation stage of the populationstudied: cross-linking slgM promotes proliferation of restingtonsillar follicular mantle (FM) B lymphocytes but induces apoptosisin the susceptible Epstein- Barr virus genome-negative Burkittlymphoma (BL) cell line Ramos (Ramos-BL). This study investigateswhether phosphatidylinositol-3-kinase (Pl3-kinase), which hasbeen reported to be intimately involved in the regulation ofcellular growth, plays a role in the regulation of these sig-promoted B cell responses, and uses the selective and irreversibleinhibitor of Pl3-kinase activity, wortmannin (Wm). In Ramos-BLB cells, at 8 h post-treatment, Wm triggers a transient increasein apoptosis of 16 ± 6.9% with a concomitant cellularloss of 16 ± 6.1% from the G₁ phase of cell cycle; [³H]thymidineincorporation also decreases by 33 ± 5.0%, from 37,274c.p.m. ± 10% to 25,127 c.p.m. ± 4.0%. Moreover,at 72 h culture, Wm inhibits anti-lgM-induced FM B lymphocytelevels of [³H]thymidine incorporation typically by 47% and triggers80% apoptosis from the G₀G₁ phase of cell cycle. Ramos-BL Bcells exhibit high basal levels of Pl3-kinase activity, as determinedby immunoprecipitation with antibody to the p85 regulatory subunitof Pl3-kinase and ³²P incorporation into phosphatidylinositol,which is not significantly affected by anti-lgM stimulation;by contrast, anti-lgM stimulates significant Pl3-kinase activityover negligible basal levels in FM B lymphocytes. Pre-treatmentwith Wm inhibits Pl3-kinase activity in both cell types. Takentogether these data indicate that in Ramos-BL B cells slgM-triggeredgrowth arrest and apoptosis is Pl3- kinase independent, whereasPl3-kinase activity is critical for slgM-triggered mitogenesisof FM B lymphocytes. Thus Pl3-kinase plays a pivotal role inthe regulation of both normal and neoplastic B lymphocyte progressionthrough the cell cycle, such that if this Pl3-kinase-dependentpathway is inhibited these cells default to apoptosis.     

A case of cystadenocarcinoma of the liver

A case of cystadenocarcinoma of the liver is reported. The patient was a 73-year-old woman in whom a tumor was detected in the lateral segment of the liver during a health examination. Ultrasonograms and computed tomograms showed a multilocular cystic mass. Magnetic resonance imaging (MRI) showed a multilocular lowintensity mass, including a high-intensity portion and a portal branch compressed by the tumor. MRI with gadolinium showed an enhanced cyst wall. The cystic part of the tumor became smaller and the solid part became larger over a 1-month period, indicating that the tumor was malignant. Subsegmentectomy (S₃) was performed and cystadenocarcinoma with cystadenoma was diagnosed by histopathological examination. Identification of changes in the appearance of a tumor should be helpful for the differential diagnosis of cystadenoma and cystadenocarcinoma.