高低剂量醛红叶酸合并氟脲嘧啶治疗晚期胃肠道癌

 本文观察了国产酸氢叶酸(CF)两种不同剂量(20mg/M²和200mg/M²)合并5-Fu静脉持续120小时滴注治疗晚期胃肠道癌52例的疗效.认为采用低剂量国产CF合并5-Fu联合化疗方案在临床上更合适,安全经济,有一定推广价值.     

硒酵母和亚硒酸钠对大鼠诱发性肺癌抑制作用的初步观察

 流行病学资料早已提示硒与癌的发病率呈负相关^[1]。近几年来的许多实验研究也证明硒对化学致癌质诱发性皮肤癌^[2]、肝癌^[3、4]、结肠癌^[5、6]、乳腺癌^[7、8]以及病毒诱发性小鼠乳腺癌^[9、10]有抑制作用。     

早期乳腺癌的围手术辅助化疗

 1977～1980年,我院采用Cu联合化疗辅助手术治疗病检腋淋巴结阴性T₁N₀M₀和T₂N₀M₀早期乳腺癌42例,并以同期相同病例49例做对照。用药组5年治愈率100%,对照组85.7%（P<0.05）,10年两组分别为92.2%及81.6%（P>0.05）,当T₁N₀M₀时,两组预后相似,T₂N₀M₀时,5年健在率分别为100%及82.8%（P<0.05）,10年为95.7%及75.9%（P<0.05）,指出固手术辅助化疗能改善早期乳腺癌,特别是T₂N₀M₀的预后。     

CXCR4和CXCL12及PTEN在乳腺癌中的表达及临床意义

 目的  分析乳腺癌、乳腺纤维腺瘤及癌旁正常乳腺组织中趋化因子受体4（CXCR4）、趋化因子12（CXCL12）与人第10号染色体缺失的磷酸酶及张力蛋白同源的基因（PTEN）的表达及临床意义。方法  采用免疫组化技术SABC法检测60例乳腺癌组织标本CXCR4、CXCL12、PTEN的表达情况,分析乳腺癌中CXCR4、CXCL12及PTEN表达与年龄、肿瘤大小、组织学分级、TNM分期、淋巴结转移、雌激素受体（ER）、人类表皮生长因子2（Her-2）及脉管侵犯的关系。另取20例乳腺纤维腺瘤及20例癌旁正常乳腺组织作为对照组。结果  免疫组化结果显示,CXCR4（χ²=48.750,P=0.000）、CXCL12（χ²=47.611,P=0.000）及PTEN（χ²=19.994,P=0.000）在乳腺癌、乳腺纤维腺瘤与癌旁正常组织中的表达差异均具有统计学意义,其中CXCR4、CXCL12阳性表达与乳腺癌的组织学分级（χ²=11.080,P=0.004;χ²=6.978,P=0.031）、TNM分期（χ²=9.819,P=0.007;χ²=10.163,P=0.006）、淋巴结转移（χ²=6.213,P=0.013;χ²=8.031,P=0.005）、ER（χ²=12.774,P=0.000;χ²=7.330,P=0.007）、脉管侵犯（χ²=5.860,P=0.013;χ²=5.185,P=0.020）及Her-2（χ²=5.487,P=0.019;χ²=4.689,P=0.030）相关;PTEN在乳腺癌组织中的表达与TNM分期（χ²=7.366,P=0.025）、淋巴结转移（χ²=5.511,P=0.019）及ER（χ²=4.077,P=0.043）状态相关。CXCR4与CXCL12在乳腺癌中的表达呈正相关（r =0.336,P=0.004）;CXCR4与PTEN、CXCL12与PTEN在乳腺癌中的表达呈负相关（r =-0.362,P=0.004;r =-0.360,P=0.004）。结论  趋化因子CXCL12及其受体CXCR4的高表达及PTEN的低表达与乳腺癌的发生和转移有关,可能在促进乳腺癌的生长和发展中起重要作用。     

抗肿瘤新药甘磷酰芥临床观察

 甘磷酰芥(M₂₅、6202)是由中国医学科学院药物研究所合成的一种抗肿瘤新药,对实验性动物肿瘤具有明显的抑制作用。我科自1977年2月～1978年12月共试用 M₂₅治疗恶性肿瘤36例。其中资料完整,可供分析者28例。现将临床观察情况总结如下。     

Treatment of the T98G glioblastoma cell line with antisense oligonucleotides directed toward mRNA encoding transforming growth factor-α and the epidermal growth factor receptor

Antisense oligonucleotides (oligos) complementary to mRNA encoding transforming growth factor-α (TGF-α) and its target, the epidermal growth factor receptor (EGFR), are efficacious against human prostate and breast cancers carried in athymic nude mice. Glioblastomas, also regulated by EGFR expression, would appear to be similarly susceptible, and we now employ them against the T98G tumor model. T98G cells were distributed into wells and allowed to adhere prior to addition of oligos (12.5 μM) directed against TGF-α and/or EGFR for 6 d of treatment before thymidine radiolabeling. Supplemental media and oligos (25 μM final concentration) were added after d 3. Statistically significant inhibition by oligos directed against TGF-α, EGFR, and their combination was 13.8%, 26.3%, and 18.1%, respectively. In a subsequent experiment cells were incubated with increasing amounts of each oligo and their combination for 3 d prior to radiolabeling. Statistically significant inhibition of growth for either oligo at every concentration was found. Cells incubated with 6.25, 12.5, 25, and 50 μM antisense directed against TGF-α had a mean inhibition of 29.3%, 33.3%, 21.7%, and 46.6%, respectively. Cells similarly treated with oligos against EGFR had a mean inhibition of 77.9%, 80.3%, 82.0%, and 83.7%, respectively, and cells incubated with 6.25, 12.5, 25 and 50 μM of each oligo had a mean inhibition of 74.7%, 70.6%, 70.8%, and 76.3%, respectively. Lastly, in a paired experiment, cells treated with 0, 0.39, 0.78, 1.56, 3.125, and 6.25 μM of oligos, either specifically directed against EGFR or a random control, for 3 d were evaluated for both thymidine incorporation and EGFR expression. Statistically significant inhibition of ³H-thymidine incorporation was seen in cells with the oligo specifically directed against EGFR at 3.125 μM and 6.25 μM when compared to non-oligo containing controls. This was accompanied by a comparable significantly decreased expression of a low-MW reactive derivative of EGFR at 3.125 μM and 6.25 μM in Western blots, and of a high-MW reactive EGFR at 6.25 μM. The significant effect against high-MW EGFR was observed vs both the non-oligo containing control and the random sequence. Oligo concentrations between 0.78 and 1.5 μM also resulted in decreased expression of the low-MW form, but not significant differences in thymidine radiolabeling. In recovery experiments, cells treated initially with greater oligo concentrations required significantly increased time to recover, particularly in cells treated with EGFR directed oligos. Intracellular uptake and nuclear localization was demonstrated with FITC tagged oligos. In summary, even at relatively low oligo concentrations and short exposure, oligos against TGF-α, and particularly EGFR, significantly inhibit in vitro growth of the T98G glioblastoma, possibly mediated by decreased EGFR expression.     

38例乳腺癌组织中酸性同功铁蛋白与P53蛋白免疫组化的检测分析

 目的:为了探讨酸性同功铁蛋白在乳腺癌组织中的表达水平及其与P⁵³表达的关系,明确酸性同功铁蛋白作为乳腺癌诊断指标的意义。方法:采用抗人胎盘酸性同功铁蛋白单克隆抗体和免疫组化方法(LSAB法)对38例乳腺癌和30例乳腺腺病组织进行了检测。结果:73.7%(28/38例)的乳腺癌和67%(2/30例)的乳腺腺病患者AIF呈阳性表达,阳性细胞胞浆着色明显,阳性细胞主要是癌细胞和增生的导管上皮细胞；44.7%(17/38例)的乳腺癌和33%(1/30例)的乳腺腺病组织P⁵³呈阳性表达,阳性着色位于核内,阳性细胞为癌细胞和非典型增生的导管上皮细胞;P⁵³表达与AIF表达符合率为60.5%,二者有一定的相关性(0.05     

Enhanced retention of cytosine arabinoside and its metabolites and synergistic cytotoxicity by sequential treatment with dipyridamole in L5178Y leukemia

Summary Sequential treatment of murine leukemia L5178Y with cytosine arabinoside (ara-C) followed by dipyridamole (DP) resulted in synergistic cytotoxicity. Viability of cells exposed to 1 μM ara-C for 4 h was 88% of control values, but if DP was included in the cloning medium, cell viability was reduced to only 30%. When cells exposed to 1 μM ara-C were resuspended in ara-C-free medium containing 10 μM DP, intracellular ara-C and its metabolites were retained for a significantly longer period than when cells were resuspended in drug-free medium. At 4 h after resuspension in ara-C-free medium, total intracellular [³H] was 1.9 pmol/10⁶ cells in control cells but amounted to 6.2 pmol/10⁶ cells in DP-treated cells. Unchanged ara-C was 5.5-fold higher in the DP-treated cells. Presumably because of its effect on the concentration of intracellular ara-C, DP increased the half-life for ara-CTP from 97 to 250 min. Ara-CDP-choline declined with a half-life of 76 min on the transfer of cells to control medium, but levels of this metabolite remained constant or increased slightly in cells transferred to medium containing DP. After 4 h in ara-C-free medium with DP, [³H]-ara-C incorporated into the acid-insoluble fraction was 140% of the level attained when cells were transferred to control medium. The increased levels of ara-C metabolites presumably represent the basis for the enhancement of ara-C cytotoxicity by sequential DP treatment. This research was supported by grant CH-35H from the American Cancer Society and grant CA12197 from the National Institutes of Health     

香菇多糖对肺癌患者免疫功能的调节作用

 应用香菇多糖治疗化疗后休疗期肺癌患者30例，观察治疗前后细胞免疫和体液免疫变化，结果显示治疗前后各项体液免疫指标均无明显改变。NK细胞，CD₃⁺细胞，CD₄⁺细胞的百分率显著增加（P＜0．05），淋巴细胞转化率增加，CD₈⁺细胞百分率下降，CD₄⁺/CD₈⁺细胞比值上升。提示香菇多糖对肺癌患者免疫功能有正向调节作用。     

131铯扫描鉴别甲状腺单个结节良恶性的临床价值

 自从¹³¹碘和⁹⁹m锝应用于临床以来,甲状腺扫描已成为诊断甲状腺肿物的常规方法之一,其临床价值已得到充分肯定。但用¹³¹碘(或^99m锝)示踪作甲状腺扫描主要反映甲状腺结节的位置、大小、功能状态和形态上的异常,对良恶性病变的鉴别有一定限度。实践证明,¹³¹碘(或⁹⁹m锝)扫描为冷结节则提示有癌变的可能,国外文献报道认为单个冷结节癌变的发生率为15%-58%。     

鼻咽癌细菌L型、EB病毒感染的检测及与P21、P53基因突变的关系

 用免疫组化染色和革兰染色等技术,对129例鼻咽癌、20例鼻咽粘膜慢性支进行细菌L型、EB病毒检测,同时对L型阳性、EBV阳性和L型阴性、EBV阴性组织的P ²¹、P⁵³表达进行对比分析.结果显示,鼻咽癌组的L型检出率为69.8%;EBV检出率为27.1%,两者有显著性差异(P<0.05).鼻咽癌组的P²¹、P⁵³阳性表达率显著高于慢性炎组(P＜O.005).L型阳性、EBV阳性伴P²¹、P⁵³阳性的表达率也分别高于L型阴性、EBV阴性伴P²¹、P⁵³阳性的表达率.表明L型、EBV感染与鼻咽癌关系密切;P²¹、P⁵³过度表达与鼻咽癌的发生也有关.此外,L型和EBV感染与P²¹、P⁵³的过度表达存在着相关性.提示,L型和EBV参与了P²¹、P⁵³基因突变,并在鼻咽癌的发生中可能起协同作用.     

Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo

Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity. Inhibition of farnesyltransferase (IC₅₀ 80 μM) and geranylgeranyltransferase I (IC₅₀ 17 μM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine. Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean±SD IC₅₀ 289±328 μM (range 38–985 μM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner. In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls. Single doses up to 25 mg/kg were well tolerated. The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo.     

Rituximab alone was effective for the treatment of a diffuse large B-cell lymphoma associated with hemophagocytic syndrome

We report here the case of a 63-year-old man who had a diffuse large B-cell lymphoma associated with hemophagocytic syndrome (HPS). The lymphoma involved the spleen, bilateral adrenal glands, and paraaortic lymph nodes of the abdomen. In both the bone marrow and lymph nodes, hemophagocytosis was evident, and the laboratory findings were consistent with HPS. The lymphoma cells showed a CD4⁺, CD5⁺, CD10⁻, CD19⁺, CD20⁺, CD25⁺ and surface immunoglobulin μα/κ⁺ immunophenotype. The patient was unintentionally treated with rituximab alone, resulting in complete resolution of the lymphomatous lesions as well as the features of HPS in response to the initial two doses of rituximab, although he developed gastric hemorrhage requiring vigorous resuscitation. After the completion of eight doses of rituximab, the patient remains free of disease with an excellent performance status.     

P53、P16蛋白在卵巢上皮癌中的表达

 目的:探索抑癌基因P⁵³、P¹⁶表达与卵巢上皮癌发生的关系。方法:采用免疫组化SP法对27例卵巢上皮癌组织中P⁵³蛋白,P¹⁶蛋白进行检测。结果:卵巢上皮癌P⁵³蛋白阳性表达率为44.44%。P¹⁶蛋白在卵巢上皮癌中表达阳性率为18.52%,P⁵³及P¹⁶表达与病理类型无关。P⁵³蛋白过度表达与临床分期无关。P¹⁶晚期表达阳性率明显减少(P<0.05)。结论:P⁵³、P¹⁶基因表达的改变在卵巢上皮癌发生中起重要的作用。     

直肠癌P21、P53基因表达及其临床意义

 目的: 研究P²¹、P⁵³基因在直肠癌组织中的表达情况与直肠癌病理特征的关系及其在预后判定方面的意义。方法: 采用SP免疫组化法对110例手术后石蜡包埋标本行P²¹、P⁵³基因表达检测, 同时选用正常组织为实验对照。结果: 直肠癌组织P²¹、P⁵³基因表达阳性率分别为54.5 %、42.7 %;P53组织表达情况与临床病理因素无相关性; P²¹表达阳性病例3 、5年生存率降低, 组 织分化差, 淋巴转移率增高(P<0.05 %)。结论: P⁵³基因与直肠癌形成密切相关, 与直肠癌预后未见相关性。P²¹基因表达情况可能成为直肠癌的预后指标。     

特异性抗膀胱癌单克隆抗体对膀胱肿瘤的临床研究

 采用一组特异性抗膀胱癌单克隆抗体MAb（T₁₆、M₃₄₄、T₁₃₈、T₄₃），以APAAP免疫细胞化学方法，对63例膀胱移行细胞癌及10例非肿瘤患者的膀胱冲洗液作了研究。T₁₆在全部63份标本呈阳性。随着肿瘤分期、分级的升高，M₃₄₄阳性率逐渐降低，T₁₃₈及T₄₃阳性率逐渐升高。此三种MAb与肿瘤复发也有一定的对应关系。尿细胞学与MAb联合应用，可弥补相互间的不足，使肿瘤检出率进一步提高。结果表明：M₃₄₄、T₁₃₈及T₄₃MAb的阳性表达与肿瘤的分期、分级及预后密切相关，可作为膀胱肿瘤恶性程度、复发及早期诊断的估价指标。     

小儿非何杰金淋巴瘤P53基因突变与预后的研究

 目的: 探讨小儿非何杰金淋巴瘤(NHL)P⁵³基因突变与预后的关系。方法: 31例颈部与腹部Ⅱ、Ⅲ期NHL 患儿, 应用PCR-SSCP技术检测石腊标本中P⁵³基因第5-6外显因子, 并对31例患者进行了近8年的随访。结果: 31例中11例存在着P⁵³基因突变, 此11例中有7例复发。而无P⁵³基因突变20例中仅1例复发。结论: 说明小儿NHL中P⁵³基因突变是不良预后的指标, 与早期复发有关。     

癌基因(Oncogenes)

 1682年曾被称为“癌基因之年”^[1]。其后,有关癌基因的研究一直异常活跃,成果亦多,择其要者有:ras 等癌基因结构与组织的阐明^[2-6];c-onc 假基因的发现^[7、8];人基因组中c-onc 的定位^[9];c-onc 与肿瘤染色体畸变的关系——“转位激活”机制的进一步确定^[10-13];“突变激活”机制的再次肯定及其与化学致癌的联系的初步证据^[14-18];c-ras “不同突变位点与不同突变方式”激活的证明^[9-20];c-onc 不同阅读框架及其转录本不同剪接方式的研究^{[8、21、22]};sis等癌基因产物结构和功能的初步鉴定^[23-33];正常细胞癌变至少需要两个不同痛某因协同作用模式的提出^[34-37];等等.     

转染P53基因对胶质瘤细胞株SHG44裸鼠致癌性的作用研究

 目的:探讨转染野生型P⁵³(wt-P⁵³)和突变型P⁵³(mtP⁵³)基因,对人胶质瘤细胞株SHG44裸鼠致瘤性的影响及意义.方法:采用质脂体介导法,分别将wt-P⁵³和mt-P⁵³基因导入人胶质瘤细胞株SHG44,体内外检测转导细胞的生长状况和裸鼠致瘤性.结果:转染mt-P⁵³基因的细胞株,G418筛选细胞集落数、软琼脂平皿细胞集落数以及裸鼠瘤组织重量和体积,均显著高于对照组(P <0.01);而转染Wt-P⁵³ 基因的细胞株均显著低于对照组(P<0.01),表明导入wt-P⁵³基因的细胞株,瘤细胞生长速度明显低于对照细胞株和导入.mt-P53基因的细胞株,即导入mt-P⁵³基因的细胞株瘤细胞生长速度最快,而导入Wt-P⁵³基因的细胞株瘤细胞生长速度最慢.结论:Wt-P⁵³基因能有效地抑制人胶质瘤细胞生长;mt-P⁵³基因则可以明显地促进瘤细胞生长.     

PCR-SSCP法检测宫颈癌P53基因突变

 目的：探讨抑癌基因P⁵³突变与宫颈癌发生发展之间的关系,并为该病的临床检测提供一种分子生物学方法。方法：应用多聚酶链反应－单链构象多态性（PCR SSCP）分析方法对宫颈癌及慢性宫颈炎组织中P⁵³基因5～6外显子的突变进行了检测。结果：35例宫颈癌组织中有2例出现突变,突变率为5.71%;而作为对照的慢性宫颈炎组织中无一例出现突变。结论：宫颈癌的发生与抑癌基因P⁵³5～6外显子的突变有关;此方法可有效地检测抑癌基因P⁵³的突变。