进展期胃癌S-1与5-FU基础化疗有效性和安全性Meta分析

目的 S-1被应用于进展期胃癌一线化疗中,其疗效也备受关注.本研究评估S-1基础化疗对比5-氟尿嘧啶(5-Fluorouracil,5-FU)基础化疗方案在进展期胃癌一线化疗中的有效性和安全性.方法 用“胃癌、替吉奥或S-1、5-氟尿嘧啶和随机对照研究”等检索词,在Pubmed、Embase、Cochrane Library、ASCO会议摘要、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和中文科技期刊全文数据库(VIP)等检索相关的临床随机对照试验,检索时间截止至2016-10.提取总生存期、无疾病进展生存期、有效率、3～4级不良反应等数据.采用Revman 5.3和STATA 12.0进行数据分析.结果 共纳入18个随机对照研究,3 581例患者.结果显示,S-1基础化疗在总生存期(HR=0.92,95％CI为0.84～1.01,P=0.07)及无疾病进展生存期(HR=0.90,95％CI为0.76～1.07,P=0.25)方面与5-FU基础化疗方案差异无统计学意义,但有更高的有效率,RR=1.46,95％CI为1.22～1.74,P＜0.001.S-1基础化疗方案3～4级中性粒细胞减少(P＜0.001)、白细胞减少(P＜0.001)、血小板减少(P=0.01)、口腔炎(P＜0.001)和脱发(P=0.02)等不良反应较5-FU基础化疗发病率更低,差异有统计学意义.结论 相比于5-FU基础化疗,S-1基础化疗在进展期胃癌一线治疗中均是有效且更安全的化疗方案.     

The MDR1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes

The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested several concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S (aphidicolin, cyclosporin A, rapamycin) or G2+M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 ± 6.5%) and S (42.3 ± 8.0%) phases. Cell distribution in G2+M was 12.7 ± 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ≈60–70% and both drugs decreased it to ≈30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ≈70% with a decrease in G1 to ≈30%. Cyclosporin A and rapamycin increased the percentage of the cells in G1 to ≈70% and decreased it to ≈25% in S phase. Nocodazole increased cell distribution in G2+M to ≈60% and induced a decrease in G1 to ≈10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (P-glycoprotein). In contrast, a probe for MRP (P-190) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (cyclosporin A, nocodazole, thymidine) (24 h) did not upregulate its message and cell treatment with -butathione (S,R)-sulfoximine only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the intrinsic multidrug resistance of leukemic Jurkat T cells does not appear to involve the MDR1 and MRP members of the ABC family of reverse drug transporters and these observations raise the possibility of the involvement of multifaceted mechanisms.     

Gli1在鼻咽癌组织中的表达及临床意义

目的:探讨神经胶质瘤相关癌基因1(Gli1)在鼻咽癌组织中的表达及其临床意义.方法:免疫组化方法检测89例鼻咽癌组织及21例正常鼻咽组织中Gli1的表达情况,分析Gli1的表达与与鼻咽癌患者临床病理参数及预后之间的关系.结果:Gli1在鼻咽癌组织的表达水平显著高于正常鼻咽组织(P＜0.01),且Gli1的表达水平与鼻咽癌的T分期、淋巴结转移程度及临床分期显著相关(P＜0.05).此外,Gli1蛋白表达越高,患者的生存时间也明显缩短.结论:Gli1在鼻咽癌组织中呈过表达,可能在鼻咽癌的发生、发展中起重要作用,Gli1有可能成为鼻咽癌治疗的新靶点之一.     

Herbimycin A Suppresses the Reduction of Gap-junctional Intercellular Communication Induced by Tumor-promoting Phorbol Ester in 3T3-L1 Cells

We have examined the suppressive effect of herbimycin A on the reduction of gap-junctional Intercellular communication that is induced by a tumor-promoting phorbol ester in 3T3-L1 cells. Most cells in growth arrest participated in dye-coupling, as evaluated by the transfer between cells of a fluorescent dye (Lucifer Yellow CH). Treatment of cells with 0.25 μg/ml herbimycin A slightly enhanced the dye-coupling. This enhancement required treatment for periods as long as 24 h. Addition of 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid reduction of dye-coupling. However, addition of TPA did not suppress dye-coupling in cells pretreated for more than 24 h with herbimycin A. Pretreatment of cells for less than 6 h with herbimycin A did not suppress the TPA-induced reduction of dye-coupling. These results suggest that herbimycin A suppresses the reduction of gap-junctional intercellular communication that is induced by TPA through enhancement of the ability of the cells to participate in gap-junctional intercellular communication     

The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

垂体腺瘤nm23-H_1基因表达的临床意义

目的明确nm23-H_1基因在垂体腺瘤中的表达及其临床意义。方法采用免疫组织化学染色（SP）法对62例垂体腺瘤nm23-H_1基因表达进行回顾性研究。结果侵袭型垂体腺瘤nm-H_1基因表达水平显著低于非侵袭型（P＜0.01）;Ⅲ、Ⅳ级垂体腺癌nm23-H_1基因表达水平显著低于Ⅰ、Ⅱ级（P＜0.05）;nm23-H_1基因表达水平下降与垂体腺瘤患者的性别、年龄及肿瘤分泌功能无显著相关性（P＞0.05）。结论nm23-H_1基因可能在会作腺瘤的侵袭过程中起重要作用,其表达改变是反映垂体腺癌侵袭性的敏感指标。     

扶桑花抗生育成分对早孕小鼠黄体影响的定量研究

本文处用图像分析仪 ,以核浆比和数密度为指标 ,研究了不同浓度的扶桑花提取物—HR 1对早孕小鼠黄本组织学的影响。结果表明 :(1)小鼠黄体细胞的核浆比和数密度 ,随给药剂量 (0、 4、 10、 10 0、10 0 0mg/kg/d)的增加而增加 ,其中 10 0和 10 0 0mg/kg/d两组的黄体细胞核浆比和数密度明显高于对照组(p <0 .0 5) ;(2 )黄体组织学的定性观察显示 ,给药各组的黄体细胞明显退化 ,细胞缩小 ,细胞界限不清。这些结果提示 ,扶桑花提取物的抗早孕作用与妊娠黄体受损有关。     

大鼠肺鳞癌发生发展过程中肿瘤血管生成及血液供应研究

目的　探讨肺癌发生发展过程中肿瘤血管生成和血液供应 ,以及血管内皮细胞生长因子(VEGF)及其受体Flk 1与肿瘤血管生成的关系。方法　 10 0只Wistar大鼠左肺下叶支气管灌注致癌质碘油 ,分批处死获取肺鳞癌癌变及进展期病变标本 ,使用油画颜料染成黄、绿两种颜色的液态硅橡胶分别灌注支气管动脉与肺动脉 ,免疫组化检测病变组织中VEGF、Flk 1的表达及vWF染色切片上的微血管密度 (MVD)。结果　经支气管动脉灌注黄色液态硅橡胶显示 ,肿瘤病灶呈黄色的新生血管团与曲张的支气管动脉相连通 ,镜下见癌巢间质肿瘤微血管腔充盈硅橡胶颗粒 ;经肺动脉灌注绿色液态硅橡胶 ,肿瘤区绿色的血管呈不连续的枯树枝、断枝、残枝状 ,与肿瘤血管不连续 ,镜下肿瘤微血管腔无硅橡胶颗粒。原位癌的MVD计数 ( 3 9.5 0± 12 .60 )与不典型增生 ( 8.92± 3 .80 )及侵袭癌 ( 61.0 5± 19.92 )比较 ,差异均有显著性 (P <0 .0 1)。从支气管粘膜上皮增生→鳞状化生→不典型增生→原位癌→侵袭癌 ,VEGF和Flk 1阳性系数逐渐升高。MVD与VEGF和Flk 1表达均呈正相关 (r分别为 0 .9798和 0 .90 78,P <0 .0 0 5 )。结论　肺癌新生血管形成是大鼠肺鳞癌发生发展的重要现象 ,新生的肿瘤血管与支气管动脉相连通 ,与肺动脉不相连通 ,证明肺鳞癌发生     

红外热成像技术辅助腓动脉穿支皮瓣修复口腔颌面部缺损的应用研究

目的探讨红外热成像（infrared thermography，IRT）技术辅助腓动脉穿支皮瓣在修复口腔颌面部缺损中的应用价值。方法回顾分析2020年10月—2021年12月行腓动脉穿支皮瓣修复的20例口腔颌面部恶性肿瘤患者临床资料。男13例，女7例；年龄32～76岁，平均56.5岁。舌癌8例、腮腺癌5例、颊癌4例、下颌牙龈癌3例；鳞状细胞癌12例，腺样囊性癌3例，黏液表皮样癌5例。术前常规行彩色多普勒超声（color Doppler ultrasound，CDU）和IRT技术对腓动脉穿支进行定位并辅助设计皮瓣，与术中实际探查情况比较，分析CDU、IRT技术检查的灵敏度、特异度、阳性预测值和阴性预测值；比较CDU和IRT技术检测穿支数目及最具活力穿支点的准确性。术后定期随访，观察患者供受区恢复情况、并发症发生及肿瘤复发转移情况等。结果与术中探查结果比较显示，术前IRT技术检查腓动脉穿支的灵敏度、特异度、阳性预测值和阴性预测值分别为72.22%、50.00%、92.86%、16.67%，均高于CDU检查结果（分别为64.17%、33.33%、84.62%、14.29%）。术前CDU检查共发现腓动脉穿支45支，术中探查证实35支，准确率77.8%；IRT技术检查共发现43个“热点”，术中证实“热点”范围内腓动脉穿支32支，准确率74.4%；两者比较差异无统计学意义（χ²=0.096，P=0.757）。CDU和IRT技术检查发现的最具活力穿支点的准确率分别为80.95%（17/21）和94.74%（18/19），两者比较差异无统计学意义（χ²=0.115，P=0.734）。CDU与IRT技术的穿支定位误差分别为（5.12±2.10）、（4.23±1.87）mm，两者比较差异无统计学意义（t=1.416，P=0.165）。20例穿支皮瓣均成活，供、受区切口均Ⅰ期愈合。所有患者均获随访，随访时间5～18个月，平均11个月。皮瓣质地柔软、血运良好；下肢瘢痕隐蔽，功能良好。无下肢肿胀、疼痛、麻木、踝关节不稳定等并发症发生，随访过程中未见肿瘤复发和转移。 结论与CDU比较，采用IRT技术辅助腓动脉穿支皮瓣术前设计修复口腔颌面部缺损具有较高的临床应用价值。     

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5

The abnormal expression of long noncoding RNAs (lncRNAs) is frequently observed in gastric cancer (GC) and considered an important driving force in GC progression. However, little is known regarding the involvement of TMEM147-AS1 in GC. Therefore, we examined TMEM147-AS1 expression in GC and determined its prognostic value. In addition, TMEM147-AS1 expression was depleted to identify the functional changes in response to TMEM147-AS1 deficiency. Using the cancer genome atlas dataset and our own cohort, we identified a strong expression of TMEM147-AS1 in GC. Increased TMEM147-AS1 levels in GC showed a significant association with poor prognosis. TMEM147-AS1 interference resulted in the inhibition of GC cell proliferation, colony-forming, migration, and invasion in vitro. Additionally, depletion of TMEM147-AS1 restricted the growth of GC cells in vivo. Mechanistically, TMEM147-AS1 functioned as a microRNA-326 (miR-326) sponge. Furthermore, SMAD family member 5 (SMAD5) was experimentally validated as the functional effector of miR-326. TMEM147-AS1 was demonstrated to sequester miR-326 away from SMAD5; consequently, knocking down TMEM147-AS1 downregulated SMAD5 levels in GC cells. The functional suppression of miR-326 or reintroduction of SMAD5 effectively reversed the attenuated behavior of GC cells caused by TMEM147-AS1 downregulation. In summary, TMEM147-AS1 exhibits tumorigenic activities in GC, which is likely the result of an altered miR-326/SMAD5 axis. Therefore, targeting TMEM147-AS1/miR-326/SMAD5 may represent a target for the treatment of GC.