Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Transduction of Fas gene or Bcl-2 antisense RNA sensitizes cultured drug resistant gastric cancer cells to chemotherapeutic drugs

AIM To compare the expression level of Fas gene and Bcl-2 gene in gastric cancer cells SGC7901 and gastric cancer MDR (multidrug resistant) cells SGC7901/VCR, to transduce Fas cDNA and Bcl-2 antisense nucleic acid into SGC7901/VCR cells respectively, and to observe the expression of two genes in transfectants and non-transfectants as well as their drug sensitivity.METHODS Eukaryotic expression vector pBK-Fas cDNA and pDOR-anti Bcl-2 were constructed and transfected into SGC7901/VCR cells by lipofectamine, respectively. Northern blot and Western blot were used to detect the expression of mRNA and protein in SGC7901/VCR and SGC7901 cells and transfectants, and drug sensitivity of transfectants for VCR, CDDP and 5-FU was analyzed with MTT assay.RESULTS After gene transfection, 80 for Fas and 120 for antisense Bcl-2 drug-resistant clones were selected from 2×105 cells, transfection rate being 0.04% and 0.06%. Two clones of SGC7901 Fas/VCR cells and SGC7901 anti Bcl-2/VCR cells were randomly selected for further incubation. Hybridization results showed that the expression level of Fas mRNA and protein in SGC7901/VCR cells was much lower, but that of Bcl-2 mRNA and protein was higher than that in SGC7901 cells. The expression of Fas mRNA and protein in SGC7901 Fas/VCR cells was higher, and of Bcl-2 mRNA and protein was lower in SGC7901 anti Bcl-2/VCR cells than that in non-transfectants. MTT assay showed that transfectants were more sensitive to VCR, CDDP, 5-FU than non-transfectants.CONCLUSION Bcl-2 gene displayed high expression while Fas gene had low expression in drug resistant gastric cancer cells. Expression of Bcl-2 protein was effectively blocked in SGC7901 anti Bcl-2/VCR cells by gene transfection. In contrast, the expression of Fas mRNA and protein in SGC7901 Fas/VCR cells increased. Fas gene and Bcl-2 antisense nucleic acid transfection sensitized drug resistant gastric cancer cells to chemotherapeutic drugs. These results suggest cell apoptosis plays an important role in the mechanism of MDR, and enhancing apoptosis might reverse MDR.

胃癌治疗的新靶点:铁死亡

胃癌是我国人口死亡的主要原因之一,近年来确诊为早期胃癌的患者数量逐年上升,然而肿瘤细胞耐药性的产生严重限制了手术和化学治疗的效果,极有必要探索胃癌治疗的新靶点。铁死亡是一种铁依赖性细胞程序性死亡方式,其显著特征是细胞内脂质过氧化。胃癌细胞对细胞内铁代谢水平非常敏感,铁死亡在胃癌的发生、进展、治疗及耐药机制中发挥着至关重要的作用。胃癌细胞内铁死亡相关基因和非编码RNA与胃癌转移、耐药和预后密切相关,近年来关于铁死亡对胃癌细胞增殖的调节作用研究已获得一定的进展,因此,靶向铁死亡可能是胃癌的有效治疗策略。本文通过阐述铁死亡在胃癌细胞增殖、侵袭、转移及耐药机制中的作用,总结与铁死亡相关的靶点基因,并对靶向调节铁死亡在胃癌治疗中的前景进行展望。

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients

AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG0/G1 tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.

Suppression of P-gp induced multiple drug resistance in a drug resistant gastric cancer cell line by overexpression of Fas

AIM To observe the drug sensitizing effect andrelated mechanisms of fas gene transduction onhuman drug-resistant gastric cancer cellSGC7901/VCR(resistant to Vincristine).METHODS The cell cycle alteration wasobserved by FACS.The sensitivity of gastriccancer cells to apoptosis was determined by invitro apoptosis assay.The drug sensitization ofcells to several anti-tumor drugs was observedby MTT assay.Immunochemical method wasused to show expression of P-gp and Topo Ⅱ ingastric cancer cells.RESULTS Comparing to SGC7901 and pBK-SGC7901/VCR,fas-SGC7901/VCR showeddecreasing G2 cells and increasing S cells,theG2 phase fraction of pBK-SGC7901/VCR wasabout 3.0 times that of fas-SGC7901/VCR,but Sphase fraction of fas-SGC7901/VCR was about1.9 times that of pBK-SGC7901/VCR,indicatingS phase arrest of fas-SGC7901/VCR.FACS alsosuggested apoptosis of fas-SGC7901/VCR,fas-SGC7901/VCR was more sensitive to apoptosisinducing agent VM-26 than pBK-SGC7901/VCR.MTT assay showed increased sensitization offas-SGC7901/VCR to DDP,MMC and 5-FU,butsame sensitization to VCR according to pBK-SGC7901/VCR.SGC7901,pBK-SGC7901/ VCRand fas-SGC7901/VCR had positively stainedTopo Ⅱ equally.P-gp staining in pBK- SGC7901/VCR was stronger than in SG07901,but there was little staining of P-gp in fas.SGC7901/VCR.CONCLUSION fas gene transduction couldreverse the MDR of human drug-resistant gastriccancer cell SGC7901/VCR to a degree,possiblybecause of higher sensitization to apoptosis anddecreased expression of P-gp.

Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Effects of San Qi on Gastric Secretion and Protective Factors of Gastric Mucosa in the Rat with Precancerous Lesion of Stomach

In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.The results indicated that gastric secretion,gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly,and malondialdehyde (MDA) increased significantly (P<0.01) in the model group as compared with the normal group;after treatment with San Qi Powder for 12 weeks,both gastric secresion and GMBF increased,and MDA content decreased as compared with the negative control group (P<0.01),with no significant increase of aminohexose content.It is suggested that San Qi (三七 Radix Notoginseng) may improve gastric secretion,and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.

Point injection of Injectio Radici Astragali for Treatment of Post-chemotherapy Adverse Reactions

With injection of Injectio Radici Astragli into the point Zusanli (ST 36), we have obtained quite satisfactory therapeutic results for treating leukopenia and the impairment in immune functions occurred in cancer chemotherapy. A report follows.

Treatment of Interstitial Peumopathy by Fei Tong Oral Liquid in the Malignant Tumor Patients after Radio-and/or Chemotherapy

Fei Tong Kou Fu Ye (肺通口服液 Fei Tong Oral Liquid) was used to treat 30 cases of interstitial pneumopathy after radio- and/or chemotherapy.In comparison with the control group (15 cases) treated with hormones,the therapeutic effects in improving dyspnea,cough,respiratory rate,cyanosis,findings in X-films and CT examination,partial pressure of oxygen in artery,FVC and VC were found significantly better (P<0.05).The total effective rate obtained was 83.33%.

THE EFFECTS OF CHINESE DRUGS FOR SUPPORTING HEALTHY ENERGY AND REMOVING BLOOD STASIS ON POSTOPERATIVE METASTASIS OF GASTRIC CARCINOMA AND ORNITHINE DECARBOXYLASE

32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in the control group treated by western medicine. After 6 months of treatment, in the TCM group, the rate of metastatic recurrence was significantly reduced, and the level of ornithine decarboxylase was also markedly lowered. Therefore, it is considered that the action of anti-metastatic recurrence of TCM drugs in postoperative cases of gastric carcinoma is probably related to the lowered activity of ornithine decarboxylase.

PDE1B表达与胃癌预后和肿瘤微环境的生物信息学分析

目的:通过生物信息学方法筛选胃癌中具有差异预后意义的调节性细胞死亡和衰老基因,分析磷酸二酯酶1(PDE1)B对胃癌患者生存预后的影响。方法:自TCGA公共数据库下载胃癌基因表达数据和临床数据,本地数据库中随机抽取50例胃癌患者,收集其临床信息和石蜡样本,包括胃癌组织和癌旁正常组织。采用R软件“limma”程序包筛选差异表达基因(DEGs),单因素COX分析和Kaplan-Meier生存分析筛选有预测生存价值的DEGs,获取影响胃癌患者生存预后的交集基因,筛选与临床病理特征最具关联的基因PDE1B。TCGA数据库和Kaplan-Meier生存分析检测胃癌患者癌旁正常组织和胃癌组织中PDE1B mRNA表达水平及其与胃癌患者生存期的关系,采用基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)信号通路富集分析PDE1B生物学功能,CIBERSORT算法、肿瘤免疫数据库(TISIDB)和GSCA在线网站分析PDE1B与肿瘤微环境、免疫特征分子和药物敏感性的相关性。实时荧光定量PCR(RT-qPCR)法检测胃癌患者胃癌组织和癌旁正常组织中PDE1B mRNA表达水平。结果:共筛选716个DEGs,其中505个DEGs表达上调(P<0.05),211个DEGs表达下调(P<0.05),获得10个影响生存预后的交集基因,PDE1B mRNA表达水平与胃癌患者临床病理特征关系最为密切,其与年龄、肿瘤分级、肿瘤分期和肿瘤T、N及M期有关联(P<0.05);与G1-G2、StageⅠ、T1-T2、N0和M0期胃癌患者比较,G3-G4、StageⅡ-Ⅳ、T3-T4、N1-N3和M1分期胃癌患者胃癌组织中PDE1B mRNA表达水平均明显升高(P<0.05)。与癌旁正常组织比较,胃癌患者胃癌组织中PDE1B mRNA表达水平明显降低(P<0.05);与PDE1B低表达胃癌患者比较,PDE1B高表达胃癌患者总体生存率明显降低(P<0.01)。PDE1B表达、年龄和肿瘤分期是胃癌患者预后的危险因素(P<0.05)。在调整了性别、年龄、肿瘤分级和肿瘤分期后,PDE1B表达是影响胃癌患者预后的独立危险因素(P<0.05)。PDE1B主要富集于免疫球蛋白产生、钙离子转运、第二信使介导的信号转导等生物过程(BP),T淋巴细胞受体复合体、细胞膜信号受体复合体和含胶原蛋白的细胞外基质等细胞成分(CC),抗原结合、糖胺聚糖结合和细胞外基质结构成分等分子功能(MF);PDE1B主要参与了神经活性配体-受体相互作用、钙信号通路、环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)信号通路及细胞因子-细胞因子受体的相互作用等途径。PDE1B与调节性T淋巴细胞(r=0.488)、髓源性抑制细胞(r=0.474)和巨噬细胞(r=0.617)呈正相关关系(P<0.01);与PDE1B低表达胃癌患者比较,PDE1B高表达胃癌患者促进肿瘤的调节性T淋巴细胞、单核细胞和M2型巨噬细胞浸润均明显增加(P<0.05)。PDE1B mRNA表达水平与免疫抑制剂转化生长因子β(TGF-β)1(r=0.535)、集落刺激因子1受体(CSF1R)(r=0.519)、免疫激活剂外核苷三磷酸二磷酸水解酶1(ENTPD1)(r=0.593)和CXC趋化因子配体12(CXCL12)(r=0.646)呈正相关关系(P<0.01)。PDE1B高表达的胃癌组织对氟尿嘧啶(-0.3<r<-0.1)、甲氨蝶呤(-0.3<r<-0.1)和地西他滨(-0.3<r<-0.1)等药物较为敏感(P<0.05)。与癌旁正常组织比较,胃癌患者胃癌组织中PDE1B mRNA表达水平明显降低(P<0.01);与PDE1B低表达胃癌患者比较,PDE1B高表达胃癌患者总体生存率明显降低(P<0.05);与T1-T2期胃癌患者比较,肿瘤T3-T4期胃癌患者胃癌组织中PDE1B mRNA表达水平明显升高(P<0.01)。结论:PDE1B是胃癌患者预后的独立危险因素,可作为胃癌预后不良的有效指标。

GLI1表达与肿瘤免疫浸润及胃癌临床预后的关系

目的:探讨胃癌中胶质瘤相关癌基因1(GLI1)的表达与免疫浸润相关性,及其与临床预后的相关性。研究GLI1的表达对胃癌化疗药物耐药性的影响。方法:运用TCGA数据库分析GLI1在胃癌和正常组织中的表达差异,分析胃癌患者临床特征和GLI1基因表达水平对患者预后的影响;分析胃癌组织中GLI1基因表达与肿瘤免疫细胞浸润的相关性,探究其对化疗药物及靶向药物耐药性的影响。收集临床标本,分析GLI1在胃癌和癌旁组织中的表达差异。结果:胃癌组织中GLI1高表达是正常组织的1.7倍,其高表达患者总生存期、无病生存期较低表达患者更短(P<0.05)。胃癌组织中GLI1的高表达组间质评分、免疫评分、免疫浸润细胞丰度更高,GLI1高表达对药物敏感性降低并且和免疫检查点标志物PDCD1表达呈正相关(P<0.05)。GLI1在低分化胃癌患者中表达明显升高(P<0.05)。结论:GLI1表达与胃癌患者预后及免疫浸润相关,并且其可能通过调节化疗耐药而导致患者的不良预后,可能是胃癌潜在的治疗靶点和分子标志物。

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

胃癌(GC)是极具异质性和侵袭性的消化系统恶性肿瘤之一,传统化疗药物及曲妥珠单抗等人表皮生长因子受体2(HER2)靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此,研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷,但在某些情况下无效或产生耐药,这与HER2在某些GC细胞中低表达有关,HER2低表达(HER2 IHC1+或IHC2+/ISH-)约占全部类型的40%~60%,但在临床实践中,这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物(ADC)的出现为HER2阳性GC提供了新的治疗选择,凭借其精准高效的抗肿瘤作用,有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性,相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述,并讨论HER2靶向ADC在应用和研发过程中面临的挑战。

五阶梯营养支持对胃癌术后辅助化疗患者营养状态及化疗毒副反应的影响

【目的】探讨五阶梯营养支持对胃癌术后辅助化疗患者营养状态及化疗毒副反应的影响。【方法】行胃癌术后辅助化疗的80例患者,随机分成两组,每组40例。观察组给予五阶梯营养支持,对照组给予常规营养支持,比较两组干预前后营养状态、血液生化指标水平、化疗毒副反应和生存质量。【结果】干预后,两组主观整体营养状况评估量表(PG-SGA)评分降低,体重指数(BMI)、小腿最大周径升高(P<0.05),且观察组PG-SGA评分低于对照组,BMI、小腿最大周径高于对照组(P<0.05);干预后,两组血红蛋白(Hb)、血清白蛋白(Alb)、血清前蛋白(PA)水平较干预前均升高(P<0.05),且观察组高于对照组(P<0.05);观察组化疗毒副反应总发生率(17.50%)低于对照组(45.00%)(P<0.05);干预后3个月、6个月,两组胃癌患者生命质量测量量表评分均低于干预前,且观察组低于对照组(P<0.05)。【结论】在胃癌术后辅助化疗患者中应用五阶梯营养支持可以改善患者营养状态、血液生化指标,减轻化疗毒副反应,改善患者生存质量,值得临床推广应用。

胃癌手术后局部灌注化疗预防局部复发和肝转移的临床研究

目的探讨胃癌术后局部灌注化疗预防局部复发和肝转移的价值.方法将收治的352例胃癌术前随机分为两组,治疗组术后行局部动脉灌注化疗(184例);对照组术后行全身静脉化疗(168例),对两组的疗效进行比较.结果随访时间3～6年,随访328例,失访24例,随访率93.2%.治疗组1,3,5年生存率分别为95.7%,78.3%, 46.3%;对照组是86.8%,48.2%,21.4%.局部复发率和肝转移率治疗组为9.2%,12.5%,对照组为22.0%,26.8%.两组上述各项指标差异均有显著意义(均P<0.01).结论局部灌注化疗是胃癌术后预防局部复发和肝转移的一种有效方法,其疗效明显优于术后全身静脉化疗,且毒副作用小.

人增殖抑制基因(HSG)对肿瘤细胞系化疗敏感性的作用

目的:将人增殖抑制基因 (hHSG)用电子穿孔的转基因方式转染到体外培养的人肿瘤细胞系中,观察hHSG基因对内源性hHSG表达水平不同的肿瘤细胞系的化疗敏感性的影响。方法:首先用免疫组化方法检测不同组织来源的肿瘤细胞系中hHSG的表达水平,然后选择内源性hHSG表达水平较低的肺腺癌 (A549 )和内源性hHSG表达水平较高的宫颈癌(HeLaS3)细胞系,用电穿孔方法转染含有hHSG的真核表达载体 (pEGFP hHSG) 24h后,加入放线菌酮(CHX),采用细胞计数、MTT法观察hHSG对肿瘤细胞增殖抑制作用及对CHX的化疗敏感性的影响。结果:hHSG在不同组织来源的肿瘤细胞系都有不同程度的表达, pEGFP hHSG转染到两种内源性hHSG表达水平不同的肿瘤细胞系后,这两种肿瘤细胞的生长增殖都明显受到抑制,同时外源性的hHSG也增强了这些肿瘤细胞系对CHX的敏感性。结论:外源性hHSG可不依赖其内源性表达水平而抑制肿瘤细胞的增殖,与CHX并用可增强肿瘤细胞对CHX的敏感性,具有协同作用。

进展期胃癌新辅助化疗效果的临床观察

目的评估新辅助化疗对进展期胃癌的治疗效果。方法选取48例进展期胃癌(IIIb和IV期)患者,术前行氟尿嘧啶+甲酰四氢叶酸钙+乐沙定化疗,采用双周疗法;经2～3个疗程后,行CT,超声内镜复查,分期。对可切除者行手术治疗。结果新辅助化疗总有效率为58.4%;其中IIIb期为64.1%,IV期为22.2%。39例III期患者中,手术根治率达71.8%。9例IV期患者中,2例行姑息手术切除,1例行探腹术。结论新辅助化疗可有效提高IIIb期胃癌患者的手术根治率,而对IV期患者疗效不显著。

金龙蛇方对人胃癌MKN-45裸小鼠原位移植瘤生长转移及多种粘附分子蛋白表达的影响

目的:通过观察金龙蛇方及拆方对裸鼠人胃癌模型中转移和多种相关粘附分子表达的影响,探讨其抗胃癌转移的机制。方法:50只动物随机分为消痰组、散结组、金龙蛇组、5Fu组和对照组,建立人胃癌MKN45裸鼠原位种植模型,造模后第3天开始给药,对照组给予生理盐水0.2mL/d,腹腔注射,5Fu组给予5Fu稀释液0.2mL/周,腹腔注射,中药组分别给予消痰方、散结方、金龙蛇方0.2mL/d灌胃。第6周实验结束,观察肿瘤生长及转移情况,肝脏称质量。瘤组织及转移脏器行免疫组化检测Ecad、CD44v6、GMP140、ICAM1等蛋白的表达。结果:金龙蛇方及拆方可以明显抑制裸鼠人胃癌MKN45原位种植瘤的生长,减少肝脏转移,不同程度下调肿瘤细胞CD44v6、GMP140蛋白的表达。结论:金龙蛇方可以下调多种异质性粘附分子蛋白的表达,可能是其抗胃癌转移的机制之一。