中药乳宁Ⅱ号对Ca761小鼠移植性乳腺癌的抑制作用

目的 中药乳宁Ⅱ号对Ca761荷瘤小鼠抑瘤作用及对化疗药物抗肿瘤影响的研究。方法 对Ca761荷瘤小鼠进行为期3周的灌胃,腹腔注射环磷酰胺(CTX),通过抑瘤率及胸腺、脾重来判断乳宁Ⅱ号对小鼠移植瘤的抑制作用及对CTX抗肿瘤作用的影响。结果 乳宁Ⅱ号对Ca761荷瘤小鼠肿瘤大小、瘤重抑制率分别为28.29％、26.28％,CTX组为46.5％、47.62％,乳宁Ⅱ号 CTX组为66.77％、68.86％。结论 (1)中药乳宁Ⅱ号有较好的抑瘤作用。(2)中药乳宁Ⅱ号对CTX抑瘤有增效作用。(3)中药乳宁Ⅱ号有缓解CTX对免疫功能的抑制作用。     

鼠白细胞介素-12质粒联合小剂量环磷酰胺对荷瘤小鼠NK及巨噬细胞功能的影响

目的探讨联合应用鼠白细胞介素-12双亚基共表达质粒(pCmIL-12)和小剂量环磷酰胺(CTX)治疗小鼠黑色素瘤的效果以及对NK和巨噬细胞功能的影响.方法荷瘤小鼠经肌注pCmIL-12和皮下注射CTX后,观察肿瘤大小,测定小鼠NK细胞杀伤活性、腹腔巨噬细胞杀伤活性及NO释放量.结果肿瘤重量、NK和巨噬细胞杀伤活性及NO释放量的结果提示pCmIL-12与CTX合用具有交互(协同)作用.结论联合应用pCmIL-12质粒和小剂量环磷酰胺有较明显的抑瘤作用,并可增强荷瘤小鼠NK及巨噬细胞的功能.     

香葵精油的药理研究

香葵精油为(牛龙)牛儿苗科植物香叶天竺葵(Pelargonium Graveolen sL、Herit)经蒸馏所得的挥发油。资料报告该油对动物移植性肿瘤有一定的抑瘤作用,临床试用证明对宫颈癌有较好的近期疗效,据此我们观察该药对正常大鼠的免疫功能、对小鼠肉瘤 S180瘤组织中 RNA 和 DNA 含量的影响,以探讨该药的作用原理,并对部分动物移植性肿瘤的抑瘤试验进行了复试,现将结果报告如下:     

氧化苦参碱对荷瘤小鼠免疫功能的影响

目的研究氧化苦参碱(OMT)的抑瘤作用和免疫功能变化的关系.方法应用HEP-A-22肝癌小鼠模型进行免疫指标比较.结果显示OMT在近期内(15天)对荷瘤小鼠有明显抑瘤作用.结论氧化苦参碱可明显提高荷瘤小鼠免疫功能,并产生抑瘤效应.     

带瘤小鼠肝RNA的抑瘤效应

本文结果表明带瘤小鼠肝RNA对肿瘤的生长有抑制作用,尤其在肿瘤植入初期更为明显,且有肿瘤特异性。用RNase处理后,其抑瘤作用消失,表明只有完整的RNA分子才具有抑瘤作用。正常小鼠肝RNA的抑瘤作用较弱,且无肿瘤特异性。这两种RNA制剂在聚丙烯酰胺凝胶电泳谱上未见差异,表明具抑瘤作用的免疫RNA含量甚微。     

植酸和魔芋干预二甲肼诱发ICR小鼠大肠癌的初步研究

饮食与大肠癌的关系极为密切,植酸(PA)和魔芋(KM)均为天然食物。本实验表明在二甲肼诱发ICR 小鼠大肠癌过程中,2%PA 饮水25周能使肿瘤发生率和浸润性生长发生率分别从100.0%和70.0%下降至42.9%14.3%;5～10%KM 饲料喂饲25周能使肿瘤发生率从100.0%下降至50.0%,但未能观察到 PA 和 KM协同抑癌作用。PA 和 KM 也能显著地减轻与肿瘤密切有关的超氧化物歧化酶、丙二醛等生化指标的变化程度。     

基础理论

人乳头状瘤病毒18型阳性肿瘤疫苗的构建及体外活性鉴定,淫羊霍苷体内抑瘤作用及其机制,基因佐剂的肿瘤疫苗对肿瘤特异性细胞毒性T淋巴细胞功能的影响,三联菌苗对小鼠肉瘤180的抑制作用,IL-12基因重组腺病毒对不同肿瘤抗瘤作用的研究,冻融人树突状细胞基因疫苗体外抗肿瘤免疫效应,     

参芪注射液抗肿瘤作用的实验研究

参芪注射液与化疗药物配合使用,治疗消化道肿瘤取得很好的疗效。体外抑癌实验表明,不同剂量的参芪注射液对HL—60和L1210癌细胞株无直接抑制作用。体内抑癌实验,对小鼠移植性肿瘤S_(180)有明显的抑制作用并呈量效关系。能明显延长荷瘤小鼠化疗模型(注射中毒剂量的甲氨蝶呤)的生存期。参芪注射液对小鼠血中白细胞磷酸二酯酶(PDE)活性有明显的抑制作用,能升高小鼠血浆患cAMP含量,对大鼠血小板的钙调蛋白(CAM)有明显的抑制作用。提示该药可能通过调节机体的免疫功能发挥其抗癌作用,是一种中药免疫调节剂。     

大豆蛋白酶抑制物和皂甙抑瘤作用的实验研究

已有研究表明从大豆中提取的蛋白酶抑制物（ＰＩ）和皂甙有预防肿瘤的作用。本研究发现它们增加环磷酰胺（ＣＴＸ）对小鼠的抑瘤作用，又能减低对小鼠外周血细胞和骨髓有核细胞的毒性副作用，同是也发现它们对小鼠的免疫功能有促进作用。这些提取物可望作为人体肿瘤化疗的辅助用药。     

紫松果菊对荷瘤小鼠的抑瘤作用及产生肿瘤坏死因子的影响

目的:探索紫松果菊对荷瘤小鼠的抑瘤及产生肿瘤坏死因子( TNF) 的作用。方法:测量小鼠荷S180瘤株前后体重及瘤重,微量NAG释放法测血清TNF。结果:紫松果菊对小鼠S180没有抑瘤效应,但能明显降低荷瘤小鼠产生TNF 的水平。结论:紫松果菊有抑制小鼠产生TNF 的作用,因此可能具有抗炎和抗过敏的作用。     

人参皂甙Rg3抑制小鼠肝癌淋巴道转移作用及其对免疫功能的影响

目的：观察人参皂甙Rg3抑制小鼠肿瘤生长及抗淋巴结转移的作用及对免疫功能的影响。方法：以Hca-F25//6A3-F（F）接种于615近交系小鼠，建立肝癌淋巴道转移动物模型，分为5组：Rg3预防组（接种肿瘤前给Rg3）、Rg3治疗组（Rg3）、阳性对照组（PDD）、联合治疗组（Rg3＋PDD）和阴性对照组（生理盐水），比较各组的原发瘤抑制率和转移淋巴结抑瘤率，并通过流式细胞仪方法分析各组免疫指标CD4／CD8的变化。结果：联合治疗组原发瘤的抑瘤率明显提高，与阴性对照组相比具有统计学上明显差异（P〈0．05）；淋巴结转移抑制率含Rg3组均较阴性对照组高；Rg3预防组和Rg3治疗组CD4／CD8比值与阴性对照组相比升高，具有统计学上明显差异（P〈0．05）。结论：人参皂甙Rg3具有明显的抗肿瘤作用，可以增强化疗药物PDD的抗癌作用，及抑制淋巴道转移作用，并提高荷瘤小鼠免疫功能。     

Squamous cell carcinoma antigen 1 is associated to poor prognosis in esophageal cancer through immune surveillance impairment and reduced chemosensitivity

Squamous cell carcinoma antigen‐1 (SCCA1) overexpression is associated with poor prognosis and chemoresistance in several tumor types, however, the underlying mechanisms remain elusive. Here, we report SCCA1 in relation to the immune and peritumoral adipose tissue microenvironment in early and advanced esophageal adenocarcinoma (EAC). In our series of patients with EAC, free SCCA1 serum levels were associated with significantly worse overall survival, and SCCA1‐IgM serum levels showed a trend to a worse overall survival. Serum SCCA1 and intratumoral SCCA1 were inversely correlated with immune activation markers. In agreement with these findings, SCCA1 induced the expression of the immune checkpoint molecule programmed death ligand‐1 on monocytes and a direct correlation of these 2 molecules was observed in sequential tumor sections. Furthermore, SCCA1 mRNA expression within the tumor was inversely correlated with stem cell marker expression both within the tumor and in the peritumoral adipose tissue. In vitro, in EAC cell lines treated with different chemotherapeutic drugs, cell viability was significantly modified by SCCA1 presence, as cells overexpressing SCCA1 were significantly more resistant to cell death. In conclusion, poor prognosis in EAC overexpressing SCCA1 is due to reduced tumor chemosensitivity as well as intratumoral immunity impairment, likely induced by this molecule .     

黄芩苷对肝癌细胞株SMMC-7721裸鼠移植瘤生长抑制作用及其机制

目的：以裸鼠人肝癌细胞株SMMC-7721移植瘤动物模型为研究对象,观察黄芩苷对移植瘤生长能力的影响,初步探讨黄芩苷对CyclinD1和Caspase-3表达的影响。方法：BALB／c裸鼠右前腋部皮下接种人肝癌SMMC-7721细胞5×10^6个,建立人肝癌实体瘤模型。将20只成瘤裸小鼠随机分为空白对照组与黄芩苷组,每组10只。对照组腹腔注射生理盐水10ml／kg,黄芩苷组腹腔注射黄芩苷注射液100mg/kg,每2d给药1次,间断给药8次后称体重、处死,瘤块离体称重,计算抑瘤率;用免疫组织化学方法检测实验组和对照组移植瘤中CyclinD1和Caspase-3的表达水平。结果：黄芩苷组100ml/kg对裸鼠肝癌SMMC-7721实体瘤的抑制率为308％,两组间肝脏与肾脏指数比较,P均大于0.05。黄芩苷处理组凋亡指数为（13.6±11）％,高于对照组的（2.2±19）％,（P〈0.01）。黄芩苷能够抑制CyclinD1表达及上调Caspase-3表达,（均P〈0.05）。结论：黄芩苷对人肝癌SMMC-7721的裸鼠皮下移植瘤具有生长抑制作用,其抑瘤作用可能通过下调cy—clinD1表达和上调Caspase-3表达来达到抑制瘤体增殖并有促进其凋亡的作用。在保护免疫器官功能方面,黄芩苷无明显优势。黄芩苷可能成为治疗原发性肝癌的有效手段之一,但是其在保护免疫器官方面还需要进一步研究。     

红景天在肿瘤患者化疗中的免疫功能调节作用

目的：观察红景天在肿瘤患者化疗中对机体免疫功能的影响及调节作用。方法：在肿瘤患者化疗期间用红景天连服20天，同时使用胸腺肽和空白对照对比观察72例肿瘤患者化疗前后体液免疫与细胞免疫功能的指标变化。结果：治疗1、2组肿瘤患者化疗前后细胞免疫功能无下降（P〉0．05），对照组的细胞免疫功能有下降（P〈0．05、P〈0．001），三组患者体液免疫功能均无变化（P〉0．05）。结论：联合服用红景天能使肿瘤患者在肿瘤治疗中的细胞免疫保持相对的平稳，红景天是一种安全有效的免疫调节剂。     

131I-angoistatin对H22肝癌小鼠的治疗作用

目的:研究肿瘤血管抑制剂血管抑素和放射性核素131I以及两者联合对H22肝癌小鼠的抑瘤作用。方法:选择40只C57雄性小鼠,分别以每只0.20ml（含H22肝癌细胞2.8×106个）接种于小鼠右后肢根部腹侧皮下,待移植瘤长至直径约10mm时,开始进行干预实验。全部小鼠随机分为4组,分别经尾静脉注射AS(12.5mg／kg)、131I-AS(含131I 10MBq、AS 12.5mg／kg)、131I（10MBq)和生理盐水各0．2ml,分别于3、6、10、14天测量肿瘤体积(肿瘤体积V=ab／2,a、b分别为肿瘤的最大径和最小径),以生理盐水组作为对照组,计算各治疗组的抑瘤率,抑瘤率=(对照组V-实验组V）／对照组V×100％。结果:在治疗结束时,对照组与三个实验治疗组肿瘤体积分别是:NS组（6670±23）mm3、131I-AS组（1979±31）mm3、131I组（5219±19.6）mm3、AS组（3849±11.9）mm3。与对照组相比各治疗组均有明显的抑瘤效应,其中131I-AS组抑瘤效果明显。结论:131I和AS以及131I-AS均可抑制肿瘤的生长,其中131I与AS两者联合对H22荷瘤鼠具有明显的抗肿瘤协同效应,差异具有统计学意义。     

Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997–2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64–0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70–0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62–0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80–1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63–1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36–0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.     

Inflammation,inflammatory cells and angiogenesis: decisions and indecisions

Endothelial-immune cell cross-talk goes well beyond leukocyte and lymphocyte trafficking, since immune cells are able to intimately regulate vessel formation and function. Here we review the evidence that most immune cells are capable of polarization towards a dichotomous activity either inducing or inhibiting angiogenesis. In addition to the well-known roles of tumor associated macrophages, we find that neutrophils, myeloid-derived suppressor and dendritic cells clearly have the potential for influencing tumor angiogenesis. Further, the physiological functions of NK cells suggest that these cells may also show a potentially important role in pro- or anti-angiogenesis regulation within the tumor microenvironment. At the same time many angiogenic factors influence the activity and function of immune cells that generally favor tumor survival and tolerance. Thus the immune system itself represents a major pharmaceutical target and links angiogenesis inhibition to immunotherapy.     

艾迪注射液在恶性肿瘤放、化疗中增效减毒作用的临床研究

目的：观察艾迪注射液在恶性肿瘤放、化疗中的增效减毒作用。方法：136例确诊的恶性肿瘤患者随机分为两组。艾迪组（68例）于放、化疗的同时给予艾迪注射液50ml加生理盐水500ml静脉滴注，每天1次，连用28天；对照组单纯放、化疗。结果：与对照组对比，艾迪组的病变进展率、外周血WBC、PLT降低程度小（P〈0．05）；T细胞亚群CD8下降明显（P〈0．05）；CD4／CD8比值上升明显（P〈0．05）；血清IgG、IgM含量明显增高（P〈0．05）；治疗后艾迪组NK细胞明显高于对照组（P〈0．05）；Kamofsky评分艾迪组明显高于对照组（P〈0．05）。结论：艾迪注射液辅助放、化疗可抑制肿瘤进展，降低毒副反应，防治放、化疗所致的骨髓抑制，提高机体的免疫功能和改善生活质量。     

Aglaroxin C对小鼠H22肝癌移植瘤的抑制作用及对其脏器的影响

目的:探讨楝酰胺衍生物Aglaroxin C对小鼠H22肝癌皮下移植瘤的影响及在实验剂量下对小鼠各脏器有无影响。方法:建立BALB/C小鼠H22腋下实体瘤模型,并随机分为Ⅰ组（尾静脉给药对照组）、Ⅱ组（尾静脉给药组,0.1 mg每只）、Ⅲ 组（瘤内给药对照组）、Ⅳ组（瘤内给药组,0.05 mg每只）、Ⅴ组（瘤内给药组,0.1 mg每只）,每组各5只。隔天给药(Aglaroxin C)一次,共4次。每日测量小鼠体重。末次给药24小时后切除肿瘤及各组小鼠主要脏器并称重,计算抑瘤率、脏器系数。用各组肿瘤及各脏器制作病理切片,苏木精-伊红染色（hematoxylin-eosin staining,HE染色）,并在光镜下观察其细胞形态学变化。结果:Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组、Ⅴ组的瘤体质量分别为（2.11±0.50） g、(1.59±0.14) g、(2.30±0.64) g、(1.66±0.12) g、(1.06±0.14) g,Ⅱ组瘤体质量明显小于Ⅰ组（P＜0.01),Ⅲ组、Ⅳ组、Ⅴ组比较差异有统计学意义（P＜0.01)。Ⅴ组的抑瘤率最高达53.91%。显微镜下观察肿瘤病理切片,给药组坏死肿瘤细胞明显增多,对照组肿瘤细胞坏死轻微;各组小鼠体质量组间变化无明显统计学意义（P＞0.05）;显微镜下观察各脏器病理切片,各给药组与对照组相比,无明显异常;脏器系数各剂量组与对照组组间比较,差异无统计学意义（P＞0.05）。结论:Aglaroxin C对小鼠H22肝癌皮下移植瘤的生长有抑制作用,在实验剂量下对小鼠各脏器无明显影响。     

The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma

BACKGROUND: Tumor viability assessed by pathologic analysis of resected specimens in patients with preoperatively treated esophageal adenocarcinoma (EAC) is a prognostic indicator. The feasibility of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) and surgery for patients with locoregionally advanced EAC has been demonstrated. In this study, the authors evaluated the efficacy of CCRT compared with traditional concurrent chemoradiotherapy (CRT). METHODS: The authors retrospectively reviewed 247 consecutive patients with EAC who presented for planned surgery after treatment with either CCRT or CRT from January 1997 through August 2003. Patient demographics, comorbidities, and tumor characteristics were analyzed. Pathologic tumor response, overall survival, and disease-free survival were assessed according to treatment. RESULTS: One hundred seventeen patients received CCRT, and 130 patients received CRT before planned surgical resection. CCRT resulted in a 64% tumor response rate compared with a 51% tumor response rate in the CRT group (odds ratio, 1.73; P = .035). In the CCRT group, the median overall survival was 55 months, and the 3-year overall survival rate was 59%; in the CRT group, the median overall survival was 25 months, and the 3-year overall survival rate was 41% (hazard ratio [HR], 0.69; P = .041). In the CCRT group, the median disease-free survival was 43 months, and the 3-year disease-free survival rate was 54%; in the CRT group, the median disease-free survival was 18 months, and the 3-year disease-free survival rate was 36% (HR, 0.72; P = .047). Subset analysis of patients with clinical Stage III/IVA disease showed a median overall survival of 51 months with a 3-year overall survival rate of 58% in the CCRT group and a median overall survival of 20 months with a 3-year overall survival rate of 28% in the CRT group (HR, 0.57; P = .019). CONCLUSIONS: In patients with EAC, CCRT improved tumor response significantly compared with traditional CRT alone. Overall survival and disease-free survival were increased in patients who received CCRT, especially in the subset of patients who had more advanced disease.