岩五加中具有抗癌转移活性的吲哚类生物碱的分离

[目的]对岩五加(Tetrastigma obtectum)全植株进行植物化学研究,分离出2种新的吲哚类生物碱。[方法]通过有机波谱解析鉴定结构,并以人乳腺癌细胞系MDA-MB-231为模型进行抗癌转移活性筛选。[结果]分离得到2种新的吲哚类生物碱,分别为崖爬藤碱A(1)和崖爬藤碱B(2)。[结论]在以人乳腺癌细胞系MDA-MB-231为模型进行抗癌转移活性筛选过程中,化合物1和2显示出阳性抗癌转移作用。

20(R)—人参皂苷Rh_2抗癌细胞转移实验研究

本文报道有关 2 0 (R)—人参皂苷Rh2 (简称“Rh2 ”)对抗B1 6—BL6小鼠黑色素瘤细胞自发性转移的作用。以Taxol作为阳性对照药 ,以二种方式给药 ,一种是模型建立后给药 ,一种为模型建立前给药 ,结果表明后种给药方式的抗转移作用明显优于前者。另外 ,根据本项实验结果以及相关的报道来探讨人参皂苷化合物的抗转移作用的构效关系 ,认为 ,分子量小 ,极性小 ,易吸收的人参皂苷次生苷或苷元 。

层粘连蛋白总糖肽的抗癌细胞转移作用及其作用机制

增殖失控及侵袭与转移是恶性肿瘤细胞的根本特性,也是夺去癌患者生命的根本原因。不单在癌症发展过程中可自发的发生广泛转移,而且在癌症常规诊疗过程中也有可能人为的促进癌细胞的转移(医源性转移),如诊疗操作中的种植及对患者免疫功能的损伤等。癌细胞转移是一个多步骤的复杂过程。然而。

刺五加在小鼠实验性肺癌侵袭转移过程中的作用

背景与目的:探讨刺五加对小鼠Lewis肺癌侵袭转移干预作用的效果。材料与方法:Lewis肺癌C57/BL雌性小鼠分成刺五加+环磷酰胺组、环磷酰胺组、刺五加组和肿瘤组,通过检测各组小鼠的瘤重和抑瘤率,应用酶联免疫吸附试验(Enzyme-linkedimmunosorbentassay,ELISA)法检测血浆、瘤和肺组织中I型纤溶酶原激活剂抑制剂(Plasminogenactivatorinhibitor-Ⅰ,PAI-1)、尿激酶型纤溶酶原激活剂(uroleinasetypePlasminogenActivator,uPA)活性观察刺五加对Lewis肺癌的干预作用。结果:刺五加较肿瘤组瘤重、血浆和瘤,肺组织中PAI-1、uPA活性明显降低。结论:刺五加有抑制肿瘤生长、减少瘤、肺组织和血浆中uPA、PAI-1活性,对实验性小鼠肺癌侵袭转移过程中显示出了一定的干预作用。刺五加适于被开发为常规抗癌辅助药物。刺五加+环磷酰胺组的效果比单独用环磷酰胺或刺五加的效果更好。

血管生成与癌转移

现已发现了新生血管和与肿瘤转移进程之间的关系。通常血管生成是继发性肿瘤形成的必要前提，但是它的出现并不意味着一定发生癌转移：如今已研究出一种抗癌细胞转移的新途径，即把新生成肿瘤的血管床作为攻克目标，通过动物实验证明，这种治疗途径是有效的，但还有待于临床应用。

Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer

AIM:To compare and evaluate the appropriate prog-nostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection.METHODS:A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer(UICC)N staging methods and the metastatic lymph node ratio(MLNR)staging.Ho-mogeneity,discriminatory ability,and gradient mono-tonicity of the various staging methods were compared using linear trend χ2,likelihood ratio χ2 statistics,and Akaike information criterion(AIC)calculations.The area under the curve(AUC)was calculated to compare the predictive ability of the aforementioned three stag-ing methods.RESULTS:Optimal cut-points of the MLNR were cal-culated as MLNR0(0),MLNR1(0.01-0.30),MLNR2(0.31-0.50),and MLNR3(0.51-1.00).In univariate,multivariate,and stratified analyses,MLNR staging was superior to the 6th and 7th edition UICC N stag-ing methods.MLNR staging had a higher AUC,higher linear trend and likelihood ratio χ2 scores and lower AIC values than the other two staging methods.CONCLUSION:MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edi-tion UICC N classif ications and should be considered as an alternative to current pathological N staging.

Biliary carcinoembryonic antigen levels in diagnosis of occult hepatic metastases from colorectal carcinoma

AIM:To prospectively explore the role of carcinoembryonic antigen (CEA) in gallbladder bile in patients with colorectal carcinoma and the morphological and clinical features of neoplasia and the occurrence of hepatic metastases. METHODS:CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis.CEA samples were collected from the gallbladder bile and peripheral blood during the operation,immediately before extirpating the colorectal neoplasia or cholecystectomy. Values of up to 5 ng/ml were considered normal for bile and serum CEA. RESULTS:In the 44 patients with colorectal carcinoma who underwent operation with curative intent,the average level of serum CEA was 8.5 ng/ml (range:0.1 to 111.0 ng/ ml) and for bile CEA it was 74.5 ng/ml (range:0.2 to 571.0 ng/ml).In the patients with uncomplicated cholelithiasis who underwent cholecystectomy,the average level of serum CEA was 2.9 ng/ml (range:1.0 to 3.5 ng/ml) and for bile CEA it was 1.2 ng/ml (range:0.3 to 2.9 ng/ml). The average duration of follow-up time was 16.5 months (range:6 to 48 months).Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastases between three and seventeen months after removal of the primary colorectal neoplasia.Three of them successfully underwent extirpation of the hepatic lesions. CONCLUSION:High CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastases.Such patients must be followed up with special attention to the diagnosis of such lesions.

Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells

AIM： To examine whether antithrombin （AT） could prevent hepatic ischemia/reperfusion （I/R）-induced hepatic metastasis by inhibiting tumor necrosis factor （TNF）-α-induced expression of E-selectin in rats. METHODS： Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS： AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION： AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.

Inhibiting effects of ^(131)I-labeled anti-CEA monoclonal antibodies injected intrasplenically on liver metastasis from human colonic adenocarcinoma

I-labeled anti-CEA monoclonal antibody injected intrasplenically has better effects on inhibiting liver metastasis from human colonic adenocarcinoma than that through tail vein in nu/nu mice model.

十全大补汤和人参养荣汤在抗癌细胞转移作用中的器官选择性

研究发现,十全大补汤和人参养荣汤具有抗癌细胞转移作用。本次研究了2个方剂在抗癌细胞转移作用中是否具有器官选择性。

Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer

Maximum androgen blockade （MAB）, consisting of an antiandrogen plus either a luteinizing hormone- releasing hormone agonist （LHRHA） or orchiectomy, is a standard care for patients with prostate cancer. Although, clinical trial results have been equivocal, none has shown a significant advantage in favor of MAB over castration alone in metastatic prostate cancer and MAB has been the subject of considerable controversy. The aim of this study was to compare MAB （orchiectomy or LHRHA＂Goserelin＂） and anti-androgen ＂Bicalutamide＂ with castration alone （orchiectomy or LHRHA） in previ- ously untreated metastatic prostate cancer patients. Methods： Hundred eligible patients with adequate performance status and adequate hematologic, hepatic and renal functions were included. MAB arm, fifty patients underwent castration either surgically by orchiectomy or medically by receiving Goserelin （3.6 rag） depot, which was injected subcutaneously every 28 days plus bicalutamide 50 mg once daily. Castration alone arm, fifty patients underwent castration alone either surgically by orchiectomy or medically by receiving Goserelin （3.6 mg） depot. Results： During the period from January 2011 to January 2013, with a median follow up of 18 months （range 6 to 24 months）, there were eight deaths （16%）, in MAB arm and ten deaths （20%） in castration alone arm. At three months, there were 35 patients （70%） with prostate specific antigen （PSA） normalization （-〈 4 mg/dL） in MAB arm versus 17 patients （34%） with PSA normalization in castration alone arm （P = 0.001）. The median progression free survival （PFS） times were 22.18 months （95% CI, 19.7 to 24.2 months） for MAB arm versus 22 months in castration alone arm （95% CI, 18 to 25.9 months; P = 0.045）. The survival rates for MAB arm were 82% at 18 months and 70.6% at 24 months versus 78.7% at 18 months and 75.1% at 24 months in castration alone arm （P 〉 0.05）. The median overall survival （OS） was not reached in either arm. Both hematological and non-hematological toxicities were com- parable in both arms. Conclusion： MAB significantly improves the PSA normalization rate at 12 weeks and PFS compared to castration alone with no significant difference in overall survival and with comparable acceptable toxicities. However further studies are needed to document such findings.

Cetuximab plus irinotecan in pretreated metastatic colorectal cancer patients:The ELSIE study

AIM:To evaluate the efficacy and safety of cetuxim-ab plus irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients from South-East Asia and Australia. METHODS:In this open-label,phase Ⅱ study,the main eligibility criteria were epidermal growth factor receptor-positive mCRC with progressive disease within 3 mo of an irinotecan-based regimen as the most recent chemotherapy. Patients received cetuximab 400 mg/m2 initially,then 250 mg/m2 every week,with the same regimen of irinotecan on which the patients had progressed (4 pre-defined regim-ens allowed). The prim-ary objective was evaluation of progression-free survival (PFS) at 12 wk. Secondary objectives included a further investigation of PFS,and an assessment of the overall response rate (ORR),duration of response,time to treatment failure (TTF),overall survival and the safety profile. RESULTS:One hundred and twenty nine patients were enrolled from-25 centers in the Asia-Pacific region and of these 123 received cetuximab plus irinotecan. The most common recent irinotecan regimen used was 180 mg/m2 every 2 wk which had been used in 93 patients (75.6%). The PFS rate at 12 wk was 50% (95% confidence interval (CI,41-59) and m-edian PFS tim-e was 12.1 wk (95% CI:9.7-17.7). The ORR was 13.8% (95% CI:8.3-21.2) and disease control rate was 49.6% (95% CI:40.5-58.8). Median duration of response was 31.1 wk (95% CI:18.0-42.6) and median overall survival was 9.5 mo (95% CI,7.5-11.7). The median TTF was 11.7 wk (95% CI:9.1-17.4). Treatment was generally well tolerated. The most common grade 3/4 adverse events were diarrhea (13.8%),neutropenia (8.9%),rash (5.7%) and vomiting (5.7%).CONCLUSION:In patients from Asia and Australia,this study confirm-s the activity and safety of cetuxim-ab plus irinotecan observed in previous studies in Europe and South America.

The efficacy and its related issues of combination of bevacizumab and taxanes-based regimens in Chinese patients with metastatic breast cancer

Objective: Bevacizumab has been challenging in the treatment of metastatic breast cancer. To investigate its efficacy, optimal partner to combine with and maintenance therapy, we performed a retrospective study based on Chinese patients with metastatic breast cancer (MBC). Methods: Patients with MBC treated with bevacizumab-contained regimens at the Sun Yat-sen University Cancer Center from 2006 to 2010 were recruited to the study. The primary endpoints were overall survival (OS), time to progression (TTP), objective response rate (ORR), and disease control rate (DCR). These endpoints were analyzed using the Kaplan-Meier and Chi-squared tests, respectively. Results: (1) A total of 229 cycles of bevacizumab with a median cycle of 7 (1-34) were administered among 25 patients. (2) In the whole group, ORR and DCR were 60% (15/25) and 76% (19/25), respectively. The mTTP was 5 months (1-21), mOS from diagnosis was 48 months (13-172), mOS from bevacizumab administration was 24 months (1-45). (3) Both ORR (73.7% vs. 16.7%, P = 0.023) and DCR (94.7% vs. 33.3%, P = 0.005) were significant higher once patients treated with the combination of taxanes-based regimen and bevacizamab when compared with the combination with non-taxanes-based regimens. (4) In the taxanes-based group, no matter bevacizumab used in first line or non-first line, the differences of ORR (P = 0.637) and DCR (P = 0.316) were insignificant. However, the maintenance therapy with bevacizumab will bring more longer TTP (P < 0.001) than those without maintenance therapy. Conclusion: Taxanes-based regimens were the optimal candidate to combine with bevacizumab regardless the timing in palliative setting, however, the maintenance therapy with bevacizumab should be considered once indicated.

The efficacy of bevacizumab in Chinese patients with metastatic colorectal cancer and its effect in different line setting

Objective: We aimed to evaluate the effect of bevacizumab in the palliative treatment of Chinese metastatic colorectal cancer(mCRC) and its efficacy in different lines. Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2005 to 2013 were recruited as the study group and control group. The endpoints were objective response rate(ORR), disease control rate(DCR), overall survival(OS) and progression free survival(PFS). The OS and PFS of first-, second- and third-line treatment groups were compared between study group and control group. Results: The median PFS of the study and the control group were 8.2 months(7.0–9.4 months), 5.7 months(4.7–6.6 months), P = 0.001; OS were 26 months(5.4–130.5 months), 18 months(16.6–19.4 months), P < 0.001, respectively. The ORR and DCR of first-, second- and third-line were 30.3%(20/66), 20%(6/30), 17.6%(3/17) and 97%(64/66), 86.7%(26/30), 100%(17/17). In the first-line chemotherapy group, the OS of the study group and the control group were 22.9(5.4–96.7) months and 18(16.6–19.4) months(P < 0.001); PFS were 9.4(8.4–10.4) months and 5.7(4.7–6.6) months(P < 0.001), respectively. While in the second- and third-line setting, only OS were statistically different, PFS had no significant difference. Conclusion: The combination of bevacizumab and chemotherapy had a promising short-term and long-term efficacy in Chinese mCRC patients than those without bevacizumab regimens, and the effect could be better reflected in the first-line treatment.

Pseudocirrhosis after the Use of Taxanes and Bevacizumab in Metastatic Breast Cancer： Case Reports

Currently, multiple lines of cytotoxic chemotherapy for treatment of metastatic breast cancer are available, and Taxanes, used as monotherapy or in combination with anti-angiogenic drugs, such as Bevacizumab, are one of the most used schemes in clinical practice. These drugs have different side effects and the liver is one of the most affected organs. The objective of this paper is to report three cases of metastatic breast cancer with positive expression of hormone receptors and without amplification of HER-2 protein that were treated with Taxane and Bevacizumab, developed pseudocirrosis probably caused by these drugs and died due to liver failure. It can be drawn from the study that liver failure, as a pseudocirrhosis evolution, is an unusual but lethal event that may occur during the treatment of metastatic breast cancer with Taxanes and Bevacizumab. This warns the importance of diagnostic suspicion of this pathology.

具有抗癌活性的漆树提取物

以水或90％醇于30～95℃提取漆树Rhus verniciflua Stokes，过滤，滤液浓缩得到固体物质，向其中加入10～100倍95％～99．5％乙醇，过滤，浓缩去除溶剂。再加入1～30倍的正己烷，去除正己烷可溶成分，加入1～50倍水，提取，去除水溶性成分，浓缩，冻干。该提取物具抗癌、抗癌转移、抑制逆转录酶活性和抗氧化作用，同时能增加精子的数量并提高其活动性。

硫酸软骨素的研究进展及其应用前景

硫酸软骨素(CS)是由重复二糖单位组成的结构多样化的阴离子多糖链,具有多种药理活性。在查阅CS研究的最新文献基础上,综述了CS在骨关节炎治疗、抗癌转移、促神经细胞生长、促进伤口愈合、抗病毒、骨生成领域中的药理以及相关应用领域的研究进展,讨论了目前研究和应用中存在的问题,以及应用化学酶学途径规模化合成结构专一的硫酸软骨素,用于骨关节炎治疗、癌转移预防与治疗等的可能性。