恶性血液病血清肿瘤细胞特异性生长因子检测的临床意义

目的 探讨肿瘤细胞特异性生长因子 (tumorspecificgrowthfactor,TSGF)在恶性血液病 (malignanthemoblas tosis,MH)中的临床意义。方法 采用TSGF专用试剂盒检测MH患者 86例。结果 MH患者血清TSGF水平明显高于正常对照组 (P <0 .0 0 1) ;恶性淋巴瘤 (ML)、急性淋巴细胞白血病 (ALL)组TSGF明显高于急性非淋巴细胞白血病 (ANLL) (P <0 .0 10 ) ;慢性白血病 (慢淋〈CLL〉、慢粒〈CML〉恶化 /加速 /急变期血清TSGF水平明显高于慢性期 (P <0 .0 0 5 ) ;急性白血病 (AL)、完全缓解期 (CR)、骨髓纤维化 (BMF)、真性红细胞增多症 (PV)患者血清TS GF水平基本正常 (P <0 .0 5 0 )。结论 血清TSGF水平与患者体内恶性肿瘤细胞的增殖潜能及负荷量呈正相关关系 ,可以作为判断预后。

安罗替尼与紫杉醇联合顺铂化疗方案治疗晚期非小细胞肺癌的效果

目的 探讨安罗替尼与紫杉醇联合顺铂化疗方案在晚期非小细胞肺癌(NSCLC)患者治疗中的应用效果。方法 选取信阳市中心医院2019年2月至2021年2月信阳市中心医院62例NSCLC患者,按照随机数字表法分为两组,各31例。对照组接受紫杉醇联合顺铂方案治疗,研究组在对照组的基础上接受安罗替尼治疗。比较两组近期疗效、治疗前后肿瘤细胞生长因子[基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(BFGF)]水平、细胞免疫功能[T淋巴细胞(CD3^(+)、CD4^(+)、CD8^(+))、CD4^(+)/CD8^(+)]、生存期、生活质量及毒副反应。结果 研究组疾病缓解率、疾病控制率高于对照组(P<0.05);治疗后,研究组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)较对照组升高,MMP-9、VEGF、BFGF、CD8^(+)较对照组降低(P<0.05);研究组中位无进展生存期、总生存期长于对照组(P<0.05);治疗后研究组功能评价系统-肺癌模块评分高于对照组,欧洲癌症研究与治疗组织生命质量量表评分低于对照组(P<0.05);两组毒副反应发生率差异无统计学意义(P>0.05)。结论 安罗替尼与紫杉醇联合顺铂化疗方案治疗晚期NSCLC效果确切,可抑制肿瘤细胞生长,减轻免疫功能损伤,延长患者生存期,提高生活质量,且安全性较好。

In vitro growth inhibition of human colonic tumor cells by Verapamil

AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.

Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice

AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P＜0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P＜0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.

Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib(Iressa^(TM))and to the antiangiogenic agent ZD6474:Cytotoxic and biomolecular effects

AIM： To analyze the biological effects of prolonged in vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib （Iressa^TM）, an inhibitor of epidermal growth factor receptor （EGFR） activity, and ZD6474, an inhibitor of both KDR and EGFR activities. METHODS： Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent （4 d of drug exposure followed by 3 d of washout each week） schedule. RESULTS： In both cell types, prolonged exposure （up to 14 d） to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erkl/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. CONCLUSION： We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.

Effects of hepatocyte growth factor/scatter factor on the invasion of colorectal cancer cells in vitro

AIM: Hepatocyte growth factor (HGF) is a multifunctional growth factor which has pleiotrophic biological effects on epithelial cells, such as proliferation, motogenesis, invas-iveness and morphogenesis. There are few reports about the role of HGF played in the colorectal cancer invasion. In the present study, we tried to investigate the possible mechanism of HGF involved in the invasion of colorectal cancer cells in vitro. METHODS: Matrigel migration assay was used to analyze the migrational ability of Caco-2 and Colo320 in vitro. We detected the mRNA expressive levels of MMP-2, MMP-9 and their natural inhibitors TIMP-1, TIMP-2 in Caco-2 cells by reverse-transcription polymerase chain reaction (PCR) technique. RESULTS: After 48 h incubation, there were notable differences when we compared the migrational numbers of Caco-2 cells in the group of HGF and PD98059 (the inhibitor of p42/p44MAPK) with the control (104.40±4.77 vs 126.80±5.40, t= 7.17, P = 0.002<0.01; 104.40±4.77 vs 82.80±4.15, t= 7.96, P = 0.001<0.01). The deviation between the HGF and PD98059 was significant (P<0.01). Compared with controls, MMP-2 and MMP-9 mRNA expres-sions were up-regulated by HGF (0.997±0.011 vs 1.207±0.003, t = 35.002,P= 0.00K0.01; 0.387±0.128 vs 0.971±0.147, t = 106.036, P= 0.0000<0.01, respectively); compared with controls, TIMP-1, TIMP-2 mRNA expressions were increased by PD98059 (1.344±0.007 vs 1.905±0.049, t = 17.541, P= 0.003<0.01; 1.286±0.020 vs 1.887±0.022, t= 24.623, P= 0.002<0.01, respectively). CONCLUSION: HGF promoted Caco-2 migration mainly by p42/p44MAPK pathway; HGF/SF stimulated the expression of MMP-2, MMP-9 in Caco-2 and enabled tumoral cells to damage the ECM and reach the distant organ and develop metastasis; HGF played the function of promoted-invasion and promoted-metastasis, in which cellular selection was possible.

Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients

The fibroblast growth factor receptor(FGFR) family plays important roles in regulating cell growth, proliferation, survival,differentiation and angiogenesis. Deregulation of the FGF/FGFR signaling pathway has been associated with multiple development syndromes and cancers, and thus therapeutic strategies targeting FGFs and FGFR in human cancer are currently being explored.However, few studies on the FGF/FGFR pathway have been conducted in sarcoma, which has a poor outcome with traditional treatments such as surgery, chemotherapy, and radiotherapy. Hence, in the present review, we provide an overview of the role of the FGF/FGFR pathway signal in sarcoma and FGFR inhibitors, which might be new targets for the treatment of sarcomas according to recent research.

Expressions of MVD, VEGF, Ki67 in Residual Prostate Cancer after Cryoablation

OBJECTIVE To analyze the effects of cryoablation on the mice bearing Rm-I prostate cancer through detecting tumor angiogenesis and cancer cell proliferation in the mice after cryoablation, and to explore the effects of cryoablation on vascular endothelium growth factor （VEGF）, Ki67 protein expression and microvessel density （MVD） in the mice bearing prostate cancer. METHODS Sixty Rm-1 mouse models of prostate cancer were established. Experimental mice were randomized into 2 groups： the cryoablation group （n = 30） and the control group （n = 30）. After file therap）4 tumor tissues of the mice in group A and B were obtained at day 0 （without cryoablation）, 1st, 3rd, 5th, 7th, 14th day, respectivelj6 after cryoablation, and the expressions of MVD, VEGF and Ki67 proteins were detected at the same time points. RESULTS The expressions of MVD, VEGF and Ki67 proteins in group A were decreased. The lowest values of the factors were detected on the 3rd day after cryoablation, and increased slowly after that. The expressions of MVD, VEGF and Ki67 proteins in the control group were not changed. Significant changes of the expressions of MVD, VEGF and Ki67 proteins in the group A were found at different time points. Correlation analysis suggested a positive correlation between the expressions of VEGF and MVD proteins （r = 0.8793）, a positive correlation between the expressions of Ki67 and MVD proteins （r = 0.7614）, and a positive correlation between the expressions of VEGF and ki67 proteins （r = 0.6921）. CONCLUSION After argon-helium cryoablation treatment for the mice bearing prostate cancer, the expressions of MVD, VEGF and Ki67 proteins in local tumor were reduced on the 1st day. The lowest values of the factors were detected on the 3rd day after cryoablation, and then increased after that. Cryoablation combined with other modalities of treatment may effectively improve the treatment effects of cryoablation for prostate cancer.