TrkA基因的表达抑制神经母细胞瘤血管生成的实验研究

目的:探讨TrkA基因通过抑制神经母细胞瘤(NB)血管生成而阻止其生长、转移的可行性.方法:常规培养对照组SY5Y细胞、TrkA基因高表达的实验组细胞(SY5Y-TrkA)和表达载体基因的空载体组细胞(SY5Y-Vec);比较三组细胞的裸鼠皮下致瘤性:通过RT-PCR、免疫组织化学、微血管面积计算检测并比较三种细胞所致的肿瘤瘤体内血管生成情况.结果:SY5Y-Trk A细胞在裸鼠皮下的致瘤性和其所致肿瘤的血管生成能力明显下降.肿瘤终体积:对照组1.736±0.485cm3,空载体组1.803±0.751cm3,实验组0.3945±0.015cm3(P＜0.01);对照组与实验组相比,血管内皮生长因子(VEGF)的表达差别显著(P＜0.01);微血管密度(MVD):对照组27.2l±14.58,空载体组27.76±14.15,实验组4.08±4.72(P＜0.01).结论:TrkA基因能有效抑制神经母细胞瘤的血管生成和肿瘤生长,为应用基因抗血管治疗神经母细胞瘤提供理论依据.     

Expression of the neurotrophin receptor TrkA down-regulates expression and function of angiogenic stimulators in SH-SY5Y neuroblastoma cells

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors. Mechanisms regulating the expression of angiogenic factors in tumor cells are largely unknown. High expression of the neurotrophin receptor TrkA in neuroblastomas (NBs) is associated with a favorable prognosis, whereas TrkB is mainly expressed on aggressive, MYCN-amplified NBs. To investigate the biological effects of TrkA and TrkB expression on angiogenesis in NB, we examined the expression of angiogenic factors in the human NB cell line SY5Y and its TrkA and TrkB transfectants. In comparison with parental SY5Y cells, mRNA and protein levels of the examined angiogenic factors were significantly reduced in SY5Y-TrkA cells, whereas SY5Y-TrkB cells did not demonstrate a significant change. Conditioned medium of TrkB transfectants and parental SY5Y cells induced endothelial cell proliferation and migration, but this effect was completely absent in SY5Y-TrkA cells. TrkA expression also resulted in severely impaired tumorigenicity in a mouse xenograft model and was associated with reduced angiogenic factor expression and vascularization of tumors, as determined by immunohistochemistry and an in vivo Matrigel assay. TrkA expression inhibits angiogenesis and tumor growth in SY5Y NB cells by down-regulation of angiogenic factors, whereas expression of TrkB does not down-regulate the production of these angiogenic factors. The biologically different behavior of TrkA- and TrkB-expressing NBs may be explained in part by their effects on angiogenesis.     

裸鼠肺癌移植瘤中NRP-1的表达及其意义

Objective:To establish angiogenesis model of xenografts of lung cancer cell in nude mouse and investigate the expression of the neuropilin-1 (NRP-1) protein in tumors and its role in progression and angiogenesis of lung cancer.Methods:Human lung adenocarcinoma cells A549 were analyzed for the expression of vascular endothelial growth factor165(VEGF165)mRNA using RT-PCR in vitro.TWo groups of nude mice were subcutaneously inoculated with A549 at different tumor-loading time.Two groups of xenografts were jdentified by hematoxylin and eosin (HE) staining.their microvessel density (MVD) were analyzed meanwhile.Two groups were analyzed for the expression of NRP-1 protein and their mean absorbency by using immunohistochemistry and automatic image analysis system respectively.Results:A549 expressed VEGF165 mRNA,and xenografts of A549 in nude mice were successfully established and confirmed by HE staining.The atypia of cancer cells and angiogenesis were occurred in two groups.Two groups of MVD were 13.06±1158.23.61±3.11(vessels/mm2)(P＜0.01).NRP-1 protein was expressed in cytoplasm of vascular endothelium cells and partial tumor cells.Two groups of mean absorbency of NRP-1 were 0.1095±O.0228,0.1784±0.0151 (P＜0.01).Conclusion:The angioqenesis models of xenografts in nude mice with lung cancer cell A549 expressing VEGF165 mRNA at different tumor-loading times were established successfully.The expression of NRP-1 protein and MVD were increased with the tumor progression.Our results demonstrate that NRP-1 protein in lung cancer is related to angiogenesis.     

Human neuroblastoma cells produce extracellular matrix-degrading enzymes,induce endothelial cell proliferation and are angiogenic in vivo

Direct experimental evidence shows that tumor growth and metastases are angiogenesis-dependent. Neuroblastoma (NB) is the most common extracranial malignant solid tumor of childhood. In this study, we investigated 2 human NB cell lines, LAN-5 and GI-LI-N, for their capacity to secrete 2 extracellular matrix-degrading enzymes, MMP-2 and MMP-9, and to induce <0R><0B>in vitro<0R><0B> human microvascular endothelial cells (EC) to proliferate and in vivo angiogenesis in the chick embryo chorio-allantoic membrane (CAM) assay. Conditioned medium (CM) from both cell lines stimulated in vitro EC proliferation and the effect of LAN-5 CM was higher than that of GI-LI-N cells. Moreover, anti-VEGF, but not anti-FGF2 antibodies, prevented growth increment of EC. NB cell lines secreted the active form of MMP-2 almost exclusively, LAN-5 cells more than GI-LI-N cells. Both cell lines, LAN-5 cells more than GI-LI-N ones, induced angiogenesis in the CAM assay. Our data suggest that the 2 NB cell lines are angiogenic, to LAN-5 cells more than GI-LI-N ones. LAN-5 cells are indeed endowed with a more aggressive and invasive phenotype. Int. J. Cancer 77:449–454, 1998. © 1998 Wiley-Liss, Inc.     

Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human Hepatocel-Lular Carcinoma in Nude Mice

Objective To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) in combination of ganciclovir (GCV) against human hepatocellular carcinoma in nude mice. Methods HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups (n=8 each group) Ganciclovir group (Ⅰ), Ad group (Ⅱ), AdCMV-tk/GCV group (under the driving of CMV promoter) (Ⅲ) and AdKDR-tk/GCV group (Ⅳ). Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/(kg·d), ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and Ⅳ (P＜0.05). The mean MVDs in group Ⅰ, Ⅱ, Ⅲand Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 (microvessels/mm2), respectively. Significant differences were found between group Ⅲ and Ⅱ (P＜0.05), Ⅳ and Ⅱ (P＜0.01), and Ⅳ and Ⅲ (P＜0.01). Conclusion Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC.     

Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer

To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer.     

Small renal masses progressing to metastases under active surveillance

BACKGROUND:

The authors systematically reviewed the literature and conducted a pooled analysis of studies on small renal masses who underwent active surveillance to identify the risk progression and the characteristics associated with metastases.

METHODS:

A search of the MEDLINE database was performed to identify all clinical series that reported the surveillance of localized renal masses. For studies that reported individual‐level data, clinical and radiographic characteristics of tumors without progression were compared with the characteristics of tumors that progressed to metastases.

RESULTS:

Eighteen series (880 patients, 936 masses) met screening criteria; and, among these, 18 patients were identified who had tumors that progressed to metastasis (mean, 40.2 months). Six studies (259 patients, 284 masses) provided individual‐level data for pooled analysis. At a mean (±standard deviation) follow‐up of 33.5 ± 22.6 months, the mean initial greatest tumor dimension was 2.3 ± 1.3 cm, and mean linear growth rate was 0.31 ± 0.38 cm per year. Sixty‐five masses (23%) exhibited zero net growth under surveillance, and none of those masses progressed to metastasis. A pooled analysis revealed increased age (age 75.1 ± 9.1 years vs 66.6 ± 12.3 years; P = .03), an initial greatest tumor dimension (4.1 ± 2.1 cm vs 2.3 ± 1.3 cm; P < .0001), initial estimated tumor volume (66.3 ± 100.0 cm³ vs 15.1 ± 60.3 cm³; p = .0001), linear growth rate of (0.8 ± 0.65 cm per year vs 0.3 ± 0.4 cm per year; P = .0001), and a volumetric growth rate of 27.1 ± 24.9 cm³ per year (vs 6.2 ± 27.5 cm³ per year; P < .0001) in the progression cohort.

CONCLUSIONS:

A substantial proportion of small renal masses remained radiographically static after an initial period of active surveillance. Progression to metastases occurred in a small percentage of patients and generally was a late event. The current results indicated that, in patients who have competing health risks, radiographic surveillance may be an acceptable initial approach, and delayed intervention may be reserved for patients who have tumors that exhibit significant linear or volumetric growth. Cancer 2012;. © 2011 American Cancer Society.     

兔VX2脑瘤血管生成的灌注CT研究

Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.     

Lentivirus-mediated CD/TK fusion gene transfection neural stem cell therapy for C6 glioblastoma

A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat’s neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells’ transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p?<?0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6 %, p?<?0.05) either in vitro or in vivo (35.47 %, p?<?0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76?±?1.37 mm³, which is smaller than the others (group2 27.28?±?4.11 mm³, group3 27.94?±?2.08 and 28.61?±?2.97 mm³; p?<?0.05). The other groups’ tumor size was not significant (p?>?0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p?<?0.05; group 1 48.86?±?1.97, group 2 28.67?±?3.75, group 3 31.5?±?1.27, group 4 29.3?±?1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl–guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.     

Effects of perioperative cimetidine administration on tumor cell nuclear morphometry and DNA content in patients with gastrointestinal cancer

Cimetidineisawell-knownhistaminetype2receptorantagonistwidelyusedtotreatpepticulcer.Recentclinicaltrialsandcasereportsalsohaveconfirmeditsantitumoreffect.Colorectalcancerpatientstreatedwithcimetidinehadsurvivaladvantageoverthosewhodidnotreceivethisdrug.["'lInvitrostudieshavealsodemonstrateditsinhibitoryeffectoncoloncancercells.[3]Theseeffectsgenerallyhavebeenattributedtoimmunomodulatoryfunctionofcimetidine.[1-3]Andourpreviousstudyalsosupportedthisview.I4]Arethereothermechanismsbywhichcimetid…     

Local anesthetics inhibit kinesin motility and microtentacle protrusions in human epithelial and breast tumor cells

In breast cancer, there is a correlation between tissue factor (TF) expression, angiogenesis and disease progression. TF stimulates tumour angiogenesis, in part, through up-regulation of vascular endothelial growth factor (VEGF). Therefore, this study aimed to establish whether TF stimulates angiogenesis and tumour progression directly and independent of VEGF up-regulation. Initially, the effects of TF and VEGF were assessed on endothelial cell migration (Boyden chamber) and differentiation (tubule formation on Matrigel). Subsequently, MDA-MB-436 breast cancer cells, which produce high levels of both TF and VEGF (western blot analysis), were established in vivo, following which tumours were treated three times per week for 3 weeks with intra-tumoural injections of either anti-VEGF siRNA, anti-TF shRNA, the two treatments combined, or relevant controls. Both VEGF and TF significantly stimulated endothelial cell migration and tubule formation (P < 0.02). Breast cancer xenografts (MDA-MB-436) treated with TF or VEGF-specific agents demonstrated significant inhibition in tumour growth (VEGFsiRNA 61%; final volume: 236.2 ± 23.2 mm³ vs TFshRNA 89%; 161.9 ± 17.4 mm³ vs combination 93%; 136.3 ± 9.2 mm³ vs control 400.4 ± 32.7 mm³; P < 0.005). Microvessel density (MVD), a measure of angiogenesis, was also significantly inhibited in all groups (MVD in control = 29 ± 2.9; TFshRNA = 18 ± 1.1; VEGFsiRNA = 16.7 ± 1.5; both = 12 ± 2.1; P < 0.004), whereas the proliferative index of the tumours was only reduced in the TFshRNA-treated groups (control = 0.51 ± 0.011; TFshRNA = 0.41 ± 0.014; VEGFsiRNA = 0.49 ± 0.013; both = 0.41 ± 0.004; P < 0.008). These data suggest that TF has a direct effect on primary breast cancer growth and angiogenesis, and that specific inhibition of the TF-signalling pathway has potential for the treatment of primary breast cancer.     

Antitumor and antivascular effects of AC-7700, a combretastatin A-4 derivative,against rat liver cancer

Background. Unlike the many chemotherapeutic agents that do not effectively stop blood flow or induce necrosis in hepatocellular carcinoma, AC-7700 has been shown to inhibit tubulin polymerization and selectively stop tumor blood flow. The aim of this study was to elucidate the antivascular and antitumor effects of AC-7700 on rat hepatoma. Methods. AH-130 cells, a rat hepatoma cell line, were solidified and implanted into the liver of Donryu rats. Vascularity of the liver tumor was directly identified by in-vivo fluorescence microscopy from 0 to 60 min after the injection of 10 mg/kg AC-7700. To observe the antivascular effect of AC-7700, the vascular density of the tumor was measured and assessed as the ratio of preinjection to postinjection values. The antitumor effects were evaluated with histopathologic findings and analysis of animal survival. Results. In-vivo microscopic observation showed that tumor perfusion diminished within 30 min after AC-7700 administration. Vascular density in the AC-7700 group was significantly less than that in the control group at 60 min (AC-7700, 26.3 ± 16.4%; control, 88.5 ± 9.2%; P < 0.001). After AC-7700 injection, marked necrosis of tumor cells was observed histologically, and tumor area was decreased significantly (AC-7700, 11.5 ± 15.4 mm²; control, 43.5 ± 18.3 mm²; P < 0.05). The survival rate (50%) of the AC-7700 group animals was better than that of the control group (0%; P < 0.01). Conclusion. Markedly decreased tumor perfusion was induced by AC-7700 within 30 min, and this decrease may have contributed to the tumor necrosis and favorable outcome in the treatment group. AC-7700 appears to be a promising agent for the treatment of hepatocellular carcinoma. Received: September 14, 2001 / Accepted: February 21, 2002     

Diminished visceral adipose tissue in cancer cachexia

To estimate the relationship between the visceral adipose tissue (AT) area and cancer cachexia, 13 cachectic patients (7 males, 6 females; age 65.2 ± 11.0 years; body mass index 20.8 ± 4.1 kg/m²) were examined by computed tomography (CT) scanning. Cachectic cancer patients who had a 10% decrease of body weight and died within 6 months because of gastrointestinal carcinoma had a significantly smaller visceral AT area than control subjects (mean ± sd: 43.9 ± 42.2 cm² vs. 93.4 ± 56.0 cm², P < 0.05, P=0.014). Otherwise, there were no significant differences between the visceral AT areas of cachectic cancer patients and those of cancer patients with resectable tumors treated by curative operation (mean ± sd: 68.8 ± 57.7 cm²) (NS, P=0.206). There was, however, a tendency for cachectic cancer patients to have a smaller visceral AT area than those with resectable tumors. This result suggests that the visceral AT area is not preserved in the cachectic state associated with cancer. © 1994 Wiley-Liss, Inc.     

Adriamycin Thermotherapy through the Hepatic Artery Using VX2 Carcinoma in Rabbit liver as a Model

OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.     

Inhibitory effect of suramin in rat models of angiogenesis in vitro and in vivo

The aim of the present study was to test the ability of the chemotherapeutic agent suramin to inhibit angiogenesis in experimental models in vitro and in vivo. In the culture of rat aortic rings on fibronectin, suramin dose-dependently inhibited vascular cell growth, achieving the maximal effect (mean − 88% versus controls, P < 0.05) at 400 μg/ml. Image analysis showed that suramin could inhibit microvessel sprouting in fibrin from rat aortic rings as evaluated by the ratio between the cellular area and the mean gray value of the sample (sprouting index); suramin at 50 μg/ml significantly reduced the sprouting index from the control value of 0.35 ± 0.04 to 0.14 ± 0.02 mm²/gray level (P < 0.05). Likewise, the area occupied by cells was 19.2 ± 1.8 mm² as compared with 41.8 ± 4.2 mm² in controls (P < 0.05). In the rat model of neovascularization induced in the cornea by chemical injury, suramin at 1.6 mg/eye per day reduced the length of blood vessels (0.7 ± 0.1 mm as compared with 1.5 ± 0.1 mm in controls, P < 0.05). In the same model the ratio between the area of blood vessels and the total area of the cornea (area fraction score) was decreased by suramin from 0.19 ± 0.02 in controls to 0.03 ± 0.003 (P < 0.05). Suramin given i.p. at 30 mg/kg per day markedly inhibited the neovascularization induced in the rat mesentery by compound 48/80 or conditioned medium from cells secreting the angiogenic protein fibroblast growth factor-3 (FGF-3). The area fraction score in control rats treated with compound 48/80 was 0.31 ± 0.03, and this was reduced to 0.07 ± 0.01 by suramin (P < 0.05). After i.p. administration of FGF-3 the area fraction score was reduced by suramin from 0.29 ± 0.03 to 0.05 ± 0.01 (P < 0.05). These results provide evidence that suramin exerts inhibitory effects on angiogenesis in both in vitro and in vivo models. Received: 9 January 1998 / Accepted: 29 June 1998     

Radiosurgical decompression of metastatic epidural compression

BACKGROUND:

Surgical decompression of metastatic epidural compression (MEC) improved ambulatory function. Spine radiosurgery can accurately target the epidural tumor and deliver high radiation doses for tumor control. Therefore, a clinical trial was performed to quantitatively determine the degree of epidural decompression by radiosurgery of metastatic epidural compression.

METHODS:

Sixty‐two patients with a total of 85 lesions of metastatic epidural compression were treated. Epidural compression was diagnosed by magnetic resonance imaging (MRI) scans. Main criteria of inclusion were neurological status with muscle power 4 of 5 or better. Radiosurgery was performed to the involved spine segment, including the epidural mass with median dose of 16 Gy (range 12‐20 Gy) in a single session. All patients had prospective clinical follow‐up, ranging from 1‐48 months (median 11.5 months), and 36 patients had pretreatment and post‐treatment imaging, ranging from 2‐33 months (median 9.3 months). Primary endpoints were epidural tumor control and thecal sac decompression.

RESULTS:

The mean epidural tumor volume reduction was 65 ± 14% at 2 months after radiosurgery. The epidural tumor area at the level of the most severe spinal cord compression was 0.82 ± 0.08 cm² before radiosurgery and 0.41 ± 0.06 cm² after radiosurgery (P < .001). Thecal sac patency improved from 55 ± 4% to 76 ± 3% (P < .001). Overall, neurological function improved in 81%.

CONCLUSIONS:

This study demonstrated a radiosurgical decompression of epidural tumor. Although neurosurgical decompression and radiotherapy is the standard treatment in patients with good performance, radiosurgical decompression can be a viable noninvasive treatment option for malignant epidural compression. Cancer 2010. © 2010 American Cancer Society.     

Doxorubicin hydrochloric increases tumour coagulation and end-point survival in percutaneous microwave ablation of tumours in a VX2 rabbit tumour model

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually.

Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5?min and 40 W for 5?min), intravenous injection of 4?mg/kg DOX, and combined therapy. Tumours were analysed at 4?h and 24?h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24?h after treatment.

Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52?cm² ± 0.48 (SD), 4.08?cm² ± 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52?cm² ± 0.48 (SD), 1.69?cm² ± 0.34?cm², respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4?h and 24?h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4?h and 24?h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p < 0.01) or the DOX group (mean 35.17 days ± 7.63, p < 0.01).

Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.     

Expression of vascular endothelial growth factor in primary non-small cell lung carcinoma

TumorgrowthisdependentuponangiogenesisifitdevelopsfromminimalsizesuchasImm3toabiggersize.[]]Themechanismbywhichtumorsinduceangiogenesishavereceivedconsiderableattentioninrecentyears.Oneofthetumor-secretedangiogenesisfactors,vascularendothelialgrowthfactor(VEGF),appearstoplayanimportantroleintumorangiogenesis.["']VEGFexpressionhasbeendetectedinseveralhumantumors,includingglioblastoma,["']ovarian,[']breast,l']colorectal,[']kidney,[']bladderll()Iandgastriccarcinomas.lll]Blockingwithanti-VEG…     

Investigation of a plasmid containing a novel immunotoxin VEGF165‐PE38 gene for antiangiogenic therapy in a malignant glioma model

Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165‐PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38‐IRES2‐EGFP plasmid. ELISA was used to confirm the expression of VEGF165‐PE38 in the transfected cells. These cells released 1396 ± 131.9 pg VEGF165‐PE38/1×10⁴ cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary‐like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38‐IRES2‐EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 ± 0.69/0.74 mm², and was significantly lower than that in the control groups (9.33 ± 1.99/0.74 mm², 8.09 ± 1.39/0.74 mm² and 8.49 ± 1.69/0.74 mm²). Immunohistochemistry analysis indicated that immunotoxin VEGF165‐PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165‐PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.