An Anti-CTGF-antibody Attenuates Tumor Invasion, Delays Tumor-growth, and Prolongs Survival Alone And In Combination With Radiation In An Orthotopic Glioma

We have previously demonstrated the effectiveness of adenovirus-mediated expression of antisense urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting tumor invasion in vitro and ex vivo. However, the therapeutic effect of the adenovirus-mediated antisense approach was shown to be transient and required potentially toxic, high viral doses. In contrast, RNA interference (RNAi)-mediated gene targeting may be superior to the traditional antisense approach, because the target mRNA is completely degraded and the molar ratio of siRNA required to degrade the target mRNA is very low. Here, we have examined the siRNA-mediated target RNA degradation of uPAR and MMP-9 in human glioma cell lines. Using RNAi directed toward uPAR and MMP-9, we achieved specific inhibition of uPAR and MMP-9. This bicistronic construct (pUM) inhibited the formation of capillary-like structures in both in vitro and in vivo models of angiogenesis. We demonstrated that blocking the expression of these genes results in significant inhibition of glioma tumor invasion in Matrigel and spheroid invasion assay models. RNAi for uPAR and MMP-9 inhibited cell proliferation, and significantly reduced the levels of phosphorylated forms of MAPK, ERK, and AKT signaling pathway molecules when compared with parental and empty vector/scrambled vector-transfected SNB19 cells. Furthermore, using RNAi to simultaneously target two proteases resulted in total regression of pre-established intracerebral tumor growth. Our results provide evidence that the use of hairpin siRNA expression vectors for uPAR and MMP-9 may provide an effective tool for cancer therapy.

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Growth-Induced Stress Inside Solid Tumor Using Thermoelasticity Model

Volume 2: Biomedical and Biotechnology Engineering; Nanoengineering for Medicine and Biology ◽

10.1115/imece2011-65745 ◽

2011 ◽

Author(s):

Zhi Zhu He ◽

Jing Liu

Keyword(s):

Stress Distribution ◽

Diffusion Equation ◽

Evolution Equation ◽

Tumor Growth ◽

Solid Tumor ◽

Tumor Invasion ◽

Host Tissue ◽

Stress Evolution ◽

Induced Stress ◽

Thermoelasticity Theory

The tumor growth strongly depends upon the availability of nutrients. Many experimental evidences recently indicated that stress play important role in tumor invasion. The growth-induced stress is from pressure imposed on tumor by surrounding tissues due to tumor expansion invasion. This paper introduces a model to characterize growth-induced stress in solid tumor by analogy with thermoelasticity theory. The model is composed of a nutrients diffusion equation and a stress evolution equation. The solid spheroid tumor stress distribution induced by tumor spatial non-uniformity growth is studied. Moreover, the mechanical interactions between the solid tumor and the surrounding host tissue are discussed detailed.

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Staging in Local Endometrial Carcinoma

Acta Radiologica ◽

10.1177/028418518903000516 ◽

1989 ◽

Vol 30 (5) ◽

pp. 525-529 ◽

Cited By ~ 6

Author(s):

B. Thorvinger ◽

T. Gudmundsson ◽

G. Horvath ◽

L. Forsberg ◽

S. Holtås

Keyword(s):

Magnetic Resonance ◽

Tumor Growth ◽

Endometrial Carcinoma ◽

Tumor Invasion ◽

False Negative ◽

Myometrial Invasion ◽

Uterine Wall ◽

Uterine Tumor ◽

Additional Tool ◽

Histopathologic Findings

Possible deep (more than an inner third of the uterine wall) myometrial invasion and cervical extension of endometrial carcinoma were evaluated prospectively using magnetic resonance (MR) and transabdominal real-time sonography (US) in 20 and 10 patients, respectively. The data obtained from these examinations were compared with hysterosalpingography (HSG) and clinical modalities including hysteroscopy, sounding and histopathologic findings after surgery. The concordance of outlining cervical extension was between MR and hysteroscopy 85 per cent, and between US and hysteroscopy 50 per cent. Deep myometrial tumor invasion was suggested in 4/10 patients by US and in 6/20 by MR, and was confirmed in all but one in each group at histologic examination of the resected uterus. There were no false negative US or MR examinations. Transabdominal US did not prove accurate in defining local endometrial carcinoma (distinguishing between stages I and II), but it may be used as an additional tool in revealing myometrial invasion. MR, however, seems to refine the delineation of uterine tumor growth.

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Continuous intracranial administration of suberoylanilide hydroxamic acid (SAHA) inhibits tumor growth in an orthotopic glioma model

Journal of Neuro-Oncology ◽

10.1007/s11060-007-9337-z ◽

2007 ◽

Vol 83 (3) ◽

pp. 267-275 ◽

Cited By ~ 44

Author(s):

Hasan C. Ugur ◽

Naren Ramakrishna ◽

Lorenzo Bello ◽

Lata G. Menon ◽

Seung-Ki Kim ◽

...

Keyword(s):

Tumor Growth ◽

Hydroxamic Acid ◽

Suberoylanilide Hydroxamic Acid ◽

Glioma Model ◽

Orthotopic Glioma

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Alteration of blood-CSF barrier by tumor invasion into the meninges

Journal of Neurosurgery ◽

10.3171/jns.1981.55.3.0445 ◽

1981 ◽

Vol 55 (3) ◽

pp. 445-449 ◽

Cited By ~ 20

Author(s):

Yukitaka Ushio ◽

Keiji Shimizu ◽

Yasuo Aragaki ◽

Norio Arita ◽

Toru Hayakawa ◽

...

Keyword(s):

Tumor Growth ◽

Survival Time ◽

Tumor Invasion ◽

Early Stage ◽

Tumor Inoculation ◽

Maximum Increase ◽

Walker 256 Carcinosarcoma ◽

Content Type ◽

Walker 256 ◽

Prevent Tumor Growth

✓ Cyclophosphamide and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were found to have an equivalent cytostatic effect in rats with subcutaneous transplants of Walker 256 carcinosarcoma. Rats with meningeal carcinomatosis received a single intravenous dose of cyclophosphamide (30 mg/kg) or ACNU (15 mg/kg) at various times after intracisternal inoculation of 1 × 104 Walker 256 carcinosarcoma cells. Cyclophosphamide, administered 1 day after tumor inoculation, failed to prevent tumor growth in the subarachnoid space. The survival time of these rats was prolonged only 10% to 14% compared to the controls, while ACNU produced a maximum increased survival time of 180%. If administered 2, 3, 4, and 5 days after tumor inoculation, both drugs were effective; cyclophosphamide yielded a maximum increase in median survival time of 109%, 94%, 90%, and 52%, and ACNU 127%, 139%, 240%, and 100%, respectively. These results indicate that the blood-cerebrospinal fluid (CSF) barrier was circumvented in the early stage of subarachnoid tumor growth, although some areas remained where the infiltrating tumor cells were protected from systemically administered drugs by the intact barrier.

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