Variable Sensitivity of Endothelial Cells to Epirubicin in Xenografts of Human Nasopharyngeal Carcinoma CNE-2 Cells

Zhang, Xiao Shi; Zhu, Xiao Feng; Gao, Jin Song; Ye, Yan Li; Feng, Qi Sheng; Liu, Zong Chao; Zeng, Yi Xin

doi:10.4161/cbt.78

Cited by 7 publications

(6 citation statements)

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“…15 Strikingly, while slowly released low-dose 5-FU from microcapsules was cytotoxic for a prostatic tumor vasculature, it is a bolus injection and single exposure to free EPI that is apparently cytotoxic to the VX2 tumor target. This is an observation that is in line with Zhang et al study 43 and may pave the way for our technique to possibly become a cryo-assisted antivascular chemotherapy. For the Co-CACH technique to be effective at whole tumor ablation, the injectate should have been distributed to the whole ice ball and tumor margin.…”

Section: Discussionsupporting

confidence: 88%

Percutaneous Tumor Ablation

Xiao

et al. 2016

Technol Cancer Res Treat

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This acute study was aimed at exploring the ability of a cryoablative lesion to drive the distribution of a concomitant in situ injection of a free epirubicin-ethanol-ethiodol-methylene blue mixture. We report the feasibility and safety of this new percutaneous computed tomography-guided combinatorial ablative procedure on VX2 tumors. Eight New Zealand white rabbits bearing 16 tumors on both side of the back muscle were randomly selected and treated on the same day with the following procedures: (1) 8 concomitant cryoablation and interstitial chemotherapy and (2) 8 intratumor marginal chemotherapy. For the latter, an injection needle was positioned at the inner distal margin of a first selected tumor side, where the chemotherapy was delivered during 5 serial sequences. For the concomitant therapy, a single cryoneedle maintained the ice front at the tumor margin, where a needle delivered the drug dose during 5 freeze-injection-thaw sequences. Enhanced computed tomography scans on days 3, 7, and 10 assessed the tumor contours and the tracer localization. Two rabbits were killed on days 0, 3, 7, and 10 for gross and histopathological analyses. During the concomitant therapy, ioversol was distributed at the tumor and iceball margins along with the methylene blue. Enhanced computed tomography on days 3, 7, and 10 showed a focal enlarging defect of the tumor marginal enhancing rim. The rim coincided with focal necrosis at histopathology. During the intratumor chemotherapy procedure, computed tomography showed that the tracers distributed mostly over the tumor mass. No marginal necrosis was detected at histopathology. On day 10, the tumor size for the intratumor chemotherapy group was twice that of the concomitant therapy group. No adverse events were observed. In this VX2 tumor model, our image-guided concomitant therapy is feasible and may enhance the effectiveness of a free epirubicin tracer mixture at the tumor margin.

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Section: Discussionsupporting

confidence: 88%

Percutaneous Tumor Ablation

Xiao

et al. 2016

Technol Cancer Res Treat

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“…Reductions in tumor RNA integrity by epirubicin/docetaxel chemotherapy may stem from activation of tumor cell RNases [33,34] or from the release of lysosomal RNases upon tumor cell death [33,35]. Since both epirubicin and docetaxel are cytotoxic to endothelial cells of the tumor vasculature [36][37][38], their effects on tumor RNA quality may also be through nutrient/growth factor deprivation, and/or the induction of hypoxia upon destruction of tumor blood vessels. Consistent with the latter view, MCF-7 breast tumor cells cultured in the laboratory of AP for 72 h under hypoxic conditions with 9 nM epirubicin and 6 nM We also observed that mid-treatment dose-dependent reductions in tumor RIN (but not tumor cellularity) were Tumor RIN may be a much more effective biomarker for measurement of drug response or tumor viability than tumor cellularity, since the former changed in proportion to drug dose level and was correlated with pCR earlier in treatment.…”

Section: Discussionmentioning

confidence: 99%

Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients

Parissenti

Chapman

Kahn

et al. 2009

Breast Cancer Res Treat

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The CAN-NCIC-MA22 phase I/II clinical trial evaluated women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel at 2 or 3 weekly intervals in sequential cohorts. The relationship between various biomarkers and treatment response was assessed. Breast biopsy cores were obtained from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was performed to determine baseline levels of estrogen receptor (ER), progesterone receptor (PR), Her2/Neu protein (HER2), and topoisomerase II (Topo 2),expressed as percent positive stain. Tumor RNA integrity(RIN) and tumor cellularity were measured pre-, mid- and post-treatment by capillary electrophoresis and light microscopy after hematoxylin/eosin staining, respectively.Associations between 1) maximum RIN and 2) tumor cellularity at the three time points with baseline levels of ER,PR, Her2, and topo II were assessed using Spearman and Pearson correlation coefficients. Associations between RIN and tumor cellularity with chemotherapy dose level orpathologic response were assessed using one-way ANOVA.In this study, we observed that low mid-treatment maximum RIN (but not tumor cellularity) was associated with high chemotherapy drug dose level (P = 0.05) and eventual pathologic complete response (pCR) (P = 0.01). Posttreatment,low maximum RIN was found to be associated with low tumor cellularity (P = 0.004), and low tumor cellularity with pCR (P = 0.01). Post-treatment tumor cellularity was lowest in patients with tumors having high baseline PR levels (P = 0.05). The association of midtreatment RIN with drug dose level and with pCR suggests that tumor RIN may represent an important new biomarker for measuring response to chemotherapy in breast cancer patients.

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“…The activation of KDR has also been shown to correlate with tumor growth, lymph node metastasis, and resistance to chemotherapy in many kinds of tumors (Thakker et al, 1999;Baek et al, 2000). Binding of VEGF to KDR receptor on the surface of endothelial cells facilitates its autophosphorylation of the protein tyrosine kianse domain (Takahashi et al, 1999;Ichikura et al, 2001;Zhang et al, 2002). Activation of KDR by VEGF results in activation of phosphatidyl inositol 3-kinase/AKT, MAPK, and protein kinase C; the ultimate cellular response is DNA synthesis and cell proliferation.…”

mentioning

confidence: 99%

“…Activation of KDR by VEGF results in activation of phosphatidyl inositol 3-kinase/AKT, MAPK, and protein kinase C; the ultimate cellular response is DNA synthesis and cell proliferation. Vascular endothelial growth factor receptors (VEGFRs) are up-regulated on endothelium at sites of active angiogenesis, providing an opportunity for selective therapeutic intervention (Hanahan, 1997;Zhang et al, 2002).…”

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confidence: 99%

Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone), a Component from Chinese Herbal Medicine

Zhu

Xie²,

Zhou³

et al. 2005

Mol Pharmacol

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Antiangiogenesis is a promising strategy of cancer treatment. Vascular endothelial growth factor receptor [fetal liver kinase/ kinase-inserting domain-containing receptor (KDR)] is a tyrosine kinase receptor and has been strongly implicated in tumor angiogenesis. In this study, we report that 2Ј,4Ј-dihydroxy-6Ј-methoxy-3Ј,5Ј-dimethylchalcone (ON-III), extracted from the dried flower Cleistocalyx operculatus, used in traditional Chinese medicine, reversibly inhibited KDR tyrosine kinase phosphorylation, but epidermal growth factor receptor tyrosine kinase phosphorylation was unaffected under the same concentrations of ON-III. ON-III also inhibited mitogenactivated protein kinase (MAPK) and AKT activation of KDR signal transduction in downstream molecules without reduced total MAPK and AKT. The results in vitro showed that ON-III inhibited growth of human vascular endothelial HDMEC cells in the presence of VEGF preferentially, compared with epidermal growth factor. Systemic administration of ON-III at nontoxic doses in nude mice resulted in inhibition of subcutaneous tumor growth of human hepatocarcinoma Bel7402 and lung cancer GLC-82 xenografts. The tumor vessel density decreased, as determined by immunohistochemical staining, for CD31 after ON-III treatment. These results indicated that ON-III inhibited KDR tyrosine kinase, shut down KDR-mediated signal transduction, and inhibited tumor growth of human xenografts in vivo.

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Variable Sensitivity of Endothelial Cells to Epirubicin in Xenografts of Human Nasopharyngeal Carcinoma CNE-2 Cells

Cited by 7 publications

References 20 publications

Percutaneous Tumor Ablation

Percutaneous Tumor Ablation

Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients

Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone), a Component from Chinese Herbal Medicine

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