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Cancer-Research-UpdatesWEB

EGCG Suppresses Melanoma Tumor Angiogenesis and Growth without Affecting Angiogenesis and VEGF Expression in the Heart and Skeletal Muscles in Mice
Pages 19-29
Kevan B. Tucker, Kristina L. Makey, Edmund Chinchar, Min Huang, Natale Sheehan, Srinivasan Vijayakumar and Jian-Wei Gu

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.3

Published: 31 January 2014

Open Access 


Abstract: Melanoma is a highly malignant cancer with a potent capacity to metastasize distantly and has a higher mortality. There is no effective therapy for high risk melanoma patients to prevent relapse or distant metastasis. Therefore effective chemoprevention strategies are needed. The present study mainly evaluates the effects of EGCG on melanoma angiogenesis, growth, and capillary density (CD) in the heart and skeletal muscles of mice. 5 x 10^5 B16F10 cells were inoculated into the right proximal dorsal of the back in the eight week old male mice (n=12). Then, 6 mice received EGCG at 50–100 mg/kg/d in drinking water for 4 weeks and 6 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, hearts, and limb muscles were collected and measured for VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. Compared to the control, EGCG treatment significantly reduced tumor weight (2.9±0.5 vs. 5.9±1.1 g; P<0.01; n=6), melanoma CD (117±9 vs. 167±23; P<0.01), and melanoma VEGF expression (32±1.5 vs. 42±2 pg/mg; P < 0.01), respectively. Also EGCG had no effects on body weight, heart weight, angiogenesis or VEGF expression in the heart and skeletal muscle of mice. EGCG (20-50 µg/ml) significantly inhibited the proliferation, migration, VEGF expression, and the activation of HIF-1α and NFκB in cultured B16F10 cells, respectively. These findings support the hypothesis that EGCG, a major green tea polyphenol, directly targets tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of melanoma, and that the down-regulation of VEGF expression by EGCG is associated with the inhibition of HIF-1α and NFκB activation. EGCG has great potential as a chemopreventive agent because it has no effect on angiogenesis in normal tissue and has low toxicity.

Keywords: Melanoma, angiogenesis, proliferation, migration, EGCG, green tea polyphenols,VEGF,HIF-1α, NFκB, and capillary density in the heart.
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Cancer-Research-UpdatesWEB

Intraparenchymal chordoid MeningiomaAfter Radiotherapy for Hodgkin Lymphoma: A Case Report and Review of the Literatur
Pages 30-41
Mustafa Efendioglu, Recep Basaran, Dogan Gundogan, Fatih Han Bolukbası, Mustafa Kaksi, Aydin Sav and Tuncay Kaner

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.4

Published: 31 January 2014

Open Access 


Abstract: Objective: Hodgkin lymphoma can be treated by radiotherapy or chemotherapy alone or combined. Meningiomas account for 1-4.2% of all primary intracranial tumors in children, and chordoid meningioma is a very rare subtype. In this study, we investigated a case of an intraparenchymal chordoid meningioma that developed during the early stage in a patient with Hodgkin lymphoma who had been treated with radiotherapy.

Case: A 10-year-old male patient was diagnosed with Hodgkin lymphoma and was treated with a combination of radiotherapy and chemotherapy. He presented at our emergency service 6 years later. He had a fever and was suffering from discomfort and insignificant left hemiparesis (4/5). Contrast-enhanced cranial magnetic resonance imaging (MRI) showed a mass in the right temporoparietal region. The intracranial lesion was surgically excised. The tumor was identified as a WHO grade 2 chordoid meningioma by the pathological examination. The Ki-67 proliferation index was found to be 20-25%.

Conclusion: Surgeons must remember that radiation-associated meningiomas may occur in the early stage of the treatment as well as in the late stage. Young patients with grade 2 chordoid meningiomas must be followed-up in case of recurrence, and tumors with high Ki-67 indexes are highly expected to relapse.

Keywords: Meningioma, Hodgkin lymphoma, radiation, secondary tumor, chordoid, intraparenchymal.
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Cancer-Research-UpdatesWEB

Factors Influencing Percentage Yield of Side Population Isolated in Ovarian Cancer Cell LineSK-OV-3
Pages 30-41
Yuling Chen, Sui-Lin Mo, Felix Wu Shun Wong, George Qian Li, Yen Siew Loh, Basil D. Roufogalis, Maureen V. Boost and Daniel Man-Yuen Sze

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.5

Published: 31 January 2014

Open Access 


Abstract: Isolation of side population (SP) cells has been recognized as a useful technique for the isolation and identification of hematopoietic stem cells or cancer stem cells (CSCs). Thus the yield and purity of isolated SP cells would have a profound influence on the research outcomes in these two important areas. Hoechst 33342 exclusion assay technique has been used for the identification of SP cells. However, diverse Hoechst staining protocols giving different SP yields even from the same tissue type or same cell line have been reported in different laboratories. In this study we systematically investigated the underlying factors influencing the SP yield using Hoechst dye staining and a robust platform of flow cytometric analysis of the human ovarian cancer cell line SK-OV-3. Our study revealed that SP yield was not only affected by the Hoechst 33342 concentration, staining cell density, staining cell viability, staining duration, staining medium, flow cytometric setting and SP gating strategy, but was also affected by the cell passage number in SK-OV-3. This is the first systematic study on the factors affecting SP yield in adherent cells that mimic many solid tumour tissues. Our results provide important technical guidelines to help ensure reproducible and comparable results in SP and CSCs study.

Keywords: Side population (SP), SK-OV-3, cancer stem cells (CSCs), flow cytometry (FCM), Hoechst 33342.
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Cancer-Research-UpdatesWEB

B5H7, a Morpholine Derivative of 23-Hydroxybetulinic Acid, Reverses Doxorubicin Resistance in HepG2/ADM
Pages 59-66
Nan Yao, Dao-Lu Liu, Ying-Jie Li, Zhe-Sheng Chen, Zhi Shi, Wei-Min Chen, Zhe Yao, Dong-Mei Zhang and Wen-Cai Ye

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.6

Published: 31 January 2014

Open Access 


Abstract: Multidrug resistance (MDR) is the major cause of the failure of cancer chemotherapy. Development of MDR reversers is an important strategy to improve the efficacy of cancer chemotherapy. Here, we have found a morpholine derivative of 23-hydroxybetulinic acid, B5H7, with a reversal effect on MDR cancer cells. Our studies showed that B5H7 enhanced cytotoxicity of doxorubicin, but no cisplatin in MDR cancer cells HepG2/ADM. And we found that B5H7 not only increased the intracellular accumulation of P-glycoprotein substrates doxorubicin and rhodamine123, but also reduced the efflux of rhodamine123 in HepG2/ADM cells. Further studies showed B5H7 did not alter the protein level of P-glycoprotein and it also had no effect on P-glycoprotein ATPase activity. Taken together, we have found that B5H7 could reverse doxorubicin resistance in HepG2/ADM cells by inhibiting the transport function of P-glycoprotein. These findings contribute to developing B5H7 as an adjuvant to anticancer chemotherapy with doxorubicin.

Keywords: Doxorubicin resistance, ABC transporter, P-glycoprotein, 23-HBA derivative B5H7, HepG2/ADM.
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