A novel targeting modality for renal cell carcinoma: human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D3

2010 ◽  
Vol 12 (11) ◽  
pp. 892-903 ◽  
Author(s):  
Nicole A. Johnson ◽  
Bing-Hung Chen ◽  
Shian-Ying Sung ◽  
Chia-Hui Liao ◽  
Wan-Chi Hsiao ◽  
...  
2012 ◽  
Vol 19 (8) ◽  
pp. 558-565 ◽  
Author(s):  
K C B Chaves ◽  
J P S Peron ◽  
R Chammas ◽  
L T Turaça ◽  
J B Pesquero ◽  
...  

2018 ◽  
Vol 40 (1) ◽  
pp. 24-32
Author(s):  
K CB Chaves ◽  
E M Costa ◽  
L F Teixeira ◽  
M H Bellini

Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b+Gr-1+ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b+Gr-1+ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b+Gr-1+ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b+Gr-1+ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment.


2021 ◽  
Vol 55 (5) ◽  
pp. 553-568

BACKGROUND/AIMS: Maintenance of whole-body ascorbate levels and distribution is mediated via sodium-dependent vitamin C transporters (SVCTs). The kidney is one of a few organs that express both SVCT1 and SVCT2. Recent evidence suggests that accumulation of ascorbate may be different in tumour compared to normal tissue, but data on SVCT levels in tumours is sparse. METHODS: The role of the two SVCT isoforms in ascorbate uptake in renal cell carcinoma (RCC) was investigated in vitro and in clinical samples. In three human RCC cell lines, we investigated SVCT protein levels and cellular location in response to ascorbate supplementation and withdrawal. In clinical RCC samples (n=114), SVCT patterns of staining and protein levels were analysed and compared to ascorbate levels. RESULTS: In cell culture, transporter levels and cellular location were not modified by ascorbate availability at any time up to 8h, although basal SVCT2 levels governed maximal ascorbate accumulation. In clinical samples, SVCT1 protein levels in papillary RCC (pRCC) were similar to matched normal renal cortex, but were increased in clear-cell RCC (ccRCC). Native SVCT2 (72 kDa) was significantly decreased in both pRCC and ccRCC tissues compared to cortex (p<0.01), whereas a modified form of SVCT2 (100 kDa) was significantly increased (p<0.001). There was no association between the transporters (SVCT1, native or modified SVCT2) and ascorbate concentrations in either normal or tumour tissues. SVCT1 and SVCT2 displayed diffuse cytoplasmic staining in both pRCC and ccRCC tumour cells, with cortex showing distinct membrane staining for SVCT1. CONCLUSION: We observed a re-distribution of ascorbate transporters in tumour tissue compared to normal cortex and a shift from native to modified SVCT2 in cell culture and clinical samples. Data presented here show that SVCT protein levels do not appear to predict intracellular ascorbate accumulation in RCC.


2010 ◽  
Vol 59 (9) ◽  
pp. 1357-1365 ◽  
Author(s):  
Flávia Gomes de Góes Rocha ◽  
Karen Cristina Barbosa Chaves ◽  
Roger Chammas ◽  
Jean Pierre Schatzmann Peron ◽  
Luiz Vicente Rizzo ◽  
...  

2006 ◽  
Vol 5 (9) ◽  
pp. 2165-2171 ◽  
Author(s):  
Hiroki Matsubara ◽  
Yoichi Mizutani ◽  
Fumiya Hongo ◽  
Hiroyuki Nakanishi ◽  
Yasunori Kimura ◽  
...  

2012 ◽  
Vol 66 (6) ◽  
pp. 464-468 ◽  
Author(s):  
Karen Cristina Barbosa Chaves ◽  
Lauro Thiago Turaça ◽  
João Bosco Pesquero ◽  
Gregory Mennecier ◽  
Maria Lucia Zaidan Dagli ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document