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Case Reports
. 2016 Apr;14(2):e187-93.
doi: 10.1016/j.clgc.2015.11.004. Epub 2015 Nov 11.

Antitumor Response to Combined Antiangiogenic and Cytotoxic Chemotherapy in Recurrent Metastatic Chromophobe Renal Cell Carcinoma: Response Signatures and Proteomic Correlates

Affiliations
Case Reports

Antitumor Response to Combined Antiangiogenic and Cytotoxic Chemotherapy in Recurrent Metastatic Chromophobe Renal Cell Carcinoma: Response Signatures and Proteomic Correlates

Abhishek Maiti et al. Clin Genitourin Cancer. 2016 Apr.
No abstract available

Keywords: Cell signaling pathways; Morphoproteomics; Refractory; Resistance; Resistant.

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Conflict of interest statement

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed by the authors.

Figures

Figure 1
Figure 1. Analysis of chromophobe renal cell cancer
Immunohistochemical staining showed a. expression of p-IGF-1 receptor phosphorylated on tyrosine 1165/1166 at up to 2+ (on a scale of 0 to 3+) in the cytoplasmic compartment and up to 1+ on the plasmalemmal aspect, b. absence of expression (0 signal intensity) of p-c-Met (Tyr1234/1235) in the tumor cells, c. expression with nuclear translocation of p-ERK 1/2 (Thr 202/Tyr204) in nearly one-third of the tumor cells, d. Up to 3+ nuclear expression of p-mTOR (Ser 2448), e. expression of p-Akt (Ser 473) up to 1+ in the plasmalemmal and nuclear compartments. f. Overnight negative control. g. Absence of mutant p53 expression in viable tumor, and h. expression of mutant p53 in perinecrotic tumor cells.
Figure 2
Figure 2. Analysis of tumor after patient failed vandetanib and everolimus combination
a. The mitotic index is 6 mitotic figures per 10 high power fields. Immunohistochemical staining showed b. the antiapoptotic protein, Bcl-2 was expressed at up to 3+ in the cytoplasm of the tumor cells, c. nuclear immunopositivity for p-STAT3 (Tyr705) up to 3+. Analysis for angiogenic pathway proteins showed d. mild expression (up to 1+) of hypoxia-inducible factor (HIF)-1 alpha, confined to the cytoplasm, e. moderate expression of HIF-2 alpha (up to 2+) in the cytoplasmic compartment, and f. moderate expression (up to 2+) of vascular endothelial growth factor (VEGF)-A isoform on the plasmalemmal aspect. g. CD44 was variably expressed from 0 to 3+ on the plasmalemmal aspect of the tumor cells. There was greater plasmalemmal expression in the viable tumor cells adjacent to the necrotic tumor cells consistent with the influence of the hypoxic microenvironment. h. Glioma-associated oncogene protein (Gli) 2 showed variable expression in the tumoral nuclei (up to 3+), once again most pronounced in the viable tumor cells adjacent to the necrotic region.
Figure 3
Figure 3
CT scan of the abdomen showing response to hepatic arterial infusion therapy in the liver metastases. a. pre-therapy scans showing large liver metastases. b. post- therapy scans showing reduced tumor bulk

References

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