Limits...
Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.

Nakao K, Tanaka S, Miura T, Sato K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Tanabe M - Cancer Sci. (2015)

Bottom Line: JNJ-28841072 suppressed in vitro phosphorylation of histone H3 with induction of cell polyploidy and death in a dose-dependent manner (IC50  = 0.8-1.2 μM).Our preclinical studies indicate that JNJ-28841072 is a promising novel therapeutic approach for the treatment of HCC.It might be worthy of evaluation in further studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Show MeSH

Related in: MedlinePlus

Pharmacobiological analysis of orthotopic xenograft models of hepatocellular carcinoma using HuH-7 cells (a,b) and SK-Hep1 cells (c,d). (a,c, upper) Transverse sections of liver tumor (T) or host normal liver (N) were stained with H&E. Magnification, ×40. The same sections were analyzed for expression of phosphohistone H3 (PhH3). (a,c, middle) magnification, ×40; (a,c, lower) magnification, ×200. (b,d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556391&req=5

fig04: Pharmacobiological analysis of orthotopic xenograft models of hepatocellular carcinoma using HuH-7 cells (a,b) and SK-Hep1 cells (c,d). (a,c, upper) Transverse sections of liver tumor (T) or host normal liver (N) were stained with H&E. Magnification, ×40. The same sections were analyzed for expression of phosphohistone H3 (PhH3). (a,c, middle) magnification, ×40; (a,c, lower) magnification, ×200. (b,d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).

Mentions: The liver xenograft model in HuH-7 described above was subjected to histological analysis by immunostaining to investigate the pharmacobiological effects of JNJ-28841072 in the hepatic microenvironment. Twenty-four hours after treatment with JNJ-28841072, there was a substantial decrease in PhH3 compared with the control (Fig.4). One week after treatment with JNJ-28841072, the total blood vessel area were substantially decreased by treatment with JNJ-28841072 and distance between tumor vessels and adjacent ischemic area compared with the control (Fig.5). Similar results were observed in SK-Hep1 orthotopic xenografts by treatment with JNJ-28841072 (Figs4c,d and 5d,e). The hepatocytes from the host liver were histologically normal at all points following JNJ-28841072 administration.


Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.

Nakao K, Tanaka S, Miura T, Sato K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Tanabe M - Cancer Sci. (2015)

Pharmacobiological analysis of orthotopic xenograft models of hepatocellular carcinoma using HuH-7 cells (a,b) and SK-Hep1 cells (c,d). (a,c, upper) Transverse sections of liver tumor (T) or host normal liver (N) were stained with H&E. Magnification, ×40. The same sections were analyzed for expression of phosphohistone H3 (PhH3). (a,c, middle) magnification, ×40; (a,c, lower) magnification, ×200. (b,d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556391&req=5

fig04: Pharmacobiological analysis of orthotopic xenograft models of hepatocellular carcinoma using HuH-7 cells (a,b) and SK-Hep1 cells (c,d). (a,c, upper) Transverse sections of liver tumor (T) or host normal liver (N) were stained with H&E. Magnification, ×40. The same sections were analyzed for expression of phosphohistone H3 (PhH3). (a,c, middle) magnification, ×40; (a,c, lower) magnification, ×200. (b,d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
Mentions: The liver xenograft model in HuH-7 described above was subjected to histological analysis by immunostaining to investigate the pharmacobiological effects of JNJ-28841072 in the hepatic microenvironment. Twenty-four hours after treatment with JNJ-28841072, there was a substantial decrease in PhH3 compared with the control (Fig.4). One week after treatment with JNJ-28841072, the total blood vessel area were substantially decreased by treatment with JNJ-28841072 and distance between tumor vessels and adjacent ischemic area compared with the control (Fig.5). Similar results were observed in SK-Hep1 orthotopic xenografts by treatment with JNJ-28841072 (Figs4c,d and 5d,e). The hepatocytes from the host liver were histologically normal at all points following JNJ-28841072 administration.

Bottom Line: JNJ-28841072 suppressed in vitro phosphorylation of histone H3 with induction of cell polyploidy and death in a dose-dependent manner (IC50  = 0.8-1.2 μM).Our preclinical studies indicate that JNJ-28841072 is a promising novel therapeutic approach for the treatment of HCC.It might be worthy of evaluation in further studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus