BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against g...BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Box, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm(3), P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 a展开更多
In this paper we study a free boundary problem modelling tumor growth, proposed by A. Friedman in 2004. This free boundary problem involves a nonlinear second-order parabolic equation describing the diffusion of nutri...In this paper we study a free boundary problem modelling tumor growth, proposed by A. Friedman in 2004. This free boundary problem involves a nonlinear second-order parabolic equation describing the diffusion of nutrient in the tumor, and three nonlinear first-order hyperbolic equations describing the evolution of proliferative cells, quiescent cells and dead cells, respectively. By applying Lp theory of parabolic equations, the characteristic theory of hyperbolic equations, and the Banach fixed point theorem, we prove that this problem has a unique global classical solution.展开更多
In this paper, we study a free boundary problem arising from the modeling of tumor growth. The problem comprises two unknown functions： R = R（t）, the radius of the tumor, and u = u（r, t）, the concentration of nut...In this paper, we study a free boundary problem arising from the modeling of tumor growth. The problem comprises two unknown functions： R = R（t）, the radius of the tumor, and u = u（r, t）, the concentration of nutrient in the tumor. The function u satisfies a nonlinear reaction diffusion equation in the region 0 〈 r 〈 R（t）, t 〉 0, and the function R satisfies a nonlinear integrodifferential equation containing u. Under some general conditions, we establish global existence of transient solutions, unique existence of a stationary solution, and convergence of transient solutions toward the stationary solution as t →∞.展开更多
文摘BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Box, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm(3), P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 a
基金Supported by the National Natural Science Foundation of China （No.10171112）.
文摘In this paper we study a free boundary problem modelling tumor growth, proposed by A. Friedman in 2004. This free boundary problem involves a nonlinear second-order parabolic equation describing the diffusion of nutrient in the tumor, and three nonlinear first-order hyperbolic equations describing the evolution of proliferative cells, quiescent cells and dead cells, respectively. By applying Lp theory of parabolic equations, the characteristic theory of hyperbolic equations, and the Banach fixed point theorem, we prove that this problem has a unique global classical solution.
基金Project supported by the China National Natural Science Foundation,Grant number:10171112
文摘In this paper, we study a free boundary problem arising from the modeling of tumor growth. The problem comprises two unknown functions： R = R（t）, the radius of the tumor, and u = u（r, t）, the concentration of nutrient in the tumor. The function u satisfies a nonlinear reaction diffusion equation in the region 0 〈 r 〈 R（t）, t 〉 0, and the function R satisfies a nonlinear integrodifferential equation containing u. Under some general conditions, we establish global existence of transient solutions, unique existence of a stationary solution, and convergence of transient solutions toward the stationary solution as t →∞.
