OBJECTIVETo establish three orthotopically transplanted model of human primary malignant spleen lymphoma in the nude mice.

METHODSOrthotopic transplantation of histologically intact human primary malignant splenic lymphoma tissue obtained from patients was introduced into the splenic parenchyma of nude mice. Tumorigenicity, invasion, metastasis and morphological characteristics of the transplanted tumor were studied by light microscopy, electron microscopy and immunohistochemical methods.

RESULTSThe first kind, a strain of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, BFNHL-HMN-1) screened from 11 patients which had been passaged in vivo for 41 generations, a second kind, a liver metastasis model of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, LM-BFNHL-HMN-2) which had been passaged for 47 generations and a third kind of human primary malignant spleen lymphoma (non-Hodgkin's, T-immunoblastic cell, TINHL-HMN-3) having passaged for 37 generations were all successfully transplanted in 611 nude mice. Models of BFNHL-HMN-1 and TINHL-HMN-3 tumor gave nodular growth and lymph node metastasis in the spleen hilum but without any metastasis in the abdominal lymph nodes or organs. In the LM-BFNHL-HMN-2 model, not only did the tumor cells grow in the spleen, but in spleen hilum, lymph nodes and liver also. The orthotopically transplanted tumor cells were similar to the original human tumor in light histopathology, ultrastructure features, DNA content and chromosomal karyotype.

CONCLUSIONThese three models are able to serve as useful tools for the study of biologic characteristics and experimental treatment of human primary malignant lymphoma.

Animals ; Disease Models, Animal ; Humans ; Lymphoma ; pathology ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Splenic Neoplasms ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoricidal mechanism.

METHODSCultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9 MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay.

RESULTSThe tumor model was successfully developed. The tumor in the nude mice emitted the red fluorescence under the Leica LT-9 MACIMSYSPULS. The tumor volumes were (0.189+/-0.010) cm(3), (0.183+/-0.011) cm(3), (0.185+/-0.019)cm(3), (0.182+/-0.015)cm(3) for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294+/-0.010) cm(3), (0.280+/-0.013) cm(3), (0.278+/-0.016) cm(3), (0.183+/-0.014) cm(3); at day 7, (0.409+/-0.016) cm(3), (0.411+/-0.009) cm(3), (0.407+/-0.015) cm(3), (0.221+/-0.008) cm(3); at day 14, (0.970+/-0.055) cm(3), (0.976+/-0.054) cm(3), (0.981+/-0.032)cm(3), (0.318+/-0.005) cm(3); at day 21, (1.495+/-0.059) cm(3), (1.513+/-0.057) cm(3), (1.524+/-0.063) cm(3), (0.446+/-0.042) cm(3) (F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups.

CONCLUSIONS5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic acid-mediated photodynamic therapy (ALA- PDT) appears to be a promising therapy for human gastric cancer, whose mechanism involves in the destruction of the tumors partly by apoptosis other than necrosis.

Aminolevulinic Acid ; therapeutic use ; Animals ; Cell Line, Tumor ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental ; Photochemotherapy ; Stomach Neoplasms ; therapy ; Xenograft Model Antitumor Assays

OBJECTIVE: To investigate apoptosis induced by vesicular stomatitis virus (VSV) in HNE-1 cancer cells of human nasopharyngeal carcinoma by models of nude mice-BALB/c in vivo. METHOD: HNE-1 cells are collected from culture bottle and infected infra right-side post-back epithelium of nude mice-BALB/c (6 x 10(6) cells/0.1 ml/each mice) to create HNE-1 tumor models of nude mice-BALB/c. When the diameter of HNE-1 tumors is 5 to 8 millimeter, HNE-1 tumor models are treated with VSV (1 x 10(8) pfu /ml) or Saline. By Hoechst 33258-staining under fluorescence microscope, induction of apoptosis by VSV in HNE-1 tumor models are recorded and studied, compared with that by Saline in HNE-1 tumor models in vivo. RESULT: Compared with control group of saline, apoptosis of HNE-1 cancer cells of human nasopharyngeal carcinoma increase apparently in the remaining tumor cells of nude mice treated by VSV (P < 0.01). CONCLUSION The present study suggests that the treatment with VSV could augment the apoptosis cells of human nasopharyngeal carcinoma in vivo.
Animals ; Apoptosis ; Cell Line, Tumor ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; Neoplasm Transplantation ; Oncolytic Virotherapy ; Vesiculovirus ; Xenograft Model Antitumor Assays

OBJECTIVETo establish PEG10 transgenic mice model and study the effect of PEG10 transgene on tumor growth and metastasis in mice.

METHODSThe linearized expression element of pALB-PEG10, which contained mouse albumin promoter, structural gene of PEG10, and polyaenylation signal sequence, was microinjected into 3741 KM mouse fertilized ova. The manipulated embryos were then transplanted into the oviducts of 94 pseudopregnant recipient mice. All the newborn mice were screened by PCR to detect genomic DNA in tail tissue, then PEG10 mRNA and protein expression were detected by RT-PCR and western blot, respectively in the positive mice. Hepatoma cell H22 was subcutaneously inoculated into the right armpit of wild type mice and No.17, No.33 transgenic mice. Tumor size was measured every week. Mice were sacrificed on day 12 and then the tumors were exercised and weighted. Tumors and livers were fixed in formaldehyde and sectioned. The sections were stained with hematoxylin/eosin and examined under microscope. The expression of PEG10 protein was detected with immunohistochemistry method.

RESULTSAmong the 43 off-springs, 3 were positive for tail tissue PEG10 gene examination, PEG10 was successfully expressed in the liver of the randomly selected transgenic mouse. H22 tumor grew faster in all the transgenic mice than in wild type mice. The average size and weight of tumors between the transgenic mice and wild type mice were significantly different (P < 0.05). Most tumors in the transgenic mice invaded the surrounding tissues and showed liver metastasis, PEG10 protein was expressed in liver. In contrast, nearly all the tumors in wild type mice were capsulized and PEG10 was not expressed in liver.

CONCLUSIONOur results showed that the PEG10 gene could be expressed in the liver of the transgenic mice. PEG10 promotes growth, invasion, and metastasis of transplanted H22 tumors in mice.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Genetic Vectors ; Humans ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Mice ; Mice, Transgenic ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transgenes ; Xenograft Model Antitumor Assays

OBJECTIVETo compare the metastatic characteristics of HCCLM3 cells and SMCC-7721 cells in nude mice model.

METHODSNude mice were divided into two groups (n = 8, each), mice were transplanted with HCCLM3 cells (group A) and SMMC-7721 cells (group B). Tumor size, metastasis rate and other clinical parameters were compared between the two groups. Statistical analysis was performed with the help of SPSS 16.0 for Windows computer software (SPSS, Inc., Chicago, IL). P values of less than 0.05 were considered statistically significant.

RESULTSIntrahepatic metastases rate was 100% (8 / 8), mean intrahepatic primary tumor volume was (6954+/-1945) mm(3) in group A, Intrahepatic metastases rate was 62.5% (5/8), and mean intrahepatic primary tumor volume was (6034+/-2035) mm(3) in the group B. There was no statistical difference in the primary liver tumor size and intrahepatic metastases rate (P = 0.20; t = 6.38, P = 0.37, respectively). The numbers of intrahepatic metastases and the involved lobes, and the volume of tumor were 4.5 (median), 3, and 975 mm(3) (median) respectively, in group A, and these were 1 (median), 1 and 274 mm(3) (median) respectively in group B. The difference between two groups was statistically significant (Z values, -2.818, -2.289, and -1.975, respectively).The rate of lung metastasis and other organ metastasis in the A group was significantly higher than that in group B (P less than 0.001, P less than 0.041, respectively).

CONCLUSIONHCCLM3 cells have higher metastatic potential than SMMC-7721 cells in nude mice.

Animals ; Carcinoma, Hepatocellular ; pathology ; secondary ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms, Experimental ; pathology ; Lung Neoplasms ; secondary ; Male ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Xenograft Model Antitumor Assays

OBJECTIVETo elucidate the killing activity of yeast cytosine deaminase/5-fluorocytosine (YCD/5-FC) gene therapy system on gene-transferred tumorigenic cell line K562B in vivo.

METHODK562B cell was infected with high titer virus and a gene transferred cell clone, YCD-K562B, was selected. Twelve male SCID mice of 4 week old were divided into 2 groups at random and both YCD-K562B and K562B cells were implanted to each mice. 5-FC or saline was given i. p for 10 days after tumor developed, and relative tumor volume was measured every 3 days. At the end of experiment, animals were sacrificed and the specimens were processed for histopathological examination.

RESULTSAt the end of experiment (21 days after tumor cell implantation), the relative tumor volume of the 4 groups were: YCD-K562B + 5-FC 2.922 +/- 0.581, YCD-K562B + saline 24.434 +/- 4.790, K562B + 5-FC 22.701 +/- 2.350 and K562B + saline 24.460 +/- 1.670; t-test analysis showed that 5-FC could kill cells (YCD-K562B) in vivo (P = 0.0001), but had no effect on the growth of gene-untransferred cells (K562B) (P = 0.096). In YCD-K562B + 5-FC group, relative tumor volume reduced in 3 approximately 6 days after treatment (the minimum was 0.681). Necrosis around artery could be found in the tumor of YCD-K562B + 5-FC group.

CONCLUSIONYCD/5-FC suicide gene therapy system has a significant in vivo killing activity to gene-transferred tumorigenic YCD-K562B cell.

Animals ; Cytosine Deaminase ; Flucytosine ; metabolism ; pharmacology ; Genetic Therapy ; methods ; Humans ; K562 Cells ; Male ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms, Experimental ; genetics ; therapy ; Nucleoside Deaminases ; genetics ; metabolism ; Saccharomyces cerevisiae ; enzymology ; Transfection ; Treatment Outcome ; Xenograft Model Antitumor Assays

OBJECTIVE: This study was designed to evaluate the effect of zhongjiefeng extracts on telomerase activity and apoptosis of implanted human nasopharyngeal carcinoma cell lines in nude mice. METHOD: Nude mice with implanted human nasopharyngeal carcinoma cell lines CNE1 and CNE2 were randomly divided into three groups, which were the group of zhong-jiefeng, normal control group, and CTX therapy group. The weight of nude mice and the volume of tumor were regularly measured. After a course of treatment (30 d), tumor tissues were obtained with autopsy, and then they were weighed to calculate the inhibitive rate of the growth of tumor. The changes of ultra micro-structure of NPC cells were observed by transmission electron microscope. Expressions of Bcl-2 and Bax of xenografts were investigated by immunohistochemistry. The apoptosis of CNE1 and CNE2 cells was observed using TUNEL and FACS with PI-staining. The telomerase activity was observed by TRAP-ELISA method. RESULT: The zhongjiefeng extracts significantly inhibit the growth of tumor compared to normal control group. The inhibitory rate were 40.8% (P < 0.01) and 46.8% (P < 0.01), respectively. The expression of Bcl-2 was lower (P < 0.01) and the expression of Bax was higher (P < 0.01) in the zhongjiefeng group than that in normal control group. Electron microscopy indicated the typical apoptosis of tumor cells, such as marginal nuclei, chromatin condensation and nuclei fragmentation, and apoptotic bodies. As result of the flow cytometry showed, the exhibition rate of apoptosis of cell in the group treated with zhongjiefeng was higher than that of normal control group (P < 0.01) in G0/G1 phase. Zhongjiefeng arrested cells in G0/G1 phase of the cell cycle. The telomerase activity of zhongjiefeng and CTX group was lower than that of the normal group (P < 0.01). CONCLUSION Zhongjie feng suppressed the growth of tumor in vivo. The anticancer effects of zhongjiefeng were associated with the induction of apoptosis and partly with the suppression of telomerase activity.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; drug therapy ; metabolism ; pathology ; Neoplasm Transplantation ; Telomerase ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVE: To investigate the effect of arsenic trioxide (As2O3) combined with cisplatin on expression of RASSF1A in nude mice with human nasopharyngeal carcinoma xenograft. METHOD: The models of human poorly differentiated nasopharyngeal carcinoma in nude mice were established and randomly divided into four groups, control group (NaCl group), As2O3 group, DDP group and As2O3 + DDP group. The expression of RASSF1A mRNA and protein were detected by Real-time RT-PCR and immunohistochemistry respectively. The methylation rate of RASSF1A promoter CpG islands was analyzed by HRM. RESULTS: Experimental groups could obviously inhibit the growth of tumor and up-regulate the expression of RASSF1A. The methylation rate of RASSF1A in transplanted tumors in experimental groups was lower than the control group. Especially As2O3 combined with DDP were superior to the single drug use. CONCLUSION As2O3 inhibits the growth of human nasopharyngeal carcinoma cell strain CNE2 xenograft in nude mice and increases mRNA expression of RASSF1A. As2O3 inhibits the malignant phenotypes of human nasopharyngeal carcinoma cells and reverses hypermethylation of RASSF1A.
Animals ; Arsenic Trioxide ; Arsenicals ; pharmacology ; Carcinoma ; Cell Line, Tumor ; Cisplatin ; pharmacology ; DNA Methylation ; drug effects ; Humans ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Transplantation ; Oxides ; pharmacology ; Tumor Suppressor Proteins ; genetics ; Xenograft Model Antitumor Assays

OBJECTIVETo study the effect of Xiaotan Sanjie Recipe (XTSJD) and its mechanism on vasculogenic mimicry (VM) of human gastric cancer xenografts in nude mice.

METHODSThe tumor-bearing mice model was established by subcutaneous inoculating with xenografts of human gastric cancer into the right armpit of 30 BALB/c nude mice. After modeling, the tumor-bearing mice were randomly divided into the normal saline group, the XTSJD group, and the doxycycline hyclate (DH) group, 10 in each. And the mice were administered with corresponding medicine by gastrogavage for 4 weeks. Then all mice were killed by cervical dislocation. The tumor mass were weighed and the tumor inhibition rate calculated. The amount of VM in tumor was counted. Expressions of matrix metalloproteinase (MMP) -2 and MMP-9 were tested using immunohistochemical method.

RESULTSTumor weight in the XTSJD group and the OH group decreased significantly when compared with the NS group (P<0.01). The amount of VM in the XTSJD group (24.50+/-3.03) and the OH group (14.70+/-1.34) was significantly less than that in the NS group (33.10+/-2.64) (P<0.01). The positive expressions of MMP-2 and MMP-9 in the XTSJD group and the OH group was significantly lower than that in the NS group (P <0.01).

CONCLUSIONXTSJD could inhibit the formation of VM in xenografted tumor of nude mice. The mechanism might be correlated with the down-regulation of MMP-2 and MMP-9 expressions.

Animals ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Stomach Neoplasms ; blood supply ; metabolism ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo explore the effect of antisense gene to human telomerase reverse transcriptase (hTRT) on reversing malignant phenotypes of liver cancer cell lines.

METHODSSense and antisense eukaryotic expressing vector of hTRT gene was transfected into human liver cancer line HepG(2) with the DOTAP liposomal transfection method. Changes of cellular malignant phenotypes through proliferation capacity, telomerase activity, cloning formation in soft agar, invasive capacity in Borden's chamber model and tumorigenicity in nude mice were examined.

RESULTSSense and antisense eukaryotic expressing vector was successfully transfected into HepG(2). The obtained transfectants termed HepG(2)-sense (HepG(2)-S) and HepG(2)-antisense (HepG(2)-AS) stably produced sense and antisense hTRT, respectively. HepG(2)-AS showed an obvious decrease in growth and telomerase activity. HepG(2)-AS penetrated cells through Matrigel were decreased significantly compared with HepG(2) and HepG(2)-S. Cloning efficiency in soft agar and tumorigenicity in nude mice was also markedly inhibited in HepG(2)-AS.

CONCLUSIONSAntisense gene to hTRT can significantly suppress cancer cell growth, partially reverse malignant phenotypes of HepG(2), which indicates that hTRT may be a new target gene for antisense gene therapy of liver cancer.

Animals ; DNA, Antisense ; genetics ; DNA-Binding Proteins ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Humans ; Liver Neoplasms ; genetics ; pathology ; therapy ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Phenotype ; Rats ; Telomerase ; genetics ; Transfection ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays