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Sample records for bearing nude mice

  1. Experimental study of radiotargeting-therapy with small molecular polypeptide in nude mice bearing lung adenocarcinoma

    International Nuclear Information System (INIS)

    Background: Integrin signal transduction pathways provide an important basis for molecular targeting therapy of cancer in tumor growth, infiltration and transfer. Existing research data have shown that small molecular peptide labeled with radionuclide has good clinical application prospects, but the successful researches on lung cancer have not been reported so far. It is considered that the main reason is the lack of small molecule peptide for specific targeting lung cancer. Purpose: Based on the small molecular peptide cNGQGEQc for specifically identifying integrin α3 and β1 found previously, polypeptide cNGQGEQc is selected and radiolabelled with 131I. And the inhibitory effect of 131I-cNGQGEQc in nude mice bearing lung adenocarcinoma is observed. Methods: The coupling of cNGQGEQc and tyrosine was done in the processing of solid phase synthesis of small molecular peptide. Chloramine-T method was used for radiolabelling of cNGQGEQc with 131I. Twenty nude mice bearing NCI-H1975 were built and randomly divided into four groups with five mice in each group, including the group of 131I-cNGQGEQc, the group of 131I-cNAQAEQc, the group of 131I and the saline control group. The general condition was observed in nude mice bearing tumor after tail vein injection of corresponding drugs. And the tumor sizes after grafting were measured per 3 days in 30 days. The inhibitory rate of tumor in each group was calculated. Results: The labeling efficiencies of 131I-cNGQGEQc and 131I-cNAQAEQc were greater than 90% with the radiochemical purity of more than 95%, and 131I-cNGQGEQc had obvious inhibitory effect for transplantation tumor in nude mice bearing NCI-H1975 adenocarcinoma of lung. After a treatment for 30 days the tumor inhibitory rates were 60.93% for the group of 131I-cNGQGEQc, 11.63% for the group of 131I-cNAQAEQ and 10.70% for the group of 131I. Conclusion: 131I-cNGQGEQC has a good affinity and effective inhibit effect for the NCI-H1975 lung adenocarcinoma. Integrin is

  2. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

    Directory of Open Access Journals (Sweden)

    Zhu Y

    2014-12-01

    Full Text Available Yin Zhu,1,* Ming Cheng,2,* Zhen Yang,3 Chun-Yan Zeng,3 Jiang Chen,3 Yong Xie,3 Shi-Wen Luo,3 Kun-He Zhang,3 Shu-Feng Zhou,4 Nong-Hua Lu1,31Department of Gastroenterology, 2Department of Orthopedics, 3Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of China; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workAbstract: Mesenchymal stem cells (MSCs have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP. Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor

  3. Preliminary research on dendritic cells loaded with resistant breast cancer antigens in breast cancer-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Wei Zhuang; Limin Lun

    2015-01-01

    Objective The aim of the study was to investigate the inhibitory ef ects of dendritic cel s (DCs) loaded with resistant breast cancer antigens on breast cancer in nude mice. Methods A single-cel suspension was prepared from a primary breast cancer and chemotherapeutic drugs were screened using the ATP-PCA susceptibility testing system. Cancer cel s were treated with 1/10 × IC50, 1/5 × IC50, 1/2 × IC50, 1 × IC50, and 2 × IC50 medium until their growth became steady in the 2 × IC50 medium. Peripheral blood mononuclear cel s (PBMCs) were obtained from the peripheral blood of patients with leukapheresis. The obtained adherent cel s were induced by granulocyte-macrophage colony-stimu-lating factor (GM-CSF) and interleukin-4 (IL-4) to generate DCs, which carried resistant strain cel lysis compounds or non-treated cancer cel lysis compounds. The former mature DCs carried resistant breast tumor antigens. A breast tumor-bearing nude mouse model was established with these resistant strains and the mice were randomly divided in three groups. The mice in the treatment group were injected with DCs loaded with resistant breast cancer antigens. The control group consisted of mice injected with DCs loaded with primary tumor cel antigens and the blank group consisted of mice injected with the same volume of normal saline. Changes in the cancers were observed. Results After treatment with the ef ector cel s, the cancer volume and weight were significantly dif erent to those before treatment in every group of mice (P Conclusion DCs loaded with resistant breast cancer antigens demonstrated a significant inhibition ef ect on the cancers of breast tumor-bearing nude mice.

  4. Distribution and radioimmunoimaging of 131I labeled anti-NPC monoclonal antibody BAC5 in tumor bearing nude mice

    International Nuclear Information System (INIS)

    To provide an evidence for clinical applications, the distribution and radioimmunoimaging of 131I labeled anti nasopharyngeal carcinoma (NPC) monoclonal antibody BAC5 in tumor bearing nude mice were studied. McAb BAC5, against NPC, was labeled with 131I and injected into nude mice bearing NPC cell line CNE-2. The biodistribution of 131I-BAC5 and whole body ECT imaging were studied at various intervals after injection. The % ID/g were 6.38, 11.27 and 14.19 for tumor and 7.78, 3.48 and 2.59 for liver at 48, 96 and 144h postinjection respectively. The T/NT ratios were 0.82, 3.24 and 5.47 for liver at 48, 96 and 144h postinjection respectively. Tumor showed clearly at 3 days after injection. The quality of tumor images was relevant to the T/NT ratio. The results demonstrated that McAb BAC5 has specifically bind to NPC tissue and may also possess the capability of leading to human NPC

  5. Molecular imaging of tumor angiogenesis with VEGFR2 targeting microbubbles in colon cancer bearing nude mice

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of tumor neovascularization imaging in a nude mouse model of colon cancer by contrast ultrasound molecular imaging (UMI) of VEGF receptor 2 (kinase insert domain receptor, KDR). Methods: Targeted microbubbles (MBt) were built by conjugating K237, a small peptide with high affinity for KDR, to liposome microbubbles through a biotin-avidin bridge. Control microbubbles (MBc) with control peptide were prepared by the same method. Nude mice models of LS174T human colon cancer were established. MBt and MBc were injected intravenously in twelve mice in random order with an interval of 30 min. MBt were injected in another six mice after K237-peptide blocking. UMI was performed in all mice at 5 min postinjection to observe the imaging difference and measure the video intensity (Ⅵ) of tumor tissues in different groups. One-way analysis of variance and the least significant difference t test were performed to analyze the difference of tumor Ⅵ in the groups with MBt, MBc and K237 blocking. Immunohistochemistry was applied to detect the expression and distribution of KDR in tumor tissue and adjacent tumor tissues. Results: K237 peptide was successfully conjugated to the surface of microbubbles through biotin-avidin mediation. Ultrasound imaging signal of the tumor was high in the MBt group, while there were no significant enhancement in the groups of K237 blocking and MBc. The Ⅵ in MBt, MBc and K237 blocking groups was significantly different (F=39.130, P<0.01). There was a significant difference of Ⅵ in the MBt group compared to the MBc group (30.18 ± 9.56 vs 8.28 ± 4.74, t=6.91, P<0.01). In the K237 blocking group Ⅵ was significantly lower than that in the MBt group (9.23 ± 3.44 vs 30.18 ± 9.56, t=4.91, P<0.01). Immunohistochemistry results showed that KDR was highly expressed in tumor tissue. Conclusions: KDR-targeting liposome contrast microbubbles may specifically and efficiently link to tumor vascular endothelial cells in

  6. Preparation of 90Y-labeled different cyclic RGD peptides and evaluation in nude mice bearing human glioma xenografts

    International Nuclear Information System (INIS)

    90Y-DTPA-Bz-NH-SA-c(KRGDf) and 90Y-DTPA-Bz-NH-c(ERGDf) were prepared, and their in vitro and in vivo properties were compared. ITLC and HPLC show that the labeling yields of both compounds are more than 99% under the optimal conditions(pH=5.5, reac- ting at 80 degree C for 20 min), and they are stable in vitro. The biodistribution in nude mice bearing human glioma xenografts reveals no significant difference between these two radiolabeled com- pounds on uptake for all of tissues at the experimental time points; and pretty good tumor targeting and in vivo stability; and two radiolabeled compounds are mainly excreted through kid- neys, partly excreted through hepatobiliary system. The experimental data demonstrate that both of cyclic KRGDf and cyclic ERGDf are suitable for the further development of polymerconjugated RGD peptide drugs. (authors)

  7. Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with all-trans retinoic acid (ATRA), trichostatin A (TSA) or ATRA combined with TSA. Methods: After the induction with ATRA, TSA, or ATRA combined with TSA in different concentrations for 96 h, the iodine uptake of FTC-133 cells was observed. The concentrations for different groups were as follows: ATRA 1.0 ×10-6 mol/L(Alow group), ATRA 1.0 × 10-4 mol/L (Ahigh group), TSA 1.65 ×10-7 mol/L (T group), Alow + T group, Ahigh + T group and ethanol (control group). Cell quantities and morphology were observed by HE staining. FTC-133 cells were subcutaneously injected into nude mice. Twelve nude mice were randomly divided into 4 groups after tumor formation: ATRA group (2 mg/kg, intragastric administration), TSA group (10 mg/kg, intraperitoneal injection), combined therapy group (ATRA + TSA, the same doses as above) and saline control group (10 ml/kg, intragastric and intraperitoneal administration, respectively). Drugs were administered to the tumor-bearing mice according to the mouse body mass daily. At the 22nd day, the tumor-bearing mice were injected with 37 MBq 131I intraperitoneally. The biodistribution of 131I and gamma imaging were performed at 4, 6, 12 and 24 h after the injection respectively. Histopathological examinations of the tumor samples were taken after imaging completion. The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0. Results: The cellular iodine uptake were (23 885 ± 616.0) and (13 849 ±728.2) counts · min-1 · 10-6 cells in the Alow + T group and Ahigh + T group respectively, and the data were (985 ± 84.2) - (17 600 ± 782.7) counts · min-1 · 10-6 in the other groups (F=600.879, P<0.001). The % ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h. The % ID/g of

  8. The preparation of 99Tcm-J591 and its SPECT imaging of nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Objective: To study the binding performance of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody J591 (99Tcm-J591) and prostate cancer cells in vitro,the biodistribution and SPECT imaging of 99Tcm-J591 in nude mice bearing human prostate cancer in vivo. Methods: The monoclonal antibody J591 was labeled with 99Tcm by improved Schwarz method.Labeled antibody was purified by Sephadex G-50. The labeling efficiency and radiochemical purity were measured by paper chromatography and trichloroacetic acid method. The binding performance of J591 and prostate cancer cells was measured by flow cytometry in vitro. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts served as experiment group, mice bearing PSMA-negative PC3 tumors served as control group. 6.2-8.5 MBq of 99Tcm-J591 (25 μg) was intravenously injected into mice. Gamma imaging was performed 2, 6, 12 and 24 h after injection, T/NT was calculated by ROI technique. After scanned 12 h post injection, 4 mice of the experiment group and 5 mice of the control group were sacrificed and the tracer in vivo biodistribution was measured by gamma-counting, and the % ID/g was calculated. Two-sample t test was carried out to validate significant difference of % ID/g between two groups. Results: The labeling efficiency and radiochemical purity of 99Tcm-J591 were (78.9±6.2)% and (92.3±5.1)%, respectively, and the specific activity of 99Tcm-J591 was 68.7 MBq/mg. The antibody J591 and 99Tcm-J591 could strongly combine with PSMA-positive C4-2 cells in vitro, and didn't combine with PSMA-negative PC3 cells in vitro. SPECT imaging results showed that radioactive concentration was obvious in tumor 6 h post injection, the concentration scope became large and the tumor image was clear 12 h post injection. T/NT was 1.9±1.1 at 2 h, 4.3±1.8 at 6 h, 5.6±2.7 at 12 h, 1.4±0.6 at 24 h, respectively. In the control group, no radioactivity concentration was found in tumor, and T

  9. Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment

  10. Alphastatin downregulates vascular endothelial cells sphingosine kinase activity and suppresses tumor growth in nude mice bearing human gastric cancer xenografts

    Institute of Scientific and Technical Information of China (English)

    Lin Chen; Tao Li; Rong Li; Bo Wei; Zheng Peng

    2006-01-01

    AIM: To investigate whether alphastatin could inhibit human gastric cancer growth and furthermore whether sphingosine kinase (SPK) activity is involved in this process.METHODS: Using migration assay, MTT assay and Matrigel assay, the effect of alphastatin on vascular endothelial cells (ECs) was evaluated in vitro. SPK and endothelial differentiation gene (EDG)-1, -3, -5 mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR). SPK activity assay was used to evaluate the effect of alphastatin on ECs. Matrigel plug assay in nude mice was used to investigate the effect of alphastatin on angiogenesis in vivo. Female nude mice were subcutaneously implanted with human gastric cancer cells (BGC823) for the tumor xenografts studies.Micro vessel density was analyzed in Factor Ⅷ-stained tumor sections by the immunohistochemical SP method.RESULTS: In vitro, alphastatin inhibited the migration and tube formation of ECs, but had no effect on proliferation of ECs. RT-PCR analysis demonstrated that ECs expressed SPK and EDG-1, -3, -5 mRNAs. In vivo,alphastatin sufficiently suppressed neovascularization of the tumor in the nude mice. Daily administration of alphastatin produced significant tumor growth suppression. Immunohistochemical studies of tumor tissues revealed decreased micro vessel density in alphastatin-treated animals as compared with controls.CONCLUSION: Downregulating ECs SPK activity may be one of the mechanisms that alphastatin inhibits gastric cancer angiogenesis. Alphastatin might be a useful and relatively nontoxic adjuvant therapy in the treatment of gastric cancer.

  11. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the biodistribution and planar gamma camera imaging characteristics of 188Re labeled insulin-like growth factor 1 analogue (188Re-IGF-1A) in tumor-bearing mice. Methods: (1)To label IGF-1A with 188Re directly and to determine the labeling efficiency. (2)To establish nude mice model which bearing human pancreatic carcinoma cell Patu8988. (3)To scan those nude mice at 15 min, 1 h, 4 h, 24 h, 3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors. (4)To scan those nude mice at 15 min, 1 h, 2 h, 4 h and 24 h after intratumor injection with 188ReO4- into their tumors. To calculate the tumor to normal tissue ratio (T/NT) and the percentages of injected dose per gram tissue (%ID/g) of different organs. Results: (1)The labeling efficiency of 188Re-IGF-1A was (94.07 ± 0.32)%. (2)The largest uptake of tumors was (42.38 ± 17.82)%ID/g at 4 h after injection of 188Re-IGF-1A. Then the tumor to normal tissue ratios 5ncreased and the largest tumor to muscle ratio was 6531.79 ± 4930.26 at 5 d after injection. (3) 188ReO4- was major distributed in thyroid glands, stomachs, tumors and blood in nude mice after injection at first. Then %ID/g decreased rapidly in tumors. (4) The difference of %ID/g was significant (t=5.877, t=13.287, P188Re-IGF-1A group than in 188ReO4- group. The largest ratio of tumors in the two groups was 74.10 at 24 h after injection. (5) After being injected, 188Re-IGF-1A formed clear images in tumors, 5 d later, nothing but tumors can be seen. Conclusions: 188Re-IGF-1A has good affinity with human pancreatic cancer, and the tumor to muscle ratios in nude mice is high. So 188Re-IGF-1A is expected to be used for targeting therapy of human pancreatic carcinoma. (authors)

  12. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Objective: To study the binding affinity of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99Tcm-J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99Tcm-J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99Tcm-J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99Tcm-J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  13. Biodistribution and radioimmunoimage of iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts

    International Nuclear Information System (INIS)

    Objective: To investigate the biodistribution of Iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts. Methods: The anti-human ADAM15 polyclonal antibody was labeled with I-125 using Chloramine-T method. The labeling efficiency and radiochemical purity of 125I-anti-ADAM15 antibody were measured. The SPECT planar imaging of nude mice bearing gastric carcinoma xenografts were performed at 1, 4, 8, 24, and 48 h post-injection and the biodistribution of 125I-anti-ADAM15 antibody was measured at 48 h after injection. Results: The labeling efficiency of 125I-anti-ADAM15 antibody was (75.16±9.43)% and its radiochemical purity was (99.44±0.21)% . Tumors could be cleanly visualized in SPECT planar images, and the radioactivity ratio of tumor to non-tumor tissue was 3.84±0.43 at 48 h post-injection. Conclusion: 125I-anti-ADAM15 antibody can target the gastric carcinoma in vivo, and provide good radioimmunoimages. (authors)

  14. Preparation and evaluation of 99Tcm-(HYNIC-[Lys3] -bombesin) (tricine) (TPPTS) for imaging the Balb/c nude mice bearing human pancreatic cancer

    International Nuclear Information System (INIS)

    Objective: To synthesize 99Tcm- (hydrazinonictinamide- [Lys3] -bombesin) (tricine)(trisodium triphenylphosphine-3,3',3-trisulfonate) ((HYNIC-[Lys3]-BBS) (tricine) (TPPTS)) and evaluate its biodistribution and binding capability with tumor tissue in Balb/c nude mice bearing human pancreatic cancer xenografts. Methods: HYNIC was conjugated to the [Lys3] -BBS at pH=9.0 with SnCl2 as reducing agent and both tricine and TPPTS as coligands for 99Tcm-labeling. 99Tcm-HYNIC-[Lys3]-BBS)(tricine) (TPPTS) was purified by Sep-Pak C18 cartridge and was analysed by HPLC. The radiochemical purity and radiolabeling yield were measured. The stability of 99Tcm-(HYNIC-[Lys3]-BBS) (tricine)(TPPTS) in serum, biodistribution (% ID/g) in the normal mice and imaging of the Balb/c nude mice bearing human pancreatic cancer xenografts in vivo were studied. Results: The radiolabeling yield was (90±2)% and the radiochemical purity was over 95%. The radiochemical purity after 4 h in serum was over 85%. The distribution in normal mice showed rapid clearance from blood (the uptake was (0.07±0.01) %ID/g at 2 h postinjection). 99Tcm-(HYNIC-[Lys3]-BBS) (tricine) (TPPTS) was excreted mainly via the kidney with little radioactivity accumulation in the liver and gastrointestinal tract (the uptake of liver, stomach, intestine was (0.27±0.03), (0.06±0.03), (0.04±0.00) %ID/g at 2 h postinjection). Marked uptake of radioactivity was found in tumor tissue of the Balb/c nude mice bearing human pancreatic cancer with maximum T/NT ratio of 3.71±0.57 at 2 h postinjection. Conclusions: 99Tcm-(HYNIC-[Lys3]-BBS)(tricine) (TPPTS) can be easily prepared with high radiolabeling yield and radiochemical purity. The stability in serum and good biodistribution characteristics make it useful for the diagnosis of human pancreatic cancer with over-expression of the gastric-releasing peptide(GRP) receptor. (authors)

  15. Biodistribution and SPECT Imaging Study of 99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

    Directory of Open Access Journals (Sweden)

    Wenhui Ma

    2014-01-01

    Full Text Available A peptide containing Asn-Gly-Arg(NGR sequence was synthesized and directly labeled with Tc. Its radiochemical characteristics, biodistribution, and SPECT imaging were evaluated in nude mice bearing human HepG2 hepatoma. Nude mice bearing HepG2 were randomly divided into 5 groups with 5 mice in each group and injected with ~7.4 MBq Tc-NGR. The SPECT images were acquired in 1, 4, 8, and 12 h postinjection via caudal vein. The metabolism of tracers was determined in major organs at different time points, which demonstrated rapid, significant tumor uptake and slow tumor washout. The control group mice were blocked by coinjecting unlabelled NGR (20 mg/kg. Tumor uptake was (2.52±0.83% ID/g at 1 h, with the highest uptake of (3.26±0.63% ID/g at 8 h. In comparison, the uptake of the blocked control group was (1.65±0.61% ID/g at 1 h after injection. The SPECT static images and the tumor/muscle (T/NT value were obtained. The highest T/NT value was 7.58±1.92 at 8 h. The xenografted tumor became visible at 1 h and the clearest image of the tumor was observed at 8 h. In conclusion, Tc-NGR can be efficiently prepared and it exhibited good properties for the potential SPECT imaging agent of tumor.

  16. Effects of Different High Fat Diets on Fatty Acid Composition of Skeletal Muscle and Liver in Nude Mice Bearing Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-jie DUAN; Feng WANG; Zhong-wen LIU; Ming YU

    2014-01-01

    Objective To investigate the impacts of different dietary fatty acids on fatty acid composition in skeletal muscle and liver in nude mice bearing pancreatic cancer.MethodsSixty C57BL/6 nude mice were randomly divided into 6 groups: saturated fatty acid-fed group (SFA group), monounsaturated fatty acid-fed group (MUFA group), n-6 polyunsaturated fatty acid-fed group (n-6 PUFA group), n-3 polyunsaturated fatty acid-fed group (n-3 PUFA group), iso-caloric control (ISO-C) and normal control (NC). Four high fat diets containing 15% oils derived from coconut (SFA group), olive (MUFA group), soybean (n-6 PUFA group) andflaxseed (n-3 PUFA group) respectively, were prepared. ISO-C and NC groups were fed diet containing 4%-5% soybean oil. After one week of feeding, HPAF-Ⅱ human pancreatic cancer cells were transplanted orthotopically. The mice were fed corresponding diets in the following 14 weeks and then sacrificed. Skeletal muscle and liver tissues were sampled. Fatty acids in the samples were analyzed by gas chromatography-mass spectrometry.ResultsFatty acid composition of skeletal muscle and liver were similar between ISO-C group and NC group.Compared to ISO-C group, the contents of fatty acids in skeletal muscle were: (1) palmitic acid (C16:0), hepentadecane acid (C17:0), stearic acid (C18:0) and arachidonic acid (C20:0) increased inSFA group (P< 0.05); (2)oleic acid (C18:1) increased in MUFA group (P< 0.05); (3)γ-linolenic acid (γ-C18:3) increased in n-6 PUFA group (P<0.05);(4) linolenic acid (C18:3), eicosapentaenoic acid (C20:5) and clupanodonic acid (C22:5) increased in n-3 PUFA group (P<0.05). In the liver, the contents of fatty acids were: (1) saturated fatty acids not increased in SFA group; (2) eicosenoic acid (C20:1) increased in MUFA group (P< 0.05); (3) eicosadienoic acid (C20:2) and arachidonic acid (C20:4) increased in n-6 PUFA group (P < 0.05); (4) linolenic acid, eicosapentaenoic acid, clupanodonic acid and docosahexaenoic acid increased in n-3 PUFA

  17. Reversal of multidrug resistance with KR-30035: evaluated with biodistribution of Tc-99m MIBI in nude mice bearing human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Kyun; Lee, Jae Tae; Lee, Byung Ho [Kyungpook National Univ. Hospital, Taegu (Korea, Republic of)] [and others

    2001-06-01

    KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake in nude mice bearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. P-gp (+) HCT15/CLO2 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice x 6 groups). Group 1 (Gr1) mice received 10mg/kg Kr i.p. 3 times (x3); Gr2, 10mg/kg VP i.p. x3; Gr3, 10mg/kg KR i.p. x2 + 25mg/kg KR i.p. x1; Gr4, 10mg/kg KR i.p. x 2 + 50mg/kg i.p. x1; Gr5, 10mg/kg Kr i.p. x2 + 25mg/kg KR i.v. x1, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Tu in P-gp (+) and (-)tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell (0.93) than the control. Percentage increases in Tu were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 min (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% in Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 3C min, likely due to cardiovascular effects. No mice died. These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

  18. Preparation of 99Tcm labeled c-myc mRNA antisense peptide nucleic acid and its biodistribution in tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Objective: The aim of this work was to study a 99Tcm labeling method for c-myc mRNA antisense peptide nucleic acid (PNA) fragments and the biodistribution of the labeled product in tumor- beating nude mice. Methods: A four amino acid sequence Gly-(D)-Ala-Gly-Gly [G-(D)-A-G-G] was used as a chelator. N-GAGG-Aba-GCATCGTCGCGG, a chelator-antisense PNA specific for the human c- myc oncogene mRNA initiation region, was synthesized, purified and characterized. N-GAGG-Aba-GCAT- GTCTGCGG, a chelator mismatched PNA, was synthesized and used as a control. G-(D)-A-G-G provided an N4 configuration for strong, efficient chelation of 99Tcm. The labeled PNA was identified with high performance liquid chromatography (HPLC) and the labeling yield and radiochemical purity were measured by paper chromatography. The biodistribution was studied with nude mice bearing colon carcinoma and the percentage activity of injected dose per gram of tissue (%ID/g) was calculated. ASA 6.12 was used for data analysis. Results: The results of HPLC and paper chromatography confirmed that 99Tcm was joined to the PNA or the mismatched PNA with a high radiochemical purity (> 95%). Both were stable in vitro or incubated with human fresh serum and were excreted through urine. Results of biodistribution studies showed that the highest radioactivity levels were in the kidneys and spleen. The radioactivity of 99Tcm labeled antisense PNA in tumor was high whereas that of 99Tcm labeled mismatch PNA was very low [(1.11% ± 0.12)% ID/g and (0.14 ± 0.02)% ID/g, respectively; t=14.75, P99Tcm by the method presented in this paper, with good yield, radiochemical purity and stability. It was an efficient method to label antisense PNA with 99Tcm. The product seemed to be a potential tumor imaging agent. (authors)

  19. The transplantation barrier of nude mice

    OpenAIRE

    Moll, Heidrun; Bösing-Schneider, Rita

    2010-01-01

    Syngeneic memory cells can be stimulated to yield a secondary immune response after their transfer into irradiated euthymie recipients as well as into young thymusless nude mice. It is shown that nude mice older than twelve weeks of age are not permissive towards memory cell activation as it is found in non-irradiated euthymie animals. This barrier to isogeneie or congeneic cells seems to be caused by a pool of cyclophosphamide-sensitive cells. Since young nude mice could be rendered as unper...

  20. The experimental study on anti-tumor effect of 131I-Tyr-octreotide in nude mice bearing human non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: Radionuclide-labeled low molecular weight polypeptide is recently advocated for the diagnosis and treatment of malignant tumor. The purpose of this study was to evaluate the anti-tumor effect of 131I-Tyr-octreotide in nude mice bearing human non-small cell lung cancer (NSCLC). Methods: 131I-Tyr-octreotide was prepared by Ch-T method. The radiochemical purity was measured and biodistribution was evaluated. The nude mice models bearing human NSCLC were studied and divided into four groups: group A injected 131I-Tyr-octreotide through tail vein, group B injected normal saline, group C injected 131I-Tyr-octreotide through stroma and group D injected 131I through stroma. The radioactivity ratio of tumor to normal tis- sue (T/NT) was calculated over region of interest (ROI). The tumor cell cycle and cell apoptosis were analyzed by flow cytometry (FCM), terminal deoxynucleotidyl transferase mediated dUTP-biotion nick end labeling (TUNEL) and histopathological analysis. Statistical analysis was performed with SPSS 11.0, and the comparison for difference between groups performed with one-way ANOVA analysis. Results: The labeled radiochemical purity was (95.23 ± 1.67)% and specific activity of 3.5 x l06 Bq/μg. The biodistribution showed high uptake in kidney, and low uptake in liver and spleen. The radioactive uptake in group C was higher than the other groups, and the retention time was longer. The T/NT was 52.74 ± 0.13 after 24 h, which was much higher than that of the other groups (group D: 8.90 ± 0.23, group A: 6.42 ± 0.02, q=628.81 and 664.33, all P1 phase was blocked most remarkably in group C than the other groups [group C: (83.17 ± 6.86)%, group A: (57.02 ± 18.81)%, group D: (49.29 ± 7.80)%, group B: (45.88 ± 5.13)%, q=5.29, 6.86, 7.55, 1.56, 2.26, 0.69, all P131I-Tyr-octreotide was easily labeled by Ch-T. 131I-Tyr-octreotide could induce tumor cell apoptosis and inhibit the tumor cell of NSCLC. It might be a potential target-directed agent in

  1. Biodistribution and γ imaging of 125I-labeled goat anti-human IgG polyclonal antibody in nude mice bearing human colon cancer xenografts

    International Nuclear Information System (INIS)

    The possibility of IgG secreted from tumor cells as a target for radioimmunoimaging and targeted therapy of cancers were investigated. Goat anti-human IgG polyclonal anti- body (GAHG) was radioiodinated using Iodogen method, and the in vitro stability and pharmacokinetics were evaluated. The biodistribution and γ imaging of 125I-GAHG were performed in nude mice bearing HT-29 human colon cancer xenografts. 125I-GAHG showed good in vitro stability, and its blood clearance was defined as a two-compartment model, with T1/2α and T1/2β were 1.19 h and 43.99 h, respectively. The tumor uptake of 125I-GAHG was higher than that of 125I-labeled normal goat IgG control (125I-GIgG). 125I-GAHG showed good tumor retention when injecting via intra-tumor. In the biodistribution study, the highest tumor uptake of 125I-GAHG was 6.71±2.19%ID/g at 72 h postinjection and the T/NT increased along with the postinjection time. The results show that 125I-GAHG have good tumor-specific uptake which may provide a novel idea for radioimmunoimaging and targeted therapy of cancers. (authors)

  2. Study on in vivo imaging of 99Tcm-hTERT mRNA as antisense molecular probe in breast cancer tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Objective: Antisense imaging is one of the important modalities in the domain of molecular nuclear medicine. The purpose of this study was to design and synthesize an antisense oligonucleotide (ASON) molecular probe targeting human telomerase reverse transcriptase (hTERT) mRNA, and to validate the potential application value using animal model experimental study in early diagnosis of the tumor. Methods: Antisense and sense molecular probes targeting hTERT mRNA were radiolabeled with 99Tcm through bifunctional chelator N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (S-Acetyl NHS-MAG3). The BALB/c nu/nu nude mice were inoculated with MCF-7 mammary tumor cells in the right upper limbs. 99Tcm-hTERT mRNA ASON and 99Tcm-hTERT mRNA sense oligonucleotide (SON) with or without mediated by liposome was injected intravenously in mammary tumor-bearing BALB/c nude mice, respectively. Imaging it, vivo was performed periodically. All data were analyzed by the statistic software of SPSS 12.0. Results: The in vitro study showed that the labeling efficiencies of 99Tcm-hTERT mRNA ASON reached (76 ± 5)%, with radiochemical purity greater than 96% and specific activity of 1850 kBq/μg. The stability of 99Tcm-hTERT mRNA ASON in room temperature and serum incubation after 24 h was still above 93%. The in vivo study showed that tumor uptake of 99Tcm-hTERT mRNA ASON was high from 4 to 8 h after injection. On the contrary, there was little 99Tcm-hTERT mRNA SON accumulated in tumor within 8 h. The radioactivity ratio of tumor-to-nontumor (T/NT) of antisense probe group with or' without liposome mediation was 8.02 ± 0.03 and 7.55 ± 0.12, respectively (t=-1.99, P>0.05), and that of sense probe group with or without liposome mediation was 1.23 ± 0.06 and 1.33 ± 0.15, respectively (t=0.42, P>0.05). However, there was significant difference between antisense and sense probe groups with or without liposome mediation (t= 26.30, 28.71, both P99Tcm could be used as a

  3. Somatostatin receptor subtype 2-mediated scintigraphy and localization using 99mTc-HYNIC-Tyr3-octreotide in human hepatocellular carcinoma-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Yong Li; Jian-Ming Si; Jun Zhang; Jin Du; Fan Wang; Bing Jia

    2005-01-01

    AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma.METHODS: The expression of somatostatin receptor 2(SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTC uptake between tumor tissue and vital organs.RESULTS: We demonstrated the expression of SSTR2mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue,liver and kidney of the tumor-bearing mice.CONCLUSION: Based on expression of the SSTR2 mRNA in human NCC, 99mTc-NYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionuclide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclidelabeled somatostatin analog for HCC are of great value to be further studied.

  4. Preparation of 99Tcm labeled survivin mRNA antisense PNA and gene imaging in nude mice bearing lung carcinoma A549 xenografts

    International Nuclear Information System (INIS)

    Objective: To prepare the 99Tcm-survivin mRNA antisense peptide nucleic acid (PNA)and investigate its value as a gene imaging agent in tumor bearing mice and early diagnosis in tumor. Methods: Survivin mRNA antisense PNA and mismatch PNA were synthesized. Four amino acids (Gly- (D)Ala-Gly-Gly) and Aba (4-aminobutyric acid) were linked to the 5' end of PNA. Gly- (D)Ala-Gly-Gly served as a chelating moiety for strong chelation of 99Tcm and Aba acted as a spacer to minimize the steric hindrance. PNAs were labeled with 99Tcm by the ligand-exchange method. The labeling efficiency and radiochemical purity were measured by HPLC and ITLC methods. There were five BALB/c nude mice bearing human lung carcinoma (A549) in each of antisense PNA and mismatch PNA groups. Gene imaging of 99Tcm-survivin mRNA antisense and mismatch PNAs were performed at 1, 2 and 4 h post the injection, respectively, and the T/NT ratio was measured by the method of ROI. The statistical comparisons of average values were performed with the two-group t-test for independent sample by SPSS 13.0. Results: The product kept stable in vitro. The labeling efficiency of 99Tcm-survivin mRNA antisense PNA was (95.48 ±1.92)% and more than 85% after the incubation for 24 h in serum. The radiochemical purity was >95%. The labeling efficiency of mismatch PNA was similar to the antisense PNA. 99Tcm-survivin mRNA antisense PNA was especially uptaken by tumor lesion, and its accumulation reached the top at 4 h post the injection. T/NT ratios at 1, 2, and 4 h were 2.70 ± 0.28, 3.44 ± 0.35,4.21 ± 0.63, respectively. In the comparison, the T/NT ratio of 99Tcm-survivin mRNA mismatch PNA at 4 h (3.12 ±0.50) was significantly lower (t=2.918, P=0.019). Conclusions: 99Tcm-survivin mRNA antisense PNA has high labeling efficiency,good stability and no need of purification. Its characteristic of especial uptake by tumor lesion provides the potential value in early diagnosis of tumor. (authors)

  5. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude...... mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2....... endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer....

  6. The resistance-reversal effect of artesunate on human esophageal cancer transplanted in nude mice

    OpenAIRE

    Liu, Liang; Zuo, Lian-Fu; Jin-ya LI; Guo, Jian-Wen; Wang, Jing

    2011-01-01

    Objective To explore the relationship between ABCG2 and multidrug resistance of esophageal cancer and the mechanism of resistance-reversal effect by artesunate(Art).Methods To establish the bearing cancer nude mice model by inoculating with Eca109/ABCG2 cells subcutaneously on the left subscapularis and study the resistance-reversal effect of artesunate on esophageal cancer using nude mice model.Injection drugs after subcutaneous tumor formation.Intraperitoneal injection with artesunate and a...

  7. Anomalies in the hormonal status of athymic nude mice.

    Science.gov (United States)

    Köpf-Maier, P; Mboneko, V F

    1990-01-01

    The serum levels of hormones that are known to influence growth, development, and differentiation of the skin and its appendages were analyzed in female haired (NMRI) and nude (NMRI, nu/nu) mice. Whereas the concentrations of testosterone, prolactin, and triiodothyronine did not differ in nude animals from those found in normal mice of the same age in the anestrous phase of the sexual cycle, the serum levels of estradiol, progesterone, and thyroxine were found in female nude mice at significantly lower levels than in normally haired animals. These results point to a hormonal situation that contributes to the poor fertility of homozygous (nu/nu) female mice and may promote impairment of growth and differentiation of skin and hair, resulting in the macroscopic nudity of athymic, nude mice. PMID:2370246

  8. Effects of tumour mass and circulating antigen on the biodistribution of 111In-labelled F(ab')2 fragments of human prostatic acid phosphatase monoclonal antibody in nude mice bearing PC-82 human prostatic tumor xenografts

    International Nuclear Information System (INIS)

    We have evaluated the effects of tumour mass and circulating antigen (prostatic acid phosphatase, PAP) on the biodistribution and the incorporation of 111In-labelled F(ab')2 monoclonal antibody (MoAb) fragments directed against human PAP into human prostatic tumours (PC-82; 0.1-8.9 g) growing in nude mice. The radioactivities in the blood, liver, spleen, kidney and tumour were compared at 1, 3, 4 and 6 days after the intravenous administration of the antibody fragments. There was a significant correlation between the tumour size and the serum PAP concentration in the model employed. Even tissue of a small tumour (111In-labelled F(ab')2 fragments. This relationship had levelled off by 72 h and most likely reflected a better vascularisation of the smaller tumours. Our results show that the increase in tumour size and in the concentration of circulating antigen in the blood led to decreased tumour-to-blood ratios, since there was a tendency for higher blood activities in mice with larger tumours and higher serum PAP concentrations. There was no correlation between tumour size and label uptake by the liver during the follow-up over 144 h, although serum PAP concentrations ranged from 3.1 μg/l to 352 μg/l. On the other hand, when compared with our previous data obtained with non-tumour-bearing mice, there was a significant increase in the uptake by the liver and spleen. These results indicate that even a small concentration of circulating antigen was able to trigger an abnormal change in the biodistribution of MoAbs. (orig.)

  9. Synthesis of 2'-deoxy-2'-[18F]-fluoro-5-iodo-1-β-D-arabinofuranosyluracil ([18F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [18F]-FHPG and [18F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [18F]-FHBG is more useful than [18F]-FHPG for this purpose. [124I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [18F]-FHPG and [18F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [18F]-FHPG and [18F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [18F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [14C]-FMAU. (orig.)

  10. Intravesical Instillation in Pure Line LEW Rats and Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; XIE Shusheng; GUO Xiaoyun; MO Zengnan

    2007-01-01

    In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and angle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activities of animals weren't influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

  11. Impact of exogenous growth hormone on GH/IGF/IGFBP axis in colon cancer-bearing nude mice%生长激素荷人结肠癌裸鼠GH/IGF-I/IGFBP-3轴的影响

    Institute of Scientific and Technical Information of China (English)

    张毅; 梁道明; 李思齐; 袁勇; 赵辉; 陈嘉勇

    2013-01-01

    目的:探讨外源性生长激素(GH)对荷瘤裸鼠GH/胰岛素样生长因子(IGF)/胰岛素样生长因子结合蛋白3(IGFBP-3)轴的影响.方法:采用人结肠癌细胞株(HCT116)建立人结肠癌细胞裸鼠移植瘤模型.取48只荷瘤裸鼠随机均分为生理盐水处理组(NS组)、氟尿嘧啶处理组(FU组)、GH处理组(GH组),FU+GH处理组(FU+GH组).每组连续给药6d,在给药结束后24,72 h分别处死每组6只动物,取血及移植瘤标本,应用ELISA法检测血清GH,IGF-I,IGFBP-3含量和RT-PCR法检测移植瘤IGF-I,IGF-I受体(IGF-IR),IGFBP-3的mRNA表达.结果:ELISA结果显示,给药结束后24 h,GH组和FU+GH组血清GH,IGF-I,IGFBP-3含量较NS组与FU组明显升高(均P<0.05);给药结束后72 h,各组GH,IGF-I的水平无统计学差异(均P>0.05),但GH组和FU+GH组IGFBP-3水平仍高于NS组和FU组(均P<0.05).RT-PCR结果显示,给药结束后24 h,GH,FU,FU+GH组移植瘤组织IGF-I mRNA与IGF-IR mRNA的表达较NS组明显降低,而IGFBP-3 mRNA表达明显增加;给药结束后72 h,IGF-I mRNA与IGF-IR mRNA表达各组间无差别,但GH组,FU组和FU+GH组IGFBP-3 mRNA表达量仍明显高于NS组.结论:短期应用外源性GH所致GH/IGF/IGFBP-3轴的变化对人结肠癌移植瘤生长无促进作用.%Objective: To observe the impact of exogenous growth hormone (GH) on the axis of GH/insulin-like growth factor I (IGF-I)/insulin-like growth factor binding protein (GFBP) in colon cancer-bearing nude mice. Methods: Nude mice xenograft models of human colon cancer were established by using human colon cancer HCT116 cells. Subsequently, 48 tumor-bearing mice were equally randomized into normal saline treatment group (NS group), fluorouracil treatment group (FU group), GH treatment group (GH group) and FU plus GH treatment group (FU+GH group), and all treatment regimens were continued for 6 days. Mice were sacrificed to collect the blood and tumor xenograft samples at 24 and 72 h after the termination of regimens with 6

  12. Tumor uptake of radioiodinated anti-human pulmonary surfactant-associated protein monoclonal antibody PE 10 in nude mice bearing human pulmonary adenocarcinoma in combination with an unlabeled preload

    International Nuclear Information System (INIS)

    This study assessed the potential use of radioimmunoscintigraphy of pulmonary alveolar Type II cells tumor with the radiolabeled anti-human surfactant-associated protein (SP) monoclonal antibody (MAb) PE 10 in combination with preloads of unlabeled MAb. The in vitro binding of iodine-125 (125I)-labeled MAb PE 10 (1 μg), which had a specific radioactivity of 400 MBq/mg, on human pulmonary papillary adenocarcinoma NCI-H441 cells that produced SP was investigated. In NCI-H441 tumor-bearing nude mice, the tumor uptake of 125I-MAb PE 10 (5 μg) was examined in combination with preloads of unlabeled MAb PE 10 (0, 5, 10, and 50 μg). An isotype-matched unassociated murine MAb was used as a control both in vitro and in vivo. 125I-MAb PE 10 showed specific cell binding compared with 125I-control MAb. Tumor uptake of 125I-MAb PE 10 in vivo reached a peak of 4.97±0.33% injected dose per gram (%ID/g) at 48 h postinjection. Preloads of 5 and 10 μg unlabeled MAb PE 10 significantly enhanced tumor uptake at 48 h postinjection ( 5.94±0.29% ID/g and 5.72±0.29% ID/g, respectively), whereas preload of 50 μg unlabeled MAb PE 10 significantly decreased tumor uptake ( 2.75±0.32% ID/g) at 48 h. Preload of 5 μg unlabeled MAb PE 10 significantly increased the tumor-to-blood radioactivity ratio at 48 h ( 2.39±0.16). Preloads of unlabeled control MAb did not cause any significant change in tumor uptake. Immunohistochemistry showed the intracellular and pericellular patterns of SP expression in tumor cells. In conclusion, radioimmunoscintigraphy with MAb PE 10 labeled with a γ-emitting radioiodine such as 123I might be a useful means of targeting pulmonary alveolar Type II tumor cells in combination with preloading with an optimal dose of the unlabeled MAb

  13. Radioimmunoimaging in human transitional cell carcinoma xenografted nude mice with monoclonal antibody L4B4

    International Nuclear Information System (INIS)

    The monoclonal antibody L4B4 against transitional cell carcinoma (TCC) was prepared and radioimmunoimaging (RII) was studied in nude mice bearing human TCC using L4B4. L4B4 was identified in vitro by immunohistochemistry. Radioimmunoimaging was performed in human transitional cell carcinoma xenografted nude mice. Immunohistochemistry study showed that L4B4 had high specificity for TCC (23/24), compared to that for other malignant tumors (2/24) and benign tumors (0/7). RII study showed that xenografted tumor was demonstrated clearly on the 3rd and 5th day after injection of 125I labeled L4B4. The T/NT was greater than 4 on the 5th day. The results indicated that L4B4 might be useful in the study of TCC and is worthy to do further investigation

  14. An UVB-carcinogenesis model with KSN nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishigaki, Yasuhito; Nikaido, Osamu [Kanazawa Univ. (Japan). Faculty of Pharmaceutical Sciences; Suzuki, Fumio; Hayakawa, Jun-ichiro; Hiai, Hiroshi

    1998-03-01

    We established and characterized a systematic ultraviolet light-induced carcinogenesis model using KSN nude mice. We prepared five groups of KSN mice and exposed them six times a week to five levels of daily ultraviolet B (UVB) doses; 1340, 670, 320, 160 and 0 J/m{sup 2}/day. In 670, 320 and 160 J/m{sup 2}/day, the latency period tended to become shorter in proportion to the daily doses and prevalence data fitted well to log-normal distribution. In the log-log plot of days till 50% prevalence versus daily dose, we saw a linear relationship for 1 mm tumor diameter. From this analysis, we determined that days necessary to reach 50% prevalence is in proportion to the -0.49 power of daily dose. The average number of tumors per survivor correlated with prevalence data. Direct measured rates of tumor growth were independent of daily UVB-dose. Therefore we speculated that UV-irradiation did not affect tumor growth after its appearance. Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. We concluded that our experimental data with nude mice was in accordance with data with hairless mice in nature. (author)

  15. Subcutaneous growth of human acoustic schwannomas in athymic nude mice

    DEFF Research Database (Denmark)

    Charabi, S.; Rygaard, J.; Klinken, Leif; Tos, M.; Thomsen, J.

    Neuropathology, acoustic schwannomas, subcutaneous implantation, nude mouse, growth, pcna, ki-67......Neuropathology, acoustic schwannomas, subcutaneous implantation, nude mouse, growth, pcna, ki-67...

  16. A comparison of UVB-carcinogenesis between nude mice and nude beige mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishigaki, Yasuhito; Yasuda, Kazuhiro; Hashimoto, Noriyoshi; Hayakawa, Jun-ichiro; Nikaido, Osamu [Kanazawa Univ. (Japan). Faculty of Pharmaceutical Sciences; Hiai, Hiroshi

    1998-06-01

    To gain an insight into the relationship between UVB-carcinogenesis and natural killer activity, we examined ultraviolet light-induced carcinogenesis in mice with high natural killer activity (KSN) and mice with natural killer deficiency (KSN-bg). We exposed mice six times a week to three levels of daily ultraviolet B (UVB) doses; 320, 160 and 0 J/m{sup 2}/day. During the latency period of skin tumor development in KSN mice, we detected no suppression of the natural killer activity at both 320 and 160 J/m{sup 2}/day. Even at 1340 J/m{sup 2}/day, we could not detect any significant suppression of NK activity in KSN mice. When we irradiated spleen cells in vitro, we observed NK activity suppression. Next, we compared the carcinogenic effects of UVB-irradiation on KSN and KSN-bg mice. At 320 J/m{sup 2}/day, we detected no significant differences between them. In contrast, at 160 J/m{sup 2}/day, KSN-bg mice showed a significantly higher rate of skin tumor induction than KSN mice (p<0.05). Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. Our results suggest that NK activity plays a protective role against UVB-carcinogenesis from low daily-doses of UVB-irradiation. (author)

  17. Radioimmunoimaging of human colon carcinoma xenografts in nude mice with 111In-labelled monoclonal antibody

    International Nuclear Information System (INIS)

    A nude mouse model bearing human colon carcinoma xenograft from human fresh surgical specimens was established. The anti-colon carcinoma monoclonal antibody 2C10 was labelled with 111In using bifunctional chelating agent DTPA. The labelled antibodies were injected intraperitoneally into the tumor-bearing mice. The tissue distribution of labelled antibody was studied and whole body scintigraphies were obtained with a γ camera at different times. 96 hours after administration, the tumor to muscle ratio was 10.48, tumor to blood ratio 3.94 and tumor to liver ratio 1.58. There were significant difference in T/N ratio between animals receiving the specific antibody and labelled unrelated mouse IgG. Imaging showed clear tumor pictures in all animals receiving the specific McAb, while the two animals receiving unrelated mouse IgG showed negative imaging

  18. Effects of a fraction from Naja naja atra venom on transplanted hepatic carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    XuT; LiuZT

    2002-01-01

    The effects of a fraction from Naja naja atra venom(FNNAV) on inhibiting the growing of hepatic carcinoma and inducing the apoptosis of hepatic carcinoma were studied.It showed that the weight of transplants of hepatic carcinoma was lower both in middle and high concentration FNNAV groups compared with the control group after ten days treatment with FNNAV,and the nude mice of high concentration FNNAV group lived longer than those of the control group.It has been found that the expression of bcl-2 gene in transplants of hepatic carcinoma in FNNAV groups was decreased by using SABC method.By counting the peripheral blood WBC and bone marrow cells it proved that FNNAV did not affect the function of bone marrow in a short period.These results suggest that FNNAV has the anti-tumor effects on transkplanted hepatic carcinoma in nude mice and could prolong the life of mice bearing the tumor.No inhibitory effect of FNNAV on bone marrow was observed.

  19. Virus-Induced Demyelination in Nude Mice Is Mediated by γδ T Cells

    OpenAIRE

    Dandekar, Ajai A.; Perlman, Stanley

    2002-01-01

    Infection of mice with mouse hepatitis virus (MHV), strain JHM, results in acute and chronic demyelination with many similarities to the human disease multiple sclerosis. This pathological process is primarily T cell-mediated and MHV infection of mice lacking B and T cells does not result in demyelination. In apparent contradiction to these results, robust demyelination is detected in MHV-infected young nude (athymic) mice. Herein, we show that demyelination in nude mice was mediated by γδ T ...

  20. 6-Deoxy-6-[131I]iodo-L-ascorbic acid for the in vivo study of ascorbate. Autoradiography, biodistribution in normal and hypolipidemic rats, and in tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Normal female rat distribution studies showed high and specific uptake of 6-deoxy-6-[131I]iodo-L-ascorbic acid (6-131IAsA) into the adrenal glands, known to highly express the ascorbate sodium-dependent vitamin C transporter-2 (SVCT-2), and the adrenal gland was clearly visualized by whole-body autoradiography. Preinjection of sulfinpyrazone, a known blocker of ascorbate transport, with 6-131IAsA resulted in decreased uptake of radioactivity in rat adrenal glands compared to the control group, seemingly illustrating the participation of the SVCT transporter (probably the SVCT-2 subtype) in the uptake process in vivo. 4-Aminopyrazolo[3,4-d]pyrimidine-induced hypolipidemic rats showed a 1.7-fold increase in adrenal uptake of radioactivity at 30 min postinjection of 6-131IAsA, compared to the control, with increased adrenal-to-liver and adrenal-to-kidney ratios. To further characterize 6-131IAsA for its tumor uptake properties, biodistribution studies were also performed using male nude mice implanted with either Y-1 adrenocortical tumor cells or adrenal medulla-derived PC12 cells. None of these tumors exhibited relevant uptake of 6-131IAsA while normal adrenal glands showed high uptake of radioactivity, suggesting that these tumors in this model have only a poor transport capacity for this agent. The present study demonstrates that the use of radioiodinated 6-IAsA may help to obtain information about functional alterations in diseased adrenal glands, but it does not exhibit desirable properties as a tumor-seeking agent for ascorbic acid bioactivity. (author)

  1. Effect of thumus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice

    International Nuclear Information System (INIS)

    Nude mice, partially backcrossed to Balb/c or DBA/2, were injected iv with 5 x 107 thymus cells from the respective inbred strain. The response of these mice to immunization with Brucella abortus antigen was studied, with respect to both antibody production and the formation of germinal centers in their lymphoid tissues. The results were compared to those obtained with nude mice to which no thymus cells were given, as well as to Balb/c, DBA/2, or +/question litter mate controls. Nude mice formed less 19S as well as 7S antibody than did litter mate controls and completely lacked germinal centers in lymph nodes and gut-associated lymphoid tissue. Those nude mice which had been injected with thymus cells made a much better secondary response, both for 19S and for 7S antibody, and had active germinal centers in their lymph nodes as early as 3 wk after thymus cell injection. Intestinal lymphoid tissue in nude mice showed only slight reconstitution of germinal center activity several months after thymus cell injection and none at earlier times. Irradiated (3000 R) thymus cells appeared as effective as normal cells in facilitating germinal center appearance and 7S antibody production in the nude mice

  2. Experimental study of 32P-CP-PLLA microparticle on human pancreatic carcinoma in nude mice

    International Nuclear Information System (INIS)

    Objective: To study the therapeutic and toxic effects of 32P-chromic phosphate-poly (L-lactic) acid (32P-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma. Methods: Twenty four nude mice bearing tumors were injected with 0, 9.3, 18.5 and 37.0 M Bq 32P-CP-PLLA microparticle, respectively. The relative tumor growth rates were observed every day, and white blood cells, platelets and body weight were measured. At 14 d after administration, the tumors were removed, histological examination and immunohistochemical analysis were performed. Results: The relative tumor growth rates of each treatment group was lower than 40%. Histological examination showed the degenerative necrosis at the site nearby the microparticle. Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast, the expression of bax in treated group were higher than those in control group. The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43, 0.47 ± 0.13, 1.10 ± 0.32, 2.19 ± 0.57 for 0, 9.3, 18.5 and 37.0 MBq 32P-CP-PLLA microparticle, respectively (t=2.36-2.77, P<0.05). MVD were 31.2 ± 2.3, 23.8 ± 1.5, 14.8 ±0.8, 11.0 ± 1.2, respectively. Dose dependence was observed in both HE and IHC staining after 14 d treatment (t=2.30-2.57, P<0.05). Conclusions: Intratumoral injection of 32P-CP-PLLA microparticle might be a safe, easy and effective radionuclide interventional therapy for pancreatic carcinoma. (authors)

  3. MR imaging of nude mouse bearing human hepatocellular carcinoma by using two-step pretargeting strategy

    International Nuclear Information System (INIS)

    Objective: To improve the sensitivity of MR molecular imaging by using targeting and magnifying effects of biotin-avidin system (BAS). Methods: After preparing biotinylated monoclonal antibody HAb18, the number of biotin molecules coupled to each antibody and the binding capacity of biotinylated antibody were determined. Two-step pretargeting tumor imaging was first achieved by intravenously injecting biotinylated monoclonal antibody HAb18 into 8 BALB/c nude mice bearing QGY-7723 tumor cells line. 24 h later, Gd-DTAP-streptavidin (Gd-DTPA-SA) was injected. Gd-DTPA-HAb18 and Gd-DTPA were respectively injected intravenously into the other 12 tumor-bearing mice as contrast groups. MR imaging was performed before and 10, 30, 60 min, 3, 6, 12, 24 h, and 48 h after injection of MR contrast agents. All images were obtained using SE T1-weighted imaging sequence. After MR imaging, enhancement time course of three different groups was determined by using enhancement data measured in the region of interest in the tumor. Enhancement ratio and contrast-to-noise of tumor were also calculated. Results: The average number of biotin conjugated with each monoclonal antibody molecular was 20. And the immunoactivity of biotinylated antibody was 91%. In two-step pretargeting strategy, SI of tumor increased slowly and reached the maximum value at 6 h after injection of Gd-DTPA-SA, enhancement ratio and CNR of tumor had significant difference with other two enhancement methods. The enhancing effect of tumor was still perceptible even after 48 h.When using Gd-DTPA-HAb18, the tumor enhancement pattern was slow and slight. Even at 24 h after injection of Gd-DTPA-HAb18, enhancement ratio of tumor was 13.5%. After Gd-DTPA was injected, signal intensity of tumor increased rapidly, and reached the maximum value at 30 min after injection of Gd-DTPA, and then decreased rapidly. Conclusion: Two-step pretargeting strategy based on BAS has specific and signal magnifying effects in tumor MR imaging

  4. Detection of esophageal squamous cell carcinoma by cathepsin B activity in nude mice.

    Directory of Open Access Journals (Sweden)

    Wei Ma

    Full Text Available BACKGROUND AND OBJECTIVE: Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice. METHODS: Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109 and one normal human esophageal epithelial cell line (HET-1A for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology. RESULTS: CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro. CONCLUSIONS: CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.

  5. Anti-tumor effect of thalidomide and paclitaxel on hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-lin; LIU Zhi-su; SUN Quan

    2005-01-01

    Background Thalidomide is reviving for its antiangiogenic effect on corneal neovascularization models. Recently, it has been employed in tumor research in several types of solid carcinomas. However, its effect on hepatocellular carcinoma (HCC) has not yet been clarified. Methods A total of 48 nude mice bearing human HCC with a high metastatic potential were randomly divided into 4 groups. Thalidomide (200 mg/kg), paclitaxel (13 mg/kg), or their combination, which was dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension, was intraperitoneally injected in each group since the second day of the establishment of animal model. The group simply administered with 0.5% CMC was set as placebo-control. The mice were sacrificed on the 30th day, for the measurement of tumor size, weight and metastasis in the lungs. The levels of CD34 and endothelial growth factor (VEGF) mRNA in tumor tissues were detected by immunohistochemistry and semiquantitative RT-PCR, respectively, and microvessel density (MVD) was evaluated. Results No statistical difference was found in tumor weight and volume between the thalidomide group and control (P>0.05). Paclitaxel showed a growth-inhibiting effect on tumors (P<0.05). The value of MVD and VEGF mRNA and metastases to the lungs in each group were lower than those in the placebo-control group (P<0.05); such difference in the combination group was statistically significant (P<0.05). Conclusions Paclitaxel, but not thalidomide, has significant growth inhibitory effect on tumors, but both significantly inhibit angiogenesis and metastasis of human HCC in nude mice, such effects of paclitaxel can be amplified by thalidomide.

  6. Experimental infection of Balb/c nude mice with Hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  7. Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis

    OpenAIRE

    Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R.; Parelkar, Nikhil K.; Jokar, Iman; Vielhauer, George A.; Neufeld, Kristi L.

    2014-01-01

    Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are hetero...

  8. Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice

    OpenAIRE

    SUN, Lin-Quan; Buchegger, Franz; COUCKE, Philippe; MIRIMANOFF

    2001-01-01

    This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios...

  9. Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice.

    OpenAIRE

    Ramani, P; Balkwill, F.R.

    1988-01-01

    Therapy with human lymphoblastoid interferon HuIFN-alpha(N1), or recombinant human interferon gamma, rHuIFN-gamma, inhibited experimental pulmonary metastases of the human melanoma cell line, DX3-azac, in BALB/c nude mice and significantly prolonged survival. The human IFNs had no effect on nude mouse lung and spleen NK cell activity, lung macrophage activity, haemoglobin or white cell counts. HuIFN-alpha(N1) had no effect on the levels of the IFN induced enzyme 2-5A synthetase in nude mouse ...

  10. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  11. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  12. Detection of Corynebacterium bovis infection in athymic nude mice from a research animal facility in Korea

    OpenAIRE

    Kim, Tae-Hyoun; Kim, Dong-Su; Han, Ju-Hee; Chang, Seo-Na; Kim, Kyung-Sul; Seok, Seung-Hyeok; Kim, Dong-Jae; Park, Jong-Hwan; Park, Jae-Hak

    2014-01-01

    Corynebacterium (C.) bovis infection in nude mice causes hyperkeratosis and weight loss and has been reported worldwide but not in Korea. In 2011, nude mice from an animal facility in Korea were found to have white flakes on their dorsal skin. Histopathological testing revealed that the mice had hyperkeratosis and Gram-positive bacteria were found in the skin. We identified isolated bacteria from the skin lesions as C. bovis using PCR and 16S rRNA sequencing. To the best of our knowledge, thi...

  13. 雷帕霉素抑制子宫内膜癌裸鼠移植瘤生长活体成像的观察%Bioluminescence imaging evaluation of the inhibitory effect of rapamycin in nude mice bearing endometrial cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    李田; 杨越波; 孟丽荣; 李小毛; 许成芳; 李征然

    2011-01-01

    目的:观察雷帕霉素(RAPA)对不同PTEN表达子宫内膜癌裸鼠移植瘤的抑制作用.方法:通过慢病毒转染构建稳定表达绿色荧光蛋白(GFP)的HEC-1A(PTEN阳性)和Ishikawa( PTEN阴性)细胞抹,建立裸鼠移植瘤模型.活体成像系统观察肿瘤的生长情况.观察RAPA治疗后肿瘤的体积及重量的变化.HE染色观察肿瘤的病理形态学变化.结果:建立稳定表达GFP的子宫内膜癌细胞系及裸鼠移植瘤模型,活体荧光成像显示,治疗组裸鼠荧光强度较对照组明显减弱.治疗组肿瘤体积及重量明显小于对照组(P<0.05),Ishikawa细胞纽的抑瘤率(67.1%)较高于HEC-1A细胞组的抑瘤率(48.1%).治疗组的肿瘤组织可见大片肿瘤细胞坏死,对照组肿瘤细胞坏死少.结论:RAPA对PTEN阳性及阴性的子宫内膜癌生长均有明显的抑制作用,PTEN的丢失可增加RAPA抗子宫内膜癌的敏感性.%OBJECTIVE: To investigate the inhibilpry effect of ra-pamycin (RAPA) in nude mice bearing endometrial cancer cell lines with different PTEN status. METHODS: HEC-1A (PTEN positive) and Ish-ikawa (PTEN negative) cell lines with stable expression of green fluorescent protein (GPP) were established by transfection via lentiviral vec-lor. The HEC-1A-GFP and IshikawaGFP cells were inoculated into the nude mice to prepare the subcutaneously xenografted tumor model. The dynamic growth of xenografted tumor was observed using fluorescence imaging system in vivo. After treated with RAPA, the volume and weight of transplanted tumors in nude mice were measured. Morphology of transplanted tumor tissues was observed by HE staining. RESULTS; The stable GFP-expressing endometrial cancer cell lines and xenografted tumor model were obtained. Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control. As compare with control group,the tumor volume and weight of treated group were signicandy decreased ( P< 0-05). The

  14. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry and......The purpose of this study was to develop a suitable animal model for the investigation of the pathogenesis and therapy of uveal malignant melanoma. Eight choroidal malignant melanomas from eight patients were transplanted into nude mice in an attempt to establish a serially transplantable tumour...... electron microscopy. Only one of the eight transplanted primary tumours (13%) was established as a xenograft in nude mice. Furthermore, the take rate of the transplantable tumour was low (13%). The growth of the tumour fitted a Gompertz function, and the calculated tumour volume doubling time was 54 days...

  15. In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice.

    Science.gov (United States)

    Feng, Mingqian; Zhang, Jingli; Anver, Miriam; Hassan, Raffit; Ho, Mitchell

    2011-01-01

    Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo. PMID:21479131

  16. In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

    Directory of Open Access Journals (Sweden)

    Mingqian Feng, Jingli Zhang, Miriam Anver, Raffit Hassan, Mitchell Ho

    2011-01-01

    Full Text Available Malignant mesothelioma (MM causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

  17. Spontaneous pulmonary metastasis of human cancer cells in X-irradiated and nonirradiated nude mice

    International Nuclear Information System (INIS)

    The effect of whole body X-irradiation on the spontaneous pulmonary metastasis of human cancer cells transplanted into adult nude mice was investigated. Human cancer cells were inoculated into footpads of adult nude mice following 3 Gy whole body X-irradiation. The incidence of pulmonary metastasis was increased in the irradiated mice. Cytotoxicity of splenocytes, particularly adherent cells, was lower in the irradiated mice than in the nonirradiated mice. Histological examinations revealed decreased mononuclear cell infiltration around the primary tumor and pulmonary metastatic foci in the irradiated mice. The suppressive effect of cytotoxicity of the splenocytes by whole body X-irradiation may thus relate to ensuing metastasis both in the phase of release and intravasation from the primary tumor and in the phase of lodgement and proliferation in the target organ. (author)

  18. Development and characterization of multidrug resistant human hepatocarcinoma cell line in nude mice

    Institute of Scientific and Technical Information of China (English)

    Bao-Jin Zhai; Ze-Yong Shao; Chun-Liang Zhao; Kai Hu; Feng Wu

    2006-01-01

    AIM: To establish a multidrug resistant (MDR) cell subline from the human hepatocarcinoma cell line (HepG2)in nude mice.METHODS: HepG2 cell cultures were incubated with increasing concentrations of adriamycin (ADM) to develop an ADM-resistant cell subline (HepG2/ADM) with crossresistance to other chemotherapeutic agents. Twenty male athymic BALB/c-nu/nu mice were randomized into HepG2/nude and HepG2/ADM/nude groups (10 in each group). A cell suspension (either HepG2 or HepG2/ADM)was injected subcutaneously into mice in each group.Tumor growth was recorded, and animals were sacrificed 4-5 wk after cell implantation. Tumors were prepared for histology, and viable tumor was dispersed into a single-cell suspension. The IC50 values for a number of chemotherapeutic agents were determined by 2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (MTT) assay. Rhodamine-123retention/efflux and the level of resistance-associated proteins were determined by flow cytometry. The mRNA expression of mdr1, mrp and Irp genes was detected using reverse transcriptase polymerase chain reaction (RT-PCR) in HepG2/nude and HepG2/ADM/nude groups.RESULTS: The appearances of HepG2/nude cells were slightly different from those of HepG2/ADM/nude cells.Similar tumor growth curves were determined in both groups. A cross-resistance to ADM, vincristine, cisplatin and 5-fiuorouracil was seen in HepG2/ADM/nude group.The levels of P-glycoprotein and multidrug resistanceassociated proteins were significantly increased. The mRNA expression levels of mdr1, mrp and Irp were higher in HepG2/ADM/nude cells.CONCLUSION: ADM-resistant HepG2 subline in nude mice has a cross resistance to chemotherapeutic drugs.Tt may be used as an in vivo model to investigate the mechanisms of MDR, and explore the targeted approaches to overcoming MDR.

  19. Serum steroid levels in intact and endocrine ablated BALB/c nude mice and their intact littermates

    DEFF Research Database (Denmark)

    Brünner, N; Svenstrup, B; Spang-Thomsen, M; Bennett, P; Nielsen, A; Nielsen, J

    1986-01-01

    An investigation was made of the serum steroid levels found in intact and endocrine ablated nude mice of both sexes and in their intact homozygous littermates. The results showed that nude mice have a normal steroidogenesis, but with decreased levels of circulating steroids compared to those of t...

  20. Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn1nu Mice

    Directory of Open Access Journals (Sweden)

    Shahnaz Begum

    2014-01-01

    Full Text Available Eclipta alba (L. Hassk, Asiasarum sieboldii (Miq. F. Maek (Asiasari radix, and Panax ginseng C. A. Mey (red ginseng are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly P>0.001 than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs. The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss.

  1. Total Aglycones from Marsdenia tenacissima Increases Antitumor Efficacy of Paclitaxel in Nude Mice

    Directory of Open Access Journals (Sweden)

    Rui-Jing Zhu

    2014-09-01

    Full Text Available Marsdeniae tenacissimae Caulis (MTC is a Chinese herbal medicine used mainly for treatment of cancer, whose pharmacologically active constituents responsible for its in vivo activity and clinical efficacy have not been clearly elucidated. In this study, total aglycones of MTC (ETA showed the ability to sensitize KB-3-1, HeLa, HepG2 and K562 cells to paclitaxel treatment. More inspiringly, ETA markedly enhanced the antitumor activity of paclitaxel in nude mice bearing HeLa or KB-3-1 xenografts. Compared to treatment with paclitaxel alone, treatment with combination of paclitaxel and ETA achieved significant reduction in volume and weight of HeLa tumors (p < 0.05, and remarkable inhibition to the growth of KB-3-1 tumors (p < 10−6. ETA was characterized by the presence of a group of tenacigenin B ester derivatives, among which four reference compounds, 11α-O-tigloyl-12β-O-acetyltenacigenin B, 11α,12β-di-O-tigloyltenacigenin B, 11α-O-2-methylbutanoyl-12β-O-tigloyltenacigenin B, and 11α-O-(2-methylbutanoyl-12β-O-benzoyltenacigenin B, accounted for 42.14% of the total peak area of 19 detectable components assayed by HPLC. Our study has identified ETA as a promising sensitizer for cancer chemotherapy.

  2. Pluripotent Embryonic Stem Cells Developed into Medulloepithelioma in Nude Mice Eyes

    Institute of Scientific and Technical Information of China (English)

    Yongping Li; Xiufeng Zhong; Jianhua Yan; Jianxian Lin; Song Tang; Xuan Wu; Shulong Li; Guanguang Feng; Yuzhen Yi

    2002-01-01

    Purpose: The pluripotent embryonic stem cells can differentiate into various kinds offormal tissues. There is no previous report on the differentiation of embryonic stem cellin the intraocular environment. In this paper, the authors tried to investigate theintraocular growth character of mice embryonic stem cells in nude mice.Methods: Murine embryonic stem cells were cultured and maintained in anundifferentiated state in vitro. They were transplanted into the right eyes of 20 nude miceby microinjection under operating microscope. Animal eye observation, light microscopeand immunohistochemical examinations were implemented.Results: Two to three days after transplantation, small pieces of gray-white materialcould be viewed in the vitreous cavity. Between the 15th and 20th day, the gray-whitemass grew into the anterior chamber in 4 nude mice eyes. Then, the mass at the anteriorchamber extended extraocularly. On the 30th day, a remarkable proptosis was observedin two of the four nude mice. In 6 to 45 days, the mice were executed for morphologicalexamination which showed the following typical structures: (1) Undifferentiated cellswith prominent nucleolius. (2) Flexner-Wintersteiner-like rosettes. (3) Medulloepithe-lioma-like structure: the cells were arranged in sheets, cords, tubes, and cysts. (4) Large,spindle-or astrocyte-like cells. (5) Cartilage-like structure. Immunohistochemically, mostof the cells were highly positive in NSE staining and a few cells were moderately positivein GFAP staining.Conclusions: Both animal eye findings and morphologic examinations certificated thatthe transplanted embryonic stem cells could grow in the eyes of nude mice anddifferentiate into intraocular medulloepithelioma.

  3. Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution

    DEFF Research Database (Denmark)

    Hougen, H P; Röpke, C

    1975-01-01

    far the most numerous in the lymph nodes seemed to be more sessile than para-cortical lymphocytes. The life-span of these latter cells are comparable to those of thoracic duct lymphocytes, and the scarcity of cells in the paracortex reflects the small number of recirculating lymphocytes in nude mice....

  4. Effect of phosphorus-32 glass microspheres on human hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dong-Sheng Zhang; Lu Liu; Li-Qiang Jin; Mei-Ling Wan; Qun-Hui Li

    2004-01-01

    AIM: To study the effects of phosphorus-32 glass microspheres (32P-GMS) on human hepatocellular carcinoma in nude mice.METHODS: Human liver cancer cell line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice.Then the 40 tumor-bearing BALB/c nude mice were allocated into treatment group (n=-32) and control group (n=8). In the former group different doses of 32P-GMS were injected into the tumor mass, while in the latter nonradioactive 31PGMS was injected into the tumor mass. The experimental animals were sacrificed on the 14th day. The ultrastructural changes of tumor in both treatment group and control group were studied with transmission electron microscopy (TEM)and stereology.RESULTS: In treatment group, a lot of tumor cells were killed and the death rate of tumor cells was much higher (35-70%). Ultrastructurally, severe nuclear damage was observed in the death cells. The characteristics of appoptosis such as margination of heterochromatin was also found in some tumor ceils. Besides, well differentiated tumor cells,degenerative tumor cells and some lymphocytes were seen.The skin and muscle adjacent to the tumor were normal. In control group, the tumor consisted of poorly differentiated tumor cells, in which there were only a few of dead cells (5%). Stereologicl analysis of ultrastructral morphology showed that Vv of nuclei (53.31±3.46) and Vv of nucleoli (20.40±1.84) in the control group were larger than those (30.21±3.52 and 10.96±2.52) in the treatment group respectively (P<0.01), and Vv of RER (3.21±0.54) and Vv of mitochondria (4.53±0.89) in the control group were smaller than those (8.67±1.25 and 7.12±0.95) in the treatment group respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi (27.12 um2/100 um3±11.84 um2/100 um3) in the control group was smaller than that (78.81 um2/100 um3±19.69 um2/100 um3) in the treatment group (P<0.01). But Vv of lipid particles (3.71±1.97) and Vv of vacuoles (5.72±1

  5. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    Science.gov (United States)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  6. Inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1.

    Science.gov (United States)

    Wang, X; He, X J; Xu, H Q; Chen, Z W; Fan, H H

    2016-01-01

    The aim of this study was to explore the inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1 and its mechanism. For this study, athymic nude mice were injected with either normal pituitary tumor RC-4B/C cells or LRIG1-transfected RC-4B/C cells. We then calculated the volume inhibition rate of the tumors, as well as the apoptosis index of tumor cells and the expression of Ras, Raf, AKt, and ERK mRNA in tumor cells. Tumor cell morphological and structural changes were also observed under electron microscope. Our data showed that subcutaneous tumor growth was slowed or even halted in LRIG1-transfected tumors. The tumor volumes were significantly different between the two groups of mice (χ2 = 2.14, P tumor apoptosis index was found to be 8.72% in the control group and 39.7% in LRIG1-transfected mice (χ2 = 7.59, P tumor cells appeared to be in early or late apoptosis under an electron microscope, while only a few subcutaneous tumor cells appeared to be undergoing apoptosis in the control group. In conclusion, the LRIG1 gene is able to inhibit proliferation and promote apoptosis in subcutaneously implanted human pituitary tumors in nude mice. The mechanism of LRIG1 may involve the inhibition of the PI3K/ Akt and Ras/Raf/ERK signal transduction pathways. PMID:27173312

  7. Differentiation of Embryonic Stem Cells into Neurons and Retina—like Structure in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    LiYP; GeJ

    1999-01-01

    Purpose:To investigate the intraocular growth and biological characteristics of mice embryonic stem cells in nude mice.Methods:Murine embryonic stem cells(D3 cell line)were cultured and maintained in an undifferentiated state in vitro,then transplanted into the anterior chamber of nude mice.Mophological and immunohistochemical examinations were implemented.Results:Two to three days after transplantation,yellow-white floating granules,sheets and masses were seen inside the anterior chamber and vitreous cavity,and enlarged gradually,14-20days later,the mice were executed.Morphological examination showed that there were undifferentiated cells and some round or polygonal differentiated cells in anterior chamber and vitreous cavity.The morphology of these differentiated cells were similar to that of the retina.The cells were highly positive in NSE staining.Conclusion:The tranplanted embryonic stem cells cold grow in the eyes of nude mice with tendency to differentiate into neurons and retina-like structure.

  8. Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    MAO Yi; XIA Rui; WANG Lei; WANG Yu-qing; GAO Fa-bao

    2013-01-01

    Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and

  9. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

    Institute of Scientific and Technical Information of China (English)

    Zhao-You Tang; Lun-Xiu Qin; Hui-Chuan Sun; Lu Wang; Jian Zhou; Yah Li; Zeng-Chen Ma; Xin-Da Zhou; Zhi-Quan Wu; Zhi-Ying Lin; Bing-Hui Yang; Fan-Xian Sun; Jian Tian; Sheng-Long Ye; Yin-Kun Liu; Kang-Da Liu; Qiong Xue; Jie Chen; Jing-Lin Xia

    2001-01-01

    Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.``

  10. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

    International Nuclear Information System (INIS)

    This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies

  11. Radioimmunodetection of hepatic metastases from human colon cancer in nude mice with a gamma-detecting probe

    International Nuclear Information System (INIS)

    The utility of a gamma detecting probe (GDP) in the detection of experimental hepatic metastases in nude mice using radiolabeled monoclonal antibody (mAb) was assessed. Twelve mice with established hepatic metastases from the HT-29 LMM cell line, 5 mice with s.c. tumors in the left flank and 6 non-tumor-bearing control mice were given i.v. injections of 40 microCi/4 micrograms of 125I-labeled mAb HT-29-15. Six tumor-bearing mice were given i.v. injections of an isotype-matched control mAb (BL-3). Using the GDP, measurements were obtained daily over the region of the heart, the region of the liver (i.e., the right flank), and the s.c. tumor when applicable. Intraoperative measurements were obtained at laparotomy on days 5 and 7. Subsequently, the metastases, normal liver, and blood were resected and the radioactivity/g tissue was measured in a gamma well counter. External right flank/heart ratios were significantly higher in the tumor-bearing group than in controls. External measurements allowed detection of small tumors weighing only 161 ± 87 (SD) mg and occupying 11.5 ± 4% of the entire liver weight. Metastases counted intraoperatively with the GDP measured 1 to 7 mm in greatest diameter. The mean metastasis/heart GDP ratio was 1.7 ± 0.4:1. Tumors weighing as little as 51 ± 42 mg could be identified. These experimental results confirm the usefulness of the GDP for the detection of small hepatic metastases from colon cancer and illustrate important features of probe measurement of radiolabeled mAb uptake

  12. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    International Nuclear Information System (INIS)

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion

  13. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

    2013-09-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

  14. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg'd)], (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.

  15. Antitumor and radiosensitizing effects of (E)-2'-Deoxy-2'-(Fluoromethylene) cytidine, a novel inhibior of ribonucleotide diphosphate reductase on human colon carcinoma xenografts in nude mice.

    OpenAIRE

    Sun, Lin-Quan; Li, Ye-Xiong; Guillou, Louis; Mirimanoff, René-Olivier; Coucke, Philippe

    1997-01-01

    Antitumor and radiosensitizing effects of (E).2'-deoxy.2'-(fluromethyl ene) cytidine (FMdC), a novel inhibitor of ribonucleotide reductase, were evaluated on nude mice bearing s.c. xenografts and liver metastases of a human colon carcinoma. FMdC given once daily or twice weekly has a dose-dependent antitumor effect. The maximum tolerated dose In the mice was reached with 10 mgi'kg applied daily over 12 days. Twice weekly administration of FMdC reduced its toxicity but lowere...

  16. 消痰散结方对裸鼠人胃癌MKN-45皮下移植瘤模型血清蛋白质组表达的影响%Comparative Serum Proteomic Study of Xiaotan Sanjie Recipe Intervened MKN-45 Human Gastric Tumor-bearing Nude Mice

    Institute of Scientific and Technical Information of China (English)

    陈天池; 魏品康; 贾占民; 魏振

    2012-01-01

    目的 观察消痰散结方对裸鼠人胃癌MKN-45皮下移植瘤模型血清蛋白质组表达的影响.方法 30只BALB/c-nu/nu裸鼠随机分为正常组、模型组、干预组,采用瘤块接种方法造模.正常组自由饮食,模型组、干预组分别给予生理盐水、消痰散结方灌胃.运用蛋白质组学的双向凝胶电泳技术,观察3组之间的血清蛋白质组表达差异,筛选出与消痰散结方作用相关的差异表达蛋白质,并对其进行质谱鉴定,确认差异表达蛋白质的身份.结果 去除血清中高丰度蛋白质后获得分辨率高、重复性稳定性好的血清2-DE图谱.与正常组比较,模型组中找到25个差异表达蛋白点,其中12个表达上调,13个表达下调.与模型组比较,干预组中找到19个差异表达蛋白点,其中14个表达上调,5个表达下调.3组间比较共找到差异表达蛋白点9个,与正常组比较,在模型组中表达上调、在干预组表达回调至正常组水平的3个,最终鉴定为结合珠蛋白、泛素蛋白连接酶、组蛋白甲基转移酶;与正常组比较,在模型组中表达下调、在干预组表达回复至正常组水平的有6个,其中3个鉴定为载脂蛋白A1、过氧化物酶1、超氧化物歧化酶.结论 消痰散结方对载脂蛋白A1、过氧化物酶1等功能蛋白表达的综合性调节可能是其发挥抗胃癌作用的重要机制.%Objective To observe the serum protein spectrum changes of MKN-45 gastric cancer cell bearing nude mice intervened by Xiaotan Sanjie Recipe on the platform of proteomics. Methods Thirty BALB/c-nu/nu mice were randomly divided into normal group, model group and intervention group. MKN45 gastric cancer cells were subcutaneously implanted into immune-incompetent nude mice in model group and intervention group to establish tumor bearing model. The control group was fed freely. The model group and the intervention group was separately administrated with saline and Xiaotan Sanjie Recipe, which

  17. Investigation of phyotographic distribution of anti-P-gp antibody PHMA02 in nude mice

    International Nuclear Information System (INIS)

    Objective: To investigate the photographic distribution of anti-P-gp monoclonal antibody PHMA02 in nude mice transplanted with K562/A02 cell tumor. Methods: PHMA02 were prepared by hybridoma technique, sodium dodecyl sulfate-polyacrylamide gel electrophorsis and Western-blot were used to analyzed its purity, fluorescence-activated cell sorting (FACS) was also used to determine its binding with K562 and K562/A02 cells. Nude mice were injected i.v with 125I labeled PHMA02, and were scanned on different time by SPECT. Results: The purity and binding affinity of PHMA02 were both satisfactory. On the second day from injection, radioactivity appeared in all tumor regions of the P-gp+(K562/A02) group nude mice, and intensified in the following days. Concludsion: The photographic difference of PHMA02 distribution between P-gp+(K562/A02) and P-gp-(K562) group could specifically distinguish the P-gp+ tumor tissue. (authors)

  18. Immunohistochemical investigations of xenotransplanted human adenocarcinomas on nude mice: Correlation to radioimaging

    International Nuclear Information System (INIS)

    Immunohistochemical investigations of xenotransplanted human adenocarcinomas on nude mice; correlation to radioimaging Human carcinomas were subcutanously grafted to nude mice (Balb/c-nu/nu) and were investigated in four passages by immunohistochemical methods and by the fluorochrome bisbenzimid. In this way there could be observed a successful differentiation between the nourishing murine stroma and the human tumor parenchym. Especially the use of a monoclonal antibody (rat/mouse fusion) directed against human tissue turned out to be a suitable method. Four adenocarcinomas were tested: Colon-, mamma-, stomach- and testicle carcinoma. During the first four passages atypical parts of murine connective tissue and some changes in the human parenchyma could be seen. These results demonstrate that also in nude mice variations of the transplanted tumor material could happen. They could be detected in time with a routine immunohistochemical test. The consequences of tumor morphological variations for the development of therapeutic and diagnostic tools were studied with the help of radioimaging by external scintigraphy. Furthermore the biodistribution, tumoruptake and the whole body counting were studied by means of radionuclid marked monoclonal antibodies. The morphological variations of the passages of mammary, testicle and colon carcinomas were not big enough to influence the results in a certain way. Therefore especially the relation between the activity uptake in the tissue, the size of the tumor and the whole body uptake was studied in view of immunoscintigraphy. (orig./MG)

  19. INHIBITION OF ANGIOSTATIN TO THE GROWTH AND METASTASIS OF GASTRIC CANCER IN NUDE MICE

    Institute of Scientific and Technical Information of China (English)

    刘炳亚; 陈雪华; 朱正纲; 林言箴; 卢伟新; 郭礼和; 朱丽华

    2002-01-01

    Objective To study the inhibition effect on tumor angiogenesis and metastasis of angiostatin, which generated from human plasminogen. Methods Plasminogen was isolated from human plasma by Sepharose chromatography and then catalyzed by elastase. Angiostatin was isolated by Sepharose 4B-Lysine chromatography. Nude mice model of metastatic gastric cancer was set up by intact tumor tissue implantation orthotopically. From the day of operation, mice received daily intraperitoneal injections of human angiostatin ,intact plasminogen, or saline, respectively. 24μg(1.2mg/kg) of angiostatin or plasminogen was given on the day of operation, followed by a daily dose of 12μg (O. 6mg/kg) via intraperitoneal injection for three weeks.Ten weeks after implantation, mice were sacrificed and autopsied. Microvascular density was measured by immunohistochemistry. Results Molecular weight of plasminogen isolated from plasma was 94KD. Plasminogen was catalyzed into two fragment peptides by elastase, which were 41 ~ 43KD and 51 ~ 53KD in molecular weight. Growth of the orthotopieally implanted tumor was significantly reduced in size in the mice treated with angiostastin with an inhibition rate of 54.0%. Tumor metastasis to the liver and peritoneum was also significantly inhibited by angiostatin with inhibition rate of 61.9% and 55.6% respectively. The microvaseular density was also decreased significantly in the angiostatin treated mice. Conclusion Angiostatin may be generated from plasma, and has inhibitory effect both on tumor growth and metastasis in nude mice model of human gastric cancer.

  20. CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholanthrene

    DEFF Research Database (Denmark)

    Boesen, M; Svane, I M; Engel, A M; Rygaard, J; Thomsen, Allan Randrup; Werdelin, O

    2000-01-01

    An attempt was made to identify the selection pressures put upon a growing tumour by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell-deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted to nu/+ recipients. The rejection rate of the sarcomas...... from nude mice was almost twice that of the sarcomas from nu/+ mice. Depletion of CD8+ T cells from nu/+ recipients prior to transplantation made them accept nude tumours that were consistently rejected by untreated nu/+ recipients. These findings suggest that a methylcholanthrene sarcoma during its...

  1. Effect of reconstituted basement membrane components on the growth of a panel of human tumour cell lines in nude mice.

    OpenAIRE

    Topley, P.; Jenkins, D C; Jessup, E. A.; Stables, J. N.

    1993-01-01

    Previous reports have indicated that reconstituted basement membrane (matrigel), when co-injected with either established or primary human tumour cells, can improve the growth of subcutaneous xenografts in nude mice. The human adenocarcinoma cell lines A549, SW480, and WiDr, and the human fibrosarcoma cell line HT1080scc2 exhibit varying degrees of tumourigenicity in nude mice. All these lines showed increased tumorigenicity and/or growth rate, together with a change towards a more differenti...

  2. Radioimmunotherapy for pancreatic carcinoma using 131I-labeled monoclonal antibody Nd2 in xenografted nude mice

    International Nuclear Information System (INIS)

    We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of 131I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. 131I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of 131I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of 131I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus 131I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer. (author)

  3. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  4. Growth kinetics of four human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Rygaard, K; Hansen, L;

    1989-01-01

    in nude mice were investigated. The proliferative tumor characteristics were examined by growth curves, thymidine labelling technique, and flow cytometric DNA analysis performed on fine-needle aspirations. The results showed that the tumors had growth kinetics comparable to other human tumor types......The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts...... with cell generation times of 42 to 60 hours. The three receptor-positive tumors had slower growth rate, larger tumor volume doubling time, and smaller growth fraction and labelling index than the receptor-negative tumor. However, no single proliferation parameter was sufficient to characterize the...

  5. Biokinetics of 111In-DTPA-D-Phe1-octreotide in nude mice transplanted with a human carcinoid tumor

    International Nuclear Information System (INIS)

    The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe1-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe1-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe1-octreotide (0.1 μg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe1-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues

  6. Pharmacokinetics and biodistribution of Erufosine in nude mice - implications for combination with radiotherapy

    International Nuclear Information System (INIS)

    Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice. NMRI (nu/nu) nude mice were treated by intraperitoneal or subcutaneous injections of 5 to 40 mg/kg body weight Erufosine every 48 h for one to three weeks. Erufosine-concentrations were measured in brain, lungs, liver, small intestine, colon, spleen, kidney, stomach, adipoid tissue, and muscle by tandem-mass spectroscopy. Weight course, blood cell count and clinical chemistry were analyzed to evaluate general toxicity. Intraperitoneal injections were generally well tolerated in all dose groups but led to a transient loss of the bodyweight (<10%) in a dose dependent manner. Subcutaneous injections of high-dose Erufosine caused local reactions at the injection site. Therefore, this regimen at 40 mg/kg body weight Erufosine was stopped after 14 days. No gross changes were observed in organ weight, clinical chemistry and white blood cell count in treated compared to untreated controls except for a moderate increase in lactate dehydrogenase and aspartate-aminotransferase after intensive treatment. Repeated Erufosine injections resulted in drug-accumulation in different organs with maximum concentrations of about 1000 nmol/g in spleen, kidney and lungs. Erufosine was well tolerated and organ-concentrations surpassed the cytotoxic drug concentrations in vitro. Our investigations establish the basis for a future efficacy testing of Erufosine in xenograft tumor models in nude mice alone and in combination with chemo- or radiotherapy

  7. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    , identified as ATP-ase positive dendritic cells, have almost disappeared from the transplanted epithelium whereas at day 21 after transplantation such cells were abundant. It is suggested that the ATP-ase positive cells which reappear in the transplanted epithelium are of mouse origin.......A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells...

  8. PDT of tumor-bearing mice using liposome delivered texaphyrins

    International Nuclear Information System (INIS)

    The krypton ion laser (752.5 nm) induced photodynamic effects in bladder tumor-bearing nude mice after i.v. application of waterinsoluble cadmium texaphyrins were investigated. Liposomes using sojalecithin as phospholipid act as carriers. Cd-texaphyrin synthesized by Sessler, possesses strong absorption transitions at 765 nm and a high quantum efficiency of singlet oxygen production. The phototreatment 2 hours after i.v. injection of the photosensitizer led to significant tumor destruction, whereas the treatment 24 hours after administration shows no effect. This corresponds well to studies on the accumulation behaviour of the carriers in tumor, skin and inner organs using fluorophore-labeled liposomes. (author). 7 refs., 3 figs., 1 tab

  9. Interferon gamma is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection

    OpenAIRE

    1990-01-01

    Athymic nude mice recover from an infection with recombinant vaccinia virus (VV) encoding murine interleukin 2 (IL-2), but treatment with a mAb to IL-2 accentuated infection. Administration of a mAb against interferon gamma (IFN-gamma) to mice infected with the IL-2-encoding virus completely prevented the IL-2-induced mechanisms of recovery. Both asialo-GM1+ (NK) and asialo-GM1- (non-NK) cells were participants in the IFN-gamma-mediated recovery of nude mice from infection with the IL-2-encod...

  10. 磁性纳米氧化铁颗粒在人肝癌Bel7402细胞裸鼠模型中的定向浓集及其生物学效应%Investigation on the migration and biologic effects of nano FeOx powders under the exposure of extremely low frequency altering electric magnetic fiek in human heptoma-bearing nude mice in vivo

    Institute of Scientific and Technical Information of China (English)

    居会祥; 戴真煜; 孙明忠

    2011-01-01

    Objective To investigate the mechanism and biologic effects of 37 nm magnetic nano FeOx powders (MNPs) on human hepatoma-bearing nude mice. Methods 37 nm MNPs were prepared by coprecipitation methods and then injected into human hepatoma (Bel-7402) bearing-nude mice through the tail vein. After injection of MNPs, the mice were first exposed under static magnetic field and then treated under extremely low frequency altering-electric magnetic field directing to the tumor area. The migration and trafficking of MNPs were determined by MMR. Tumor growth was monitored with calipers every 5 days and rumor volume was calculated on the basis of three-dimensioned measurements. The apoptosis of tumor cells was analyzed by flow cytometry analysis. The expressions of apoptosis-associated proteins Bcl-2, Bax and HSP27 were determined using western-blot analysis. Results Static magnetic field could direct the migration and trafficking of MNPs to the tumor site with a higher ratio of 98.9%. Extremely Low Frequency Electric-Magnetic Field (EMF) treatment could inhibit the proliferation of tumor cells and prolong the survive time of tumor-bearing mice injected with MNPs. In addition, the survival time of tumor-bearing mice and percentages of prohibition on tumor cell growth were 27.4 ± 0.7 days and 37.5 ± 0.8%( F = 0.005, P < 0.05), respectively.The results of flow cytometry analyses showed that about 18. 1士 0.6% ( F = 0.030, P < 0.05) of tumor cells were induced into early apoptosis. Furthermore, expressions of apoptosis-associated proteins Bcl-2 and Bax were significantly induced by MNPs under EMF treatment. The ratio of Bcl/Bax in both MNPs and EMF treatment 0.05). Heat shock protein-27 (Hsp-27) was not significantly induced in different treatment groups. Conclusion Injection of MNPs with EMF exposure on human hepatoma-bearing nude mice could significantly prolong the survival time, inhibit the tumor proliferation and growth. and induce tumor cells into apoptosis.%目的

  11. Localization of 131I-chTNT in a nude mice model with human hepatoma

    International Nuclear Information System (INIS)

    Purpose: In order to evaluate the targeting activity in the animal model with human hepatoma, the 131I-chTNT radioimmunoimaging was explored. Methods: Radioimmunoimages were taken on different intervals after injection of 131I-chTNT 5.55 MBq to the nude mice, and tissue distribution was measured. The results of 131I-chTNT monoclonal antibody group were compared with that of 131I control group. Results: The experimental group developed tumor positive images after one day of radio-labelled monoclonal antibodies injection and held on until the end of the experiment. The radioactivity in tumor mass was stable, and the half life of 131I-chTNT in hepatoma mass was 6.0 +- 1.6 days. there was no special radioactivity accumulation in normal liver tissue in the nude mice and the radioactivity in it disappeared rapidly. Statistics indicated the tumor/liver ratio in 1, 2, 3, 5, 7 days were 1.03, 2.43, 5.71, 7.96, 10.67, respectively. Conclusions: The results suggest that 131I-chTNT monoclonal antibody has a considerable targeting activity, and provide an evidence for that it can be used as a new radiopharmaceutical agent for the imaging and radio therapy of hepatoma

  12. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    OpenAIRE

    1984-01-01

    The presence in athymic nude mice of precursor T cells with self- recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate ...

  13. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    and to develop an essential part of the determination of proliferation parameters for the tumors. The results indicate that the course of tumor growth can be described with good approximation by the Gompertz function. A transformation of this function depicts the growth rectilinearly and appears to be......Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... suitable as a standard, e.g. in therapeutic experiments. The course of tumor growth is independent of the size of the transplant, and whether tumors are transplanted in the right or left or both flanks of the recipient mice. Furthermore, the growth does not vary in a systematic way with the number of...

  14. Imaging of human melanoma xenografts in nude mice with a radiolabeled monoclonal antibody

    International Nuclear Information System (INIS)

    External photoscanning with display of radioactivity data as a color-scaled image detected xenografts of human melanoma in male nude inbred mice of BALB/c background 48 hours after injection of 131I-labeled monoclonal IgG 225.28S that is specific for human melanoma. A 131I-labeled polyclonal goat IgG against human melanoma-associated antigens could also image the tumor, but with this preparation there was considerable localization of radioactivity in normal tissues, resulting in less satisfactory tumor definition. Labeled normal mouse IgG did not image the melanoma grafts. Assay of radioactivity in tissues of melanoma-grafted mice confirmed tumor-specific localization of the antimelanoma antibodies. The tumor:blood ratio of radioactivity was 6.55 with the monoclonal antimelanoma IgG and 0.45 with the polyclonal IgG

  15. Antitumor and Antiangiogenic Activities of Curcumin in Cervical Cancer Xenografts in Nude Mice

    Directory of Open Access Journals (Sweden)

    Pornphrom Yoysungnoen-Chintana

    2014-01-01

    Full Text Available To evaluate the effects of curcumin (CUR on tumor progression and angiogenesis in cervical cancer- (CaSki- implanted nude mice and on the angiogenic biomarkers: vascular endothelial growth factor (VEGF, cyclooxygenase-2 (COX-2, and epidermal growth factor receptor (EGFR. CaSki cells were subcutaneously injected in nude mice to establish subcutaneous tumors. One month after injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg of CUR daily × 30 consecutive days. Tumor volume was measured every 3-4 days. At the end of the study, tumor microvasculature was observed under confocal microscope, and immunohistochemical analyses were performed to detect CD31, VEGF, COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant tumor growth retardation (21.03% and 35.57% versus CaSki + vehicle group. The microvascular density (MVD in CaSki + vehicle group was significantly increased versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500 mg/kg. VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle group and attenuated significantly by CUR (1,000 and 1,500 mg/kg. In conclusion, high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a role in treating human cervical cancer and should be explored further.

  16. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    OpenAIRE

    Yongqi CUI; Geng, Qin; Gu, Aiqin; Miaoxin ZHU; Hanwei KONG; Sun, Lei; Liu, Lei; Yan, Mingxia; Yao, Ming

    2013-01-01

    Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left ca...

  17. Intratumoral injection with [188Re]rhenium sulfide suspension for treatment of transplanted human liver carcinoma in nude mice

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Direct intratumoral injection of non removable radioactive material has been widely studied because it could deliver high doses of radiation to target sites and minimize radiation leakage to non-target organs or tissues. Thirty nude mice bearing SMMC 7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [188Re]rhenium sulfide suspension or sodium [188Re]perrhenate solution. Another 30 tumor-bearing mice were divided into six groups, four groups of which were treated with a 0.1 ml [188Re]rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, to study the tumor inhibiting ratio, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. The injections were repeated 6 days later. The retention percentages of radioactivity (%ID) in tumors injected with [188Re]rhenium sulfide suspension were 90.96 ± 6.63%, 86.09 ± 22.58% and 87.62 ± 13.97% at 1, 24 and 48 h, respectively. Tumor inhibition ratios are as high as 89% when the outer space of tumor (0.5-0.6 cm from center) received about 507.6 Gy doses. Intratumoral injection of [188Re]rhenium sulfide suspension results in high tumor retention indicating this approach has strong potential for the treatment of hepatic carcinoma

  18. Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice

    International Nuclear Information System (INIS)

    A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl)porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 μg/g of glioma and up to 45 μg/g of carcinoma were observed when up to 102 μg/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by ∼80% on the average correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thromboxytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies

  19. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery.

    Directory of Open Access Journals (Sweden)

    Fuminari Uehara

    Full Text Available The aim of this study is to determine if fluorescence-guided surgery (FGS can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP (HT-1080-GFP, in nude mice, bright-light surgery (BLS was performed on all tumor-bearing mice (n = 22. After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11 or the combination of BLS + FGS (n = 11. The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2 and 10.5 ± 2.4 mm(2, respectively; p = 0.006. Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2 and 11.7 ± 6.9 mm(2, respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p < 0.001. Mice treated with BLS+FGS had a significantly higher disease-free survival rate than mice treated with BLS-only at five weeks after surgery. These results suggest that combination of BLS + FGS significantly reduced the residual fibrosarcoma volume after BLS and improved disease-free survival.

  20. Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres (131I-GMSs) following intratumoral injection

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of 131I gelatin microspheres (131I-GMS) on human breast cancer cells (MCF-7) in nude mice and the biodistribution of 131I-GMSs following intratumoral injections. A total of 20 tumor-bearing mice were divided into a treatment group and control group and received intratumoral injections of 2.5 mci 131I-GMSs and nonradioactive GMSs, respectively. Tumor size was measured once per week. Another 16 mice received intratumoral injections of 0.4 mci 131I-GMSs and were subjected to single photon emission computed tomography (SPECT) scans and tissue radioactivity concentration measurements on day 1, 4, 8 and 16 postinjection. The 20 tumor-bearing mice received intratumoral injections of 0.4 mci [131I] sodium iodide solution and were subjected to SPECT scans and intratumoral radioactivity measurements at 1, 6, 24, 48 and 72 h postinjection. The tumors were collected for histological examination. The average tumor volume in the 131I-GMSs group on post-treatment day 21 decreased to 86.82 ± 63.6%, while it increased to 893.37 ± 158.12% in the control group (P < 0.01 vs. the 131I-GMSs group). 131I-GMSs provided much higher intratumoral retention of radioactivity, resulting in 19.93 ± 5.24% of the injected radioactivity after 16 days, whereas the control group retained only 1.83 ± 0.46% of the injected radioactivity within the tumors at 1 h postinjection. 131I-GMSs suppressed the growth of MCF-7 in nude mice and provided sustained intratumoral radioactivity retention. The results suggest the potential of 131I-GMSs for clinical applications in radiotherapy for breast cancer

  1. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice.

    Science.gov (United States)

    Yang, Yang; Huang, Fang; Ren, Yun; Xing, Lu; Wu, Ying; Li, Zhushi; Pan, Huazhen; Xu, Caimin

    2009-01-01

    The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer. PMID:19911698

  2. The effect of multidrug resistance modulator HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in xenograft-nude mice.

    Science.gov (United States)

    Zhang, Yanyan; Feng, Yidong; Darshika, Kodithuwakku Nandani; Zhang, Bo; Hu, Yahui; Fang, Weirong; Li, Yunman; Huang, Wenlong

    2015-01-23

    To overcome MDR (multidrug resistance) of cancer mediated by P-gp (P-glycoprotein) has become a key strategy to improve the survival rate in clinic. Therefore, it is imperative to develop advanced modulators that have no side effects or interactions with cytotoxic drugs. HZ08, which acts as a P-gp inhibitor, shows a notable reverse effect with low cytotoxicity in vitro. Based on the previous results, the goal of this experiment is to elucidate the effect of HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in tumor-bearing nude mice. Several criterions and methods, such as tumor weight and volume, in vivo imaging, western blot, immunohistochemistry as well as ATPase hydrolysis assay were selected to evaluate the reversing activity and mechanism of HZ08 on MDR; Furthermore, fluorescence detection assay was applied to determine the distribution of adriamycin in the blood and tissues. This study revealed that HZ08 potentiated the anti-tumor activity of adriamycin but with little effect on the expression of P-gp in vivo. Adriamycin accumulation in tumor was enhanced by HZ08 via ATPase activity inhibition. In addition, HZ08 did not alter the pharmacokinetic characteristic of adriamycin in plasma or tissues. In conclusion, HZ08 showed dramatic MDR reversing activity and had no influence on the pharmacokinetics of adriamycin. PMID:25459530

  3. Sequential imaging of indium-111-labeled monoclonal antibody in human mammary tumors hosted in nude mice

    International Nuclear Information System (INIS)

    Using a bifunctional chelating agent, indium-111 was attached to a monoclonal antibody 10-3D2, specific for a 126-kilodalton phosphoglycoprotein antigen associated with human mammary carcinoma, and was then used to localize and visualize human mammary tumors hosted in nude mice. Simultaneous tumor concentration of In-111-10-3D2 was eight times greater than that of control I-125-MOPC-21. Uptake of F(ab')2 and Fab of 10-3D2 was also compared. The scintigrams demonstrated that intact antibody provided the best images. Control In-111-labeled MOPC-21 and plasma did not show specific localization in the tumor. Uptake of In-111-labeled 10-3D2 was also compared in two lines of human mammary tumors, BT-20 and HS-578T. Imaging with 10-3D2 was better for BT-20 than for HS-578T

  4. Membrane cell grafts, fresh and frozen to cover full thickness wounds in athymic nude mice

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    objective: To find a new way to cover full-thickness wounds. Methods: Biobrane(r), an adherent, flexible temporary wound dressing was incubated with cultured human keratinocytes. The cells adhered quickly forming "membrane-celgrafts" (MCG). Some of the grafts were frozen and after thawing viability was verified with a XTT colorimetric assay.MCGs, fresh and cryopreserved, were transplanted on full thickness wounds created on athymic nude mice. Conventional cultured epidermal grafts (CEG) and wounds without cell grafts served as control. Results: MCGs resulted in a differentiated epithelium of human phenotype and immunohistochemistry, immunofluorescence and electronmicroscopy were performed.Compared with CEG-grafted sites a reduced wound contraction was noticed and complete remodelling of the basement membrane zone was found. Conclusion: The efficiency of the easy, uncomplicated production, cryopreservation and use as well as the short culture period could lead to a new approach in the treatment of burn and chronic wounds.

  5. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    International Nuclear Information System (INIS)

    High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors. Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy). In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy

  6. Angiostatin up-regulation in gastric cancer cell SGC7901 inhibits tumorigenesis in nude mice

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Yong-Quan Shi; Kai-Chun Wu; De-Xin Zhang; Jing-Hua Yang; Dai-Ming Fan

    2003-01-01

    AIM: To explore the influence of angiostatin up-regulationon the biologic behavior of gastric cancer cells in vitro andin vivo, and the potential of angiostatin gene therapy in thetreatment of human gastric cancer.METHODS: Mouse angiostatin cDNA was subcloned intothe eukaryotic expression vector pcDNA3.1(+) and identifiedby restriction endonucleases digestion and sequencing. Therecombinant vector pcDNA3. 1(+)-angio was transfected intohuman gastric cancer cells SGC7901 with liposome andparalleled with the vector control and the mock control.Angiostatin transcription and protein expression wereexamined by RT-PCR and Western blot in the stable celllines selected by G418. Cell proliferation and growth in vitroof the three groups were observed respectively undermicroscope, cell number counting and FACS. The cellsoverexpressing angiostatin, vector transfected and untreatedwere respectively implanted subcutaneously into nude mice.After 30days the size of tumors formed was measured, andmicrovessel density count (MVD) in the tumor tissues wasassessed by immunohistochemistry with the primary anti-vWF antibody.RESULTS: The recombinant vector pcDNA3.1(+)-angio wasconfirmed with the correct sequence of mouse angiostatinunder the promoter CMV. After 30 d of transfection andselection with G418, macroscopic resistant cell clones wereformed in the experimental group transfected with pcDNA3.1(+)-angio and the vector control. But no untreated cellssurvived in the mock control. Angiostatin mRNAtranscription and protein expression were detected in theexperimental group. No significant differences wereobserved among the three groups in cell morphology, cellgrowth curves and cell cycle phase distributions in vitro.However, in nude mice model, markedly inhibitedtumorigenesis and slowed tumor expansion were observedin the experimental group as compared with the controls,which was paralleled with decreased microvessel density inand around tumor tissues (P<0. 05).CONCLUSION: Angiostatin

  7. Experimental study of the antitumor effect of phosphorus-32 glassmicrospheres on the tumor loaded nude mice

    Institute of Scientific and Technical Information of China (English)

    Lu Liu; Pei Lin Huang; Guan Sheng Tong

    2000-01-01

    AIM To evaluate the pharmacological effect of phosphorus-32 glass microspheres (32p-GMS) injected intothe implanted human liver cancer cell mass in nude mice.METHODS Fifty-two Balb/c tumor loaded nude mice were allocated into treatment group (n =38) andcontrol group (n = 14), in the former group different doses of 32p-GMS were injected into the tumor mass,while in the latter group 31 P-GMS or no treatment were given instead of 32 P-GMS. After dynamicallyobserving the growth of tumor for d 3 - d 28, the experimental animals were killed in batches, the tumor andits nearby tissues were examined by light and electronic microscopy.RESULTS In comparing with the control group, the treatment group showed the tumor inhibiting rates of59.7% -93.6% (Variance analysis of the mean weight of different doses and control group after square rootcorrection, F= 579.62, P<0.01). As the tumor mass attained the absorbed dose of 7320Gy, the tumor cellswere completely destroyed and at this maximal dose in one case, the epithelial tissue neighboring to this massshowed the signs of metaplasia. When the absorbed doses ranged from 1830Gy to 3660Gy, most of the tumorcells showed the evidences of injury or necrosis, and some well differentiated tumor cells appeared. As theabsorbed dose being 366Gy or less, some tumor cells remained in active proliferative stage with a lot offibroblasts and lymphocytes presented in the neighboring interstitial tissues.CONCLUSION When the experimental model of implanted human liver cancer cells received 32p-GMS of1830Gy-3660Gy, it produces excellent anticancer action without any injury to the normal neighboringtissues and the prominent anticancer effect is found within d 3 after intratumor injection.

  8. Angiostatin inhibits pancreatic cancer cell proliferation and growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    Ding-Zhong Yang; Jing He; Ji-Cheng Zhang; Zhuo-Ren Wang

    2005-01-01

    AIM: To observe the biologic behavior of pancreatic cancer cells in vitro and in vivo, and to explore the potential value of angiostatin gene therapy for pancreatic cancer.METHODS: The recombinant vector pcDNA3.1(+)-angiostatin was transfected into human pancreatic cancer cells PC-3 with Lipofectamine 2000, and paralleled with the vector and mock control. Angiostatin transcription and protein expression were determined by immunofluorescence and Western blot. The stable cell line was selected by G418. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope. Cell growth curves were plotted.The troms-fected or untroms-fected cells overexpressing angiostatin vector were implanted subcutaneously into nude mice. The size of tumors was measured, and microvessel density count (MVD) in tumor tissues was assessed by immunohistochemistry with primary anti-CD34antibody.RESULTS: After transfected into PC-3 with Lipofectamine 2000 and selected by G418, macroscopic resistant cell clones were formed in the experimental group transfected with pcDNA 3.1(+)-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in vitro in the three groups were observed respectively under microscope. After treatment with supernatant, significant differences were observed in endothelial cell (ECV-304) growth in vitro. The cell proliferation and growth were inhibited. In nude mice model, markedly inhibited tumorigenesis and slowed tumor expansion were observed in the experimental group as compared to controls, which was parallel to the decreased microvessel density in and around tumor tissue.CONCLUSION: Angiostatin does not directly inhibit human pancreatic cancer cell proliferation and growth in vitro,but it inhibits endothelial cell growthin vitro. It exerts the anti

  9. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

    OpenAIRE

    Jia, Lin; Shang, Yuan-Yuan; Li, Yu-Yuan

    2008-01-01

    AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and selective serotonin reuptake inhibitor (SSRI) antidepressant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancreatic carcinoma xenografts in nude mice.

  10. Nutritional and supranutritional levels of selenate differentially suppress prostate tumor growth in adult but not young nude mice

    Science.gov (United States)

    Selenium (Se) is known to regulate carcinogenesis and immunity at nutritional and 26 supranutritional levels. Because the immune system provides critical defenses against 27 cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop 28 CD8+ and CD4+ T cells extrathymicall...

  11. Observation the inhibitory effect and expression of MMP -2, CD44v6 of common turmeric among tumor-bearing nude mice%温郁金对荷肿瘤裸鼠抑瘤作用和MMP -2、CD44v6表达影响的观察

    Institute of Scientific and Technical Information of China (English)

    王光亮; 张俊会

    2012-01-01

    Objective To study the inhibitory effect of common turmeric and the expression of MMP - 2 and CD44v6 proteins in human gastric SGC -7901 cell, explore the possible mechanisms on gastric cancer metastasis. Method Established nude mouse orthotopic transplantation mode of SGC - 7901 and then randomly divided the nude mouse into control group and common turmeric group. The tumor growth and metastasis were observed, the expression of MMP - 2 and CD44v6 proteins in the tumor tissue were detected by immunohisto-chemistry. Results The rate of successfully orthotopic transplantation was 100%. The weight of the tumors in common turmeric group was (2.73 ±0.92) g, in control group was (4. 09 ± 1.17) g, there was statistical significance between the two group (P <0.05) , The inhibitory rate of common turmeric group was 33. 25%. The metastasis of cavitas peritonealis, liver and lymph node in common turmeric group were significantly lower than those of control group (P < 0. 05) . Meanwhile, we found that the positive rates of MMP - 2 and CD44v6 expression in the common turmeric group were obviously lower than that in control group (P<0.05) . Conclusions Common turmeric can inhibit gastric cancer growth and metastasis in orthotopic transplantation model of nude mice, the mechanism might be related to down - regulation of MMP - 2 and CD44v6 expression.%目的 观察温郁金对胃癌细胞抑制作用和MMP-2、CD44v6蛋白表达的影响,探讨其抗胃癌细胞转移的作用机制.方法 以SGC - 7901胃癌细胞株建立胃癌裸鼠原位移植瘤模型,将裸鼠随机分为对照组(0.9%氯化钠溶液)及实验组(温郁金水煎剂).观察裸小鼠胃癌种植后肿瘤生长及转移灶情况,用免疫组化法检测2组肿瘤组织中MMP-2和CD44v6蛋白的表达.结果 2组荷瘤鼠胃壁均有肿瘤生长,荷瘤率100%,对照组瘤重(4.09±1.17) g,实验组瘤重(2.73±0.92) g(与对照组比较P<0.05),抑瘤率为33.25%;实验组肝、腹腔和淋巴结转

  12. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice

    OpenAIRE

    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto, Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Ming ZHAO

    2014-01-01

    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  13. A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP-expressing tumor cells in nude mice.

    Science.gov (United States)

    Yamamoto, Akihiko; Yano, Seiji; Shiraga, Minoru; Ogawa, Hirohisa; Goto, Hisatsugu; Miki, Toyokazu; Zhang, Helong; Sone, Saburo

    2003-03-01

    The lung is the common target organ of hematogenous metastasis that restricts the prognosis of cancer patients. MMPs play a pivotal role in metastasis by promoting tumor invasion and angiogenesis; therefore, a large number of MMPIs have been developed. Our purpose was to determine the therapeutic efficacy of a selective-spectrum MMPI, ONO-4817 (inhibits MMP-2 and MMP-9 but not MMP-1), against established lung micrometastasis in combination with a cytotoxic anticancer drug, DOC, in a nude mouse model. Human non-small cell lung cancer PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells, expressing MMP-2, MMP-9 and/or MMP-1, were injected i.v. into nude mice on day 0. Mice received a single injection of DOC on day 7 (after establishment of micrometastasis) and/or ONO-4817 mixed with food from day 7 to the end of experiments. Monotherapy with ONO-4817 or DOC inhibited formation of lung metastasis by PC14PE6 and H226 cells. In addition, combined use of ONO-4817 with DOC significantly suppressed the tumor burden of H226 and PC14PE6 cells in the lung and prolonged the survival of PC14PE6-bearing mice compared to ONO-4817 or DOC alone. These therapies did not affect the body weight or food intake of tumor-bearing mice. FIZ revealed that lung lesions, but not nontumor parenchyma of the lung, expressed gelatinolytic activity and that treatment with ONO-4817 abrogated the gelatinolytic activity in lung lesions. These results suggest that the combined use of MMPIs with cytotoxic anticancer drugs may be helpful in the control of established lung micrometastasis by tumor cells expressing MMPs. PMID:12516105

  14. Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    Shu-Man Jiang; Jian-Hua Wu; Lin Jia

    2012-01-01

    AIM:To investigate the effect of Mirtazapine on tumor growth,food intake,body weight,and nutritional status in gemcitabine-induced mild cachexia.METHODS:Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups.Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation.A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d,13 d,and 16 d after tumor implantation.Tumor size,food intake,body weight,and nutritional status were measured during the experiment.All mice were sacrificed at day 28.RESULTS:(1) After 7 d of gemcitabine administration,body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period,food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant).After 21 d,mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g,P =0.004).After 25 d,mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g,P =0.014).CONCLUSION:Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice.Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice.It was believed to provide a potential therapeutic perspective for further studies on cachexia.

  15. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    International Nuclear Information System (INIS)

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

  16. Growth inhibition of human pancreatic cancer grafts in nude mice by boron neutron capture therapy

    International Nuclear Information System (INIS)

    Cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons to release alpha-particles (4He) and lithium-7 ions (7Li). The 4He kills cells in the range of 10 μm from the site of 4He generation. Therefore, it is theoretically possible to kill tumor cells without affecting adjacent healthy tissues, if 10B-compounds could be selectively delivered. We have described that 10B atoms delivered by immunoliposomes exerted cytotoxic effect on human pancreatic carcinoma cells (AsPC-1) in a dose-dependent manner by thermal neutron irradiation in vitro as reported previously. In the present study, the cytotoxic effect of a locally injected 10B compound solution or multilamellar liposomes containing a 10B compound to human pancreatic carcinoma xenograft in nude mice was evaluated after thermal neutron irradiation. AsPC-1 cells (1 x 107) injected subcutaneously into a nude mouse grew to a tumor weighing 100-300 mg after 2 weeks. At this time 200 μg 10B compounds was locally injected in the tumor and irradiated with 2 x 1012 n/cm2 thermal neutron. Tumor growth of 10B-treated groups was suppressed as compared with control group. Histopathologically, hyalinization and necrosis were found in the tumor tissues. For effective tumor destruction, 10B dose more than 60 μg was necessary. The tumor tissue injected with saline only and irradiated showed neither destruction nor necrosis. These data indicate that the accumulation of 10B atoms to the tumor site is mandatory for the cytotoxic effect by thermal neutron irradiation. (author)

  17. Hiwi knockdown inhibits the growth of lung cancer in nude mice.

    Science.gov (United States)

    Liang, Dong; Dong, Min; Hu, Lin-Jie; Fang, Ze-Hui; Xu, Xia; Shi, En-Hui; Yang, Yi-Ju

    2013-01-01

    Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of SSCloAldebr cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell SSCloAldebr cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers. PMID:23621188

  18. Transplantation of human glioma stem cells in nude mice with green fluorescent protein expression%人脑胶质瘤干细胞移植于表达绿色荧光蛋白裸小鼠的研究

    Institute of Scientific and Technical Information of China (English)

    吴自成; 黄强; 邵义祥; 薛智谋; 董军; 刁艺; 王爱东; 兰青

    2008-01-01

    Objectives To investigate the possibility of transplantation of human glioma stem cells (HGSCs) in nude mice stably expressing green fluorescent protein (GFP) so as to clearly identify the incubated HGSCs from the host tissues. Methods Transgenic C57BL/6J mice expressing GFP was crossed with nude mice of the line NC, then hairless male nude mice expressing GFP were crossed with hairy female pubescent mice to obtain nude mice with GFP expression the expression of GFP in the skin and organs of these nude mice were evaluated by naked eyes, and immunohistochemical and immunofluorescence assays. HGSCs were transplanted orthotopically into the caudate nuclei of nude mice expressing GFP. Immunohistochemistry was used to observe the transplanted tumor. Results The structures rich in adipose tissue of the 8th generation nude mice were dark green and the other organs were light green. However, green fluorescence was emitted from all tissues under fluorescence microscopy. Confocal fluorescence microscopy showed that the tumor cells were stained red, distinguished from the host ceils distinctly in the brains bearing tumor transplanted orthotopically. Conclusion Nude mice expressing GFP can be obtained by crossing the trangenic mice bearing naive immunity with nude mice. Orthotopic transplantation of HGSCs may be used in the investigation of tumor tissue reconstitution because of the easy identification between the transplantation tumor and host tissue.%目的 培育表达绿色荧光蛋白(GFP)的裸小鼠,并探讨将其用于人胶质瘤干细胞(HGSC)移植实验研究.方法 将C57BL/6J-GFP转基因小鼠与NC系裸小鼠进行交配,在继代时严格挑选都表达GFP的无毛雄鼠与有毛母鼠交配,通过肉眼、免疫组织化学和荧光显微镜等方法观察GFP在裸小鼠皮肤和脏器中的表达情况,继将HGSC原位移植于表达GFP的裸小鼠,以观察移植瘤的生长情况.结果 传至8代的裸小鼠,包括脑在内的全身主要器官和细胞

  19. Effects of exogenous human leptin on heat shock protein 70 expression in MCF-7 breast cancer cells and breast carcinoma of nude mice xenograft model

    Institute of Scientific and Technical Information of China (English)

    XUE Rong-quan; GU Jun-chao; YU Wei; WANG Yu; ZHANG Zhong-tao; MA Xue-mei

    2012-01-01

    Background It is important to identify the multiple sites of leptin activity in obese women with breast cancer.In this study,we examined the effect of exogenous human leptin on heat shock protein 70 (HSP70) expression in MCF-7 human breast cancer cells and in a breast carcinoma xenograft model of nude mice.Methods We cultured MCF-7 human breast cancer cells and established nude mice bearing xenograffs of these cells,and randomly divided them into experimental and control groups.The experimental group was treated with human leptin,while the control group was treated with the same volume of normal saline.A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to quantify the mRNA expression of HSP70 in the MCF-7 human breast cancer cells and in tumor tissues.Western blotting analysis was applied to quantify the protein expression of HSP70 in the MCF-7 cells.Immunohistochemical staining was done to assess the positive rate of HSP70 expression in the tumor tissues.Results Leptin activated HSP70 in a dose-dependent manner in vitro:leptin upregulated significantly the expression of HSP70 at mRNA and protein levels in MCF-7 human breast cancer cells (P <0.001).There was no significant difference in expression of HSP70 mRNA in the implanted tumors between the leptin-treated group and the control group (P>0.05).Immunohistochemical staining revealed no significant difference in tumor HSP70 expression between the leptin-treated group and the control group (P>0.05).Conclusions A nude mouse xenograft model can be safely and efficiently treated with human leptin by subcutaneous injections around the tumor.HSP70 may be target of leptin in breast cancer.Leptin can significantly upregulate the expression of HSP70 in a dose-dependent manner in vitro.

  20. Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice

    Institute of Scientific and Technical Information of China (English)

    Chun-Gen Xing; Bao-Song Zhu; Xiao-Qing Fan; Hui-Hui Liu; Xun Hou; Kui Zhao; Zheng-Hong Qin

    2009-01-01

    AIM: To investigate the effects of class Ⅰ phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment,the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed.RESULTS: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis.The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%),and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical staining.CONCLUSION: The class Ⅰ PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

  1. Effects of heavy ion radiation on cancer stem cells of xenograft tumor in nude mice

    International Nuclear Information System (INIS)

    Experiments were design to determine the effects of Carbon ion radiation on cancer stem cells within xenograft tumors, and to assess the impact of high LET radiation on radiocurability. HCT116 human colon cancer cells were inoculated into nude mice and animals were irradiated when tumors reached a certain size. When irradiated with 15 Gy Carbon ions, the xenograft tumors re-grew after 60 days. However, when irradiated with 30 Gy all tumors were eradicated without relapse within the 90 day follow-up period. In comparison, with X-ray radiation, the tumors were suppressed for 31 days with a dose of 30 Gy and eradicated following a 60 Gy dose. The relative biological effectiveness (RBE) value of Carbon ion relative to X-rays was calculated at 3.82. At an isodose of 30 Gy, Carbon ion radiation predominantly induced tumor cell cavitation and fibrosis, whereas X-ray radiation only partially destroyed the tumor cell mass. Tumor-supplying blood vessels were markedly reduced in mice following Carbon ion irradiation compared to mice irradiated with X-rays. The expression of cancer stem cell related markers or proteins, such as CD133, EpCAM, HIF-1α and B-catenin was predominantly suppressed following Carbon ion radiation. In contrast, X-rays actually increased the expression of these factors. In conclusion, heavy ion radiation can disrupt cancer stem cell populations more effectively than conventional X-ray treatment. These findings emphasize the importance of utilising heavy ion radiation as a tool to achieve high tumor radiocurability. (author)

  2. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    OpenAIRE

    Reiter, Russel J.; Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those ...

  3. Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice.

    Science.gov (United States)

    Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

    2014-01-01

    Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR-Ras-Raf-MEK-ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [(3)H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras-MAPK activity could be important in its anticancer activity. PMID:24853419

  4. Novel immunocytokine IL12-SS1 (Fv) inhibits mesothelioma tumor growth in nude mice.

    Science.gov (United States)

    Kim, Heungnam; Gao, Wei; Ho, Mitchell

    2013-01-01

    Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies. PMID:24260587

  5. Novel immunocytokine IL12-SS1 (Fv inhibits mesothelioma tumor growth in nude mice.

    Directory of Open Access Journals (Sweden)

    Heungnam Kim

    Full Text Available Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12 and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv, was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG. The single-chain IL12-SS1 (Fv immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226 and ovarian (OVCAR-3 cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226 grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies.

  6. Modulation of cell cycle regulatory protein expression and suppression of tumor growth by mimosine in nude mice.

    Science.gov (United States)

    Chang, H C; Weng, C F; Yen, M H; Chuang, L Y; Hung, W C

    2000-10-01

    Our previous results demonstrated that the plant amino acid mimosine blocked cell cycle progression and suppressed proliferation of human lung cancer cells in vitro by multiple mechanisms. Inhibition of cyclin D1 expression or induction of cyclin-dependent kinase inhibitor p21WAF1 expression was found in mimosine-treated lung cancer cells. However, whether mimosine may modulate the expression of these cell cycle regulatory proteins and suppress tumor growth in vivo is unknown. In this study, we examined the anti-cancer effect of mimosine on human H226 lung cancer cells grown in nude mice. Our results demonstrated that mimosine inhibits cyclin D1 and induces p21WAF1 expression in vivo. Furthermore, results of TUNEL analysis indicated that mimosine may induce apoptosis to suppress tumor growth in nude mice. Collectively, these results suggest that mimosine exerts anti-cancer effect in vivo and might be useful in the therapy of lung cancer. PMID:10995875

  7. Comparison of characteristics of human small cell carcinoma of the lung in patients, in vitro and transplanted into nude mice

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L;

    1986-01-01

    Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast-free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of the...... cases. Fifty-four % of the tumours could be established as serially transplantable tumours in nude mice. The tumours were characterized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency and by...... doubling time. The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light microscopic constitution of small cell carcinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro...

  8. Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

  9. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

    Science.gov (United States)

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J

    1992-01-01

    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies. PMID:1400563

  10. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice

    International Nuclear Information System (INIS)

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 107 were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth

  11. Radioimmunoimaging of human colon carcinoma grafted into nude mice using 131I-labeled monoclonal anti-CEA antibody (C50)

    International Nuclear Information System (INIS)

    131I-labeled monoclonal anti-CEA antibody C50 was injected intraperitoneally into nude mice bearing human colon carcinoma xenografts for tumor localization and radioimmunoimaging studies. Radioimmunoimaging and biodistribution was performed at the 1st, 2nd, 3th, 4th and 6th day after injection and transplanted tumors were visualized in 24 hr by SPECT. Satisfactory tumor imaging was obtained at 48 hr after injection and at the 6th day T/NT (tumor/colon) reached 10.40 +- 0.69. These in vivo studies demonstrate the specificity of McAb C50 and indicate that it may be used for clinical diagnosis and targeting treatment of human colon carcinoma

  12. Glomerular filtration rate after alpha-radioimmunotherapy with 211At-MX35-F(ab')2: a long-term study of renal function in nude mice

    DEFF Research Database (Denmark)

    Back, T.; Haraldsson, B.; Hultborn, R; Jensen, H.; Johansson, M.E.; Lindegren, S.; Jacobsson, L.

    2009-01-01

    Besides bone marrow, the kidneys are often dose-limiting organs in internal radiotherapy. The effects of high-linear energy transfer (LET) radiation on the kidneys after alpha-radioimmunotherapy (alpha-RIT) with the alpha-particle emitter, (211)At, were studied in nude mice by serial measurements.......0 +/- 4.1 Gy (mean +/- SEM), tumor- and non-tumor-bearing animals, respectively. The reduction in GFR progressed with time, and at the later time interval, (31-67 weeks) the corresponding absorbed doses were 7.5 +/- 2.4 and 11.3 +/- 2.3 Gy, respectively, suggesting that the effects of radiation on the...... kidneys were manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to...

  13. Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by non-invasive imaging

    OpenAIRE

    Ren, Pei-Gen; Huang, Zhinong; Ma, Ting; Biswal, Sandip; Smith, Robert L. (Robert Lee), 1955 August 21-; Goodman, Stuart B.

    2010-01-01

    Macrophages constitute a major part of the cell response to wear particles produced at articulating and non-articulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/ml UHMWPE suspe...

  14. Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting

    DEFF Research Database (Denmark)

    Türeci, O; Fischer, H; Lagoda, P; Issinger, O G

    1990-01-01

    Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA...... fingerprint pattern. However, differences in the DNA fingerprint patterns were shown to occur depending upon the above mentioned parameters....

  15. Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

    Directory of Open Access Journals (Sweden)

    Ming-Che Shen

    Full Text Available Stearic acid (C18:0 is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil, or oleic acid (corn oil enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1 compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2 and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

  16. An experimental study on the treatment of nude mice with liver carcinoma by intratumoral injection with 188Re rhenium sulfide suspension

    International Nuclear Information System (INIS)

    Objective: To prepare a [188Re] rhenium sulfide suspension and to evaluate its therapeutic effects on liver carcinoma by intratumoral injection. Methods: 30 nude mice bearing SMMC-7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [188Re] rhenium sulfide suspension or sodium [188Re] perrhenate solution. Another 30 tumor-bearing nude mice were divided into six groups, four groups of them were treated with a 0.1 mL [188Re] rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. Every injection was repeated 6 days later. Results: The retention percentages of radioactivity (% ID) in tumors injected with [188Re] rhenium sulfide suspension were (90.96 +- 6.63)%, (86.09 +- 22.58)% and (87.62 +- 13.97)% at 1, 24 and 48 h, respectively, which were much higher than retention in normal organs evaluated. In the case of sodium 188Re-perrhenate solution, the % ID values were only (1.66 +- 0.35)%, (0.02 +- 0.01)% and (0.01 +- 0.01)%, respectively. Tumor inhibition ratios were as high as 89% when the peripheral portion of tumor (0.5 - 0.6 cm from center) absorbed an activity share of about 507.6 Gy . Conclusion: Intratumoral injection of [188Re] rhenium sulfide suspension results in significant tumor restraint and it is indicated that this is a highly potential approach to the treatment of hepatic carcinoma

  17. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

    Directory of Open Access Journals (Sweden)

    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  18. Thyrotropin dependent and independent thyroid cell lines selected from FRTL-5 derived tumors grown in nude mice

    International Nuclear Information System (INIS)

    FRTL-5 cells were used to set up a thyroid tumor model system in C3H nu/nu mice. FRTL-5 tumors could be grown in nude mice provided serum TSH levels were elevated. Persistent TSH elevation was obtained by administration of Na131I, rendering the mice hypothyroid. After 4 weeks FRTL-5 cells were injected sc resulting in tumor growth within 2 weeks in eight out of eight mice. Although the tumors showed an apparently undifferentiated histology, lacking normal follicular structures, they were functional since the tumors were capable of concentrating [131]iodine, as demonstrated by nuclear imaging. From one of the tumors a new cell line was isolated (FRTL-5/T) that, like the parental FRTL-5 cell line, was TSH dependent for growth. In a control group of six euthyroid nude mice FRTL-5 tumor growth could not be obtained with one exception. After 3 months one animal developed a small tumor that grew rapidly thereafter. This tumor was easily transplantable in other euthyroid nude mice, showed an undifferentiated histology, and was nonfunctional, as it could not concentrate [131]iodine. From this tumor two cell lines were derived: one cultured in the presence of TSH (FRTL-5/TP) and one in the absence of TSH (FRTL-5/TA). The cell lines were analyzed for TSH responsive functions and TSH receptor expression. Responsiveness to TSH in FRTL-5/T and the parental FRTL-5 cell line were similar for most thyroid specific functions tested. However, FRTL-5/T was less sensitive than FRTL-5 for TSH induced [3H]thymidine incorporation. Both cell lines had two classes of TSH binding sites with high and low affinity respectively. FRTL-5/TP and FRTL-5/TA were both able to grow in TSH free medium and were nonresponsive to TSH in vitro, as tested for [3H]thymidine and [3H]uridine incorporation, iodine uptake, thyroglobulin iodination, and thyroglobulin secretion

  19. Thyrotropin dependent and independent thyroid cell lines selected from FRTL-5 derived tumors grown in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ossendorp, F.A.; Bruning, P.F.; Schuuring, E.M.; Van Den Brink, J.A.; van der Heide, D.; De Vijlder, J.J.; De Bruin, T.W. (Netherlands Cancer Institute, Amsterdam (Netherlands))

    1990-07-01

    FRTL-5 cells were used to set up a thyroid tumor model system in C3H nu/nu mice. FRTL-5 tumors could be grown in nude mice provided serum TSH levels were elevated. Persistent TSH elevation was obtained by administration of Na131I, rendering the mice hypothyroid. After 4 weeks FRTL-5 cells were injected sc resulting in tumor growth within 2 weeks in eight out of eight mice. Although the tumors showed an apparently undifferentiated histology, lacking normal follicular structures, they were functional since the tumors were capable of concentrating (131)iodine, as demonstrated by nuclear imaging. From one of the tumors a new cell line was isolated (FRTL-5/T) that, like the parental FRTL-5 cell line, was TSH dependent for growth. In a control group of six euthyroid nude mice FRTL-5 tumor growth could not be obtained with one exception. After 3 months one animal developed a small tumor that grew rapidly thereafter. This tumor was easily transplantable in other euthyroid nude mice, showed an undifferentiated histology, and was nonfunctional, as it could not concentrate (131)iodine. From this tumor two cell lines were derived: one cultured in the presence of TSH (FRTL-5/TP) and one in the absence of TSH (FRTL-5/TA). The cell lines were analyzed for TSH responsive functions and TSH receptor expression. Responsiveness to TSH in FRTL-5/T and the parental FRTL-5 cell line were similar for most thyroid specific functions tested. However, FRTL-5/T was less sensitive than FRTL-5 for TSH induced (3H)thymidine incorporation. Both cell lines had two classes of TSH binding sites with high and low affinity respectively. FRTL-5/TP and FRTL-5/TA were both able to grow in TSH free medium and were nonresponsive to TSH in vitro, as tested for (3H)thymidine and (3H)uridine incorporation, iodine uptake, thyroglobulin iodination, and thyroglobulin secretion.

  20. The effect of hyperbaric oxygenation on the viability of human fat injected into nude mice.

    Science.gov (United States)

    Shoshani, O; Shupak, A; Ullmann, Y; Ramon, Y; Gilhar, A; Kehat, I; Peled, I J

    2000-11-01

    Autologous free-fat injection for the correction of soft-tissue defects has become a common procedure in plastic surgery. The main shortcoming of this method for achieving permanent soft-tissue augmentation is the partial absorption of the injected fat, an occurrence that leads to the need for both overcorrection and repeated fat reinjection. Improving the oxygenation of the injected fat has been suggested as a means of helping to overcome the initial critical phase that occurs postinjection (when the fat cells are nourished by osmosis), increasing phagocyte activity, accelerating fibroblast activity and collagen formation, and enhancing angiogenesis. In addition, the hyperbaric oxygen-mediated decrement in endothelial leukocyte adhesion will decrease cytokine release, thereby reducing edema and inflammatory responses. The purpose of the present study was to examine the effect of hyperbaric oxygenation on improving the viability of injected fat. Adipose tissue obtained from human breasts by suction-assisted lipectomy was injected into the subcuticular nuchal region in nude mice. The mice were then exposed to daily hyperbaric oxygen treatments, breathing 100% oxygen at 2 atmospheres absolute (ATA) for 90 minutes. The duration of the administered hyperbaric oxygen therapy was 5, 10, or 15 days, according to the study group. Mice exposed to normobaric air alone served as the control group, and each group included 10 animals. The rats were killed 15 weeks after fat injection. The grafts were dissected out, weight and volume were measured, and histologic evaluation was performed. In all of the study groups, at least part of the injected fat survived, giving the desired clinical outcome. No significant differences could be found between the groups regarding fat weight and volume. Histopathologic examination of the dissected grafts demonstrated a significantly better integrity of the fat tissue in the group that received hyperbaric oxygen for 5 days (p = 0.047). This

  1. Experimental chemo- and radio-therapy on human cholangiocarcinoma transplanted to nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, T.; Hanatani, Y.; Yamada, Y.; Tsuyuki, K.; Nakada, M. (Keio Univ., Tokyo (Japan). School of Medicine)

    1981-06-01

    A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and combination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, /sup 3/H-thymidine uptake labeling index (L.I.), and mitotic (M.I.) on 24 and 48 hrs. after MMC (0.5 mg/kg) and radiation (500 rads/mouse). By MMC and radiation, 4 n cells increased with the decrease of 2 n cells. And this change was remarkable in radiation than MMC. L.I. was depressed almost 10% on 24 hrs. after MMC and radiation. Although M.I. was depressed slightly by MMC, it was stable after radiation. From these findings the recruitment of cells from G/sub 1/ to G/sub 2/M and the G/sub 2/ block by MMC and radiation was suggested. As these changes were more remarkable by radiation, the combination chemoradiotherapy was thought to be more effective when the radiation was performed before MMC administration.

  2. Experimental chemo- and radio-therapy on human cholangiocarcinoma transplanted to nude mice

    International Nuclear Information System (INIS)

    A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, 3H-thymidine uptake labeling index (L.I.), and mitotic (M.I.) on 24 and 48 hrs. after MMC (0.5 mg/kg) and radiation (500 rads/mouse). By MMC and radiation, 4 n cells increased with the decrease of 2 n cells. And this change was remarkable in radiation than MMC. L.I. was depressed almost 10% on 24 hrs. after MMC and radiation. Although M.I. was depressed slightly by MMC, it was stable after radiation. From these findings the recruitment of cells from G1 to G2M and the G2 block by MMC and radiation was suggested. As these changes were more remarkable by radiation, the combination chemoradiotherapy was thought to be more effective when the radiation was performed before MMC administration. (author)

  3. Multimodality imaging of 131I uptake in nude mice thyroid based on Cerenkov radiation

    International Nuclear Information System (INIS)

    Objective: To perform the multimodality 131I thyroid imaging using Cerenkov luminescence tomography (CLT) and gamma imaging, and to compare the results of CLT and gamma imaging. Methods The nude mice (n=4, mass: (21 ±3) g) were injected with 1.67 ×107 Bq 131I. CLT and gamma imaging were acquired at 0.5, 3, 12 and 24 h after the injection. Three-dimensional biodistribution of 131I uptake in thyroid was reconstructed using Cerenkov source reconstruction method based on the diffusion equation (DE), and the reconstructed power of 131I in different acquisition time points was obtained. Additionally, the ROIs were drawn over the gamma images of the mouse neck, and the counts were read. The correlation between the reconstructed power of CLT and gamma ray counts of gamma imaging was analyzed. Results: The power of 131I uptake in thyroid at 0.5, 3, 12 and 24 h were 7.80 ×10-13, 1.62×10-12, 2.20×10-12 and 2.68 × 10-12 W, respectively. CLT results showed that reconstructed power increased with the increasing of acquisition time. Gamma imaging results indicated that 131I uptake decreased in abdomen and increased in thyroid with the collection time. The results of CLT were consistent with that of gamma imaging (r2=0.7620, P<0.05). Conclusion: CLT has the potential to identify and monitor functioning thyroid tissue at before and (or) after 131I treatment. (authors)

  4. Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

    OpenAIRE

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-01-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, ...

  5. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice

    International Nuclear Information System (INIS)

    We have studied the effect of altering the level of circulating epidermal growth factor (EGF) on the function and growth of newborn rat thyroids transplanted into nude mice. Preliminary studies confirmed that sialoadenectomy reduced circulating EGF levels in nude mice (from 0.17 +/- 0.02 to 0.09 +/- 0.02 ng/ml), and that ip injection of 5 micrograms EGF raised EGF levels (the peak level of 91.7 +/- 3.3 ng/ml was achieved at 30 min, with a subsequent half-life of about 1 h). The radioiodine uptake by newborn rat thyroid transplants in the sialoadenectomized and sham-operated animals correlated inversely with the circulating EGF levels determined when the mice were killed (r = -0.99). Low-dose TSH treatment (0.1 microU/day) generally stimulated the radioiodine uptake, but high-dose TSH groups (100 microU/day) were not significantly different from the control group. The 5-day nuclear [3H]thymidine labeling index was 6.8 +/- 0.5% IN newborn rat thyroid transplants grown in sialoadenectomized animals, 13.1 +/- 0.3% in sham-operated animals, and 16.8 +/- 0.5% in nude mice receiving 5 micrograms EGF ip daily. In general, both low-dose and high-dose TSH promoted DNA synthesis under low EGF conditions but were ineffective in the presence of higher levels of EGF. Adult rat thyroid transplants showed no significant responses. Although sialoadenectomy may alter other factors besides EGF, it appears that changes in the levels of circulating EGF within the physiological range affect the function and growth of newborn rat thyroid transplants. Circulating EGF may play a role in thyroid maturation and may also be involved in the regulation of thyroid function throughout life

  6. Radiobiological parameters of four glioblastoma compared to four other histological types of human tumor xenografts in nude mice

    International Nuclear Information System (INIS)

    Purpose/Objective: Glioblastoma Multiforme (GBM) is a highly malignant tumor of the central nervous system with aggressive biological behavior and a fatal clinical outcome. Several radiobiological parameters might contribute to these poor results. In this study, we investigated seventeen biological parameters of four GBM xenografts and compared the results with four other histological types of human tumor xenografts in nude mice. Methods and Materials: Most of the xenografts retained the individual histological features of their original tumor types. Four GBM xenografts (U87, HP555, MMC1 and HGL21), two squamous cell carcinomas (SCC21 and FaDu), one soft tissue sarcoma (STS26T), and colon cancer (HCT15) xenografts were used. The tumors were implanted in the hindleg of 5-6 Gy WBI nude mice. The following parameters were investigated for most of the xenografts: fractionated TCD50 (the dose of radiation which controls 50% of the tumors) using 30 fractions in 15 days. The parameters pO2, IFP (interstitial fluid pressure), Tpot, SF2 (plastic and Courtenay), PE (plating efficiency), D0, GSH, TCD50 single dose in oxic and hypoxic conditions, the rate of metastasis in SCID mice, VDT (volume doubling time), spontaneous apoptosis, induced apoptosis after 30 and 60 Gy and p53 over-expression. Results: Using the t-test, there was a significantly less spontaneous apoptosis in GBM xenografts when compared with the other histological types. However, no significant difference was found between both groups of xenografts in the remaining biological parameters investigated. Conclusion: These data demonstrate that, with the exception of spontaneous apoptosis, no significant difference was found in fifteen biological parameters between GBM xenografts and the other histological types implanted into the subcutaneous tissue of nude mice. The data suggests that the classical radiobiological parameters cannot explain the poor response of GBM to radiation. Supported by NCI Grant CA13311

  7. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  8. Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice

    Directory of Open Access Journals (Sweden)

    Baoan Chen

    2009-03-01

    Full Text Available Baoan Chen1,* Jian Cheng1,* Yanan Wu1, Feng Gao1, Wenlin Xu2, et al 1Department of Hematology;2Department of Hematology, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, PR China *These authors have contributed equally to this workAbstract: In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet and magnetic nanoparticle of Fe3O4 (MNP-Fe3O4 combined with daunorubicin (DNR in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 × 107 cells/each respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice were assigned randomly into five groups which were treated with normal saline; DNR; NP-Fe3O4 combined with DNR; 5-BrTet combined with DNR; 5-BrTet and MNP-Fe3O4 combined with DNR, respectively. The incidence of formation, growth characteristics, weight, and volume of tumors were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of Bcl-2, and BAX were detected by Western blot. Bcl-2, BAX, and caspase-3 genes were also detected. For K562/A02 cells xenograft tumors, 5-BrTet and MNP-Fe3O4 combined with DNR significantly suppressed growth of tumor. A histopathologic examination of tumors clearly showed necrosis of the tumors. Application of 5-BrTet and MNP-Fe3O4 inhibited the expression of Bcl-2 protein and upregulated the expression of BAX and caspase-3 proteins in K562/A02 cells xenograft tumor. It is concluded that 5-BrTet and MNP-Fe3O4 combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model.Keywords: 5-bromotetrandrine, magnetic nanoparticle of Fe3O4, multidrug-resistance, xenograft model

  9. Therapeutic effect of intratumoral injection of 188Re labeled stannic sulfur suspension in liver cancer. A comparative study with chemical agents in nude mice

    International Nuclear Information System (INIS)

    Objectives: Hepatoma is a common disease in some countries. The intervention therapy was used often for non-resectable tumor. The aim of our study was to compare the therapeutic effect of 188Re labeled stannic sulfur suspension to ethanol, acetic acid and the mixture of mitomycin and lipiodol for hepatoma in an animal model by intermittently injection. Methods: Forty-nine nude mice bearing hepatic cell carcinoma were divided into six groups. Group 1 (n=14) was intratumoral y injected with 0.1 ml saline. There were 5 experimental groups (group 2 to 6). Each group consisted of 7 mice. The mice in group 2 was intratumoral y injected with 18.5 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, the mice in group 3 was injected intratumorally with 9.25 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, group 4 was injected intratumorally with 0.1 ml ethanol, the mice in group 5 was injected with 0.1 ml 30% acetic acid and group 6 was injected intratumorally with 30 μg mitomycin in 0.1 ml lipiodol respectively. The mice were sacrificed 7 days post injection and the specimen were collected for pathological analysis. Results: The average tumor weight were 1.75±0.29 g (mean±S.D.), 0.26±0.03 g, 0.44±0.17 g, 1.38±0.25 g, 0.91±0.28 g, 1.38±0.28 g for group 1 to 6 respectively. Tumors in all experimental groups were significantly smaller than group 1 (control group, P88Re labeled stannic sulfur suspension injection had the smallest tumor weight among all the experimental groups (P188Re labeled stannic sulfur suspension shows better therapeutic effect. (authors)

  10. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Min-Hua Zheng; Bao-Ming Yu; Bo Feng; Jian-Wen Li; Ai-Guo Lu; Ming-Liang Wang; Wei-Guo Hu; Ji-Yuan Sun; Yan-Yan Hu; Jun-Jun Ma

    2005-01-01

    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  11. Immunoscintigraphy of human neuroblastoma xenografted in nude mice using a panel of 125I-labelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Neuroblastoma is the most frequent tumour of the childhood under the age of 5. The staging and the follow up are achieved by MIBG scintigraphy, considered as the method of reference, but sometimes difficult to interpret. The availability of monoclonal antibodies against the ganglioside GD2, expressed on the cell membrane of neuroblastoma and neuro-endocrine cancers offers novel tools that deserve to be carefully explored. We investigated four mouse monoclonal antibodies (3 lgG3: BW704, 7A4, 60C3, and the lgG1 variant of BW704: MAK704), on nude mice xenografted with a human neuroblastoma (REM). Sixty one nude mice were included. The three former MAbs provided tumour imaging, the best results being obtained with BW704, followed by 7A4 and 60C3. MAK704 was disappointing. A control antiphosphorylcholine antibody (P51-1) did not give any tumour image in the three tested mice. Scintigraphy ratios tumour/liver and tumour/muscle reached 20 and 100 with BW704, respectively, on the 10th day. Good imaging quality was already obtained from the 24th h. The tumour uptake, calculated from radioactivity countings of resected samples, reached 22 ± 3% of injected dose per gram. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications. (authors). 18 refs., 6 figs., 1 tab

  12. Interaction between three subpopulations of Ehrlich carcinoma in mixed solid tumours in nude mice: evidence of contact domination

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Spang-Thomsen, M

    1994-01-01

    Clonal interaction between three subpopulations of Ehrlich carcinoma were studied during growth as mixed solid tumours and as ascites tumours in immune-incompetent nude NMRI mice. The tumour cell lines differed in DNA content as determined by DNA flow cytometry (FCM). Tumour growth was evaluated ...... line had no dominating effect on the E1.15 or E1.95. It is concluded that non-immunologically mediated cellular dominance in heterogeneous tumours may contribute to the evolution of these tumours and may be involved in fundamental tumour biological phenomena....

  13. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    Directory of Open Access Journals (Sweden)

    Yongqi CUI

    2013-09-01

    Full Text Available Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left cardiac ventricle of mice in the four experimental groups (0.2 mL/mouse respectively; meanwhile, mice in the control group were injected with normal saline (0.2 mL/mouse in the same manner. Periodical radiological examination was carried out to supervise the variation of the mice since the second week after injection. When mice in each group became thin obviously, end the experiment of this group. Before the end, pathological sections of bone tissues were made. We classified the bone metastatic sites into axial skeleton and limb bone, in order to compare the metastatic rates of these two different parts. The bone metastatic abilities of the four cell lines was statistically analyzed by comparing the average time cost in the appearance of bone metastases and the percentage of bone metastases among the experimental groups. Results Different metastatic sites which had been identified both by MicroCT and pathological sections appeared in each group of the four experimental groups. By contrast, no metastasis was observed in the control group. The percentage of cancer metastasizing to axial skeleton was remarkably higher than the percentage of tumor metastasizing to the limb bone in each experimental group, which was consistent with the clinical regularity and characteristics of skeletal metastases with lung cancer. Thus, the model has been established triumphantly. However, there were no statistical differences in the average time consumed and skeletal metastatic

  14. Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies

    International Nuclear Information System (INIS)

    Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers

  15. Clonal evolution demonstrated by flow cytometric DNA analysis of a human colonic carcinoma grown in nude mice

    DEFF Research Database (Denmark)

    Vindeløv, L L; Spang-Thomsen, M; Visfeldt, J;

    1982-01-01

    A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation whi...... evolution of a tumor would be less pronounced if old subpopulations often become extinct as new ones emerge. Heterogeneity of human tumors is of clinical importance because the individual subpopulations may have different sensitivity patterns to antineoplastic drugs.......A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which...... in three passages completely overgrew the original population. The DNA content of the new subpopulation was twice that of the original population. The observation supports the hypothesis of clonal evolution of tumor cell populations. The growth rates of the tumor before and after the change showed no...

  16. Different metastasis patterns of a human melanoma cell line in nude mice and rats: Influence of microenvironment

    International Nuclear Information System (INIS)

    The metastatic capacity of intravenously injected human FEMX-I melanoma cells in athymic nude mice and rats was compared. Young rats given 1 x 10(6) ascites tumor cells all died of lung tumors with a life span of 50 ± 10 days (mean± SD). In contrast, in accordance with previous findings, only extrapulmonary metastases developed in mice. This host-dependent difference in metastasis pattern permitted studies on the role of factors that may influence the organ specificity of metastases. The tissue distribution of 125I-labeled FEMX-I cells did not differ in the two nude species during the first 12 hours after cell injection. The plating efficiency of FEMX-I cells in soft agar was increased by the addition of conditioned medium prepared from rat lungs, resulting also in a significant increase in colony size. In contrast, conditioned medium prepared from mouse lungs reduced the clonogenic capacity of the FEMX-I cells in a dose-dependent manner. Conditioned media prepared from rat and mouse liver, kidney, and spleen tissues either inhibited or had no effect on colony formation. The results suggest that the unexpected differential metastatic patterns observed in vivo may reflect differences in the presence of growth-modulating paracrine factors in the host lungs

  17. Localization of pulmonary human sarcoma xenografts in athymic nude mice with indium-111-labeled monoclonal antibodies

    International Nuclear Information System (INIS)

    In order to study localization of metastatic tumors with a radiolabeled monoclonal antibody, a pulmonary metastases model was devised in athymic mice. Metastatic pulmonary sarcoma colonies were verified by histological examination. A murine monoclonal antibody (MAb 19-24) directed against a human sarcoma antigen was labeled with indium-111 (111In) by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). MAb P3 was similarly labeled as a negative control. In the group given MAb 19-24, the percent injected dose per gram lung tissue bearing tumor colonies (30.1%, 29.6%, and 27.7% on Days 1, 2, and 3, respectively) was significantly (p less than 0.05) higher than in those receiving MAb P3. Hepatic activities of both 111In-MAb 19-24 and 111In-MAb P3 were low. The lungs with tumor colonies demonstrated clearest images on Day 3. The specific binding of 111In-SCN-Bz-DTPA-labeled MAb 19-24 to pulmonary xenografts without appreciable liver uptake indicates that it may be useful in the clinical localization of pulmonic metastatic lesions

  18. Radioimmunoimaging of 131I-anti human colon carcinoma monoclonal antibodies in nude mice with tumor xenografts

    International Nuclear Information System (INIS)

    The paired labeled antibodies, 131-labeled anti-human colon carcinoma monoclonal antibody 2C10 and 125I-labeled mice IgG, were used in the radioimmunolocalization study in nude mice with human colon carcinoma xenograft. The antibodies were radioiodinated with Iodogen method, and the incroporation efficiency and immune activity of the labeled antibodies were satisfactory. 96 hours after injection of the antibodies, good tumor localization was observed. Tumor/L. intestinal ratio was 7.08, tumor/S. intestinal 6.02, tumor/muscle 7.53, tumor/blood 1.10. Tumor imaging with camera was clear. The entrance of the antibodies into tumor tissues is a slow passive process and the accumulation of the antibodies in tumor is a combined result of specific immune reactivity and nonspecific deposition

  19. Uptake of the 188Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry

    International Nuclear Information System (INIS)

    The uptake of the rhenium-188 (188Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52±0.76% of the injected activity per gram (n=4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63±8.40 MBq h and an equivalent dose per injected activity of 260±8.91 mSv/MBq. Pharmacokinetics and dosimetry of the 188Re(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine

  20. Human Islet Oxygen Consumption Rate and DNA Measurements Predict Diabetes Reversal in Nude Mice

    OpenAIRE

    Papas, K.K.; Colton, C. K.; Nelson, R A; Rozak, P.R.; Avgoustiniatos, E.S.; Scott, W E; Wildey, G.M.; Pisania, A.; Weir, G C; Hering, B.J.

    2007-01-01

    There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in ...

  1. Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy, radiotherapy, thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy.METHODS: Human colon cancer cell line (HT29)was transplanted into the hind limbs of nude mice.Under laboratory simulated conditions of hyperthermia (43℃, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy,radiotherapy, thermochemotherapy, thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining.RESULTS: All of the six treatment modalities downregulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ±0.0013 vs 0.207 ±0.027, P < 0.01) compared with any single therapy.CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

  2. Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model

    OpenAIRE

    Bi, Dongbin; Yang, Mingshan; Zhao, Xia; Huang, Shiming

    2015-01-01

    Background Cnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis. Material/Methods We randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/...

  3. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Yu-Qin Chen

    2015-01-01

    Full Text Available Objective: This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2, vascular endothelial growth factor-C (VEGF-C, and vascular endothelial growth factorreceptor-3 (VEGFR-3 to determine the mechanism of action and to explore the potential applications of the new effective drug therapy in lung cancer. Materials and Methods: The nude mice model of lung cancer xenografts was established, and mice were randomly divided into the metformin group, the cisplatin group, the metformin + cisplatin group, and the control group. The animals were killed 42 days after drug administration, and the tumor tissues were then sampled to detect the messenger ribonucleic acid (mRNA and protein expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR. Results: The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the cisplatin group and the combined treatment group were lower than that in the control group (P < 0.05. In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P < 0.05. The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the combined treatment group were lower than that in the cisplatin group and the metformin group (P < 0.05. Conclusions: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.

  4. Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Solid tumors usually develop local hypoxia, which renders them resilient to radiotherapy. MiR-210 is the most consistently and robustly induced miRNA under hypoxia and functions as a micro-controller of a wide range of cellular responses to hypoxia. Hence, it is important to investigate the effect of knockdown of miR-210 in tumorigenesis and evaluate the efficacy of knockdown of miR-210 in combination with radiotherapy on human tumor xenograft in nude mice. SMMC-7721 Cells with stable integration of the anti-sense miR-210 were generated through lentiviral-mediated gene transfer and were subcutaneously implanted into nude mice. Mice were monitored for tumor growth and survival after radiotherapy. MiR-210 expression in tumor tissues was assessed by real-time Reverse transcription-Polymerase Chain Reaction (RT-PCR). Protein expression of HIF-1α and miR-210 targeted genes in human hepatoma xenograft was assessed by Western blot. Tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers by immunohistochemistry staining. Tumor growth was delayed in miR-210 downregulated xenograft. Knockdown of miR-210 increased protein expression of miR-210 targeted genes, but decreased HIF-1α protein in hepatoma xenograft. Knockdown of miR-210 in combination with radiotherapy is more effective than radiotherapy alone or miR-210 knockdown therapy alone in suppressing tumor growth and extending survival duration. Combined therapy decreased Ki-67-positive cells and CD31-positive cells and increased TUNEL-positive cells in tumor xenograft. Knockdown of miR-210 in combination with radiotherapy showed an enhanced anti-tumor effect on human hepatoma xenograft. Our experiments demonstrated specific inhibition of miR-210 expression might be a means to enhance the effectiveness of radiotherapy to human hepatoma

  5. Experimental study on ultrasound-guided intratumoral injection of "Star-99" in treatment of hepatocellular carcinoma of nude mice

    Institute of Scientific and Technical Information of China (English)

    Li-Wu Lin; Xiao-Dong Lin; Yi-Mi He; Shang-Da Gao; En-Sheng Xue

    2003-01-01

    AIM: To investigate the anti-cancer effect and the immunological mechanism of ultrasound-guided intratumoral injection of Chinese medicine "Star-99" in hepatocellular carcinoma (HCC) of nude mice.METHODS: Twenty-eight human hepatocellular carcinoma SMMC-7721 transplanted nude mice, 14 of hypodermically implanted and 14 of orthotopic liver transplanted, were randomly divided into three groups of which 14 mice with Star-99, and 7 with ethanol and saline respectively. Ten days after the transplantation the medicines were injected into the tumors of all the nude mice once every 5 days.After 4 injections the nude mice were killed. The diameters of three dimension of the tumors were measured by high frequency ultrasound before and after the treatment and the tumor growth indexes* (TGI) were calculated.Radioimmunoassay was used to detect the serum levels of interleukin-2 (IL-2) and tumor necrosis factor (TNF)-alpha.The tumor tissues were sent for flow cytometry (FCM) DNA analysis. Apoptotic cells were visualized by TUNEL assay.All the experiments were carried out by double blind method. zRESULTS: The TGI of Star-99 group (0.076±0.024) was markedly lower than that of the saline group (4.654±1.283)(P<0.01). It also seemed to be lower than that of the ethanol group (0.082±0.028), but not significantly different (P>0.05).Serum levels of IL-2 and TNF-α were markedly higher than those of ethanol group and saline groups (P<0.05). The mean apoptotic index (AI: percentage of TUNEL signal positive cells)in Star-99 group (48.98±5.09 %) was significantly higher than that of the ethanol group (11.95±2.24 %) and the saline group (10.48±3.85 %) (P<0.01). FCM DNA analysis showed that the appearance rate of the apoptosis peak in Srar-99group was 92.9 %, markedly higher than that of the ethanol group (14.3 %) and the saline group (0.0 %) (P<0.01).Correlation (r=0.499, P<0.05) was found between AI and serum level of TNF-α.CONCLUSION: Star-99 has an effect on the

  6. Comparative study of intact A7 MoAc and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice

    International Nuclear Information System (INIS)

    Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab)2 fragments were studied in human colon cancer (LS-174T)-bearing nude mice. The authors examined the yield and the immunoreactivity of F(ab)2 fragments after treatment with ficin as a function of time. The yield of F(ab)2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab)2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab')2 was preferentially taken up by the tumor, cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. The tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy. (author)

  7. Improvement of epidermal differentiation and barrier function in reconstructed human skin after grafting onto athymic nude mice.

    Science.gov (United States)

    Higounenc, I; Démarchez, M; Régnier, M; Schmidt, R; Ponec, M; Shroot, B

    1994-01-01

    To determine whether epidermis reconstructed in vitro at the air-liquid interface on de-epidermized dermis has the capacity to normalize the expression of differentiation-specific markers, its lipid composition and stratum corneum barrier properties, human skin equivalents were transplanted onto athymic nude mice and investigated at different stages ranging from 1 to 4 months after grafting. Indirect immunofluorescence with species- or non-species-specific antibodies revealed that as early as 1 month after transplantation keratinization, and involucrin, loricrin and transglutaminase patterns were normalized. Human melanocytes were observed in the basal layer of the pigmented graft. As revealed by high-performance thin-layer chromatography and transmission electron microscopy after ruthenium tetroxide fixation, the lipid profile and the intracellular lamellar organization were similar to those found in natural epidermis. Transepidermal water loss measurements and penetration studies showed that the barrier properties of the reconstructed epidermis after transplantation were comparable to those of normal human skin. PMID:8154923

  8. Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H; Engelholm, S A; Nielsen, A; Vindeløv, L

    1985-01-01

    A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth...... curves, and by the changes in the cell cycle distribution monitored by flow cytometric DNA analysis. The results demonstrated that both oestradiol and tamoxifen induced a temporary growth delay, whereas ovariectomy of the host had no effect on the growth of the tumour. The oestradiol-induced tumour...... growth delay was accompanied by a decrease in the G1 fraction, an accumulation of cells in the S-phase, and polyploidy, whereas neither treatment with tamoxifen nor ovariectomy influenced cell cycle distribution. The results indicate that oestradiol and tamoxifen have different mechanisms of action. In...

  9. Detection of early malignant changes in tissue cultured cells using a novel tumorigenicity assay in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.S.; Campbell, E.W.; Holland, L.M.; Schwartzendruber, D.E.; Kraemer, P.M.

    1979-01-01

    Cultured cells were tested for tumorigenicity in nude mice using a new test involving implantation of cells grown on small gelatin sponges. The test was applied to mouse, hamster, and human cells, and the results were compared to a conventional tumorigenicity assay (injection of cell suspensions). The sponge assay was at least as sensitive as the conventional assay in all cases tested so far. In several instances the sponge assay could detect events not seen in the standard assay. Use of the sponge assay has led to interesting possibilities for studying in vitro and early in vivo cellular changes that may be associated with the ability to form tumors. In studies with two human squamous cell carcinoma cell lines, the two assays yielded comparable results. Such cell lines might provide a system in which the lack of terminal differentiation within a cell population could be examined as a parameter of neoplastic change.

  10. Dermal penetration and systemic distribution of sup 14 C-labeled vitamin E human skin grafted athymic nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Klain, G.J.

    1989-03-13

    In vivo percutaneous penetration and tissue distribution of 14C-labeled vitamin E applied to human skin grafted onto athymic nude mice were determined. At 1 hr, mouse skin contained the highest level of radioactivity, followed by the muscle, blood, liver, lung, adipose tissue, spleen, kidney, brain, heart, and eyes. A linear increase with time in tissue radioactivity was observed throughout the 24 hr experimental period. At 4 and 24 hrs skin grafts were highly radioactive. At 4 hrs the epidermis and the upper portion of the dermis contained more radioactivity than the remaining portion of the dermis. In contrast, at 24 hrs the highest level of radioactivity was detected in the lower dermis. No radioactivity was detected in expired air while 0.2% of the dose was found in the urine. The data show that vitamin E does penetrate skin and that the dermis acts as a barrier or reservoir for this highly lipophilic compound.

  11. Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2

    International Nuclear Information System (INIS)

    Angiopoietin-2 (Ang-2) plays critical roles in vascular morphogenesis and its upregulation is frequently associated with various tumors. Previous studies showed that certain selenium compounds possess anti-tumor effects. However, the underlining mechanism has not been elucidated in detail. Plus, results of research on the anti-tumor effects of selenium compounds remain controversial. We investigated levels of Ang-2 and vascular endothelial growth factor (VEGF) on the estrogen-independent bone metastatic mammary cancer (MDA-MB-231) cells in response to treatment by methylseleninic acid (MSeA), and further examined the effects of MSeA oral administration on xenograft mammary tumors of athymic nude mice by RT-PCR, Western, radioimmuno assay, and Immunohistochemistry. Treatment of MDA-MB-231 cells with MSeA caused significant reduction of Ang-2 mRNA transcripts and secretion of Ang-2 proteins by the cells. Level of VEGF protein was accordingly decreased following the treatment. Compared with the controls, oral administration of MSeA (3 mg/kg/day for 18 days) to the nude mice carrying MDA-MB-231 induced tumors resulted in significant reduction in xenograft tumor volume and weights, significant decrease in microvascular density, and promotion of vascular normalization by increasing pericytes coverage. As expected, level of VEGF was also decreased in MSeA treated tumors. Our results point out that MSeA exerts its anti-tumor effects, at least in part, by inhibiting the Ang-2/Tie2 pathway, probably via inhibiting VEGF

  12. Exogenous stimulation with Eclipta alba promotes hair matrix keratinocyte proliferation and downregulates TGF-β1 expression in nude mice.

    Science.gov (United States)

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Jamil; Sung, Chang Keun

    2015-02-01

    Eclipta alba (L.) Hassk (E. alba) is a traditionally acclaimed medicinal herb used for the promotion of hair growth. However, to the best of our knowledge, no report has been issued to date on its effects on genetically distorted hair follicles (HFs). In this study, we aimed to identify an agent (stimuli) that may be beneficial for the restoration of human hair loss and which may be used as an alternative to synthetic drugs. We investigated the effects of petroleum ether extract (PEE) and different solvent fractions of E. alba on HFs of nude mice. Treatment was performed by topical application on the backs of nude mice and the changes in hair growth patterns were evaluated. Histological analysis was carried out to evaluate the HF morphology and the structural differences. Immunohistochemical (IHC) staining was performed to visualize follicular keratinocyte proliferation. The histological assessments revealed that the PEE-treated skin specimens exhibited prominent follicular hypertrophy. Subsequently, IHC staining revealed a significant increase (p<0.001) in the number of follicular keratinocytes in basal epidermal and matrix cells. Our results also demonstrated that PEE significantly (p<0.001) reduced the levels of transforming growth factor-β1 (TGF-β1) expression during early anagen and anagen-catagen transition. Our results suggest that PEE of E. alba acts as an important exogenous mediator that stimulates follicular keratinocyte proliferation and delays terminal differentiation by downregulating TGF-β1 expression. Thus, this study highlights the potential use of PEE of E. alba in the treatment of certain types of alopecia. PMID:25484129

  13. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    International Nuclear Information System (INIS)

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy

  14. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    2012-04-01

    Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

  15. Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in nude mice implanted with cervical cancer

    International Nuclear Information System (INIS)

    The aim of this study was to examine the effects of the crude extract of Acanthus ebracteatus Vahl (AE) on tumor growth and angiogenesis by utilizing a tumor model in which nude mice were implanted with cervical cancer cells containing human papillomavirus 16 DNA (HPV-16 DNA). The growth-inhibitory effect of AE was investigated in four different cell types: CaSki (HPV-16 positive), HeLa (HPV-18 positive), hepatocellular carcinoma cells (HepG2), and human dermal fibroblast cells (HDFs). The cell viabilities and IC50 values of AE were determined in cells incubated with AE for different lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6–7 weeks, weighing 20–25 g) were used. A cervical cancer-derived cell line (CaSki) with integrated HPV-16 DNA was injected subcutaneously (1 × 107 cells/200 μL) in the middle dorsum of each animal (HPV group). One week after injection, mice were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day for 14 or 28 days (HPV-AE groups). Tumor microvasculature and capillary vascularity were determined using laser scanning confocal microscopy. Tumor tissue was collected from each mouse to evaluate tumor histology and vascular endothelial growth factor (VEGF) immunostaining. The time-response curves of AE and the dose-dependent effect of AE on growth inhibition were determined. After a 48-hour incubation period, the IC50 of AE in CaSki was discovered to be significantly different from that of HDFs (P < 0.05). A microvascular network was observed around the tumor area in the HPV group on days 21 and 35. Tumor capillary vascularity in the HPV group was significantly increased compared with the control group (P < 0.001). High-dose treatment of AE extract (HPV-3000AE group) significantly attenuated the increase in VEGF expression and tumor angiogenesis in mice that received either the 14- or 28-day treatment period (P < 0.001). Our novel findings demonstrated that AE crude extract could

  16. Inhibition of K562 cell growth and tumor angiogenesis in nude mice by transfection of anti-VEGF hairpin ribozyme gene into the cells

    Institute of Scientific and Technical Information of China (English)

    许文林

    2006-01-01

    Objective To explore the effect of anti-VEGF hairpin ribozyme gene on the tumor cell growth and tumor angiogenesis in nude mice. Methods The recombinant eukaryotic expression plasmid pcDNA-RZ containing anti-VEGF hairpin ribozyme gene and the empty vector plasmid pcDNA were introduced separately into K562 cells

  17. Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF). hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. 131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging

  18. The MRI study of supraparamagnetic ironic oxide loaded polymeric nano-vesicles in human colonic carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Objective: To synthesize the hydrophobic supraparamagnetic ironic oxide (SPIO) loaded and hydrophilic SPIO loaded polymeric nano-vesicles and to investigate the feasibility of using hydrophobic SPIO loaded and hydrophilic SPIO loaded polymeric nano-vesicles to display the tumor in MRI in vivo through animal experiments. Methods: The polymeric nano-vesicles were prepared from poly (D, L-lactic acid) (PDLLA) and poly (ethylene glycol) (PEG) by a multiple emulsion/solvent evaporation method. The hydrophobic SPIO and hydrophilic SPIO were loaded in the polymeric, nano-vesicles respectively., Eighteen nude mice models with human colorectal carcinoma xenograft were established. They were divided equally into three groups (n=6). The three groups of nude mice models were injected with water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle via the mice caudal vein respectively., Dynamic MRI scan were performed in all the mice models. T2WI signal intensity and T2 relaxation time were measured in the tumor, liver and muscle by using T2 mapping software. ANOVA of repeated measurement was used to analyze if there were significant differences of signal intensity changes among the three groups, while Bonferroni method was used for pair-wise comparison. Results: On T2WI, tumors showed decrease in signal intensity after hydrophobic or hydrophilic SPIO loaded polymeric nano-vesicle injection, while no signal intensity decrease was found in the tumor after water-soluble SPIO administration. The maximum percentage of signal intensity decrease in tumor caused by hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 11.00%, 11.40%, respectively. There was statistical significant difference of signal intensity changes among these three groups (F=10.96, P 0.05), The three agents could lead to signal intensity decrease in the liver. The maximum percentage of signal intensity decrease in liver caused by water-soluble SPIO, hydrophobic SPIO loaded and

  19. The effectiveness of 125I seed interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice: an experiment in vivo

    International Nuclear Information System (INIS)

    Objective: To discuss the effectiveness and therapeutic mechanism of 125I interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice. Methods: The human pancreatic cell line Sw1990 was subcutaneously injected into the right lower limb partially dorsal area next to the groin of the immunodeficient BABL /c nude mice. The tumor was removed and cut into small pieces after it was formed,then the tumor pieces were inoculated in nude mice. The tumor developed to 8-10 mm in size after six weeks. A total of 16 nude mice with the suitable tumor size were used in this study. The 16 experimental mice were randomly and equally divided into two groups. The mice in study group (n = 8) were implanted with 125I seeds, while the mice in control group (n = 8) were implanted with ghost seeds. After the implantation both the long and short diameter of the tumors as well as the mouse body weight were measured every 4 days. The tumor weight was measured when the mouse was sacrificed. The paraffin-embedded samples were sent for histopathological examination. Apoptotic cells were checked with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Expression of proliferating cell nuclear antigen (PCNA) was detected with immuno-histochemical staining. Results: The tumor grew slowly in the study group, but rapidly in the control group. The tumor weight in the study group and the control group was (2.68 ± 0.70)g and (4.68 ± 1.45)g, respectively, the difference between two groups was statistically significant (P = 0.021). The tumor inhibition rate was about 42.66%. No significant difference in body weight of nude mice existed between two groups both before and after the treatment (P > 0.05). Marked tumor necrosis was seen in study group, but no obvious, or only a little, tumor necrosis could be observed in the control group. The apoptotic index checked with the TUENL method in the study group and control group was (23.2 ± 1.9)% and

  20. Selenized milk casein in the diet of BALB/c nude mice reduces growth of intramammary MCF-7 tumors

    International Nuclear Information System (INIS)

    Dietary selenium has the potential to reduce growth of mammary tumors. Increasing the Se content of cows’ milk proteins is a potentially effective means to increase Se intake in humans. We investigate the effects of selenized milk protein on human mammary tumor progression in immunodeficient BALB/c nude mice. Four isonitrogenous diets with selenium levels of 0.16, 0.51, 0.85 and 1.15 ppm were formulated by mixing low- and high-selenium milk casein isolates with a rodent premix. MCF-7 cells were inoculated into the mammary fat pad of female BALB/c nude mice implanted with slow-release 17 β-estradiol pellets. Mice with palpable tumors were randomly assigned to one of the four diets for 10 weeks, during which time weekly tumor caliper measurements were conducted. Individual growth curves were fit with the Gompertz equation. Apoptotic cells and Bcl-2, Bax, and Cyclin D1 protein levels in tumors were determined. There was a linear decrease in mean tumor volume at 70 days with increasing Se intake (P < 0.05), where final tumor volume decreased 35% between 0.16 and 1.15 ppm Se. There was a linear decrease in mean predicted tumor volume at 56, 63 and 70 days, and the number of tumors with a final volume above 500 mm3, with increasing Se intake (P < 0.05). This tumor volume effect was associated with a decrease in the proportion of tumors with a maximum growth rate above 0.03 day-1. The predicted maximum volume of tumors (Vmax) and the number of tumors with a large Vmax, were not affected by Se-casein. Final tumor mass, Bcl-2, Bax, and Cyclin D1 protein levels in tumors were not significantly affected by Se-casein. There was a significantly higher number of apoptotic cells in high-Se tumors as compared to low-Se tumors. Taken together, these results suggest that turnover of cells in the tumor, but not its nutrient supply, were affected by dairy Se. We have shown that 1.1 ppm dietary Se from selenized casein can effectively reduce tumor progression in an MCF-7 xenograft

  1. Therapeutic effect against human xenograft tumors in nude mice by the third generation microtubule stabilizing epothilones.

    Science.gov (United States)

    Chou, Ting-Chao; Zhang, Xiuguo; Zhong, Zi-Yang; Li, Yong; Feng, Li; Eng, Sara; Myles, David R; Johnson, Robert; Wu, Nian; Yin, Ye Ingrid; Wilson, Rebecca M; Danishefsky, Samuel J

    2008-09-01

    The epothilones represent a promising class of natural product-based antitumor drug candidates. Although these compounds operate through a microtubule stabilization mechanism similar to that of taxol, the epothilones offer a major potential therapeutic advantage in that they retain their activity against multidrug-resistant cell lines. We have been systematically synthesizing and evaluating synthetic epothilone congeners that are not accessible through modification of the natural product itself. We report herein the results of biological investigations directed at two epothilone congeners: iso-fludelone and iso-dehydelone. Iso-fludelone, in particular, exhibits a number of properties that render it an excellent candidate for preclinical development, including biological stability, excellent solubility in water, and remarkable potency relative to other epothilones. In nude mouse xenograft settings, iso-fludelone was able to achieve therapeutic cures against a number of human cancer cell lines, including mammarian-MX-1, ovarian-SK-OV-3, and the fast-growing, refractory, subcutaneous neuroblastoma-SK-NAS. Strong therapeutic effect was observed against drug-resistant lung-A549/taxol and mammary-MCF-7/Adr xenografts. In addition, iso-fludelone was shown to exhibit a significant therapeutic effect against an intracranially implanted SK-NAS tumor. PMID:18755900

  2. Antitumor effects of inductive hyperthermia using magnetic ferucarbotran nanoparticles on human lung cancer xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Araya T

    2013-03-01

    Full Text Available Tomoyuki Araya,1 Kazuo Kasahara,1 Shingo Nishikawa,1 Hideharu Kimura,1 Takashi Sone,1 Hideo Nagae,2 Yoshio Ikehata,3 Isamu Nagano,3 Masaki Fujimura11Department of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 2Cooperative Research Center for Kanazawa University, 3Department of Information and Systems Engineering, Kanazawa University, Kanazawa, JapanBackground: The effects of inductive hyperthermia on lung cancer have yet to be fully investigated. Magnetic nanoparticles used in inductive hyperthermia are made-to-order and expensive. This study was performed to investigate the use of ferucarbotran in inductive hyperthermia and to clarify whether inductive hyperthermia using ferucarbotran promotes antitumor effects in vivo using a lung cancer cell line.Methods: We injected A549 cells subcutaneously into the right thighs of BALB/c nu/nu nude mice. Forty mice with A549 xenografts were then classified into three groups. Group 1 was the control group. All mice in groups 2 and 3 had ferucarbotran injected into their tumors, and mice in group 3 were then subjected to alternating magnetic field irradiation. We evaluated tumor temperature during the hyperthermic procedure, the time course of tumor growth, histologic findings in tumors after hyperthermic treatment, and adverse events.Results: Intratumor temperature rose rapidly and was maintained at 43°C–45°C for 20 minutes in an alternating magnetic field. Tumor volumes in groups 1 and 2 increased exponentially, but tumor growth in group 3 was significantly suppressed. No severe adverse events were observed. Histologic findings for the tumors in group 3 revealed mainly necrosis.Conclusion: Inductive hyperthermia using ferucarbotran is a beneficial and promising approach in the treatment of lung cancer. Ferucarbotran is a novel tool for further development of inductive hyperthermia.Keywords: inductive hyperthermia, ferucarbotran, magnetic

  3. TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors

    Directory of Open Access Journals (Sweden)

    Peh Bee

    2009-01-01

    Full Text Available Abstract Background Members of the TRIP-Br/SERTAD family of mammalian transcriptional coregulators have recently been implicated in E2F-mediated cell cycle progression and tumorigenesis. We, herein, focus on the detailed functional characterization of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2 (SERTAD2. Methods Oncogenic potential of TRIP-Br2 was demonstrated by (1 inoculation of NIH3T3 fibroblasts, which were engineered to stably overexpress ectopic TRIP-Br2, into athymic nude mice for tumor induction and (2 comprehensive immunohistochemical high-throughput screening of TRIP-Br2 protein expression in multiple human tumor cell lines and human tumor tissue microarrays (TMAs. Clinicopathologic analysis was conducted to assess the potential of TRIP-Br2 as a novel prognostic marker of human cancer. RNA interference of TRIP-Br2 expression in HCT-116 colorectal carcinoma cells was performed to determine the potential of TRIP-Br2 as a novel chemotherapeutic drug target. Results Overexpression of TRIP-Br2 is sufficient to transform murine fibroblasts and promotes tumorigenesis in nude mice. The transformed phenotype is characterized by deregulation of the E2F/DP-transcriptional pathway through upregulation of the key E2F-responsive genes CYCLIN E, CYCLIN A2, CDC6 and DHFR. TRIP-Br2 is frequently overexpressed in both cancer cell lines and multiple human tumors. Clinicopathologic correlation indicates that overexpression of TRIP-Br2 in hepatocellular carcinoma is associated with a worse clinical outcome by Kaplan-Meier survival analysis. Small interfering RNA-mediated (siRNA knockdown of TRIP-Br2 was sufficient to inhibit cell-autonomous growth of HCT-116 cells in vitro. Conclusion This study identifies TRIP-Br2 as a bona-fide protooncogene and supports the potential for TRIP-Br2 as a novel prognostic marker and a chemotherapeutic drug target in human cancer.

  4. Study on the radiosensitivity of nude mice model transplanted lung adenocarcinoma cell treated by β-elemene

    International Nuclear Information System (INIS)

    Objective: To explore the effect of β-element on the radiosensitivity of transplanted tumor, and its relationship with the expression of surviving. Methods: The transplanted mice model was established through the cell suspension inoculation. The mice with transplanted tumor size of 0.8-1.0 cm3 were randomly divided into 8 groups as blank control, 25, 45 and 100 mg/kg group, irradiation group, 25 mg/kg + irradiation group, 45 mg/kg + irradiation group, 100 mg/kg + irradiation group. The tumor size was measured every other day until tumor size was double, and the growth curve was obtained. The average tumor growth inhibition rate of β-element and tumor size were attained at 2, 4, 6 and 8 d after β-element injection. The expression of surviving was detected with immunohistochemistry. Results: The nude mice model was successfully established and the growth curves were obtained according to the tumor size. Between 2 and 8 d after β-elemene injection, the variation tendency of the average tumor growth inhibition rate was consistent with the size in β-elemene treatment groups. The antitumor effect of β-elemene was in a dose-dependent manner. The values of radiosensitivity enhancement factor were 0.84, 1.24, 2.04 for 25, 45 and 100 mg/kg group, respectively, and the optimal dose was 45 mg/kg. β-element had little effect on the expression of surviving, and the expression of surviving significantly enhanced in irradiation group and decreased in β-element + irradiation groups. Conclusions: β-elemene could enhance the tumor radiosensitivity through inhibition the expression of surviving. (authors)

  5. Labelling of anti-human bladder tumor chimeric antibody with 99Tcm and radioimmunoimaging of bladder carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Objective: To study the in vitro immunoreactivity and in vivo tissue distribution, tumor targeting property of anti-human bladder tumor human-murine chimeric antibody (ch-BDI) labeled with 99Tcm and to investigate its possibility for being used in guiding diagnosis and guiding therapy of bladder cancer. Methods: The ch-BDI was labeled with 99Tcm by improved Schwarz method and the labeled antibody was purified by Sephadex G-50. Labeling yield and radiochemical purity were measured by paper chromatography. The immunoreactive fraction and association constant (Ka) were measured by Lindmo method and Scatchard analysis, respectively. 11.1 MBq (30 μg) 99Tcm-ch-BDI was intravenously injected into nude mice bearing human bladder cancer xenografts in the right thigh and radioimmunoimaging (RII) was performed 2, 6, 20 and 24 h postinjection. The images were processed by region of interest (ROI) method to acquire the counts of whole body and the tumor and the counts ratios of tumor to contralateral normal tissue or to tissues of other non-tumor bearing organs. The mice were killed after 24 h postinjection imaging and tissue distribution was measured. %ID/g and target to nontarget (T/NT) ratios were calculated. Results: The labeling yield and radiochemical purity of 99Tcm-ch-BDI were (66.5±7.3)% and >90%, respectively. The immunoreactive fraction was 76% and Ka was 3.56 x 109 L/mol. RII showed that the tumor was clearly visualized 6 h postinjection and becoming clearer along with time prolonging. The radioactivity of whole body decreased rapidly with time, whereas the radioactivity of the tumor decreased slowly. The T/NT ratios was increased with time. Biodistribution results showed that tumor uptake was 17.4%ID/g 24 h postinjection. T/NT ratios were very high except for the kidney. T/NT ratios for brain, muscle, intestinal wall, bone and heart wall were 136.0, 55.1, 39.3, 29.7 and 27.9, respectively. Conclusion: 99Tcm-ch-BDI exhibits excellent immunoreactivity and tumor

  6. Effects of Medicated Diet to Eradicate Helicobacter spp. on Growth, Pathology, and Infection Status in Rag1–/– and Nude Mice

    OpenAIRE

    Garrett, Caroline M; Muth, Dillon; Watson, Julie

    2014-01-01

    The use of a commercial 4-drug diet has been shown to eradicate Helicobacter spp. from immunocompetent mice and those with innate immunodeficiencies. However the efficacy of this diet has not been confirmed in mice with altered adaptive immunity. We hypothesized that an 8-wk treatment with medicated diet would eradicate H. hepaticus and H. typhlonius from young naturally infected nude and Rag1 mice lacking functional T cells (Foxn1nu) or T and B cells (B6.129S7-Rag1tm1Mom/J), respectively. We...

  7. Anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice

    International Nuclear Information System (INIS)

    Objective: To study the anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice and clarify their anti-tumor mechanisms. Methods 120 nude mice transplantated with human breast cancer cells MCF-7 were randomly divided into 3 groups (n=40): 125I radioactive particles implanted group, non-radioactive particles implanted group and non-particles implanted group. The articles were implanted into mice according to Pairs system principle. The expressions of Fas mRNA and protein and the activaties of caspase-3 and caspase-8 enzyme were detected by RT-PCR and Western blotting. The changes of cell cycle were detected by flow cytometry. Results: Compared with non-radioactive particles implanted group and non-particles implanted group, the size of cancer tissues in 125I radioactive particles implanted group was reduced significantly (P0/G1 phase was significantly increased (P125I radioactive particles into transplantated tumor model of human breast cancer cells can kill tumor cells, inhibit the growth cycle of tumor cells and induce the apoptosis of tumor cells in nude mice. (authors)

  8. Pharmacokinetics of cisplatin with and without amifostine in tumour- bearing nude mice

    NARCIS (Netherlands)

    Korst, A.E.C.; Boven, E.; Sterre, M.L.T. van der; Fichtinger-Schepman, A.M.J.; Vijgh, W.J.F. van der

    1998-01-01

    Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against platinum-induced toxicities. We have previously reported that amifostine induced a potentiation of the antitumour activity of carboplatin in human ovarian cancer xenografts. An influence of amifostine on the pharmacokinetics

  9. Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin.

    Science.gov (United States)

    Fan, Dominic; Yano, Seiji; Shinohara, Hisashi; Solorzano, Carmen; Van Arsdall, Melissa; Bucana, Corazon D; Pathak, Sen; Kruzel, Ewa; Herbst, Roy S; Onn, Amir; Roach, Jennifer S; Onda, Masanori; Wang, Qing-cheng; Pastan, Ira; Fidler, Isaiah J

    2002-06-01

    Several tumors, including mesothelioma and ovarian cancer, can overexpress mesothelin, a glycosylphosphatidylinositol-linked differentiation glycoprotein. The membrane-bound type of mesothelin is found in the blood of cancer patients at a very low level, which makes mesothelin a good candidate for targeted therapy of certain cancers. An antimesothelin disulfide-linked Fv (SS1 Fv) was fused to a truncated mutant of Pseudomonas exotoxin A to produce the recombinant immunotoxin SS1(dsFv)-PE38, which has a high binding affinity to mesothelin (Kd = 0.7 nM). Our studies in vitro showed that SS1(dsFv)-PE38 is significantly more cytotoxic to the high-mesothelin-producing NCI-H226 human non-small cell lung cancer cells than to human lung adenocarcinoma PC14PE6 cells, which do not express mesothelin. When administered at a nontoxic dose of 500 microg/kg on days 7, 9, and 11 to nude mice injected i.v. with the two human lung cancer cell lines, SS1(dsFv)-PE38 selectively inhibited experimental lung metastases produced by the mesothelin-producing NCI-H226 cells. Our data indicate that mesothelin-producing squamous cell carcinoma of the lung may be a good target for this immunotoxin. PMID:12479219

  10. Study on therapy of leukemia through proliferated NK cell induced by low-dose radiation in nude mice

    International Nuclear Information System (INIS)

    Objective: To separate NK cells of mice from NK cell separation medium and study inhibitory effect of proliferated NK cell induced by low dose radiation on the leukemia model of K562 cells. Methods: Flow cytometry and 3H-TdR methods were respectively used to measure proliferation index and activity of NK cells treated with low-dose radiation (which means exposure dose in 20 cGy low LET beam or 5 cGy high LET beam). CD13 + cells were measured by flow cytometry and TNF-α content in blood-serum was detected by ELISA. In vivo, peripheral blood leucocyte count, index of liver, indexes of spleen and kidney were observed in control group and experimental group. Results: The purity of NK cell separation was (82.54±0.18)%.The proliferation index of NK cells at 24 hours after 80 mGy irradiated was 36.31±1.32%, (t=24.69, P<0.05). Killing activity of NK cell induced by low dose radiation to K562 cell was (12.59±0.63)%(t=6.63, P<0.05) and the inhibition ratio was 29.52%. Conclusion: The injection of proliferated NK cell induced by low dose radiation demonstrated significant inhibitory effect on the growth of leukemia nude mouse. (authors)

  11. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 (177Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  12. [Microvascular architecture of human tumors transplanted in nude mice--its relationship to sensitivity to antineoplastic agents].

    Science.gov (United States)

    Okazaki, M; Kubota, T; Hanatani, Y; Maruyama, K; Tsuyuki, K; Nakada, M; Asanuma, F; Ishibiki, K; Abe, O

    1982-08-01

    Microangiographic study was performed with ten human tumors serially transplanted into nude mice to clarify the role of tumor vessels on the chemosensitivity of the human tumors. Five gastric carcinomas, two colon carcinomas, one breast carcinoma, one cholangiocarcinoma, and one hemangiopericytoma were used for the experiments. Seven tumors revealed hypervascular network of vessels, whereas hypovascular patterns of tumor vessels were observed in the other three tumors. It was found that the histologically differentiated tumors were hypervascular and undifferentiated tumors were hypovascular, with statistically significant differences (p less than 0.05). Each tumor possessed the vascular network similar to human tumors originated from the same organs. No discernible changes of microangiographic features were noticed by serial transfers. As the chemosensitivities of these tumors depended mainly on their original tissues, these chemosensitivities could not be explained only by tumor vascularities or drug transferences. However, in the tumors with similar chemosensitive spectra, less susceptible tumors were observed to possess the irregular vascular networks in comparison with sensitive strains. From these considerations, tumor vessels were thought to have some role on vascular flow and drug transference which affected chemosensitivity of human tumors. PMID:7184456

  13. Anti-tumorigenic and Pro-apoptotic effects of CKBM on gastric cancer growth in nude mice

    Directory of Open Access Journals (Sweden)

    2004-08-01

    Full Text Available Natural botanical products can be integrated with western medicine to optimize the treatment outcome, increase immune function and minimize the side effects from western drug treatment. CKBM is a combination of herbs and yeasts formulated based on traditional Chinese medicinal principles. Previous study has demonstrated that CKBM is capable of improving immune responsiveness through the induction of cytokine mediators, such as TNF-α and IL-6. In this study, we aimed to investigate the effect of this immunomodulatory drug on gastric cancer growth using a human xenograft model. Gastric cancer tissues were implanted subcutaneously into athymic nude mice followed by a 14-day or 28-day of CKBM treatment. Results showed that higher doses of CKBM (0.4 or 0.8 ml/mouse/day produced a dose-dependent inhibitory effect on gastric tumor growth after 28-day drug treatment. This was associated with a decrease of cellular proliferation by 30% with concomitant increase in apoptosis by 97% in gastric tumor cells when compared with the control group. In contrast, CKBM showed no effect on angiogenesis in gastric tumors. This study demonstrates the anti-tumorigenic action of CKBM on gastric cancer probably via inhibition of cell proliferation and induction of apoptosis, and provides future potential targets of this drug candidate on cancer therapy.

  14. Marked antitumor activity of cat's whiskers tea (Orthosiphon stamineus extract in orthotopic model of human colon tumor in nude mice

    Directory of Open Access Journals (Sweden)

    Foaud Saleih R Al-Suede

    2012-08-01

    Full Text Available Orthosiphon stamineus is used to treat kidney ailments including angiogenesis-dependent diseases. O. stamineus has shown to possess strong anti-angiogenic activity. In present study, an orthotopic nude mouse model of colon cancer was employed to study the factors that influence suppression of tumor by standardized 50% ethanol extract of O. stamineus leaves (EOS. Human colorectal cancer cells (HCT116 were surgically injected into the cecal wall of mice. Two different oral doses (100 and 200 mg/kg/day were given for 5 weeks. EOS suppressed 61.62±3.7% and 82.8±1.5% tumor growth at 100 and 200 mg/kg, respectively. Tumor histology revealed significant reduction in vascularization. Anti-angiogenic efficacy of EOS was investigated in human endothelial cells (HUVEC. In vitro, EOS inhibited migration and tube formation of HUVECs. HPLC data showed high content of rosmarinic acid in EOS. This work supports previous anti-tumor works on the plant in which suppression of VEGFR phosphorylation is thought to be involved.

  15. Growth kinetics and in vivo radiosensitivity in nude mice of two subpopulations derived from a single human small cell carcinoma of the lung

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Clerici, M; Engelholm, S A;

    1986-01-01

    The growth kinetics and the in vivo radiosensitivity of two human small cell carcinomas of the lung (SCCL) grown in nude mice were investigated. The tumors, CPH SCCL 54A and 54B, were derived by in vitro cloning of a single SCCL and were subsequently serially grown in nude mice. The growth curves...... were described according to a transformed Gompertz function, and the cell kinetics were examined by flow cytometric DNA analysis (FCM) and by the technique of labelled mitoses. The effect of single-dose irradiation was estimated by the specific growth delay calculated from the growth curves, and by the...... cell cycle distribution changes monitored by FCM. The results showed that the tumors differed in the in vivo radiosensitivity despite similarities in the growth kinetics. The results support the concept that difference in sensitivity among tumor subpopulations is an important reason for therapeutic...

  16. Influences of androgen on the growth of human prostate cancer PC-3M model in nude mice and the changes of the androgen receptor levels and protein kinase C activity

    International Nuclear Information System (INIS)

    Nude mice bearing transplanted human prostate cancer cell line PC-3M were treated with male sex hormone. Results demonstrated that low dose of testosterone propionate (TP) (50 mg/kg wt.) stimulated the tumor growth, and the androgen receptor (AR) levels and protein kinase C (PKC) activity were elevated in the tumor tissue. On the contrary higher dose of TP (400 mg/kg wt.) inhibited the tumor growth, and the AR level and PKC activity in tumor tissue were reduced significantly. These results showed that TP has a biphasic effect on the growth of human prostate cancer PC-3M cell line. The mechanism of the biphasic effect and its relationship between AR and PKC levels are also discussed

  17. Undifferentiated Human Adipose-derived Stromal/Stem Cells loaded onto Wet-Spun Starch-polycaprolactone Scaffolds Enhance Bone Regeneration: Nude Mice Calvarial Defect in vivo Study

    OpenAIRE

    Carvalho, Pedro P.; Leonor, Isabel B.; Smith, Brenda J.; Dias, Isabel R.; Reis, Rui L.; Jeffrey M Gimble; Gomes, Manuela E.

    2013-01-01

    The repair of large bony defects remains challenging in the clinical setting. Human adipose-derived stromal/stem cells (hASCs) have been reported to differentiate along different cell lineages, including the osteogenic. The objective of the present study was to assess the bone regeneration potential of undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a critical-sized nude mice calvarial defect.

  18. Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human HepatocelLular Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    LI Bao-jin; ZHANG Chao; YI Yuan-xue; HAO Ying; LIU Xiao-ping; OU Qing-jia

    2007-01-01

    Objective: To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) in combination of ganciclovir (GCV) against human hepatocellular carcinoma in nude mice. Methods: HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups (n=8 each group): Ganciclovir group (Ⅰ), Ad group (Ⅱ), AdCMV-tk/GCV group (under the driving of CMV promoter) (Ⅲ) and AdKDR-tk/GCV group (Ⅳ). Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/(kg·d), ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results: Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and Ⅳ (P<0.05). The mean MVDs in group Ⅰ, Ⅱ, Ⅲand Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 (microvessels/mm2), respectively. Significant differences were found between group Ⅲ and Ⅱ (P<0.05), Ⅳ and Ⅱ (P<0.01), and Ⅳ and Ⅲ (P<0.01). Conclusion: Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC.

  19. Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dao-Ming Liang; Jia-Yong Chen; Yi Zhang; Ping Gan; Jie Lin; An-Bao Chen

    2006-01-01

    AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo.METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model wasestablished successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method.RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%,58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P <0.05), whereas there were no significant differences (P >0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group.CONCLUSION: rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

  20. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice.

    Science.gov (United States)

    Goto, Hisatsugu; Yano, Seiji; Zhang, Helong; Matsumori, Yuka; Ogawa, Hirohisa; Blakey, David C; Sone, Saburo

    2002-07-01

    ZD6126 (ANG453) is a novel vascular targeting agent that selectively disrupts the cytoskeleton of endothelial cells in tumor. In mouse s.c. xenograft models, ZD6126 was found to induce selective occlusion of tumor blood vessels, cessation of tumor blood flow, and death of tumor cells because of the starvation of oxygen and nutrition. Here, we investigated whether ZD6126 inhibited the metastatic formation of human non-small cell lung cancer cells. PC14PE6 (adenocarcinoma) and H226 (squamous cell carcinoma) cells were injected into the tail vein of nude mice, and lung metastases were estimated. ZD6126 treatment involved either a single dose on 24 h before killing or daily doses from day 14 until the end of the experiment. Single treatment with i.p. injection of 200 mg/kg ZD6126 caused bleeding and necrotic changes in the tumor by 24 h. Histological analysis revealed that apoptotic tumor cells were markedly increased in the ZD6126-treated group. Moreover, ZD6126 induced the apoptosis of CD31-positive vascular endothelial cells in tumors but not in the normal lung parenchyma. When mice were treated daily with 100 mg/kg ZD6126 from day 14 until the end of the experiment, the lung weight was significantly less in the ZD6126-treated group than that of the control group, despite no difference in the number of metastatic nodules. These data suggest that ZD6126 could demonstrate its antitumor activity against both already established and early phase of lung cancer metastasis by causing the selective apoptosis of tumor endothelial cells and destruction of the tumor vasculature. PMID:12097279

  1. Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Atsushi B.; Sogawa, Chizuru; Sugyo, Aya [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sudo, Hitomi [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Toyohara, Jun [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 206-8670 (Japan); Koizumi, Mitsuru [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Abe, Masaaki; Hino, Okio [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Harada, Yoshi-nobu; Furukawa, Takako [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Suzuki, Kazutoshi [Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Saga, Tsuneo [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: saga@nirs.go.jp

    2009-05-15

    Introduction: Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers. Methods: Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG), 3'-[{sup 18}F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[{sup 11}C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and thymidine kinase 1 (TK{sub 1}) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining. Results: In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [{sup 11}C]S-dThd was significantly higher than that of [{sup 18}F]FDG. On the other hand, in sarcomatoid models, [{sup 18}F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and TK{sub 1} activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors. Conclusions: We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary

  2. Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts

    International Nuclear Information System (INIS)

    Introduction: Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers. Methods: Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [18F]fluoro-2-deoxy-D-glucose (FDG), 3'-[18F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[11C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [14C]FDG and [3H]FLT and thymidine kinase 1 (TK1) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining. Results: In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [11C]S-dThd was significantly higher than that of [18F]FDG. On the other hand, in sarcomatoid models, [18F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [14C]FDG and [3H]FLT and TK1 activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors. Conclusions: We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary: [18F]FLT and [11C]S-dThd seemed suitable for the epithelioid subtype and [18F]FDG seemed

  3. Establishment of orthotopic impact/metastasis model of human ovary cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    侯向华; 辛晓燕; 杨红; 王德堂; 郭慧玲

    2003-01-01

    Objective:To establish a patient-like human ovary carcinoma/spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue.Methods:An highly metastatic ovarian tumor line(HO8910PM:Human serum carcinoma of the ovary)previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations.Results:All mice developed ovary tumors and the metastatic rates were about 75%.The tumors only metastasized to liver but no other organs.The earliest appearance of metastasis was 14 d and the average survival period was 20.7 ± 4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted.Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage.Conclusion:Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties.This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.

  4. Effects of Chinese Jianpi herbs on cell apoptosis and related gene expression in human gastric cancer grafted onto nude mice

    Institute of Scientific and Technical Information of China (English)

    Ai-Guang Zhao; Hai-Lei Zhao; Xiao-Jie Jin; Jin-Kun Yang; Lai-Di Tang

    2002-01-01

    AIM: To explore the mechanism of the Sijunzi decoction and another Chinese herbal recipe (SRRS) based mainly on the Sijunzi decoction in treatment of gastric cancer.METHODS: A human gastric adenocarcinoma cell line SGC7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representative experimental conditions. Ahimals in the two experimental groups received either Sijunzi decoction or SRRS over a 40-day period starting at 1st day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted.The effect of therapy was assessed by two ways: (1)tumor size was periodically measured during the life of the animals; (2) tumor weight was determined by a electron balance immediately after the animals killed. For detection of apoptotic cells, apoptotic indices(AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuddine tdphosphate fluorescence nick end labeling (TUNEL) method.Morphological alterations were observed with electron microscopy. S-P immunohistochemical method was used to detect the expression of Ki-67 in xenografts. Expression of bcl-2 and p53 was semiquantitatively detected using a reverse transcriptase-polymerase chain reaction (RT-PCR)technique.RESULTS: When compared with controls, tumor growth (size and weight) was significantly inhibited by treatment with the Sijunzi decoction (P<0.05) or SRRS (P<0.01). The tumor inhibitory rate in the Sijunzi decoction group was 34.33 % and SRRS group 46.53 %. AI of human gastric cancer xenografts in nude mice was significantly increased to 16.24±3.21% using TUNEL method and 11.38±6.46 % by FACScan in the Sijunzi decoction group compared with the controls (TUNEL: 2.63±1.03 %, P<0.01; FACScan: 7.15± 1.32 %, P<0.05). SRRS group was also found a significantly increased AI by using TUNEL method and flow cytometry analysis compared with the controls (TUNEL: 13.18±3

  5. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Pornprom Yoysungnoen; Ponthip Wirachwong; Chatchawan Changtam; Apichart Suksamrarn; Suthiluk Patumraj

    2008-01-01

    AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2).METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 x 106 human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured.RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%,P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05).CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

  6. Adipose stem cells' antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function.

    Science.gov (United States)

    Wang, Haiying; Wei, Shuyue; Xue, Xinxin; You, Yuntian; Ma, Qiang

    2016-09-01

    This study aims to discuss adipose stem cells' (ASCs) antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function; the study also aims to explore a new mechanism of anti-aging to provide clinical anti-aging therapy with new thoughts and methods. We selected 40 healthy specific pathogen-free (SPF) nude mice and divided them randomly into four groups which were: blank control group; D-galactose + phosphate buffer saline (PBS) group; D-galactose + ASCs treatment group; and D-galactose + aminoguanidine (AG) group. Results showed that the superoxide dismutase (SOD) level of mice in the D-galactose-induced model group (87.15 ± 4.95 U/g) decreased significantly compared with that of control group (146.21 ± 4.76 U/g), while malonaldehyde (MDA) level of mice in D-galactose induced model group (11.12 ± 2.08 nmol/mg) increased significantly compared with that of control group (5.46 ± 2.05 nmol/mg) (P bioluminescence, and they survive for a short time in the skin after transplantation, which provides a basis for the application of ASC transplantation in clinical practices. Moreover, ASCs can control glycosylation level of D-galactose-induced skin aging of nude mice, reverse expression of aging-related biomarkers as well as restrain formation of advanced glycation end products, which are similar to the effects of AG inhibitors of advanced glycation end products. Thus, ASCs can prevent glycosylation-induced skin aging as well as recover functions of skin. PMID:26916459

  7. Experimental study on selective cyclooxygenase-2 inhibitor combined with radiotherapy for human prostate carcinoma xenografts in nude mice

    International Nuclear Information System (INIS)

    Objective: To investigate the anti-tumor and radiation-enhancement effects and observe a coordinate repression of celecoxib, a selected cyclooxygenase -2 inhibitor in prostate carcinoma. Methods: An animal model of human prostate carcinoma in BALC/C male nude mice was establised by injecting suspension of PC-3 cells and the mice were randomly divided into 4 groups which were interfered with celecoxib, radiation, and both celecoxib and radiation respectively, with 6 rats in each group. The effect of treatment was assessed by tumor growth delay (TGD) and radiosensitization enhancement effector (EF); the tumor tissues were collected and assessed for the detection of cyclooxygense-2 mRNA and prostaglandin E2 by RT-PCR and ELISA, and histopathological changes of transplanted mouse's important organs were observed. Results: The time that the longest diameters of all tumors growing from 8.0mm to 12.0mm for the control group and the celecoxib group was(6.18 ± 0.72)d and(7.87 ± 0.76)d, respectively ,while the time for the radiation group and celecoxib + radiation group was (9.16 ± 0.89)d and (12.62 ± 1.28)d respectively. The growth of tumors was significantly different among these groups (P2 levels between the control group and other groups (P2 levels between the radiation group and celecoxib + radiation group (P>0.05). Significant correlations were found between the growth delayed by celecoxib and the drop of prostaglandin E2 levels (r=0.807); Analysis of variance showed that there was no significant difference in cyclooxygense-2 mRNA among these four groups (P > 0.05). No significant toxic pathological changes of transplanted mouse's important organs were observed. Conclusion: Our results suggest a coordinative repression between celecoxib and radiation in inhibiting human prostate carcinoma xenografts by the anti-tumor and radiation-enhancement, which is safe and effective in some extent and may contribute to enlighten the future study and clinical therapy of

  8. The effect of finasteride and dutasteride on the growth of WPE1-NA22 prostate cancer xenografts in nude mice.

    Directory of Open Access Journals (Sweden)

    Alexander B Opoku-Acheampong

    Full Text Available BACKGROUND: 5α-reductase 1 (5αR1 and 5α-reductase 2 (5αR2 convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. METHODOLOGY/PRINCIPAL FINDINGS: Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet diet groups. Pre- and post-groups began their treatment diets 1-2 weeks prior to or 3 weeks after subcutaneous injection of 1×10⁵ WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. CONCLUSION: The lack of response of WPE1-NA22 prostate cancer cells to androgen

  9. Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP.

    Science.gov (United States)

    Hoffman, Robert M; Bouvet, Michael

    2016-09-28

    We have developed a multi-color, imageable, orthotopic mouse model for individual patients with pancreatic cancer. The tumors are labeled by first passaging them orthotopically through transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP). Passage of the tumors in these colored transgenic mice labels the stromal cells of the tumor. The cancer cells in the PDOX are labeled in situ with GFP by telomerase-dependent adenovirus OBP-401. The models are termed imageable patient-derived orthotopic xenografts (iPDOX). The tumors acquired brightly-fluorescent stromal cells from the transgenic host mice, which were stably associated with the tumors through multiple passages. The colored fluorescent protein-expressing stromal cells included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment. PMID:26742463

  10. Preliminary study on guiding therapy of subcutaneous human hetero graft in nude mice by 211-At labelled monoclonal antibody against gastric cancer

    International Nuclear Information System (INIS)

    In short time, 211At labelled monoclonal antibody 3H11 inhibited the growth of human gastric cancer grafted in nude mice effectively. The most evident inhibition was observed at the 9th day after treatment, and the tumor inhibition rates were 80%, 93%, 48% in the groups of intravenous injection, internal tumor injection (both 211At-3H11 5 μCi per animal), Na211 At (5 μCi per animal) treatment respectively. On the 20th day, when animals were killed, the tumor inhibition rates were 66%, 81%, 6%, respectively. Inhibition treated with Na211At showed obviously lower than those at the 9th day

  11. Effect of melphalan on growth curves and cell cycle distribution of four human small cell carcinomas of the lung grown in nude mice

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L;

    1986-01-01

    Four human small cell carcinomas of the lung grown in nude mice were exposed to melphalan. Two of the tumors were derived from subpopulations isolated by in vitro cloning from the same tumor biopsy. The chemosensitivity of the tumors was determined by calculating the specific growth delay. Drug......-induced changes in the cell cycle were detected by flow cytometric DNA analysis. The specific growth delay of the tumors was very different with the greatest differences between the two subpopulations originating from the same tumor. Melphalan induced a dose-related S phase accumulation in three sensitive tumors...

  12. Effect of 17 beta-oestradiol on growth curves and flow cytometric DNA distribution of two human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Vindeløv, L;

    1983-01-01

    The effect of 17 beta-oestradiol on a "receptor positive" and on a "receptor negative" human breast carcinoma grown in nude mice was studied. Experimental growth data were used to determine the effect on tumour growth. Flow cytometric DNA analysis (FCM) performed on tumour tissue obtained by...... sequential fine-needle aspirations was used to estimate the effect on the cell cycle. In the receptor-positive breast carcinoma, oestradiol induced complete tumour regression and characteristic cell cycle changes. In the receptor-negative breast carcinoma, no changes in tumour growth and cell cycle...

  13. Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice.

    Science.gov (United States)

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-03-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs. PMID:23215868

  14. Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA-peptide in tumor-bearing mice

    International Nuclear Information System (INIS)

    A bifunctional chelating agent, DOTA-Gly3-L-(p-isothiocyanato)-phenylalanine amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer xenografts (HBT 3477) to determine its potential for radioimmunoconjugate therapy. Indium-111 and yttrium-90 were attached to an anti-adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by purification. The unique characteristic of the DOTA-peptide-NCS to form neutral complexes with trivalent metals was utilized to separate the resulting 111In and 90Y radiochelates from excess chelating agent and other anionic by-products resulting from metal impurities. The purified radiochelates were then conjugated to ChL6. The paramacokinetics of 111In- and 90Y-DOTA-peptide-ChL6 were obtained for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results were compared with the pharmacokinetics of 125I-ChL6 obtained in the same mouse model. The whole-body clearance of 125I-ChL6, 90Y-and 111In-DOTA-peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr, respectively. Blood clearances of the three radiopharmaceuticals were biphasic. The radiometal immunoconjugates had greater tumor uptake and slower clearances. Indium-111- and 90Y-DOTA-peptide-ChL6 can be produced at high specific activity with fewer than one chelate per MAb by using a pre-labeling method that permits radiochelate purification by charge selection. Studies in mouse xenografts indicate that tumor uptake in enhanced and a favorable therapeutic index is achieved using these agents. 29 refs., 7 figs., 2 tabs

  15. Effects of Wei Chang An on expression of multiple genes in human gastric cancer grafted onto nude mice

    Institute of Scientific and Technical Information of China (English)

    Ai-Guang Zhao; Ting Li; Sheng-Fu You; Hai-Lei Zhao; Ying Gu; Lai-Di Tang; Jin-Kun Yang

    2008-01-01

    AIM:To investigate the expression of multiple genes in Chinese jianpi herbal recipe Wei Chang An (WCA) in human gastric cancer cell line SGC-7901.METHODS:A human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mice was used as the animal model.The mice were randomly divided into 3 groups,one control and the two representing experimental conditions.Animals in the two experimental groups received either WCA over a 34-d period or 5-fluorouracil (5-FU) over 6-d period starting at 8th d after grafting.Control animals received saline on an identical schedule.Animals were killed 41 d after being grafted.The expression profiles in paired WCA treated gastric cancer samples and the N.S.control samples were studied by using a cDNA array representing 14181 cDNA clusters.The alterations in gene expression levels were confirmed by Real-time Quantitative polymerase chain reaction (qPCR).RESULTS:When compared with controls,the average tumor inhibitory rate in WCA group was 44.32%±5.67% and 5-FU 47.04% 4±11.33% (P<0.01,respectively).The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group.Apoptotic index (AI) was significantly increased to 9.72%±4.51% using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method in WCA group compared with the controls 2.45%±1.37%.5-FU group was also found to have a significantly increased AI compared with the controls.The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively.There were 45 different expressed sequence tags (ESTs) among the control sample pool and WCA sample pool.There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated.By using qPCR,the expression level of Stat3,rap2 interacting protein x (RIPX),regulator of differentiation 1 (ROD1) and Bcl-2 was lower in WCA group than that in control

  16. Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    汤亭亭; 徐小良; 戴尅戎; 郁朝锋; 岳冰; 楼觉人

    2005-01-01

    Objective: To evaluate the osteogenic potential of bone morphogenetic protein (BMP)-2 gene transfected goat bone marrow-derived mesenchymal stem cells (MSCs). Methods: Goat bone marrow- derived MSCs were transfected by Adv-human bone morphogenetic protein (hBMP)-2 gene(Group 1), Adv-beta gal transfected MSCs (Group 2)and uninfected MSCs(Group 3). Western blot analysis, alkaline phosphatase staining, Von Kossa staining and transmission electron microscopy were adopted to determine the phenotype of MSCs. Then the cells were injected into thigh muscles of the nude mice. Radiographical and histological evaluations were performed at different intervals. Results: Only Adv-hBMP-2 transfected MSCs produced hBMP-2. These cells were positive for alkaline phosphatase staining at the 12th day and were positive for Von Kossa staining at the 16th day after gene transfer. Electron microscopic observation showed that there were more rough endoplasmic reticulum, mitochondria and lysosomes in Adv-hBMP-2 transfected MSCs compared to MSCs of other two groups. At the 3rd and 6th weeks after cell injection, ectopic bones were observed in muscles of nude mice of Group 1. Only fibrous tissue or a little bone was found in other two groups. Conclusions: BMP-2 gene transfected MSCs can differentiate into osteoblasts in vitro and induce bone formation in vivo.

  17. Qualitative and semi quantitative analysis in the healing area of athymic nude mice skin engrafted with human skin sterilized with gamma radiation

    International Nuclear Information System (INIS)

    In recent decades there has been a great interest in the radio-sterilized grafts for human skin grafts. This tissue is taken from a cadaver or multi-organ donor and samples are processed and stored in glycerol at concentrations above 85%. Although this procedure is carried out under aseptic conditions, after the final packaging one can sterilize the tissues with ionizing radiation in order to increase the safety level of sterility. The purpose of this study was to evaluate the behavior of the healing repair process that occurs between the graft and the skin of athymic NUDE mice. The samples of human skin treated with glycerol were divided into three groups: the control group 1 (non-irradiated), irradiated group 2 at 25 kGy and irradiated group 3, at 50 kGy. These tissues were grafted onto athymic NUDE mice which were sacrificed after 3, 7 and 21 days. After the sacrifice, part of the back fur of the animals containing human skin graft was removed with hematoxylin and eosin (H/E). The histological sections were analyzed for the integrity of tissue, presence and location of keratinocytes, fibroblasts, defense cells and blood vessels. Thus it was examined whether over time the graft was incorporated into the body or if there was a process of healing by secondary intention. (author)

  18. Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Otani, Sanae [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ayata, Minoru, E-mail: maverick@med.osaka-cu.ac.jp [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Takeuchi, Kaoru [Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki (Japan); Takeda, Makoto [Department of Virology 3, National Institute of Infectious Diseases, Tokyo (Japan); Shintaku, Haruo [Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ogura, Hisashi [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan)

    2014-08-15

    Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

  19. Qualitative and semi quantitative analysis in the healing area of athymic nude mice skin engrafted with human skin sterilized with gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Jurandir Tomaz de; Bringel, Fabiana; Alves, Nelson Mendes; Antebi, Uri; Funari, Ana Paula; Mathor, Monica B., E-mail: tomaz_ju@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    In recent decades there has been a great interest in the radio-sterilized grafts for human skin grafts. This tissue is taken from a cadaver or multi-organ donor and samples are processed and stored in glycerol at concentrations above 85%. Although this procedure is carried out under aseptic conditions, after the final packaging one can sterilize the tissues with ionizing radiation in order to increase the safety level of sterility. The purpose of this study was to evaluate the behavior of the healing repair process that occurs between the graft and the skin of athymic NUDE mice. The samples of human skin treated with glycerol were divided into three groups: the control group 1 (non-irradiated), irradiated group 2 at 25 kGy and irradiated group 3, at 50 kGy. These tissues were grafted onto athymic NUDE mice which were sacrificed after 3, 7 and 21 days. After the sacrifice, part of the back fur of the animals containing human skin graft was removed with hematoxylin and eosin (H/E). The histological sections were analyzed for the integrity of tissue, presence and location of keratinocytes, fibroblasts, defense cells and blood vessels. Thus it was examined whether over time the graft was incorporated into the body or if there was a process of healing by secondary intention. (author)

  20. Inhibitory effect of parvovirus H—1 on the formation of colonies of human hepatoma cell line in vitro and its tumors in nude mice

    Institute of Scientific and Technical Information of China (English)

    YANSHANGJUN; CHENGWUMA; 等

    1994-01-01

    The inhibitory effect of parvovirus H-1 on the colonyforming ability.in vitro of QGY-7703,a cultured human hepatoma cell line,and on the formation and growth of its tumors in nude mice was studied.With higher multiplicity of infection(MOI) of H-1 given,survival of the QGY-7703 cells was found to be decreased.H-1 DNA amplification level at 30h postinfection(p.i.) was detected to be 7.4 times higher than that at 2h by dispersed cells assay,while the cells were delayed to enter into S phase.Plaques were formed in the indicator cells(new-born human kidney cell line,NBK) by progeny H-1 virus particles released from the infected QGY-7703 cells by infectious cell center assay.The formation of tumors in nude mice by QGY-7703 cells which were injected s c at 2h postinfection was observed to by prevented in 2 proups with given MOI 25 and 50.The tumor growth of MOI 10 group occurred at a lower exponential rate than that of control,after a 20d latent period.It was evident that parvovirus H-1 exhibited a direct inhibitory effect on the formation and growth of human hepatoma cells in vivo as well as in vitro.

  1. 不同化疗方案对MCF-7乳腺癌荷瘤裸鼠的抑瘤作用及对PCNA表达的影响%The effects of various chemotherapy regimens on the expression of PCNA and human breast cancer xenograft (MCF-7) transplanted in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xenograft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the value of PCNA as predictive factor for the response of chemotherapy and individualized treatment. Methods: (1) 88 nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control group and 10 chemotherapy groups (each group, n = 8). Among them, the mice of 5 chemotherapy groups were treated intraperitoneally/orally by 5 combination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at 1/3 LD10 dosage schedule (dose lethal to 10%of the mice), and that in another 5 chemotherapy groups were treated at 2/3 LD10 dosage schedule. Control animals were administered intraperitoneally with normal saline. (2) The body weight of nude mice and transplanted tumor growth were observed and recorded, then inhibition rate of tumor growth was calculated. (3) The pathological features of transplanted tumor were studied under microscope. The expression of proliferating cell nuclear antigen (PCNA) was comparatively studied in chemotherapy group and control group by SP immunohistochemical method and flow cytometry analysis. Results: (1) Body weight, tumor weight and inhibition rate of tumor growth of athymic mice bearing cancer: Body weights and tumor weights of nude mice in every 2/3 LD10 chemotherapy group were significantly lower than those of the control group (P < 0.05), and the inhibition rates of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. Body weights of athymic mice in every 1/3 LD10 chemotherapy group were lower than that of the control (P < 0.05). The results showed that the 2/3 LD10chemotherapy groups could reflect the effect of combination chemotherapy on the nude mice and the clinical dependability was better. So the data of 2/3 LD10 chemotherapy groups were appropriated

  2. Endostar combined with cryoablation for subcutaneous xenografted tumor model of lung adenocarcinoma cell line A549 in BALB/c nude mice: an experimental study

    International Nuclear Information System (INIS)

    Objective: To investigate the inhibitory effect of Endostar combined with cryoablation on Lung adenocarcinoma cell line A549 in BALB/c nude mice, and to discuss its interaction mechanisms. Methods: The lung adenocarcinoma A549 model in BALB/c nude mice were established. When the largest diameter of tumor reached 1.0 cm, a total of 24 mice were randomly and equally divided into 4 groups: control group, Endostar group, cryoablation group and cryoablation plus Endostar group. The largest diameter and the vertical diameter of the tumors were measured at different points of time after treatment. At the 21st day, the mice were sacrificed and the tumors were removed and the rate of tumor cell apoptosis, the microvessel density (MVD) and the expression level of vascular endothelial growth factor (VEGF) were determined by using immunohistochemistry method. The results were statistically analyzed. Results: The tumor growth velocity of the control group, Endostar group, cryoablation group and cryoablation plus Endostar group was (2.36.68±51.23)%, (220.02±30.61)%, (159.46±29.33)% and (103.34±25.50)%, respectively (P<0.01). The rate of apoptosis of the four groups was (21.67±2.34)%, (22.17±1.47)%, (38.33±1.37)% and (49.17±1.72)%, respectively (P<0.01). The MVD and the expression levels of VEGF of the cryoablation plus Endostar group were significantly lower than those of the other three groups (P<0.01). Statistical analysis revealed that a positive correlation existed between the express of VEGF and MVD. Conclusion: Endostar can obviously enhance the therapeutic efficacy of cryoablation on lung adenocarcinoma A549 in BALB/c nude mice. The underlying mechanisms may be the Endostar-inhibited angiogenesis through down-regulating the expression of VEGF, and the cooperative effect of Endostar and cryoablation on the promotion of tumor cell apoptosis. (authors)

  3. Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice

    DEFF Research Database (Denmark)

    Kragh, M; Spang-Thomsen, M; Kristjansen, P E

    1999-01-01

    , 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i......We examined the effect of the anti-angiogenic compound TNP-470 on early tumor growth characteristics following subcutaneous implantation of 1 mm3 tissue blocks of human glioblastoma U87, in nude mice. The mice received daily injections with TNP-470, 7 mg/kg, from one day before until either 3, 7......) the onset of growth of U87 xenografts was effectively inhibited by concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose...

  4. Molecular imaging of human breast cancer xenografts in nude mice by epidermal growth factor labelled by near infrared fluorescent dye

    International Nuclear Information System (INIS)

    Objective: This work was to determine the feasibility of using epidermal growth factor (EGF) labeled with a near-infrared fluorescent (NIRF) dye (Cy5.5) to selectively localize and image epidermal growth factor receptor (EGFR)of the human breast cancer. Methods: MDA-MB-231 of human mammary adenocarcinoma and MDA-MB-435S of human mammary ductal carcinoma were detected using a flow cytometry. Laser confocal microscopy was used to examine the intake of EGF-Cy5.5 by MDA-MB-231 and MDA-MB-435S cells. MDA-MB-231 and MDA-MB435S human breast cancer orthotopic xenograft nude mice models were established. In vivo NIRF imaging was acquired after intravenous injection of EGF-Cy5.5 (1 nmol/0.2 ml)immediately and different time intervals. The up-take of EGF-Cy5.5 in MDA-MB-231 and MDA-MB-435S was detected using ROI technique. The blockage of the monocolonal antibody C225 to the EGF-Cy5.5 uptake were observed in viovo and ex vivo. Ex vivo tumor tissue fluorescent imaging was executed and the histological sections were stained by HE method for pathobiology assay. Student t test was used for statistical analysis with SPSS for Windows. Results: Flow cytometry indicated the EGFR expression percentage of MDA-MB-231 was 41.96% and the percentage of MDA-MB-435S was 0.12%. The fluorescence showed that the uptake of EGF-Cy5.5 by MDA-MB-231 cells could be observed by the laser confocal microscopy. There was no specific uptake of EGF-Cy5.5 by MDA-MB-435S. In vivo NIRF images showed mean fluorescence intensity in MDA-MB-231 tumors was (38 220±3 144)au, which was significantly higher than MDA-MB435S's ( 11 885 + 1 144 ) au (t = 17. 600, P < 0.01) or normal region' s (11 980 ±1 496) au(t=17. 491, P<0.01) at 24 h postinjection of EGF-Cy5.5. The mean fluorescence intensity was significantly reduced in MDA-MB-231 group with preadministration of C225, whose mean intensity was (10 472±842) au (t=16.772, P<0.01), while the mean intensity was not apparently decreased in MDA-MB-435S block group

  5. Nude mice multi-drug resistance model of orthotopic transplantation of liver neoplasm and Tc-99m MIBI SPECT on p-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Yu Han; Xiao-Ping Chen; Zhi-Yong Huang; Hong Zhu

    2005-01-01

    AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy.METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected subdermally to form the tumorsupplying mice. The orthotopic drug-resistant tumors were formed by implanting the tumor bits under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and visual inspection were used to examine tumor progression. RT-PCR and immunohistochemistry wereused to detect expression of mdr1 mRNA and its encodedprotein p-glycoprotein (p-gp). Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 20 min after injection, and the liver/heart ratios werecalculated.RESULTS: Post-implantation mortality was 0% (0/25),tumor implantation success was 90% (22/25), and the rate of implanting successfully for the second time was 100% (3/3). Tumor induction using Pharmorubicin was 80% (16/20). The mdr1 mRNA expression of the induced group was 23 times higher than that of the control group, and p-gp protein expression was 13-fold higher compared to the control group. The liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased significantly in the induced group as compared to the control group. CONCLUSION: We have established an in vivo model of mdr1 in nude mice by orthotopic transplantation of liver neoplasm coupled to chemotherapy. We propose that identification of drug resistance as characterized by decreased 99mTc-ppm radiography due to enhanced clearance by p-gp may be useful in detecting in vivo drug resistance, as well as a useful tool in designing more effective therapies.

  6. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    International Nuclear Information System (INIS)

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm3, mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

  7. Radiosensitizing effects of 9401 on mice bearing H22 hepatoma

    International Nuclear Information System (INIS)

    Objective: To investigate the radiosensitizing effects of 9401 on mice bearing H22 hepatoma. Methods: Mouse model bearing H22 hepatoma cells were established. Mice were randomly divided into six groups, the control group,the radiation group and four treatment groups including 9401 at high, medium and low dosages and nicotinamide combined with radiation. After irradiated, the growth of tumor was observed, the time of tumor growth was recorded, the delay time of tumor growth and enhancement factor (EF) were calculated. After 28 days, the mice were killed, the tumors were stripped and inhibition rate was calculated. Results: Groups of 9401 combined with radiation could postpone tumor growth. The difference was statistically significant between 9401 groups at high, medium dosages combined with radiation and nicotinamide combined with radiation group (t=24.7 and 7.5, both P<0.01). Compared with radiation alone group, groups of 9401 combined with radiation had significant radiosensitizing effect. The enhancement factor of 9401 combined with radiation groups at high and medium dosages were 2.13 and 1.73 respectively, they were significant higher than nicotinamide combined with radiation group (t=2.26 and 9.04, both P<0.05). The inhibition rate of 9401 groups at high, medium and low dosages combined with radiation were 64.5%, 50.9% and 42.6% respectively. The inhibition rate of nicotinamide group combined radiation was 53.2%. The inhibition rate of 9401 at high dosage combined with radiation had significant difference with nicotinamide combined radiation (t =2.8, P<0.05). Nicotinamide combined with radiation group, 9401 combined with radiation groups could significant inhibit the growth of tumors compared with radiation alone group (t=5.7, 4.0 and 2.2, all P<0.05). Conclusion: 9401 can inhibit the tumor growth and the inhibition effect increases gradually with the drug dose increasing. It also has radiosensitizing effects on mice bearing H22 hepatoma and present broadly

  8. [11C]Sorafenib: Radiosynthesis and preclinical evaluation in tumor-bearing mice of a new TKI-PET tracer

    International Nuclear Information System (INIS)

    Introduction: Tyrosine kinase inhibitors (TKIs) like sorafenib are important anticancer therapeutics with thus far limited treatment response rates in cancer patients. Positron emission tomography (PET) could provide the means for selection of patients who might benefit from TKI treatment, if suitable PET tracers would be available. The aim of this study was to radiolabel sorafenib (1) with carbon-11 and to evaluate its potential as TKI-PET tracer in vivo. Methods: Synthetic methods were developed in which sorafenib was labeled at two different positions, followed by a metabolite analysis in rats and a PET imaging study in tumor-bearing mice. Results: [methyl-11C]-1 and [urea-11C]-1 were synthesized in yields of 59% and 53%, respectively, with a purity of > 99%. The identity of the products was confirmed by coinjection on HPLC with reference sorafenib. In an in vivo metabolite analysis [11C]sorafenib proved to be stable. The percentage of intact product in blood–plasma after 45 min was 90% for [methyl-11C]-1 and 96% for [urea-11C]-1, respectively. Due to the more reliable synthesis, further research regarding PET imaging was performed with [methyl-11C]-1 in nude mice bearing FaDu (head and neck cancer), MDA-MB-231 (breast cancer) or RXF393 (renal cancer) xenografts. Highest tracer accumulation at a level of 2.52 ± 0.33 %ID/g was observed in RXF393, a xenograft line extensively expressing the sorafenib target antigen Raf-1 as assessed by immunohistochemistry. Conclusion: In conclusion, we have synthesized [11C]sorafenib as PET tracer, which is stable in vivo and has the capability to be used as PET tracer for imaging in tumor-bearing mice

  9. New Insights in Tissue Distribution, Metabolism, and Excretion of [3H]-Labeled Antibody Maytansinoid Conjugates in Female Tumor-Bearing Nude Rats.

    Science.gov (United States)

    Walles, Markus; Rudolph, Bettina; Wolf, Thierry; Bourgailh, Julien; Suetterlin, Martina; Moenius, Thomas; Peraus, Gisela; Heudi, Olivier; Elbast, Walid; Lanshoeft, Christian; Bilic, Sanela

    2016-07-01

    For antibody drug conjugates (ADCs), the fate of the cytotoxic payload in vivo needs to be well understood to mitigate toxicity risks and properly design the first in-patient studies. Therefore, a distribution, metabolism, and excretion (DME) study with a radiolabeled rat cross-reactive ADC ([(3)H]DM1-LNL897) targeting the P-cadherin receptor was conducted in female tumor-bearing nude rats. Although multiple components [total radioactivity, conjugated ADC, total ADC, emtansine (DM1) payload, and catabolites] needed to be monitored with different technologies (liquid scintillation counting, liquid chromatography/mass spectrometry, enzyme-linked immunosorbent assay, and size exclusion chromatography), the pharmacokinetic data were nearly superimposable with the various techniques. [(3)H]DM1-LNL897 was cleared with half-lives of 51-62 hours and LNL897-related radioactivity showed a minor extent of tissue distribution. The highest tissue concentrations of [(3)H]DM1-LNL897-related radioactivity were measured in tumor. Complimentary liquid extraction surface analysis coupled to micro-liquid chromatography-tandem mass spectrometry data proved that the lysine (LYS)-4(maleimidylmethyl) cyclohexane-1-carboxylate-DM1 (LYS-MCC-DM1) catabolite was the only detectable component distributed evenly in the tumor and liver tissue. The mass balance was complete with up to 13.8% ± 0.482% of the administered radioactivity remaining in carcass 168 hours postdose. LNL897-derived radioactivity was mainly excreted via feces (84.5% ± 3.12%) and through urine only to a minor extent (4.15% ± 0.462%). In serum, the major part of radioactivity could be attributed to ADC, while small molecule disposition products were the predominant species in excreta. We show that there is a difference in metabolite profiles depending on which derivatization methods for DM1 were applied. Besides previously published results on LYS-MCC-DM1 and MCC-DM1, maysine and a cysteine conjugate of DM1 could be

  10. Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-mian; YANG Xiao-yun; DENG Shu-hai; XU Wei; GAO Hai-qing

    2007-01-01

    Background Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide(DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.Methods DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n=29) were divided into 4 groups: normal saline(NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P<0.05) without causing weight loss (P>0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice

  11. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    International Nuclear Information System (INIS)

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 μg CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n,α)7Li reaction

  12. Suppression of the growth of human colorectal carcinoma cells (LS174T) by radiolabeled monoclonal antibody (131I-MAbC27) in tissue culture and nude mice

    International Nuclear Information System (INIS)

    A monoclonal antibody against carcinoembryonic antigen (CEA), MAbC27, and its F(ab')2 fragments were prepared and labeled with 131I. They effectively suppressed the growth of a human colorectal carcinoma cell line, LS174T, both in culture medium and in inoculated nude mice, whereas 131I-labeled normal mouse immunoglobulin or 131I itself did not have similar effects. Intravenous injection of 131I-MAbC27 or 131I-MAbF(ab')2 following inoculation of carcinoma cells suppressed their growth in vivo. The suppression effect was even more effective when intact antibody rather than its F(ab')2 fragments was used, especially when the treatment was repeated. This study indicates that radiolabeled MAbC27 may be used as a therapeutic agent in CEA-secreting human colorectal carcinomas

  13. Dissemination in athymic nude mice of lacZ transfected small cell lung cancer cells identified by X-gal staining

    DEFF Research Database (Denmark)

    Rømer, M U; Christiansen, J; Brünner, N;

    1995-01-01

    with the chromogenic substrate X-gal. lacZ expressing cells were investigated after subcutaneous (s.c.) inoculation and intravenous (i.v.) injection. The X-gal detection of beta-D-galactosidase activity proved to be a rapid and easy means for specific and highly sensitive identification of metastases. All primary s.......c. tumors stained by X-gal. The primary tumors of GLC-2 regularly demonstrated local invasive growth and produced multiple metastases in several organs. In contrast, primary DMS 456 tumors only occasionally demonstrated local invasion and very rarely generated secondary foci. No experimental metastases were......The small cell lung cancer cell lines GLC-2 and DMS 456 were genetically labeled with the lacZ gene and examined for invasive and metastatic potential in META/Bom nude mice. The lacZ gene encodes the enzyme beta-D- galactosidase, and cells expressing this enzyme were identified by staining...

  14. The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. Results: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p pot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen

  15. Anti-tumor effect of RNA interference silencing survivin gene combined with X-ray irradiation on human hepatoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Objective: To investigate the anti-tumor effect of RNA interference silencing Survivin gene combined with X-ray irradiation on human hepatoma xenograft in nude mice. Methods: siRNA expression plasmids targeting Survivin genes packed by liposome were injected into human hepatoma xenograft which were irradiated with 5 Gy X-ray later. Tumor volumes at different time points and mean survival period of mice were observed. Expression level of Survivin, PCNA and intratumoral microvessel density were detected by Immunohistochemical staining. Apoptotic cells in tumor tissue were detected by TUNEL method. Results: Tumor volumes of pGenesil-survivin+5 Gy group were significantly lower than those of the control, pGenesil-survivin and 5 Gy groups 3 ∼ 21 days after the beginning of therapy. Mean survival period of mice in pGenesil-survivin+5 Gy group was the longest. Expression level of PCNA and intratumoral microvessel density in pGenesil-survivin+5 Gy group were significantly lower than those of pGenesil-survivin group and radiotherapy group 1 day after therapy. Percentage of apoptotic cells in tumor tissue in pGenesil-survivin+5 Gy group was significantly higher than other groups. Conclusion: RNA interference silencing Survivin gene combined with radiotherapy could effectively inhibit cell proliferation and tumor angiogenesis, enhance apoptosis in tumor xenograft and its anti-tumor effect was more powerful than that of radiotherapy or RNA interference silencing Survivin gene. (authors)

  16. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    International Nuclear Information System (INIS)

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX

  17. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  18. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: mfhsieh@cycu.edu.tw [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)

    2010-12-28

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

  19. Effect of Spleen Lymphocytes on the Splenomegaly in Hepatocellular Carcinoma-bearing Mice

    Institute of Scientific and Technical Information of China (English)

    FANG Jing Jing; ZHU Zhen Yuan; DONG Hui; ZHENG Guo Qiang; TENG An Guo; LIU An Jun

    2014-01-01

    Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of IL-2 were measured, and two-dimensional gel electrophoresis (2-DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3+ T lymphocytes and CD8+ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.

  20. Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice%重组人生长激素联合氟尿嘧啶对人胃癌裸小鼠皮下移植瘤作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    Fangfang Shi; Suyi Li

    2007-01-01

    Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neoplasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stomach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5-FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index(PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

  1. Tumor penetration with intact MAb and fragments demonstrated in vitro on tumor spheroids and in vivo in the nude mouse model

    International Nuclear Information System (INIS)

    Tumor spheroids grown in culture represent a good in vitro model for the study of tumor penetration phenomena of potential radiotherapeutics. Using this system, it was found that Fab-fragments penetrate tumors more quickly and deeply than complete antibodies. These results were confirmed in tumor bearing nephrectomized nude mice

  2. Effect of Paris Saponin on Antitumor and Immune Function in U14 Tumor-Bearing Mice

    OpenAIRE

    GuangLie, Chen; WeiShi, Gao; GaiLing, Hou; Jianping, Cao

    2013-01-01

    We evaluated the effect of Paris saponin on inhibition of cervical cancer in mice and on immune regulation in tumor-bearing mice. MTT assay was used to examine the effect of Paris saponin on U14 cell proliferatiosn in vitro; the ascites tumor model of U14 cervical cancer was established to observe the effect of Paris saponin on inhibition of the tumor and on survival time of mice; and serum IL-4 and IFN-γ levels in tumor-bearing mice were detected. The Paris saponin showed significant inhibit...

  3. 蜂毒素对胃癌SGC-7901细胞裸鼠移植瘤的抑制作用及其部分机制%Study of melittin on tumor inhibition and partial mechanism of human gastric cancer SGC-7901 cell xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    楼蓉; 李俊; 吕雄文; 金涌; 赵斌; 吴宝明; 任丹阳; 王亚丽

    2011-01-01

    目的 研究蜂毒素对人胃癌SGC-7901细胞裸鼠移植瘤的抑制作用,并初步探讨其作用机制.方法 建立人胃癌SGC-7901细胞裸鼠移植瘤模型,采用抑瘤率指标评价蜂毒素对荷瘤小鼠的抑瘤作用,采用脏器指数、中性红法测定腹腔巨噬细胞吞噬功能,改良的四甲基偶氮唑盐(MTT)比色法检测自然杀伤(NK)细胞活性,ELISA法测定血清白介素2(IL-2)的含量,观察机体免疫变化情况.结果 蜂毒素(2、4 mg/kg)能抑制荷瘤小鼠的肿瘤生长,提高脾脏指数,增强腹腔巨噬细胞吞噬功能和NK细胞的活性,蜂毒素(4 mg/kg)能增加血清中IL-2的含量.结论 蜂毒素对荷瘤小鼠具有较强的抑瘤作用,可能与其提高机体免疫功能有关.%Objective To explore the effects and mechanism of melittin on tumor growth of human gastric cancer SGC-7901 cell xenografts in nude mice. Methods The xenografts derived from SGC-7901 cells were established in nude mice. The effect of melittin on tumor-bearing mice was evaluated by inhibition rate. Phagocytosis of peritoneal macrophage was measured by neutral red method. NK cell activity was detected by improved MTT assay. Concent of interleukin-2 ( IL-2 ) in serum was determined by ELISA method. The changes of immunity of tumor-bearing mice were observed by above-mentioned and organ index. Results Melittin ( 2, 4 mg/kg) could inhibit the tumor growth, while improve the index of spleen, enhance phagocytosis of peritoneal macrophage and NK cell activity, and melittin ( 4 mg/kg ) could increase IL-2 level in serum. Conclusion Melittin has significant inhibition on tumor-bearing mice, which is related to reinforcing the immunity of mice.

  4. Effects of low dose radiation on antioxidant enzymes after radiotherapy of tumor-bearing mice

    International Nuclear Information System (INIS)

    Objective: To search for effects of low dose radiation on the activities of antioxidant enzymes after radiotherapy of tumor-bearing mice. Methods: Superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) were all determined by chemical colorimetry. Results: Low dose radiation increase the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) in serum of tumor-bearing mice more markedly than those in the unirradiated controls. The activities of antioxidant enzymes SOD, GST, CAT in serum of tumor-bearing mice (d5, d3) irradiated with 5cGy 6h before 2.0 Gy radiation are obviously higher than those of the group (c3, c5) given with radiotherapy only. Conclusion: The increase in the activities of antioxidant enzymes in serum of tumor-bearing mice triggered by low dose radiation could partly contribute to the protective mechanism. (authors)

  5. Comparative study of intact A7 MoAb and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice

    International Nuclear Information System (INIS)

    Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab')2 fragments were studied in human colon cancer (LS-174T)-bearing nude mouse. First of all, we examined the yield and the immunoreactivity of F(ab')2 fragments after treatment with ficin as a function of time. The yield of F(ab')2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab')2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab')2 was preferentially taken up by the tumor, was cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. In addition, the tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy. (author)

  6. Effects of 125I-Labeled Peptide Nuclear Acid Targeting Ki67 on the Growth of Implanted Human Renal Cell Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    JiacunChen; JunnianZheng; SongWu; HaibiaoLai; XiaoqingSun; JunjieLiu

    2004-01-01

    OBJECTIVE To investigate the potential of 125I-labeled anti-sense peptide nucleic acids (125I-AS-PNAs) to inhibit the expression of the Ki-67 gene and growth of implanted human renal carcinoma cells in nude mice.METHODS Anti-sense peptide nucleic acids (AS-PNAs) targeting the Ki67 gene were synthesized and labeled with 125I by the Chloraseptine-T method. Drugs including PNAs and 125I-AS-PNAs capsulated by cationic lipid were directly injected into tumors in nude mice. The Ki67 expression in tumors was detected by an immunohistochemical technique and Western blot. The apoptosis of tumor cells was detected by a TUNEL assay. Tumor volumes were measured every 3 days and tumor suppression rates were calculated at 12 days after treatment. Control groups were treated with AS-PNA, MMPNAs (mismatch PNAs) and 125I-Na.RESULTS The Ki67 expression rate of tumors treated by 125I-AS-PNAs [(15.3±1.8)%] was lower than that treated by AS-PNAs [(23.0±2.4)%] (P<0.01). The Ki67 protein production rate of tumors treated by 125I-AS-PNAs [(43.6±3.5)%] was lower than that treated by AS-PNAs [(59.7±2.3)%] (P<0.01 ). The apoptosis rate of tumors treated by 125I-AS-PNAs [(40.3±2.4)%] was higher than that treated by AS-PNAs [(31.1 ±2.0)%] (P<0.01). The volume of tumors treated by 125I-AS-PNAs [(330.4±57.8) mm3 ]was smallerthan that treated by AS- PNAs [(513.2±64.2 ) mm3] (P<0.01 ).CONCLUSION 125I-AS-PNAs targeted against the Ki67 gene have a greater inhibitory effect on the expression of the Ki67 gene and a larger apoptotic action on human renal carcinoma cells and can more efficiently inhibit tumor growth than AS-PNAs. 125I-AS-PNAs targeting the Ki67 gene may be a promising anti-sense/anti-gene radiotherapy method for treating renal cell carcinoma.

  7. Preliminary study of MR diffusion weighted imaging in nude mice models of hepatic Bel7402 tumors after adenovirus-mediated cytosine diaminase-thymidine kinase gene therapy

    International Nuclear Information System (INIS)

    Objective: To study the characteristics of DWI in nude mice models of hepatic Bel7402 tumors after treatment with adenovirus-mediated cytosine diaminase-thymidine kinase (Ad. CD-TK) double suicide gene therapy, and then to identify whether DWI can be used for assessing curative effect of postoperative tumors. Methods: Thirty nude mice models of hepatic Bel7402 tumors were successfully created using cell suspension method, after the tumor grew to more than 1 cm in diameter, 20 tumor models were treated by intratumoral administration of Ad. CD-TK for 3 days plus intraperitonea (i.p.) treatment with 5-Fc and GCV for the duration of the study.Then they were randomly divided into three groups during 5-Fc and GCV treatment. The remaining 10 tumor models were used as controls. MR scanning were performed in 10th day before and after tumor implantation in all models by using EPI-SE series and SENSE technology for treatment group. Tumor volumes and ADC values were calculated pretreatment and posttreatment. Cell apoptosis were determined by using TUNEL method. Analyze the change of ADC and apoptosis index (AI) in different times, t test was used for comparison the difference of AI and ADC values respectively. Results: After 10 days,the tumor volumes of the treatment groups and controls were respectively (724.16 ±57.45) mm3, (754.57 ± 66.84) mm3, with no significant difference (t=0.488, P >0.05). The ADC values of the treatment groups were (0.98 ±0.11) × 10-3 mm2/s,the ones of the control groups were (0.68 ±0.04) × 10-3 mm2/s; AI of the treatment groups were (23.25 ±6.57)%, the ones of the control groups were (2.57 ± 0.58)%. There were difference in both groups (t=4.473, 5.874; P<0.01). Conclusion: DWI can be effectively to monitor the early pathological changes of hepatic Bel7402 tumors after Ad. CD-TK double suicide gene therapy, and provide experimental evidences for clinical application. (authors)

  8. Anti-tumor effect of silencing HIF-1α and survivin genes combined with radiotherapy on human hepatoma xenograft in nude mice

    International Nuclear Information System (INIS)

    In order to investigate the anti-tumor effect of RNA interference silencing HIF-1α and survivin genes combined with X-rays irradiation on human hepatoma xenograft in nude mice, siRNA expression plasmids targeting HIF-1α and/or survivin genes packed by liposome were injected into human hepatoma xenograft which were irradiated with 5 Gy X-rays later. Tumor volumes and mean survival period of mice at different time points were observed. Expression level of HIF-1α, survivin, PCNA and intratumoral microvessel density was detected by Immunohisto-chemical staining respectively. Apoptotic cells in tumor tissue were detected by TUNEL method. The results showed that tumor volumes of pGenesil-survivin-HIF+5 Gy group were significantly lower than that of pGene-sil-survivin+5 Gy group and pGenesil-HIF+5 Gy group on the 9th-21th day after the beginning of therapy. Mean survival period of mice in pGenesil-survivin-HIF+5 Gy group was the longest. Expression level of HIF-1α, survivin, PCNA and intratumoral microvessel density in pGenesil-survivin-HIF+5 Gy group were significantly lower than that of the control group and the radiotherapy group on the 1st day after therapy. Percentage of apoptotic cells in tumor tissue in pGenesil-survivin-HIF+5 Gy group was significantly higher than that in the other groups. These results suggested that RNA interference silencing HIF-1α and survivin genes combined with radiotherapy could effectively inhibit cell proliferation and tumor angiogenesis and enhance apoptosis in tumor xenograft. Its anti-tumor effect was more powerful than that of radiotherapy, RNA interference silencing HIF-1α or survivin gene combined with radiotherapy respectively. (authors)

  9. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M; Rygaard, J

    2006-01-01

    BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also...

  10. Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy.SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

  11. Biodistribution of the novel anticancer drug sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] KP-1339/IT139 in nude BALB/c mice and implications on its mode of action.

    Science.gov (United States)

    Bytzek, Anna K; Koellensperger, Gunda; Keppler, Bernhard K; G Hartinger, Christian

    2016-07-01

    The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP-1339/IT139) has entered clinical trials as the more soluble alternative to the indazolium compound KP1019. In order to get insight into its distribution and accumulation throughout a living organism, KP-1339/IT139 was administered intravenously in non-tumor bearing nude BALB/c mice and the Ru content in blood cells and plasma, bone, brain, colon, kidneys, liver, lung, muscle, spleen, stomach and thymus was determined at several time points. The Ru concentration in blood cells and plasma was found to increase slightly within the first hours of analysis, with the Ru concentration being 3-times higher in plasma compared to blood cells. The plasma samples were subjected to analysis by capillary zone electrophoresis (CZE) and size exclusion/anion exchange chromatography (SEC-IC) both coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and a large majority of the total Ru content was found attached to mouse serum albumin (MSA), confirming similar behavior to KP1019 in an in vivo setting. Within 1h, the peak ratio of approximately 1.2-1.5 Ru per albumin molecule was reached which declined to about 1 Ru per albumin molecule within 24h. Beside the MSA adduct a higher molecular weight species was observed probably stemming from MSA conjugates. In addition, the tissue samples were mineralized by microwave digestion and analyzed for their Ru content. The highest Ru levels were found in colon, lung, liver, kidney and notably in the thymus. The peak Ru concentrations in these tissues were reached 1-6h after administration and declined slowly over time. PMID:26993078

  12. Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice

    International Nuclear Information System (INIS)

    In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v

  13. ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties

    Institute of Scientific and Technical Information of China (English)

    Fang Wang; Yong-Ju Liang; Xing-Ping Wu; Xiao-Dong Su; Li-Wu Fu

    2012-01-01

    S1-M1-80 cells,derived from human colon carcinoma S1 cells,are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance (MDR).In this study,S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo.Our results showed that the proliferation,cell cycle,and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells).Consistently,xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan,but remained sensitive to the non-ABCG2 substrate cisplatin.Furthermore,the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan.These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks.Thus,this model could serve as a good system for further investigation of ABCG2-mediated MDR.

  14. Effect of tamoxifen on the receptor-positive T61 and the receptor-negative T60 human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Vindeløv, L;

    1985-01-01

    A study was made of the in vivo effect of the anti-oestrogen tamoxifen on the growth and cell cycle kinetics of the oestrogen and progesterone receptor-positive T61 human breast carcinoma and of the oestrogen and progesterone receptor-negative T60 human breast carcinoma grown in nude mice. The T61...... tumour was exposed to single doses of 0.1, 1.0, 5 or 10 mg tamoxifen, resulting in serum concentrations 1 day after treatment ranging from less than 27 to 134 nM. The T60 tumour was exposed to a single dose of 1.0 mg tamoxifen. The effect on the tumour growth curves was determined according to a...... transformed Gompertz function, and the effect on the cell cycle distributions was estimated by flow cytometric DNA analysis on tumour tissue obtained by fine-needle aspirations at intervals after the treatment. The results showed that in the T61 tumour, tamoxifen induced a dose-related growth inhibition...

  15. Topical administration of Tetrasodium-Mesotetraphenyl-Porphinesulfonate (TPPS): correlations between drug penetration and depth of necrosis in skin of nude mice following red light irradiation

    International Nuclear Information System (INIS)

    The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. The photosensitizing properties of a 2% solution of TPPS (Tetrasodium-Tetraphenylpophinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice has been tested. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after applications. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS applications, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this methodology need further investigation

  16. Inhibition of human tumor xenograft growth in nude mice by a conjugate of monoclonal antibody LA22 to epidermal growth factor receptor with anti-tumor antibiotics mitomycin C

    International Nuclear Information System (INIS)

    Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22-MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively. Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both showed that 125I-labeled-LA22-MMC enriched in tumor sites prominently. Most importantly, in vivo assays showed LA22-MMC was significantly more effective than free drug MMC in the treatment of subcutaneous xenografts of human A431 cells in nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22-MMC could be a very potent drug for treatment of solid tumors

  17. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

    Science.gov (United States)

    The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

  18. Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.

    OpenAIRE

    Kanaly, S T; Hines, S.A.; Palmer, G H

    1996-01-01

    Rhodococcus equi, and intracellular respiratory pathogen, causes sever e granulomatous pneumonia in humans with AIDS and in young horses. Pulmonary clearance of R. equi requires functional CD4+ T cells and gamma interferon (IFN-gamma) expression from bronchial lymph node cells. The purpose of this study was to investigate whether R. equi-specific CD4+ Th1 cells could effect clearance of R. equi from the lung. Adoptive transfer of a clearance of R. equi from the lungs. In contrast, mice transf...

  19. Radioimmunodetection of choriocarcinoma in nude mouse by radiolabeled antibody to human chorionic gonadotropin. beta. -subunit

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Nozomu (Kobe Univ. (Japan). School of Medicine)

    1983-06-01

    Photoscans and organ radioactivity were assessed with radiolabeled antibodies to hCG or hCG-..beta.. subunit in nude mice bearing hCG-producing tumors. /sup 125/I-anti hCG or /sup 125/I-anti-hCG-..beta.. subunit was administered to nude mice bearing an hCG-producing tumor, GCH-lnu. Measurement of radioactivity revealed specific accumulation of both antibodies into the tumor. Especially the accumulation of /sup 125/I-anti hCG-..beta.. subunit on the 3rd day of administration was high, being about 4 times higher than the nonspecific accumulation in the liver. The localization of hCG in the tumor was examined by the indirect peroxidase-antiperoxidase method using anti-hCG. and anti hCG-..cap alpha.. subunit, and hCG-..beta.. subunit. The immunoperoxidase reaction was positive, and the accumulation of these radiolabeled antibodies in the tumor is suggested to be an immunologically specific phenomenon. The tumor in the tumor-bearing nude mouse injected with /sup 131/I-anti hCG or /sup 131/I-anti hCG-..beta.., subunit could be visualized as a hot area by external scintigraphy. Especially, the tumor image produced by the accumulation of anti hCG-..beta.. subunit was very clear against the background radiation.

  20. Sensing vascularization of ex-vivo produced oral mucosal equivalent (EVPOME) skin grafts in nude mice using optical spectroscopy

    Science.gov (United States)

    Vishwanath, Karthik; Gurjar, Rajan; Kuo, Shiuhyang; Fasi, Anthony; Kim, Roderick; Riccardi, Suzannah; Feinberg, Stephen E.; Wolf, David E.

    2014-03-01

    Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20 animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue absorption and scattering coefficients, which were then used to extract blood flow information by fitting the experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow (from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters remained relatively constant throughout 4 weeks for the off-site measurements.

  1. Vitrified canine testicular cells allow the formation of spermatogonial stem cells and seminiferous tubules following their xenotransplantation into nude mice

    Science.gov (United States)

    Lee, Kyung Hoon; Lee, Won Young; Kim, Dong Hoon; Lee, Seung Hoon; Do, Jung Tae; Park, Chankyu; Kim, Jae Hwan; Choi, Young Suk; Song, Hyuk

    2016-01-01

    Belgian Malinois (BM), one of the excellent military dog breeds in South Korea, is usually castrated before sexual maturation. Therefore, the transfer of their genetic features to the next generation is difficult. To overcome this, testicular cells from 4-month-old BMs were frozen. Testicular cells were thawed after 3 months and cultured in StemPro-34 medium. Spermatogonial stem cell (SSC) characteristics were determined by the transplantation of the cultured germ cell-derived colonies (GDCs) into empty testes, containing only several endogenous SSCs and Sertoli cells, of immunodeficient mice, 4 weeks after busulfan treatment. Following the implantation, the transplanted cells localized in the basement membrane of the seminiferous tubules, and ultimately colonized the recipient testes. Xenotransplantation of GDCs together with testicular somatic cells conjugated with extracellular matrix (ECM), led to the formation of de novo seminiferous tubules. These seminiferous tubules were mostly composed of Sertoli cells. Some germ cells were localized in the basement membrane of seminiferous tubules. This study revealed that BM-derived SSCs, obtained from the castrated testes, might be a valuable tool for the transfer of BM genetic features to the next generation. PMID:26907750

  2. Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer.

    Science.gov (United States)

    Wang, Zhaoxia; Li, Li; Wang, Yang

    2016-06-01

    The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT‑qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis‑associated gene 1 (MTA‑1) and tumor metastasis suppressor gene, non‑metastasis protein 23‑H1 (nm23‑H1), and the expression change of autophagy‑associated signal transduction pathway, phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA‑1 protein expression was significantly reduced when compared with the phosphate‑buffered saline (PBS) control and empty plasmid groups, while nm23‑H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy

  3. Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

    Science.gov (United States)

    WANG, ZHAOXIA; LI, LI; WANG, YANG

    2016-01-01

    The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT-qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis-associated gene 1 (MTA-1) and tumor metastasis suppressor gene, non-metastasis protein 23-H1 (nm23-H1), and the expression change of autophagy-associated signal transduction pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA-1 protein expression was significantly reduced when compared with the phosphate-buffered saline (PBS) control and empty plasmid groups, while nm23-H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3

  4. Protective Effect of Propolis (Bee Glue) in Mice Bearing Ehrlich Ascites Carcinoma

    International Nuclear Information System (INIS)

    Cancer is considered one of the most common causes of morbidity and mortality worldwide. Many studies were carried out to investigate the discovery of natural and synthetic compounds that can be used in the prevention and/or treatment of cancer. Natural products of either plant or animal origin that exhibit antitumour activity have been discovered. The present study was undertaken to evaluate the protective effect of ethanolic extract of propolis without or with radiation exposure in Ehrlich ascites carcinoma- bearing female albino mice. The animals were randomly distributed into three major groups as follows: group A (control group): consists of 10 mice kept on normal standard rodent diet without any treatment and housed in two cages: mice of the first cage served as control for non tumour-bearing group and the second cage served as control for tumour-bearing group. Group B (non tumour-bearing group): consists of 15 mice and used to study the effect of the vehicle solution (gum acacia), propolis and gamma irradiation on normal mice. Mice of this group were equally distributed into three subgroups receiving gum acacia, propolis for two weeks and gamma irradiated. Group C (tumour bearing group): consists of 20 mice randomly and equally distributed into 4 subgroups: Ehrlich ascites carcinoma, Ehrlich ascites carcinoma and 2 Gy irradiated, Ehrlich ascites carcinoma and propolis treated, and Ehrlich ascites carcinoma and propolis irradiated. Plasma and hepatic lipid peroxidation index (TBARS), superoxide dismutase (SOD) and glutathione (GSH) were assessed in RBC and liver together with hepatic aspartate amino transferase (AST) and alanine amino transferase (ALT) and histopathological examination of liver sections. There was decrease in the levels of SOD and GSH as well as an increase in TBARS in mice bearing EAC in addition to increase in hepatic levels of AST and ALT. The microscopical examination of liver sections of mice bearing EAC showed various histopathological

  5. Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

    International Nuclear Information System (INIS)

    The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

  6. Luciferase bioluminescence imaging monitoring gene therapeutic effect of apoptosis-inducing ligand for lung cancer A549 cells nude mice transplantation tumor in vivo

    International Nuclear Information System (INIS)

    Objective: To detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand (hTRAIL) in vivo,by using a novel double expressing adenoviral vector encoding hTRAIL and firefly luciferase (luc) gene (ad-luc-hTRAIL), in which luc was used as reporter gene. Methods: Lung cancer A549 cell xenografts in 16 nude mice models were established in subcutaneous inoculation way, the adenovirus vectors (ad-luc-hTRAIL, ad-hTRAIL, ad-luc) and phosphate buffer saline (PBS) (n=4) as control were injected into tumor respectively. The size of the tumor was measured at different time points (4, 7, 10, 14, 21, 28 d) after injection. The activity of luciferase in surface of the tumor was detected in vivo by using high-sensitivity cooled-charged coupled device (CCD) camera. The expression of hTRAIL was demonstrated by immunohistochemistry staining after sacrificing the animals at different time points, and immunohistochemical scores (IHS) were measured. The apoptosis rate of tumor cells was detected by using TUNEL and calculated. Analysis of variance, the paired t test and linear correlation analysis was used for the statistics. Results: The growing speed of tumour xenografts was more slowly in ad-luc-hTRAIL and ad-hTRAIL groups than PBS group (t=2.71, 2.72, P<0.05). The tumor volumes of ad-luc-hTRAIL, ad-hTRAIL, ad-luc and PBS groups 28 days after injection were (208.4 ± 42.3), (181.5 ±23.9), (403.1 ± 54.0) and (427.0 ± 59.3) mm3, respectively. There was no significant difference between ad-luc group and PBS group (t=2.07, P>0.05). The expression of luciferase in ad-luc-hTRAIL group reached its peak at 7th day (1.37 ± 1.04), and then decreased quickly. The IHS and apoptosis rate in ad-luc-hTRAIL and ad-hTRAIL groups reached their peaks at 7th day, the peak values of IHS were 6.25 ±2.06 and 6.5 ± 2.89, the peak values of apoptosis rate were (60.75 ± 8.06)% and (61.50 ± 8.47)%,respectively. The amount of luciferase expression (absolute number of

  7. In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [125I]MRK-16 monoclonal antibody

    International Nuclear Information System (INIS)

    Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with 125I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [125]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [125I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g ± SD) (18.76 ± 2.94 vs 10.93 ± 0.96; p 125I]MRK-16 was confirmed by comparison to [131I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [125I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors

  8. MR immuno-imaging study using avidin-biotin pre-targeting system on nude mice grafted with human colorectal carcinoma

    International Nuclear Information System (INIS)

    Objective: To further improve the amount of gadolinium located on tumor, a gadolinium chelate enhanced magnetic resonance imaging pre-targeting with avidin-biotin system technique was adopted and the enhancing characteristics of difference of signal intensity at various scan timing were investigated in author's experiment. Methods: (1) Anti-CEA antibody CL-3 was biotinylated in a mixture with antibody to NHS-LS-biotin with a molar ratio of 1/30-50. (2) After the reaction of GdCl3 and DTPA-B, the unconjugated gadolinium was removed by chromatography on G-10 column. (3) Steps for pre-targeting tumor: First step, McAb-B was injected intravenously into nude mice on the first day. Second step, avidin (Av) and streptavidin (SA) were injected intraperitoneally 24 hours later. Third step, Gd-DTPA-Bt was injected intravenously 48 hours after the first injection. MRI was performed with plain scans, enhanced scans at 20 minutes, 2 hours, 8 hours, and 24 hours after the third step. Signal intensities of tumor and muscles were measured. The pre-targeting effect was compared with those of Gd-DTPA-McAb and Gd-DTPA. Results: (1) Each monoclonal antibody conjugated with 11-23 biotin and the immuno-activity of biotinylated antibody with 12 biotin/antibody was 94.9%. (2) The enhancing effect of pre-targeting approach was tumor specific. Contrarily that of Gd-DTPA was not. (3) The enhancing rate of signal intensity specificity of pre-targeting approach was 43%, while that of McAb-Gd-DTPA was 17.9% only, so the enhancing ratio was 2.4. Conclusion: Pre-targeting approach using avidin-biotin system improves the amounts of gadolinium locating on tumors and yields a specific enhancing effect. It is a promising modality which promotes the ability of Gd labelled magnetic resonance immuno-imaging in the detection of colon cancer and its recurrence

  9. Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

    Directory of Open Access Journals (Sweden)

    Hongxiu Ning

    Full Text Available Efforts to develop peripheral blood-derived nature killer (NK cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs and umbilical cord blood (UCB requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs, which are abundant and natively CD34+, into NK-like cells. When grown in hematopoietic induction medium, ADSCs formed sphere clusters and expressed hematopoietic markers CD34, CD45, and KDR. Further induction in NK cell-specific medium resulted in a population of cells that expressed NK cell marker CD56, and thus termed ADSC-NK. Alternatively, the hematopoietically induced ADSCs were transduced with NK cell-specific transcription factor E4BP4 prior to induction in NK cell-specific medium. This latter population of cells, termed ADSC-NKE, expressed CD56 and additional NK cell markers such as CD16, CD94, CD158, CD314, FasL, and NKp46. ADSC-NKE was as potent as NK leukemia cell NKL in killing breast cancer cell MCF7 and prostate cancer cells DU145, PC3, LnCap, DuPro, C4-2 and CWR22, but exhibited no killing activity toward normal endothelial and smooth muscle cells. In nude mice test ADSC-NKE was able to significantly delay the progression of tumors formed by MCF7 and PC3. When injected into immunocompetent rats, ADSC-NKE was detectable in bone marrow and spleen for at least 5 weeks. Together, these results suggest that ADSCs can be converted into NK-like cells with anti-tumor activities.

  10. Effect of administration of some antitumor extracts on Ehrlich ascites carcinoma-bearing mice

    International Nuclear Information System (INIS)

    Cancer is considered one of the most common causes of morbidity and mortality worldwide. Many researches have been studied on the discovery of natural and synthetic compounds that can be used in the prevention and/or treatment of cancer. Many chemo preventive agents have been associated with antiproliferative and apoptotic effects on cancer cells because of their high antioxidant activity. The present study was undertaken to investigate the antioxidant and antitumor effects of three natural extracts including (propolis, green tea and Chlorella vulgaris) without or with radiation exposure in Ehrlich ascites carcinoma (EAC) - bearing female albino mice. The animals were randomly distributed into three major groups as follows:- Group A (control group).This group consists of 10 mice kept on normal standard rodent diet without any treatment and housed in two cages: mice of the first cage served as control for non tumor-bearing group and the second cage served as control for tumor-bearing group. Group B (Non tumor - bearing group).This group consists of 30 mice and used to study the effect of the vehicle solutions (gum acacia, DMSO), propolis, green tea, Chlorella vulgaris and gamma irradiation on normal mice. Mice of this group were equally distributed into six subgroups receiving gum acacia, DMSO, propolis, green tea and Chlorella vulgaris for two weeks and whole body gamma irradiated. Group C (Tumor- bearing group): This group consists of 160 mice randomly and equally distributed into 8 subgroups: Ehrlich ascites carcinoma(mice were inoculated with 2.5 x 106 intra-peretoneally(i.p), Ehrlich ascites carcinoma and 2 Gy irradiated, Ehrlich ascites carcinoma and propolis treated (150 mg/kg b.w), Ehrlich ascites carcinoma, propolis treated and irradiated, Ehrlich ascites carcinoma and green tea treated (150 mg/kg b.w), Ehrlich ascites carcinoma, green tea treated and irradiated, Ehrlich ascites carcinoma and Chlorella vulgaris treated (150 mg/kg b.w) and Ehrlich ascites

  11. Gallium Chloride Potentiate the Radiation Effects on Solid Tumor in Ehrlich Carcinoma Bearing Mice

    International Nuclear Information System (INIS)

    The objective of this study is to evaluate the effect of co-administration of Gallium Chloride ( GaCl3 ) with gamma irradiation (R) on solid tumor in Ehrlich Carcinoma (EC) bearing mice. Animals were divided into 5 groups. 1-Control: normal healthy mice. 2-Tumour: EC bearing mice. 3- Tumor + GaCl3 : EC bearing mice receiving orally GaCl3 (300 mg/ Kg body weight) for 5 consecutive days/week during 3 weeks. 4- Tumor + R: EC bearing mice whole body gamma irradiated with 2 Gy/week for 3 weeks. 5- Tumor + GaCl3 + R: EC bearing mice receiving orally GaCl3 (300 mg/ Kg body weight) for 5 consecutive days/week and whole body gamma irradiated with 2 Gy/week for 3 weeks. Biochemical analysis in tumor and liver tissues of EC bearing mice revealed a significant increase of malondialdehyde (MDA) level parallel to a significant decrease of glutathione (GSH) content, compared to their respective levels in control rats, indicating oxidative stress. In addition, tumor necrosis factor-alpha (TNF-α) level showed a significant increase. Biochemical analysis in the serum of EC bearing mice showed a significant increase of serum alanine amino transferase (ALT) activity, and bilirubin content and a significant decrease of albumin, compared to their re - spective levels in control rats, indicating alteration of liver function. The results showed also a significant decrease in serum iron level. The co-administration of GaCl3 with R to EC bearing mice potentiate the radiation-induced increase of MDA and TNF-α levels in tumor tissues which was associated to a higher reduction of tumor volume. On the other side, the co-administration of GaCl3 and R had no effect on radiation-induced oxidative stress in liver tissues, but increased TNF-α. Moreover, the co-administration of GaCl3 and R has not intensified radiation-induced alteration of liver function while intensified the decrease of iron. It can be concluded that the effect of radiation on tumor tissue can be potentiated by using GaCl3 , in

  12. Bear

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The famous physicist made for his scholars this riddle. A fellow encountered a bear in a wasteland. There was nobody else there. Both were frightened and ran away. Fellow to the north, bear to the west. Suddenly the fellow stopped, aimed his gun to the south and shot the bear. What colour was the bear?

  13. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Directory of Open Access Journals (Sweden)

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  14. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    International Nuclear Information System (INIS)

    Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  15. 蜂毒素对裸鼠骨肉瘤治疗作用及安全性的实验研究%Experimental Study of Treatment and Safety of Melittin on Xenotransplanted Models of Nude Mice

    Institute of Scientific and Technical Information of China (English)

    高启龙; 杨峰; 姚亚民; 王怀章; 刘怀民; 陈永强

    2011-01-01

    目的:观察蜂毒素对骨肉瘤裸鼠移植瘤生长抑制作用及毒副反应.方法:建立裸鼠骨肉瘤原位移植瘤模型,随机分4组:生理盐水组,蜂毒素低、高剂量组,顺铂组.观察各组裸鼠骨肉瘤的体积和体质量抑制率;放射免疫法测定血清碱性磷酸酶活性;测定外周血常规、骨髓有核细胞数目;光镜观察心肝脾肺肾及肿瘤的病理组织学情况;电镜观察肿瘤细胞的微细结构.结果:蜂毒素低剂量组肿瘤体积和体质量抑制率分别为42.98%、39.03%,高剂量组分别为67.54%、48.66%,蜂毒素能明显降低血清AKP水平;光镜与电镜下蜂毒素能诱导骨肉瘤细胞凋亡或坏死;高剂量蜂毒素给药后可见扭体动作、精神不振、萎靡少动等毒性反应,肾脏病理切片可见肾小管间质扩张充血,肾细胞间隙炎性细胞集聚.蜂毒素各组骨髓及心肺肝脾等脏器未造成明显毒副反应.结论:蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,并能促使肿瘤细胞凋亡或坏死,无明显的毒副作用.%Objective; To study the antitumor effects and toxic and side effects of Melittin on xenotransplanted models of nude mice. Methods: Xenotransplanted models of SD rat osteosarcoma cell UMR - 106 in the laevo - hind tibia of nude mice were established. Inoculated mice were randomly divided into normal saline group,positive controlgroup,low and high dose Melittin group. All the nude mice were sacrificed after treatment,the size and weight of tumor were measured and the tumor volumes and the inhibition rates of tumor were calculated,and peripheral blood cells,alkaline phosphatase and medullary karyote in one femur of nude mice were counted by hematology analyzer. Tumor tissues, myocardium, lung, liver, spleen, kidney and brain were sectioned, stained with hematoxylin and eosin.and then observed by light and electron microscope. Results-.The mice treated with high dose Melittin groups showed significantly smaller volume

  16. 多时间节点荷人胰腺癌SW1990细胞裸鼠模型的建立及其MRI表现%Establishment of the nude mouse model bearing human pancreatic adenocarcinoma in multiple timepoints and its 3.0T MRI findings

    Institute of Scientific and Technical Information of China (English)

    潘璜; 邵成伟; 田建明

    2012-01-01

    Objective To establish nude mouse tumor models bearing human pancreatic adenocarcinoma SW1990 cells in multiple sites at different time-points and investigate the feasibiilty of multiple tumor-bearing in these models; then the findings and detection rate of 3.0T magnetic resonance image (MRI) in subcutaneous transplanted tumors was analyzed. Methods A total of 6 BALB/C nude mice were randomized into 3 groups (2 mice per group ).At the 1st,8th,15th day,the mice were injected subcutaneously with the suspension of SW1990 cells at left axilla and right axilla and right groin in sequence.Three weeks later,all the bearing-tumor mice were performed with MRI non-contrast enhanced scanning plus Gd-DTPA enhanced scan and the subcutaneous masses were subjected to pathological analysis.Results All the 6 nude mice were alive during the study and obvious mass was observed in every injected site.The tumor size was positively associated with the grwing time.There were 9 tumors which could be de.ted by noncontrast enhanced MRI scanning and one more tumor was detected by contrast enhanced scanning.2 tumors were not detected,the 2 tumors were located at subcutaneous of right groin,with the shortest growing time,and the major axis of the 2 un-detected tumors was less than 5mm.Despite the MRI findings of the transplanted masses similar to that of human pancreatic adenocarcinoma with bleeding,necrosis,they presented the characteristics of a clear rim,with "pseudocapeule" sign.All the 12 masses were similar with human pancreatic adenocarcinoma under light microscope.Conclusions It is feasible to transplant human pancreatic adenocarcinoma cell at three different subcutaneous sites (injected at three different points of time) in the nude mouse,with a minimal survival time of three weeks.However,routine 3.0T MRI cannot detect the early tumors (growing time within 1 week,major axis <5 mm).%目的 研究裸鼠荷载多时间节点人胰腺癌细胞的能力,分析其MRI表现及

  17. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity

    International Nuclear Information System (INIS)

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells

  18. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice

    OpenAIRE

    Reelma Velho-Pereira; Kumar, A.; Pandey, B. N.; Mishra, K. P.; Aarti G Jagtap

    2012-01-01

    The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues. This was done to mimic the clinical setting where in, normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretre...

  19. Modulatory Effect of a Unani Formulation (Jawarish amla sada) on Cyclophosphamideinduced Toxicity in Tumour Bearing Mice

    OpenAIRE

    Ahmad, Firoz; Rashid, Hina; Bhatia, Kanchan; Rehman, Hasibur; Kaur, Manpreet; Anjum, Sameya; Ansari, Rizwan A.; Raisuddin, Sheikh

    2012-01-01

    Aims: Our aim was to study the modulatory effect of a Unani herbal formulation Jawarish amla sada against cyclophosphamide-induced toxicity in tumour bearing mice. Study Design: Non randomized control study. Place and Duration of Study: The study was conducted at the Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi during 2008-10. Methodology: Study was conducted in Swiss albino mice divided in five groups (n=6). Animals were challenged with Ehrlich’s ascites ...

  20. Influence of melittin on growth of human K562 cell xenografts in nude mice%蜂毒素对人K562细胞裸鼠皮下移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    秦进; 王春光

    2011-01-01

    Objective To investigate the growth inhibitory effect of melittin on xenografted human K562 cells in nude mice and its relation with the expression change of Bax and Bcl-2. Methods Human K562 cells were inoculated BALB/C nude mice, and then the tumor-bearing were classified randomly into 5 groups, including low concentration (30μg/kg), middle concentration (60μg/kg) and high concentration (120 μg/kg) melittin groups, negative crontrol group and hydroxy urine group. The growth of xenografted tumors was observed. Apoptosis morphological transformation of K562 cells induced by melittin was detected by HE staining and transmission electronic scan microscope. Apoptosisrelated protein levels of Bax and Bcl-2 were determined by Western Blot. The levels of Bax and Bcl-2 mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR). Results Compared to negative control group, all the melittin treatment groups showed having statistical significance ( P < 0.05 ). The high concentration melittin group showed similar inhibition ratio as the hydroxy urine negative control group ( P > 0.05). Apoptosis and necrosis of tumor cells were found in all melittin groups under the light and electronic sean microscope, and the high concentration melittin group had the strongest effect. The tumor cells in hydroxy urine group were mainly necrosis. The results of Western Blot indicated that the expression of Bax protein was up-regulated by melittin, while Bcl-2 protein was down-regulated in K562 cell tumor tissue. The results of RT-PCR indicated the expression of Bax mRNA was upregulated by melittin, while Bcl-2 mRNA was down-regnlated in K562 cell tumor tissue. Conclusions Melittin suppresses significantly the growth of K562 cells in nude mice. Melittin increases the expression of Box and decreases the expression of Bcl-2 to induce the apoptosis of K562 cells. This is one of the possible mechanisms of antitumor.%目的 探讨蜂毒素对K562细胞裸鼠移植瘤的

  1. Dendritic cells generated from naïve and tumor-bearing mice uniquely restores different leukocyte subpopulations in chemotherapy-treated tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Mohamed Labib Salem

    2016-01-01

    Full Text Available Background: Dendritic cell (DC-based vaccination has shown promising application in tumor immunotherapy. However, it is not clear whether the presence of tumor impacts the efficacy of generation and functionality of DCs. Aim: To compare the phenotype of DCs generated from naïve or tumor bearing mice and their capability to restore leukopenia-associated chemotherapy. Materials and Methods: DCs were generated from bone marrow (BM of naïve or Ehrlich ascites carcinoma (EAC bearing mice. EAC is an undifferentiated breast cancer cell line with the high transplantable capability and rapid proliferation. BM cells were cultured in vitro for 7 days with granulocyte macrophage colony-stimulating factor and interleukin-4 (20 ng/ml each, loaded with different concentrations of EAC cell lysate (0.5, 1, 3 and 5 mg/106 DCs followed by activation with the toll-like receptor 3 ligand poly(I:C. For DC-based vaccination, CD1 mice (n = 5/group were inoculated with an intraperitoneal (i.p. injection of 0.25 × 106 EAC cells to form ascites, treated on day 14 with an i.p. injection of cyclophosphamide (4 mg/mouse and on day 15 with subcutaneous injection of 2 × 106 DCs from control or EAC bearing mice. Injected DCs were loaded with or without EAC lysate followed by i.p. injection of 50 μg/mouse poly(I:C. On day 21, mice were bled and sacrificed for peripheral blood count and spleen and BM cellularity. Results: Yield of DCs generated from naÏve or EAC bearing mice, as well as their phenotype (CD11c+ CD11b+ and activation (CD40 and CD80 with poly(I:C were similar. Loading DCs with 1 mg EAC lysate induced better viability and activation phenotype as compared with the other concentrations. Regardless the source of DCs, DCs vaccination restored the total numbers of leukocytes in blood but not in the spleen and BM. The effect on peripheral blood leukocytes was coincided with the restoration of the relative numbers of lymphocytes, monocytes, and granulocytes

  2. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity.

    OpenAIRE

    Lapidot, T; Lubin, I; Terenzi, A; Faktorowich, Y; Erlich, P; Reisner, Y

    1990-01-01

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraft...

  3. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model

    International Nuclear Information System (INIS)

    Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line. (orig.). With 4 figs., 1 tab

  4. In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [{sup 125}I]MRK-16 monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Andrew M.; Rosa, Eddie; Mehta, Bippin M.; Divgi, Chaitanya R.; Finn, Ronald D.; Biedler, June L.; Tsuruo, Takashi; Kalaigian, Hovannes; Larson, Steven M

    1995-05-01

    Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with {sup 125}I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [{sup 125}]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [{sup 125}I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g {+-} SD) (18.76 {+-} 2.94 vs 10.93 {+-} 0.96; p < 0.05). Quantitative autoradiography verified these findings (19.13 {+-} 0.622 vs 12.08 {+-} 0.38, p < 0.05). Specific binding of [{sup 125}I]MRK-16 was confirmed by comparison to [{sup 131}I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [{sup 125}I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors.

  5. Functional lymphatic imaging in tumor-bearing mice

    OpenAIRE

    Kwon, Sunkuk; Sevick-Muraca, Eva M

    2010-01-01

    The lymphatic system provides a route for dissemination of metastatic cancer cells. Yet to date transient changes in lymphatic drainage pathways and function as a result of tumor growth and metastasis has not been completely elucidated. Herein, we non-invasively imaged functional and architectural lymphatic changes in mice with regional, palpable lymph node (LN) involvement using dynamic near-infrared (NIR) fluorescence imaging with intradermal injection of indocyanine green (ICG) to both tum...

  6. ANTI-OXIDANT ACTIVITY OF MORINDA CITRIFOLIA ON LYMPHOMA-BEARING MICE

    OpenAIRE

    Anitha, T.; S. Mohandass

    2006-01-01

    Oral treatment with 50 mg Kg-1 day-1 of crude methanol extract of Morinda citrifolia leaves for 14 days significantly increased the anti-oxidant enzymes, like catalase, glutathione peroxidase (GSHPx) and superoxide dismutase (SOD), and anti-oxidants like glutathione (GSH) and ascorbic acid decreased in lymphoma-bearing mice.

  7. Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Lurong; Jiang, Guorong; Yao, Fei; Liang, Guoqiang; Wang, Fei; Xu, Heng; Wu, Yan; Yu, Xiao; Liu, Haiyan

    2015-06-01

    Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC. PMID:25975579

  8. MicroSPECT/CT imaging and pharmacokinetics of 188Re-(DXR)-liposome in human colorectal adenocarcinoma-bearing mice.

    Science.gov (United States)

    Chen, Min-Hua; Chang, Chih-Hsien; Chang, Ya-Jen; Chen, Liang-Cheng; Yu, Chia-Yu; Wu, Yu-Hsien; Lee, Wan-Chi; Yeh, Chung-Hsin; Lin, Feng-Huei; Lee, Te-Wei; Yang, Chung-Shi; Ting, Gann

    2010-01-01

    Nanoliposome can be designed as a drug delivery carrier to improve the pharmacological and therapeutic properties of drug administration. (188)Re-labeled nanoliposomes are useful for diagnostic imaging as well as for targeted radionuclide therapy. In this study, the in vivo nuclear imaging, pharmacokinetics and biodistribution of administered nanoliposomes were investigated as drug and radionuclide carriers for targeting solid tumor via intravenous (i.v.) administration. The radiotherapeutics ((188)Re-liposome) and radiochemotherapeutics ((188)Re-DXR-liposome) were i.v. administered to nude mice bearing human HT-29 colorectal adenocarcinoma xenografts. (188)Re-liposome and (188)Re-DXR-liposomes show similar biodistribution profile; both have higher tumor uptake, higher blood retention time, and lower excretion rate than (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA). In contrast to tumor uptake, the area under the curve (AUC) value of tumor for (188)Re-liposome and (188)Re-DXR-liposome was 16.5- and 11.5-fold higher than that of free (188)Re-BMEDA, respectively. Additionally, (188)Re-liposome and (188)Re-DXR-liposome had a higher tumor-to-muscle ratio at 24 h (14.4+/-2 .7 and 17.14+/-4.1, respectively) than (188)Re-BMEDA (1.6+/-0.1). The tumor targeting and distribution of (188)Re-(DXR)-liposome (representing (188)Re-DXR-liposome and (188)Re-liposome) can also be acquired by signal photon-emission computed tomography/computed tomography images as well as whole body autoradiograph. These results suggest that (188)Re-(DXR)-liposomes are potentially promising agents for passive targeting treatment of malignant disease. PMID:20150618

  9. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  10. Inhibition of metastasis to lung of a human nasopharyngeal carcinoma cell line CNE-2L2 transfected with pRc/CMV-antisense 6A8 cDNA in nude mice

    Institute of Scientific and Technical Information of China (English)

    张立新; 刘玉琴; 马凤蓉; 顾蓓; 史耕先; 赵雪梅; 李波; 高进; 赵方萄; 张淑珍; 李国燕; 王讯; 朱立平

    1999-01-01

    The growth of CNE-2L2 cell, a cloned line of human nasopharyngeal carcinoma with a high potentiality of metastasis to lung was inhibited to a certain extent after transfection with a recombinant antisense expression vector of a cDNA encoding a human α-mannosidase (pRc/CMV-antisense 6A8 cDNA)( the Genbank accession number of 6A8 cDNA is U37248) in comparison with that of the cell transfected with the Mock and of the wild cell. Two months after a subcutaneous inoculation of CNE-2L2 cell into the axilla of nude mice metastatic lesions in the lung were observed in 9/10 mice (90%) with grade Ⅲ in 8 mice and grade Ⅱ in one mouse in the wild cell group, in 6/8 mice (75%) with grade Ⅲ in one mouse, grade Ⅱ in 2 mice and grade Ⅰ in 3 mice in the Mock-transfection group, in only 3/10 mice (30%) with all grade Ⅰ in pRc/CMV-antisense 6A8 cDNA-transfection group.

  11. Hypothalamo-neurohypophysial complex in leukemia L 1210-bearing mice.

    Science.gov (United States)

    Jasiński, A; Skraba, A

    1975-02-01

    Mice of the DBA strain were inoculated with 4.5 x 10(6) L1210 ascites cells and the time response of the hypothalamo-neurohypophysial complex was studied. The amount of neurosecretory material was determined in the neuroendocrine cells of supraoptic and paraventricular nuclei, throughout the hypothalamo-neurohypophysial tract and in the neural lobe of the hypophysis. Three methods of response evaluation were employed: the amoount of neurosecretory material was estimated according to an arbitrary scale, by cytophotometry while for the hypothalamic cell-nuclei the karyometric method was used. The existence of a functional interrelation between the presence of leukemic cells and the activity of the hormonogenic sites in the hypothalamus is suggested. A clear response to the tumor inoculation was established both in the amount of stainable substance and in the nuclear volume of the secretory neurones. It is suggested that an accelerated synthesis and release of neurosecretory material in tumor recipient mice reduces renal excretion in order to compensate a dehydration caused by the production of ascitic fluid. PMID:1227831

  12. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    International Nuclear Information System (INIS)

    Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin

  13. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Kim Sung-Ho

    2009-03-01

    Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

  14. A dominated and resistant subpopulation causes regrowth after response to 1,3-bis(2-chloroethyl)-1-nitrosourea treatment of a heterogeneous small cell lung cancer xenograft in nude mice

    DEFF Research Database (Denmark)

    Aabo, K; Roed, H; Vindeløv, L L;

    1994-01-01

    In order to address the question of the influence of a primarily chemoresistant tumor cell subpopulation on the progression of a heterogeneous tumor after cytotoxic therapy, in vitro established human small cell lung cancer cell lines of a 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-sensitive (592......) and a resistant (NYH) tumor were used to produce mixed solid tumors in nude mice. Mixtures of 592/NYH (9:1 and 1:1) were inoculated s.c. After 3-4 weeks of tumor growth, the mice were stratified according to tumor size and randomized to treatment with BCNU 40 mg/kg i.p. (10% of lethal dose) or no...

  15. Establishment of lung metastasis model of human primary malignant melanoma in the small intestine in nude mice%人原发性小肠恶性黑色素瘤裸鼠肺转移模型的建立

    Institute of Scientific and Technical Information of China (English)

    张宁; 脱帅; 杨波; 刘秋珍

    2009-01-01

    目的 建立原发性小肠恶性黑色素瘤肺转移动物模型.方法 采用人原发性小肠恶性黑色素瘤肺转移瘤的新鲜瘤组织块植入裸鼠小肠黏膜层内,当裸鼠体内形成肺转移瘤后重复筛选4次,再将肺转移瘤植入另一只裸鼠小肠黏膜行鼠问连续传代.观察原位移植成瘤率和转移率,进行形态学、染色体核型和流式细胞仪分析.结果 建成的人原发性小肠恶性黑色素瘤裸鼠肺转移模型命名为HSIM-0601,瘤细胞胞质内可见大量黑色素颗粒及黑色素复合体,S-100、HMB-45呈阳性表达.染色体数57~59条;流式细胞DNA指数值1.49,均为异倍体.HSIM-0601已传至26代,共移植裸鼠173只,成瘤率和液氮冻存复苏成活率均为100%.肺转移率为100%(173/173),淋巴结转移率为61.3%(106/173).结论 首次成功地建立了人原发性小肠恶性黑色素瘤裸鼠原位移植肺转移模型HSIM-0601.完整地模拟了人小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤肺转移机制和抗转移治疗提供了理想的动物模型.%Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and

  16. 三种癌裸鼠移植瘤肝脾转移的比较研究%A Comparative Study on the Liver and Spleen Metastasis of Three Transplanted Carcinomas in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    褚芳; 余华; 方铝; 周艳艳; 郑国安; 范其坤; 丁琦

    2012-01-01

    Objective To observe and compare the liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice. Method The human ovarian cancer, gastric cancer and colon cancer were transplanted to the nude mice. The growth rate of the solid tumors, the survival time, and the pathological changes in the liver and spleen metastasis of three transplanted carcinomas were observed. Results The rates of tumor formation and the liver metastasis of xenografted human ovarian cancer, gastric cancer and colon cancer in nude mice were 100% . The spleen metastasis rate of human ovarian cancer was 100% , that of gastric cancer was 62. 5% , and that of colon cancer was 75% . The tumor growth rate of solid tumor of human ovarian cancer in nude mice was higher than that of solid tumor of gastric cancer and colon cancer, and spleen metastasis of human ovarian cancer was rapider with a short survival time. There were differences in the pathological changes in the liver and spleen metastasis of three transplanted carcinomas. Conclusion The models of liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice can reproduce clinical processes of the liver and spleen metastasis of three transplanted carcinomas, which makes for the studies on biological mechanism of liver and spleen metastasis of human ovarian cancer, gastric cancer and colon cancer and anti-metastasis.%目的 利用人卵巢癌、胃癌、结肠癌裸鼠移植瘤动物模型观察比较肝脾转移情况.方法 分别将人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,在建立人卵巢癌、胃癌、结肠癌裸鼠实体瘤模型的基础上,观察裸鼠实体瘤生长速度、存活时间及肝脾转移病理形态学变化.结果 人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,移植成瘤率、肝转移率皆为100%;卵巢癌脾转移100%;胃癌脾转移62.5%;结肠癌脾转移75%.人

  17. Pharmacokinetics of Polymersomes Composed of Poly(Butadiene-Ethylene Oxide); Healthy versus Tumor-Bearing Mice.

    Science.gov (United States)

    Wang, G; de Kruijff, R M; Abou, D; Ramos, N; Mendes, E; Franken, L E; Wolterbeek, H T; Denkova, A G

    2016-02-01

    Vesicles composed of block copolymers (i.e., polymersomes) are one of the most versatile nano-carriers for medical purposes due to their tuneable physicochemical properties and the possibility to encapsulate simultaneously hydrophobic and hydrophilic substances, allowing, for instance, the combination of therapy and imaging. In cancer treatment, these vesicles need to remain long enough in the blood stream to be sufficiently taken up by tumors. Here, we have investigated the biodistribution and the pharmacokinetics of polymersomes, composed of poly(butadiene-b-ethylene oxide) having dimensions around 80 nm. The polymersomes have been radiolabeled with ¹¹¹In via the so-called active loading method achieving a loading efficiency of 92.9 ± 0.9% with radionuclide retention in mouse serum of more than 95% at 24 h. The optimized ¹¹¹In containing polymersomes have been intravenously administered in healthy and tumor bearing mice for pharmacokinetic determination using microSPECT (Single Photon Emission Computed Tomography). In healthy mice these polymersomes have been found to exhibit relatively long blood circulation (> 6 h), low liver uptake (6 ± 1.5%ID/g, 48 h p.i.) and elevated spleen uptake (188 ± 30%ID/g). The blood circulation in tumor bearing mice is dramatically reduced (< 1.5 h) most likely due to elevated splenic filtration, clearly indicating the importance of in vivo studies in diseased mice. Finally, the polymersomes have been injected subcutaneously in tumor bearing mice revealing retention of 77% in the mice, primarily accumulated at the site of injection, up to 48 hours after administration. PMID:27305765

  18. Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

    International Nuclear Information System (INIS)

    Introduction: We assessed the suitability of the radiolanthanide 155Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods: 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (∼ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results: The total yield of the two-step separation process of 155Tb was 86%. 155Tb was obtained in a physiological L-lactate solution suitable for direct labeling processes. The 155Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155Tb-DOTATATE and 155Tb-MD, respectively. The relatively long physical half-life of 155Tb matched in particular the biological half-lives of 155Tb-cm09 and 155Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions: The radiolanthanide 155Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161Tb, 166Ho, and the pseudo-radiolanthanide 90Y

  19. CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.

    Science.gov (United States)

    Matsuo, Kazuhiko; Itoh, Tatsuki; Koyama, Atsushi; Imamura, Reira; Kawai, Shiori; Nishiwaki, Keiji; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

    2016-08-01

    CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. PMID:27132989

  20. Inhibitory efficacy of the quantified prunellae spica extract on H22 tumor bearing mice

    Science.gov (United States)

    Wang, Zhi-ping; Chen, Tong-sheng

    2013-02-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistence of the advanced hepatocarcinoma to chemotherapy. In this report, we assessed the antitumor activity of a prunellae spica aqueous extract (PSE) in vitro and in vivo. PSE was quantified by HPLC and UV. MTT assay showed that PSE did not effectively inhibit the growth of H22 cells. The in vivo anti-tumor activity was assessed by using the mice bearing H22 tumor. In vivo studies showed the higher antitumor efficacy of PSE without significant side effect assessed by the reduced tumor weight, and the extended survival time of the mice bearing H22 solid and ascites tumor. Collectively, PSE is a promising Chinese medicinal herb for treating hepatocarcinoma.

  1. Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin

    International Nuclear Information System (INIS)

    The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non-melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma

  2. 蜂毒素对人肝癌细胞裸鼠移植瘤生长的影响及其部分机制%Effect and partial mechanisms of melittin on human hepatocellular carcinoma cells xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    王朋景; 李俊; 黄艳; 吴宝明

    2011-01-01

    Objective To study the effects of melittin on the growth of human hepatocellular carcinoma HepG-2 cells xenograft in BALB/c nude mice and explore its possible mechanism of antitumor action in vivo. Methods The nude mice with HepG-2 cell xenografts were randomly divided into control group, melittin group(1 ,2,4 mg/ kg ), 5-FU group( 2 mg/kg ), administered for 10 days. The mice were killed 2 days after treatment. The xenograft tumor growth in mice was measured after injection of melittin. Tumor volume , tumor weight and spleen index were calculated. The levels of interlukin-l( IL-1 ) and tumor necrosis factor-a( TNF-α ) in serum of nude mice were detected by enzyme-linked immunosorbent assay( ELISA ). The apoptosis index of tumor tissue was measured by TUNEL method. Results While injected with l,2 and 4 mg/kg of melittin, the inhibitory rate of tumor growth were 41. 2% . 60. 9% and 71. 0% , respectively. The tumor volume of xenograft in nude mice was significantly smaller in melittin groups than that in control group( P <0. 01 ). Levels of IL-I and TNF-a. the apoptosis index in the melittin groups were significantly higher than those in the control group( P <0. 05 .P <0. 01 ) . Conclusion Melittin could inhibit the growth of tumor in vivo. which might be related to reinforcement of the immunity of mice and the apoptosis of tumor cells.%目的 探讨蜂毒素对人肝癌HepG-2细胞株裸鼠移植瘤的抑制作用.方法 建立人肝癌HepG-2细胞裸鼠皮下移植瘤模型,随机分为模型组、蜂毒素组(1、2、4 mg/kg)和氟尿嘧啶 (5-FU,2 mg/kg) 组,各组腹腔注射给药10 d,用药结束后隔天处死动物.观察蜂毒素腹腔注射对人肝癌细胞在裸鼠体内生长的的影响,计算各组裸鼠肿瘤的大小、瘤重及脾指数.ELISA法检测裸鼠血清白介素-1(IL-1)及肿瘤坏死因子-α(TNF-α).TUNEL法检测裸鼠移植瘤细胞凋亡情况.结果 蜂毒素(1、2、4 mg/kg)组的抑瘤率分别为41.2%、60.9%、71.0%,蜂

  3. Increased translocation of bacteria from the gastrointestinal tracts of tumor-bearing mice.

    OpenAIRE

    Penn, R L; Maca, R D; Berg, R D

    1985-01-01

    Aerobic gram-negative bacilli and other indigenous gastrointestinal (GI) bacteria are important opportunistic pathogens in immunosuppressed cancer patients. These same bacteria frequently translocate from the GI tracts of mice immunosuppressed by single injections of certain anticancer drugs or by T-lymphocyte impairments. Since similar cellular and humoral immune deficiencies may be present in the tumor-bearing host, we sought to determine if progressive growth of a tumor alone would be suff...

  4. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    OpenAIRE

    Kim Sung-Ho; Jung Uhee; Jo Sung-Kee; Ju Eun-Jin; Park Hae-Ran; Yee Sung-Tae

    2009-01-01

    Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of ...

  5. Antitumorigenic Potential of Diallyl Sulfide in Ehrlich Ascites Tumor Bearing Mice

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To study the effects of diallyl sulfide (DAS), an organosulfur compound present in garlic (Allium sativum),on the life span ofehrlich ascites (EA) tumor bearing Swiss albino mice, cytotoxicity and angiogenesis. Methods EA tumor cells were maintained by serial transplantation in peritoneal cavity of male Swiss albino mice. EA tumor cells were inoculated at concentrations of 1 × 106EA cells, 2.5 × l06EAcells and 5 × 106 EA cells. DAS was given in 0.2 mi normal saline i. p., daily for seven days followed one hour later by inoculation with EA cells in respective groups. Results The results revealed that administration of DAS increased the life span of EA tumor bearing animals by more than 25 percent. A significant dose dependant cytotoxic response of DAS was also observed on EA tumor cells. DAS was also found to inhibit the angiogenesis in EA tumor bearing mice in a dose dependent manner. Conclusion It is suggested that DAS may exert its anticarcinogenic effects by more than one mechanism and is a useful chemopreventive and chemotherapeutic agent.

  6. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy. PMID:20136435

  7. 量子点-RGD探针光动力疗法联合吉西他滨治疗胰腺癌荷瘤裸鼠初探%Efficacy of Quantum Dots-RGD Based Photodynamic Therapy Combined with Gemcitabine for Treatment of Pancreatic Cancer Xenograft in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    高双; 倪倩雯; 周敏; 徐雷鸣

    2014-01-01

    Background:Pancreatic cancer is obscure in onset and progresses rapidly with very poor prognosis. Photodynamic therapy( PDT)has been developed as a novel anti-tumor treatment modality since 1980s. At present,there are only limited researches on pancreatic cancer treated with PDT in vivo. Aims:To investigate the efficacy of quantum dots-RGD ( QDs-RGD)based PDT combined with gemcitabine for treatment of pancreatic cancer xenograft in nude mice. Methods:QDs-RGD probe was synthesized and nude mice bearing pancreatic cancer xenograft was established. Nude mice were imaged at 1,5,10 and 24 hours after injection of QDs-RGD and QDs by in vivo imaging system. Forty model nude mice were randomly divided into five groups:control group( without any treatment),simple illumination group( laser 630 nm, 120 J/cm2,20 min),PDT group(QDs-RGD 0. 5 nmol+laser irradiation),gemcitabine group(gemcitabine 50 mg/kg)and combination group(QDs-RGD 0. 5 nmol+laser irradiation+gemcitabine 50 mg/kg). All the nude mice were sacrificed 18 days later. Tumor weight and volume were measured and tumor inhibition rate was calculated. Results:Fluorescence of tumor was shown 1 hour after injection and became clearest at the 5th hour,then showing a decrescendo trend. Density of QDs surrounding tumor was significantly less than that of QDs-RGD and faded away at the 10th hour. Tumor weight and volume in PDT group,gemcitabine group and combination group were all significantly lower than those in control group and simple illumination group(P0. 05),as well as between PDT group and gemcitabine group(P >0. 05). Tumor inhibition rate in combination group,gemcitabine group and PDT group was 70. 5%,43. 5% and 37. 1%, respectively. Conclusions:QDs-RGD based PDT combined with gemcitabine can inhibit the growth of pancreatic cancer xenograft in nude mice,which introduces a new idea to the treatment of pancreatic cancer.%背景:胰腺癌发病隐匿,进展迅速,预后极差。光动力疗法( PDT)是20

  8. Tumor inhibiting and immunoloregulation effects of Mylabris Mixture on H22 cancer-bearing mice

    Directory of Open Access Journals (Sweden)

    A-Gao ZHOU

    2006-09-01

    Full Text Available Objective: To investigate the mechanisms of tumor inhibiting and immunoloregulation of Mylabris Mixture on H22 cancer-bearing mice. Methods: H22 cancer-bearing mice were chosen to observe the effects of tumor inhibiting and detect the proliferation function of T lymphocytes, the toxicity function of NK cells, the changes of T lymphocytes and the contents of interferon-γ and interleukin-4. Results: Mylabris Mixture could obviously inhibit the growth of H22 cancer in mice, and the tumor inhibition rat was 65.76%. The stimulation index of T lymphocyte transformation and percentage of NK cells in Mylabris Mixture-treated group were obviously higher than those in the normal control group. The subpopulation proportion of T lymphocytes in Mylabris Mixture-treated group was changed more than the normal control group. The production of interferon-γ and interleukin-4 by T lymphocytes obviously increased in Mylabris Mixture-treated group(P<0.05, P<0.001. Conclusion: Mylabris Mixture has the effect of inhibiting the growth of tumor constitution, and regulating immunological function on mice with tumor. Its mechanisms include the reinforcement of T lymphocyte immune function, NK cell killing function and humoral immune function.

  9. Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene.

    OpenAIRE

    Huang, S K; F. J. Martin; Jay, G; Vogel, J.; Papahadjopoulos, D; Friend, D S

    1993-01-01

    Transgenic mice bearing the HIV tat gene develop dermal lesions resembling a common malignant tumor in AIDS, Kaposi's sarcoma (KS). To evaluate the permeability characteristics of these lesions and the therapeutic potential of drug-carrying liposomes, we have studied the localization of sterically stabilized liposomes, which show long circulation time in blood and increased accumulation in tumors. Liposomes encapsulating colloidal gold were injected intravenously into transgenic mice bearing ...

  10. 光动力疗法联合贝伐珠单抗治疗裸鼠U87胶质瘤的实验研究%Combination of Photodynamic Therapy with Bevacizumab for Nude Mouse Bearing U87 Glioblastoma

    Institute of Scientific and Technical Information of China (English)

    孙影; 刘巍; 杨方

    2011-01-01

    目的 观察光动力疗法(PDT)联合贝伐珠单抗治疗裸鼠原位U87脑胶质瘤的效果并探讨其作用机制.方法 裸鼠颅内种植U87脑胶质瘤细胞7 d后,随机分为对照组、PDT组(ALA300 mg/kg,能量密度80 J/cm2)和联合治疗组(PDT+贝伐珠单抗).种植后第21天处死动物并取出脑组织.HE染色切片计算肿瘤体积;免疫组化染色检测Ki67、VEGF表达,分析肿瘤细胞的增殖和VECF地表达;TUNEL染色分析肿瘤细胞的凋亡.结果 与对照组比较,治疗组的肿瘤体积明显减小,细胞的凋亡也明显增加;与PDT组相比,联合治疗组的作用更为明显.单用PDT并不能抑制肿瘤细胞的增殖,但联合治疗的抑制作用非常明显.PDT的照射可诱导肿瘤周围组织中VEGF的表达增高,此作用可被贝伐珠单抗所抑制.结论 PDT联合贝伐珠单抗可明显抑制脑胶质瘤的生长,作用效果优于单用PDT,其作用机制为促进肿瘤细胞的凋亡、抑制细胞的增殖及PDT引起的肿瘤局部血管形成,本研究结果为临床联合应用PDT和贝伐珠单抗治疗脑胶质瘤提供了可靠的实验依据.%Objective To evaluate the effects of combination of photodynamic therapy (PDT) with bevacizumab on intracranial glioblastoma xenografts in nude mice.Methods Nude mice bearing intraeerebral U87 glioblastoma were treated with PDT and its combination ( PDT + bevacizumab).Tumor volume was analyzed to evaluate the outcome of different treatment modalities.In addition, the immunohistochemical expression of VEGF in the brain adjacent to the tumor; and in the tumor area TUNEL and immunohistoehemical stainings were used to measure apoptosis and proliferation.Results Compared with control, both of treatment methods could reduce the tumor volume and stimulate apoptosis; furthermore, compared with PDT alone, the combined treatment significantly increased apoptosis and reduced the tumor size.At the same time, Ki67 expression (a marker to indicate cells

  11. Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Bronzert, D; Vindeløv, L L;

    1989-01-01

    determined by repeated flow cytometric DNA analyses in vitro and in vivo and by the technique of labeled mitosis in nude mouse-grown tumors. Under in vitro conditions, estradiol induced a pronounced increase in S-phase fraction and cell number. TAM inhibited growth of MCF-7 cells with a concomitant increase...... cytometric DNA analysis and percentage of labeled mitosis investigations revealed no significant differences in the proliferation kinetics of TAM-treated and control tumors. Calculating the cell loss factor demonstrated an increase from 69% in control tumors to 107% in TAM-treated tumors. These experiments...

  12. Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice

    OpenAIRE

    Yang, Xiaoya; Li, Zhu; Ma, Yintu; Gao, Jun; Liu, Surui; Gao, Yuhua; Wang, Gengyin

    2014-01-01

    Background Human umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC). Methods hUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mic...

  13. Effects of Melittin on Angiogenesis of Human Hepatocellular Carcinoma BEL-7402 Cell Xenografts in Nude Mice%蜂毒素对人肝癌裸鼠移植瘤的抗血管生成作用

    Institute of Scientific and Technical Information of China (English)

    宋长城; 吕祥; 程彬彬; 李柏; 凌昌全

    2011-01-01

    Objective To study the effects of Melittin on the growth and angiogenesis of human hepatocellular carcinoma BEL-7402 cells xenograft in BALB/C nude mice. Methods The xenografts derived from BEL-7402 cells were established in BALB/C nude mice. The xenograft tumor growth in mice was measured after introtumoral injection of Melittin. SABC method of immunohistochemistry was used to measure microvessel density ( MVD ) and the expression of basic fibroblast growth factor ( Bfgf ),Hypoxia inducible factor-lct( HIF-lct ) and nuclear factor Kb ( NF-Kb ). Results When injected introtumorally with 40、60 and 80 μg/kg of Melittin, the relative tumor proliferation rate were 48. 78% 、38. 33% and 33. 82% respectively. The tumor volume of xenograft of nude mice was significantly smaller in Melittin groups than in normal saline ( NS ) control group ( P <0.01 ). MVD of Melittin-treated groups was significantly lower than that of NS control group ( P < 0.01 ). Immunohistochemical technique showed the expression of Bfgf,HIF-1α and NF-Kb of Melittin-treated groups was down-regulated significantly as compared with NS control group ( P <0.01 ). Conclusion Melittin could inhibit the growth of human hepatocellular carcinoma BEL-7402 cell xenografts in Nude Mice. The inhibition of angiogenesis by the down-regulation of b-FGF, HIF-1α and NF-Kb expression might play a key role in the anti-neoplastic effect of Melittin.%目的 探讨蜂毒素对人肝癌裸鼠移植瘤生长的影响及其抗血管生成作用.方法 建立人肝癌裸鼠皮下移植瘤模型,观察蜂毒素对肿瘤生长的影响.采用免疫组织化学法,检测肿瘤组织微血管密度 (microvessel density,MVD) 及碱性成纤维细胞生长因子 (basic fibroblast growth factor,bFGF)、缺氧诱导因子-1α (hypoxia inducible factor-1α,HIF-1α) 和核转录因子κB (nuclear factor κB,NF-κB) 的水平.结果 蜂毒素低、中、高剂量组相对肿瘤增殖率分别为 48.78%、38.33% 和33.82%.与生理

  14. Effect of combined treatment with cyclophosphamidum and allicin on neuroblastoma-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Xiang-Yang Gao; Xian-Jie Geng; Wen-Long Zhai; Xian-Wei Zhang; Yuan Wei; Guang-Jun Hou

    2015-01-01

    Objective:To evaluate the efficacy of allicin combined with cyclophosphamide on neuroblastoma (NB)-bearing mice and explore the immunological mechanism in it.Methods:A total of30 NB-bearing mice were equally randomized into model group, cyclophosphamide group and combined therapy group,10 nudemice were set as normal saline(NS) group.Cyclophosphamide group and combined therapy group were weekly injected with60 mg/kg cyclophosphamide for four weeks; besides, combined therapy group was given with allicin(10 mg/kg/d) by gastric perfusion for4 weeks; model group and NS group were given with the same volume of NS.Serum VEGF content was detected byELISA pre-treating(0 d) and on the3rd d,14th d and28th d; on 29th d, all mice were sacrificed and the tumor, liver, spleen and thymic tissues were weighted. Tumors were made into paraffin section for detecting tumor cell apoptosis and proliferation by TUNEL and BrdU method, respectively.Survival curves were drawn byKaplan-Meier method. Results:After treatment, both treatment groups relieved on viscera indexes,VEGF level,T cell subsets distribution and tumor growth and each index of combined therapy group was better than cyclophosphamide group(P<0.05 or0.01); only combined therapy group could significantly increase the lifetime of NB-bearing mice(χ²=5.667,P=0.017).Conclusions:Allicin can improve T cell subsets distribution and inhibitVEGF expression through its immunomodulatory activity, thereby improve the efficiency onNB in coordination with cyclophosphamide.

  15. Effect of combined treatment with cyclophosphamidum and allicin on neuroblastoma-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Xiang-Yang; Gao; Xian-Jie; Geng; Wen-Long; Zhai; Xian-Wei; Zhang; Yuan; Wei; Guang-Jun; Hou

    2015-01-01

    Objective:To evaluate the efficacy of allicin combined with cyclophosphamide on neuroblastoma(NB)-bearing mice and explore the immunological mechanism in it.Methods:A total of 30NB-bearing mice were equally randomized into model group,cyclophosphamide group and combined therapy group,10 nudemice were set as normal saline(NS) group.Cyclophosphamide group and combined therapy group were weekly injected with 60 mg/kg cyclophosphamide for four weeks;besides,combined therapy group was given with allicin(10 mg/kg/d) by gastric perfusion for 4 weeks;model group and NS group were given with the same volume of NS.Serum VEGF content was detected by ELISA pre-treating(0 d) and on the 3rd d.14 th d and 28 th d;on29th d,all mice were sacrificed and the tumor,liver,spleen and thymic tissues were weighted.Tumors were made into paraffin section for detecting tumor cell apoptosis and proliferation by TUNEI.and BrdU method,respectively.Survival curves were drawn by Kaplan-Meier method.Results:After treatment,both treatment groups relieved on viscera indexes,VEGF level,T cell subsets distribution and tumor growth and each index of combined therapy group was better than cyclophosphamide group(P<0.05 or 0.01);only combined therapy group could significantly increase the lifetime of NB-bearing mice(χ~2=5.667,P=0.017).Conclusions:Allicin can improve T cell subsets distribution and inhibit VEGF expression through its immunomodulatory activity,thereby improve the efficiency on NB in coordination with cyclophosphamide.

  16. A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.

    Science.gov (United States)

    Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

    2016-01-01

    5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53±1.65 mg/L(*)h vs 7.80±0.83 and 5.82±0.83 mg/L(*)h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU. PMID:27042001

  17. Dose-dependent effect of 17 beta-estradiol determined by growth curves and flow cytometric DNA analysis of a human breast carcinoma (T61) grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Vindeløv, L;

    1985-01-01

    An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17 beta-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 X 10(-8) to 6.9 X 10(-10) M. The effect of the...... fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle are a...... reflection of the estradiol-induced cell destruction. Since no tumor growth stimulation could be observed even at very low serum estradiol concentrations, the T61 human breast carcinoma may represent a new aspect in the study of human breast cancer....

  18. In vivo pharmacokinetics, biodistribution and the anti-tumor effect of cyclic RGD-modified doxorubicin-loaded polymers in tumor-bearing mice.

    Science.gov (United States)

    Wang, Chen; Li, Yuan; Chen, Binbin; Zou, Meijuan

    2016-10-01

    In our previous study, we successfully produced and characterized a multifunctional drug delivery system with doxorubicin (RC/GO/DOX), which was based on graphene oxide (GO) and cyclic RGD-modified chitosan (RC). Its characteristics include: pH-responsiveness, active targeting of hepatocarcinoma cells, and efficient loading with controlled drug release. Here, we report the pharmacokinetics, biodistribution, and anti-tumor efficacy of RC/GO/DOX polymers in tumor-bearing nude mice. The objective of this study is to assess its targeting potential for tumors. Pharmacokinetic and biodistribution profiles demonstrated that tumor accumulation of RC/GO/DOX polymers was almost three times higher than the others, highlighting the efficacy of the active targeting strategy. Furthermore, the tumor inhibition rate of RC/GO/DOX polymers was 56.64%, 2.09 and 2.93 times higher than that of CS/GO/DOX polymers (without modification) and the DOX solution, respectively. Anti-tumor efficacy results indicated that the tumor growth was better controlled by RC/GO/DOX polymers than the others. Hematoxylin and eosin (H&E) staining showed remarkable changes in tumor histology. Compared with the saline group, the tumor section from the RC/GO/DOX group revealed a marked increase in the quantity of apoptotic and necrotic cells, and a reduction in the quantity of the blood vessels. Together, these studies show that this new system could be regarded as a suitable form of DOX-based treatment of the hepatocellular carcinoma. PMID:27244048

  19. Experimental study of different platinum alone or combined with taxanes or vinoreibine on nude mice implanted human non-small cell lung cancer NCI-H460 cells in vivo%不同铂类联合紫杉类或长春瑞滨对非小细胞肺癌荷瘤裸鼠抑瘤作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    秦叔逵; 黄勇; 隋东虎; 李进; 楼丽广

    2011-01-01

    目的 探讨洛铂(LBP)、顺铂(DDP)和卡铂(Cab)单用或联合紫杉醇(PTX)、多西他赛(DOC)和长春瑞滨(NVB)对非小细胞肺癌(NSCLC)荷瘤裸鼠的抑瘤作用.方法 选用人大细胞肺癌细胞株NCI-H460接种于裸小鼠皮下成瘤.单药抑瘤实验中设LBP(3.75、7.5、15 mg/kg)3组及Cab(60mg/kg)、DDP(5mg/kg)各1组;联合抑瘤实验设LBP(7.5mg/kg)、DPP(2.5mg/kg)分别与DOC(5mg/kg)、PTX(12mg/kg)、NVB(5mg/kg)联合共6组以及各自单药5组,每组均随机分配6只成瘤小鼠,经静脉d0、d7给药(PTX d0、d2、d4给药除外).各设1组对照组,每组12只.每周2~3次记录瘤体体积和裸鼠体重,并计算相对肿瘤增殖率(T/C).结果 (1)单药抑瘤实验中,LBP抑瘤效果与剂量相关,中、高剂量组的T/C分别为51.1%和36.3%,低于Cab组(51.6%),但LBP高剂量组有1只小鼠出现药物相关性死亡.对裸鼠体重的影响由大到小依次为:DDP组>LBP高剂量组>LBP中剂量组>Cab组>LBP低剂量组.(2)联合抑瘤实验中,LBP+PTX组的T/C最低,为24.4%,明显优于DDP+PTX组(P<0.05);LBP+DOC组和DDP+DOC组亦对小鼠体重有明显影响.结论 LBP单药对NCI-H460荷瘤小鼠的抑瘤作用呈剂量依赖性,介于DDP与Cab之间;而LBP联合PTX的抑瘤作用最强,明显优于DDP联合PTX及其他两药联合.%Objective To investigate the inhibitory effects of lobaplatin (LBP), cisplatin (DDP) and caboplatin ( Cab ) alone or combined with paclitaxel ( PTX ), docetaxel ( DOC ) and vinorelbine ( NVB ) respectively against nude mice bearing human non-small cell lung cancer(NSCLC) NCI-H460 cells in vivo.Methods NCI-H460 cells were implanted into nude mice.In monotherapy treatment study, the nude mice beating human NSCLC NCI-H460 cells were randomly divided into 5 groups with 6 mice in each group.In concomitant treatment study, the nude mice bearing human NSCLC NCI-H460 cells were randomly divided into 11 groups, and each group had 6 mice.The volume of tumor, the weight of nude

  20. Dynamic Contrast-Enhanced Magnetic Resonance Imaging Rapidly Indicates Vessel Regression in Human Squamous Cell Carcinomas Grown in Nude Mice Caused by VEGF Receptor 2 Blockade with DC101

    Directory of Open Access Journals (Sweden)

    Fabian Kiessling

    2004-05-01

    Full Text Available The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF receptor 2 antibody (DC101 using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI. Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value and kep (exchange rate constant. Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31. Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P = .02. In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 ± 843 mm3 and control animals (596 ± 384 mm3 were significantly different (P = .03. After 14 days, treated tumors showed further growth reduction (83 ± 93 mm3, whereas untreated tumors (1208±822 mm3 continued to increase (P=.02. Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

  1. Saccharomyces cerevisiae, the Baker's Yeast, suppresses the growth of Ehrlich carcinoma-bearing mice.

    Science.gov (United States)

    Ghoneum, Mamdooh; Badr El-Din, Nariman K; Noaman, Eman; Tolentino, Lucilene

    2008-04-01

    This study was undertaken to evaluate the effectiveness and mechanisms of anti-tumor activity of Baker's yeast, Saccharomyces cerevisiae, in immunocompetent mice. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich Ascites Carcinoma (EAC) cells. At day 8, mice bearing Solid Ehrlich Carcinoma tumor (SEC) were intratumorally (IT) injected with killed S. cerevisiae (10 x 10(6) and 20 x 10(6) cells) for 35 days. Histopathology of yeast-treated mice showed extensive tumor degeneration, apoptosis, and ischemic (coagulative) and liquefactive necrosis. These changes are associated with a tumor growth curve that demonstrates a significant antitumor response that peaked at 35 days. Yeast treatment (20 x 10(6) cells) three times a week resulted in a significant decrease in tumor volume (TV) (67.1%, P Yeast administered three and two times per week induced significant decrease in TV as early as 9 and 25 days post-treatment, respectively. Administration of yeast significantly enhanced the recruitment of leukocytes, including macrophages, into the tumors and triggered apoptosis in SEC cells as determined by flow cytometry (78.6%, P yeast treatment elevated TNF-alpha and IFN-gamma plasma levels and lowered the elevated IL-10 levels. No adverse side effects from the yeast treatment were observed, including feeding/drinking cycle and life activity patterns. Indeed, yeast-treated mice showed significant final body weight gain (+21.5%, P yeast, which is known to be safe for human consumption. PMID:17891396

  2. Isotype profiles of anti-influenza antibodies in mice bearing the xid defect

    International Nuclear Information System (INIS)

    The humoral response to influenza A/PR8 virus was examined in the CAB/N and C3J.xid strains of mice, both of which bear an X-linked genetic defect (xid), and in strains lacking this defect. Hemagglutination-inhibiting antibody titers and measurement of virus-specific antibodies by solid-phase radioimmunoassay indicated that the xid defect does not impair the production of an adequate anti-influenza antibody response. However, investigation of the isotopes of PR8 virus-specific antibodies disclosed a relative decrease in the levels of IgG3 and IgG1 in the xid-bearing strains. This was observed after both intraperitoneal immunization and aerosol infection. The isotope differences were not reflected in the susceptibility of these strains to influenza virus infection

  3. Distribution of 14C-ambazone in normal and leukemia P 388-bearing mice

    International Nuclear Information System (INIS)

    There is some evidence in the literature that the pharmacokinetics of anticancer agents can be influenced by the presence of a tumor. Therefore several authors recommend pharmacokinetic studies of such drugs to be performed also in tumor-bearing animals. The aim of the present study was to evaluate the influence of different stages and routes of inoculation of leukemia P 388 in B6D2F1-hybrid mice on the tissue distribution of ambazone, a new potential antineoplastic drug. It could be emphasized that the drug levels in liver, kidneys and thymus were higher in advanced tumor-bearing than in control animals whereas in the spleen and in whole blood the opposite was true. The differences can be explained partially by changes in the erythrocyte binding of ambazone. (author)

  4. Enhancement of radiomodulatory effect through liposome encapsulated radio-modifier on cancer bearing mice

    International Nuclear Information System (INIS)

    Efficacy of a radioprotective drug, 2-mercaptopropionylglycine (MPG), in its free form and after its encapsulation into liposomes have been studied in normal and cancer bearing mice. Cancer was induced in micy by oral administration of aqueous extract of betel nut (AEBN) for 3 months. Radioprotection afforded by free MPG and liposome encapsulated MPG (LEM) in normal and cancerous tissue were evaluated by monitoring levels of glutathione (GSH) and γ-glutamyltranspeptidase (GGT) enzyme and state of structural organization of chromatin. The results of our studies reveal that in cancerous tissues LEM afforded better radioprotection than the free form of MPG. (orig.)

  5. Biodistribution in sarcoma 180-bearing mice of N-succinyl-chitosan nanoparticles for tumor targeting

    OpenAIRE

    Cheng, Yan; Yan, Chengyun; Gu, Jiwei; Wang, Xi; Huang, Zhan; Chen, Dawei

    2011-01-01

    In the present study, we sought to systemically evaluate the biodistribution and the tumor-accumulation of N-succinyl-chitosan nanoparticles (Suc-Chi-NPs, 200 nm in diameter) in model tumor-bearing mice and also the binding of Suc-Chi-NPs to k562 cells was evaluated by flow cytometry. In vitro studies showed that all Suc-Chi-NPs displayed high affinity to k562 cells. After intravenous injection of Suc- Chi-NPs via the tail vein, a small amount of Suc-Chi-NPs was found in liver and spleen for ...

  6. Inhibitions of Several Antineoplastic Drugs on Serum Sialic Acid Levels in Mice Bearing Tumors

    OpenAIRE

    Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

    2012-01-01

    Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, ...

  7. UHPLC-MS-based metabolomics analysis on mice bearing neoplasm (H22) for hispidulin.

    Science.gov (United States)

    Li, Fuqiang; Li, Xiang; Miao, Yunjie; Shan, Chenxiao; Yuan, Fei; Ma, Chengyao; Wang, Qiwen; Chen, Jianwei; Chen, Yong

    2016-06-01

    Although some physiological and pathological function parameters of hepatitis and liver cancer have been investigated in relation to hispidulin (5,7,4'-trihydroxy-6-methoxyflavone), the changes of small metabolites in biofluids have been reported rarely. Recent research has shown that metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis provides a good understanding of hispidulin effects on mice vaccinated intraperitoneally with H22 tumor cells. Twenty-five potential biomarkers, up- or down-regulated (Pniacinamide, cortisol, uracil and 5-thymidylic acid are potential biomarkers that may explain the link between hispidulin and the metabolism of mice bearing neoplasm (H22). Most of the potential biomarkers related to the function of TCA (tricarboxylic acid cycle). The rise of potential biomarkers in the drug groups promoted the up-regulation of TCA cycle compared with the model group. PMID:27077962

  8. Inhibitory effect of low dose irradiation on tumor metastases in tumor bearing in mice

    Institute of Scientific and Technical Information of China (English)

    魏道严; 金敖兴; 等

    1996-01-01

    By using the models of tumor blood-borne metastasis and spontaneous one,the antitumor metastasis effect of 75mGy X-ray whole body irradiation on tumor bearing mice is investigated.The results demonstrate that irradiation could significantly inhigit B16 Melanoma blood borne pulmonary metastases(P<0.05) and Lewis lung carcinoma(LLC) spontaneous pulmonary metastases(P<0.01),The immunofunction test of B16 melanoma beraing mice shows that the NK(P<0.05) and LAK(P<0.001) cytotoxicities,and responsibility of splenocytes to IL-2(P<0.005) for the irradiated group are increased greatly comperaed with those of control group.These results suggest that the enhancement of immunofunctions is induced by low dose radiation to raise antitumor metastasis effects.

  9. Anticancer activity of Jasminum angustifolium Linn against Ehrlich ascites carcinoma cells bearing mice

    Directory of Open Access Journals (Sweden)

    Pradeep Rajkumar

    2012-06-01

    Full Text Available Objective: Present investigations were carried out for evaluation of antitumor and in vitro antioxidant activity of ethanol and aqueous extracts of Jasminum angustifolium Linn. Methods: For its antitumor activity, Ehrlich ascites carcinoma (EAC induced swiss albino mice were used and were divided into five group with 6 animal each.The antitumor effect was assessed using viable tumour cell count, packed cell volume, body weight, mean survival time and percentage increase in life span. Apart from that, hematological and liver enzyme studies were noticed upon the ethanol and aqueous extracts of Jasminum angustifolium Linn administered at 500 mg/kg per day for 14 days, after 24 hours of tumor inoculation. Results: Treatment with extracts significantly restored the altered parameters to normal when compared to cancer control group. Conclusion: The results suggest that ethanol extract of Jasminum angustifolium Linn possess significant antitumor effects in EAC tumour bearing mice. [J Exp Integr Med 2012; 2(3.000: 271-275

  10. Radioprotection by seed extract of Syzygium cumini in normal tissues of fibrosarcoma bearing mice

    International Nuclear Information System (INIS)

    Syzygium cumini Linn. (family Myrtaceae), commonly known as Jamun, is a medicinal plant and utilizable species which is widely used for its antioxidant activities to treat different ailments in many parts of the world. The current study was undertaken to study the effect of seed extract of Syzygium cumini in normal as well as in tumor bearing mice against gamma radiation-induced cellular damage in biological tissues. This was done to mimic the clinical setting wherein, normal tissues of cancer patients undergoing, radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analyzed in peripheral blood leucocytes of whole-body irradiated mice following pretreatment with hydo-alcoholic seed extract of Syzygium cumini (100 mg/kg b. wt./day), using alkaline comet assay and by estimating biochemical parameters such as antioxidant enzymes i.e. (superoxide dismutase and catalase), GSH, LPO and total proteins in organs like spleen, liver and intestine. For this purpose, Swiss albino mice were administered Syzygium cumini extract (SCE) orally once daily for 5 consecutive days, then exposed to a single dose of 3, 6 and 9 Gy of gamma radiation. The results showed that the seed extract of Syzygium cumini protected the liver, spleen and intestine both in normal as well as tumor bearing mice. This study concludes that seed extract of Syzygium cumini has protective effects against radiation-induced cellular damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties. Hence, seed extract of Syzygium cumini may be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating side effects of radiation to normal tissues during radiotherapy. (author)

  11. Distribution of Selenium and Oxidative Stress in Breast Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Pei-Chung Chen

    2013-02-01

    Full Text Available The present study investigated the effects of breast tumors on the blood and tissue distribution of essential trace mineral selenium (Se, and oxidative stress status of mice. Female 10-week-old BALB/cByJNarl mice were randomly assigned into control (CNL and breast tumor-bearing (TB groups. TB mice were injected subcutaneously into the right hind thigh with 5 × 106 EMT6 mouse mammary tumor cells. After 22 days, we measured Se concentrations, Se-dependent glutathione peroxidase (GPx activities, and malondialdehyde (MDA products (indicator of oxidative stress in plasma, various tissues, and plasma vascular endothelial growth factor (VEGF concentrations. There were no significant differences in body weights and daily intake between both groups. Compared with the CNL group, TB mice have decreases in plasma Se concentrations and GPx activities, as well as higher plasma VEGF and MDA concentrations. Plasma Se concentrations were also negatively correlated with plasma MDA and VEGF concentrations. Furthermore, tissue Se concentrations and GPx activities in TB animals were lower; whereas the MDA concentrations higher in various tissues including liver, kidney, brain, lung, spleen, and thymic tissues. In conclusion, disruption of Se homeostasis critically reflects oxidative stress in target tissues, thus may increase the risk for progression of breast cancer and metastasis.

  12. Inhibition of lymphangiogenesis, nodal and lung metastasis by dihydroartemisinin in mice bearing Lewis lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the activity of anti-malarial dihydroartemisinin (DHA) on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma (LLC). Methods: The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups: control group, DHA group, DHA + ferrous sulfate (FS) group and FS group, with 25 mice in each group. Tumor volumes and weights, nodal and lung metastasis, and survival were monitored. Tumor lymphatic microvessel density (LMVD) was determined by lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) immnohistochemistry. After LLC cells were treated with DHA or DHA + FS, protein and mRNA levels of vascular endothelial growth factor (VEGF) -C were evaluated by Western blotting and real time quantitative RT-PCR, respectively. Results: Oral administration of DHA or DHA+FS inhibited lymph node and lung metastasis, and prolonged survival. However, no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions, but not in the in-tratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion; DHA effectively inhibits LLC transplantation tumor lymphangiogenesis, nodal and lung metastasis, and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.

  13. Dexamethasone modulates the radiotherapeutic effect of labeled iodo-ancitabine in solid tumor bearing mice

    International Nuclear Information System (INIS)

    Ancitabine is one of the potent chemotherapeutic anticancer drugs. iodoancitabine (125I-ANC) was prepared by electrophilic substitution using iodogen as an oxidizing agent which produce yield above 90 % at ph 7 with heating on a water bath to 65 degree C within 10 min as reaction time. The labeled drug was stable for 48 h post labeling . Biodistribution study of 125I-ANC in normal mice reflected that its uptake was increased in organ of high proliferation like stomach. In solid tumor bearing mice 125I-ANC was incorporated rapidly in tumor site and declined slowly, while declined rapidly from other tissues like blood. The therapeutic activity of 125I-ANC was significantly increased with the increase of radioactivity by decreasing the percent viability when examined on EAC cells. Significant increase in the percent survival was observed by locoregional administration (intramuscular in the inoculated thigh) than in the control. Also, starting treatment at the third day was the best day to start treatment . Furthermore,125I-ANC has been showed significant decrease in the size of the tumor treated leg when compared to the control tumor one. Mice received dexamethasone (DEX) showed significant increase in the uptake of 125I-ANC in tumor site. Radiotherapy using DEX produced significant decrease in the size of tumor especially when mice received DEX 10 days before inoculation.

  14. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2013-01-01

    Full Text Available Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET’s anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo.

  15. Inhibition and SAHA combined with DDP on cervical cancer xenografts in nude mice%SAHA联合顺铂对裸鼠宫颈癌抑瘤作用及其机制

    Institute of Scientific and Technical Information of China (English)

    田志华; 郝钢华; 侯晓静; 邢军

    2015-01-01

    目的:观察组蛋白去乙酰化酶抑制药SAHA联合顺铂(cis-diamminedichloroplatinum,DDP)抑瘤作用及机制。方法饲养40只Balb/c-nu/nu雌性裸鼠,细胞悬液皮下注射法构建人宫颈癌SiHa细胞株裸鼠移植瘤模型,当移植瘤8~10 mm大小时,36只荷瘤裸鼠被随机分为6组(对照组、25 mg/kg SAHA组、50 mg/kg SAHA组、5 mg/kg DDP组、25 mg/kg SAHA+DDP组、50 mg/kg SAHA+DDP组),给药第17天拉颈处死裸鼠。对移植瘤的湿重、瘤体积、肿瘤生长抑制率输入SPSS 19.0软件进行统计学分析。结果与各对照组比,联合组显示出最大程度的肿瘤体积的缩小及肿瘤生长抑制率增加(P<0.05)。结论 SAHA与DDP联合治疗宫颈癌,其作用机制可能与组蛋白去乙酰化酶1(histone deacetylase 1,HDAC1)蛋白水平下调有关。%[Absrract]ObjectiveTo study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N-phenyloctanediamide) combined with cis-diamminedichloroplatinum (DDP) on cervical cancer cells (SiHa) in nude mice.MethodsCervical cancer cell suspension was subcutaneously injected into 40 nude mice to establish cervical cancer model. When the transplanted tumor was about 8 mm in length, 36 mice with tumor in similar size were selected and divided into six groups (control group, 25 mg/kg SAHA group, 50 mg/kg SAHA group, 5 mg/kg DDP group, 25 mg/kg SAHA+DDP group) , and 50 mg/kg SAHA+DDP group. Nude mice were killed on the 17th day. Wet weight of tumor, inhibitory rate and tumor volume were collected. SPSS 19.0 software was used for statistical analysis.ResultsCompared with the control group, the DDP plus SAHA group showed superiority in inhibiting tumor growth (P<0.05).ConclusionThe effects from SAHA and DDP might be associated with down-regulating expressions of HDAC1 protein.

  16. Dynamic Observation on In vivo Bioluminescence Imaging of Experimental Metastatic Animal Models in Nude Mice%实验性肿瘤细胞转移动物模型的活体成像观察

    Institute of Scientific and Technical Information of China (English)

    闫明霞; 朱淼鑫; 刘蕾; 李静; 林河春; 赵方瑜; 姚明

    2012-01-01

    Objective To observe the tumor metastasis in deep organisms of the nude mice by in vivo bioluminescence imaging system. Methods The SMMC-7721-GFP/Luc cells with different concentrations were intravenously inoculated into the tail vein and spleen of the BALB/c-nu/nu mice, the distribution and expression of luciferase in nude mice were monitored by in vivo bioluminescence imaging system. Results The experimental metastatic animal models had been successfully established. The distribution and expression of luciferase ascended with cell concentration increased and decreased with the passage of time. Conclusion The in vivo bioluminescence imaging system may monitor the in vivo growth and metastasis of tumors and provide for studying the mechanisms of tumor metastasis and development of anticancer drug.%目的 利用小动物活体成像系统观察肿瘤细胞在动物体内的转移情况.方法 分别将不同浓度的绿色荧光蛋白(GPF)和荧光素酶(luciferase,Luc)双标的SMMC-7721细胞接种入裸小鼠尾静脉和脾,建立实验性转移动物模型,采用活体成像技术监测不同浓度的细胞在小鼠体内的转移情况,动态观察同一细胞于不同时间点在小鼠体内的转移情况.结果 成功建立了尾静脉接种肺转移及脾内接种肝转移的实验性转移动物模型,经小动物活体成像系统检测发现,随着接种细胞浓度的增加,荧光素的表达面积和强度逐渐增加,二者呈正比关系;随着接种时间的延长,荧光素的表达面积和强度逐渐减弱,二者呈成反比关系.结论 活体荧光成像系统可较好地观测肿瘤在动物体内深部脏器的转移情况,它将为肿瘤转移机制、抗转移治疗等研究提供有益的帮助.

  17. Inhibition of rhabdomyosarcoma in nude mice by TNF related apoptosis inducing ligant combined with diamminedichloroplatinum%TRAIL蛋白联合顺铂抑制裸鼠横纹肌肉瘤生长的实验研究

    Institute of Scientific and Technical Information of China (English)

    苗金红; 徐玉生; 王家祥

    2009-01-01

    目的 探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)蛋白及联合顺铂对RD人横纹肌肉瘤裸鼠移植瘤生长的影响及其可能的作用机制.方法 将RD人横纹肌肉瘤细胞制成细胞悬液后接种于裸鼠皮下,成瘤后将裸鼠随机分4组:生理盐水组、TRAIL组、顺铂组及两药联合组.检测裸鼠的重量和体积;测定裸鼠肝功能、尿素氮及肌酐;另取肝肾组织进行切片,HE染色观察;用FCM方法检测肿瘤组织Fas表达;用RT-PCR检测DR4和DR5mRNA的表达.结果 各组裸鼠实验前后的体重变化无明显差异;DDP组和TRAIL+DDP组裸鼠的血清丙氨酸转氨酶高于生理盐水组,DDP组与TRAIL+DDP组裸鼠尿素氮和肌酐值比较,无明显差异;TRAIL组、DDP组和TRAIL+DDP组移植瘤的重量均明显降低;各组肝肾组织切片观察未见明显改变;TRAIL+DDP组Fas表达水平高于DDP组和TRAIL组;DDP组和TRAIL+DDP组裸鼠移植瘤细胞的DR5mRNA、DR4mRNA表达水平明显升高,而TRAIL组没有明显改变.结论 TRAIL和顺铂对裸鼠移植瘤的生长有抑制作用,联用有协同作用.%Objective To observe the effect of inhibition of rhabdomyosareoma in nude mice treated by TNF related apoptosis inducing ligant (TRAIL) combined with diamminedichloroplatinum (DDP), and try to explore the mechanism. Methods Human rhabdomyosareoma cells were inoculated in nude mice subcutaneouly. The nude mice were randomly divided into 4 groups: mice in the TRAIL groups accepted TRAIL injection with the dose of 10μg/Kg; mice in the DDP group accepted DDP in-jection with the dose of 3 mg/kg; mice in the TRAIL + DDP group accepted TRAIL and DDP injection with the abovementioned doses; mice in the control group accepted normal saline injection. The chan-ges of tumor weight and size and the tumor growth inhibition rate were recorded. The functions of liv-er and kidney were evaluated. HE staining was utilized to observe the morphologic changes of livers and kidneys. The expression

  18. Determination of liposomal boron biodistribution in tumor bearing mice by using neutron capture autoradiography

    International Nuclear Information System (INIS)

    It is necessary to accumulate the 10B atoms selectively to the tumor cells for effective boron neutron capture therapy (BNCT). In order to achieve accurate measurements of 10B concentrations in biological samples, we employ a technique of neutron capture autoradiography (NCAR) of the sliced whole body samples of tumor bearing mice using CR- 39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University. We obtained NCAR images for mice injected intraveneously by 10B-polyethylene-glycol (PEG) binding liposome or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha and lithium track density measurements. In this study, we increased the accumulation of 10B atoms in the tumor tissues by binding PEG chains to the surface of liposome, which increase the retension in the blood flow and escape the phagocytosis by reticulo-endotherial systems. Therefore, 10B-PEG liposome is a candidate for an effective 10B carrier in BNCT.(author)

  19. Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment

    Directory of Open Access Journals (Sweden)

    Nicol B.M.

    2002-01-01

    Full Text Available Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight or cisplatin (ip, 8 mg/kg body weight treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 µmol/g increased with tumour progression (1.44-1.59 µmol/g; P<=0.05 in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain also increased (~40, 10, 30 and 58%, respectively in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA. It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression.

  20. Antagonism between gene therapy and epigenetic therapy on human laryngeal carcinoma tumor-bearing mice

    Institute of Scientific and Technical Information of China (English)

    LIAN Meng; WANG Qi; FANG Ju-gao; WANG Hong; FAN Er-zhong

    2013-01-01

    Background Gene therapy and epigenetic therapy have gained more attention in cancer treatment.However,the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet.To study the mechanism and clinical application,human laryngeal carcinoma cell (Hep-2) tumor-bearing mice were used.Methods A xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice.The mice with well-formed tumor were randomly divided into six groups.Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor.Tumor growth was monitored by measuring tumor volume and growth rate.p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining.The mRNA levels were monitored with FQ-PCR.Results Gene therapy was much more effective than single epigenetic therapy and combined therapy.The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin.Conclusions The combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma,because gene therapy shows an antagonistic effect to epigenetic therapy.However,the mechanisms of action are still unclear.

  1. Treatment of established colon carcinoma-bearing mice by dendritic cells pulsed with lysates of heat-treated tumor cells

    Institute of Scientific and Technical Information of China (English)

    YING MinGang; ZHEN QiuHong; LIU Sheng; GONG FuSheng; XIE YunQing

    2009-01-01

    To investigate the therapeutic effect of dendritic cells pulsed with lysates of heat-treated CT26 colon carcinoma cells. Bone marrow-derived DCs were pulsed with lysates of heat-treated tumor cells and were used to immunize BALB/c mice with established colon carcinoma. Cytotoxic T lymphocyte (CTL) response was detected. The therapeutic effect induced by DCs was observed by tumor weight and survival time. DCs pulsed with lysates of heat-treated tumor cells markedly induced specific cytotoxic activity of CTLs. Tumor growth in the immunized BALB/c mice was significantly inhibited and the survival time of the tumor-bearing mice was prolonged, DCs pulsed with lysates of heat-treated tumor cells have an observable therapeutic effect on established colon carcinoma-bearing mice.

  2. Tumor inhibitory activity of methanolic and ethyl acetate soluble extracts of Thuja occidentalis L. on mice bearing Ehrlich ascites carcinoma.

    Directory of Open Access Journals (Sweden)

    Archana M Navale

    2014-06-01

    Full Text Available Thuja occidentalis (Cupressaceae is an ornamental plant of European origin. It has been used in folk medicine for the treatment of cancer. Mice bearing Ehrlich Ascites Carcinoma (EAC mice were treated with methanolic extract (165 mg/kg, ethyl acetate soluble fraction (30 mg/kg and combination of both extracts of TO. Inhibition of tumor growth, increase in survival time of animal with treatment, and hematological parameters were determined. Both methanolic and ethyl acetate soluble fractions of TO exerted tumor growth inhibitory activity in mice bearing EAC. Combination treatment of two extracts showed more pronounced effect. In conclusion, Methanolic and ethyl acetate soluble extracts of TO exhibit anticancer activity against Ehrlich ascites carcinoma in mice. Thus, it has anticancer potential and should be further evaluated in higher models.

  3. Treatment of established colon carcinoma-bearing mice by dendritic cells pulsed with lysates of heat-treated tumor cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To investigate the therapeutic effect of dendritic cells pulsed with lysates of heat-treated CT26 colon carcinoma cells. Bone marrow-derived DCs were pulsed with lysates of heat-treated tumor cells and were used to immunize BALB/c mice with established colon carcinoma. Cytotoxic T lymphocyte (CTL) response was detected. The therapeutic effect induced by DCs was observed by tumor weight and survival time. DCs pulsed with lysates of heat-treated tumor cells markedly induced specific cytotoxic activity of CTLs. Tumor growth in the immunized BALB/c mice was significantly inhibited and the survival time of the tumor-bearing mice was prolonged. DCs pulsed with lysates of heat-treated tumor cells have an observable therapeutic effect on established colon carcinoma-bearing mice.

  4. STAT1基因转染对人肺腺癌裸鼠移植瘤生长的影响%Effect of STAT1 gene transfection on human lung carcinoma xenograft growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    马源; 陈俊杰; 陈成水; 王梦怡; 李晓丹; 陈超蕾; 陈乐夫; 余静; 周伶俐

    2013-01-01

    Objective:To investigate the effects of signal transduction and activators of transcription 1 in the progression of lung cancer in vivo.Methods:STAT1 gene or empty vectors were transfected into NCL-H 1299 cells with plasmids constructed as previous.Nude mice were transplanted subcutaneously with H 1299 cells,H1299 cells transfected with empty vectors,H1299 stably transfected with STAT1,respectively.The size of tumor was examined by caliper every two days.Five weeks after inoculation,the tumors were resected and weighed.Western blot was used to detect the level of STAT1 protein in tumor tissues.Results:Both volume and weight of the tumor in the STAT1 transfected group were less than those in the other groups (P<0.05).Western blot revealed that the protein level of STAT1 and phosphorylated-STAT1 in STAT1 transfected group were rises notably.Conclusion:The recombinant plasmid STAT1 can significantly suppress the tumor growth of human lung cancer cell NCL-H1299 subcutaneous xenografts in nude mice through up-regulate of STAT1 expression.%目的:探讨信号转导和转录活化因子1 (signal transduction and activators of transcription 1,STAT1)基因转染对肺癌移植瘤生长的影响.方法:构建稳定转染STAT1基因(转染组)及空载体(空载体组)的肺腺癌NCL-H1299细胞,使用未转染的细胞及上述两种转染细胞分别建立裸鼠皮下移植瘤模型,连续观察并测量肿瘤生长情况,Western blot法检测肿瘤组织内STAT1活化情况.结果:STAT1基因转染组裸鼠移植瘤接种33 d后瘤体积及瘤重小于未转染组及空载体组(均P<0.05).Western blot检测结果提示STAT1转染组的肿瘤组织STAT1表达及磷酸化水平均明显升高.结论:STAT1基因转染可提高移植瘤组织内STAT1活化水平,并对肿瘤生长起抑制作用.

  5. Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

    Science.gov (United States)

    Koga, Y; Naraparaju, V R; Yamamoto, N

    1999-01-01

    Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor. PMID:9893164

  6. Influence of concomitant infusion of thymidine and inosine on methotrexate activity in normal and P388-bearing mice

    NARCIS (Netherlands)

    Uitendaal, Martin P.; Schornagel, J.H.; Leyva, A.; Pinedo, H.M.

    1984-01-01

    Combinations of thymidine and inosine (ranging from 0 to 7.5 mg/hr) were co-administered during a 72-hr continuous i.v. infusion of 3 μg/hr methotrexate in normal and P388 solid tumor-bearing DBA/2 mice. Methotrexate alone was lethal to all normal mice. Inosine at 1.0–7.5 mg/hr could reverse toxicit

  7. Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice

    International Nuclear Information System (INIS)

    The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because Nω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression

  8. Evaluation of radiogallium-labeled, folate-embedded superparamagnetic nanoparticles in fibrosarcoma-bearing mice

    Directory of Open Access Journals (Sweden)

    Seyyedeh Leila Hosseini-Salekdeh

    2012-01-01

    Full Text Available Context: Elevated expression of the folate receptor (FR occurs in many human malignancies. Thus, folate targeting is widely utilized in drug delivery purposes specially using nano-radioactive agents. Aims: In this work, we report production and biological evaluation of gallium-67 labeled superparamagnetic iron oxide nanoparticles, embedded by folic acid ( 67 Ga-SPION-folate complex especially in tumor-bearing mice for tumor imaging studies. Settings and Design: The structure of SPION-folate was confirmed by X-ray diffraction (XRD, transmission electron microscopy (TEM and foureir transform infrared spectroscopy (FT-IR analyses. The radiolabeled SPION-folate formation was confirmed by instant thin layer chromatography (ITLC. Tumor induction was performed by the use of poly-aromatic hydrocarbon injection in rodents as reported previously. Materials and Methods: [ 67 Ga]-SPION-folate was shown to possess a particle size of ≈5-10 nm using instrumental methods followed by ITLC test. Biocompatibility of the compound was investigated using an 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay followed by stability tests and tumor accumulation studies in fibrosarcoma-bearing mice after subcutaneous (s.c. application. Statistical Analysis Used: All values were expressed as mean ± standard deviation (mean ± SD and the data were compared using Student t-test. Statistical significance was defined as P95% radiochemical purity. Biodistribution studies demonstrated tumor:blood, tumor:bone and tumor:muscle ratios of 4.23, 4.98 and 11.54 respectively after 24 h. Conclusions: Due to the nano-scale size and high-penetrative property of the developed folate-containing nano-complex, this system can be an interesting drug delivery modality with therapeutic applications and folate receptor-targeting behavior, while possessing paramagnetic properties for thermotherapy.

  9. Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

    International Nuclear Information System (INIS)

    Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD50) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

  10. Dosimetric measurements and radiobiological consequences of radioimmunotherapy in tumor bearing mice

    International Nuclear Information System (INIS)

    With the development of the hybridoma technology, the production of highly specific tumor associated monoclonal antibodies has provided new optimism for the adjuvant delivery of therapeutic radiation doses via radioimmunotherapy. The authors have used a modified form of the well-established TL dosimetry technology to measure the dose resulting from radioimmunotherapy experiments in tumor bearing mice. Their laboratory has designed and tested a miniature CaSO4:D TLD which fits conveniently inside a 20 gauge needle for the direct implantation of the dosimeter in an animal model undergoing radiolabeled antibody therapy. Direct measurement of absorbed dose from beta and gamma radiation in the animals may be obtained upon removal of the dosimeter at animal sacrifice or by surgery. This absorbed dose data may then be related to antibody affinity and localization data obtained by serial biodistribution studies. Using p96.5 melanoma antibody with a Brown Tumor Model in athymic mice, localization indices measured in the range of 2 to 4 and scored 4 to 7 days post antibody injection, yielded a tumor dose/whole body dose ratio of 1.10 +/- 0.04 (no enhancement). The dose to liver showed marker time-dependent enhancement relative to the whole body, however. An outline of suggested control radiobiological experiments to be performed in conjunction with radioimmunotherapy experiments has been included in order to provide comparative dose response data. 11 references, 14 figures, 3 tables

  11. Macrophages support splenic erythropoiesis in 4T1 tumor-bearing mice.

    Directory of Open Access Journals (Sweden)

    Min Liu

    Full Text Available Anemia is a common complication of cancer; a role of spleen in tumor-stress erythropoiesis has been suggested. However, the molecular mechanisms involved in the splenic erythropoiesis following tumor maintenance remain poorly understood. Here we show that tumor development blocks medullar erythropoiesis by granulocyte colony-stimulating factor (G-CSF and then causes anemia in murine 4T1 breast tumor-bearing mice. Meanwhile, tumor-stress promotes splenic erythropoiesis. Splenectomy worsened tumor-induced anemia, and reduced tumor volume and tumor weight, indicating the essential role of spleen in tumor-stress erythropoiesis and tumor growth. Tumor progression of these mice led to increased amounts of bone morphogenetic protein 4 (BMP4 in spleen. The in vivo role of macrophages in splenic erythropoiesis under tumor-stress conditions was investigated. Macrophage depletion by injecting liposomal clodronate decreased the expression of BMP4, inhibited splenic erythropoiesis, aggravated the tumor-induced anemia and suppressed tumor growth. Our results provide insight that macrophages and BMP4 are positive regulators of splenic erythropoiesis in tumor pathological situations. These findings reveal that during the tumor-stress period, the microenvironment of the spleen is undergoing changes, which contributes to adopt a stress erythropoietic fate and supports the expansion and differentiation of stress erythroid progenitors, thereby replenishing red blood cells and promoting tumor growth.

  12. Immunological response in mice bearing LM3 breast tumor undergoing Pulchellin treatment

    Directory of Open Access Journals (Sweden)

    de Matos Djamile

    2012-07-01

    Full Text Available Abstract Background Ribosome-inactivating proteins (RIP have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer. Methods The percentage of dendritic cells and CD4+ and CD8+ T cells in the spleen (flow cytometry, cytokines’ release by PECs and splenocytes (ELISA and nitric oxide production by PECs (Griess assay were determined from tumor-bearing mice injected intratumorally with 0.1 ml of pulchellin at 0.75 μg/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test. Results Pulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-γ and Th2 cytokines (IL-4 and IL-10, while IL-6 and TGF-β levels were decreased. There was also an increase in macrophage’s activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively. Conclusions Our results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.

  13. Effect of 5-aminolevulinic acid-mediated photodynamic therapy on human gastric cancer xenografts in nude mice in vivo%5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

    Institute of Scientific and Technical Information of China (English)

    周广军; 黄宗海; 俞金龙; 厉周; 丁涟沭

    2008-01-01

    Objective To investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoreidal mechanism. Methods Cultured 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-9MACIMSYSPULS 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. Results The tumor model was successfully developed. The tumor in the nude mice emited the red fluorescence under the Leica LT-9MACIMSYSPULS. The tumor volumes were (0.189±0.010)cm3, (0.183±0.011)cm3, (0.185±0.019) cm3, (0.182±0.015)cm3 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)cm3, (0.280±0.013)cm3, (0.278±0.016)cm3, (0.183±0.014)cm3;at day 7, (0.409±0.016)cm3, (0.411±0.009)cm3, (0.407±0.015)cm3, (0.221±0.008)cm3;at day 14, (0.970±0.055)cm3 (0.976±0.054)cm3, (0.981±0.032)cm3, (0.318±0.005)cm3;at day 21, (1.495±0.059)cm3, (1.513±0.057)cm3, ( 1.524±0.063)cm3, (0.446±0.042)cm3(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. Conclusions 5-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

  14. Effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized nude mice

    Institute of Scientific and Technical Information of China (English)

    WU Qian; JIN NianZu; YU Jing; ZHAO RenChen; YU ZePing; QIAO ShanLei; LU XiaoHe; ZHANG ChunWen

    2009-01-01

    In this study,we explored the effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice.The ovariectomized athymic mice were implanted with MCF-7 cells.They were fed with low,moderate and high doses of soy isoflavone extracts,at dietary concentrations of 6.25,12.5 and 25 g/kg,respectively.The expression of ki-67 was detected by immunohistochemistry.The pS2 expression in tumors was analyzed by real-time PCR.Estrogen level in the serum was measured by chemiluminescence enzyme immunoassay.Com-pared with the control group,dietary soy isoflavone extracts had a significant stimulatory effect on MCF-7 tumor growth in mice (P 0.05).The ki-67 and pS2 mRNA expressions in tumors were signifi-cantly increased by 6.25 and 12.5 g/kg dose of soy isoflavone extracts (P 0.05).And,estrogen level in serum of 6.25 and 12.5 g/kg dose groups was higher than that of control group (P 0.05).In conclusion,in the tested dietary concentration range soy isoflavone extracts had a stimulatory effect on tumor growth.6.25 and 12.5 g/kg doses of soy isoflavone extracts can increase the cell proliferation in tumors and induce estrogen-responsive pS2 expression.

  15. Suppression of the growth of subcutaneous transplanted human liver cancer and lung metastasis in nude mice treated by sorafenib combined with fluorouracil%索拉非尼联合氟尿嘧啶抑制荷人肝癌裸鼠肿瘤生长和肺转移

    Institute of Scientific and Technical Information of China (English)

    沈沪佳; 王艳红; 徐建

    2013-01-01

    Objective The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice,and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu.Methods The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells,and the tumor-bearing nude mice were treated with sorafenib,5-Fu or both,respectively,and mock-treated tumor-beating nude mice as negative control.To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases.Moreover,the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK),P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo Ⅱa) in the nude mice were assayed by immunocytochemistry and Western blot.Results The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group,(0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group,(0.786 ± 0.212) g and 5.429 ±4.315 in the Sorafenib +5-Fu combination group,and (2.438 ± 0.793)g and 10.429 ± 6.241 in the 5-Fu group.Statistically,the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased,compared with that in the control group (P < 0.05).There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P > 0.05).The expression levels of p-ERK,P-gp and Topo Ⅱ a proteins in the tumors after normalization were: negative control (0.017 ±0.010,0.085 ± 0.012,0.103 ± 0.093),sorafenib group (0.010 ±0.008,0.044 ±0.020,0.020 ±0.018),combination group (0.011 ±0.007,0.043 ±0.023,0.062 ±0.026),and 5-Fu group (0.018 ±0.009,0.063 ±0.032,0.065 ± 0.034),respectively.Statistically,the expression of p-ERK,P-gp and Topo Ⅱ a in the

  16. Histopathologic validation of 3′-deoxy-3′-18F-fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice18F-FLT PET repopulation -->

    International Nuclear Information System (INIS)

    Background and purpose: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing 18F-FLT PET. Material and methods: Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm] = 3.0 Gy), either daily or every second day. 18F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. Results: Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P < 0.05) and 18 fractions in 18 days (P < 0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P > 0.05) and 18 fractions in 36 days (P > 0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P < 0.05), and increases with every-second-day irradiation (P > 0.05). 18F-FLT parameters correlated strongly with proliferation markers (r2: 0.679–0.879, P < 0.001). Conclusions: 18F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for 18F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy

  17. Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using 64Cu-DOTA-VEGF121 and microPET

    International Nuclear Information System (INIS)

    KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino] -3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with 64Cu-DOTA-VEGF121. KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups. After injections occurred daily for 28 days, all groups of mice underwent post-treatment microPET imaging after injection with 64Cu-DOTA-VEGF121. The post-treatment images showed high tumor uptake in the control group and reduced tumor uptake in both the blocking and treatment groups. ROI analysis of the tumor images revealed 6.25%±1.18% ID/g at 1 h, 6.55%±0.69% ID/g at 2 h, and 4.68%±0.63% ID/g at 16 h in the control group; 3.87%±0.45% ID/g at 1 h, 4.50%±0.44% ID/g at 2 h, and 3.63%±0.25% ID/g at 16 h in the blocking group; and 4.03%±0.74% ID/g at 1 h, 4.37%±0.67% ID/g at 2 h, and 3.83%±0.90% ID/g at 16 h in the treatment group. Biodistribution obtained after the post-treatment microPET imaging also demonstrated high tumor uptake (3.74%±0.27% ID/g) in the control group and reduced uptakes in both the blocking group (2.69%±0.73% ID/g, P<.05) and the treatment group (3.11%±0.25% ID/g, P<.05), which correlated well with microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2 and CD31 expressions in tumor tissues of the control and blocking groups than in tumor tissues of the treatment group. These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831.

  18. Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 can be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity

  19. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Simona Perboni; Cyril Bowers; Shinya Kojima; Akihiro Asakawa; Akio Inui

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo-therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin ago-nist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased com-pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  20. Rembrandt and the Female Nude

    OpenAIRE

    Sluijter, Eric Jan

    2006-01-01

    Rembrandt's extraordinary paintings of female nudes - Andromeda, Susanna, Diana and Her Nymphs, Danaë, Bathsheba - as well as his etchings of nude women, have fascinated many generations of art lovers and art historians, but they have also elicited vehement criticism. They were considered against-the-grain, anti-classical, even ugly and unpleasant. However, Rembrandt chose conventional subjects, keeping close to time-honored pictorial schemes, and was well aware of the high prestige accorded ...

  1. The thymus reconstituted nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B

    1987-01-01

    The monoclonal antibodies OX6, OX19, W3/13, OX7, OX8, and W3/25 were used to gain information about the distribution of different lymphocyte subpopulations in peripheral lymphoid organs of neonatally isogeneic and allogeneic thymus reconstituted nude rats. Splenic mitogen responsiveness, xenogeneic...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  2. Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice.

    Science.gov (United States)

    Bing, C; Russell, S; Becket, E; Pope, M; Tisdale, M J; Trayhurn, P; Jenkins, J R

    2006-10-23

    Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of 'slimmed' adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPalpha), CCAAT/enhancer binding protein beta, peroxisome proliferator-activated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBPalpha and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia. PMID:17047651

  3. Herbal compound 'Songyou Yin' reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice

    International Nuclear Information System (INIS)

    Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches. Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound 'Songyou Yin,' interferon-alfa-1b (IFN-α), or their combination to assess their effects. In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, 'Songyou Yin,' IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively. Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. 'Songyou Yin' reinforced the ability of IFN-α to inhibit the

  4. No evidence for a different magnitude of the time factor for continuously fractionated irradiation and protocols including gaps in two human squamous cell carcinoma in nude mice

    International Nuclear Information System (INIS)

    Background and purpose: To study whether the magnitude of the time factor is different for continuously fractionated irradiation and for fractionation protocols including gaps. Materials and methods: Two human head and neck squamous cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were given either as a continuous course or with a mid-course gap of 3 weeks. The end-point of the experiments was local tumor control at day 120 (FaDu) or day 180 (GL) after the end of treatment. Results: In FaDu tumors, two experimental cohorts (A, B) yielded significantly different results and were analyzed separately. In cohort A, the tumor control dose 50% (TCD50) increased from 37 to 89 Gy when the treatment time of continuous fractionated irradiation was extended from 2 to 10 weeks. The recovered dose/day (Dr) was 0.98 Gy (95% confidence interval, 0.72; 1.27). In cohort B, the TCD50 increased from 35 to 63 Gy, and the Dr was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD50 for continuously fractionated irradiation increased from 41 to 48 Gy. This increase was not significant, and the Dr was 0.15 Gy (0; 0.30). None of the TCD50 and Dr values obtained in both tumor models for continuous irradiation vs. irradiation with a gap were significantly different. Conclusions: Prolongation of the overall treatment time of fractionated irradiation resulted in a pronounced decrease of local control in human FaDu SCC and little decrease of local control in human GL SCC. No evidence was found that the magnitude of the time factor in these tumors is different for continuous fractionation or fractionation protocols including gaps

  5. A comparative study of {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun-Young [Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju 220-710 (Korea, Republic of); Department of Nuclear Medicine, Yonsei University Health System, Seoul 120-752 (Korea, Republic of); Lee, Tae-Sup; Choi, Tae-Hyun; Cheon, Gi-Jeong; Choi, Chang-Woon [Laboratory of Nuclear Medicine, Korea Institute of Radiological and Medical Science, Seoul 139-706 (Korea, Republic of); Awh, Ok-Doo [Department of Nuclear Medicine, Yonsei University Health System, Seoul 120-752 (Korea, Republic of)], E-mail: immunoch@yonsei.ac.kr

    2007-11-15

    Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, {sup 188}Re complexes with diastereomeric DMSA were prepared to compare the properties of {sup 188}Re(V)-rac-DMSA with those of {sup 188}Re(V)-meso-DMSA in in vitro and in vivo models. Methods: rac-2,3-DMSA was synthesized and radiolabeled with {sup 188}Re. The biodistribution and gamma camera imaging of {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. Results and conclusions: Both {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with {sup 188}Re(V)-meso-DMSA, {sup 188}Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. {sup 188}Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas {sup 188}Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of {sup 188}Re(V)-rac-DMSA was 3.5 times higher than that of {sup 188}Re(V)-meso-DMSA at 1 h (P<.01). Gamma camera images showed that {sup 188}Re(V)-rac-DMSA was more selectively localized than {sup 188}Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that {sup 188}Re(V)-rac-DMSA may have better potential than {sup 188}Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors.

  6. A comparative study of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

    International Nuclear Information System (INIS)

    Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, 188Re complexes with diastereomeric DMSA were prepared to compare the properties of 188Re(V)-rac-DMSA with those of 188Re(V)-meso-DMSA in in vitro and in vivo models. Methods: rac-2,3-DMSA was synthesized and radiolabeled with 188Re. The biodistribution and gamma camera imaging of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. Results and conclusions: Both 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with 188Re(V)-meso-DMSA, 188Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. 188Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas 188Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of 188Re(V)-rac-DMSA was 3.5 times higher than that of 188Re(V)-meso-DMSA at 1 h (P188Re(V)-rac-DMSA was more selectively localized than 188Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that 188Re(V)-rac-DMSA may have better potential than 188Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors

  7. Effects of Marsdenia tenacissima polysaccharide on the immune regulation and tumor growth in H22 tumor-bearing mice.

    Science.gov (United States)

    Jiang, Shuang; Qiu, Limin; Li, Yiquan; Li, Lu; Wang, Xingyun; Liu, Zhi; Guo, Yan; Wang, Haotian

    2016-02-10

    One water-soluble polysaccharide (Marsdenia tenacissima polysaccharide, MTP), with an average molecular weight of 4.9 × 10(4) Da, was isolated from the dried rattan of M. tenacissima. MTP contained 93.8% carbohydrates, 5.6% proteins and 21.3% uronic acid, and were composed of arabinose, mannose, galactose, xylose, glucuronic acid at a molar ratio of 9.1, 17.7, 30.2, 22.4 and 20.6. The experiments on the animals showed that MTP could increase the serum hemolysin, promote the formation of antibody-forming cells and improve the phagocytosis of mononuclear macrophage in normal mice. Meanwhile, MTP could also inhibit the growth of tumor in H22 tumor-bearing mice dose-dependently, and increase the spleen index, thymus index and serum albumin level in the mice. In addition, MTP could elevate the serum level of TNF-α and IL-2, increase the activity of GSH-Px, CAT and SOD in the liver tissue, and reduce the content of VEGF and MDA. These results suggest that MTP can regulate the immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its antitumor activity may be related to its antioxidant and immunomodulatory effects. PMID:26686104

  8. 不同细胞促进脂肪移植存活的实验研究%Effects of different human adipose-derived cells in promoting human adipose tissue engraftment in nude mice

    Institute of Scientific and Technical Information of China (English)

    朱茗; 鲁峰; 高建华; 廖云君

    2012-01-01

    目的 探讨应用自人脂肪组织来源的不同细胞辅助脂肪移植,寻找促进移植物存活率的最佳种子细胞的有效方法,为干细胞进一步运用于临床提供实验依据.方法 从临床抽脂病人获取脂肪组织并提炼细胞,将0.3 ml待移植的脂肪颗粒分别与以下细胞进行混合处理:(1)低氧脂肪来源间充质干细胞(A组);(2)脂肪来源间充质干细胞(B组);(3)血管基质层细胞(SVFs)(C组);(4)加完全培养基的单纯脂肪颗粒为对照组(D组)脂肪颗粒与相应细胞混合后,注射移植于6只裸鼠背部皮下.术后3个月观察移植物情况,通过组织学、HE染色等方法进行分析.结果 A~D组湿重分别为(61.67±8.165)、(91.67±1.472)、(96.67±5.164)和(40.83±4.916)mg,A、B、C组脂肪存活率均高于D组(P<0.05),B、C两组之间比较差异无统计学意义(P>0.05)且都高于A组.A、B、C组血管密度均高于组D,且C组明显高于其他3组(P<0.05).A、B、C组存活脂肪细胞计数均高于D组,且B、C组最高(P<0.05),纤维组织计数均低于D组(P<0.05).结论 来源于人自体干细胞复合脂肪颗粒能够显著提高移植脂肪组织的成活率,其中血管基质层细胞及脂肪来源间充质干细胞移植脂肪的存活率最高.%Objective To explore the optimal seed cells derived from human adipose tissue for promoting the engraftment of transplanted adipose tissue in nude mice. Methods Human adipose tissue granules (0.3 ml) obtained from patients undergoing liposuction were mixed with hypoxic adipose-derived stem cells (ADCs, group A), ADCs (Group B), stromal vascular fraction (SVF) cells (group C), or pure adipose tissue granules in complete culture medium particles (group D). The mixtures were injected subcutaneously on the back of 6 nude mice, and the transplanted adipose tissues were harvested 3 months later to examine the engraftment using histological method and HE staining. Results The wet weights of the adipose

  9. Pathomorphology observation on nude mice immunized and challenged with third-stage infective hook worm (Ancylostoma caninum) larvae%犬钩虫第三期钩蚴免疫裸鼠再感染AcL3的组织病理学观察

    Institute of Scientific and Technical Information of China (English)

    郭俭; 吴嘉形; 杨元清; 薛剑; 强慧琴; 肖树华

    2009-01-01

    Objective To observe the inflammatory responses and morphology changes in the lung and skin of nude mice immunized and challenged with third stage hookworm larvae of Ancylostoma caninum (AcL3),and then,to investigate the feasibility of nude mice as vaccine screening animal model.Methods Nude mice BALB/c-nu/nu were immunized subcutaneously with three doses of 500 AcL3 at 2-week intervals,and then challenged percutaneously with 500 AcL3.Lungs and skins were excised from post-challenged nude mice after 6,24,72 h and 7 d,and then examined by light microscopy.Non-immunized nude mice served as negative controls.Results In both non-immunized mice and majority of immunized mice,the AcL3 exhibited no structural damage and infiltrating inflammatory cells were absent at the surrounding tissues.There were no changes in the architecture of skin and lung tissues.However.about 0.5%-2.2% AcL3 in the skin of immunized mice exhibited euticular swelling,damage and even death,and the surrounding tissue was infihrated by polymorphonuclear inflammatory cells.From 24 h to 72 h post-challenge,granulomata were observed surrounding the dead AcL3.ConchLsion Weak post-vaccination host immune response against challenged AcL3 was seen in nude mice,indicating that it was unsuitable to be used as vaccine screening animal model.%目的 观察裸鼠经犬钩虫第三期钩蚴(AcL3)免疫后,其皮肤和肺内AcL3的形态变化及宿主的组织细胞反应,评价其作为疫苗筛选动物模型的可能性. 方法取BALB/c-nu/nu 小鼠,每两周由皮下免疫接种活的AcL3 500条,共3次,并丁末次免疫后1周由皮肤攻击感染AcL3 500条.用未免疫的感染AcL3 裸鼠作对照,攻击感染后不同时间取感染部位皮肤和肺脏,观察宿卡皮肤和肺内AcL3的组织病理学变化. 结果攻击感染后6、24、72 h及7 d,皮肤内的绝人部分虫体切面形态和组织结构与感染对照裸鼠皮肤内的相似,仪0.5%~2.2%的虫体切而示有变性、死亡,偶见

  10. The effect of Fe3O4 nanometer magnetic fluid induced hyperthermia on implanted liver cancer in nude mice%交变磁场下Fe3O4纳米磁流体对裸鼠移植性肝癌的杀伤作用

    Institute of Scientific and Technical Information of China (English)

    彭健; 唐琦; 潘一峰; 陈伟; 黄远飞; 张阳德

    2011-01-01

    Objective To study the therapeutic effect of Fe3O4 nanometer magnetic fluid-induced hyperthermia on implanted liver cancer in nude mice under alternating magnetic field. Methods Nude mice model bearing implanted HepG2 was established. Mice were then randomly divided into 3 groups: the blank control group; the magnetic field group; nanometer magnetic fluid group. The magnetic field group were just put under the magnetic field; Nanometer magnetic fluid group received injection of PEG-PEI/Fe3O4 nanometer magnetic fluid under the alternating magnetic field. At the frequency of 40 kHz, and magnetic field of 5 kA/m, 15 minutes one day in the next 14 days. On the 7th day and the 15th day, the changes of tumor volume and weight were recorded, cell apoptosis were observed and recorded and pathological examination was done. Results On the 7th and the 15th day, in the nanometer magnetic fluid group, tumors' volume was smaller and the weight was lighter than other groups, and the tumor inhibitory rate of 54. 20% (t = 14. 506,P <0. 01 ) was significantly higher than the control group and the magnetic field group 22. 66% ( t = 7.497, P < 0. 05 ). In the control group, tumor cells grew well, high density, the nucleus engrained, the shape irregular, the nuclear fission clear; compared with the control group, in the magnetic field group, tumor cells scatter thinly, intercellular substance increases, and necrosis area formed;in the nanometer magnetic fluid group, many of tumor cells died, their cell nucleus broke up and vanished,the blood vessel reduced obviously, and the tumor cell spread thinly. Conclusions Under the alternating magnetic field, PEG-PEI/Fe3O4 nanometer magnetic fluid inhibits liver cancer growth in nude mice model of HepG2.%目的 研究交变磁场作用下Fe3O4纳米磁流体对HepG2裸鼠移植性肝癌细胞的杀伤作用.方法 建立HepG2裸鼠肝癌移植模型,将荷瘤裸鼠随机分成空白对照组、磁场空白组、Fe3O4纳米磁流体组3组.

  11. Production and preclinical evaluation of diagnostic and therapeutic radionuclides in tumor-bearing mice. Recent developments at Paul Scherrer Institute

    International Nuclear Information System (INIS)

    At PSI we have initiated a close collaboration of the Laboratory of Radiochemistry and Environmental Chemistry and the Center for Radiopharmaceutical Sciences to bring novel diagnostic and therapeutic radiopharmaceuticals to the point of clinical trials. Pre-clinical studies using tumor-bearing mice were conducted at PSI and ETH Zürich. At the university hospital in Bern the required infrastructure for clinical trials was established. (author)

  12. The change of the pathology and anti-oxidase in the tumor-bearing mice liver with dose irradiation

    International Nuclear Information System (INIS)

    Objective: To understand the change of tumor-bearing mice malignant tissue pathology and liver anti-oxidase. Method: Using enzymological and pathological analysis to study the active of SOD, GSH-Px, content of LPO in liver as well as the change of carcinoma tissue. Results: The study shown that the active of anti-oxidase in liver were aroused for the tumor-bearing mice whose whole body pre-exposed to 50 mGy low dose X-ray. The level of MDA was reduced. In the condition of large dose X-ray local irradiation radiotherapy increased gradually after low dose irradiation, the active of the SOD and GSH-Px showed a tendency of increase more than that of contrast groups. At that time the content of the MDA reached that of contrast group. Under optical microscope many lymphocytes were found to be invaded by the neighboring malignant tissue, capillaries, to be dilated and hyperemia occurred. Conclusion: low dose irradiation can stimulate the active of anti-oxidase system in liver of tumor-bearing mice and enhance it to high; Under the condition of large dose radiotherapy SOD, GSH-Px can be induced by the pre-exposed 50 mGy low dose irradiation, on the contrary, LPO be reduced; Low dose irradiation can promote the effect of radiotherapy and play a role as radio-protect effect on the normal physiological function

  13. Adenovirus mediated angiostatin gene therapy for ovarian cancer: experiment with nude mice%重组腺病毒载体介导血管抑素基因治疗裸鼠卵巢癌的实验研究

    Institute of Scientific and Technical Information of China (English)

    贾长茹; 杨树艳; 韩世愈; 孙蕾

    2008-01-01

    Objective To built an expression vector of angiostatin (AG) gene with recombinated replication defective adenovirus and investigate the therapeutic effect of human AG gene on ovarian cancer. Methods (1) Human AG K ( 1-3 ) cDNA was inserted into the vector pShuttle to build the recombinant plasmid pShttle-AG ( K1-3 ). pAdeno-X-AG (K1-3) was built by double-cut and recombinated pShttle-AG (K1-3) to vector pAdeno-X, and then recombinant adenovirus was finally prepared by transinfection of pAdeno-X-AG (K1-3) into to the human embryo kidney cells of the line 293. (2) Human ovarian cancer cells of the line SKOV3 were inoculated subcutaneously into nude mice of the line BALB/c nu/nu to establish model of human ovarian cancer. Then the mice were randomly divided into 3 groups to be injected with Ad = AG (K1-3), Ad-LacZ, or phosphate buffered saline (PBS) around the cancer every 5 days. The tumor size was measured every 5 days to calculate the tumor volume and tumor inhibition rate. Three days after the last injection the mice were killed. The tumor tissues, livers, and kidneys of the mice underwent imunohistochemistry to calculate the microvessel density (MVD) and expression of vessel endothelial growth factor (VEGF) and AG. Results The tumor volume and weight of the Ad-AG ( K1-3 ) group were significantly less than those of the PBS and Ad-LacZ groups ( all P 0. 05). The expression levels of CD34 and VEGF of the Ad-AG( K1-3 ) group were both significantly lower than those of the PBS and Ad-LacZ groups (all P 0. 05 ). Conclusion Human angiostatin mediated by adenovirus suppresses the angiogenesis and the growth of human ovarian cancer in the nude mice model, which suggests that it is promising in clinical application.%目的 构建携带血管抑素(AG)基因K(1-3)重组复制缺陷型腺病毒表达载体,研究腺病毒介导的人血管抑素基因对卵巢癌的治疗作用.方法 (1)将人血管抑素K(1-3)cDNA插入穿梭载体pShuttle产生重组质粒pShttle-AG(K1

  14. Anti-tumor effect and influence of Gekko gecko Linnaeus on the immune system of sarcoma 180-bearing mice.

    Science.gov (United States)

    You, Qi; Han, Shiyu; Zhang, Yuanlong; Zheng, Jianhua

    2009-01-01

    Gekko gecko Linnaeus (GgL) is an extract used in traditional Chinese medicine. In the present study, we examined the anti-tumor activity of GgL and its effect on the immune system of mice. Sarcoma 180-bearing mice were used as the animal model, and cisplatin was applied as the positive control drug. The mice were randomly divided into six groups, and each group was treated with a different drug or drug concentration. The effects of GgL were evaluated based on its anti-tumor activity and prolongation of the lifespan, the lymphocyte transformation rate and pathological changes observed in the tumors. The results suggest that GgL has anti-tumor activities and up-regulates the immune system in a dose-dependent manner. This study provides original data related to the anti-tumor and immune up-regulating function of GgL. PMID:21475868

  15. Establishment of whole-body visualization models of ovarian cancer orthotopic and metastatic model in nude mice.%整体可视化卵巢癌原位及转移动物模型的建立

    Institute of Scientific and Technical Information of China (English)

    黎静; 王雪飞; 钟梅

    2012-01-01

    Objective To establish visualization model of orthotopic growth and metastasis of ovarian cancer. Methods The pEGFP - N1 plasmid was transfected into human ovarian carcinoma cell line HO -8910 for construction of enhanced green fluorescent protein (EGFP) consistent expression pEGFP - N1/H0 -8910 cells. pEGFP - N1/HO -8910 cells were inoculated subcutaneously in nude mice, and the orthotopic tumor growth was evaluated in real time using fluorescence stereo microscope. Whole - body visualization model of ovarian carcinoma was established surgically, and evaluated by conventional pathological methods. Results EGFP was consistently expressed at high level in pEGFP - N1/ HO -8910 cells. Subcutaneous injection of pEGFP - N1/HO - 8910 cells resulted in tumor growth in nude mice, assessed with fluorescence stereo microscope producing visualized real - time tumor growth. Visualization animal model was established successfully with surgical orthotopic implantation (SOI) of the tumor. Two weeks after surgery, all the mice developed ovarian carcinoma without metastasis. Six weeks after surgery, peritoneal metastasis was observed in 2 mice, in which liver metastasis was also presented. The whole - body visualization animal model was validated by pathological detection. Conclusion Whole - body visualization model of orthotopic and metastatic tumor growths provides a reliable model for observing the pathogenic behavior of human ovarian carcinoma.%目的 建立整体可视化卵巢癌原位及转移动物模型,实时观察卵巢癌发展、转移的规律.方法 将pEGFP-N1表达质粒转染入人卵巢癌细胞株HO-8910中,建立稳定表达绿色荧光蛋白(EGFP) 的卵巢癌细胞株 pEGFP-N1/HO-8910,裸鼠皮下接种pEGFP-N1/HO-8910细胞,利用肿瘤细胞表达EGFP的特点,借助整体荧光成像系统,并利用IPP5.0软件采集、分析卵巢癌细胞发出的荧光信号,实时观察卵巢癌细胞在裸鼠皮下的生长情况,利用卵巢癌外科原位手术移

  16. Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich's carcinoma.

    Science.gov (United States)

    Ali, Shimaa A; Zaitone, Sawsan A; Moustafa, Yasser M

    2015-08-01

    This study aimed to test whether boswellic acids add to the antitumor effects of doxorubicin against solid tumors of Ehrlich's ascites carcinoma (EAC) grown in mice, and to investigate the protective effects of boswellic acids against doxorubicin-induced cardiotoxicity. Sixty-four female Swiss albino mice bearing EAC solid tumors were distributed among 8 groups as follows: group 1, EAC control group; group 2, doxorubicin treatment group [mice were injected with doxorubicin (6 mg·(kg body mass)(-1)·week(-1)) for 3 weeks]; groups 3-5, these mice were treated with boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively; groups 6-8, these mice were treated with a combination of doxorubicin and boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively, for 3 weeks. The results indicated that boswellic acids synergized the antitumor activity of doxorubicin. Doxorubicin-treated mice showed elevated serum activities of lactate dehydrogenase and creatine kinase isoenzyme MB as well as cardiac malondialdehyde. Further, decreases in cardiac levels of reduced glutathione, superoxide dismutase, and catalase activities were observed. These effects were accompanied by an increase in cardiac expression of caspase 3. Thus, treatment with boswellic acids attenuated doxorubicin-evoked disturbances in the above-mentioned parameters, highlighting antioxidant and antiapoptotic activities. Therefore, boswellic acids could be potential candidates for ameliorating the cardiotoxicity of doxorubicin. PMID:26230640

  17. ENHANCED ANTITUMOR EFFECTS OF SUICIDE GENE THERAPY BY SIMULTANEOUS TRANSFER OF GMCSF GENE IN LEUKEMIA-BEARING MICE

    Institute of Scientific and Technical Information of China (English)

    Ju Dianwen; Cao Xuetao; Yu Yizhi; Tao Qun; Wang Baomei; Wan Tao

    1998-01-01

    In the present report, antitumor effect of combined transfer of suicide gene and cytokine gene was studied.Adenovirus engineered to express E. Coli. Cytosine deaminase (AdCD) and/or adenovirus engineered toexpress murine granulocyte-macrophage colonystimulating factor (AdGMCSF) were used for the treatment of leukemia-bearing mice. The mice were inoculated s.c. With FBL-3 erythroleukemia cells and 3days later received intratumoral injection of AdCD in the presence or absence of AdGMCSF followed by intraperitoneal 5-fluorocytosine (5FC) treatment. The results demonstrated that mice received combined therapy of AdCD/5FC and AdGMCSF developed tumors most slowly and survived much longer when compared with mice treated with AdCD/5FC alone, AdGMCSF alone, AdlacZ/5FC or PBS. Combined transfer of CD gene and GM-CSF gene achieved higher specific CTL activity than control therapies. Pathological examination illustrated that the tumor mass showed obvious necrosis and inflammatory cell infiltration in mice after combined therapy. The results demonstrated that combined transfer of suicide gene and cytokine gene could synergistically inhibit the growth of leukemia in mice and induce antitumor immunity of the host. The combination therapy might be a potential approach for cancer gene therapy.

  18. PET hypoxia imaging with FAZA: reproducibility at baseline and during fractionated radiotherapy in tumour-bearing mice

    International Nuclear Information System (INIS)

    Tumour hypoxia is linked to treatment resistance. Positron emission tomography (PET) using hypoxia tracers such as fluoroazomycin arabinoside (FAZA) may allow identification of patients with hypoxic tumours and the monitoring of the efficacy of hypoxia-targeting treatment. Since hypoxia PET is characterized by poor image contrast, and tumour hypoxia undergoes spontaneous changes and is affected by therapy, it remains unclear to what extent PET scans are reproducible. Tumour-bearing mice are valuable in the validation of hypoxia PET, but identification of a reliable reference tissue value (blood sample or image-derived muscle value) for repeated scans may be difficult due to the small size of the animal or absence of anatomical information (pure PET). Here tumour hypoxia was monitored over time using repeated PET scans in individual tumour-bearing mice before and during fractionated radiotherapy. Mice bearing human SiHa cervix tumour xenografts underwent a PET scan 3 h following injection of FAZA on two consecutive days before initiation of treatment (baseline) and again following irradiation with four and ten fractions of 2.5 Gy. On the last scan day, mice were given an intraperitoneal injection of pimonidazole (hypoxia marker), tumours were collected and the intratumoral distribution of FAZA (autoradiography) and hypoxia (pimonidazole immunohistology) were determined in cryosections. Tissue section analysis revealed that the intratumoral distribution of FAZA was strongly correlated with the regional density of hypoxic (pimonidazole-positive) cells, even when necrosis was present, suggesting that FAZA PET provides a reliable measure of tumour hypoxia at the time of the scan. PET-based quantification of tumour tracer uptake relative to injected dose showed excellent reproducibility at baseline, whereas normalization using an image-derived nonhypoxic reference tissue (muscle) proved highly unreliable since a valid and reliable reference value could not be determined

  19. Alloantigen-activated lymphocytes from mice bearing a spontaneous nonimmunogenic adenocarcinoma inhibit its growth in vivo by recruiting host immunoreactivity

    International Nuclear Information System (INIS)

    Nylon wool columns eluting lymphocytes from the spleen of mice bearing a clinically evident spontaneous, nonimmunogenic adenocarcinoma of recent origin (TS/A) do not display cytotoxic response, release of lymphokines, and proliferation in vitro against TS/A cells, nor do they inhibit TS/A tumor growth in a Winn-type neutralization assay in vivo. After 5-day co-culture with allogeneic spleen cells from mice differing at multiple minor histocompatibility antigens only, these lymphocytes are still noncytolytic against TS/A cells, whereas they release interferon-γ, mediate delayed-type hypersensitivity (DTH) reactions, and inhibit TS/A tumor growth in the Winn assay. In the Winn test, alloactivated lymphocytes from TS/A tumor-bearing mice are more effective than those from normal mice on a per cell basis. The induction of this TS/A tumor inhibition ability depends on the presence in the cultures of Thy-1+ lymphocytes. The presence of Lyt-2+ lymphocytes is also important, whereas that of asialo GM1+ is not. The TS/A inhibition in vivo by alloactivated lymphocytes mostly depends on Thy-1+, Lyt-2- and asialo GM- lymphocytes, even though a few Thy- cells are also very efficient tumor inhibitors. The alloactivated lymphocytes inhibit TS/A tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor rejection. TS/A tumor rejection leaves a specific DTH and an immunologic memory resulting in rejection of a second lethal TS/A challenge in a significant number of mice

  20. Gluten-induced enteropathy in nude mice

    Czech Academy of Sciences Publication Activity Database

    Farré, Maria; Funda, David; Tlaskalová, Helena

    1995-01-01

    Roč. 76, č. 1 (1995), s. S75. ISSN 0090-1229. [International congress of mucosal immunology /8./. San Diego, 17.07.1995-20.07.1995] R&D Projects: GA ČR GA310/93/1093; GA AV ČR IAA720401 Impact factor: 2.088, year: 1995

  1. Effects of simvastatin on human breast cancer osteolytic bone metastasis in a nude mice model%辛伐他汀在裸鼠模型中对乳腺癌骨转移的影响

    Institute of Scientific and Technical Information of China (English)

    陈明霞; 张蔚; 曲建力; 李强; 王海

    2015-01-01

    目的 观察辛伐他汀在裸鼠模型中对乳腺癌骨转移的作用.方法采用完全随机分组方法 将60只裸鼠分为3组,每组20只,裸鼠左心腔注射乳腺癌骨转移细胞株(MDA-MB-231),7d后,分别皮下注射辛伐他汀、生理盐水及无任何处理(2次/周,19 d).应用图像分析软件评估骨转移瘤的面积.随后处死裸鼠,用放射免疫法检测骨转移癌髓腔内甲状旁腺素相关蛋白(PTHrP)浓度;应用骨密度检测软件进行组织形态学分析,计数骨转移灶每毫米癌组织与临近骨小梁之间破骨细胞的数量.计量资料比较采用方差分析,P<0.05为差异有统计学意义.结果 与生理盐水组和无处理组相比,注射辛伐他汀的裸鼠骨转移癌面积明显减小(0.51±0.18 mm2 vs 2.13±1.24 mm2 vs 2.29±1.22 mm2;F=15.600,P=0.002; F=15.673,P=0.001),骨转移癌周围髓腔内PTHrP浓度明显降低(0.98±0.20 pmol/L vs 2.11±0.31 pmol/L vs 1.99±0.29 pmol/L;F=61.469,P<0.001;F=58.274,P<0.001),并且其转移灶破骨细胞的数量明显减少(4.00±1.73个/mm vs 11.40 ±4.93个/mm vs 10.91±3.87个/mm;F=17.820,P=0.001,F=17.184,P=0.002).结论 辛伐他汀能够降低乳腺癌细胞PTHrP的分泌,从而抑制乳腺癌细胞在骨内生长及其对骨质的破坏.%Objective To observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model.Methods Sixty mice were divided into three groups randomly with 20 in each group.Mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle.After 7 days,mice were treated with either simvastatin,saline,or nothing twice per week for 19 days.The area of osteolytic metastases was subsequently measured in long bones of all mice using an image analysis system.After sacrifice,parathyroid hormone-related protein (PTHrP) concentrations in bone marrow from all mice were determined using a two-site immunoradiometric assay.Osteoclast number expressed per millimeter of tumor/bone interface was assessed

  2. 具有摄锝功能甲状腺乳头状癌移植瘤裸鼠模型的建立%Establishment of nude mice xenograft model of papillary thyroid carcinoma with the ability of 99mTc-intake

    Institute of Scientific and Technical Information of China (English)

    张蓉; 俞立波; 李梅芳; 郭明高; 李连喜; 陆汉魁; 陆俊茜; 包玉倩; 贾伟平

    2014-01-01

    目的 建立具有摄锝功能甲状腺乳头状癌皮下移植瘤裸鼠模型,为研究甲状腺乳头状癌的发病机制及放射性碘治疗提供工具.方法 取人甲状腺乳头状癌细胞系IHH-4,以1×107细胞数制成200μl细胞悬液接种于9只裸鼠(5周龄雌性裸鼠,品系BALB/c-nu/nu)皮下,观察成瘤时间,并用PET-CT观察肿瘤大小及形态,用放射性核素发射式计算机断层(ECT)观察移植瘤的摄锝功能.结果 裸鼠皮下成瘤率为100.0% (9/9),细胞接种后1周裸鼠皮下可以形成肉眼可见的肿瘤,4周时PET-CT检测肿瘤大小约1.8cm×2.4cm,ECT显示腹腔注射放射性99m锝后15 min移植瘤可以显像.结论 应用人甲状腺乳头状癌细胞系IHH4成功建立甲状腺乳头状癌皮下移植瘤裸鼠模型,移植瘤具有良好的摄锝功能,为甲状腺乳头状癌发病机制及放射性碘治疗等的研究提供了良好的动物模型.%Objective To establish the nude mice xenograft model of papillary thyroid carcinoma with the ability to accumulate 99mTc,and to provide a tool for further study in both pathogenesis and radioactive iodine treatment of papillary thyroid carcinoma.Methods 1 × 107 cells in 200 μl suspension liquids of the human papillary thyroid carcinoma cell lines IHH-4 were inoculated into nine nude mice (five week-old female nude mice,BALB/c-nu/ nu).Tumor formation was recorded,and the size and morphology of tumor were observed by PET-CT.Emission computed tomography (ECT) was used to observe the function of 99mTc intake by xenografts.Results The percentage of the formation of xenografts in nude mice was 100.0% (9/9).One week after the cells were injected into nude mice,visible tumors were formed.PET-CT performed by the fourth week demonstrated that tumor size was about 1.8 cm × 2.4 cm.Xenograft' image was displayed by ECT after 15 minutes of intraperitoneal injection of 99mTc.Conclusion The nude mice xenograft model of papillary thyroid carcinoma was successfully

  3. Treatment of brain glioblastoma multiforme with pcDNA3.1-Egr. 1p-p16 combined with gamma knife radiation: An experimental study on nude mice

    Directory of Open Access Journals (Sweden)

    Liu Wenke

    2013-01-01

    Full Text Available Background: High post-operative recurrence and poor prognosis are likely to be related to the infiltrative growth of the glioblastoma multiforme (GBM. Objectives: The primary objective of this study is to investigate the possible synergistic effect of the combined treatment of gamma knife radio-surgery (GKRS and gene therapy for GBM and secondary objective is to explore the role of GKRS for the temporal and spatial regulation of the gene expression. Materials and Methods: The study performed on 70 nude mice and randomly divided into seven groups. Subcutaneous injection of human GBM tumor cells (T98G was carried out to establish the animal models. Various doses of liposome-mediated pcDNA3.1-Egr. 1p-p16 recombinant plasmid were transfected through intra-tumor injection. GKRS was scheduled following the plasmid transfection. Tumor volumes were measured every 4 days after the treatment. Subcutaneous tumor nodule specimens were collected to analyze the cell apoptosis and p16 gene expression using terminal-deoxynucleoitidyl transferase mediated nick end labeling staining and reverse transcription-polymerase chain reaction. Tumor volumes, levels of cell apoptosis and p16 gene expression were compared between groups. Results: Rates of tumor growth were significantly lower in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS groups than that in the remaining groups 28 days following the GKRS management. The p16mRNA expression was noted in both of the pcDNA3.1-Egr. 1p-p16 plasmid group and the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with marginal-dose of 20 Gy group. The level of messenger ribonucleic acid expression was higher in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with the marginal-dose of 20 Gy group, with a markedly increased apoptotic and necrotic cells, than that in the pcDNA3.1-Egr. 1p-p16 plasmid group. Conclusions: In animal studies, pcDNA3.1-Egr. 1p-p16 in combination with GKRS is a preferable management option for the GBM to the sole use of GKRS or gene

  4. Pharmacokinetics and tissue distribution of parenterally administered human alpha-lymphotoxin in normal and meth-A tumor-bearing BALB/c mice

    International Nuclear Information System (INIS)

    These in vivo studies examine the pharmacokinetics of parenterally administered purified, native human alpha-lymphotoxin (LT) in normal and Meth-A bearing BALB/c mice. We found that the lytic activity of alpha-LT was inactivated within 5 h in the blood of both normal and tumor-bearing mice in vivo. However, LT bioactivity in vitro was not affected by incubation with fresh serum. Radioiodinated LT was rapidly sequestered in the kidneys of both normal and tumor-bearing animals. Systemically administered, radioiodinated LT did not selectively localize in tumor tissues

  5. 人弥漫性大B细胞淋巴瘤移植瘤模型的建立及生长特性观察%Establishment and characterization of a nude mice model of human diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    于宝华; 周晓燕; 张铁成; 张太明; 施达仁

    2011-01-01

    Objective To establish a diffuse large B-cell lymphoma (DLBCL)-mice model using human DLBCL cell line LY8, to investigate its characteristics of growth and to provide a model for in vivo study of DLBCL pathogenesis and treatment. Methods LY8 cells were injected subcutaneously into the right flank of nude mice. Harvested tumor tissues were cut into small pieces of 1.5 mm × 1.5 mm × 1.5 mm and implanted subcutaneously into nude mice. Tumor growth was visualized and the histologic characteristics were documented. Expression of LCA, CD20, CD79α, Ki-67, CD3, CD45RO, bcl-6, MUM-1, CD1O and bcl-2 were examined by using immunohistochemistry. IgH clonal rearrangement and status of three microsatellite loci (D14S68, D18S69, D20S199) in the xenografted tumor samples and the parental cell line LY8 were detected using PCR amplification followed by PAGE. Results The subcutaneous xenograft DLBCL model was successfully established by using cell line LY8, and a stable growth was achieved up to the 9th generation. The tumor in each generation showed similar growth characteristics and the rate of subcutaneous tumor formation was 91.9% (114/124). The tumor growth was observed from the 2nd week after implantation, reaching 1.3 cm in major diameter at the 3rd week and 2. 0 cm at the 4th week. The tumor had identical morphological characteristics with those of human DLBCL, and expressed LCA, CE0,CD79α, bcl-6, MUM-1, CD1O and bcl-2. The tumor of xenograft mice and cell line LY8 showed identical IgH rearrangement and microsatellite length. Conclusions A human DLBCL bearing mouse model was successfully established. The mice model is similar to human counterpart with high stability and repeatability. Therefore, it provides an ideal animal model for in vivo studies of the biological characteristics and treatment of DLBCL.%目的 建立人弥漫性大B细胞淋巴瘤(DLBCL)细胞株LY8裸鼠皮下移植瘤模型并观察其生长特性,为探讨淋巴瘤发病机制及治

  6. AUGMENTATION OF IMMUNE FUNCTIONS AND AUTOLOGOUS TUMOR-KILLING ACTIVITY BY KAPPA-SELENOCARRAGEENAN IN MICE BEARING SARCOMA 180

    Institute of Scientific and Technical Information of China (English)

    Wei Hulai; Jia Zhengping; Zhao Huishun

    1998-01-01

    Objective: To study the enhancement of the immune functions and autologous tumor-killing (ATK) activity by kappa-selenocarrageenan (KSC) in mice bearing sarcoma 180. Methods: To measure the effects of KSC and/or Cyclophosphamide (Cy) on natural killer (NK) activity,lymphokine-activated killer (LAK) activity, the production of interleukin-2 (IL-2), ATK activity and the growth of sarcoma 180 (S180). Results: KSC promoted NK activity, LAK activity and ATK activity in vivo, increased IL-2 production at 40 mg/kg/d×9d. It also enhanced the antitumor action of Cy (20 mg/kg/d×9d) and offset the inhibition of Cy on immunocopetent cells. The ATK activity in splenocytes of S180-bearing mice could be induced and increased by recombinant interleukin-2 (rIL-2) in vitro. Conclusion: KSC has an up- regulating effect on the immune functions and ATK activity in tumorbearing mice. It can be used as a biological response modifier (BRM) in cancer biotherapy.

  7. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice

    Indian Academy of Sciences (India)

    Jingtao Hu; Chunfeng Wang; Liping Ye; Wentao Yang; Haibin Huang; Fei Meng; Shaohua Shi; Zhuang Ding

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN- (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

  8. Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

    Directory of Open Access Journals (Sweden)

    Kretzer IF

    2016-03-01

    Full Text Available Iara F Kretzer,1,2 Durvanei A Maria,3 Maria C Guido,1 Thaís C Contente,1 Raul C Maranhão1,2 1Laboratory of Metabolism and Lipids, Heart Institute of the Medical School Hospital, 2Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo, 3Biochemistry and Biophysics Laboratories, Butantan Institute, São Paulo, Brazil Purpose: Lipid nanoemulsions (LDEs that bind to low-density lipoprotein (LDL receptors used as carriers of paclitaxel (PTX can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva, which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX. Materials and methods: B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls, Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 µmol/kg (three intraperitoneal injections, 3 alternate days: Simva 50 mg/kg/day by gavage, 9 consecutive days. Results: Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and

  9. A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

    OpenAIRE

    Seo, Juyi; Yun, Chae-Ok; Kwon, Oh-Joon; Choi, Eun-Jin; Song, Jae-Young; Choi, Inho; Cho, Kyung-Hyun

    2012-01-01

    We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A-I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group sh...

  10. Effect of ketogenic diet on growth of human colon cancer cells in nude mice%生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    郝光伟; 王海玉; 何德明; 陈榆升; 吴国豪; 张波

    2014-01-01

    Objective:To observe the effect of ketogenic diet on the growth of human colon cancer cells in nude mice and to de-termine its possible mechanisms. Methods:A total of 24 male BALB/C nude mice were injected subcutaneously with the tumor cells of the colon cancer cell line HCT116. These animals were randomized into two feeding groups. One group was fed with a ketogenic diet (KD group;n=12), and the other group was given a standard diet (SD group;n=12) ad libitum. Experiments were completed upon at-taining a target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on body weight, serum glucose, ketone body, insulin, tumor growth, and survival time, which is the interval between tumor cell injection and attainment of target tumor vol-ume. Results:The tumor growth was significantly more delayed in the KD group than in the SD group. Tumors in the KD and SD groups reached the target tumor volume at 33.8 ± 6.7 days and 24.8 ± 3.1 days, respectively. The ketone body in the KD group was ele-vated with a slight reduction in serum insulin, and the difference in serum glucose in the two groups was insignificant. Importantly, the KD group had significantly larger necrotic areas and less vessel density than the SD group. Conclusion:The application of an unre-stricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and its effect on other tumor-relevant functions, such as invasive growth and metastasis.%目的:观察生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响;探讨生酮饮食可能的作用机制。方法:24只雄性BALB/C裸鼠皮下注射人结肠癌HCT116细胞系后随机分成2组,分别给予正常饮食(standard diet,SD)及生酮饮食(ketogenic diet,KD),两组饮食均不限制总量。当肿瘤体积达到600~700 mm3时实验终止,并将接种当日至肿瘤达到目标体积的时间定义为肿瘤生长期

  11. Melanoma-targeted delivery system (part 2): Synthesis, radioiodination and biological evaluation in B16F0 bearing mice.

    Science.gov (United States)

    El Aissi, Radhia; Miladi, Imen; Chezal, Jean-Michel; Chavignon, Olivier; Miot-Noirault, Elisabeth; Moreau, Emmanuel

    2016-09-14

    Here we report the synthesis and radiolabelling with iodine-125 of a melanoma-selective prodrug (17a*) and its parent drug IUdR. The in vivo and ex vivo biodistributions of [(125)I](17a*) and [(125)I]IUdR were evaluated in a model of melanoma B16F0-bearing mice. The pharmacokinetic profile of [(125)I](17a*) suggests rapid release of the active drug [(125)I]IUdR after i.v. administration of [(125)I](17a*). Preliminary metabolism studies in dedicated compartments (i.e. blood, urine and tumour) yielded results consistent with this hypothesis. PMID:27214141

  12. A nude mouse model of endometriosis and its biological behaviors

    Institute of Scientific and Technical Information of China (English)

    WANG Dan-bo; ZHANG Shu-lan; NIU Hui-yan; LU Jing-ming

    2005-01-01

    @@ Endometriosis (EM) as a common and intractable gynecological disease is characterized by unknown etiology and complex pathologic changes. Many factors of the disease are uncertain at the molecular level and it is difficult to study clinically. In this study, we attempted to establish a nude mice model of EM for dynamical observation of the genesis and development of the disease, morphological changes in tissue, and biological behaviors.

  13. Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice.

    OpenAIRE

    Lenti, L; Lipari, M.; Lombardi, D; Zicari, A.; Dotta, A.; Pontieri, G. M.

    1986-01-01

    The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl...

  14. A New Method of Establishing Orthotopic Bladder Transplantable Tumor in Mice

    International Nuclear Information System (INIS)

    The present study aims to find a convenient, rapid, and stable method to establish bladder tumor in mice. Female Balb/C-nu-nu nude mice (or female T739 mice) were narcotized by sodium pentobarbital at a dosage of 60 mg/kg. The stylet of the 24# venous retention needles was bent in a 5° to 7° angle at a distance of 15 mm from the needlepoint to form a circle with 2.61 mm to 3.66 mm radius when the stylet is rotated. The pipe casing was lubricated with liquid paraffin, and inserted into the bladder cavity. The drift angle stylet was inserted into the pipe casing slowly, rotated for five times, and then pulled out. A cell suspension (0.1 mL) of approximately 1×106 T24 cells (or BTT cells) was then injected immediately. A total of 60 T739 mice and 60 Balb/C-nu-nu nude mice were inoculated with BTT cells and T24 cells, respectively. The bladder tumor incidence and the average survival time of the tumor-bearing mice were 100% and (26.69±9.24) d and 100% and (34.59±9.8) d for the T739 mice and Balb/C-nu-nu nude mice, respectively. Using the drift angle stylet to injure the mucous membrane of the urinary bladder can establish a stable bladder transplantable tumor model in mice

  15. Effect of Ganoderma lucidum (G. lucidum) on the Liver of Mice Bearing Ehrlich Solid Tumor (EST) and Exposed to γ-Radiation

    International Nuclear Information System (INIS)

    The present study was performed to investigate the antitumor and radio sensitizing efficacy of Ganodarma lucidum (G. lucidum) and to evaluate its potential to improve hepatic dysfunction in Ehrlich solid tumor (EST) bearing mice. G. lucidum (100 mg/Kg body weight) was administered orally to EST bearing mice for 15 days before and 15 days after tumor inoculation. Irradiation was carried out the 8th day of tumor inoculation when the diameter of the tumor reached approximately 10 mm. Mice were exposed to fractionated doses of whole body γ-radiation (3x2Gy) at two days interval to attain a total dose of 6 Gy. Mice were divided into 6 groups (15 mice in each group) as follows: normal control, mice treated with G. lucidum for 30 days, EST bearing mice, EST bearing mice exposed to fractionated doses of γ-radiation (2Gy x 3), EST bearing mice treated with G. lucidum for 15 days before and 15 days after tumor inoculation and EST bearing mice received combined treatment radiation and G. lucidum. Five mice from each group were sacrificed, after 18 hr fasting after the last dose of G. lucidum treatment. Blood was collected, liver and tumor were removed for biochemical and histopathological studies. The remaining animals were observed for recording survival percentage and tumor size. In vitro study on Ehrlich Ascites Carcinoma cells showed that the percentage of nonviable cells (NVC%) increase with increasing G. lucidum concentration. The results revealed also that treatment of EST bearing mice with G. lucidum and/or γ- radiation increased the survivability and decrease the tumor size as compared to EST group. The biochemical analysis for EST bearing group recorded an elevation in the activities of lactate dehydrogenase (LDH), asparta amino transferase (AST) and alanine amino transferase (ALT) in the serum. Also, there was an elevation in the concentration of malondialdehyde (MDA), a marker of lipid peroxidation, accompanied by a decrease in superoxide dismutase (SOD

  16. Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors.

    Science.gov (United States)

    Yang, Meng; Reynoso, Jose; Jiang, Ping; Li, Lingna; Moossa, Abdool R; Hoffman, Robert M

    2004-12-01

    We report here the development of the transgenic green fluorescent protein (GFP) nude mouse with ubiquitous GFP expression. The GFP nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives GFP expression in essentially all tissues. In crosses between nu/nu GFP male mice and nu/+ GFP female mice, the embryos fluoresced green. Approximately 50% of the offspring of these mice were GFP nude mice. Newborn mice and adult mice fluoresced very bright green and could be detected with a simple blue-light-emitting diode flashlight with a central peak of 470 nm and a bypass emission filter. In the adult mice, the organs all brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, and duodenum. The following systems were dissected out and shown to have brilliant GFP fluorescence: the entire digestive system from tongue to anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The skinned skeleton highly expressed GFP. Pancreatic islets showed GFP fluorescence. The spleen cells were also GFP positive. Red fluorescent protein (RFP)-expressing human cancer cell lines, including PC-3-RFP prostate cancer, HCT-116-RFP colon cancer, MDA-MB-435-RFP breast cancer, and HT1080-RFP fibrosarcoma were transplanted to the transgenic GFP nude mice. All of these human tumors grew extensively in the transgenic GFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor-host interaction by whole-body imaging and at the cellular level in fresh and frozen tissues. The GFP mouse model should greatly expand our knowledge of human tumor-host interaction. PMID:15574773

  17. Dietary rice component, Oryzanol, inhibits tumor growth in tumor-bearing Mice

    Science.gov (United States)

    Scope: We investigated the effects of rice bran and components on tumor growth in mice. Methods and results: Mice fed standard diets supplemented with rice bran, '-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet fo...

  18. Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene.

    Science.gov (United States)

    Huang, S K; Martin, F J; Jay, G; Vogel, J; Papahadjopoulos, D; Friend, D S

    1993-07-01

    Transgenic mice bearing the HIV tat gene develop dermal lesions resembling a common malignant tumor in AIDS, Kaposi's sarcoma (KS). To evaluate the permeability characteristics of these lesions and the therapeutic potential of drug-carrying liposomes, we have studied the localization of sterically stabilized liposomes, which show long circulation time in blood and increased accumulation in tumors. Liposomes encapsulating colloidal gold were injected intravenously into transgenic mice bearing KS lesions, and tissues were processed 24 hours later for both electron microscopy and for light microscopy with silver enhancement. Liposomes and silver marker were detected predominantly in the dermis surrounding the early and mature KS lesions, which were characterized by a proliferation of fibroblast-like spindle cells and abnormal blood vessels close to the epidermis. The silver-enhanced gold marker often surrounded vascular channels and scattered erythrocytes. As determined by electron microscopy, some spindle cells and macrophages had ingested intact liposomes. Transendothelial transport of liposomes was observed both through open channels between endothelial cells and also through endothelial cells lining intact vessels. Both extravasation and transcytosis of liposomes through irregular endothelium were much higher in KS lesions than in the adjacent normal skin. The high accumulation of sterically stabilized liposomes in KS lesions and their intracellular uptake by some spindle cells enhances their potential as carriers of chemotherapeutic agents against this neoplasm. PMID:8317543

  19. Experiment study on bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice%裸鼠原位和异位脑肿瘤生物发光信号成像实验研究

    Institute of Scientific and Technical Information of China (English)

    步星耀; 章翔; Walter E. Laug

    2006-01-01

    目的应用生物发光成像技术,非侵入性地连续检测活体裸鼠原位和异位脑肿瘤发展演进过程.方法用SMPU-R-MND-luc载体转染人脑肿瘤U87MG细胞系,形成具有高荧光素酶活性的细胞克隆.在裸鼠脑内和胁腰部皮下植入持续表达荧光素酶的肿瘤细胞,建立原位和异位脑肿瘤模型,用影像学资料显示肿瘤部位.用光子发射定量分析动态监测肿瘤生长情况.结果成功地建立了表达荧光素酶活性的原位和异位脑肿瘤动物模型.采集反映肿瘤生长的生物发光信号,肿瘤细胞植入后不同时间点的发光信号值呈显著正相关,而且原位和异位脑肿瘤间存在明显差异.但生物发光脑肿瘤生物发光信号值在第4 d和第14 d时无显著差异.结论体内生物发光成像可以非侵入性地动态检测活体内脑肿瘤演进过程,为研究肿瘤发展机制及最佳治疗策略的选择提供了新的手段和工具.%Objective To investigate the bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice for noninvasive monitoring on progression of brain tumor in vivo.Methods The human brain tumor cell line U87MG cells were transduced by using the SMPU-R-MND-luc vector then a clone with high luciferase activity was cloned and used for in vivo experiments. Tumor cells were implanted into the brains and flanks of the animals, and whole body images revealing tumor location were obtained. Tumor burden was monitored over time by quantity of photon emission.Results Orthotopic brain tumor and heterotopic flank tumor models were established by implanting constitutively expressing luciferase tumor cells in the brains and flanks of the animals. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated with the time after injection of luciferin, indicating that the time of post-injection signal quantification was of special importance. Furthermore, the time courses in the heterotopic and

  20. Experimental treatment of breast cancer-bearing BALB/c mice by artemisinin and transferrin-loaded magnetic nanoliposomes

    Directory of Open Access Journals (Sweden)

    Amir Gharib

    2015-01-01

    Full Text Available Background: The combination of artemisinin and transferrin exhibits versatile anticancer activities. In previous, we successfully prepared artemisinin and transferrin-loaded magnetic nanoliposomes and evaluated their anti-proliferative activity against MCF-7 and MDA-MB-231 cell lines in vitro. In this study, we investigate the in vivo anti-breast cancer activity of artemisinin and transferrin-loaded magnetic nanoliposome against breast transplanted tumors in BALB/c mice model. Materials and Methods: Artemisinin and transferrin-loaded magnetic nanoliposomes were prepared and characterized for some physiochemical properties. Pieces of tumor tissue from the breast cancer-bearing BALB/c mice were transplanted subcutaneously to the syngeneic female BALB/c mice. In the presence of the external magnet that placed at the breast tumor site, the tissue distribution and tumor-suppressing effects of prepared nanoliposomes on tumor growth was evaluated. Results: The prepared nanoliposomes have fine spherical shape, rough surface, nano-sized diameter and magnetic properties. At 2 h after treatment, the intravenous administration of artemisinin and transferrin-loaded magnetic nanoliposomes followed using the magnetic field approximately produced 10- and 5.5-fold higher levels of artemisinin and transferrin in the tumors, respectively, compared with free artemisinin and transferrin. Moreover, in the presence of an external magnetic field, the prepared nanoliposomes could significantly induce apoptosis in the mice breast cancer cells as well as could reduce tumor volume in tumorized mice at 15 days after treatment. Conclusion: The data suggested that the artemisinin and transferrin-loaded magnetic nanoliposomes would be a good choice for the breast tumor-targeted therapy, due to its high targeting efficiency.

  1. Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian cancer model

    International Nuclear Information System (INIS)

    Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with 90Y-labeled OC 125-monoclonal antibody; these mice received the antibodies intratumorally, intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between 90Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between 90Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera. (orig.)

  2. Seropositivity in Dutch Crohn's disease patients against primed nude mouse lymph nodes, and the difference with lymphocytotoxic antibodies.

    OpenAIRE

    Pena, A.S.; Kuiper, I.; Walvoort, H.C.; Verspaget, H.W.; Weterman, I T; Ruitenberg, E. J.; Das, K. M.

    1986-01-01

    Sera from patients with Crohn's disease have been reported to show positive immunofluorescence with lymph nodes of nude mice primed with a filtrate of intestinal tissue affected with Crohn's disease. An indirect immunofluorescence assay was used to test sera of 63 unrelated patients with Crohn's disease, 21 with ulcerative colitis and 36 control subjects against lymph nodes of athymic nude (nu/nu) mice which had been injected with Crohn's disease and ulcerative colitis intestinal tissue filtr...

  3. 单发性裸鼠人肝癌实验模型的建立%Experimental Model of Solitary Human Hepatocellular Carcinoma in Nude Mouse

    Institute of Scientific and Technical Information of China (English)

    尹美珍; 苏振宏

    2013-01-01

      为了建立单发性人肝癌动物模型,将1×107个/mL Bel -7402细胞接种于5~6周龄裸鼠左右侧颈背部皮下,待瘤体积约为2 cm3时,取其瘤组织,剪碎,制成悬液,再接种于实验裸鼠右侧颈背部皮下,每日观察裸鼠的成瘤情况,测量并计算其瘤体积及生长率,大体解剖濒死荷瘤鼠,取瘤组织做病理形态学检查。结果显示:裸鼠单发性人肝癌移植瘤的成瘤率为96%,移植瘤生长快,不发生转移,具有肿瘤形态、肝癌组织特点及肝癌细胞超微结构的形态学特征。成功构建了单发性裸鼠人肝癌模型,是进行生物学研究尤其是治疗药物筛选研究的一种理想的肝癌动物模型。%Objective: The experimental model of solitary human hepatocellular carcinoma in nude mouse was established.Method:The Bel-7402 human hepatocarcinoma cells were transplanted subcutaneously into the right and left nape of every 5~6 weeks old nude mice with a cell number of 1 ×107/mL.After the tumor grew to about 2 cm3 in volume, the tumors were extracted and transformed into cell suspensions that were in-jected subcutaneously into the right nape of the experimental nude mouse .Tumor formation was observed dai-ly, the long diameter and short diameter of the tumors were measured to calculate the tumor volumes and the tumor growth rate, and gross anatomy was observed in dying mouse bearing cancer and the tumor issue was taken for morphological examination .Result: The formation rate of solitary Subcutaneous transplantation tumor in nude mice was 96%, and the transplantation tumor with rapid tumor growth and without metastasis possess a specific morphological feature of tumor .Conclusion: The experimental model of solitary human hepatocellular carcinoma in nude mice was successfully established ,and it was a ideal animal model for local therapy study.

  4. Low dose radiation increased the therapeutic efficacy of cyclophosphamide on S180 sarcoma bearing mice

    International Nuclear Information System (INIS)

    We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S180 sarcoma cells were given 75 mGy whole body γ-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G1 phase in the groups treated with CTX and CTX+LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX+LDR mice were higher than those in the untreated mice. LDR or CTX+LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy. (author)

  5. Experimental Study of the Relation of Inhibiting Vasculogenic Mimicry and Inducing Cell Apoptosis of Melittin on Osteosarcoma Xenotransplanted Models of Nude Mice%蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、调亡的关系

    Institute of Scientific and Technical Information of China (English)

    高启龙; 姚亚民; 杨峰; 田同德; 陈永强

    2011-01-01

    目的:探讨蜂毒素抑制骨肉瘤裸鼠移植瘤的作用及机制.方法:建立裸鼠骨肉瘤原位移植瘤模型,裸鼠18只,随机分3组:生理盐水组,蜂毒素组,顺铂组.观察各组裸鼠骨肉瘤体积和瘤体质量抑制率;应用免疫组化CD34与PAS双重染色法检测各组裸鼠瘤体血管生成拟态密度;免疫组织化学法检测增值细胞核抗原(PCNA)蛋白表达;TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、凋亡的关系.结果:蜂毒素组瘤体积和瘤体质量抑制率分别为42.98%、39.03%,蜂毒素能明显抑制CD34与PAS双重染色法标记的肿瘤血管生成拟态密度,能明显抑制肿瘤细胞增殖、促进细胞凋亡,且蜂毒素抑制肿瘤血管生成拟态密度与肿瘤细胞增殖呈正相关、与细胞凋亡呈负相关.结论:蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成拟态、诱导肿瘤细胞凋亡、抑制细胞增殖有关.%Objective:To study the antitumor effects and mechanism of Melittin on osteosarcoma xenotransplanted models of nude mice. Methods ; Xenotransplanted models of nude mice osteosarcoma cell UMR - 106 in the laevo - hind tibia of nude mice were established. Inoculated mice were randomly divided into normal saline group, positive control group, Melittin group. All the nude mice were sacrificed after treatment, the size and weight of tumor were measured and the tumor volumes and the inhibition rates of tumor were calculated, Expression of PCNA was deteced by immunohistochemical method. The VM density in tumor tissues was detected by CD34 and PAS double staining in vivo. TUNEL semi - quantitative assay was used to study the melittin - induced apoptosis in OS cell line. To study mainly the relation of inhibiting vasculogenic mimicry and inducing cell apoptosis. Results : Inhibiting rate ofmelittin in tumor

  6. Comparison of tumorigenic effect between inoculating method of slicing subaxillary skin and suturing and method of adopting paracentesis trocar of human nasopharyngeal carcinoma on nude mice%裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞成瘤效果比较

    Institute of Scientific and Technical Information of China (English)

    吴媛; 周训钊; 钟昌桃; 颜魁; 韦正波; 谢莹

    2015-01-01

    目的:比较裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞成瘤效果。方法制备鼻咽癌HONE-1细胞裸鼠皮下移植瘤块样本。将8只BALB/c裸鼠随机分为A、B组,各4只。 A、B组分别使用皮肤切开缝合接种和穿刺套针接种方法于裸鼠右侧腋下接种细胞株移植瘤组织块,比较两组裸鼠肿瘤出现时间、体积、质量。结果 A、B组肿瘤出现时间均为接种后第3天。与B组相比,A组裸鼠较早出现精神萎靡、皮肤粗糙、毛发光泽不良、食欲不振、活动量减低、脊椎明显、弓背等状况。两组裸鼠体质量均有所下降,A组比B组肿瘤生长迅速,但差异无统计学意义。 A、B组肿瘤质量分别为(0.85±0.39)、(0.75±0.30) g,两组比较,P>0.05。结论裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞均能达到好的成瘤效果。%Objective To compare the tumorigenic effect between the inoculating method of slicing the subaxillary skin and suturing and the method of adopting the paracentesis trocar of human nasopharyngeal carcinoma on the nude mice. Methods The samples of subcutaneous transplanted tumors in nude mice were established with nasopharyngeal carcinoma HONE-1 cells.Eight BALB/c nude mice were randomly divided into two groups:group A and B, 4 mice in each group. The right subaxillary skin of each mouse was subcutaneously inoculated with the tissue masses through slicing the skin, or adopting the paracentesis trocar in the two groups, respectively.The occurrence time, volume and mass of tumor in each group were compared.Results The occurrence time of tumor in each group was 3 days after being inoculated.Compared with group B, the occurrence time of dispirited mind, coarse skin, shineless hair, loss of appetite, low activity, distinct spinal column, hunched backs and other conditions were earlier in the group A.The weight of mice was decreased in both

  7. 寡脱氧核苷酸致敏树突状细胞对SKOV -3卵巢癌移植瘤抑瘤作用的研究%Study on the immunosuppressive action of dendritic cells sensitized by CpG ODN on human SKOV -3 ovarian carcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    叶明殊; 李娜; 黄秀敏

    2011-01-01

    Objective: To investigate the immunosuppressive action of dendritic cells (DCs) sensitized by oligonucleotides containing " un - methylated cytimidine - phosphodiester bond - guanylie acid" motif (CpG ODN) on human ovarian carcinoma xenografts in nude mice. Methods: Human peripheral blood -derived dendritic cells were isolated and co - incubated with CpG ODN2006, CA125, or CPG OND + CA125. T cells were obtained from DCs, and the suspensions of different groups of pulsed DCs were co - incubated with T cells. The cytotoxic T lymphocyte ( CTL) reaction were used to detect the proliferating activity of T cells. Ovarian carcinoma cells of the line SKOV - 3 were added into the culture fluid of T cells induced by different groups of DCs. MTT colorimetry were performed to calculate the killing activity. Then nude mice bearing SKOV - 3 transplanting tumor were immuned with the activated T cells by intraperitoneal injection, and tumor growth was observed. Results: Human peripheral blood - derived dendritic cells were activated significantly by CpG ODN2006 associated with CA125 in vitro. The activated DCs promoted the proliferation of T cells, and there was significant difference with impulsed DC and CA125 - pulsed DC (all P <0.01) . CTLs induced by CpG ODN + CA125 - pulsed DC appeared stronger specific cytotoxicity on SKOV3 cells than those by CpG ODN - pulsed DC, CA125 - pulsed DC and impulsed DC at the same effectors: target ratios ( all P < 0. 01). More marked growth inhibition of SKOV -3 transplanting tumor was observed in CpG OND + CA125 - pulsed group than CpG ODN - pulsed and CA125 -pulsed groups (PCpGODN <0. 05, PCA125 <0. 01) in vivo. Conclusion: DCs sensitized by CpG ODN + CA125 can inhibit the growth of ovarian carcinoma. It may provide a new alternative for the immunotherapy of ovarian carcinoma.%目的:探讨含未甲基化胞嘧啶-磷酸二酯键-鸟嘌呤(CpG)基序的寡脱氧核苷酸(CpG ODN)致敏树突状细胞(DCs)对裸鼠人卵巢癌移植瘤生长

  8. 恶性横纹肌样瘤(MRT)的起源研究——高变异率HeLa细胞致裸鼠产生MRT的实验研究%Studies of the Origin of Malignant Rhabdoid Tumor(MRT)——Experimental Researches on the MRT Evolving in Nude Mice Inoculated with Violently Variable HeLa Cells

    Institute of Scientific and Technical Information of China (English)

    张德礼; 夏耕田; 高步先; 何旭玉; 白晓鸿; 黄高升; 李六金; 刘尚高

    2000-01-01

    致癌性;HeLa细胞染色体遗传特征决定致瘤性质,细胞染色体数目变异大小和致癌/致瘤性强弱相关,致瘤性由弱到强的顺序依次为KB株,X株和NM20/X株,但H株有例外,尚待进一步实验确定。%Under the prerequisite that the incidence of cancer or tumor in negatively?controllednudemiceinoculatedsubcutaneously with feline or canine kidney cell cultures purified in vitro at passage 3 or higher (the modal chromosome number of FKC on passage 3 was 38 of diploid at the rate of 80%) was 0%(0/22) and 0%(0/10) respectively, and the incidence of progressively negative growing tumor in controlled nude mice inoculated subcutaneously with repeatedly-frozen-andthawed-HeLa cell cultures of X strain was 20%(1/5), the negative growing malignant tumor (MT) was found in half of the nude mice inoculated subcutaneously with HeLa cell cultures of H strain(with modal chromosome number of 78±2 of sub-tetraploid at the rate of 40%), the progressively-growing malignant tumor was found in all the other 40 nude mice inoculated subcutaneously with HeLa cell cultures of other strains, with the incidence of MT in nude mice with KB strain (with modal chromosome number of 60±3 of hyperdiploid at the rate of 72%~76%) 10/10, the incidence of poorly-differentiated MT originated from epithelia in nude mice with X strain (with modal chromosomal number of 62±3 of hyperdiploid at the rate of 69%) 25/25, and the incidence of MRT in nude mice with in vitro cultured tumor cell NM20/X strain (with modal chromosome number of 68±3 of both hyperdiploid and subtetraploid at the rate of 52%) 5/5. After being continuously cultivated for 20 passages in vitro, HeLa cell of X strain was subcutaneously inoculated into nude mice and cultivated for 1 passage in vivo within 15 days, and then the developed growing MT was collected as HeLa cell of NM20/X strain on passage 0 and continuously cultivated for 11 passages to prepare for

  9. Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts

    International Nuclear Information System (INIS)

    In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. A synthetic variant of the anti-HER2 ZHER2:342 Affibody molecule, ZHER2:S1, was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with 111In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-ZHER2:S1, NOTA-ZHER2:S1 and NODAGA-ZHER2:S1, respectively. A comparative study of 111In-labelled DOTA-ZHER2:S1, NOTA-ZHER2:S1 and NODAGA-ZHER2:S1 in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. 111In-NODAGA-ZHER2:S1 had the most rapid clearance from blood and healthy tissues. 111In-NOTA-ZHER2:S1 showed high hepatic uptake and was excluded from further evaluation. 111In-DOTA-ZHER2:S1 and 111In-NODAGA-ZHER2:S1 demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of 111In-NODAGA-ZHER2:S1, 5.6 ± 0.4%ID/g, was significantly lower than the uptake of 111In-DOTA-ZHER2:S1, 7.4 ± 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance. 111In-NODAGA-ZHER2:S1 provided higher tumour

  10. Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice.

    OpenAIRE

    Agarwal, A.; Kandpal, H; Gupta, H. P.; N. B. Singh; Gupta, C M

    1994-01-01

    The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes was at le...

  11. Insights into the regulation of muscle metabolism and growth in mice and hibernating grizzly bears

    OpenAIRE

    Mugahid (Megahed), Douaa (Doaa)

    2015-01-01

    Mechanotransduction plays an important role in the regulation of muscle growth and metabolic signalling in striated muscle. Muscle disuse reduces mechanical input to the muscle, which results in a loss of muscle mass. Here I describe how titin's mechanically activated kinase domain affects muscle growth and metabolism via p62 and Akt signalling. I also demonstrate how changes in metabolic and growth signalling in hibernating grizzly bear help maintain muscle mass under conditio...

  12. Therapeutic efficacy of tumor-derived heat shock protein 70 immunotherapy combining interleukin-2 on tumor-bearing mice

    Institute of Scientific and Technical Information of China (English)

    傅庆国; 孟凡东; 沈晓东; 郭仁宣

    2003-01-01

    Objective To investigate the therapeutic efficacy of compound immunotherapy of tumor-derived heat shock protein 70 (HSP70) and interleukin-2 (IL-2) on tumor-bearing mice, and to provide reference for translating this strategy to human cancer. Methods Cell culture, techniques for protein extraction and purification, SDS-PAGE, Wes tern blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used. Mice were treated with HSP70 5 or 10 μg and IL-2 50 kU, 100 kU or 2 kU (maintaining dosage) at pre viously designated intervals. Results Both the mono-administration of either HSP70 or IL-2 and the compound immunoth erapy of HSP70 and IL-2 obviously inhibited the growth of the implanted tumor and prolonged the life span of the mice to different extents. However, long periods of tumor-free suvival (over 90 days) were demonstrated only in HSP70 10 μg group, HSP70 10 μg-IL-2 50 kU group, and HSP70 10 μg-IL-2 100 kU group (4 0%, 40%, 60% respectively). On the other hand, none of the mice in the rest gr oups achieved long-term survival. Statistical significance was apparent in com parison with the groups without long period survival (P<0.025-0.05). Conclusion Our research revealed that tumor-derived HSP70 immunotherapy was much more effective than IL-2 alone. And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors. The proper combination of HSP70 and IL-2 (10 μg HSP70 and 100 kU IL-2 in this experimental mouse model) clea rly enhanced the immunotherapy efficacy which indicated that the specific immuno therapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment.

  13. Reduced white fat mass in adult mice bearing a truncated Patched 1

    Directory of Open Access Journals (Sweden)

    Zili Li, Heng Zhang, Leslie A. Denhard, Lan-Hsin Liu, Huaxin Zhou, Zi-Jian Lan

    2008-01-01

    Full Text Available Hedgehog (Hh signaling emerges as a potential pathway contributing to fat formation during postnatal development. In this report, we found that Patched 1 (Ptc1, a negative regulator of Hh signaling, was expressed in the epididymal fat pad of adult mice. Reduced total white fat mass and epididymal adipocyte cell size were observed in naturally occurring spontaneous mesenchymal dysplasia (mes adult mice (Ptc1mes/mes, which carry a deletion of Ptc1 at the carboxyl-terminal cytoplasmic region. Increased expression of truncated Ptc1, Ptc2 and Gli1, the indicators of ectopic activation of Hh signaling, was observed in epididymal fat pads of adult Ptc1mes/mes mice. In contrast, expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, adipocyte P2 and adipsin were reduced in epididymal fat pads of adult Ptc1mes/mes mice. Taken together, our results indicate that deletion of carboxyl-terminal tail of Ptc1 can lead to the reduction of white fat mass during postnatal development.

  14. Preparation of Tc-carbonyl complexes of tryptophan and histidine and biodistribution in mice bearing S180 tumor

    International Nuclear Information System (INIS)

    The Tc-carbonyl complexes of tryptophan and histidine were synthesized by two-step method. The yielded complexes were found by paper electrophoresis to be electrically neutral in three buffer solutions (pH = 4.7, 7.4, 9.2). Their possible structures were postulated based on ab initio MO calculations. The biodistribution in mice bearing S180 tumor demonstrated that the Tc-carbonyl complex of histidine showed good stability in vivo and quick clearance, selectively accumulated in tumor. The tumor/muscle ratio attained 3 to 4. However, the complex of tryptophan showed poor stability in vivo and slow clearance, and retained for a long time in organs and tissues. It also accumulated in tumor to some extent. The tumor.muscle ratio attained 2 to 3. The labelling of proteins and polypeptides with the Tc(I)-carbonyl complex was also discussed

  15. Synthesis, in vitro binding and biodistribution in B16 melanoma-bearing mice of new iodine-125 spermidine benzamide derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Moreau, Marie-France [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Papon, Janine [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Labarre, Pierre [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Moins, Nicole [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France)]. E-mail: moins@inserm484.u-clermont1.fr; Borel, Michele [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Bayle, Martine [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Bouchon, Bernadette [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Madelmont, Jean-Claude [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France)

    2005-05-01

    In the course of our investigations aimed at improving the biological characteristics of iodobenzamides for melanoma therapeutic applications, four new derivatives containing a spermidine chain have been prepared and radiolabeled with {sup 125}I. In vitro studies showed that all compounds displayed high affinity for melanin superior to the reference compound BZA, thus validating our experimental approach. In vivo biodistribution was investigated in B16 melanoma-bearing mice. All four compounds, particularly benzamide 3, showed accumulation in the tumor, but lower, however, than that of BZA. Moreover, high concentrations of radioactivity in other organs, namely, the liver and lung, demonstrated nonspecific tumoral uptake. In view of these results, compounds 1 2 3 4 do not appear to be suitable radiopharmaceuticals for melanoma radionuclide therapy.

  16. Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

    Science.gov (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2014-10-01

    Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and ppancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the 650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

  17. Roles of MAPK/ERK signaling pathway in the growth inhibition of an established A431 xenograft tumor in nude mice by resveratrol%MAPK/ERK信号转导通路在白藜芦醇抑制A431细胞株裸鼠移植瘤生长中的作用机制研究

    Institute of Scientific and Technical Information of China (English)

    郝玉琴; 黄维星; 宁晓洪; 冯红霞; 张国惠; 李衡贵; 郝春光

    2013-01-01

    evaluate the effect of resveratrol on the growth of an established A431 xenogratt tumor in nude mice.Methods The model of human skin squamous cell carcinoma was established by inoculating A431 cells in log-phase growth into the left axillary fossa of Balb/c (nu/nu) nude mice.After 7-8 days,60 mice bearing human A431 skin squamous cell carcinoma xenografts were randomly and equally divided into 6 groups:blank control group receiving no treatment,negative control group treated with intraperitoneal sodium chloride physiological solution,positive control group treated with intraperitoneal cyclophosphamide,high-,medium-and low-dose resveratrol groups treated with intraperitoneal resveratrol of 40,20 and 10 μg per gram body weight per day,respectively.Tumor size was measured at a 4-day interval during the treatment course.After 14-day treatment,the mice were sacrificed.Xenograft tumors were removed from these mice and subjected to weight measurement,pathological examination by hematoxylin and eosin (HE) staining and apoptosis detection by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).Western blot was conducted to quantify the protein expression of apoptosis-related factors,including phosphorylated extracellular signal-regulated protein kinase (p-ERK),p53 and caspase 3.Data were processed by SPSS 13.0 software,and statistical analysis was carried out by analysis of variance and Pearson correlation analysis.Results By the end of treatment,the xenograft tumor volume was (1153.56 ± 255.41) mm3,(1001.69 ± 115.08) mm3,(1206.80 ± 175.88) mm3,(1342.28 ± 211.12) mm3,(1642.34 ± 225.85) mm3 and (1564.32 ± 156.49) mm3,and the weight was (1.84 ±0.30) g,(1.72 ± 0.39) g,(1.96 ± 0.40) g,(2.67 ± 0.73) g,(3.16 ± 0.52) g,and (3.33 ± 0.59) g,respectively in the positive control group,high-,medium-and low-dose resveratrol group,negative control group and blank control group.Significant differences were observed in the xenograft tumor volume (F =16.00,P

  18. Real-time analysis of liposomal trafficking in tumor-bearing mice by use of positron emission tomography.

    Science.gov (United States)

    Oku, N; Tokudome, Y; Tsukada, H; Okada, S

    1995-08-23

    Long-circulating liposomes are known to accumulate passively in tumor tissues of tumor-bearing animals. To evaluate the in vivo behavior of such liposomes, we investigated the real-time liposomal trafficking by a non-invasive method using position emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and palmityl-D-glucuronide (PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[18F]fluoro-2-deoxyglucose ([2-18F]FDG). [2-18F]FDG-labeled liposomes sized by extrusion through a filter with various-sized pores were administered to mice bearing Meth A sarcoma, and a PET scan was performed for 120 min. Small-sized, long-circulating liposomes (100 nm in diameter) constructed with PGlcUA tended to accumulate in the tumor tissues. On the contrary, control liposomes (100 nm in diameter) containing dipalmitoylphosphatidylglycerol instead of PGlcUA accumulated in the liver. Large-sized PGlcUA-containing liposomes (> 300 nm) also accumulated in the liver, as well as in the spleen. Time-activity curves indicated that the small long-circulating liposomes (PET technique might be useful for studying real-time liposomal trafficking and for tumor imaging. PMID:7654755

  19. Impact of fractionated local irradiation on lung metastasis in H22-bearing mice and exploration of its mechanism

    International Nuclear Information System (INIS)

    Objective: To study the impact of local fractionated irradiation on lung metastasis in H22-bearing ice, and to explore its mechanism involved. Methods: Subcutaneous transplantation tumor model bearing with H22 was established. Mice were divided into three groups as healthy control, tumor control and irradiation groups. The size of subcutaneous tumors was measured and lung metastasis was observed. The expressions of PCNA, VEGF and MVD were detected immunohistochemically. The plasma levels of CD4 and CD8 were determined by using flow cytometry. Results: The tumor size in irradiated group was smaller than that in tumor control group. The tumor inhibition rate in irradiated group was 30%. Lung metastasis in irradiated group was more severe than that in tumor control group (χ2=8.31, 4.48, 9.60, P<0.05). The expressions of PCNA, VEGF and MVD in two groups were statistically different (t=23.78, -2.47, -6.43, P<0.05). The levels of CD4 and CD8 in irradiated group were statistically different compared to healthy control group (t=4.72 and 3.31, P<0.05). Conclusions: For the H22 model, radiation might inhibit the local transplantation tumor, but increase the risk of lung metastasis. (authors)

  20. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    DEFF Research Database (Denmark)

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer;

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was...... radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold....

  1. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

    OpenAIRE

    Ruud, Johan; Nilsson, Anna; Engström Ruud, Linda; Wang, Wenhua; Nilsberth, Camilla; Iresjo, Britt-Marie; Lundholm, Kent; Engblom, David; Blomqvist, Anders

    2013-01-01

    It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia–cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia–cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia...

  2. Preparation of selenium-enriched Bifidobacterium longum and its effect on tumor growth and immune function of tumor-bearing mice.

    Science.gov (United States)

    Yin, Yan; Wang, Rong-Rong; Wang, Yan; Wang, Jian-Jun; Xu, Gen-Xing

    2014-01-01

    In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic, the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice (n=8) were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice (n=12) was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α), and the leukocyte count of H22 tumor-bearing mice (n=12). PMID:24870777

  3. Non-invasive imaging of GFP-luciferase labeled orthotopic prostate cancer model in nude mice using bioluminescence system%可发光可连续检测原位前列腺癌模型的建立

    Institute of Scientific and Technical Information of China (English)

    宋超; 廖文彪; 杨嗣星; 王玲珑

    2012-01-01

    Objective To develop preclinical orthotopic model in nude mice for sensitive prostate cancer cell tracking during tumor progression using bioluminescent technique.Methods The human prostate cancer cell line PC3 cells were transduced with green fluorescent protein (GFP) -luciferase fusion gene by a lentivirus vector which can express high activity of luciferase and GFP.Stably transduced GFP-LucPC3 monoclonal cells were got with Blasticidin selection.Labeled or normal tumor cells ( 5 × 106 ) were implanted into the flanks of 6 animals to build up an intradermal xenograft prostate cancer model,which provided prostate cancer graft to build the orthotopic prostate tumor model,and to confirm the tumorigenesis ablitiy of GFP-Luc-PC3.Tumor tissue from the either PC3 or GFP-Luc-PC3 line tumors was harvested and cut into pieces of about 2 mm3.These were grafted into the anterior prostates of 24 male animals which were randomly divided into two groups.The tumor growth was monitored by both WIS 200 and ex vivo tumor weight analysis 2,4,6 and 8 weeks after tumor tissue grafting.The bioluminescent signal values as well as tumor weight was measured,and their relationship was analyzed accordingly.Results A GFP-LucPC3 cell line was established which had the same growth pattern as well as tumorigenesis ability as normal PC3 cells.There was a positive linear correlation between bioluminescent signal and cell number with the coefficient factor r =0.997.In orthotopic prostate cancer model,all 12 mice in GFP-Luc-PC3 group developed prostate tumor,from which the bioluminescent signal could be recorded.In normal PC3 group,there was no significant bioluminescent signal.The bioluminescent values (photons/second) in vivo were (69.13298±2.07900) E+05,(82.66208±1.231 00) E+05,(91.94257±2.321 00) E+05 and ( 130.643 40 ± 3.247 00) E + 05 respectively 2,4,6 and 8 weeks after tumor tissue implantation.The tumor weight ex vivo was ( 9.67 ± 1.07 ),( 12.47 ± 2.12),( 16.45 ± 2.57 ),and ( 21

  4. Effect of the delivery system on the biodistribution of Ge(IV) octabutoxy-phthalocyanines in tumour-bearing mice.

    Science.gov (United States)

    Soncin, M; Polo, L; Reddi, E; Jori, G; Kenney, M E; Cheng, G; Rodgers, M A

    1995-02-10

    The pharmacokinetic properties of the Ge(IV)-octabutoxy-phthalocyanines (GePc) with two axially ligated triethylsiloxy (GePcEt) or trihexyl-siloxy (GePcHex) chains were studied in BALB/C mice bearing a transplanted MS-2 fibrosarcoma. The GePcs were delivered to mice after incorporation into unilamellar liposomes of dipalmitoyl phosphatidylcholine (DPPC) or in an emulsion of Cremophor-EL. The Cremophor delivered GePcs were cleared from the blood circulation at a much slower rate than the liposome-delivered GePcs. At the same time, Cremophor induced a slower and reduced uptake of the GePcs in the liver and spleen while it greatly enhanced the uptake in the tumour as compared to liposomes. Maximum tumour uptake was observed at 24 h post-injection and was equivalent to 0.67 and 0.50 nmol/g, respectively, for the Cremophor delivered GePcHex and GePcEt. The corresponding values for the liposome-delivered drugs were approximately one fourth of that observed with Cremophor. PMID:7882292

  5. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P131I-A7 RIT displayed a marked therapeutic effect (n=8) (P131I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P131I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  6. Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

    Directory of Open Access Journals (Sweden)

    Heba Bassiony

    Full Text Available BACKGROUND: Magnetite nanoparticles (MNPs have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with ascorbic acid (size: 25.0±5.0 nm were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT or intraperitoneally (IP. Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. RESULTS: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. CONCLUSION: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

  7. FXR激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响%Effect of FXR Agonist GW4064 on the Proliferation and Angiogenesis of HCC Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    位全芳; 路菊; 陶忠芬; 黄文琪; 糜建红

    2015-01-01

    目的:探讨研究法尼酯x受体(FXR)激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响.方法:选取人肝癌细胞系HepG2进行体外培养,将细胞悬液接种于BALB/c裸鼠皮下.裸鼠成瘤后,随机分为两组,分别腹腔注射DMSO和GW4064.一周后,处死动物取肿瘤组织,通过免疫组织化学法检测肿瘤组织中Ki-67和CD31的表达,同时计数肿瘤组织中的微血管密度(CD31-MVD); Western blot法检测其FXR和白介素-8(IL-8)的蛋白表达.结果:与对照组相比,FXR激动剂GW4064处理组的肿瘤组织中FXR的蛋白表达量明显增高,微血管密度CD31-MVD值显著降低,同时Ki-67、IL-8及CD31的表达水平均显著降低.结论:FXR激动剂GW4064能显著增加FXR的表达,抑制裸鼠肝癌细胞移植瘤的增殖及新生血管的形成.%Objective:To investigate the effect of FXR agonist GW4064 on the proliferation and angiogenesis of hepatocellular carcinoma (HCC)cells in BALB/c nude mice.Methods:Human hepatocellular carcinoma cell line HepG2 were cultured in vitro,then implanted subcutaneously in nude mice.When the subcutaneous xenograft was formed,the nude mice were randomly divided into a control group and an experimental group,which were injected with DMSO and GW4064 respectively.After one week,the tumor was separated,the expression of Ki67 and CD31 were detected by immunohistochemical(IHC) method,the microvessel density (CD31-MVD) of tumors were calculated,and the expression of FXR and IL-8 were detected by Western blot assays.Results:Compared with control group,the expression of FXR increased significantly,the microvessel density CD31-MVD value decreased significantly,while the expression level ofKi-67,IL-8 and CD3 1were significantly inhibited in GW4064 group.Conclusion:FXR agonist GW4064 may stimulate the expression of FXR thereby inhibiting the cell proliferation and tumor angiogenesis of hepatocellular carcinoma cell xenografts in nude mice.

  8. 转染 p53基因对肺腺癌细胞株裸鼠 移植瘤生长的影响%Study on the Role of p53 Gene Transfer on Human Glandular Lung Cancer Cell Growth in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    李萍; 王北宁; 丁振若

    2001-01-01

    Objective: This study was designed to explore the significance and the role of wild-type p53 (wt-p53) gene and mutant p53 gene(mt-p53) transfer on human glandular lung cancer cell growth in nude mice. Methods: wt-p53 gene and mt-p53 gene were transfected and lipofectin-mediated into the human glandular lung cancer cell line GLC-82. And the growth of gene-transfected cell lines were observed in vitro and in vivo. Results: The colony number in the colong-forming experiment and the volume and weight in nude mice were greater in the mf-p53 tranfecting cells group than in the control group. The tumor resulting from the cells transfected with the wt-p53 gene grew more slowly and was smaller than that from control GLC-82 cells. In contrast, the tumor from the cells transfected with the mt-p53 gene grew faster than that produced by cells transfeted with the wt-p53 gene and that produced by control GLC-82 cells. Conclusion: The wild-type p53 gene could inhibit the glandular lung cancer cell growth in nude mice and the mutant p53 gene could enhance the glandular lung cancer cell growth in nude mice.%目的:探讨转染野生型 p53( wt-p53)和突变型 p53( mt-p53)基因对人肺腺癌细胞株 GLC-82裸鼠移植瘤生长的影响。方法:采用脂质体介导法,分别将 wt-p53和 mt-p53基因导入人肺腺癌细胞株 GLC-82,在裸鼠体内、体外实验中检测转导细胞的生长状况和裸鼠致瘤性。结果:转染 mt-p53 基因的细胞株 G418筛选的细胞集落数、 3H-TDR掺入实验、软琼脂平皿细胞集落数,以及裸鼠瘤组织重量和体积均高于对照组( P<0.01),而转染 wt p53基因的细胞株均显著低于对照组( P< 0.01),表明导入 wt p53基因的细胞株瘤细胞生长速度明显低于对照组细胞株和导入 mt p53基因的细胞株,即导入 mt p53基因的细胞株瘤细胞生长速度最快,而导入 wt p53基因的细胞株瘤细胞

  9. c-FLIP antisense oligonucleotide-loaded nanoparticles inhibit growth of human orbital rhabdomyosarcoma xenograft in nude mice%c-FLIP反义寡核苷酸纳米粒抑制人眼眶横纹肌肉瘤裸鼠移植瘤的生长

    Institute of Scientific and Technical Information of China (English)

    梁莉; 魏锐利

    2013-01-01

    Objective To investigate the effect of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP) antisense oligonucleotide (ASODN)-loaded nanoparticles (NP) on the human orbital rhabdomyosarcoma xenograft in nude mice,so as to assess the feasibility of nanoparticles as a gene vector.Methods The model of human orbital rhabdomyosarcoma xenograft was established in nude mice,and the tumors were injected with c-FLIP ASODN NP,c-FLIP ASODN or normal saline (NS).The tumor volume and histopathological changes of tumor were observed.Western blotting analysis and immunohistochemical analysis were used to examine the expression of c-FLIP in tumor tissues of each group.Apoptosis of tumor cells was detected using TUNEL method.Results The growth of human orbital rhabdomyosarcoma in nude mice was significantly inhibited in ASODN NP group compared with the other two groups.Western blotting analysis showed that c-FLIP protein expression in ASODN NP and ASODN groups was significantly decreased compared with NS group (P<0.05).Immunohistochemical study showed that c-FLIP expression was found in the endochylema,and the c-FLIP positive cells in ASODN NP group was significantly less than those in the other two groups (P<0.05).Tumor cell apoptosis was observed in both ASODN NP and ASODN groups,with more found in the former,and only a few apoptotic cells were found in the NS group.Conclusion c-FLIP ASODN NP can effectively inhibit the growth of human orbital rhabdomyosarcoma xenograft in nude mice,indicating that nanoparticles may serve as a safe and effective vector for ASODN.%目的 探讨c-FLIP反义寡核苷酸(c-FLIP ASODN)纳米粒(NP)对裸鼠体内人眼眶横纹肌肉瘤移植瘤生长的影响,评估纳米粒作为基因载体的可行性.方法 皮下种植法建立裸鼠人眼眶横纹肌肉瘤动物模型,瘤体内分别注射c-FLIP反义寡核苷酸纳米粒(ASODN NP组)、未包裹的c-FLIP反义寡核苷酸(ASODN组)及生

  10. PI-103增强顺铂对CI3K细胞裸鼠移植瘤生长的抑制作用%PI-103 Enhances Cisplatin-Caused Growth Inhibition of C13K Cell Xenografts in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘勇; 孔繁飞; 方勇; 李智敏; 孙淑华

    2013-01-01

    Objective To examine the effect of PI-103 in combination with cisplatin on the proliferation and apoptosis of C13K cells and growth of xenografts of nude mice. Methods The proliferation of C13K cells was assessed by MTT assay after exposure to PI 403, cisplatin or both. Apoptosis was evaluated by flow cytometry. Immunoblot analysis was performed to detect the ex -pression of phosphorylation of AKT and S6 kinase 1. C13K cells was subcutaneously transplanted into nude mice ( n = 16) , which were randomly divided into control group , PI-103 group, cisplatin group and combined treatment group. After treatment for 4 consecutive weeks, the tumor inhibition rate was evaluated. Results PI-103 in combination with cisplatin inhibited the proliferation of C13 K cells in a time-dependent manner. The inhibitory effect of combination therapy was superior to PI 403 or cisplatin treatment alone. PI403 increased cisplatin induced apoptosis in C13K cells. PI403 inhibited the expression of phosphorylation of AKT and S6 kinase 1 in C13K cells. PI-103 plus cisplatin significantly inhibited the growth of xenografts in nude mice and there was significant difference between combined treatment group and cisplatin group. Conclusion PI-103 may enhance growth inhibition of C13K cell xenografts by cisplatin in nude mice.%目的 通过评价PI-103联用顺铂对C13K细胞体外增殖、凋亡及裸鼠移植瘤生长的影响为卵巢癌的靶向治疗寻找新的药物.方法 C13K细胞经PI-103和/或顺铂处理后,以MTT法检测细胞的增殖情况,以流式细胞仪检测细胞凋亡,Western印迹检测p-AKT和p-S6K1的表达情况.建立C13K细胞皮下裸鼠移植瘤模型,随机分成对照组、PI-103组、顺铂组、合并组4组,连续用药4周.观察肿瘤生长情况,计算抑瘤率.结果 PI-103联合顺铂抑制C13K细胞增殖,且随时间延长抑制作用越显著,抑制效果优于单独用药.PI-103可增强顺铂在C13K细胞中引起的凋亡.经PI-103作用后的C13K

  11. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

    Directory of Open Access Journals (Sweden)

    Damon Deming

    2006-12-01

    immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV-challenged mice. VRP-N-induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.

  12. Role of Ethanol Extract of Bidens Pilosa L. Against Ehrlich Ascites Carcinoma Bearing Mice Exposed to Gamma Radiation

    International Nuclear Information System (INIS)

    Bidens pilosa L. is one of the dominant families of plants contributing to medicinal species worldwide. The present study was performed to investigate the role of ethanolic extract of B. pilosa (BpE) against Ehrlich ascites carcinoma (EAC)-induced hepatic dysfunction in gamma irradiated mice. BpE was orally administered to mice for eight consecutive days at the dose of 250 mg/kg body weight (one day before and eight days after tumour inoculation). On the 3rd day of tumour inoculation, animals were exposed to whole body gamma radiation at dose of 6 Gy. The results obtained in the present study revealed that both EAC and/or gamma radiation induced liver biochemical and histopathological alterations. In vitro short term toxicity study, Bidens pilosa extract at different experimental dose levels increased the percentage of non-viable cell count. Gamma radiation and/or EAC induced oxidative stress, inflammation and biochemical alteration in liver function. The liver oxidative stress was manifested by increase in lipid peroxidation concomitant with decrease in glutathione and superoxide dismutase levels. Liver inflammation was manifested by increased levels of tumour necrosis factor-a (TNF-a), interlukin-2 (IL-2) and alteration in leukocyte count (LC). Biochemical alteration in liver function manifested by significant increase in liver transaminases (AST and ALT) and lactate dehydrogenase (LDH). Moreover, radiation and EAC induced liver oxidative stress and significant increase in caspase-3. In vivo studies showed that BpE restored the hepatic function profile in tumour bearing mice. Histopathological studies showed that EAC and radiation caused fatty degeneration, enlargement of liver cells nuclei and presence of necrosis. Treatment with BpE modulates most of the pathological alterations. It could be concluded that the hepato protective effect of BpE is related to its phyto chemical components, which were claimed to be the mechanism of hepatic protection.

  13. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

    Science.gov (United States)

    Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

  14. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

    International Nuclear Information System (INIS)

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors. (paper)

  15. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

    Directory of Open Access Journals (Sweden)

    Pie Huda

    Full Text Available 64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

  16. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    Science.gov (United States)

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer; Midtgaard, Søren Roi; Elema, Dennis Ringkjøbing; Kjær, Andreas; Jensen, Mikael; Arleth, Lise

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold. PMID:26132074

  17. Cytotoxic chemotherapy increases sleep and sleep fragmentation in non-tumor-bearing mice.

    Science.gov (United States)

    Borniger, Jeremy C; Gaudier-Diaz, Monica M; Zhang, Ning; Nelson, Randy J; DeVries, A Courtney

    2015-07-01

    Sleep disruption ranks among the most common complaints of breast cancer patients undergoing chemotherapy. Because of the complex interactions among cancer, treatment regimens, and life-history traits, studies to establish a causal link between chemotherapy and sleep disruption are uncommon. To investigate how chemotherapy acutely influences sleep, adult female c57bl/6 mice were ovariectomized and implanted with wireless biotelemetry units. EEG/EMG biopotentials were collected over the course of 3days pre- and post-injection of 13.5mg/kg doxorubicin and 135mg/kg cyclophosphamide or the vehicle. We predicted that cyclophosphamide+doxorubicin would disrupt sleep and increase central proinflammatory cytokine expression in brain areas that govern vigilance states (i.e., hypothalamus and brainstem). The results largely support these predictions; a single chemotherapy injection increased NREM and REM sleep during subsequent active (dark) phases; this induced sleep was fragmented and of low quality. Mice displayed marked increases in low theta (5-7Hz) to high theta (7-10Hz) ratios following chemotherapy treatment, indicating elevated sleep propensity. The effect was strongest during the first dark phase following injection, but mice displayed disrupted sleep for the entire 3-day duration of post-injection sleep recording. Vigilance state timing was not influenced by treatment, suggesting that acute chemotherapy administration alters sleep homeostasis without altering sleep timing. qPCR analysis revealed that disrupted sleep was accompanied by increased IL-6 mRNA expression in the hypothalamus. Together, these data implicate neuroinflammation as a potential contributor to sleep disruption after chemotherapy. PMID:25449581

  18. Absorbed dose estimation and prediction irradiation effects in tumor-bearing mice under radionuclide therapy

    International Nuclear Information System (INIS)

    Full text: As the sizes of mouse organ are comparable with the range of the high-energy beta particles emitted by the radionuclides commonly used in radionuclide therapy a significant amount of beta radiation emitted could be imparted to the adjacent tissues. The often assumption that beta particles are fully-absorbed at the emission site is not satisfied and cross-irradiation should be included into the dose estimation formulas. Keeping in mind that the radiation effects are correlated with the absorbed dose in the target the inclusion of cross-irradiation in the dose estimation must be evaluated. The MIRD's formulation was used to perform absorbed dose calculation in mice using absorbed fractions previously reported for 131I, 90Y and 177Lu. Two approaches were considered: a) cross irradiation when a fraction of beta particles emitted can escape from the organ source and, b) full self- irradiation when the beta particles are considered fully absorbed at the emission site. The formulation of linear-quadratic model was readapted to be used in the radionuclide therapy. Treatment with a single administration in mice was simulated and radiation effects on tumor, bone marrow and kidneys under the assumption of cross-irradiation were predicted. A biphasic repair kinetics was considered in the calculation of irradiation effects on kidneys. Typical published biokinetic data for radiopharmaceutical assayed in mice and radiobiological parameters were used in the calculations. The influence of cross irradiation condition was diverse for the tissues analyzed here. The absorbed dose values in kidneys calculated for both methods were no significantly different for low energies, but variations around to 40-50% (over or under-estimation) in absorbed dose were obtained for high energies. Approximately a 30% of the beta radiation emitted from bone will cross irradiates the bone marrow. For injected activities values higher than 10MBq (300μCi), as a single injection, the

  19. Learning from nudity: lessons from the nude phenotype.

    Science.gov (United States)

    Mecklenburg, Lars; Tychsen, Birte; Paus, Ralf

    2005-11-01

    In mice, rats, and humans, loss of function of Foxn1, a member of the winged helix/forkhead family of transcription factors, leads to macroscopic nudity and an inborn dysgenesis of the thymus. Nude (Foxn1(nu)/Foxn1(nu)) mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the - grossly misleading - impression that nude mice are hairless. Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation. We focus on the mechanisms and signaling pathways by which Foxn1 modulates keratinocyte differentiation in the hair follicle and nail apparatus and summarize the current knowledge on the molecular and functional consequences of a loss of function of the Foxn1 protein in skin. Foxn1 target genes, gene regulation of Foxn, and pharmacological manipulation of the nude phenotype (e.g. by cyclosporine A, KGF, and vitamin D3) are discussed, and important open questions as well as promising research strategies in Foxn1 biology are defined. Taken together, this review aims at delineating why enhanced research efforts in this comparatively neglected field of investigative dermatology promise important new insights into the controls of epithelial differentiation in mammalian skin. PMID:16232301

  20. Protective role of coriandrum sativum oily extracts on ehrlich tumour bearing mice subjected to gamma irradiation

    International Nuclear Information System (INIS)

    This study was planned to evaluate the potency of coriandrum, sativum oily extract [in a dose of 1 mg/kg body weight; for six successive doses] as a chemopreventive agent against solid ehrlich tumour transplanted to the thigh of the left leg of mice subjected or not to gamma irradiation. The protective role of coriander oil was assessed through studying the level of serum phosphorus, calcium, prostaglandins, and anti-thyroid antibodies levels. Meanwhile, the content of cholesterol and triacylglycerols both in hepatic and tumor tissues were also measured. The levels of serum calcium ions revealed significant decline in the tested groups as compared with the control ones. Measurements of serum PGE2 and anti-thyroid antibodies levels exhibited significant fluctuated changes as compared with the control levels. Serum phosphorus levels induced only non-significant changes. The contents of cholesterol both in hepatic and tumor tissues induced significant decline in the tested proups as compared with the control ones

  1. Diversity of RGD radiotracers in monitoring antiangiogenesis of flavopiridol and paclitaxel in ovarian cancer xenograft-bearing mice

    International Nuclear Information System (INIS)

    Introduction: Although encouraging results had been shown in antiangiogenesis therapy monitoring, the underlying mechanism of RGD radiotracer accumulation needs to be further illustrated. This study was aimed to investigate the diversity of RGD radiotracers in monitoring antiangiogenic agent's effects and the underlying mechanism in ovarian cancer-bearing mice with a new agent flavopiridol compared with paclitaxel. Methods: Ovarian cancer SKOV-3 xenograft-bearing mice were established and divided into three groups, flavopiridol, paclitaxel and control. Flavopiridol (5 mg/kg body weight) and paclitaxel (20 mg/kg body weight) were administered every 3 days for 16 days. Tumor growth and proliferation were monitored by caliper measurements and immunofluorescence staining. Antiangiogenic effects were determined by tumor microvessel density (MVD) in vivo and by endothelial cell tube formation assay in vitro, respectively. 99mTc-3P-RGD2 was prepared, and its biodistribution studies were carried out. The effect of antiangiogenesis therapy on integrin αvβ3 expression was studied by immunohistochemical staining and flow cytometry. Results: Both paclitaxel and flavopiridol therapy could apparently inhibit tumor growth and proliferation, and antiangiogenic effects of therapy were validated in vivo and in vitro. However, compared with the control group, ID%/g tumor uptake of 99mTc-3P-RGD2 showed a significant decrease at 2 hours (by 39.96% ± 8.23%, P = 0.044) and at 4 hours (by 35.76% ± 11.42%, P = 0.024) post injection in the paclitaxel-treated group, but a slight increase of tumor uptake in the flavopiridol-treated group at 2 hours (by 4.42% ± 0.24%, p = 0.898) and at 4 hours (by 12.2% ± 1.84%, P = 0.702). The further studies indicated flavopiridol therapy has a dual-effect, reducing integrin αvβ3 expression on endothelial cells due to the reduction of tumor MVD and up-regulating the integrin αvβ3 expression on tumor cells. Conclusions: There is diversity in

  2. 蜂毒素(Mel)对裸鼠骨肉瘤的抑制作用与影响肿瘤血管生成、细胞增殖和凋亡的关系%The relation of inhibiting angiogenesis and inducing cell apoptosis of melittin ( Mel) on xenotransplanted models of nude mice

    Institute of Scientific and Technical Information of China (English)

    高启龙; 李寒冰; 姚亚民; 陈永强; 杨峰

    2012-01-01

    目的 探讨蜂毒素(melittin,Mel)抑制骨肉瘤裸鼠移植瘤的作用机制.方法 用SD大鼠成骨肉瘤UMR- 106细胞株建立骨肉瘤原位移植瘤裸鼠模型,将18只裸鼠随机等分为3组,生理盐水组、Mel组和顺铂组.观察各组裸鼠骨肉瘤的体积和体质量抑制率;应用免疫组织化学法检测各组裸鼠瘤体CD31、CD105、PCNA蛋白表达;应用TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究Mel抑制骨肉瘤血管生成与细胞增殖、凋亡的关系.结果 Mel组肿瘤体积和体质量抑制率分别为42.98%和39.03%,Mel能明显抑制CD31、CD105标记的血管生成密度,能明显抑制肿瘤细胞增殖,促进细胞凋亡,且Mel抑制肿瘤血管生成与细胞增殖呈正相关及与细胞凋亡呈负相关.结论 Mel具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成、诱导肿瘤细胞凋亡及抑制细胞增殖有关.%Objective To study the antitumor effects and mechanism of melittin (Mel) on xenotransplanted models of nude mice. Methods Xenotransplanted models of SD rat osteosarcoma (OS) cell UMR-106 in the laevo-hind tibia of nude mice were established. Eighteen inoculated mice were randomly divided into normal saline group, positive control group and Mel group. All the nude mice were sacrificed after treatment. The size and weight of tumor were measured and the tumor volumes, and the inhibition rates of tumor were calculated. The expressions of CD31.CD1D5 and PCNA were deteced by immunohistochemical method. TUNEL semi-quantitative assay was used to study the melittin-induced apoptosis in OS cell line. The relation of inhibiting angiogenesis and inducing cell apoptosis was analyzed by correlation test . Results The mice treated with Mel showed significantly smaller in tumor volume and weight than those of NS group after treatment. Microvessel densities and the protein expressions of CD31 ,CD1()5 and PCNA in Mel group were

  3. Radioiodination and biodistribution of Leucurolysin-B isolated from Bothrops Leucurus in mice bearing Ehrlich

    International Nuclear Information System (INIS)

    Integrins are family of heterodimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domain present in both the cell surface as the protein in the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interaction mediated by integrin and has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adherence to the natural ligands. Leucurolysin-B (Leuc-B) is a metalloproteinase class P-III isolated from Bothrops leucurus (BLV) and possesses a disintegrin-like domain (ECD). The goals of this work were to synthesize a radioactive probe analog to Leuc-B using radioiodine 125I and evaluate the interaction of 125I-Leuc-B in tumor cells through the study of biodistribution in animals bearing Ehrlich tumor.125I-Leuc-B was synthesized using lactoperoxidase with high yield (90%) and specific activity of 1.2x10-7Bq/mmol. It was observed that 125I-Leuc-B had very fast clearance from the blood stream (T1/2= 0.01 h). Tumor uptake of 125I-Leuc-B gradually increased up to (2 min) and remained for a quite long period. The tumor/normal tissue uptake ratios of 125I-Leuc-B were 1.77 (tumor/normal paw) and 8.44 tumor/skeletal muscle. The results suggest that 125I-Leuc- B may constitute a good template for development of a tool for detection of solid tumors. (author)

  4. Survival of tumor bearing mice by sequencing of low dose rate (LDR) neutron and photon radiation

    International Nuclear Information System (INIS)

    Cf-252 neutron radiation (NT) has been shown to be effective therapy for bulky, hypoxic human tumor and to produce consistent rapid clearance and 5 year cures. NT has been found to be more or less effective depending upon the schedule in which it is used and upon mixing with photon radiation. In an effort to study this scheduling and photon effect, LSA tumor was irradiated in vivo in a hypoxic, advanced state, in different schedules in combination of NT with Co-60 photons. The LSA lymphoma of C57BL/ym mice represents an accurate system to assess dose-response of tumor cells in vivo. Mean survival time was used as endpoint. A high RBE for LDR Cf-252 NT was observed with a RBE(n) of -- 5.0. The effect was not greatly sensitive to sequence in which photons were used. Comparison studies were also tested relative to LDR Cs-137 photon radiation. The results support the high efficacy of LDR NT for destruction of hypoxic tumor in vivo

  5. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J; Spang-Thomsen, M

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

  6. The influence of whole body 60Co-irradiation on distribution of 67Ga in tumor-bearing mice

    International Nuclear Information System (INIS)

    Since the initial findings that 67Ga has a preferential affinity for soft tissue tumors, in humans numerous suggestions have been advanced for the basic mechanism involved. The effects produced by whole-body X-irradiation on the excretion and tissue distribution of 67Ga have been reported by Swartzendruber and others. Bradley and coworkers have shown that these irradiation effects were associated with an increase in serum iron. The present investigation was undertaken in order to study the relationships between the change in the serum iron concentration and 67Ga accumulation in the tumor and soft tissues in mice bearing Ehrlich's ascites tumor. The following results were obtained. (1) The serum iron concentration was significantly decreased between 3 and 6 hours after 10 Gy (1,000 rad) dose of whole-body 60Co-irradiation. Subsequently, the serum iron levels were slowly elevated. (2) The uptake of 67Ga in the tumor and soft tissues was increased if the serum iron concentration was decreased by whole-body 60Co-irradiation during the early phase. On the contrary, if the serum iron concentration was high, the uptake of 67Ga in the tumor was decreased. (3) The excretion of 67Ga from the body was delayed if the serum iron concentration was decreased by whole-body 60Co-irradiation. However, if the serum iron concentration was high, the excretion of 67Ga from the body significantly increased. (author)

  7. Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice.

    Science.gov (United States)

    Guo, Huizhen; Zhang, Zhenbiao; Su, Zuqing; Sun, Chaoyue; Zhang, Xie; Zhao, Xiaoning; Lai, Xiaoping; Su, Ziren; Li, Yucui; Zhan, Janis Yaxian

    2016-04-01

    Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL-1β, TNF- α, IL-6 and TGF-β1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-β, α-SMA, p-Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM. PMID:26874212

  8. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21

    International Nuclear Information System (INIS)

    Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 106 cell culture infectious dose (CCID50), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 106 CCID50, resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains

  9. A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice

    International Nuclear Information System (INIS)

    A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy

  10. Biodistribution and SPECT imaging of 125/131I-crotoxin on mice bearing Ehrlich solid tumour

    International Nuclear Information System (INIS)

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with 125/131I using lactoperoxidase method and radiochemical analysis was performed by chromatography. 125I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while 131I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T1/2= 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). 131I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  11. Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

    Directory of Open Access Journals (Sweden)

    Amal I. Hassan

    2014-04-01

    Full Text Available Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ irradiation on nuclear factor, erythroid 2 (NFE2, P53, stromelysin-1 (matrix metalloproteinase-3 (MMP3, BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5 Gy. Sixty-four female mice, weighing 20–25 g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B, the animals were exposed to a single dose of 0.5 Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5 Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96 h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96 h of γ irradiation (IIB. On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96 h of γ irradiation (IIB. As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group when compared to control mice (1st group. Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter

  12. Future prospects for SPECT imaging using the radio-lanthanide terbium-155 production and preclinical studies in tumor bearing mice

    International Nuclear Information System (INIS)

    Full text of publication follows. Background: since SPECT continues to be the predominant technology in clinical oncology we propose the radio lanthanide 155Tb (t1/2 = 5.3 d, E = 87 keV (32%); 105 keV (25%) as a new isotope for SPECT imaging purposes [Ref. 1]. The aim of this study was the production and separation of 155Tb and its preclinical application in mice using different 155Tb-labeled tumor targeting agents. Methods: 155Tb was produced at ISOLDE (CERN, Switzerland) by high-energy (1.4 GeV) proton irradiation of a tantalum target followed by an on-line separation according to the mass-charge ratio of the ions [Ref.1]. Collected products of mass number 155 were shipped to PSI and separated from isobar and pseudo-isobar impurities by cation exchange chromatography similar to a previously reported procedure [Refs. 1,2]. Four different biomolecules, based on a peptide (DOTATATE), a folate (cm09 [Ref. 3]) and an antibody (chCE7) were radiolabeled with 155Tb. Imaging studies were performed in mice bearing somatostatin receptor positive AR42J tumors, folate receptor positive KB tumors or L1-CAM expressing SKOV-3 tumors. Results: the total yield of the two-step separation process of 155Tb was 85%. 155Tb was obtained in a physiological L-lactate solution suitable for direct labeling and in vivo application of the biomolecules. Radiolabeling was achieved in an excellent purity of > 98% at specific activities of ∼ 1.8 MBq/nmol (155Tb-DOTATATE) and ∼ 5.6 MBq/nmol (155Tb-folate). The radiolabeling of the antibody was achieved at a specific activity of ∼ 44 MBq/mg (155Tb-CHX-A''-DTPA-chCE7). SPECT/CT experiments revealed an excellent visualization of AR42J tumors in mice 1 h after injection of 155Tb-DOTATATE. The long-circulating 155Tb-cm09 allowed imaging of KB tumors even over several days. Conclusions. In this study we demonstrated the excellent features of 155Tb for SPECT imaging using fast-cleared and a long-circulating biomolecules. 155Tb may be of

  13. Water-soluble aluminium phthalocyanine–polymer conjugates for PDT: photodynamic activities and pharmacokinetics in tumour-bearing mice

    Science.gov (United States)

    Brasseur, N; Ouellet, R; Madeleine, C La; Lier, J E van

    1999-01-01

    The potential use of unsubstituted aluminium phthalocyanine (AlClPc) as a sensitizer for photodynamic therapy (PDT) of cancer has not been fully exploited in spite of its higher efficiency as compared to the sulphonated derivatives. This is largely due to the strong hydrophobic character of AlClPc which renders the material difficult to formulate for in vivo administration. We prepared two water-soluble derivatives of AlClPc by axial coordination of polyethyleneglycol (PEG, MW 2000) or polyvinylalcohol (PVA, MW 13 000–23 000) to the central aluminium ion. Their photodynamic activities were evaluated in vitro against the EMT-6 mouse mammary tumour cells and in vivo against the EMT-6 and the colon carcinoma Colo-26 tumours implanted intradermally in Balb/c mice. Pharmacokinetics were studied in the EMT-6 tumour-bearing mice. After 1 h incubation, the light dose required to kill 90% of cells (LD90) was at least three times less for AlClPc (Cremophor emulsion) as compared to AlPc–PEG and AlPc–PVA, while after 24 h incubation all three preparations were highly phototoxic. All three dye preparations induced complete EMT-6 tumour regression in 75–100% of animals at a low drug dose (0.25 μmol kg−1) following PDT (400 J cm−2, 650–700 nm) at 24 h pi. Complete tumour regression in the Colo-26 tumour model was obtained in 30% of mice at a dose of 2 μmol kg−1. In the non-cured animals, AlPc–PVA induced the most significant tumour growth delay. This dye showed a prolonged plasma half-life (6.8 h) as compared to AlClPc (2.6 h) and AlPc–PEG (23 min), lower retention by liver and spleen and higher tumour-to-skin and tumour-to-muscle ratios. Our data demonstrate that addition of hydrophilic axial ligands to AlPc, while modifying in vitro and in vivo kinetics, does not reduce the PDT efficiency of the parent molecule. Moreover, in the case of the polyvinylalcohol derivative, axial coordination confers advantageous pharmacokinetics to AlPc, which makes this

  14. Water-soluble aluminium phthalocyanine-polymer conjugates for PDT: photodynamic activities and pharmacokinetics in tumour-bearing mice.

    Science.gov (United States)

    Brasseur, N; Ouellet, R; La Madeleine, C; van Lier, J E

    1999-07-01

    The potential use of unsubstituted aluminium phthalocyanine (AlClPc) as a sensitizer for photodynamic therapy (PDT) of cancer has not been fully exploited in spite of its higher efficiency as compared to the sulphonated derivatives. This is largely due to the strong hydrophobic character of AlClPc which renders the material difficult to formulate for in vivo administration. We prepared two water-soluble derivatives of AlClPc by axial coordination of polyethyleneglycol (PEG, MW 2000) or polyvinylalcohol (PVA, MW 13,000-23,000) to the central aluminium ion. Their photodynamic activities were evaluated in vitro against the EMT-6 mouse mammary tumour cells and in vivo against the EMT-6 and the colon carcinoma Colo-26 tumours implanted intradermally in Balb/c mice. Pharmacokinetics were studied in the EMT-6 tumour-bearing mice. After 1 h incubation, the light dose required to kill 90% of cells (LD90) was at least three times less for AlClPc (Cremophor emulsion) as compared to AlPc-PEG and AlPc-PVA, while after 24 h incubation all three preparations were highly phototoxic. All three dye preparations induced complete EMT-6 tumour regression in 75-100% of animals at a low drug dose (0.25 micromol kg(-1)) following PDT (400 J cm(-2), 650-700 nm) at 24 h pi. Complete tumour regression in the Colo-26 tumour model was obtained in 30% of mice at a dose of 2 micromol kg(-1). In the non-cured animals, AlPc-PVA induced the most significant tumour growth delay. This dye showed a prolonged plasma half-life (6.8 h) as compared to AlClPc (2.6 h) and AlPc-PEG (23 min), lower retention by liver and spleen and higher tumour-to-skin and tumour-to-muscle ratios. Our data demonstrate that addition of hydrophilic axial ligands to AlPc, while modifying in vitro and in vivo kinetics, does not reduce the PDT efficiency of the parent molecule. Moreover, in the case of the polyvinylalcohol derivative, axial coordination confers advantageous pharmacokinetics to AlPc, which makes this

  15. 组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞增殖影响的动物实验研究%The Effect of Histone Deacetylase Inhibitor Combined with Chemotherapy on Breast Cancer Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    聂建云; 陈杨萍; 黄云超

    2011-01-01

    Objective: To study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N- phenyloctanediamide)combined with chemotherapy on breast cancer cells in nude mice.Methods: Breast cancer cell suspension was subcutaneously injected into 80 nude mice to establish breast cancer model When the transplanted tumor was about 10mm in length, 60 mice with tumor in similar size were selected and divided into six groups, with 10 in each group.The six groups were the control group, SAHA group,taxol group, adriamycin group, taxol plus SAHA group, and adriamycin plus SAHA group.Data including blood cell count, serum level of cholesterol, liver function ( serum glutamic-pyruvic transaminase and bilirubin ), kidney function ( serum urea nitrogen and creatinine ), body weight, wet weight of tumor, inhibitory rate and tumor volume were collected.SPSS 12.0 software was used for statistical analysis.Results: Compared with the control group, the treatment groups had higher inhibitory rate and lower tumor volume ( P< 0.05).The taxol plus SAHA group showed superiority in inhibiting tumor growth ( P< 0.05).Compared with the control group,the groups treated with taxol or adriamycin had lower body weigh, lower level of white blood cell count, lower level of serum glutamic-pyruvic transaminase and higher level of bilirubin ( P < 0.05 ).No differences were foumd in the above indices between chemotherapy groups and SAHA plus chemotherapy groups ( P > 0.05 ).Conclusion: SAHA combined with chemotherapy (taxol or adriamycin ) has synergistic inhibitory ettect on the growth of breast cancer in nude mice without increasing side effects, suggesting its possible application in breast cancer treatment in the future.%目的:通过动物模型研究组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞株增殖周期的影响.方法:饲养Balb/c-nu/nu雌性裸鼠,细胞悬液皮下注射法构建人乳腺癌细胞株MCF-7裸鼠移植瘤模型,随机分为6组(对照组、组蛋白去

  16. Effects of anti-gene and antisense therapeutics on human prostate cancer xenograft in nude mice%反基因及反义寡核苷酸对人前列腺癌裸鼠移植瘤生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    张勇; 马毅; 卢汉平; 周祥福; 谢瑶; 高锦辉; 梁昌盛

    2008-01-01

    Objective To investigate the effects of triple-helix forming oligonucleotide (TFO) and antisense oligonucleotide (ASO) on androgen receptor (AR) expression and tumor growth of human prostate cancer xenografts in nude mice.Methods Thirty-two nude mice were inoculated with human prostate cancer cells of the line LNCaP-C4-2 were randomized into 4 equal groups:TFO treatment group,undergoing intra-tum