Head and neck cancer is the seventh common cancer in the world, and various existing treatment strategies provide modest benefit for most patients with head and neck cancer. Meanwhile, therapeutic strategies lacking molecular typing significantly hinder the development of individualized treatment for head and neck cancer. In recent years, connected by preclinical models, the novel ideal has gradually reached a consensus in terms of facilitating inter-transformation of clinical problems and basic achievements. As a bridge between basic research and clinical transformation, patient-derived xenografts (PDX) models precisely replicate genetic characteristics and tumor evolution, which are displaying great vitality in elucidating the mechanism of tumorigenesis and progression. Moreover, cohorts composed of several PDX models highlight the unique advantages of mice for drug screening and biomarker analysis for patients. This ideal preclinical model explores potential treatment strategies suited the ethical standards as much as possible for patients.
Animals ; Disease Models, Animal ; Head and Neck Neoplasms ; Heterografts ; Humans ; Mice ; Xenograft Model Antitumor Assays

PURPOSE: The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (Ktrans, Kep and Ve), early changes in parameters (Ktrans, tumor volume), and heterogeneity (standard deviation of Ktrans) for radiation therapy responses via a human colorectal cancer xenograft model. MATERIALS AND METHODS: A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (Ktrans, Kep and Ve) were calculated based on the Tofts model. Early changes in Ktrans, standard deviation (SD) of Ktrans, and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted. RESULTS: The good response group (mice #1 and 2) exhibited higher pretreatment Ktrans than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment Kep, higher pretreatment Ve, and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in Ktrans and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy. CONCLUSION: The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment Ktrans and showed an early reduction in Ktrans, demonstrating a more homogenous distribution.
Animals ; Colonic Neoplasms/*pathology/*radiotherapy ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays

Animals ; Cell Cycle ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Humans ; Hyperbaric Oxygenation ; K562 Cells ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVETo assess the safety of hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis in patients with prostate cancer, and to investigate its effect on the growth of indolent prostate cancer in vivo.

METHODSThirty severe combined-immunodeficient mice received subcutaneous injection of human prostate cancer LNCaP cells. Then they were randomized to an experimental and a control group and exposed to 20 sessions of hyperbaric oxygen and normobaric air, respectively, followed by a 4-week observation on the growth of the transplanted tumors and analyses of their histopathological features at 28 days, including the volume, microvessel density (CD34), apoptosis markers (p53 and p27 proteins) and the proliferation index (Ki-67) of the LNCaP tumors.

RESULTSOn the 28th day after tumor vaccination, the tumor volume was (120 +/- 7.9) mm3 in the HBO and (122 +/- 8.2) mm3 in the control group; the microvessel density and the expressions of Ki-67, p53 and p27 were 39.3 +/- 5.2, (78.1 +/- 7.6)%, (40.4 +/- 6.2)% and (63.7 +/- 5.1)% in the former, and 36.2 +/- 4.9, (75.3 +/- 8.4)%, (44.2 +/- 5.7)% and (61.5 +/- 5.5)% in the latter. There were no significant differences in all the indexes above between the two groups (P > 0.05).

CONCLUSIONHyperbaric oxygen did not promote the growth of indolent prostate cancer in the murine model, nor did it have any significant effect on the new vessels.

Animals ; Cell Line, Tumor ; Humans ; Hyperbaric Oxygenation ; Male ; Mice ; Mice, SCID ; Prostatic Neoplasms ; Xenograft Model Antitumor Assays

OBJECTIVE: To investigate inhibitory activities of a homogenous anti-human epidermal growth factor receptor 2 (HER2)-antibody drug conjugate (ADC) on the proliferation of nine tumor cell lines with different levels of HER2 expressions, and its activities on the tumor growth of five xenograft mouse models. METHODS: The HER2 expression levels of BT-474, Calu-3, MCF-7, MDA-MB-231, MDA-MB-468, SK-BR-3, SK-OV-3, HCC1954, NCI-N87 tumor cell lines were measured using QIFI KIT. For the in vitro anti-proliferation assay, serial diluted anti-HER2-ADC, ado-trastuzumab emtansine, AS269, pAF-AS269 and paclitaxel were added to the seeded cells, and after 72 or 96 hours of incubation, the cell proliferation was analyzed. For the in vivo activity, 5-6 weeks old mice were inoculated with four HER2 positive tumor cell lines HCC1954, BT-474, SK-OV-3, NCI-N87 or one HER2 negative tumor cell line MDA-MB-468. Different amounts of anti-HER2-ADC, ado-trastuzumab emtansine, trastuzumab, paclitaxel and phosphate buffered saline control were injected after the tumor volume reached a certain size, then the tumor growth inhibition was analyzed. RESULTS: The expression levels of the six high HER2-expression cell lines SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 were between 430 000 to 800 000 receptors per cell, which were 50 times higher than those of the other three low HER2 expression tumor cell lines MDA-MB-231, MCF-7, MDA-MB-468. Anti-HER2-ADC had inhibition effects on cell lines with high level of HER2 expression in the in vitro anti-proliferation assay. The half maximal inhibitory concentrations of anti-HER2-ADC on SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 tumor cell lines were 46 pmol/L, 17 pmol/L, 17 pmol/L, 161 pmol/L, 125 pmol/L, 50 pmol/L, respectively. Anti-HER2-ADC had a dose dependent antitumor activity in vivo in all the HER2 positive xenograft mouse models. In NCI-N87 xenograft tumor model, the same dose of anti-HER2-ADC showed better anti-tumor activity compared with trastuzumab and ado-trastuzumab emtansine, and its relative tumor proliferation rates were about 1/30 to 1/20 of the two. In HCC1954 xenograft tumor model, the complete regression of the tumor was observed. As expected, anti-HER2-ADC had no tumor inhibitory effects on MDA-MB-468 xenograft models with low HER2 expression. The antitumor activities of anti-HER2-ADC in HER2 positive xenograft tumor models were the same as or better than the activities of ado-trastuzumab emtansine. CONCLUSION The homogenous site-specific anti-HER2-ADC obtained using unnatural amino acid technology can inhibit the growth of high HER2-expression tumor cells with high potency both in vivo and in vitro.
Amino Acids ; Animals ; Breast Neoplasms ; Cell Line, Tumor ; Humans ; Immunoconjugates ; Mice ; Receptor, ErbB-2 ; Trastuzumab ; Xenograft Model Antitumor Assays

OBJECTIVETo construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen.

METHODSA fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied.

RESULTSAn orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively.

CONCLUSIONSAn orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.

Animals ; Antigens, CD ; metabolism ; Disease Models, Animal ; Female ; Humans ; Lymphoma ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Stomach Neoplasms ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo observe the growth and metastasis effect of interferon alpha-1b (IFN-alpha-1b) on nasopharyngeal carcinoma cell line CNE-2 in xenografted model of mice liver. Comparing rAAV-mediated IFN-alpha-1b gene therapy with the IFN-alpha-1b protein therapy.

METHODSThe xenografted model of liver nasopharyngeal carcinoma was established by injecting the human nasopharyngeal carcinoma cell line CNE-2 under liver capsule of nude mice. Forty nude mice were randomly divided into four groups by means of random number table method, with ten mice in each one. (Group A: rAAV-IFN-alpha-1b, Group B: IFN-alpha-1b; Group C: rAAV-EGFP; Group D: PBS). After 24 hours, A, C and D group was injected with rAAV-IFN-alpha-1b encoding human IFN-alpha-1b, rAAV-EGFP and phosphate buffer saline via tail vein injection. After 5 days, mice in group B was injected with human IFN-alpha-1b protein once per two days. Three weeks later five nude mice were sacrificed and then observed their liver tumor formation and pulmonary metastasis. Tumor size was measured and tumor inhibition ratios was calculated, and apoptotic index (AI) was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL). The contents of human IFN-alpha contained in peripheral blood and mice IL-12 was determined by high performance liquid chromatography chip techniques. And another five mice were randomly chosen for the observation of surviving study.

RESULTSAfter human nasopharyngeal carcinoma implants in nude mice liver 3 weeks, the average volume of A group (0.114 +/- 0.116) cm3 and B group (0.422 +/- 0.137) cm3 were significantly lower than that of C group (2.476 +/- 0.637) cm3 and D group (2.677 +/- 0.704) cm3 (F = 38.536, P < 0.01). Compared with D group, the restrained percentage of tumor in group A was 95.74% and group B was 84.24%. The percentage of lung metastases in group A, B, C and D were 0.0%, 0.0%, 40.0%, 60.0% respectively. The apoptotic index increased significantly in group A (21. 88 +/- 3.29)% and group B (19.85 +/- 1.96)% versus group C (4.37 +/- 0.50)% and group D (3.40 +/- 1.05)% (F = 120.964, P < 0.01). The average content of human interferon-alpha in serum increased significantly in group A (101.50 +/- 11.33) pg/ml and group B (91.55 +/- 9.80) pg/ml versus group C (23.06 +/- 4.36) pg/ml and group D (16.93 +/- 9.96) pg/ml (F = 69.128, P < 0.01). The average content of IL-12 increased significantly in group A (80.36 +/- 13.35) pg/ml and group B (51.15 +/- 9.72) pg/ml versus group C (19.44 +/- 7.03) pg/ml and group D (14.49 +/- 4.21) pg/ml (F = 57.116, P < 0.01). The survival time of tumor bearing mice in group A (55.80 +/- 2.77) d and group B (48.20 +/- 2.39) d was significantly longer than group C (35.40 +/- 2.61) d and group D (36.80 +/- 1.92) d (chi2 = 25.623, P < 0.01).

CONCLUSIONSIFN-alpha-1b can inhibit the growth and metastasis of nasopharyngeal carcinoma cell line CNE-2 in xenografted model of mice liver. rAAV-mediated IFN-alpha-1b gene therapy indicated more effect than the IFN-alpha-1b protein therapy by comparing content of human IFN-alpha in serum and the survival time of tumor bearing mice.

Animals ; Cell Line, Tumor ; Genetic Therapy ; Humans ; Interferon-alpha ; pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo evaluate the inhibitory of profrin II nanoparticles photodynamic therapy on Lovo human colon cancer xenografts in athymic mice.

METHODSProfrin II nanoparticles were obtained from hypersound emulsification method. LOVO human colon cancer xenograft were established in athymic mice. Athymic mice were divided into four groups:normal control group, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles PDT group. The animals bearing xenografts were treated 30 mg/kg body weight profrin II nanoparticles and 3 h later were irradiated with 9 J/cm(2) light from a diode laser. After Profrin II nanoparticles PDT, the anti-tumor effect was assessed by measuring tumor volume over a 3-4 weeks period, the morphologic changes were observed by microscopy and microscopy via the histological examination.

RESULTSCompared with the control groups, profrin II nanoparticles control group, profrin II PDT group and profrin II nanoparticles-PDT treated tumors had regressed significantly in earlier period with the inhibiting rate being 87.9% (P<0.05), 87.5% (P<0.05) and 56.0% respectively (P<0.05). In the later period post-PDT, tumors growth resumed with a slower rate. Profrin II nanoparticles-PDT prolonged the survival time in the treated group with (38.0+/-6.0) days (P<0.05). Extensive damage to tumor tissue was found in the earlier period (7d) post-PDT, whereas in the later period (21d) post-PDT, islands of vital-looking tumor cells were observed around the damaged tissue.

CONCLUSIONProfrin II nanoparticles-PDT results in inhibition Lovo colon carcinoma growth in post-PDT earlier period in vivo, and can prolong the survival time of nude mice bearing xenografts significantly, whereas profrin II-PDT could not inhibit the growth of colon tumor completely.

Animals ; Cell Line, Tumor ; Colonic Neoplasms ; therapy ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanoparticles ; Photochemotherapy ; Photosensitizing Agents ; therapeutic use ; Xenograft Model Antitumor Assays

OBJECTIVETo provide an ideal animal model for exploring pathogenesis and experimental treatment of primary colonic lymphoma.

METHODSPrimary colonic and liver metastatic lymphoma tissues were obtained from the surgical specimens,and transplanted into colonic mucosa of nude mice respectively. The tumorigenesis, invasion, metastasis and morphology of the transplanted tumor were observed. Karyotype was analyzed and DNA content was measured.

RESULTSAccording to the new WHO classification of malignant lymphoma, two high metastatic models (HCBL-0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human primary colonic non-Hodgkin's B cell lymphoma in nude mice were established successfully by orthotopic transplantation. Pathological examination showed poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors, and immunohistochemical staining showed positive expressions of CD19, CD20 and CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL-0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%. However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%. The transplanted tumors grew autonomously and invasively in nude mice, and further developed hematogenous, lymphatic metastasis and intraperitoneal seeding.

CONCLUSIONSHCBL-0303 and HCBL-0304 are the first established high metastatic models of primary colonic lymphoma, and can be applied to the research on pathogenesis, invasion,metastasis and experimental therapy of human primary colonic lymphoma.

Animals ; Colonic Neoplasms ; pathology ; Female ; Humans ; Liver Neoplasms ; secondary ; Lymphoma ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Neoplasms, Experimental ; Xenograft Model Antitumor Assays

This study was aimed to investigate the antitumor effect of pumpkin protein (cucurmosin, CUS) on subcutaneous transplant tumor in chronic myeloid leukemia K562 cell-NOD/SCID mice and leukemia model. The subcutaneous transplant tumor in K562-NOD/SCID mice and leukemia model were established; using two models, the antitumor activity of CUS in mice was evaluated. The results indicated that the inhibitory rate of 0.5 mg/kg and 1 mg/kg CUS on subcutaneous transplant tumor were 53.45% and 59.43% respectively; survival time of mice received 0.25 mg/kg and 0.5 mg/kg CUS was 39.8 ± 5.5 d and 43.4 ± 6.6 d, antitumor rate was 24.9% and 36% respectively. It is concluded that CUS has significant inhibitory effect on mice with CML cell line K562.
Animals ; Female ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Plant Proteins ; pharmacology ; Xenograft Model Antitumor Assays