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

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

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

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 establish a stable high red fluorescent protein (RFP)-expressing orthotopic transplantation nude mice spontaneous metastasis model of pancreatic cancer.

METHODSStable high RFP-expressing cells SW1990-RFP were injected subcutaneously into mice to establish subcutaneous implantation model. Fluorescent tumor piece from subcutaneous was transplanted into the body of the pancreas to establish surgical orthotopic implantation model. The growth of primary tumor, metastasis and micrometastasis were assessed by whole-body fluorescence imaging system.

RESULTSTwelve RFP orthotopic transplantation nude mice metastasis models of pancreatic cancer were established successfully, the percentage of success rate was 100%. RFP-labeled pancreatic cancer growth could be monitored in real time way. The micrometastasis of primary lesions were detected in early stage with whole-body fluorescence imaging system.

CONCLUSIONSThe RFP orthotopic transplantation nude mice metastasis model of pancreatic cancer is stable and reliable, and can be observed dynamically in vitro in a noninvasive way, with much higher sensitivity and specificity.

Animals ; Disease Models, Animal ; Female ; Luminescent Proteins ; Male ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Pancreas ; pathology ; Pancreatic Neoplasms ; pathology ; Xenograft Model Antitumor Assays

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

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

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

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

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

OBJECTIVETo compare different Chinese medicine (CM) therapeutic methods on the pancreatic orthotopic transplantation tumors in nude mice, and to explore their features.

METHODSThe pancreatic orthotopic transplantation tumor model was established. Sixty nude mice were randomly divided into four group, i. e., the blood circulation activating and stasis resolving group, the heat clearing and dampness removing group, the Pi-strengthening and qi-regulating group, the phlegm reducing and mass resolving group, the normal control 1 group, and the normal control 2 group, 10 in each group. 0.2 mL corresponding CM decoction or normal saline was respectively administered to each group by gastrogavage, once daily, for totally 28 days. The body weight, the tumor weight, and the tumor inhibition ratio were observed.

RESULTSThe tumor inhibition ratio was 42.69% in the heat clearing and dampness removing group, 31.24% in the blood circulation activating and stasis resolving group, 2.11% in the Pi-strengthening and qi-regulating group, and -12.95% in the phlegm reducing and mass resolving group. There was statistical difference in the tumor weight between the heat clearing and dampness removing group and the normal control 1 group (g, 0.51 +/- 0.28 vs 0.90 +/- 0.25, P < 0.05). There was no statistical difference in the body weight change between the two groups (P > 0.05).

CONCLUSIONSThe CM pathogenesis of pancreatic carcinoma may possibly due to the accumulation of dampness and heat, or the accumulation of dampness, heat, and toxicity. Clearing heat and removing dampness may be the basic principle for its treatment.

Animals ; Cell Line, Tumor ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Medicine, Chinese Traditional ; methods ; Mice ; Mice, Nude ; Pancreatic Neoplasms ; therapy ; Phytotherapy ; Xenograft Model Antitumor Assays

This study was purposed to explore the anti-leukemia effect of bacillus calmette-guerin vaccine (BCG) on the human myeloid leukemia cell xenograft models. An animal model was established by inoculating the human myeloid leukemia HL-60 cells into the BALB/c (8 - 10 weeks of age) nude mice. The mice were randomly divided into two groups: control group and experimental group. Nude mice in control group were injected with physiological saline, while those of experimental group were given BCG and inactivated BCG respectively. The tumor growth was assayed by using caliper. The survival time of nude mice was determined. Necrotic extent and morphological changes of tumor were observed and examined by HE staining and immunohistochemical method. The results indicated that on 5th-7th days after tumor inoculated, 2 - 3 mm tumor mass could be observed. The tumor volume increased over the time. HE staining of tumor tissues showed that there were different degrees of tumor necrosis in BCG group and inactivated BCG group. Immunohistochemistry results demonstrated that CD20 positive cells were obviously observed in the necrotic area of BCG group, compared with the control group and inactivated BCG group. It is concluded that human myeloid leukemia HL-60 cells have been successfully transplanted in nude mice, and the systemic metastasis occurs along with the prolongation of time. BCG inoculation can delay the tumor growth and prolong the survival time of nude mice with leukemia, suggesting that BCG has an antitumor effect.
Animals ; BCG Vaccine ; therapeutic use ; HL-60 Cells ; Humans ; Leukemia, Myeloid ; therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the anti-tumor effect of a novel gene-viral therapeutic system CNHK300-murine endostatin (CNHK300-mE) on gastric cancer.

METHODSSGC-7901 gastric cancer cells (5 x 10(7) cells/mouse) were injected s.c. into the right flank of Balb/c nude mice, grown to 4-5 mm to demonstrate tumor take, and 10(9) pfu/100 microl CNHK300-mE virus was injected into tumors. Tumor sizes were measured with calipers every other day. Serum samples were obtained by retro-orbital puncture and level of endostatin expression in serum was quantitated by ELISA. Fifteen days after treatment, all mice were sacrificed and tumors were excised for immunohistochemical staining of PCNA, hexon and vWF. Tumor cell apoptosis was detected by TUNEL method.

RESULTSFrom the 7th day post-treatment, the bearing tumors of mice treated with CNHK300-mE were significantly smaller than those of control group treated with PBS. Seven days after treatment, expression of endostatin was (2115 +/- 770) ng/ml, significantly higher than that of control group. Immunohistochemical staining indicated that hexon was expressed in treated tumor cells, and PCNA LI (label index) [(55.0+/-1.4)% vs control (74.1 +/- 0.4)%, P<0.05], microvessel density (MVD) of CNHK300-mE treated tumors decreased significantly. Apoptosis obviously increased in tumor cells[(78.4 +/- 9.1)% vs control (15.2 +/- 0.5)%, P<0.01]. Apoptosis bodies and crystal grid were found in tumor cell nuclear by electron microscope.

CONCLUSIONSGene-viral therapeutic system CNHK300-murine endostatin can replicate in gastric cancer cells. The mouse endostatin gene cloned into CNHK300-mE expressed in high level. CNHK300-mE may induce tumor cells apoptosis, reduce the expression of PCNA and efficiently suppress gastric cancer growth through inhibiting tumor angiogenesis.

Adenoviridae ; genetics ; Animals ; Endostatins ; genetics ; Female ; Genetic Therapy ; Genetic Vectors ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stomach Neoplasms ; therapy ; Telomerase ; genetics ; Transfection ; Xenograft Model Antitumor Assays