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1.
Neuroscience Bulletin ; (6): 216-224, 2019.
Article in English | WPRIM | ID: wpr-775435

ABSTRACT

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.


Subject(s)
Animals , Brain Stem Neoplasms , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cellular Senescence , Female , Glioma , Genetics , Metabolism , Pathology , Histones , Genetics , Humans , Mice, Inbred NOD , Mice, SCID , Neoplasm Transplantation , Neoplastic Stem Cells , Metabolism , Pathology , Neural Stem Cells , Metabolism , Pathology , Pons , Embryology , Metabolism , Pathology , Primary Cell Culture
2.
Article in Chinese | WPRIM | ID: wpr-774512

ABSTRACT

Breast cancer is one of the leading causes for cancer-related death among women worldwide. Coptidis Rhizoma has antibacterial,anti-inflammatory,anti-tumor and other pharmacological activities,but whether exercise could synergistically promote the role of RC in the treatment of breast cancer has not been reported. In this experiment,the effects and mechanism of total alkaloids of Coptidis Rhizoma combined with exercise on the tumor growth of orthotopically transplanted 4 T1 breast cancer were systemically studied in mice. Balb/C mice transplanted with 4 T1 cells in situ were used as models. The total alkaloids of RC(145 mg·kg-1·d-1) alone or in combination with exercise(10 m·min-1,30 min/time,5 times/week) were given for 28 days,and then the changes in body weight and tumor volume,tumor weight,interleukin-1β(IL-1β),serum estradiol(E2) content,and expression levels of estrogen receptor α(ERα),cell cycle related proteins CDK4,CDK6,cyclin D1,CDK2,and cyclin E in tumor tissues. The results showed that total alkaloids of Coptidis Rhizoma could significantly inhibit the growth of 4 T1 breast cancer in mice(P< 0. 01),and exercise significantly promoted the anti-tumor activity of total alkaloids of Coptidis Rhizoma(P<0. 01),and reduced E2 and IL-1β levels in mice. Western blot and flow cytometry showed that the total alkaloids of Coptidis Rhizoma combined with exercise could down-regulate the protein expression levels of ERα,CDK4,CDK6,cyclin D1,CDK2 and cyclin E in cancer cells,block the transformation of G1/S in 4 T1 cell cycle,and inhibit DNA synthesis in breast cancer cells. The total alkaloids of Coptidis Rhizoma combined with exercise showed synergistic effect in inhibition of tumor growth in mice with orthotopically transplanted 4 T1 breast cancer.


Subject(s)
Alkaloids , Pharmacology , Animals , Breast Neoplasms , Therapeutics , Cell Cycle , Cell Line, Tumor , Drugs, Chinese Herbal , Pharmacology , Female , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Physical Conditioning, Animal , Rhizome
3.
Article in Chinese | WPRIM | ID: wpr-773487

ABSTRACT

OBJECTIVE@#To investigate the effects of on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice.@*METHODS@#Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (=20) and control group (=20) for intravenous injection of suspension (200 μL, 4 × 10 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining.@*RESULTS@#In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (=0.01); the acoustic velocity (=0.001) and the acoustic attenuation (=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (=0.0006) and larger coagulative necrosis volume (=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (=0.0134).@*CONCLUSIONS@# can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.


Subject(s)
Acoustics , Animals , Bifidobacterium , Virulence , Breast Neoplasms , Pathology , Collagen , Elasticity Imaging Techniques , High-Intensity Focused Ultrasound Ablation , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Random Allocation
4.
Article in Chinese | WPRIM | ID: wpr-773253

ABSTRACT

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-β1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Cytokines , Metabolism , Ferula , Chemistry , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Plant Extracts , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Stomach Neoplasms , Drug Therapy , bcl-2-Associated X Protein , Metabolism
5.
Electron. j. biotechnol ; 34: 22-28, july. 2018. ilus, graf
Article in English | LILACS | ID: biblio-1047453

ABSTRACT

Background: To examine the usefulness of green fluorescent protein (GFP) mice for studying the interactions between normal cells and tumor cells in a host, we used a melanoma model in such "green" mice [C57BL/6-Tg (CAG-EGFP)1Osb mice]. Mice were given a subcutaneous injection of B16-F10 cells, and the resultant primary tumors were removed. Then cells from individual tumors were cultured. Results: The proportion of EFGP+ cells was determined by fluorescence-activated cell sorting (FACS) and was 6.8% ± 3.2% (mean ± s.d.) on day 1 of culture, 0.6% ± 0.3% on day 2, and 0.02% ± 0.01% at day 7. In all cases, isolated cells grew at a constant rate, but fluorescence decreased over time and became undetectable on day 14. Cells were tested using PCR for the presence of an EGFP-specific sequence, and results were negative in all cases, thus indicating that the cells did not harbor the host's reporter gene. Cells were also tested for the presence of EGFP mRNA, which was consistently detected for 22 days after the start of culture. The tumorogenicity of the cultured cells was confirmed in GFP mice injected with cells from a selection of cultures. Conclusions: In a melanoma model in GFP mice, the detection of "green" cells in tumors was not equivalent to the detection of host-derived cells. Such "masking" was caused by a transient, but lasting, transfer of EGFP mRNA from the host's normal cells to tumor cells. Thus, an analysis of tumors postmortem by techniques that yield only a single snapshot can lead to incorrect interpretations and erroneous conclusions.


Subject(s)
Animals , Mice , Green Fluorescent Proteins , Melanoma , Neoplasm Transplantation , Polymerase Chain Reaction , Mice, Inbred C57BL , Neoplasms, Experimental
6.
Article in English | WPRIM | ID: wpr-296520

ABSTRACT

<p><b>OBJECTIVE</b>A subcutaneous transplantation tumor model of human HT-29 cells was established in nude mice to study the anticarcinogenic activities and apoptosis-regulatory mechanistic effect of aqueous extract of fermented barley with Lactobacillus plantarum dy-1 (LFBE).</p><p><b>METHODS</b>HT-29 cells were transplanted via subcutaneous injection of 1 × 107cells into the right flank of each nude mouse. Then, nude mice were treated for 30 days with LFBE (high-dose 2 g·kg-1·d-1; low-dose 1 g·kg-1·d-1) and for 7 days with 5-fluorouracil (5-FU, 25 g·kg-1·d-1) by gavage and intraperitoneal injection, respectively.</p><p><b>RESULTS</b>Tumor volume and weight decreased significantly in both groups of nude mice treated with LFBE. In addition, the cell apoptosis rate of the LFBE group was significantly higher than that of the control group and 5-FU groups as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot methods further confirmed these apoptosis-enhancing and growth-inhibiting effects. The involvement of LFBE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and cyclinD1.</p><p><b>CONCLUSION</b>The results showed that LFBE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be used as a natural nutrient supplement or chemopreventive agent in the treatment of human colon cancer.</p>


Subject(s)
Animals , Apoptosis , Caspase 3 , Metabolism , Cell Proliferation , Cyclin D1 , Metabolism , Female , Fermentation , HT29 Cells , Hordeum , Chemistry , Humans , Lactobacillus plantarum , Mice, Nude , Neoplasm Transplantation , Neoplasms, Experimental , Drug Therapy , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein , Metabolism
7.
Article in Chinese | WPRIM | ID: wpr-317585

ABSTRACT

Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor. To set up PDX model, primary or metastatic tumor are achieved to translate into immune-deficiency mice. The tumor in immune-deficiency mouse is acquired to translate to other immune-deficiency mouse to generate stable PDX model, which usually is affected by the strain of mouse, translation method and translation location in mouse. PDX models recapitulate the same histology and gene expression as the original patients' carcinoma. PDX models can accurately predict the effectiveness of novel drugs, screen more predictive biomarker for drug resistance and optimize the use of classic drugs in clinic. However, sole source of surgical resection of tumor, long time of construction, high failure rate and hardly used in evaluating immune drugs would be the barriers to be overcome to improve PDX models. The methodological issues, salient features, practical applications, and future directions of PDX models will be illustrated.


Subject(s)
Animals , Heterografts , Humans , Mice , Neoplasm Transplantation , Methods , Neoplasms , General Surgery , Translational Medical Research , Methods
8.
Protein & Cell ; (12): 114-122, 2017.
Article in English | WPRIM | ID: wpr-757355

ABSTRACT

Increasing attention is focused on the down-regulation of miRNAs in cancer process. Nuclear receptor subfamily 2 (NR2F2, also known as COUP-TFII) is involved in the development of many types of cancers, but its role in gastric cancer remains elusive. In this experiment, oncomine and Kaplan-meier database revealed that NR2F2 was up-regulated in gastric cancer and that the high NR2F2 expression contributed to poor survival. MicroRNA-27b was targeted and down-regulated by NR2F2 in human gastric cancer tissues and cells. The ectopic expression of miR-27b inhibited gastric cancer cell proliferation and tumor growth in vitro and in vivo. Assays suggested that the overexpression of miR-27b could promote MGC-803 cells' migration and invasion and retard their metastasis to the liver. In addition, down-regulation of miR-27b enhanced GES-1 cells' proliferation and metastasis in vitro. These findings reveal that miR-27b is a tumor suppressor in gastric cancer and a biomarker for improving patients' survival.


Subject(s)
Animals , Biomarkers, Tumor , Genetics , Metabolism , COUP Transcription Factor II , Genetics , Metabolism , Cell Line, Tumor , Female , Genes, Tumor Suppressor , Heterografts , Humans , Male , Mice, Nude , MicroRNAs , Genetics , Metabolism , Neoplasm Metastasis , Neoplasm Proteins , Genetics , Metabolism , Neoplasm Transplantation , RNA, Neoplasm , Genetics , Metabolism , Stomach Neoplasms , Genetics , Metabolism , Pathology
9.
Yonsei Medical Journal ; : 27-34, 2017.
Article in English | WPRIM | ID: wpr-65066

ABSTRACT

PURPOSE: Ovarian cancer (OC) is the most fatal of gynecological malignancies with a high rate of recurrence. We aimed to evaluate the expression of solute carrier family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a xenograft mouse model of metastatic OC, and to investigate the regulatory mechanisms that promote aggressive properties during OC progression. MATERIALS AND METHODS: Expression of SLC6A12 mRNA was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and DNA methylation status of its promoter CpGs was detected by quantitative methylation-specific PCR. The metastatic potential of SLC6A12 was evaluated by in vitro migration/invasion transwell assays. Gene expression and DNA methylation of SLC6A12 and clinical outcomes were further investigated from publicly available databases from curatedOvarianData and The Cancer Genome Atlas. RESULTS: SLC6A12 expression was 8.1–14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41–62% decreased in tumor metastases. After treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor, the expression of SLC6A12 was profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent epigenetic regulation of SLC6A12. Overexpression of SLC6A12 led to increased migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0-fold and 3.3-fold, respectively. The meta-analysis showed that high expression of SLC6A12 was significantly associated with poor overall survival [hazard ratio (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at specific promoter CpG site negatively affected patient survival. CONCLUSION: Our findings provide novel evidence for the biological and clinical significance of SLC6A12 as a metastasis-promoting gene.


Subject(s)
Animals , Carrier Proteins/genetics , Cell Line, Tumor , Cell Migration Assays , CpG Islands , DNA Methylation , Disease Progression , Epigenesis, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Neoplasm Invasiveness , Neoplasm Transplantation , Ovarian Neoplasms/genetics , Polymerase Chain Reaction , Prognosis , Promoter Regions, Genetic , RNA, Messenger/metabolism , Up-Regulation
10.
Yonsei Medical Journal ; : 51-58, 2017.
Article in English | WPRIM | ID: wpr-65063

ABSTRACT

PURPOSE: We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. MATERIALS AND METHODS: Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. RESULTS: Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. CONCLUSION: Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety.


Subject(s)
Animals , Brain Neoplasms/diagnostic imaging , Cell Line, Tumor , Cell Tracking/methods , Colonic Neoplasms/diagnostic imaging , Contrast Media/administration & dosage , Disease Models, Animal , Female , Ferritins/administration & dosage , Genes, Reporter , Glioma/diagnostic imaging , Humans , Injections, Intravenous , Macrophages , Magnetic Resonance Imaging/methods , Male , Mice , Neoplasm Transplantation , Skin Neoplasms/diagnostic imaging , Time Factors
11.
Article in Chinese | WPRIM | ID: wpr-328301

ABSTRACT

<p><b>OBJECTIVE</b>To study the inhibitory effect and mechanism of Ganoderma lipsiense extract (GLE) on the growth of triple-negative breast cancer (TNBC) cell line MDA-MB-231-HM in a mouse model.</p><p><b>METHODS</b>The mouse model of TNBC was established by subcutaneous injection of 1.5 x 10(6) of MDA-MB-231-HM cells into BALB/c-nu mouse. Twenty successfully modeled mice were divided into the GLE group and the negative control group according to random digit table, 10 in each group. GLE (0.2 mL 100 mg/mL) was peritoneally injected to mice in the GLE group, while equal dose of normal saline was peritoneally injected to mice in the negative control group. The medication was administered once per 3 days and discontinued after 45 days. The CD34 expression was detected using immunohistochemical assay for counting microvessels. Meanwhile, expressions of thrombospondin 1 (TSP-1) and cyclin D1 were detected using immunohistochemical assay.</p><p><b>RESULTS</b>The average weight was obviously lower in the GLE group than in the negative control group [(0.33 ± 0.16) g vs (0.68 ± 0.37)g, P < 0.05]. The tumor inhibition rate was 51.4% in the GLE group. The volume of transplanted tumor was obviously lesser in the GLE group than in the negative control group (P < 0.05). Results of immunohistochemical staining showed, the microvessel density (MVD) under every field was (20.7 ± 2.1), TSP-1 positive cell count was (66.2 ± 9.2), cyclin D1 positive cell count was (33.8 ± 16.4) in the GLE group, and they were 34.0 ± 2.0, 24.0 ± 6.6, and 168.2 ± 32.6, respectively in the negative control group. There was statistical difference in all indices between the two groups (P < 0.05).</p><p><b>CONCLUSION</b>GLE could inhibit malignant proliferation of tumor cells by suppressing angiogenesis of blood vessels in tumor tissues and regulating cell cycles, thereby inhibiting TNBC.</p>


Subject(s)
Animals , Biological Products , Pharmacology , Cell Line, Tumor , Cyclin D1 , Metabolism , Disease Models, Animal , Ganoderma , Chemistry , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Microvessels , Neoplasm Transplantation , Neovascularization, Pathologic , Random Allocation , Thrombospondin 1 , Metabolism , Triple Negative Breast Neoplasms , Drug Therapy
12.
Article in English | WPRIM | ID: wpr-287114

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo.</p><p><b>METHODS</b>Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography (HPLC). Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract.</p><p><b>RESULTS</b>HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50, 72 h) was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/(kg d)] and low-dose [0.138 mg/(kg d)] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced.</p><p><b>CONCLUSIONS</b>Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.</p>


Subject(s)
Animals , Antineoplastic Agents , Pharmacology , Therapeutic Uses , Apoptosis , Carcinoma, Hepatocellular , Drug Therapy , Pathology , Cell Proliferation , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Female , Immunohistochemistry , Liver Neoplasms , Drug Therapy , Pathology , Male , Melia , Chemistry , Mice, Inbred BALB C , Mitochondria , Metabolism , Neoplasm Transplantation , Plant Extracts , Therapeutic Uses , Reference Standards , bcl-2-Associated X Protein , Metabolism , fas Receptor , Metabolism
13.
Article in Chinese | WPRIM | ID: wpr-289881

ABSTRACT

<p><b>OBJECTIVE</b>To explore the early detection of breast cancer by ultrasonic imaging and thermal tomography of luciferase or green fluorescent protein (GFP)-labeled MDA-MB-231 breast cancer cell line-xenografts in nude mice.</p><p><b>METHODS</b>Fluorescence-tagged lentiviral vectors were transfected into the triple-negative breast cancer cell line MDA-MB-231. These cells were implanted either subcutaneously under the right breast pad or intravenously into the tail vein of nude BALB/C mice. Thermal tomography and ultrasound imaging were used to detect tumor formation and to monitor tumor growth and metastasis in vivo.</p><p><b>RESULTS</b>Triple negative breast cancer cell line-xenografts were used to successfully construct an orthotopic nude mice model of breast cancer metastasis in the peritoneum. Thermal tomography and ultrasound imaging were used together to detect small tumors. Thermal tomography imaging detected small tumors earlier than ultrasound imaging.</p><p><b>CONCLUSIONS</b>Thermal tomography can be used to monitor changes in tumor growth and detect abnormal tissue. Therefore, it can serve as a convenient,rapid,sensitive, and reliable technique for early screening of human breast cancer.</p>


Subject(s)
Animals , Cell Line, Tumor , Disease Models, Animal , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Tomography, X-Ray Computed , Triple Negative Breast Neoplasms , Diagnosis , Diagnostic Imaging , Pathology , Ultrasonography
14.
Article in Chinese | WPRIM | ID: wpr-243842

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the inhibition effect of STIM1 gene silencing on tumor growth of human hypopharyngeal carcinoma cell lines FaDu in nude mice.</p><p><b>METHODS</b>STIM1 gene in FaDu was silenced by lentiviral infection, and the effect of inhibition was detected by Real-time PCR and Western blot after lentiviral infection. Nude mice were divided into 2 groups, 5 mice in each group. Inhibition group: subcutaneous inject FaDu cells which STIM1 expression was inhibited.</p><p><b>CONTROL GROUP</b>subcutaneous inject FaDu cells infected with negative control siRNA-expressing lentivirus. Tumor volumes were measured by calipers, and small animal imaging was detected by NightOWL system on the day 10, 14, 18 and 22 after tumor inoculated. Tumor weights were evaluated in the day 22 after tumor inoculated. Statistical analysis was performed using standard student test(P value threshold was 0.05).</p><p><b>RESULTS</b>The expressions of human STIM1 gene and protein in FaDu cells were suppressed effectively after STIM1-siRNA lentiviral infection. The mean tumor volumes of control group and inhibition group were (51±25) mm3 and (40±35) mm3, respectively, on the day 10, (262±107) and (106±41) mm3 on the day 14, (716±226) and (340±158) mm3 on the day, (1 682±592) mm3 and (917±252)mm3 on the day 22 (P<0.05). On the day 22, the tumor weight was (1.22±0.41) g in control group and (0.66±0.26) g in STIM1-siRNA group (P<0.05). Small animal imaging showed that the tumors had a smaller fluorescence range with lower signal intensity in STIM1-siRNA group than in control group on the day 14, 18 and 22.</p><p><b>CONCLUSION</b>The expression of STIM1 in human hypopharyngeal carcinoma cell lines FaDu can be inhibited effectively by lentiviral infection, causing the inhibition of tumor formation and growth.</p>


Subject(s)
Animals , Cell Line, Tumor , Gene Silencing , Humans , Hypopharyngeal Neoplasms , Pathology , Lentivirus , Membrane Proteins , Genetics , Mice , Mice, Nude , Neoplasm Proteins , Genetics , Neoplasm Transplantation , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , Stromal Interaction Molecule 1
15.
Article in Chinese | WPRIM | ID: wpr-815098

ABSTRACT

To investigate the correlations among total liver CT perfusion parameters, unpaired arteries (UAs) and microvessel area (MVA) in a rabbit liver VX2 tumor model, and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.
 Methods: Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation. Perfusion parameters included blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal liver perfusion (PVP), hepatic perfusion index (HPI) for the tumor rim and the surrounding liver tissue. After the examination, the UAs and MVA of tumor tissues were obtained by immunohistochemical staining. The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared. The correlations among perfusion parameters, UAs and MVA were analyzed.
 Results: There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group (P0.05). There was positive correlation between UAs and MVA. UAs and MVA were positively correlated with BF, ALP and BV at the tumor rim. UAs and MVA were negatively correlated with PVP. HPI positively correlated with UAs, but it was not correlated with MVA.
 Conclusion: Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor, and to assess the degree of tumor angiogenesis.


Subject(s)
Animals , Arteries , Diagnostic Imaging , Blood Volume , Carcinoma , Immunohistochemistry , Liver Circulation , Liver Neoplasms , Diagnostic Imaging , Microvessels , Diagnostic Imaging , Neoplasm Transplantation , Neoplasms, Squamous Cell , Neovascularization, Pathologic , Diagnostic Imaging , Perfusion Imaging , Portal System , Diagnostic Imaging , Rabbits , Tomography, X-Ray Computed , Methods
16.
Protein & Cell ; (12): 722-734, 2016.
Article in English | WPRIM | ID: wpr-757383

ABSTRACT

Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.


Subject(s)
Animals , Apoptosis Regulatory Proteins , Genetics , Metabolism , Caco-2 Cells , Cell Proliferation , Colorectal Neoplasms , Genetics , Metabolism , Pathology , Heterografts , Humans , Male , Mice , Mice, Nude , Mice, SCID , MicroRNAs , Genetics , Metabolism , Neoplasm Proteins , Genetics , Metabolism , Neoplasm Transplantation , RNA, Neoplasm , Genetics , Metabolism , RNA-Binding Proteins , Genetics , Metabolism
17.
Article in Chinese | WPRIM | ID: wpr-263984

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of solanine on the growth of human prostate cancer cell xenograft in nude mice.</p><p><b>METHODS</b>Human prostate cancer Du145 cells were injected into the subcutaneous layers on the back of nude mice. After a week, the mice bearing subcutaneous tumor graft were randomly divided into solanine treatment group and saline control group for treatment for 3 weeks. The tumor grafts were then harvested to evaluate the inhibition rate. The mRNA and protein expressions of cell cycle-related genes in the tumors were detected by qRT-PCR and Western blotting, respectively, and tumor cell apoptosis was detected using TUNEL method.</p><p><b>RESULTS</b>The tumor growth rate in solanine-treated group was significantly slower than that in the control group (P<0.01). The mRNA and protein expressions of C-myc, cyclin D1, cyclin E1, CDK2, CDK4 and CDK6 were significantly inhibited by solanine. Solanine significantly up-regulated p21 mRNA and protein expression in the tumors and induced a higher apoptosis rate of the tumor cells than saline (P<0.01).</p><p><b>CONCLUSION</b>The tumor-inhibition effect of solanine is probably mediated by regulating the expressions of genes related with G1/S cell cycle arrest and cell apoptosis.</p>


Subject(s)
Animals , Apoptosis , Cyclin-Dependent Kinases , Metabolism , Cyclins , Metabolism , G1 Phase Cell Cycle Checkpoints , Humans , Male , Mice , Mice, Nude , Neoplasm Transplantation , Pathology , Prostatic Neoplasms , Drug Therapy , Pathology , S Phase , Solanine , Pharmacology
18.
Rev. latinoam. enferm. (Online) ; 23(4): 651-659, July-Aug. 2015. tab, ilus
Article in English | LILACS, BDENF | ID: lil-761699

ABSTRACT

AbstractObjective: to perform the translation into Brazilian Portuguese and cultural adaptation of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale, with children under 18 years old, affected by cerebral palsy, presenting or not cognitive impairment and unable to report their pain.Method: methodological development study of translation into Portuguese and cultural adaptation of the FLACCr. After approval by the ethics committee, the process aimed at translation and back-translation, evaluation of translation and back-translation using the Delphi technique and assessment of cultural equivalence. The process included the five categories of the scale and the four application instructions, considering levels of agreement equal to or greater than 80%.Results: it was necessary three rounds of the Delphi technique to achieve consensus among experts. The agreement achieved for the five categories was: Face 95.5%, Legs 90%, Activity 94.4%, Cry 94.4% and Consolability 99.4%. The four instructions achieved the following consensus levels: 1st 99.1%, 2nd 99.2%, 3rd 99.1% and 4th 98.3%.Conclusion: the method enabled the translation and cultural adaptation of the FLACCr. This is a study able to expand the knowledge of Brazilian professionals on pain assessment in children with CP.


ResumoObjetivo:realizar a tradução para a língua portuguesa do Brasil e adaptação cultural da escala Face, Legs, Activity, Cry, Consolability revised(FLACCr), com crianças de até 18 anos de idade, acometidas por paralisia cerebral, apresentando ou não comprometimento cognitivo e impossibilitadas de relatar sua dor.Método:estudo de desenvolvimento metodológico de tradução para o português e adaptação cultural da FLACCr. Após aprovação do comitê de ética, o processo contemplou tradução e retrotradução, avaliação da tradução e da retrotradução utilizando a técnica de Delphi e avaliação da equivalência cultural. O processo incluiu as cinco categorias da escala e as quatro orientações de aplicação, considerando nível de concordância igual ou maior a 80%.Resultados:foram necessários três ciclos da técnica de Delphi para consenso entre os juízes. A concordância obtida para as cinco categorias foi: Face 95,5%, Pernas 90%, Atividade 94,4%, Choro 94,4% e Consolabilidade 99,4%. As quatro orientações alcançaram os seguintes níveis de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% e 4ª 98,3%.Conclusão:o método possibilitou o desenvolvimento da tradução e adaptação cultural da FLACCr. Sendo um estudo capaz de ampliar o conhecimento de profissionais brasileiros sobre a avaliação da dor em crianças com PC.


ResumenObjetivo:realizar la traducción para el portugués de Brasil y la adaptación cultural de la escala, Face, Legs, Activity, Cry, Consolability revised(FLACCr), con niños menores de 18 años de edad, afectados por la parálisis cerebral, presentando o no deterioro cognitivo y que no pueden comunicar su dolor.Método:estudio de desarrollo metodológico de traducción al portugués y adaptación cultural de la FLACCr. Después de la aprobación por el comité de ética, el proceso incluyó la traducción y retrotraducción, evaluación de la traducción y retrotraducción utilizando la técnica Delphi y evaluación de la equivalencia cultural. El proceso incluyó las cinco categorías de la escala y las cuatro orientaciones de aplicación, teniendo en cuenta nivel de concordancia igual o superior al 80%.Resultados:fueron necesarios tres ciclos de la técnica Delphi para el consenso entre los jueces. La concordancia obtenida para las cinco categorías fue: Cara 95,5%, Piernas 90%, Actividad 94,4%, Llanto 94,4% y Capacidad de Consuelo 99,4%. Las cuatro orientaciones alcanzaron los siguientes niveles de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% y 4ª 98,3%.Conclusión:el método permitió el desarrollo de la traducción y adaptación cultural de la FLACCr. Este estudio fue capaz de aumentar el conocimiento de los profesionales brasileños en la evaluación del dolor en niños con PC.


Subject(s)
Animals , Rats , Graft Rejection/immunology , Neoplasms, Experimental/immunology , Cell Line, Tumor , Graft Rejection/genetics , Graft Rejection/pathology , Neoplasm Transplantation , Neoplasms, Experimental/genetics , Neoplasms, Experimental/pathology , Rats, Inbred Lew , Rats, Wistar
19.
Article in Chinese | WPRIM | ID: wpr-333661

ABSTRACT

<p><b>OBJECTIVE</b>To establish a two-step pretargeting approach to lymphoma radioimmunoimaging in mice using biotinynaled CD45 monoclonal antibody (McAb) and (188)Re-avidin in a tumor-bearing mouse model.</p><p><b>METHODS</b>Six Nod-Scid mice bearing lymphoma cell xenograft were randomized to receive either an intravenous injection of 50 µg/200 µL biotinyled CD45 McAb followed 24 h later by an intraperitoneal injection of 3.7 MBq (50 µg/100 µL) (188)Re-avidin (two-step pretargeting group), or a single intravenous injection of 3.7 MBq (100 µg/100 µL) (188)Re-CD45 McAb (control group). SPECT was performed at 0.5, 1, 6 and 23 h post-injection to characterize (188)Re isotope biodistribution. At 24 h pos-injection, the mice were sacrificed for measurement of radioactivity uptake in the tumor and normal tissues and calculation of the tumor-to-non-tumor (T/NT) ratios.</p><p><b>RESULTS</b>SPECT showed that the two-step pretargeting method resulted in a low radioactivity in the blood pool during the imaging and a concentrated radioactivity in the liver and spleen. The transplanted tumor began to be displayed at 1 h post-injection and was clearly displayed at 1-6 h; the images were clear even at 23 h. With the two-step pretargeting method, the radioactive uptake at 24 h post-injection were (1.34∓0.52)%, (6.77∓2.32)%, and (2.81∓1.25)% in the tumor, kidney and liver, respectively, with low radioactivity levels in other organs and high tumor/blood and tumor/muscle ratios (4.28∓0.82 and 8.00∓0.88, respectively). In the control group, SPECT revealed intense radioactivity in the liver, spleen, and kidneys with obscure display of the tumor; at 20 h, the radioactivity in the blood pool remained high but that in the tumor was low, and the tumor/blood and tumor/muscle ratios at 24 h were only 0.58∓0.06 and 3.21∓0.24, respectively.</p><p><b>CONCLUSION</b>Compared with (188)Re-CD45 McAb, the two-step pretargeting approach exhibits a good specificity in targeting lymphoma with an increased T/NT ratio in mice and allows early tumor display at 1 h post-injection.</p>


Subject(s)
Animals , Antibodies, Monoclonal , Avidin , Disease Models, Animal , Lymphoma , Diagnosis , Mice , Mice, Nude , Neoplasm Transplantation , Radioimmunodetection , Tissue Distribution , Tomography, Emission-Computed, Single-Photon
20.
Article in Chinese | WPRIM | ID: wpr-333653

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of anti-survivin oligonucleotides (ASODN) on the invasion and growth of peritoneally implanted ovarian cancer cell xenografts in nude mice.</p><p><b>METHODS</b>Nude mouse models bearing peritoneally implanted ovarian cancer cell (SKOV3) xenografts were established and subjected to intraperitoneal injection of survivin ASODN or saline (control). The number and weight of the intraperitoneal xenografts were compared between the two groups.The expressions of interleukin (IL-6), signal transducer and activator of transcription3 (STAT3), phosphorylated STAT3 (p-STAT3), and survivin protein in the tumor tissues were detected with Western blotting in both groups.</p><p><b>RESULTS</b>Compared with those in the control group, the number and weight of the intraperitoneal xenografts were significantly reduced in ASODN group (P<0.05). ASODN treatment also resulted in significantly lowered protein levels of IL-6, STAT3, p-STAT3, and survivin in the tumor tissues (P<0.05).</p><p><b>CONCLUSION</b>Survivin ASODN can suppress the invasion and migration capacity of ovarian cancer cells and inhibit peritoneal metastasis of the tumor in nude mice possibly though down-regulation of IL-6/STAT3 signaling pathway.</p>


Subject(s)
Animals , Cell Line, Tumor , Down-Regulation , Female , Humans , Inhibitor of Apoptosis Proteins , Metabolism , Interleukin-6 , Metabolism , Mice , Mice, Nude , Neoplasm Transplantation , Oligonucleotides , Pharmacology , Ovarian Neoplasms , Pathology , Therapeutics , STAT3 Transcription Factor , Metabolism
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