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1.
Arq. bras. med. vet. zootec. (Online) ; 73(5): 1067-1075, Sept.-Oct. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1345266

ABSTRACT

The aim of this study was to evaluate neovascularization of bovine xenografts implanted in intracorporeal sites of rabbits (bioreactors). 30 rabbits were used, divided into 6 groups, according to the evaluation time (7, 15, 30, 45, and 60 days); each animal received xenogenic implants in 3 different intracorporeal sites (A1 - omentum bag; A2 - intermuscular space of quadriceps femoris; A3 - subperiosteal of ilium bone). Histological assessments graded the presence of angiogenesis, the number of inflammatory cells, newly formed bone tissue, and the presence of giant cells. Histological analyses showed intense angiogenesis in all implanted xenografts. Presence of inflammatory infiltrate and giant cells at the A1 implant site and presence of bone neoformation at the A3 implant site were noted. Degeneration of implants and formation of a fibrous capsule were noted. When comparing the interaction of the site with the days of evaluation, statistical analysis showed a significant difference (p≤0.05) in any time of neovascularization analysis. The vascular endothelial growth factor (VEGF) and inflammatory cells of the omentum in its structure, may have contributed to the greater presence of neovessels and inflammatory cells, a fact that may indicate functionality as a possible bone substitute.(AU)


O objetivo deste estudo foi avaliar a neovascularização de xenoenxertos bovinos implantados em sítios intracorpóreos de coelhos (biorreatores). Foram utilizados 30 coelhos, os quais foram divididos em seis grupos, de acordo com o tempo de avaliação (sete, 15, 30, 45 e 60 dias); cada animal recebeu implantes xenogênicos em três diferentes sítios intracorpóreos (A1 - bolsa de omento; A2 - espaço intermuscular do quadríceps femoral; A3 - subperiosteal do osso ílio). Avaliações histológicas classificaram a presença de angiogênese, o número de células inflamatórias, de tecido ósseo neoformado e a presença de células gigantes. As análises histológicas mostraram intensa angiogênese em todos os xenoenxertos implantados. Observou-se presença de infiltrado inflamatório e células gigantes no local do implante A1 e presença de neoformação óssea no local do implante A3. Ao mesmo tempo, a degeneração dos implantes e a formação de uma cápsula fibrosa foram observadas. Ao comparar a interação do local com os dias de avaliação, a análise estatística mostrou diferença significativa (P≤0,05) em qualquer momento da análise de neovascularização. O fator de crescimento endotelial vascular (VEGF) e as células inflamatórias do omento em sua estrutura podem ter contribuído para a maior presença de neovasos e células inflamatórias, fato que pode indicar funcionalidade como possível substituto ósseo.(AU)


Subject(s)
Animals , Cattle , Rabbits , Bone Transplantation/veterinary , Bioreactors/veterinary , Heterografts/blood supply , Models, Animal
2.
Article in English | WPRIM | ID: wpr-922118

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As@*METHODS@#Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (n=6 in each) were treated with normal saline (control), As@*RESULTS@#Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As@*CONCLUSION@#Combination treatment with As


Subject(s)
Animals , Arsenic Trioxide , Cricetinae , Heart Transplantation , Heme Oxygenase-1/metabolism , Heterografts , Leflunomide , NF-E2-Related Factor 2/metabolism , Rats , Rats, Inbred Lew , Signal Transduction
3.
Article in English | WPRIM | ID: wpr-921383

ABSTRACT

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.


Subject(s)
Animals , Disease Models, Animal , Head and Neck Neoplasms , Heterografts , Humans , Mice , Xenograft Model Antitumor Assays
4.
J. oral res. (Impresa) ; 9(6): 449-456, dic. 31, 2020. ilus, tab
Article in English | LILACS | ID: biblio-1178938

ABSTRACT

Objetive: To determine the expressions of the bone surface marker CD44 in samples of alveolar bone previously regenerated with allograft, xenograft, and mixed, using the technique of guided bone regeneration. Material and Methods: This exploratory study was approved by the institutional research and ethics committee. By means of intentional sampling and after obtaining informed consent for tissue donation, 20 samples of alveolar bone previously regenerated with guided bone regeneration therapy with particulate bone graft and membrane were taken during implant placement. The samples were stained with hematoxylin-eosin for histological analysis, and by immunohistochemistry for the detection of CD44. Results: Sections with hematoxylin-eosin showed bone tissue with the presence of osteoid matrix and mature bone matrix of usual appearance. Of the CD44+ samples, 80% were allograft and 20% xenograft. The samples with allograft-xenograft were negative. There were no differences in the intensity of CD44 expression between the positive samples. The marker was expressed in osteocytes, stromal cells, mononuclear infiltrate, and some histiocytes. Eighty percent of the CD44+ samples and 100% of the samples in which 60 or more cells were labelled corresponded to allografts (p=0.000). A total of 67% of the samples from the anterior sector, and 40% from the posterior sector were CD44+ (p=0.689). Conclusion: This study shows for the first time that guided bone regeneration using allografts is more efficient for the generation of mature bone determined by the expression of CD44, compared to the use of xenografts and mixed allograft-xenograft, regardless of the regenerated anatomical area.


Objetivo: Determinar la expresión del marcador de membrana óseo CD44 en muestras de hueso alveolar previamente regenerado con aloinjerto, xenoinjerto y mezcla mediante la técnica de regeneración ósea guiada. Material y Métodos: Con aval del Comité de Investigación y Ética, se realizó un estudio exploratorio. Por muestreo intencional y firma de consentimiento informado de donación, se tomaron durante la colocación del implante, 20 muestras de hueso alveolar previamente regenerado con terapia de regeneración ósea guiada con injerto óseo particulado y membrana. Las muestras fueron teñidas con hematoxilina-eosina para el análisis histológico y por inmunohistoquímica para la detección del CD44. Resultados: : Los cortes con hematoxilina-eosina mostraron tejido óseo con presencia de matriz osteoide y matriz ósea madura de aspecto usual. De las muestras CD44+, 80% fueron de aloinjerto y 20% de xenoinjerto. Las muestras con aloinjerto-xeoninjerto fueron negativas. No hubo diferencias en la intensidad de la expresión del CD44 entre las muestras positivas. El marcador se expresó en osteocitos, células estromales, infiltrado mononuclear y algunos histiocitos. El 80% de las muestras CD44+ y el 100% de las muestras con marcación de 60 o más células correspondían a aloinjertos (p=0,000). El 67% de las muestras del sector anterior y el 40% del sector posterior fueron CD44+ (p=0,689). Conclusión: Este estudio muestra por primera vez que la regeneración ósea guiada usando aloinjertos, es más eficiente para la generación de hueso maduro determinado por la expresión de CD44, comparado con el uso de xenoinjertos y mezcla de aloinjerto-xenoinjerto, independientemente del sector anatómico regenerado.


Subject(s)
Humans , Male , Female , Hyaluronan Receptors/metabolism , Alveolar Bone Grafting , Osteocytes , Bone Regeneration , Dental Implants , Hyaluronan Receptors/genetics , Allografts , Heterografts
5.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 150-158, Apr.-June 2020. tab, graf
Article in English | LILACS | ID: biblio-1134018

ABSTRACT

ABSTRACT Introduction: Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production. Objectives: In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells. Methods: Our approach is based on a lentiviral vector composed by a second-generation CAR that signals through a 41BB and CD3-ζ endodomain. Conclusions: In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the results presented may contribute favoring the translation of the research to the clinical practice.


Subject(s)
Humans , In Vitro Techniques , Immunotherapy, Adoptive , Antigens, CD19 , Cytotoxicity, Immunologic , Heterografts
6.
Article in English | WPRIM | ID: wpr-782505

ABSTRACT

10% of labeled tumor cells) of TNF receptor 1 (TNFR1), the protein product of TNFRSF1A gene, was correlated with sarcomatoid dedifferentiation and was an independent predictive factor of clinically unfavorable response and shorter survivals in separated TKI-treated ccRCC cohort.CONCLUSION: TNF-α signaling may play a role in TKI resistance, and TNFR1 expression may serve as a predictive biomarker for clinically unfavorable TKI responses in ccRCC.


Subject(s)
Biomarkers , Carcinoma, Renal Cell , Cohort Studies , Dataset , Drug Resistance , Gene Expression , Gene Expression Profiling , Heterografts , Humans , Immunohistochemistry , Protein-Tyrosine Kinases , Receptors, Tumor Necrosis Factor , Receptors, Tumor Necrosis Factor, Type I , Tumor Necrosis Factor-alpha
7.
Article in Chinese | WPRIM | ID: wpr-880764

ABSTRACT

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.


Subject(s)
Animals , Bile Duct Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/genetics , Cytoskeletal Proteins , Heterografts , Humans , Imidazoles , Mice , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Pyridazines , Receptor, Fibroblast Growth Factor, Type 2 , Xenograft Model Antitumor Assays
8.
Article in Chinese | WPRIM | ID: wpr-828908

ABSTRACT

OBJECTIVE@#To investigate the difference of tumor formation in different mouse strains bearing patient-derived xenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study of individualized treatment of ESCC.@*METHODS@#The tumor tissues collected from 22 ESCC patients were used to establish tumor-bearing mouse models in B-NDG (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formation time were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing were carried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues.@*RESULTS@#The tumor-bearing models were established successfully in both NSG mice (50%, 11/22) and BALB/c nude mice (18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 91.67 days, < 0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identical to those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater genetic similarity to the patients' tumors than those in BALB/c nude mice ( < 0.0001).@*CONCLUSIONS@#Mouse models bearing xenografts of patient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the former mouse strain can be more reliable.


Subject(s)
Animals , Cell Line, Tumor , Cell Proliferation , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Heterografts , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Xenograft Model Antitumor Assays
9.
Article in Chinese | WPRIM | ID: wpr-828854

ABSTRACT

OBJECTIVE@#To investigate the effect of β-arrestin1 overexpression on tumor progression in a NCG mouse model bearing T-cell acute lymphocytic leukemia (T-ALL) Molt-4 cell xenograft.@*METHODS@#Molt-4 cells were tagged with firefly-luciferase (F-Luc) by lentiviral infection, and fluorescence intensity of the cells was detected using a luminescence detector. Molt-4 cell lines with β-arrestin1 overexpression or knockdown were constructed by lentivirus infection and injected the tail vein in sub-lethal irradiated NCG mice. Body weight changes and survival time of the xenografted mice were observed, and the progression of T-ALL in the mice was evaluated using an fluorescence imaging system. Sixteen days after xenografting, the mice were euthanatized and tumor cell infiltration was observed in the slices of the liver and spleen.@*RESULTS@#We successfully tagged Molt-4 cells with F-Luc and overexpressed or knocked down β-arrestin1 in the tagged cells. Bioluminescent imaging showed obvious luminescence catalyzed by F-Luc in Molt-4 cells. After injection of Molt-4-Luc cells into irradiated NCG mice, a gradual enhancement of luminescence in the xenografted mice was observed over time, while the body weight of the mice decreased. Compared with the control mice, the mice xenografted with β-arrestin1-overexpressing Molt-4 cells had significantly prolonged survival time ( < 0.001), while the survival time of the mice xenografted with Molt-4 cells with β- arrestin1 knockdown was significantly shortened ( < 0.001). Histological examination revealed fewer infiltrating tumor cells in the liver and spleen of the mice xenografted with β-arrestin1-overexpressing Molt-4 cells in comparison with the mice bearing parental Molt-4 cell xenografts.@*CONCLUSIONS@#β-arrestin1 overexpression suppresses tumor progression in mice bearing Molt-4 cell xenograft.


Subject(s)
Animals , Disease Progression , Heterografts , Humans , Mice , T-Lymphocytes , Transplantation, Heterologous , beta-Arrestin 1
10.
Article in Chinese | WPRIM | ID: wpr-878839

ABSTRACT

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 μmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.


Subject(s)
Animals , Capsules , Carcinoma, Hepatocellular , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Fluorouracil , Heterografts , Liver Neoplasms , Mice , Mice, Nude , Vascular Endothelial Growth Factor A , Xenograft Model Antitumor Assays
11.
Horiz. méd. (Impresa) ; 19(3): 20-26, Set. 2019. ilus, graf, tab
Article in Spanish | LIPECS, LILACS, LIPECS | ID: biblio-1022286

ABSTRACT

Objetivo: Realizar una evaluación de la cicatrización en la zona donante de injerto de piel parcial con uso de sustituto dérmico comparado con xenoinjerto, en pacientes con lesiones diversas que requirieron injerto de piel parcial. Materiales y métodos: Se presenta el reporte de 20 pacientes entre 19 y 65 años de la Unidad de Cirugía Plástica del Hospital María Auxiliadora de Lima Metropolitana-Perú, entre diciembre 2017 y junio 2018, donde se evaluó la cicatrización en zonas donantes de injerto de piel parcial. El estudio es de tipo intervención, analítico, prospectivo y longitudinal. Emplea el diseño doble ciego para controlar posibles sesgos. Para analizar la significancia estadística se usaron pruebas no paramétricas con un nivel de confianza 95 %. Resultados: Con el uso del sustituto dérmico se aprecia una mejor calidad de cicatrización de zonas donantes de epitelización en comparación con el xenoinjerto. Ambas técnicas se evaluaron con la escala de Vancouver que considera cinco aspectos (cicatrización, vascularidad, pigmentación, flexibilidad y altura), de los cuales, la cicatrización tuvo resultados significativos (p<0,05). Al estimar el riesgo de evolución de cicatrización según el modelo de riesgos proporcionales de Cox, se obtuvo un H=0,60 (IC95% 0,46-0,78), lo cual indica que el menor tiempo de cicatrización se encontró en el grupo en que se empleó el sustituto dérmico. Conclusiones: El sustituto dérmico es una alternativa importante que favorece buena calidad de la cicatrización en las zonas donantes. El sustituto dérmico es más eficiente que el xenoinjerto convencional al ser evaluado y comparado en la escala de cicatrización de Vancouver.


Objective: To evaluate healing in partial skin graft donor sites using a skin substitute compared to a xenograft in patients with different diseases requiring partial skin grafting. Materials and methods: This paper presents a report of 20 patients between 19 and 65 years from the Plastic Surgery Unit of the Hospital María Auxiliadora in Lima Metropolitan Area, Peru, between December 2017 and June 2018, where healing was evaluated in partial skin graft donor sites. An interventional, analytical, prospective and longitudinal study was conducted using a double-blind design to control possible biases. For the statistical significance analysis, nonparametric tests with a 95 % confidence interval were used. Results: Using a skin substitute, a better healing quality of donor sites of epithelialization was seen compared with xenografting. Both techniques were evaluated with the Vancouver scale, which considers five aspects (healing, vascularity, pigmentation, flexibility and height), out of which healing showed significant results (p<0.05). Estimation of the risk in the healing process according to the Cox proportional hazards model showed that H = 0.60 (95 % CI 0.46- 0.78), which indicates that the shortest healing time was found in the skin substitute group. Conclusions: Skin substitutes are an important alternative that favors the good quality of healing in donor sites. skin substitutes proved to be more effective than conventional xenografting when evaluated and compared using the Vancouver healing scale.


Subject(s)
Humans , Heterografts , Transplantation , Wound Healing , Granulation Tissue
12.
Journal of Gastric Cancer ; : 235-253, 2019.
Article in English | WPRIM | ID: wpr-764503

ABSTRACT

Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.


Subject(s)
Biomarkers, Tumor , Chemotherapy, Adjuvant , Classification , Decision Making , Drug Therapy , Heterografts , Humans , Molecular Targeted Therapy , Organoids , Precision Medicine , Prognosis , Real-Time Polymerase Chain Reaction , RNA , Stomach Neoplasms
13.
Article in Chinese | WPRIM | ID: wpr-772103

ABSTRACT

OBJECTIVE@#To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells.@*METHODS@#The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts.@*RESULTS@#MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice.@*CONCLUSIONS@#The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.


Subject(s)
Acetates , Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung , Pathology , Cell Line, Tumor , Cell Proliferation , Heterografts , Humans , Lung Neoplasms , Pathology , Methanol , Mice , Mice, Nude , Plant Extracts , Pharmacology
14.
Laboratory Animal Research ; : 194-201, 2019.
Article in English | WPRIM | ID: wpr-786403

ABSTRACT

TW-37 is a small molecule B cell lymphoma-2 (Bcl-2) homology 3 mimetic with potential anticancer activities. However, the in vivo anti-cancer effect of TW-37 in human oral cancer has not been properly studied yet. Here, we attempted to confirm antitumor activity of TW37 in human oral cancer. TW-37 significantly inhibited cell proliferation and increased the number of dead cells in MC-3 and HSC-3 human oral cancer cell lines. TW-37 enhanced apoptosis of both cell lines evidenced by annexin V/propidium iodide double staining, sub-G1 population analysis and the detection of cleaved poly (ADP-ribose) polymerase and caspase-3. In addition, TW-37 markedly downregulated the expression of Bcl-2 protein, while not affecting Bcl-xL or myeloid cell leukemia-1. In vivo, TW-37 inhibited tumor growth in a nude mice xenograft model without any significant liver and kidney toxicities. Collectively, these data reveal that TW-37 may be a promising small molecule to inhibit human oral cancer.


Subject(s)
Animals , Apoptosis , Caspase 3 , Cell Line , Cell Proliferation , Heterografts , Humans , Kidney , Liver , Mice , Mice, Nude , Mouth Neoplasms , Myeloid Cells
15.
Laboratory Animal Research ; : 221-229, 2019.
Article in English | WPRIM | ID: wpr-786400

ABSTRACT

Signal transducer and activator of transcription 3 (STAT3) modulates a variety of genes involved in the regulation of critical functions, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, and immunity. For many cancers, elevated levels of STAT3 signaling have been associated with a poor prognosis and the development of chemotherapy resistance. In this study, we investigated the inhibitory effects of a novel small-molecule inhibitor of STAT3, STX-0119, on the cell viability and survival of human lung cancer cells. STX-0119 inhibited activated STAT3 and the expression of STAT3-regulated oncoproteins such as c-Myc, cyclin D1, and survivin in lung cancer cells. STX-0119 also decreased the amount of STAT3 in the nuclear fraction as well as induced apoptosis of these lung cancer cell lines as evidenced by increases in apoptotic cells (Annexin V positive) and poly (ADP-ribose) polymerase (PARP) cleavage. The efficacy of STX-0119 in a mouse xenograft model was confirmed. However, a hematological side effect, which had not been previously reported, was observed. The level of white blood cells was significantly lowered when treated at the dose at which STX-0119 alone showed a significant tumor-suppressive effect. In conclusion, we suggest that STX-0119 may be a potent therapeutic agent against lung cancer. Consideration of the side effect suggests, it is necessary to study whether low-dose STX-0119 is effective for lung treatment with a combination of classic lung cancer therapeutics.


Subject(s)
Animals , Apoptosis , Cell Line , Cell Proliferation , Cell Survival , Cyclin D1 , Drug Therapy , Heterografts , Humans , Leukocytes , Lung Neoplasms , Lung , Mice , Neoplasm Metastasis , Oncogene Proteins , Prognosis , STAT3 Transcription Factor
16.
Journal of Gastric Cancer ; : 460-472, 2019.
Article in English | WPRIM | ID: wpr-785956

ABSTRACT

PURPOSE: Long noncoding RNA 00703 (LINC00703) was found originating from a region downstream of Kruppel-like factor 6 (KLF6) gene, having 2 binding sites for miR-181a. Since KLF6 has been reported as a target of miR-181a in gastric cancer (GC), this study aims to investigate whether LINC00703 regulates the miR-181a/KLF6 axis and plays a functional role in GC pathogenesis.MATERIALS AND METHODS: GC tissues, cell lines, and nude mice were included in this study. RNA binding protein immunoprecipitation (RIP) and pull-down assays were used to evaluate interaction between LINC00703 and miR-181a. Quantitative real-time polymerase chain reaction and western blot were applied for analysis of gene expression at the transcriptional and protein levels. A nude xenograft mouse model was used to determine LINC00703 function in vivo.RESULTS: We revealed that LINC00703 competitively interacts with miR-181a to regulate KLF6. Overexpression of LINC00703 inhibited cell proliferation, migration/invasion, but promoted apoptosis in vitro, and arrested tumor growth in vivo. LINC00703 expression was found to be decreased in GC tissues, which was positively correlated with KLF6, but negatively with the miR-181a levels.CONCLUSIONS: LINC00703 may have an anti-cancer function via modulation of the miR-181a/KLF6 axis. This study also provides a new potential diagnostic marker and therapeutic target for GC treatment.


Subject(s)
Animals , Apoptosis , Binding Sites , Blotting, Western , Cell Line , Cell Proliferation , Gene Expression , Heterografts , Immunoprecipitation , In Vitro Techniques , Mice , Mice, Nude , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding , RNA-Binding Proteins , Stomach Neoplasms
17.
Article in English | WPRIM | ID: wpr-766325

ABSTRACT

As dental implant surgery and bone grafts were widely operated in Korean dentist, many bone substitutes are commercially available, currently. For commercially used in Korea, all bone substitutes are firstly evaluated by the Ministry of Health and Welfare (MOHW) for safety and efficacy of the product. After being priced, classified, and registration by the Health Insurance Review and Assessment Service (HIRA), the post-application management is obligatory for the manufacturer (or representative importer) to receive a certificate of Good Manufacturing Practice by Ministry of Food and Drug Safety. Currently, bone substitutes are broadly classified into C group (bone union and fracture fixation), T group (human tissue), L group (general and dental material) and non-insurance material group in MOHW notification No. 2018-248. Among them, bone substitutes classified as dental materials (L7) are divided as xenograft and alloplastic bone graft. The purpose of this paper is to analyze alloplastic bone substitutes of 37 products in MOHW notification No. 2018-248 and to evaluate the reference level based on the ISI Web of Knowledge, PubMed, EMBASE (1980–2019), Cochrane Database, and Google Scholar using the criteria of registered or trademarked product name.


Subject(s)
Bone Substitutes , Dental Implantation , Dental Implants , Dental Materials , Dentists , Heterografts , Humans , Insurance, Health , Korea , Patents as Topic , Transplants
18.
Yonsei Medical Journal ; : 842-853, 2019.
Article in English | WPRIM | ID: wpr-762122

ABSTRACT

PURPOSE: Long intergenic non-protein coding RNA 665 (LINC00665) plays a vital role in the development of cancer. Its function in hepatocellular carcinoma (HCC), however, remains largely unknown. MATERIALS AND METHODS: The expressions of LINC00665, miR-186-5p, and MAP4K3 were determined by qRT-PCR. Cell viability and apoptosis were evaluated by MTT and flow cytometry, respectively. Autophagic puncta formation was observed by fluorescence microscopy. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and RNA pulldown were performed to identify associations among LINC00665, miR-186-5p, and MAP4K3. Western blot was utilized to examine the expressions of MAP4K3, Beclin-1, and LC3. Tumor growth was evaluated in a xenograft model. RESULTS: Elevations in LINC00665 were observed in HCC tissues and cells. The overall survival of HCC patients with high levels of LINC00665 was shorter than those with low levels. In vitro, LINC00665 depletion inhibited viability and induced apoptosis and autophagy. miR-186-5p interacted with LINC00665 and was downregulated in HCC tissues and cells. Upregulation of miR-186-5p inhibited viability and induced apoptosis and autophagy, which were attenuated by upregulation of LINC00665. MAP4K3 was found to possess binding sites with miR-186-5p and was upregulated in HCC tissues and cells. MAP4K3 depletion inhibited viability and induced apoptosis and autophagy, which were attenuated by miR-186-5p inhibitor. In vivo, miR-186-5p expression was negatively correlated with LINC00665 or MAP4K3 in HCC tissues, while LINC00665 was positively correlated with MAP4K3. LINC00665 knockdown suppressed tumor growth. CONCLUSION: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which may provide a new approach for HCC treatment.


Subject(s)
Apoptosis , Autophagy , Binding Sites , Blotting, Western , Carcinoma, Hepatocellular , Cell Survival , Computational Biology , Flow Cytometry , Heterografts , Humans , Immunoprecipitation , In Vitro Techniques , Luciferases , Microscopy, Fluorescence , RNA , RNA, Long Noncoding , Up-Regulation
19.
Yonsei Medical Journal ; : 500-508, 2019.
Article in English | WPRIM | ID: wpr-762086

ABSTRACT

PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.


Subject(s)
Adenocarcinoma , Blotting, Western , Cytokines , Enzyme-Linked Immunosorbent Assay , Heterografts , Homicide , Humans , Interleukin-2 , Killer Cells, Natural , L-Lactate Dehydrogenase , Luciferases , Lung Neoplasms , Lung , MicroRNAs , Necrosis , Real-Time Polymerase Chain Reaction , Serine , Transferases
20.
Yonsei Medical Journal ; : 1146-1156, 2019.
Article in English | WPRIM | ID: wpr-762070

ABSTRACT

PURPOSE: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of small RNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanisms thereof. MATERIALS AND METHODS: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blot assay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, and apoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, a xenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancer in vivo. RESULTS: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression of miR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targeting WNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancer in an in vivo xenograft tumor model. CONCLUSION: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.


Subject(s)
Apoptosis , Blotting, Western , Cisplatin , Epithelial-Mesenchymal Transition , Flow Cytometry , Gene Expression , Heterografts , Humans , In Vitro Techniques , MicroRNAs , Ovarian Neoplasms , Polymerase Chain Reaction , RNA
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