Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 241
Filter
1.
Article in Chinese | WPRIM | ID: wpr-828363

ABSTRACT

In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.


Subject(s)
Animals , Apoptosis , Bufanolides , Carcinoma, Hepatocellular , Cisplatin , Fas Ligand Protein , Liver Neoplasms , Mice
2.
Article in English | WPRIM | ID: wpr-785644

ABSTRACT

OBJECTIVE: This study aimed to examine the effect of vitrification on apoptosis and survival in human preantral follicles after thawing.METHODS: This experimental study was conducted at an acute tertiary care hospital from March 2012 to April 2013. Ovaries were sliced into 5×5×1-mm pieces and divided into the following three groups: preantral follicle isolation, ovarian tissue vitrification-warming followed by follicle isolation, and immunohistochemistry of fresh ovarian tissue. For statistical analyses, the Student t-test, chi-square test, Kruskal-Wallis test, and Kaplan-Meier survival analysis were used.RESULTS: A total of 161 preantral follicles (70% secondary) were collected from ovarian cortex tissue of six women between 30 and 37 years of age who underwent oophorectomy due to cervical cancer or breast cancer. There were no significant differences in the follicular morphology of fresh preantral follicles and vitrified follicles after thawing. The mean Fas ligand (FasL) mRNA expression level was 0.43±0.20 (relative to β-actin) in fresh preantral follicles versus 0.51±0.20 in vitrified follicles (p=0.22). The mean caspase-3 mRNA expression level in fresh preantral follicles was 0.56±0.49 vs. 0.27±0.21 in vitrified follicles (p=0.233). One vitrified-thawed secondary follicle grew and developed to an antral follicle within 6 days of culture.CONCLUSION: Vitrification did not affect preantral follicle morphology or mRNA expression of the apoptosis markers FasL and caspase-3. Further studies are required to establish whether vitrification affects the outcomes of in vitro culture and the maturation of preantral follicles.


Subject(s)
Apoptosis , Breast Neoplasms , Caspase 3 , Fas Ligand Protein , Female , Humans , Immunohistochemistry , In Vitro Techniques , Ovariectomy , Ovary , RNA, Messenger , Tertiary Healthcare , Uterine Cervical Neoplasms , Vitrification
3.
Autops. Case Rep ; 8(1): e2018001, Jan.-Mar. 2018. tab, ilus
Article in English | LILACS | ID: biblio-905418

ABSTRACT

Histiocytic sarcoma (HS) is a rare malignant neoplasia of hematopoietic origin and unknown etiology. We studied three patients with histiocytic sarcoma reviewing the morphological and immunohistochemical aspects. We evaluated in particular, if apoptosis may be unbalanced in this disease. All cases have morphological and immunohistochemical features consistent with the diagnosis of histiocytic sarcoma. The markers CD163, CD68, vimentin, lysozyme, and S-100 were positive in all cases. Similarly, the three samples were positive for Fas-ligand and Caspase-3. It is well-known that neoplasms may induce increased levels of Fas-ligand with the blockade of the apoptosis process. In the context of HS, the increased Fas-ligand expression represents a new area for research. Indeed, it is linked to proinflammatory stimulus and, maybe with the association of an infection.


Subject(s)
Humans , Male , Female , Adult , Aged , Histiocytic Sarcoma/etiology , Apoptosis , Caspase 3 , Fas Ligand Protein , Histiocytic Sarcoma/diagnosis , Immunohistochemistry
4.
Psychiatry Investigation ; : 900-906, 2018.
Article in English | WPRIM | ID: wpr-716834

ABSTRACT

OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.


Subject(s)
Adiposity , Angiopoietin-2 , Animals , Benzodiazepines , Biomarkers, Tumor , Carcinogenesis , Carrier Proteins , CD40 Ligand , Epidemiologic Studies , Epidermal Growth Factor , Fas Ligand Protein , Heparin-binding EGF-like Growth Factor , Humans , Interleukin-18 , Interleukin-8 , Interleukins , Lorazepam , Mortality , Obesity , Overweight , Plasminogen , Plasminogen Activators , Transforming Growth Factors , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor D
5.
Article in English | WPRIM | ID: wpr-229548

ABSTRACT

<p><b>OBJECTIVE</b>To explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo.</p><p><b>METHODS</b>Thirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively.</p><p><b>RESULTS</b>Compared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05).</p><p><b>CONCLUSION</b>WCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.</p>


Subject(s)
Adenocarcinoma , Drug Therapy , Pathology , Animals , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Chromatography, High Pressure Liquid , Cisplatin , Pharmacology , Drug Resistance, Neoplasm , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Fas Ligand Protein , Genetics , Metabolism , Female , Fluorescent Antibody Technique , Humans , In Situ Nick-End Labeling , Lung Neoplasms , Drug Therapy , Pathology , Mice, Nude , RNA, Messenger , Genetics , Metabolism , Tumor Burden , Xenograft Model Antitumor Assays , fas Receptor , Metabolism
6.
Article in Chinese | WPRIM | ID: wpr-286340

ABSTRACT

<p><b>OBJECTIVE</b>To observe the expression of peripheral blood CD4+ T lymphocyte apoptosis gene in rheumatoid arthritis (RA) patients with cold dampness type (CDT), and to explore its correlation with clinical indicators of RA.</p><p><b>METHODS</b>Sixteen RA patients with CDT (as the RA group) and 16 healthy subjects (as the normal control group) were recruited. CD4 T cell apoptosis rate was detected in the RA group and the normal control group using FCM. mRNA expressions of fas, fasL, caspase-3, caspase-8, bcl-2, and bax were detected using RT-PCR. Correlations between the expression of apoptosis gene and clinical activity indicators of RA (ESR, CRP, RF, CCP, integrals for Chinese medial symptoms, morning stiffness time, joint tenderness number, joint swelling number, DAS28-3) were analyzed.</p><p><b>RESULTS</b>The apoptosis rate of CD4+ T was significantly lower in the RA group than in the control group [(2. 6 +/- 0.9) % vs. (7.7 +/- 1.3) %, P < 0.01]. mRNA expression levels of fas, fasL, caspase-8, caspase-3, and bax mRNA of CD4+ T significantly decreased, but bcl-2 mRNA expression increased in the RA group (P < 0.01). The apoptosis rate of CD4+ T was negatively correlated with ESR (P < 0.05). The mRNA expression of caspase-8 was negatively correlated with joint swelling number (P < 0.05). The mRNA expression of bcl-2 was negatively correlated with integrals for Chinese medial-symptoms and joint function classification (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>Apoptosis obstacle exists in peripheral blood CD4 +T lymphocyte of RA patients, and is closely related to disease activity.</p>


Subject(s)
Apoptosis , Arthritis, Rheumatoid , Diagnosis , Metabolism , Pathology , CD4-Positive T-Lymphocytes , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Fas Ligand Protein , Humans , RNA, Messenger
7.
National Journal of Andrology ; (12): 246-251, 2016.
Article in Chinese | WPRIM | ID: wpr-304719

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.</p><p><b>METHODS</b>Models of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.</p><p><b>RESULTS</b>Compared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>By upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.</p>


Subject(s)
Animals , Apoptosis , Drugs, Chinese Herbal , Pharmacology , Fas Ligand Protein , Metabolism , Germ Cells , Glycosides , Infertility, Male , Drug Therapy , Metabolism , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Semen , Semen Analysis , Signal Transduction , Sperm Count , Sperm Motility , Tablets , Testis , Metabolism , Tripterygium
8.
Yonsei Medical Journal ; : 652-657, 2016.
Article in English | WPRIM | ID: wpr-21849

ABSTRACT

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.


Subject(s)
Acute Disease , Adult , Alanine Transaminase/blood , Biomarkers/blood , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Fas Ligand Protein/blood , Female , Hepatitis A/blood , Hepatitis A virus/genetics , Hepatitis B/blood , Hepatitis B virus/genetics , Humans , Interleukin-6/blood , Interleukin-8/blood , Interleukins/blood , Liver Failure/immunology , Male , Middle Aged , T-Lymphocytes, Cytotoxic/immunology
9.
Arq. bras. cardiol ; 104(6): 443-449, 06/2015. tab
Article in English | LILACS | ID: lil-750700

ABSTRACT

Background: The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists. Objective: Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life. Methods: This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State. Results: The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36. Conclusion: Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression. .


Fundamento: Com o envelhecimento, a prevalência de doenças crônico-degenerativas sofreu aumento progressivo. A repercussão dessas doenças sobre a capacidade funcional foi reconhecida. Outro parâmetro de saúde é a “qualidade de vida relacionada à saúde”. Na população idosa, as doenças cardiovasculares destacam-se pelo impacto epidemiológico e clínico. Elas, geralmente, vêm associadas a outras afecções. Esse conjunto de problemas pode comprometer a independência e a qualidade de vida do idoso que busca tratamento cardiológico. Objetivo: Avaliar, em uma população de idosos cardiopatas, quais são os determinantes clínicos mais relevantes de dependência e de qualidade de vida. Métodos: O grupo foi selecionado aleatória e consecutivamente, sendo aplicados quatro questionários: HAQ, SF-36, PRIME‑MD e Mini Exame do Estado Mental. Resultados: Incluiu-se 1020 idosos, 63,3% mulheres. O grupo tinha em média 75,56 ± 6,62 anos. 61,4% mostrou-se independente ou com dependência leve. O escore de qualidade de vida foi elevado (HAQ: 88,66 ± 2,68). 87,8% dos pacientes apresentou escore total do SF-36 ≥ 66. À análise multivariada, a associação entre os diagnósticos e graus elevados de dependência foi significante apenas para acidente vascular cerebral prévio (p = 0,014), obesidade (p < 0,001), sedentarismo (p = 0,016), osteoartrite (p < 0,001), déficit cognitivo (p < 0,001), e depressão maior (p < 0,001). Ao analisarmos a qualidade de vida, a depressão maior e a depressão por doença física associou-se significativamente com todos os domínios do SF-36. Conclusão: Em uma população de idosos cardiopatas, os determinantes clínicos mais relevantes de prejuízos para dependência e qualidade de vida foram as comorbidades não cardiovasculares, particularmente a depressão. .


Subject(s)
Humans , Hepatocytes/pathology , Liver Regeneration , Liver Failure, Acute/metabolism , Apoptosis , /physiology , Fas Ligand Protein/physiology , Hepatocytes/metabolism , Liver Failure, Acute/therapy , Necrosis , Receptors, Tumor Necrosis Factor/metabolism , Signal Transduction , TNF-Related Apoptosis-Inducing Ligand/physiology , Tumor Necrosis Factor-alpha/metabolism
10.
Article in Chinese | WPRIM | ID: wpr-246091

ABSTRACT

<p><b>OBJECTIVE</b>The study aimed to test if Paridis Rhizoma total saponins (PRTS) could induce apoptosis of human gastric cancer cell MKN-45.</p><p><b>METHOD</b>Based on the previous researches, PRTS was set by different concentrations to treat human gastric cancer cell for 12 h (5, 10, 20 mg x L(-1)). Fluorescent staining methods were adopted to observe apoptotic morphological changes of MKN-45. The apoptosis rates were analyzed by flow cytometry with Annexin V-FITC/PI staining. The enzymatic activities of caspase-3 and caspase-8 were measured by ELISA. The protein levels of Fas and FasL were detected by Western blotting.</p><p><b>RESULT</b>Under a fluorescence microscope, MKN-45 treated by PRTS was seen typical apoptotic morphological features. PRTS significantly increased the rate of apoptosis. Compared with the control group, there exsited significant differences in apoptosis rate of PRTS concentration of 20 mg x L(-1) (P < 0.01); besides, the enzymatic activities of caspase-3 and caspase-8 were promoted obviously after the effect of PRTS on MKN-45 cells for 12 h (P < 0.01). The protein levels of Fas and FasL in the MKN-45 were upgraded significantly.</p><p><b>CONCLUSION</b>PRTS can induce apoptosis of human gastric cancer cell MKN-45 , which is concerned with caspase-3 and caspase-8 and upgraded Fas and FasL.</p>


Subject(s)
Apoptosis , Caspase 3 , Genetics , Metabolism , Caspase 8 , Genetics , Metabolism , Cell Line, Tumor , Drugs, Chinese Herbal , Pharmacology , Fas Ligand Protein , Metabolism , Humans , Magnoliopsida , Chemistry , Rhizome , Chemistry , Saponins , Pharmacology , Signal Transduction , Stomach Neoplasms , Drug Therapy , Genetics , Metabolism , fas Receptor , Metabolism
11.
Article in English | WPRIM | ID: wpr-250355

ABSTRACT

Various kinds of schiff base metal complexes have been proven to induce apoptosis of tumor cells. However, it remains largely unknown whether schiff base zinc complexes induce apoptosis in human cancer cells. Here, we synthesized a novel schiff base zinc coordination compound (SBZCC) and investigated its effects on the growth, proliferation and apoptosis of human osteosarcoma MG-63 cells. A novel SBZCC was synthesized by chemical processes and used to treat MG-63 cells. The cell viability was determined by CCK-8 assay. The cell cycle progression, mitochondrial membrane potential and apoptotic cells were analyzed by flow cytometry. The apoptosis-related proteins levels were determined by immunoblotting. Treatment of MG-63 cells with SBZCC resulted in inhibition of cell proliferation and cell cycle arrest at G1 phase. Moreover, SBZCC significantly reduced the mitochondrial membrane potential and induced apoptosis, accompanied with increased Bax/Bcl-2 and FlasL/Fas expression as well as caspase-3/8/9 cleavage. Our results demonstrated that the synthesized novel SBZCC could inhibit the proliferation and induce apoptosis of MG-63 cells via activating both the mitochondrial and cell death receptor apoptosis pathways, suggesting that SBZCC is a promising agent for the development as anticancer drugs.


Subject(s)
Antineoplastic Agents , Pharmacology , Apoptosis , Caspase 3 , Genetics , Metabolism , Caspase 8 , Genetics , Metabolism , Caspase 9 , Genetics , Metabolism , Cell Line, Tumor , Cell Proliferation , Cell Survival , Coordination Complexes , Pharmacology , Fas Ligand Protein , Genetics , Metabolism , G1 Phase Cell Cycle Checkpoints , Gene Expression Regulation, Neoplastic , Humans , Membrane Potential, Mitochondrial , Mitochondria , Metabolism , Pathology , Osteoblasts , Metabolism , Pathology , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , Schiff Bases , Chemistry , Signal Transduction , Zinc , Chemistry , bcl-2-Associated X Protein , Genetics , Metabolism , fas Receptor , Genetics , Metabolism
12.
Article in English | WPRIM | ID: wpr-242848

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma (TCC) in vitro.</p><p><b>METHODS</b>Human bladder TCC cell line T24 was cultured and exposed to graded concentrations of sunitinib malate for 72 hours in vitro to determine the sensitivities to drug. Cell viability was measured by MTT assay. Cell apoptotic morphology was observed by fluorescence microscope following DAPI staining. Band expressions of Fas, Fas ligand, poly (ADP-ribose) polymerase (PARP) and β-actin were analyzed by Western blot. Wound healing process of T24 cells exposed to sunitinib malate was assayed.</p><p><b>RESULTS</b>Sunitinib malate exerted a concentration-dependent and time-dependent inhibitory effect on the T24 cell lines. Fluorescence microscopy showed that small vacuoles appeared in the nuclei of T24 cells and the vacuoles were bigger with higher drug concentrations. The expressions of Fas ligand and PARP in T24 cells treated with sunitinib malate exhibited a concentration-dependent increase. Moreover sunitinib malate suppressed the wound healing process in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Sunitinib malate exerted marked inhibitory activity against bladder cancer cell line T24.</p>


Subject(s)
Antineoplastic Agents , Pharmacology , Apoptosis , Carcinoma, Transitional Cell , Metabolism , Pathology , Cell Line, Tumor , Fas Ligand Protein , Metabolism , Humans , In Vitro Techniques , Indoles , Pharmacology , Poly(ADP-ribose) Polymerases , Metabolism , Pyrroles , Pharmacology , Urinary Bladder Neoplasms , Metabolism , Pathology , Wound Healing , fas Receptor , Metabolism
13.
Biol. Res ; 48: 1-9, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950802

ABSTRACT

BACKGROUND: Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in the concentration range of 10-40 µg/mL. However, the effect of DC in apoptotic signaling at much low concentrations was not studied. METHODS: The present study investigated the attenuation effect of low dose of DC on FasL-induced apoptosis in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA fragmentation, flow cytometry analysis, and western blotting. RESULTS AND CONCLUSION: In the present findings we showed that low concentration of DC (<2.0 µg/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells. FasL treatment to HeLa cells resulted in a concentration-dependent induction of cell death, and treatment with low concentrations of DC (0.1-2 µg/mL) significantly (p < 0.001) attenuated the FasL-induced cell death as measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assay. Further, the FasL-induced apoptotic features in HeLa cells, such as morphological changes, DNA fragmentation and cell cycle arrest was also inhibited by DC (0.5 µg/mL). Tetracycline and minocycline also showed similar anti-apoptotic effects but were not significant when compared to DC, tested at same concentrations. Further, DC (0.01-16 µg/mL) did not influence the hydrogen peroxide- or cisplatin-induced intrinsic apoptotic pathway in HeLa cells. Protein analysis using Western blotting confirmed that FasL-induced cleavage/activation of cas-pase-8 and caspase-3, were inhibited by DC treatment at low concentration (0.5 µg/mL). Considering the overall data, we report for the first time that DC exhibited anti-apoptotic effects at low concentrations in HeLa cells by inhibition of caspase activation via FasL-induced extrinsic pathway.


Subject(s)
Humans , Animals , Mice , Apoptosis/drug effects , Doxycycline/administration & dosage , Caspases/drug effects , Fas Ligand Protein/drug effects , HeLa Cells , Blotting, Western , Doxycycline/pharmacology , NIH 3T3 Cells , Dose-Response Relationship, Drug , Enzyme Activation , Flow Cytometry
14.
ABCD arq. bras. cir. dig ; 28(1): 48-52, 2015. tab, graf
Article in English | LILACS | ID: lil-742757

ABSTRACT

BACKGROUND: Few studies evaluated the association between nutritional disorders, quality of life and weight loss in patients undergoing bariatric surgery. AIM: To identify nutritional changes in patients undergoing bariatric surgery and correlate them with weight loss, control of comorbidities and quality of life. METHOD: A prospective cohort, analytical and descriptive study involving 59 patients undergoing bariatric surgery was done. Data were collected preoperatively at three and six months postoperatively, evaluating nutritional aspects and outcomes using BAROS questionnaire. The data had a confidence interval of 95%. RESULTS: The majority of patients was composed of women, 47 (79.7%), with 55.9% of the series with BMI between 40 to 49.9 kg/m². In the sixth month after surgery scores of quality of life were significantly higher than preoperatively (p<0.05) and 27 (67.5 %) patients had comorbidities resolved, 48 (81.3 %) presented BAROS scores of very good or excellent. After three and six months of surgery 16 and 23 presented some nutritional disorder, respectively. There was no relationship between the loss of excess weight and quality of life among patients with or without nutritional disorders. CONCLUSION: Nutritional disorders are uncommon in the early postoperative period and, when present, have little or no influence on quality of life and loss of excess weight. .


RACIONAL: Poucos estudos avaliam a associação entre distúrbios nutricionais, qualidade de vida e perda de peso em pacientes submetidos à cirurgia bariátrica. OBJETIVO: Identificar alterações nutricionais em pacientes submetidos à cirurgia bariátrica e correlacioná-las com perda de peso, controle de comorbidades e qualidade de vida. MÉTODO: Estudo de coorte, prospectivo, analítico e descritivo envolvendo 59 pacientes submetidos à cirurgia bariátrica. Os dados foram coletados no pré-operatório e aos três e seis meses pós- operatórios, quantificando aspectos nutricionais e utilizando o Bariatric Analysis and Reporting Outcomes System (BAROS) como ferramenta de sucesso. Os dados usaram intervalo de confiança de 95%. RESULTADOS: O total de mulheres foi 47 (79,7%), sendo 55,9% com IMC entre 40-49,9 kg/m². No sexto mês depois da operação os escores de qualidade de vida foram significativamente maiores do que no pré-operatório (p<0,05) e 27 (67,5%) pacientes tinham todas comorbidades resolvidas, 48 (81,3%) apresentaram conceito BAROS muito bom ou excelente. Após três e seis meses 16 e 23 pacientes apresentaram algum distúrbio nutricional, respectivamente. Não houve relação entre a perda do excesso de peso e qualidade de vida entre pacientes com ou sem distúrbio nutricional. CONCLUSÃO: os distúrbios nutricionais são pouco frequentes no pós-operatório precoce e, quando presentes, têm pouca ou nenhuma influência na qualidade de vida e na perda do excesso de peso. .


Subject(s)
Animals , Humans , Mice , Antibodies, Monoclonal/immunology , Antigens, Tumor-Associated, Carbohydrate/immunology , Neoplasms/immunology , Polysaccharides/immunology , Antibody-Dependent Cell Cytotoxicity , Cell Line, Tumor , Epitopes , Fas Ligand Protein/analysis , Fas Ligand Protein/immunology , Glycosylation , Mice, Inbred BALB C , Mice, Inbred DBA , Mannose/analysis , Vaccination
15.
Femina ; 42(3): 129-134, maio-jun. 2014. ilus
Article in Portuguese | LILACS | ID: lil-749129

ABSTRACT

Trichomonas vaginalis é um agente infectante da microbiota vaginal que vem sendo correlacionado ao câncer cervical. Um receptor denominado alectina-1 (Gal 1) pode ser expresso em células epiteliais cervicais humanas se ligando à glicofosfolipídica (LPG) de T. vaginalis. A interação de T. vaginalis com as células epiteliais é mediada por cadeias galactose e N-acetilglucosamina (LacNac). Gal 1 se liga aos sítios poly-LacNAC e está relacionada com a aderência de T. vaginalis à célula humana. A sinalização ocorre por intermédio de sítios da proteína Src (SH2) que se associam, ocorrendo sob os domínios de PI3K que fosforilam a membrana de lípides fosfatidilinositol (PIP e PIP2). Aderindo-se às membranas citoplasmáticas e secretando enzimas, T. vaginalis pode ocasionar a ruptura do envoltório celular podendo fagocitar células epiteliais em meio vaginal. O núcleo N-acetilactosamina de Gal 1 pode mediar a regulação do crescimento celular com a ajuda da proteína GRB2; entretanto, Gal 1 pode contribuir para a supressão da inflamação por meio da indução de apoptose pelas células T ativadas. (AU)


Trichomonas vaginalis is an infectious agent of the vaginal flora which has been associated with cervical cancer. Galectin-1 (Gal 1) is a cell receptor expressed in cervical epithelial cells binding T. vaginalis? lipophosphoglican (LPG). Interaction between T. vaginalis and the epithelial cell is mediated by poly-LacNac domains (galactoside and acetil-lactosamin) and is related to cell adherence as well. Cell signaling occurs by the time Src (SH2) domains are correlated with this interaction and PI3K phosphorilation brings up phosphatidil inositol lipid membranes (PIP and PIP2). T. vaginalis adheres to cytoplasm membrane and secrets specific enzymes that probably lead to membrane rupture. Moreover this parasite may phagocyte epithelial cells in vaginal discharge. Gal 1 nucleus called N-acetil-lactosamin can mediate growth development through GRB2 protein and may contribute to inflammation suppression owing to apoptosis induction of activated T cells.(AU)


Subject(s)
Humans , Female , Trichomonas vaginalis/cytology , Trichomonas vaginalis/physiology , Trichomonas vaginalis/pathogenicity , Signal Transduction , Uterine Cervical Neoplasms/parasitology , Galectin 1 , Platelet-Derived Growth Factor , Epidemiologic Factors , Apoptosis , Fas Ligand Protein
16.
Arab Journal of Gastroenterology. 2014; 15 (1): 6-11
in English | IMEMR | ID: emr-168631

ABSTRACT

This study aimed to find out non-invasive markers for the assessment of severity of non-alcoholic steatohepatitis [NASH] in an attempt to decrease the need for liver biopsy. It also aimed to evaluate the key role of apoptosis in the pathogenesis of the disease and the suggested role of anti-apoptotic factors in therapeutic modalities and disease prognosis. The serum levels of soluble Fas [s. Fas], s. Fas ligand, cytokeratin 18 [CK-18] fragment and Bcl-2 were measured in 80 patients and 15 non-hepatic subjects as control. The patients were divided based on histological examination of liver biopsy into three groups. Group I included 40 patients with NASH, group II had 40 patients with non-alcoholic fatty liver disease [NAFLD] non-NASH and group III had 15 non-hepatic subjects as control. Apoptosis of hepatocytes was assessed by morphological examination using a light microscope and expressed as number per square millimeter. There was a significant increase in the serum levels of s. Fas, s. Fas ligand and CK-18 fragments in the NASH group. The anti-apoptotic protein Bcl-2 showed significantly low levels in NASH patients. Apoptosis of hepatocytes was significantly higher in the NASH group. The degree of apoptosis was inversely correlated with the level of Bcl-2. A significant correlation between both s. Fas and CK-18 fragment with liver histology with regard to lobular inflammation and ballooning was found. Increased serum levels of s. Fas and CK-18 fragment in the NASH group and its correlation with the severity of disease suggested the key role of apoptosis in NASH pathogenesis which can be used for the assessment of the severity of NASH. A high level of anti-apoptotic Bcl-2 in NAFLD suggests its protective role in disease progress


Subject(s)
Humans , Male , Female , Apoptosis , fas Receptor , Fas Ligand Protein , Biomarkers , Biopsy/statistics & numerical data , Hospitals, University , Ultrasonography/statistics & numerical data , Enzyme-Linked Immunosorbent Assay/methods
17.
Article in English | WPRIM | ID: wpr-351097

ABSTRACT

Over-expression of Fas ligand (FasL) on tumor cell surface can induce the apoptosis of specific activated tumor infiltrating lymphocytes (TILs) via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and promoting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a target gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target (E/T) ratio of MCF-7 cells and Jurkat cells was 10:1, 5:1 and 1:1, the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16% and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associated with FasL expression, and FasL is a target gene of miR-21. miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tumor immune privilege.


Subject(s)
Apoptosis , Genetics , Breast Neoplasms , Genetics , Fas Ligand Protein , Metabolism , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic , Humans , MCF-7 Cells , MicroRNAs , Genetics , Signal Transduction
18.
Article in English | WPRIM | ID: wpr-50497

ABSTRACT

OBJECTIVES: To examine the expression profile of Fas-Fas ligand (FasL) during glutamate (Glu)-induced spiral ganglion cell (SGC) apoptosis. METHODS: Cultured SGCs were treated with 10-mM, 25-mM, and 50-mM concentrations of Glu and incubated for 24 or 48 hours. The expression intensity of FasL, Fas, caspase 3, and morphology of single SGC were evaluated using immunofluorescence staining. RESULTS: In semiquantitative analysis of the Glu-treated SGC, FasL, and caspase 3 expression intensity were increased with concentration- and time-dependent manner. Fas expression intensity did not change with different concentration at 48 hours. In morphologic analysis of the Glu-treated SGC, number of apoptotic cells were increased with concentration- and time-dependent manner. CONCLUSION: FasL was expressed in apoptotic SGCs, suggesting that the Fas-FasL signaling pathway may be involved in the Glu-induced apoptosis of dissociated SGCs.


Subject(s)
Apoptosis , Caspase 3 , Fas Ligand Protein , Fluorescent Antibody Technique , Glutamic Acid , Spiral Ganglion
19.
Acta cir. bras ; 28(7): 518-522, July 2013. ilus, graf, tab
Article in English | LILACS | ID: lil-679084

ABSTRACT

PURPOSE: To investigate the expression of FAS ligand (FASL) in ipsilateral and contralateral testicles of rats submitted to ischemia/reperfusion. METHODS: Wistar rats (n=21) distributed into groups control (GC), n=5, testicular exposure; ischemia (GI), (n=8), Torsion in the left testicular Cord (TCT) for three hours followed by orchiectomy without distortion and orchietomy of the contralateral testicle after 24 hours; and reperfusion (GR), (n=8), left TCT for 3 hours and distortion and repositioning on the scrotum and bilateral orchiectomy after 24 hours. Quantification of the FASL expression by immune-histochemistry. RESULTS: Statistical analysis showed similarity between GC and GI (p>0.05), differences detected are concentrated on the GR (p<0.05), increase in immunoexpression of FASL in the subgroups Right GR (406.8+-61.5) and Left GR (135.3 +-28.9) with significant predominance in the GR subgroup. CONCLUSION: Ischemia/reperfusion increased the FASL expression significantly in contralateral testicles in GR, in rats.


Subject(s)
Animals , Male , Rats , Fas Ligand Protein/analysis , Ischemic Preconditioning/methods , Spermatic Cord Torsion/metabolism , Testis/metabolism , Immunohistochemistry , Orchiectomy , Rats, Wistar , Time Factors , Testis/blood supply
20.
Braz. j. med. biol. res ; 46(1): 71-80, 11/jan. 2013. graf
Article in English | LILACS | ID: lil-665802

ABSTRACT

Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.


Subject(s)
Humans , Apoptosis/drug effects , Cell Survival/drug effects , Diterpenes/pharmacology , Glioblastoma/drug therapy , Mikania/chemistry , Cell Line, Tumor , /drug effects , /drug effects , Diterpenes/isolation & purification , Fas Ligand Protein , Flow Cytometry , Glioblastoma/enzymology , Glioblastoma/pathology , Real-Time Polymerase Chain Reaction , Signal Transduction , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL