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1.
Article in Chinese | WPRIM | ID: wpr-878694

ABSTRACT

Objective To evaluate the effect of methylprednisolone sodium succinate combined with tropisetron on postoperative nausea and vomiting(PONV)under microvascular decompression of hemifacial spasm.Methods From January to June 2019,485 patients undergoing microvascular decompression for facial spasm at Department of Neurosurgery,Peking University People's Hospital were randomly assigned into two groups with random number table method.For group A(n=242),2 ml saline was administrated by intravenous drip before induction and 5 mg tropisetron after operation.For group B(n=243),40 mg methylprednisolone sodium succinate was administrated by intravenous drip before induction and 5 mg tropisetron after operation.The anesthesia time,operation time,and incidence of PONV in 0-24 h and 24-48 h were recorded for the comparison of the remedial treatment rate of nausea and vomiting between the two groups.Results There was no significant difference in age,gender,smoking history,body mass index value,American Society of Anesthesiologists score,medical history,surgical side,PONV history,operation time or anesthesia time between the two groups(all P > 0.05).The incidence of PONV in group A was 35.5% and 18.2% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(18.5%,χ


Subject(s)
Antiemetics , Double-Blind Method , Hemifacial Spasm/surgery , Humans , Indoles , Methylprednisolone Hemisuccinate/therapeutic use , Microvascular Decompression Surgery , Tropisetron
2.
Chinese Journal of Oncology ; (12): 807-816, 2020.
Article in Chinese | WPRIM | ID: wpr-877492

ABSTRACT

Anlotinib hydrochloride is the only anti-angiogenic, multi-targeted tyrosine kinase inhibitor, which has been approved for non-small cell lung cancer and small cell lung cancer in China. In order to provide guidance for clinical practitioners to use anlotinib hydrochloride safely and efficiently, the Chinese Association for Clinical Oncologists, the Expert Committee of Vascular Targeted Therapy of Chinese Society of Clincal Oncology and the Cancer Targeted Therapy Professional Committee of China Anti-Cancer Association co-organized experts and integrated multiple evidences of Anlotinib Hydrochloride, from both clinical trial, post-marketed clinical data and the associated experiences of experts accumulated in clinical practice, etc. The present consensus covers the clinical data of anlotinib hydrochloride applied in advanced non-small cell lung cancer and small cell lung cancer, and the safety management recommendations.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , China , Consensus , Humans , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinolines/therapeutic use
3.
Article in English | WPRIM | ID: wpr-827415

ABSTRACT

OBJECTIVES@#To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α.@*METHODS@#After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells.@*RESULTS@#The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all <0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all <0.05).@*CONCLUSIONS@#TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.


Subject(s)
Animals , Imidazoles , Indoles , Insulin , Islets of Langerhans , Swine , Tumor Necrosis Factor-alpha , Genetics
4.
Article in English | WPRIM | ID: wpr-880736

ABSTRACT

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).


Subject(s)
Adult , COVID-19/drug therapy , China , Darunavir , Drug Combinations , Female , Humans , Indoles/therapeutic use , Lipid Metabolism , Lopinavir , Male , Middle Aged , Protease Inhibitors/therapeutic use , Retrospective Studies , Ritonavir , SARS-CoV-2/genetics
5.
Journal of Experimental Hematology ; (6): 2039-2045, 2020.
Article in Chinese | WPRIM | ID: wpr-880012

ABSTRACT

OBJECTIVE@#To compare the effect of Sheng-Xue-Xiao-Ban Capsule (SXXBC) and indirubin to the peripheral platelets of the Idiopathic thrombocytopenic purpura (ITP) model mouse.@*METHODS@#The ITP mouse model was established by the method of passive immunization. SXXBC and indirubin were used for intervention treatment. Then the hemorrhagic phenomena of ITP mice were observed and the numbers of peripheral platelets, hemoglobin and white blood cells, bone marrow megakaryocytes and their classification and coagulation function were detected and compared.@*RESULTS@#The improvement rate of hemorrhage in SXXBC group was 40% for small dose, 60% for medium dose and 80% for high dose, while the improvement rate of hemorrhage in indirubin group was 30% for small dose, 50% for medium dose and 60% for high dose. There was no statistically significant difference in the improvement rate of hemorrhage between the two groups (P>0.05). Compared with the model control group, PLT and Hb increased in different doses of SXXBC and indirubin group 4th-8th day after drug intervention (P<0.05, 0.01). However, there was no significant difference between the different doses of SXXBC group and indirubin group (P>0.05). Compared with the model control group, the WBC in each group was significantly lower (P<0.05, 0.01) on the 4th-8th day after drug intervention; However, there was no statistical significance between the two groups of SXXBC and indirubin (P>0.05). Compared with the model control group, the total number of megakaryocytes in each treatment group were decreased (P<0.05, P<0.01), in which the number of primary megakaryocytes in the large and medium dose groups of SXXBC and indirubin were decreased (P<0.05, 0.01), and the number of juvenile megakaryocytes in the large dose group of SXXBC and indirubin were also decreased (P<0.05). The number of granular megakaryocytes were decreased in each intervention groups (P<0.05, 0.01), and the number of thromocytogenic megakaryocyte was increased in the high and medium dose groups of SXXBC and indirubin (P<0.01). The time of prothrombin was shortened in the high and medium dose groups of SXXBC and indirubin (P<0.05), and the fibrinogen (FIB) content in the high and medium dose groups of SXXBC was close to that of the normal control group.@*CONCLUSION@#Both of the SXXBC and the indirubin standard all show good hemostatic effects. Indirubin shows a positive effect on increasing the peripheral platelet and hemoglobin in ITP model mice, regulating the immune response, reducing the total number of bone marrow megakaryocytes, increasing the thromocytogenic megakaryocyte, and increasing coagulation function.


Subject(s)
Animals , Blood Platelets , Capsules , Indoles , Megakaryocytes , Mice , Purpura, Thrombocytopenic, Idiopathic/drug therapy
6.
Rev. chil. enferm. respir ; 35(4): 287-292, dic. 2019.
Article in Spanish | LILACS | ID: biblio-1092709

ABSTRACT

La historia natural de la fibrosis pulmonar idiopática (FPI) es heterogénea e impredecible. Aunque el curso de la enfermedad, sin tratamiento, es inevitablemente progresiva y de mal pronóstico. Los tratamientos históricos han variado desde corticosteroides e inmunosupresores (azatioprina, ciclofosfamida), hasta colchicina y N-acetilcisteína. En las últimas décadas se han realizado múltiples ensayos terapéuticos fallidos. Sin embargo, desde el año 2014 en los Estados Unidos, Europa y otros países, dos drogas, denominadas terapia antifibrótica o modificadoras de la enfermedad, están aprobadas para el tratamiento de la FPI: nintedanib y pirfenidona. La terapia antifibrótica, tiene como objetivo enlentecer en hasta 50% la declinación de la función pulmonar en pacientes con FPI.


The natural history of idiopathic pulmonary fibrosis (IPF) is heterogeneous and unpredictable. The course of the disease without treatment, is inevitably progressive, with a poor prognosis. Historical treatments have varied from corticosteroids and immunosuppressants (azathioprine, cyclophosphamide), to colchicine and N-acetylcysteine. In the last decades, multiple failed therapeutic trials have been carried out. However, since 2014 in the United States, Europe and other countries, two drugs, called antifibrotic therapy or disease modifiers, are approved for the treatment of IPF: nintedanib and pirfenidone. The purpose of antifibrotic therapy is to slow down the decline in lung function in patients with IPF up to 50%.


Subject(s)
Humans , Pyridones/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Immunosuppressive Agents/therapeutic use , Indoles/therapeutic use
7.
Article in Chinese | WPRIM | ID: wpr-773230

ABSTRACT

According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.


Subject(s)
Antineoplastic Agents , Pharmacology , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Indoles , Pharmacology , K562 Cells , Podophyllotoxin , Pharmacology , Structure-Activity Relationship
8.
Article in English | WPRIM | ID: wpr-776898

ABSTRACT

Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC being 5.11 ± 0.53 μmol·L, and acted as a noncompetitive inhibitor based on kinetic analysis.


Subject(s)
4-Butyrolactone , Chemistry , Pharmacology , Animals , Aspergillus , Chemistry , Chemistry Techniques, Analytical , Dipeptides , Chemistry , Pharmacology , Enzyme Inhibitors , Chemistry , Pharmacology , Indoles , Chemistry , Pharmacology , Molecular Structure , Mycobacterium tuberculosis , Peptides , Chemistry , Pharmacology , Polyketides , Chemistry , Pharmacology , Porifera , Microbiology , Protein Tyrosine Phosphatases , Chemistry
9.
J. bras. pneumol ; 45(5): e20180414, 2019. tab, graf
Article in Portuguese | LILACS | ID: biblio-1040274

ABSTRACT

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.


ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/administration & dosage , Aspartate Aminotransferases/analysis , Time Factors , Vomiting/chemically induced , Algorithms , Brazil , Vital Capacity/drug effects , Reproducibility of Results , Treatment Outcome , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Diarrhea/chemically induced , Drug Tolerance , Chemical and Drug Induced Liver Injury/etiology , Transaminases/analysis , Indoles/adverse effects , Nausea/chemically induced
11.
Braz. j. med. biol. res ; 52(1): e7715, 2019. tab, graf
Article in English | LILACS | ID: biblio-974276

ABSTRACT

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.


Subject(s)
Animals , Male , Rabbits , Diabetes Mellitus, Experimental , Aluminum Hydroxide/pharmacology , Glucose/analysis , Indoles/pharmacology , Liver/drug effects , Liver/metabolism , Insulin Resistance , Biomarkers/analysis , Nanoparticles
12.
Braz. j. med. biol. res ; 52(1): e7844, 2019. tab, graf
Article in English | LILACS | ID: biblio-974274

ABSTRACT

Necroptosis is a regulated cell death mechanism. However, it is unknown whether necroptosis is involved in the death of tumor necrosis factor-α (TNF-α)-treated osteoblasts. Therefore, we conducted the study with TNF-α, Nec-1 (a specific inhibitor of necroptosis), and Z-IETD-FMK (a specific inhibitor of apoptosis) to determine whether necroptosis plays a role in the death of TNF-α-treated osteoblast cell line MC3T3-E1. Cell viability, cell death, and lactate dehydrogenase (LDH) release were assayed to evaluate cytotoxicity. Specific marker proteins receptor interacting protein kinase (RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) for necroptosis, and cleaved caspase 3 for apoptosis were detected by western blot, and mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). We found that TNF-α inhibited cell proliferation in a dose- and time-dependent manner. Nec-1 plus Z-IETD-FMK restored cell viability and significantly decreased LDH release. In addition, TNF-α alone increased the cell population of AV+PI−, while Z-IETD-FMK caused a shift in the cell population from AV+PI− to AV+PI+. Furthermore, TNF-α significantly increased protein cleaved caspase 3. TNF-α plus Z-IETD-FMK significantly increased the proteins RIPK3 and MLKL phosphorylation in MC3T3-E1 cells, while the changes in mRNA levels of RIPK3, MLKL, and caspase 3 were not consistent with the changes in the corresponding protein expression levels. In conclusion, TNF-α induced preferentially apoptosis in osteoblast cell line and necroptosis played a decisive role when TNF-α-induced death was inhibited by the inhibitor of apoptosis. Combined treatment with Nec-1 and Z-IETD-FMK protected mouse osteoblasts from death induced by TNF-α.


Subject(s)
Animals , Rabbits , Osteoblasts/pathology , Tumor Necrosis Factor-alpha/pharmacology , Caspase 8/drug effects , Caspase Inhibitors/pharmacology , Necrosis/pathology , Oligopeptides/pharmacology , Osteoblasts/drug effects , Phosphorylation , Cell Survival/drug effects , Imidazoles/pharmacology , Indoles/pharmacology , L-Lactate Dehydrogenase/pharmacology
13.
Int. braz. j. urol ; 44(3): 600-607, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-954052

ABSTRACT

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.


Subject(s)
Humans , Male , Aged , Aged, 80 and over , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/drug therapy , Apoptosis/drug effects , Adrenergic alpha-1 Receptor Antagonists/pharmacology , Quinazolines/pharmacology , Reference Values , Sulfonamides/pharmacology , Time Factors , Biopsy , Prazosin/analogs & derivatives , Prazosin/pharmacology , Immunohistochemistry , Pilot Projects , Retrospective Studies , Treatment Outcome , Prostate-Specific Antigen/blood , Doxazosin/pharmacology , Tamsulosin , Indoles/pharmacology , Middle Aged
14.
Journal of Experimental Hematology ; (6): 1589-1597, 2018.
Article in Chinese | WPRIM | ID: wpr-773051

ABSTRACT

OBJECTIVE@#To screen the differentially expressed proteins at the early stage of K562 cells treated with meisoindigo by using tandem mass tags (TMT)-based proteomics technology, and to explore the mechanism for meisoindigo-inducing apoptosis.@*METHODS@#The half inhibitory concentration (IC) of mesoindigo on K562 cells was determined by CCK8. The flow cytometry was used to assay the apoptosis of K562 cells treated by meisoindigo or DMSO. Total proteins were extracted from the cells treated with 0.2% DMSO (control) or 20 μmol/L meisoindigo (Test) for 2 hours. Then, the TMT-labeling HPLC-MS/MS was used to identify and quantify the peptides and their abundance, all the tests were repeated for 3 times. The Mascot software was used to identify the proteins; the GO annotations, enrichment and cluster analysis were used to analyze the differentially expressed proteins.@*RESULTS@#Meisoindigo-induced K562 cell apoptosis in a dose-dependent manner (r=0.98), 5 544 proteins were identified, 4792 of which were quantified. The protein with expression difference>1.5-folds in Test group accoanted for 8, out of which the expression of 4 proteins were up-regulated and 4 were down-regulated. The differentially expressed proteins mainly associated with reactive oxygen species (ROS).@*CONCLUSION@#Several proteins including DDIT4 were found to have dramatic changes in the early stage of K562 cells treated with meisoindigo by using quantitative proteomics technology. The ROS metabolic process may play important roles in meisoindigo-inducing apoptosis of K562 cells.


Subject(s)
Apoptosis , Humans , Indoles , K562 Cells , Proteomics , Tandem Mass Spectrometry
15.
National Journal of Andrology ; (12): 247-253, 2018.
Article in Chinese | WPRIM | ID: wpr-689768

ABSTRACT

<p><b>Objective</b>To investigate the therapeutic effects of commonly used selective α-adrenergic receptor antagonists (α-ARA) on benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>PubMed, Embase and CNKI databases were searched for the literature about selective α-ARAs for the treatment of BPH and the information was extracted on the common adverse reactions in the course of treatment. Multivariate meta-analysis was conducted to investigate the therapeutic effects of different α-ARAs.</p><p><b>RESULTS</b>The total rates of adverse effects of silodosin and tamsulosin were the highest, 51.9% and 34.0% respectively, with the highest incidences of headache (38.3%), weakness (23.6%) and dizziness (17.5%). Besides, tamsulosin ranked the first in inducing sexual dysfunction of the male patients with BPH (70.4%).</p><p><b>CONCLUSIONS</b>Doxazosin is preferable as the first-choice treatment of BPH for its therapeutic effect and improvement of the patient's quality of life. Silodosin and tamsulosin, however, can be selectively used according to the patient's specific tolerance to different adverse effects.</p>


Subject(s)
Adrenergic alpha-Antagonists , Therapeutic Uses , Doxazosin , Therapeutic Uses , Humans , Indoles , Therapeutic Uses , Male , Network Meta-Analysis , Prostatic Hyperplasia , Drug Therapy , Quality of Life , Sexual Dysfunction, Physiological , Tamsulosin , Therapeutic Uses
16.
Chinese Journal of Lung Cancer ; (12): 428-430, 2018.
Article in Chinese | WPRIM | ID: wpr-772422

ABSTRACT

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
.


Subject(s)
Adenocarcinoma , Drug Therapy , Genetics , Pathology , Adenocarcinoma of Lung , Aged , Antineoplastic Agents , Therapeutic Uses , Humans , Indoles , Therapeutic Uses , Lung Neoplasms , Drug Therapy , Genetics , Pathology , Male , Mutation , Proto-Oncogene Proteins p21(ras) , Genetics , Metabolism , Quinolines , Therapeutic Uses
17.
Article in Chinese | WPRIM | ID: wpr-776579

ABSTRACT

OBJECTIVE@#To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms.@*METHODS@#Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed.@*RESULTS@#Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01).@*CONCLUSIONS@#Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.


Subject(s)
Animals , Apoptosis , Carcinoma, Hepatocellular , Cell Line, Tumor , Dipeptides , Humans , Indoles , Liver Neoplasms , Male , Mice , Mice, Inbred BALB C , Mitochondrial Proteins
18.
Article in English | WPRIM | ID: wpr-690633

ABSTRACT

There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.


Subject(s)
Acute Radiation Syndrome , Blood , Allergy and Immunology , Animals , Blood Cells , Radiation Effects , Dose-Response Relationship, Drug , Gamma Rays , Hydroxamic Acids , Therapeutic Uses , Indoles , Therapeutic Uses , Matrix Metalloproteinase Inhibitors , Therapeutic Uses , Mice , Radiation Injuries, Experimental , Blood , Allergy and Immunology , Radiation-Protective Agents , Therapeutic Uses , Spleen , Allergy and Immunology , Radiation Effects , Survival Analysis , Whole-Body Irradiation
19.
IBJ-Iranian Biomedical Journal. 2018; 22 (2): 99-106
in English | IMEMR | ID: emr-192456

ABSTRACT

Background: Acute myeloblastic leukemia [AML] is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia [APL] is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein [SALL4] is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-[1-[[2, 4-Aril]imino]-2,2,2-trifluoroethyl] phenyl-1H Indole-3- carbaldehyde [TFPHC], on the expression of SALL4


Methods: Cells were cultured and treated with different concentrations [75, 150, and 300 micro g/mL] of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR


Results: Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 micro g/mL concentrations


Conclusion: SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy


Subject(s)
Gene Expression , Cell Line, Tumor , Indoles , Promyelocytic Leukemia Zinc Finger Protein , Cells, Cultured , Transcription Factors
20.
Arch. endocrinol. metab. (Online) ; 61(5): 506-509, Sept.-Oct. 2017. graf
Article in English | LILACS | ID: biblio-887589

ABSTRACT

SUMMARY Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.


Subject(s)
Humans , Male , Middle Aged , Pancreatic Neoplasms/drug therapy , Neuroendocrine Tumors/drug therapy , Cinacalcet/administration & dosage , Hypercalcemia/drug therapy , Indoles/administration & dosage , Antineoplastic Agents/administration & dosage , Pancreatic Neoplasms/complications , Pyrroles/administration & dosage , Neuroendocrine Tumors/complications , Drug Therapy, Combination , Sunitinib , Hypercalcemia/etiology
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