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1.
Braz. j. biol ; 84: e254646, 2024. tab, ilus
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1360224

RESUMEN

Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague-Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.


O estresse crônico (SC) pode contribuir para a disfunção em vários órgãos, incluindo fígado e rim. Este estudo foi realizado para investigar as alterações na bioquímica sérica, estrutura histológica, bem como na localização de proteínas tirosina fosforiladas (TyrPho) e proteína de choque térmico 70 (Hsp-70) em tecidos hepáticos e renais de ratos CS induzidas por dois estressores (restrito e natação forçada) por 60 dias consecutivos. Amostras de sangue, fígado e rim foram coletadas de ratos Sprague-Dawley machos adultos em cada grupo. Nossos resultados mostraram que os parâmetros bioquímicos séricos, incluindo corticosterona, glicemia, nitrogênio ureico, creatinina, colesterol, triglicerídeos, HDL-C, LDL-C, ALT, AST, fosfatase alcalina no grupo CS foram significativamente diferentes do grupo normal em ambos os fígados e tecidos renais. Embora a estrutura histológica não tenha sido alterada, a expressão de TyrPho aumentou significativamente no lisado hepático, mas diminuiu significativamente no rim. A expressão de Hsp-70 no fígado aumentou, enquanto que no rim diminuiu. Em conclusão, a CS pode induzir alterações nas funções hepáticas e renais.


Asunto(s)
Ratas , Estrés Fisiológico , Ratas Sprague-Dawley , Riñón/anatomía & histología , Hígado/anatomía & histología
2.
China Pharmacy ; (12): 361-367, 2024.
Artículo en Chino | WPRIM | ID: wpr-1006624

RESUMEN

OBJECTIVE To evaluate the efficacy and safety of tyrosine kinase inhibitors (TKI) in the treatment of HER2- positive breast cancer in order to provide evidence-based evidence for clinical medication. METHODS Retrieved from CNKI, Wanfang database, VIP, PubMed, Cochrane Library, Embase and Web of Science, randomized controlled trial (RCT) about TKI (trial group) versus drugs excluding TKI (control group) in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software. RESULTS Total of 24 RCT studies were included, involving 15 538 HER2-positive breast cancer patients. The meta- analysis results showed that compared with the control group, the progression-free survival (PFS) [HR=0.91, 95%CI (0.80, 1.02), P=0.12], overall survival (OS) [HR=0.95, 95%CI (0.89, 1.01), P=0.11], objective response rate (ORR) [OR=1.21, 95%CI (0.86, 1.69), P=0.27], and pathological complete response rate (pCR) [OR=1.44, 95%CI (0.91, 2.27), P=0.12] had no statistically significant difference in the trial group; among the 3/4 grade ADRs, the trial group had a higher incidence of anemia [OR=1.77, 95%CI (1.16,2.70), P=0.008], rash [OR=11.26, 95%CI (7.32,17.31), P<0.000 01], paronychia [OR=8.67, 95%CI(1.62,46.53), P=0.01], diarrhea [OR=10.17, 95%CI(5.03,20.58), P<0.000 01], oral mucositis inflammation [OR= 9.34, 95%CI (3.13, 27.83), P<0.000 1], elevated aspartate aminotransferase [OR=2.09, 95%CI (1.13,3.84), P=0.02], and hypokalemia [OR=2.37, 95%CI (1.31,4.30), P=0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group, TKI could improve OS and ORR (P<0.05), while compared with trastuzumab, TKI had no advantage in PFS, OS, ORR, and pCR, and TKI combined with trastuzumab could significantly improve PFS, OS, ORR, and pCR compared with the trastuzumab group (P< 0.05). Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low. CONCLUSIONS Compared with trastuzumab, TKI has no advantages in PFS, OS, ORR and pCR in the treatment of HER2- positive breast cancer, but TKI combined with trastuzumab can significantly improve PFS, OS, ORR and pCR; TKI can increase the risk of grade 3/4 anemia, rash, paronychia, diarrhea, oral mucositis, elevated aspartate aminotransferase, and hypokalemia.

3.
Journal of Prevention and Treatment for Stomatological Diseases ; (12): 178-187, 2024.
Artículo en Chino | WPRIM | ID: wpr-1006519

RESUMEN

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

4.
China Pharmacy ; (12): 890-895, 2024.
Artículo en Chino | WPRIM | ID: wpr-1013556

RESUMEN

Tyrosine kinase inhibitors (TKIs) represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor (GIST). Imatinib, sunitinib, regorafenib, ripretinib, and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring (TDM) of these five drugs, finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them, the absorption of imatinib, regorafenib, and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water, regorafenib is taken with a low-fat meal, while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 (CYP3A4), and when used in combination with CYP3A4 inducers or inhibitors, drug exposure levels will significantly change; apart from metabolic enzymes, the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently, research on TDM for TKIs is still in the exploratory stage, with a substantial amount of literature reporting the effective concentrations of imatinib, sunitinib and regorafenib. However, the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently, there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay, chromatography, and surface-enhanced Raman spectroscopy, providing a technical basis for clarifying the therapeutic window of TKIs.

5.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 100-108, 2024.
Artículo en Chino | WPRIM | ID: wpr-1012698

RESUMEN

ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice. MethodMale ICR mice were randomized into normal, model, paroxetine (20 mg·kg-1), and low- and high-dose (3.27, 6.54 g·kg-1, respectively) Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin (DCX) in the dentate gyrus (DG) of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB)/extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway in the hippocampus. ResultCompared with the normal group, the model group showed decreased sucrose preference rate, increased immobility time in the tail suspension test (P<0.01), and reduced residence time in the central area of the open field and the total movement distance (P<0.05, P<0.01). In addition, the modeling elevated the corticosterone level in the serum (P<0.01), decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area, reduced the expression of DCX in the DG area, and down-regulated the protein levels of BDNF, phosphorylated (p)-TrkB, p-ERK, and p-CREB in the hippocampus (P<0.05, P<0.01). Compared with the model group, low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference, open field, and tail suspension tests (P<0.05, P<0.01), and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests (P<0.05, P<0.01). In addition, Wenxiao powder lowered the serum corticosterone level (P<0.01) and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover, Wenxiao powder at both doses promoted the expression of DCX in the DG area, and high-dose Wenxiao powder up-regulated the protein levels of BDNF, p-TrkB, p-ERK, and p-CREB in the hippocampus (P<0.05, P<0.01). ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.

6.
Braz. j. biol ; 842024.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469354

RESUMEN

Abstract Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male SpragueDawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.


Resumo O estresse crônico (SC) pode contribuir para a disfunção em vários órgãos, incluindo fígado e rim. Este estudo foi realizado para investigar as alterações na bioquímica sérica, estrutura histológica, bem como na localização de proteínas tirosina fosforiladas (TyrPho) e proteína de choque térmico 70 (Hsp-70) em tecidos hepáticos e renais de ratos CS induzidas por dois estressores (restrito e natação forçada) por 60 dias consecutivos. Amostras de sangue, fígado e rim foram coletadas de ratos Sprague-Dawley machos adultos em cada grupo. Nossos resultados mostraram que os parâmetros bioquímicos séricos, incluindo corticosterona, glicemia, nitrogênio ureico, creatinina, colesterol, triglicerídeos, HDL-C, LDL-C, ALT, AST, fosfatase alcalina no grupo CS foram significativamente diferentes do grupo normal em ambos os fígados e tecidos renais. Embora a estrutura histológica não tenha sido alterada, a expressão de TyrPho aumentou significativamente no lisado hepático, mas diminuiu significativamente no rim. A expressão de Hsp-70 no fígado aumentou, enquanto que no rim diminuiu. Em conclusão, a CS pode induzir alterações nas funções hepáticas e renais.

7.
Clinics ; 79: 100329, 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1534245

RESUMEN

Abstract Objectives To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations. Methods Patients received oral infigratinib 125 mg (IN cohort, n = 125) or oral larotrectinib (LB cohort, n = 105) until unacceptable toxicity or disease progression. Results Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5-6.25] months vs. 5.5 [6-5.25] months, p < 0.0001). Patients with partial responses (p = 0.0424) and overall survival (p = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (p = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (p = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (p = 0.048). Conclusions Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.

8.
Indian J Pathol Microbiol ; 2023 Sept; 66(3): 560-563
Artículo | IMSEAR | ID: sea-223477

RESUMEN

Background: Chronic myeloid leukemia (CML) is relatively rare in pediatric and adolescent age groups. The purpose of this study was to evaluate the clinical, hematopathological, and biochemical parameters of CML in pediatric and adolescent age groups, along with an assessment of the treatment response with first-line tyrosine kinase inhibitors (TKI) and its correlation with the prognostic scoring systems of adults. Materials and Methods: A retrospective study of 44 Breakpoint Cluster Region-Abelson leukemia virus (BCR-ABL1)-positive pediatric and adolescent CML cases registered at our hospital was done. The clinical and laboratory parameters were evaluated using hospital software. The treatment response was monitored and scoring was performed using mathematical calculations. Results: The mean age was 11.6 (±4.7) years. The median hemoglobin was 8.4 g/dL and 63.6% of the cases showed white blood cell (WBC) counts >250,000/?L. The average follow-up was 21 months. A total of 97.7 and 78.1% cases achieved complete hematological response (CHR) and molecular response, respectively, during the treatment course. The maximum number of patients had low Sokal and European treatment and Outcomes Study (EUTOS) scores. Seventy-five per cent of the cases achieved CHR at 3 months, while 73.6 and 78.6% CML-Chronic phase (CP) cases with low Sokal and EUTOS scores achieved CHR at 3 months, respectively. Conclusion: This study revealed that the CML cases in pediatric and adolescent age groups are normally present with higher WBC counts at the time of diagnosis. The association of the prognostic scoring system with treatment response was statistically insignificant. However, a larger cohort study is needed to determine the treatment response of TKI in children and adolescent CML and its correlation with the prognostic scoring systems.

9.
Indian J Ophthalmol ; 2023 Apr; 71(4): 1657-1658
Artículo | IMSEAR | ID: sea-224985
10.
Artículo | IMSEAR | ID: sea-225675

RESUMEN

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

11.
Acta Pharmaceutica Sinica ; (12): 2226-2238, 2023.
Artículo en Chino | WPRIM | ID: wpr-999153

RESUMEN

Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

12.
China Pharmacy ; (12): 2695-2700, 2023.
Artículo en Chino | WPRIM | ID: wpr-998551

RESUMEN

OBJECTIVE To analyze the patents of new target oral drugs for type 2 diabetes mellitus (T2DM), and to provide references for the research and development direction and patent layout of new domestic diabetes drugs. METHODS Based on global patent data in the HimmPat database, from multiple perspectives such as the number of patent applications and authorization, development trend, regional distribution and main applicants, statistics and analysis were performed for the patents related to 3 types of new target oral drugs for T2DM, such as glucokinase activator (GKA), protein tyrosine phosphatase 1B inhibitor (PTP-1B-IN), and 11β-hydroxysteroid dehydrogenase 1 inhibitor (11β-HSD1-IN). RESULTS & CONCLUSIONS A total of 1 649 patents of GKA, 709 patents of PTP-1B-IN, 592 patents of 11β-HSD1-IN were obtained, the main applicants were well-known pharmaceutical companies, which possessed the core patents of pharmaceutical compounds. The research on GKA drugs was more mature, with a larger number of patent applications and a more comprehensive enterprise layout. Domestic enterprises, universities and research institutions had advantages in the field of PTP-1B-IN. Domestic enterprises and research institutions can leverage the advantages of traditional Chinese medicine and resources to enhance their research capabilities and improve technological competitiveness through core technology exploration, the exploration of process route, patent layout, industry- university-research cooperation and the establishment of patent pool.

13.
Journal of Public Health and Preventive Medicine ; (6): 132-135, 2023.
Artículo en Chino | WPRIM | ID: wpr-998541

RESUMEN

Objective To explore the relationship between serum levels of tyrosine hydroxylase (TH) and the risk of cerebral infarction in Parkinson's patients. Methods A total of 129 patients with confirmed Parkinson's disease who were hospitalized in our hospital were selected, among the 58 patients had Parkinson's disease complicated with cerebral infarction (complicated with cerebral infarction group), and the remaining 71 patients had Parkinson's disease alone (control group). Blood TH levels and other potential related information were collected retrospectively at the time of diagnosis. Comparative analysis of data was performed using SPSS software. Results Comparing the serum TH expression levels in patients with Parkinson's disease and patients with cerebral infarction at admission , the serum TH level in patients with cerebral infarction was lower. Results also showed that the levels of CRP, IL-6, MDA, and Hcy were higher in patients with cerebral infarction, while PON-1 level was lower. In addition, patients with cerebral infarction had lower motor ability (higher UPDRS Ⅲ score). Further regression analysis was carried out with the occurrence of Parkinson's disease complicated with cerebral infarction as the dependent variable and the potential influencing factors as the independent variable. The results indicated that factors such as low expression of TH, high expression of inflammatory factors, and high expression of oxidative stress factors were positively correlated with the risk of complications of the two diseases. Conclusion The low expression of TH, inflammatory state and high oxidative stress state are the potential risk factors for Parkinson's disease complicated with cerebral infarction, which deserves clinical attention.

14.
Chinese Journal of Lung Cancer ; (12): 874-880, 2023.
Artículo en Chino | WPRIM | ID: wpr-1010095

RESUMEN

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR are effective in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. With the application and expansion of individualized and combined therapy, more and more studies have shown that combined administration of Metformin effectively solves the problem of acquired drug resistance to EGFR-TKIs in clinical treatment and prolongs the survival of patients with NSCLC. EGFR-TKIs combined with Metformin is expected to be the treatment method of choice for NSCLC patients with EGFR-TKIs resistance. This paper intends to summarize the research progress of EGFR-TKIs combined with Metformin in the treatment of EGFR-TKIs acquired resistance in NSCLC, in order to provide a new idea for the treatment of NSCLC patients with acquired resistance to EGFR-TKIs.
.


Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Metformina/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/metabolismo , Resistencia a Antineoplásicos , Mutación
15.
Chinese Journal of Oncology ; (12): 31-38, 2023.
Artículo en Chino | WPRIM | ID: wpr-969802

RESUMEN

Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.


Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares/cirugía , Consenso , Mutación , Receptores ErbB/genética , Éteres Corona/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico
16.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 1499-1506, 2023.
Artículo en Chino | WPRIM | ID: wpr-997060

RESUMEN

@#The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.

17.
China Pharmacy ; (12): 2525-2529, 2023.
Artículo en Chino | WPRIM | ID: wpr-997013

RESUMEN

OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group (32 cases), anlotinib combined chemotherapy group (24 cases) and bevacizumab combined chemotherapy group (28 cases). Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection, and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy, patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally, once a day, for 14 consecutive days and 7 days of discontinuation, based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy, based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles, with one cycle every three weeks. The overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and the changes of serum tumor markers were compared among three groups before and after treatment; meanwhile, the occurrence of adverse drug reactions was recorded, and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles, ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group (P<0.05); mPFS of the two groups were significantly longer than chemotherapy group, and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group (P<0.05). After 4 treatment cycles, the serum levels of tumor markers in three groups were significantly lower than before treatment, and both combined chemotherapy groups were significantly lower than chemotherapy group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions such as nausea, vomiting, bone marrow suppression, and 1-year survival rate among the three groups of patients (P>0.05). CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.

18.
Malaysian Journal of Medicine and Health Sciences ; : 341-343, 2023.
Artículo en Inglés | WPRIM | ID: wpr-996802

RESUMEN

@#Madam S, who diagnosed to have stage IV lung adenocarcinoma with exon 21 L858R point mutation (T3N2M1a) was admitted for massive pericardial effusion in April 2016. She was ECOG 4 on admission. Her ECOG improved to 1 after pericardial tapping and initiation of free sample erlotinib 100 mg daily. Repeated CT thorax post treatment showed the disease was partial responded. Due to financial constraints, she had never bought any EGFR-TKI. She was given a free sample of erlotinib intermittently for total of 12 months followed by intermittent afatinib supply for 2 years. Due to this limited supply, she took half doses of afatinib by cutting a 40 mg tablet once every few days to sustain the continuation of cancer treatment. No major side effects were observed and she remained ECOG 0 with good weight gain. Up to her last clinic visit in September 2021, her PFS was more than 5 years. Intermittent doses of EGFR-TKI may prolong PFS in patients with advanced EGFRm+ NSCLC who has limited treatment options.

19.
Chinese Journal of Biologicals ; (12): 947-954, 2023.
Artículo en Chino | WPRIM | ID: wpr-996564

RESUMEN

@#Objective To evaluate the effect of tyrosine kinase inhibitor BGJ398 on the proliferation,apoptosis and migration of human hepatocellular cancer Huh-7 cells and explore the mechanism.Methods The effects of 10 tyrosine kinase inhibitors on the survival of Huh-7 cells were detected by MTT assay,and the sensitivity of Huh-7 cells to BGJ398 was analyzed by single-target kinetic equation and biphasic kinetic equation respectively.Huh-7 cells were added with 10,30 and 90 nmol/L BGJ398 respectively,and the control group(without drugs)was set.The effects of BGJ398 on the apoptosis and cell cycle of Huh-7 cells were detected by flow cytometry after culturing at 37℃for 24 h,the effect on the migration ability was detected by wound healing assay and the effect on the expression of multiple pathway-related proteins was detected by Western blot.Results All of 10 tyrosine kinase inhibitors inhibited the proliferation of Huh-7 cells,among which Huh-7 cells were most sensitive to BGJ398 and the IC_(50)was(0.020±0.013)μmol/L;The response of Huh-7 cells to BGJ398 was composed of two phases with F_1 accounted for 92.8%(K_(d1)was 36 nmol/L)and F_2 accounted for 7.2%(K_(d2)>1 000μmol/L).Compared with the control group,the apoptosis rate and the percentage of Huh-7 cells in G1 phase increased significantly in 30 and 90 nmol/L BGJ398 groups(t=-6.407~-4.459,each P<0.05),while the percentage of Huh-7 cells in S phase decreased significantly in 10,30 and 90 nmol/L BGJ398 groups(t=2.982,7.859 and 12.425,respectively,each P<0.05);After 24 and 48 h of scratching,the scratch area of 30 and 90 nmol/L BGJ398groups decreased significantly(t=5.376~18.197,each P<0.05);The expression levels of phosphorylated fibroblast growth factor receptor(FGFR)and phosphorylated extracellular signal-regulated kinase 1/2(Erk1/2)protein decreased significantly in 30 and 90 nmol/L BGJ398 groups(t=4.015~6.729,each P<0.01).Conclusion BGJ398 can inhibit the proliferation and migration of human hepatocellular cancer Huh-7 cells,induce apoptosis and cell cycle arrest,which might be achieved by inhibiting FGFR phosphorylation and MAPK signaling pathway.BGJ398 is expected to be a potential agent for the treatment of hepatocellular cancer.

20.
Chinese Journal of Biologicals ; (12): 668-672+679, 2023.
Artículo en Chino | WPRIM | ID: wpr-996446

RESUMEN

@#Objective To investigate the effect of a multi-target protein tyrosine kinase inhibitor,Ponatinib,on proliferation,homogeneity adhesion and migration ability of human liver cancer cell line SK-Hep-1.Methods SK-Hep-1 cells were cultured routinely and added with 24 tyrosine kinase inhibitors such as Ponatinib respectively,and the effect of Ponatinib on the survival and proliferation of SK-Hep-1 cells was detected by MTT assay.SK-Hep-1 cells were cultured routinely until the fusion degree reached 90%,then added with 0.1,0.5 and 1.0 μmol/L Ponatinib respectively,and the control group(without Ponatinib) was set up.The effect of Ponatinib on adhesion ability of SK-Hep-1 cells was detected by cell slow aggregation assay and dissociation assay,while the effect on migration ability by scratch test,and the effect on E-cadherin protein expression in SK-Hep-1 cells by Western blot.Results All 24 tyrosine kinase inhibitors inhibited SK-Hep-1 cells,among which Ponatinib showed the strongest inhibitory effect with a IC_(50) of(0.288±0.044) μmol/L.Compared with the control group,the number of cell mass(t=16.143,44.002 and 44.853 respectively,each P <0.001) and N_(TC)/N_(TE) [ratio of single cell number(N) after digestion by trypsin containing EDTA(TE) and CaCl_2(TC)](t=4.276,10.625 and 27.571 respectively,each P <0.05) decreased significantly and E-cadherin protein expression increased significantly(t=-3.757,-4.561and-6.922 respectively,each P <0.05) in 0.1,0.5 and 1.0 μmol/L Ponatinib groups;Scratch migration rate significantly decreased in 0.5 and 1.0 μmol/L Ponatinib groups(t=6.272~16.733 respectively,each P <0.01),while there was no significant difference in 0.1 μmol/L Ponatinib group(t=0.473 and 0.872 respectively,each P> 0.05) after 24 h and 48 h of scratch.Conclusion Ponatinib inhibited proliferation and migration of SK-Hep-1 cells and promoted cell adhesion.

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