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The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.
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RATIONALE: The morbidity and mortality of lung cancer rank the first among all kinds of cancer. In China, anaplastic lymphoma kinase-positive pulmonary tumors account for nearly 5% of non-small cell lung cancer (NSCLC), and these patients are quite likely to develop brain metastases, as high as around 45%. Although anaplastic lymphoma kinase-tyrosine kinase inhibitors crizotinib and alectinib have proved effective for controlling tumor metastases to the brain, drug resistance and disease progression cannot be ignored in the course of treatment. PATIENT CONCERNS: Most of the literature reports that traditional Chinese medicine (TCM) has produced satisfactory results in the treatment of cancer patients as an adjuvant treatment for various malignancies in a 53-year-old male patient who developed advanced NSCLC with brain metastases. As first-line crizotinib and erlotinib treatments were ineffective and the intracranial lesions progressed extensively, the patient chose to receive TCM treatment alone in the hope of prolonging his life and improving his quality of life. DIAGNOSES: A 53-year-old male patient who developed advanced NSCLC with brain metastasis. Because first-line crizotinib and alectinib have failed, and the intracranial lesions progressed in a large area. INTERVENTIONS: The patient requested that the final therapeutic strategy be Chinese medicine as monotherapy for long-term treatment. The patient took 30 mL of the decoction 1 hour after a meal, 3 times a day. The patient was not treated with dehydrating agents or diuretics during the TCM treatment. OUTCOMES: The improvement was obvious after 3 months of treatment, and significant reduction of cranial lesions. During the follow-up period, the patient developed neither severe liver damage nor kidney damage. LESSONS: This case is the first 1 in the world where TCM was introduced as monotherapy for severe conditions with extensive brain metastases and achieved remarkable efficacy.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Crizotinib/uso terapéutico , Neoplasias Pulmonares/patología , Medicina Tradicional China , Quinasa de Linfoma Anaplásico , Calidad de Vida , Neoplasias Encefálicas/secundario , Inhibidores de Proteínas Quinasas/uso terapéutico , Carbazoles/uso terapéuticoRESUMEN
The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. Mitochondria are the key organelles for the maintenance of myocardial tissue homeostasis. However, cardiotoxicity associated with BCR-ABL1 TKIs can directly or indirectly cause mitochondrial damage and dysfunction, playing a pivotal role in cardiomyocytes homeostatic system and putting the cancer survivors at higher risk. In this review, we summarize the cardiotoxicity caused by BCR-ABL1 TKIs and the underlying mechanisms, which contribute dominantly to the damage of mitochondrial structure and dysfunction: endoplasmic reticulum (ER) stress, mitochondrial stress, damage of myocardial cell mitochondrial respiratory chain, increased production of mitochondrial reactive oxygen species (ROS), and other kinases and other potential mechanisms of cardiotoxicity induced by BCR-ABL1 TKIs. Furthermore, detection and management of BCR-ABL1 TKIs will promote our rational use, and cardioprotection strategies based on mitochondria will improve our understanding of the cardiotoxicity from a mitochondrial perspective. Ultimately, we hope shed light on clinical decision-making. By integrate and learn from both research and practice, we will endeavor to minimize the mitochondria-mediated cardiotoxicity and reduce the adverse sequelae associated with BCR-ABL1 TKIs.
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Supervivientes de Cáncer , Cardiotoxicidad , Humanos , Miocardio , Mitocondrias , Proteínas de Fusión bcr-abl/genéticaRESUMEN
Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula. Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment. Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P<0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9L ï¼1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9L ï¼1 ( P<0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment. Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT.
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Antineoplásicos , Trombocitopenia , Humanos , Estudios Retrospectivos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Recuento de Plaquetas , Plaquetas , Antineoplásicos/efectos adversosRESUMEN
Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has demonstrated that mitophagy is crucial to developing colorectal cancer. This study aims to examine the association between mitophagy-related genes and the prognosis of CRC patients. Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied to establish a prognostic signature using mitophagy related genes. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to analyze patient survival and predictive accuracy. Meanwhile, we also used the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. ATG14 overexpression plasmid was used to regulate the ATG14 expression level in HCT116 and SW480 cell lines, and cell counting kit-8, colony formation and transwell migration assay were performed to validate the function of ATG14 in CRC cells. A total of 22 mitophagy-driven genes connected with CRC survival were identified, and then a novel prognostic signature was established based on 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter in both the training cohort and two independent cohorts. ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a Nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI 0.71-0.83) and more robust predictive accuracy. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more enriched in the high-risk group. Furthermore, patients in the high-risk group are more sensitive to targeted therapy or chemotherapy, including bosutinib, elesclomol, lenalidomide, midostaurin, pazopanib and sunitinib, while the low-risk group is more likely to benefit from immunotherapy. Finally, in vitro study confirmed the oncogenic significance of ATG14 in both HCT116 and SW480 cells, whose overexpression increased CRC cell proliferation, colony formation, and migration. In conclusion, we developed a novel mitophagy-related gene signature that can be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients, and we confirmed ATG14 as a novel oncogene in CRC.
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Neoplasias Colorrectales , Mitofagia , Humanos , Mitofagia/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estimación de Kaplan-Meier , Neoplasias Colorrectales/patología , Pronóstico , Microambiente Tumoral/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
Objective: To explore the efficacy comparison between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) combined with traditional Chinese medicine (TCM) and single EGFR-TKIs for advanced non-small cell lung cancer (NSCLC). Methods: A total of 91 NSCLC patients with EGFR mutation were divided into an experimental group and a control group (in a ratio of 2:1) to receive TCM and EGFR-TKIs (61 cases) or single EGFR-TKIs (30 cases). Patients in the control group took EGFR-TKIs and those in the experimental group took EGFR-TKIs plus TCM. We analyzed the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events of two groups. Results: The mPFS of the experimental group and the control group was 12.3 and 8.9 months (P = 0.02), respectively, and the mOS of the experimental group and the control group was 28.2 and 24.2 months (P = 0.02), respectively. Subgroup analysis showed that for the patients with exon 19 deletion mutation (19DEL), mPFS between experimental group and control group was 12.7 and 10.1 months, respectively (P = 0.12). For exon 21 deletion mutation (L858R), the PFS of two groups was 10.8 vs. 8.2 months, respectively (P = 0.03). The subgroup analysis also showed that, for the patients with exon 19 deletion mutation, mOS between the experimental group and the control group was 30.3 and 28.7 months, respectively (P = 0.19). For exon 21 deletion mutation, the mOS of two groups was 25.5 vs. 21.3 months, respectively (P = 0.01). The DCR of the experimental group and the control group was 93.3% and 80.1%, respectively (P = 0.77). Grade 3-4 treatment-related adverse events were less common with the experimental group (11.48%) than the control group (26.67%). Conclusion: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM had a certain effect to prolong mPFS and mOS, compared with the use of EGFR-TKIs alone, especially for the patients with L858R. This conclusion has a significant effect on improving the survival of NSCLC patients after EGFR-TKIs resistance. It deserves further study.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Supervivencia sin Enfermedad , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
OBJECTIVE: To study the use of Chinese medicine (CM) in cancer patients in southern China. METHODS: A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. RESULTS: The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. CONCLUSION: This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.
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Medicamentos Herbarios Chinos , Neoplasias , China , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Medicina Tradicional China , Neoplasias/tratamiento farmacológico , Calidad de Vida , Encuestas y CuestionariosRESUMEN
PURPOSE: To explore a new therapeutic option for patients with hepatocellular carcinoma (HCC), the efficacy and safety of a group of traditional Chinese medicines (Banxia XieXin recipe) as monotherapy for patients with advanced HCC was studied. MATERIALS AND METHODS: The study included 68 patients with advanced HCC from August 16,2016 to August 15,2019 for analysis. These eligible patients received treatment with Banxia XieXin recipe for at least 1 month. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR). In addition, safety was also assessed. RESULTS: The median treatment duration of these 68 patients was 10.3 months (range = 1.6-33.5 months), and follow-up is still ongoing. The median PFS was 6.07 months (95% confidence interval [CI] = 3.748-8.392 months), and the median OS was 12.60 months (95% CI = 8.019-17.181 months). The ORR was 10.3% and the DCR was 41.2%. In the subgroup analysis, the median OS in the transcatheter arterial chemoembolization (TACE) group was not reached, and the median OS in the NO TACE group was 11.30 months (95% CI = 3.219-19.381 months). In addition, no drug-related serious adverse events were observed during the study. CONCLUSION: This is the first clinical analysis of traditional Chinese medicine as a single treatment for advanced HCC. The obtained results are encouraging as they suggest that this panel of Chinese herbs is safe and it may be effective for patients with advanced HCC in a real-world clinical setting.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Medicamentos Herbarios Chinos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Medicina Tradicional ChinaRESUMEN
PURPOSE: The purpose of this paper is investigating the effect and mechanism of Shenfu injection (a Traditional Chinese Medicine injection form) on prevention and treatment of paclitaxel chemotherapy in peripheral nerve injury. METHODS: Wistar rat dorsal root ganglion cells were cultured in vitro and divided into groups of MOCK, PT, PT + LD, and PT + HD. Each group was cultured at a total serum concentration of 10%, including 10% blank serum in the MOCK group, 0.73 (IC30) µmol/L paclitaxel + 10% blank serum in the PT group, and 10% and 5% drug-containing serum and equal amount of paclitaxel were added into the high- and low-dosage groups, respectively. After culturing for 24 hours, the following tests were performed: (1) cell proliferation detected by using CCK-8 and a microplate reader; (2) axon length detected by cellular immunostaining and detection analysis on antibody ß-tubulin III; and (3) changes in mitochondrial membrane potential by analyzing immunofluorescence staining with JC-1 probe. RESULTS: (1) Cell proliferation: OD values of the MOCK group and PT group were 0.43 ± 0.02 and 0.25 ± 0.03, respectively (P < 0.05), while OD values of groups PT + LD and PT + HD were 0.41 ± 0.05 and 0.46 ± 0.03, respectively, higher than group PT (P < 0.05), while OD values of groups PT + LD and PT + HD were 0.41 ± 0.05 and 0.46 ± 0.03, respectively, higher than group PT (µmol/L paclitaxel + 10% blank serum in the PT group, and 10% and 5% drug-containing serum and equal amount of paclitaxel were added into the high- and low-dosage groups, respectively. After culturing for 24 hours, the following tests were performed: (1) cell proliferation detected by using CCK-8 and a microplate reader; (2) axon length detected by cellular immunostaining and detection analysis on antibody µmol/L paclitaxel + 10% blank serum in the PT group, and 10% and 5% drug-containing serum and equal amount of paclitaxel were added into the high- and low-dosage groups, respectively. After culturing for 24 hours, the following tests were performed: (1) cell proliferation detected by using CCK-8 and a microplate reader; (2) axon length detected by cellular immunostaining and detection analysis on antibody P < 0.05), while OD values of groups PT + LD and PT + HD were 0.41 ± 0.05 and 0.46 ± 0.03, respectively, higher than group PT (P < 0.05), while OD values of groups PT + LD and PT + HD were 0.41 ± 0.05 and 0.46 ± 0.03, respectively, higher than group PT (. CONCLUSION: Shenfu injection can prevent the toxicity of DRG neurons induced by paclitaxel, and its mechanism may be related to the alleviation of mitochondrial dysfunction.
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BACKGROUND Lung cancer is the most common cause of cancer-associated deaths worldwide. This study aimed to investigate the efficacy and safety of Traditional Chinese Medicine combining EGFR-TKIs in treatment of NSCLC patients harboring EGFR mutations. MATERIAL AND METHODS This study involved 153 advanced-stage NSCLC patients harboring EGFR mutations. Patients were divided into a Control group (administered EGFR-TKI, n=61) and an Experimental group (administered Traditional Chinese Medicine combining EGFR and TKI, n=92). Progression-free survival (PFS) was evaluated for exon 19 deletion and/or 21 deletion patients. Disease control rate (DCR) was assessed to observe therapeutic effects. Adverse effects, including rashes, diarrhea, ALT/AST increase, dental ulcers, and onychia lateralis, were also evaluated. RESULTS TCM combining EGFR-TKI (90.11%) demonstrated no DCR improvement compared to single EGFR-TKI (83.33%) (p>0.05). Median PFS (mPFS) of TCM combining EGFR-TKI (13 months) was significantly longer compared to that in the single EGFR-TKI group (8.8 months) (p=0.001). For 19DEL mutant NSCLC, the mPFS (11 months) in TCM combining EGFR-TKI was significantly longer compared to single EGFR-TKI (8.5 months) (p=0.007). The mPFS of L858 mutant NSCLC patients in EGFR-TKI combining CTM (14 months) was significantly longer compared to single EGFR-TKI (9.5 months) (p=0.015). TCM combining EGFR-TKI was more inclined to prolong mPFS of NSCLC with exon 21 deletion. TCM combining EGFR-TKI illustrated no additional adverse effects in NSCLC patients (p=0.956). CONCLUSIONS Application of Traditional Chinese Medicine prolonged progression-free survival and enhanced therapeutic effect in NSCLC patients harboring EGFR mutations receiving EGFR-TKI treatment. Meanwhile, adjunctive Chinese medicine combining EGFR-TKI in NSCLC with EGFR mutations caused no adverse effects.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , China , Supervivencia sin Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Medicina Tradicional China/métodos , Persona de Mediana Edad , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
OBJECTIVE: To explore the anti-virus effect of AY358935 gene cloned by our research team on vesicular stomatitis virus (VSV), and studytheanti-virus mechanism. METHODS: HEK293 cells were stably transfected by the AY358935 gene recombinant plasmid pcDNA3.1-AY358935 or pcDNA3.1 blank plasmid respectively. Then VSV was added into the cell wells to infect the above cells at the multiplicity of infection (MOI) of 0.001. The virus titers in the liquid supernatant of the above three groups of cells were detected on different time, and the mortality of cells of each group was tested with trypan blue exclusion test at 24 h post VSV infection. Total RNA was extracted from the cells that stably transfected with target gene for the whole genome-wide cDNA microarray analysis. RESULTS: â Virus titer:The virus titer in the liquid supernatant of pcDNA-3.1-AY358935 transfection cells group was obviously lower than those in pcDNA-3.1 transfection cell group and blank control cell group at 12 h post infection. The virus titerin the liquid supernatant of three groups were (7.16±2.33)×105 PFU/mL, (6.25±2.05)×106 PFU/mL and (7.75±2.54)×106 PFU/mL respectively at 18 h post infection. At that time, the virus titerin the liquid supernatant of pcDNA3.1-AY358935 group was nearly 10 times lower than those of other two groups (P < 0.01). â¡Mortality of cells:The cell mortality of pcDNA3.1-AY358935 group, pcDNA3.1 group and blank group were (35.00±6.68)%, (78.33±15.03)% and (83.34±14.98)% respectively at 24 h post infection.The cell mortality of pcDNA3.1-AY358935 group was significantly decreased comparing with other two groups (P < 0.01). â¢Result of genes chip analysis: compared with pcDNA3.1 group, 30 cell genes were up-regulated by more than 3 times in pcDNA3.1-AY358935 group. Among them, the proportion of interferon-activating gene, interferon-effect gene, cytokine and chemokine was 27%, 17%, and 20%, respectively. CONCLUSION: AY358935 gene hasan anti-VSV effect, and its anti-virus mechanism may involve the interferon-associated natural immune response.
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Proteínas Portadoras/genética , Estomatitis Vesicular/inmunología , Animales , Citocinas , Células HEK293 , Humanos , Interferones , Plásmidos , Transfección , VesiculovirusRESUMEN
OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , MutaciónRESUMEN
OBJECTIVE: To construct an eukaryotic expression plasmid for AY358935 gene and explore its function. METHODS: cDNA of the AY358935 gene was amplified by reverse transcription-PCR and cloned into pGEM-Teasy. The pGEM-T-AY was validated by sequencing and served as a template for the construction of eukaryotic expression plasmid. The pcDNA3.1-AY recombinant was validated by double enzyme digestion and used for transient transfection of M14 cells. Expression of the AY358935 protein and proliferation of the M14 cells were determined respectively by Western blotting and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetry. RESULTS: The amplicons of RT-PCR were confirmed to have similar size with the cDNA fragment of the AY358935 gene as well as cloned region of pcDNA3.1-AY. The cloned region of pGEM-T-AY was sequenced to be identical with cDNA sequence of the AY358935 gene. M14 cells were transfected by the AY358935 gene, pcDNA3.1 and liposomes, respectively. After 48 h, expression of the AY358935 protein in M14 cells transfected with the AY358935 gene was significantly higher than other two groups. They also had a significantly higher absorbance value (A=0.74) than other two groups (A=0.39 and 0.46, respectively; P<0.05). CONCLUSION: An eukaryotic expression plasmid of the AY358935 gene was successfully constructed. Product of the AY358935 gene may promote the proliferation of M14 cells.
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Plásmidos/genética , Proteínas/genética , Western Blotting , Clonación Molecular , ADN Complementario , Expresión Génica , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Células HeLa , Humanos , Plásmidos/metabolismo , Reacción en Cadena de la Polimerasa , Proteínas/metabolismo , TransfecciónRESUMEN
OBJECTIVE: To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. METHODS: Twenty-eight adult male Wister rats were randomized into 4 groups (n=7) : control group, paclitaxel group, paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection),low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively,while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL) of rats' hind paw were measured before (0 d) and after the first injection (6 d,14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia,and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. RESULTS: The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group ( P<0.05). The combination of paclitaxel with ShenFu Injection,especially the high dose ( P<0.05),significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group,there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection (P>0.05) . Compared with control group,the serum NGF level significantly decreased ( P<0.05) in paclitaxel group,while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group,particularly in the high dose group ( P<0.05). When compared to control group,the sciatic nerve fiber structure in the paclitaxel group was generally damaged,including myelin sheath swelling,fragmentation and vacuolization,endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups,especially the latter one,when compared to the paclitaxel group. CONCLUSION: Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.
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Medicamentos Herbarios Chinos/farmacología , Paclitaxel/efectos adversos , Nervio Ciático/efectos de los fármacos , Animales , Masculino , Neurotoxinas/efectos adversos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Nervio Ciático/ultraestructuraRESUMEN
BACKGROUND: CyclinD1 (CCND1) is a key cell cycle regulatory protein. A large number of epidemiological studies have assessed the potential correlation between the CCND1 G870A polymorphism and the risk of colorectal cancer (CRC), but their findings have been inconsistent. To obtain a more precise understanding of the association between the G870A polymorphism in the CCND1 gene and the CRC risk, we conducted a more comprehensive meta-analysis. METHODOLOGY: We searched PubMed, Ovid, Springer, Weipu, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering all publications (the last search was updated on January 10, 2017). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. Statistical analyses were performed using Review Manager 5.3 and STATA 10.0 software. RESULTS: A total of 7276 CRC patients and 9667 controls from 27 publications were included in this meta-analysis. We found that compared with GG homozygote genetic model, AA, AG, AAâ+âAG genetic models of the CCND1 G870A polymorphism were significantly associated with overall CRC risk (AA homozygote genetic model: ORâ=â1.28, 95% CIâ=â1.10-1.49; AG heterozygote genetic model: ORâ=â1.15, 95% CIâ=â1.06-1.25; AA homozygoteâ+âAG heterozygote genetic model: ORâ=â1.19, 95% CIâ=â1.07-1.33). Subgroup analyses by ethnicity and cancer location showed that A carriers were consistently associated with a significantly increased risk of CRC in all subsets of participants (Asian and Caucasian; colon cancer and rectal cancer). When stratified by study design, we found a significant association in hospital-based studies (HB), but no significant associations were found in either population-based studies (PB) or family-based studies (FB). According to subgroup analysis by cancer type, the risk of sporadic colorectal cancer (sCRC) and hereditary nonpolyposis colorectal cancer (HNPCC) were not correlated with the CCND1 G870A polymorphism, except AG (AG vs GG: ORâ=â1.30, 95% CIâ=â1.11-1.53). CONCLUSIONS: This meta-analysis suggests that the CCND1 G870A polymorphism is associated with an increased risk of CRC, especially that A carriers may be a major risk factor for CRC.
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Pueblo Asiatico/genética , Neoplasias Colorrectales/genética , Ciclina D1/genética , Polimorfismo de Nucleótido Simple/genética , Población Blanca/genética , Adulto , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/etnología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de RiesgoRESUMEN
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication. Deletion of C11orf83 permits viral replication easier and cells were more vulnerable to viral killing. These effects mainly were mediated by triggering OAS3-RNase L system. C11orf83 overexpression induced higher transcription of OAS3, and knockdown either OAS3 or RNase L impaired the antiviral capability of C11orf83. Interestingly, the signaling from C11orf83 to OAS3-RNase L was independent of interferon production. Thus, our findings suggested a new antiviral mechanism by bridging cell metabolic machinery component with antiviral effectors.
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2',5'-Oligoadenilato Sintetasa/inmunología , Proteínas Portadoras/inmunología , Endorribonucleasas/inmunología , Interacciones Huésped-Patógeno , Mitocondrias/inmunología , Virus de la Estomatitis Vesicular Indiana/inmunología , 2',5'-Oligoadenilato Sintetasa/genética , Animales , Sistemas CRISPR-Cas , Proteínas Portadoras/genética , Chlorocebus aethiops , Endorribonucleasas/genética , Eliminación de Gen , Regulación de la Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunidad Innata , Interferón gamma/genética , Interferón gamma/inmunología , Luciferasas/genética , Luciferasas/metabolismo , Mitocondrias/genética , Transducción de Señal , Células Vero , Virus de la Estomatitis Vesicular Indiana/genética , Replicación ViralRESUMEN
OBJECTIVES: To investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) expressed in lung carcinoma and the intervention effect of Yiqi Chutan Formula (, YQCTF). METHODS: Lung carcinoma model was established by subcutaneously inoculating LEWIS lung carcinoma cells in C57BL/6J mice. The differential expression of P4HB protein between the YQCTF (3.0 g/kg, gavage, once daily, 21 days) group and the control group was acquired by a 2 fluorescence difference gel electrophoresis (2D-DIGE), verified by Western blotting and identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS). The expression of P4HB and P4HB mRNA in cultured A549 cells from cisplatin (DDP) 1.5 µg/mL group and 15% serum combined with DDP 1.5 µg/mL group were detected by cellular immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. RESULTS: The proteomics research discovered that one-third of differential proteins including P4HB were decreased in the YQCTF group (P<0.01). Clinical pathology and tissue microarray studies showed that P4HB expression in lung cancer tissue was stronger than adjacent tissues and normal lung epithelial (P<0.01). In the YQCTF and DDP combined groups, the expression of P4HB and P4HB mRNA in A549 cell were decreased significantly (P<0.01). CONCLUSION: YQCTF could inhibit the LEWIS lung carcinoma's growth, decrease the expression of P4HB in LEWIS lung carcinoma and A549 cells. YQCTF might take effect through regulating P4HB in endoplasmic reticulum to inhibit the incidence and growth process of lung carcinoma.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Péptidos/uso terapéutico , Prolil Hidroxilasas/metabolismo , Animales , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Medicamentos Herbarios Chinos/farmacología , Electroforesis en Gel Bidimensional , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones Endogámicos C57BL , Mapeo Peptídico , Péptidos/farmacología , Prolil Hidroxilasas/genética , Proteómica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Matrices TisularesRESUMEN
The clinical efficiency of cisplatin against ovarian cancer is often limited by the development of drug resistance. In this work, we investigated PEGylated liposomal quercetin (Lipo-Que) on cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) human ovarian cancer models in vitro and in vivo to reveal whether a cisplatin-resistant ovarian cancer has susceptibility to quercetin (Que) and the mechanism of its antitumor activity. Lipo-Que was prepared using a solid dispersion method, and the obtained Lipo-Que is monodisperse with a mean diameter of 163 +/-10 nm. Besides, in vitro drug release assay showed a sustained release behavior of Lipo-Que. In vitro experiments suggested that Lipo-Que inhibited cell proliferation, induced apoptosis, and induced cell cycle arrest in both A2780s and A2780cp cells. Furthermore, antitumor activity of Lipo-Que was investigated in both cisplatin-sensitive and cisplatin-resistant human ovarian tumor xenograft models in nude mice. Lipo-Que significantly suppressed tumor growth in both models in comparison with free Que, blank liposomes (Lipo), or normal saline (NS). Furthermore, immunohistochemistry and immunofluorescence tests revealed that Lipo-Que induced apoptosis, decreased microvessel density, and inhibited proliferation of tumors in both A2780s and A2780cp tumor models. Therefore, our results suggest that Lipo-Que is an effective agent to inhibit tumor growth in both cisplatin-sensitive and cisplatin-resistant human ovarian cancers.
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Cisplatino/uso terapéutico , Nanocápsulas/administración & dosificación , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Polietilenglicoles/química , Quercetina/administración & dosificación , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antioxidantes/administración & dosificación , Antioxidantes/química , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Liposomas/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanocápsulas/química , Neovascularización Patológica/complicaciones , Neoplasias Ováricas/complicaciones , Quercetina/química , Resultado del TratamientoRESUMEN
Chinese herb medicine (CHM) is the most commonly reported traditional Chinese medicine (TCM) modality. This study aimed to assess the prevalence and associated factors of CHM use in cancer patients in southwestern China. Cancer patients from eleven comprehensive cancer centers were asked to complete a structured questionnaire. Of 587 available replies, 53.0% used CHM. Multiple logistic regression analysis showed that educational level, stage of disease, duration of cancer since diagnosis, marital status, and previous use of CHM were strongly associated with CHM use after cancer diagnosis. The source of information about CHM was mainly from media and friends/family. CHM products were used without any consultation with a TCM practitioner by 67.5% of users. The majority used CHM to improve their physical and emotional well-beings and to reduce cancer therapy-induced toxicities. About 4.5% patients reported side effects of CHM. This survey revealed a high prevalence of CHM use among cancer patients. However, these patients did not get sufficient consultation about the indications and contradictions of these drugs. It is imperative for oncologists to communicate with their cancer patients about the usage of CHM so as to avoid the potential side effects.