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1.
Cytotherapy ; 25(3): 298-309, 2023 03.
Article in English | MEDLINE | ID: mdl-36244911

ABSTRACT

BACKGROUND AIMS: M2-polarized tumor-associated macrophages contribute to the development of multiple human cancers, including renal cell carcinoma (RCC). However, the crosstalk mechanism between M2 macrophages and RCC remains unclear. METHODS: The authors constructed a co-culture system of M2 macrophages differentiated from THP-1 and RCC cells. Microscopic examination and quantitative real­time polymerase chain reaction (qRT-PCR) validated the morphology and types of macrophages. The proliferation, migration and invasion of RCC cells were assessed by Cell Counting Kit 8 (Dojindo Molecular Technologies, Inc, Santa Clara, CA, USA) and Transwell assay (Corning, Corning, NY, USA). Messenger RNA (mRNA) and protein expression of target molecules was detected by qRT­PCR and western blotting. Expression of Ki-67, E-cadherin and N-cadherin was measured by immunofluorescence staining or immunohistochemistry. Molecular interaction was evaluated by RNA pull-down, RNA immunoprecipitation and co-immunoprecipitation. A xenograft model was established to determine tumor growth in vivo. RESULTS: RCC cells triggered the activation of M2 macrophages. Functionally, M2-polarized macrophages facilitated the growth, migration, invasion and epithelial-mesenchymal transition of RCC cells by suppressing autophagy, whereas rapamycin, an activator of autophagy, significantly counteracted the tumor-promoting effects of M2 macrophages. Mechanistically, M2 macrophage-derived C-C motif chemokine 2 (CCL2) enhanced modulation of muscleblind-like protein 2 (MBNL2) expression. MBNL2 raised the stability of B-cell lymphoma 2 (Bcl-2) by directly binding to Bcl-2 mRNA, which endowed RCC cells with malignant properties via inhibition of beclin 1-dependent autophagy. CONCLUSIONS: RCC-induced M2-polarized macrophages secrete CCL2 to promote the growth and metastasis of RCC cells via inhibition of MBNL2/Bcl-2/beclin 1-mediated autophagy, which provide a novel perspective for the development of a therapeutic strategy for -RCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Beclin-1/genetics , Beclin-1/pharmacology , Tumor-Associated Macrophages/pathology , Cell Line, Tumor , Autophagy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , RNA/pharmacology , RNA, Messenger , Proto-Oncogene Proteins c-bcl-2 , Cell Movement , Cell Proliferation
2.
Eur Radiol ; 33(10): 6625-6635, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37515634

ABSTRACT

OBJECTIVES: To assess the value of positron emission tomography/computed tomography (PET/CT) in the efficacy evaluation of patients undergoing neoadjuvant immunotherapy plus chemotherapy, and to analyze its correlation with postoperative pathology. METHODS: The PET/CT metabolic parameters and CT size were retrospectively analyzed before and after neoadjuvant immunotherapy plus chemotherapy in 67 patients with resectable stage II/IIIA non-small-cell lung cancer (NSCLC). CT assessment based on immune response evaluation criteria in solid tumor criteria ((i)RECIST) was compared with PET/CT assessment based on the response criteria in solid tumors (PERCIST). The correlations between PET/CT metabolic parameters and postoperative pathology were analyzed. The value of PET/CT in the efficacy evaluation was assessed. RESULTS: The PET/CT assessment showed high consistency with postoperative pathological evaluation, yet the CT assessment showed low consistency with postoperative pathological evaluation. The (i)RECIST and PERCIST criteria showed statistically significant differences (p < 0.001). The postoperative pathological response was negatively associated with ΔSUVmax (%) (r = - 0.812, p < 0.001), ΔSUVmean (%) (r = - 0.805, p < 0.001), and ΔSUVpeak (%) (r = - 0.800, p < 0.001). The cut-off values of 75.8 for ΔSUVmax (%), 67.8 for ΔSUVmean (%), and 74.6 for ΔSUVpeak (%) had the highest sensitivity and specificity. CONCLUSION: The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. PET/CT shows high accuracy in predicting postoperative pathological response. Our study shows the important role PET/CT plays in the efficacy evaluation of NSCLC patients undergoing neoadjuvant immunotherapy plus chemotherapy, as well as in predicting the prognosis and guiding postoperative treatment. CLINICAL RELEVANCE STATEMENT: Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of non-small-cell lung cancer. And PET/CT played an important role in the efficacy evaluation following neoadjuvant immunotherapy plus chemotherapy for non-small-cell lung cancer. KEY POINTS: • Neoadjuvant immunotherapy plus chemotherapy is highly effective in the treatment of NSCLC. • The PERCIST criteria are more sensitive and accurate than (i)RECIST criteria to identify more responders when evaluating the response of neoadjuvant immunotherapy plus chemotherapy for NSCLC. • PET/CT played an important role in the efficacy evaluation; ΔSUVmax (%), ΔSUVmean (%), and ΔSUVpeak (%) following neoadjuvant immunotherapy plus chemotherapy for NSCLC had high consistency and strong correlations with postoperative pathology.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Positron Emission Tomography Computed Tomography/methods , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Neoadjuvant Therapy , Retrospective Studies , Fluorodeoxyglucose F18 , Immunotherapy , Positron-Emission Tomography/methods , Treatment Outcome
3.
Sensors (Basel) ; 23(9)2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37177618

ABSTRACT

It is important to detect and classify foreign fibers in cotton, especially white and transparent foreign fibers, to produce subsequent yarn and textile quality. There are some problems in the actual cotton foreign fiber removing process, such as some foreign fibers missing inspection, low recognition accuracy of small foreign fibers, and low detection speed. A polarization imaging device of cotton foreign fiber was constructed based on the difference in optical properties and polarization characteristics between cotton fibers. An object detection and classification algorithm based on an improved YOLOv5 was proposed to achieve small foreign fiber recognition and classification. The methods were as follows: (1) The lightweight network Shufflenetv2 with the Hard-Swish activation function was used as the backbone feature extraction network to improve the detection speed and reduce the model volume. (2) The PANet network connection of YOLOv5 was modified to obtain a fine-grained feature map to improve the detection accuracy for small targets. (3) A CA attention module was added to the YOLOv5 network to increase the weight of the useful features while suppressing the weight of invalid features to improve the detection accuracy of foreign fiber targets. Moreover, we conducted ablation experiments on the improved strategy. The model volume, mAP@0.5, mAP@0.5:0.95, and FPS of the improved YOLOv5 were up to 0.75 MB, 96.9%, 59.9%, and 385 f/s, respectively, compared to YOLOv5, and the improved YOLOv5 increased by 1.03%, 7.13%, and 126.47%, respectively, which proves that the method can be applied to the vision system of an actual production line for cotton foreign fiber detection.

4.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3565-3575, 2023 Jul.
Article in Zh | MEDLINE | ID: mdl-37474990

ABSTRACT

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.


Subject(s)
Atrial Remodeling , Heart Failure , Rats , Animals , Myocytes, Cardiac , Rats, Sprague-Dawley , Heart Failure/drug therapy , Heart Failure/metabolism , RNA, Messenger/metabolism , Potassium
5.
Scand J Gastroenterol ; 57(10): 1227-1237, 2022 10.
Article in English | MEDLINE | ID: mdl-35512233

ABSTRACT

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Prognosis , RNA, Messenger
6.
Neoplasma ; 68(6): 1225-1235, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34641698

ABSTRACT

Bladder cancer is a common malignant tumor with a high recurrence rate and mortality, while the detailed mechanisms for bladder cancer progression and metastasis are unknown. Recently, long non-coding RNAs (lncRNAs) have been reported to be involved in the development of cancers. In this study, we aim to investigate the role of lncRNA LINC00355 in bladder cancer progression and metastasis. The association between LINC00355 and the prognosis of bladder cancer patients was determined by Kaplan-Meier survival analysis. Cell migration and invasion ability were detected using the Transwell migration and invasion assay. The relationships of LINC00355, miR-424-5p, and High Mobility Group AT-Hook 2 (HMGA2) were verified through the luciferase assay and RNA pull-down assay. Xenograft tumor was established to evaluate tumor lung metastasis in vivo. qRT-PCR and western blot were used to detect gene expression. LINC00355 was upregulated in bladder cancer patients, especially in patients with higher TNM stage. Elevated LINC00355 was correlated with the poor prognosis of bladder cancer patients. Besides, overexpressed LINC00355 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) ability of bladder cancer cells. Contrarily, decreased LINC00355 suppressed migration, invasion, and EMT ability of bladder cancer cells, and lung metastasis of xenograft tumors. Furthermore, LINC00355 could regulate HMGA2 expression by acting as a sponge for miR-424-5p. Overexpression of HMGA2 induced EMT of bladder cancer cells. Additionally, LINC00355 regulated the migration, invasion, and EMT ability of bladder cancer cells through modulating HMGA2 expression via sponging miR-424-5p. LINC00355 promoted migration, invasion, and EMT ability of bladder cancer through elevating HMGA2 expression via acting as a sponge for miR-424-5p.


Subject(s)
Epithelial-Mesenchymal Transition , HMGA2 Protein/genetics , MicroRNAs , Neoplasm Metastasis/genetics , RNA, Long Noncoding , Urinary Bladder Neoplasms , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
7.
Mol Biol Rep ; 47(10): 8159-8168, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32979165

ABSTRACT

Colorectal cancer (CRC) is one of the leading causes of tumor morbidity and mortality worldwide. Endoscopy is currently the main screening method, but the invasiveness and high cost hamper the application of endoscopy in asymptomatic patients with a risk of CRC and lead to a low diagnostic rate for early CRC. In recent years, the progress of transcriptomics, epigenetics, immunomics and metabolomics has greatly contributed to the identification of novel molecular markers for the noninvasive screening of CRC, and many molecules in various biological processes have been identified and evaluated for CRC detection. However, individual molecules always have insufficient diagnostic performance as biomarkers for the detection of CRC; therefore, a frequent strategy to overcome this deficiency is the use of molecule signatures as biomarker panels to improve the diagnostic power. Here, we reviewed the diagnostic performance of blood-derived molecular signatures (mRNAs, microRNAs, autoantibodies, and metabolites) as biomarker panels for CRC detection, particularly for early detection, and discussed their limitations and prospects.


Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/diagnosis , Early Detection of Cancer , Animals , Humans
8.
Yi Chuan ; 42(12): 1192-1200, 2020 Dec 17.
Article in English | MEDLINE | ID: mdl-33509783

ABSTRACT

Nanoparticles are widely used in cosmetic, pharmaceutical, and food industries, but their safety and genetic toxicity are still unclear. In this study, the genotoxicity of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (titanium dioxide nanoparticles) were evaluated by in vitro comet assay and PIG-A assay in TK6 cells. We exposed TK6 cells to two types of nanoparticles at the highest concentration of 200 µmol/L for 4 h and conducted the in vitro comet assay. We examined the mutation results of PIG-A gene in vitro after 4 h, 24 ho and 10 days of exposure, respectively. We also examined the endocytosis of nanoparticles in TK6 cells exposed to nanoparticles for 24 h. In the endocytosis assay, with the increase of nano-material concentration, the side scatter (SSC) of TK6 cells in flow cytometry showed a concentration-dependent and time-dependent increase, indicating that TK6 cells could uptake both types of nanoparticles. In the comet assay, AgNPs could induce a concentration-dependent increase in DNA tail intensity. However, titanium dioxide NPs could not induce the concentration-dependent increase of DNA fluorescence intensity of comet tail. In the PIG-A assay, both AgNPs and TiO2NPs did not induce PIG-A gene mutation frequency in TK6 cells. The results showed that AgNPs could induce DNA damage in TK6 cells, but could not induce increase of PIG-A gene mutation frequency. TiO2NPs neither induce DNA damage in TK6 cells nor increase PIG-A mutation frequency. Further tests are needed to determine whether TiO2NPs are genotoxic.


Subject(s)
DNA Damage , Metal Nanoparticles , Silver , Titanium , Cell Line , Humans , Membrane Proteins/genetics , Metal Nanoparticles/toxicity , Mutagenicity Tests , Silver/toxicity , Titanium/toxicity
9.
BMC Nephrol ; 20(1): 127, 2019 04 11.
Article in English | MEDLINE | ID: mdl-30975094

ABSTRACT

BACKGROUND: MicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). Previous study has suggested the important regulation function of miR-10b in ccRCC. However, the direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed. METHODS: miR-10b and HOXA3 was detected by qRT-PCR. MTT, colony formation assay, wound-healing and transwell assays were performed to detect cell proliferation, colony formation, migration, and invasion abilities in ccRCC. Western blot analyses were performed to evaluate the protein expression of HOXA3, YAP, FAK and MMP-9. Dual luciferase reporter assay was employed to measure potential molecular mechanism of miR-10b in ccRCC. RESULTS: miR-10b was down-regulated in 786-O and A498 cells as compared to renal tubular HK-2 cells. By contrast, HOXA3 and YAP was up-regulated in ccRCC cells and tissues. Functionally, knockdown of YAP inhibited cell proliferation, migration and invasion. Knockdown of FAK downregulated YAP, in turn, resulted in a decrease of HOXA3 expression. Mechanically, miR-10b targets HOXA3 to exert its tumor-suppressive effect on ccRCC in vitro. CONCLUSIONS: These novel data suggest that miR-10b suppresses cell invasion and metastasis through targeting HOXA3, which partially passed through the FAK/YAP signaling pathway.


Subject(s)
Carcinoma, Renal Cell , Focal Adhesion Kinase 1/genetics , Homeodomain Proteins/genetics , Kidney Neoplasms , MicroRNAs/genetics , Adaptor Proteins, Signal Transducing/genetics , Aged , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Down-Regulation , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness/genetics , Neoplasm Metastasis/genetics , Signal Transduction , Transcription Factors/genetics , Up-Regulation , YAP-Signaling Proteins
11.
World J Urol ; 36(8): 1309-1314, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29536158

ABSTRACT

PURPOSE: To evaluate and compare flexible ureteroscopy (f-URS) and mini-percutaneous nephrolithotomy (mPNL) for 20-30 mm renal stones in obese patients regarding efficacy and safety. METHODS: Between May 2011 and June 2017, 254 obese patients who had 20-30 mm kidney stone were consecutively included in the study; 106 patients underwent mPNL and 148 underwent f-URS by the same surgeon. The following parameters were retrospectively assessed: patient and stone characteristics, surgical details, perioperative outcomes, and stone-free rates (SFR). RESULTS: F-URS group was similar to mPNL group in terms of the mean duration of surgery (92.8 ± 26.1 vs 87.4 ± 31.5 min, P = 0.137) and the final SFR (89.1 vs 92.5%, P = 0.381). The f-URS group had significantly shorter postoperative stay (1.0 ± 0.8 vs 4.3 ± 1.7 days, P < 0.001) and lower postoperative complications (11.5 vs 26.4%, P = 0.002). However, the f-URS group had a lower SFR after first session (67.2 vs 87.4%, P < 0.001) and needed more number of procedures (1.5 ± 0.4 vs 1.3 ± 0.4, P < 0.001) than the mPNL group. CONCLUSIONS: MPNL has a higher efficacy (higher SFR after first session and lower number of procedures); however, f-URS offers advantages regarding safety (lower complication rate). Therefore, both options can be offered to obese patients with renal stones from 20 to 30 mm in size. Nevertheless, these results must be confirmed by further prospective randomized trials.


Subject(s)
Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/methods , Obesity/complications , Ureteroscopy/methods , Female , Humans , Male , Middle Aged , Miniaturization , Operative Time , Retrospective Studies , Treatment Outcome
12.
Oncologist ; 22(1): 61-69, 2017 01.
Article in English | MEDLINE | ID: mdl-28126915

ABSTRACT

BACKGROUND: A subset of patients with non-small cell lung cancer (NSCLC) fosters mixed responses (MRs) to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) or chemotherapy. However, little is known about the clinical and molecular features or the prognostic significance and potential mechanisms. METHODS: The records of 246 consecutive patients with NSCLC receiving single-line chemotherapy or TKI treatment and who were assessed by baseline and interim positron emission tomography/computed tomography scans were collected retrospectively. The clinicopathological correlations of the MR were analyzed, and a multivariate analysis was performed to explore the prognostic significance of MR. RESULTS: The overall incidence of MR to systemic therapy was 21.5% (53/246) and predominated in patients with stage IIIB-IV, EGFR mutations and those who received TKI therapy (p < .05). Subgroup analyses based on MR classification (efficacious versus inefficacious) showed significant differences in subsequent treatment between the two groups (p < .001) and preferable progression-free survival (PFS) and overall survival (OS) in the efficacious MR group. Multivariate analyses demonstrated that the presence of MR was an independent unfavorable prognostic factor for PFS (hazard ratio [HR], 1.474; 95% confidence interval [CI], 1.018-2.134; p = .040) and OS (HR, 1.849; 95% CI, 1.190-2.871; p = .006) in patients with NSCLC. Induced by former systemic therapy, there were more T790M (18%), concomitant EGFR mutations (15%), and changes to EGFR wild type (19%) in the MR group among patients with EGFR mutations, which indicated higher incidence of genetic heterogeneity. CONCLUSION: MR was not a rare event in patients with NSCLC and tended to occur in those with advanced lung adenocarcinoma treated with a TKI. MR may result from genetic heterogeneity and is an unfavorable prognostic factor for survival. Further studies are imperative to explore subsequent treatment strategies. The Oncologist 2017;22:61-69Implications for Practice: Tumor heterogeneity tends to produce mixed responses (MR) to systemic therapy, including TKI and chemotherapy; however, the clinical significance and potential mechanisms are not fully understood, and the subsequent treatment after MR is also a clinical concern. The present study systemically assessed patients by PET/CT and differentiated MR and therapies. The study identified a relatively high incidence of MR in patients with advanced NSCLC, particularly those treated with targeted therapies. An MR may be an unfavorable prognostic factor and originate from genetic heterogeneity. Further studies are imperative to explore subsequent treatment strategies.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Genetic Heterogeneity , Prognosis , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Female , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Quinazolines/administration & dosage , Quinazolines/adverse effects
13.
Molecules ; 22(5)2017 May 13.
Article in English | MEDLINE | ID: mdl-28505098

ABSTRACT

Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil bath at 35 °C for 24 h. A particularly valuable feature of this method was the development of environment-friendly chemistry using alcohols 2 as both the substrates and solvents in the presence of a catalytic amount of base.


Subject(s)
Alcohols/chemistry , Indoles/chemistry , Solvents/chemistry , Catalysis , Molecular Structure , Oxindoles , Stereoisomerism
14.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2922-2926, 2016 Aug.
Article in Zh | MEDLINE | ID: mdl-28914038

ABSTRACT

Neobavaisoflavone is one of flavonoids of traditional Chinese medicine Psoralea corylifolial. It has numerous biological properties such as antibacterial, anti-inflammatory, anti-cancer, and anti-osteoporosis effects. This paper aimed to investigate the absorption mechanism of neobavaisoflavone in Caco-2 cell monolayer model. The analyte and osalmide were separated on Thermo Syncronis C18 column with methanol-0.1% formic acid solution (90∶10) as the mobile phase, at a flow rate of 0.2 mL•min⁻¹. The concentration of neobavaisoflavone was determined in eletrospray ionization(ESI) positive ion mode with osalmide as an the internal standard. The effects of time, concentration, P-gp inhibitor verapamil, MRP-2 inhibitor MK-571 and BCRP inhibitor Ko143 on the absorption of neobavaisoflavone were investigated. According to the results, neobavaisoflavone showed a good linearity within the concentration of 10-2 000 µg•L⁻¹, and the results of its specificity, matrix effect, extraction recovery, precision, accuracy and stability all met the requirements. In the Caco-2 cell monolayer model, the transport volume of neobavaisoflavone was correlated positively with the time and concentration. The ER values of 15, 30, 50 µmol•L⁻¹ neobavaisoflavone were 1.64, 1.94,0.99, respectively. As compared with the control group, all of verapamil hyduochloride, MK-571 and Ko143 could promote the transportation of neobavaisoflavone, and the effect was more obvious in verapamil hyduochloride and Ko143. The absorption of neobavaisoflavone may be mainly of active transport in Caco-2 cell monolayer model, and also involve passive transport. Excretion mechanism of intestinal transport protein may be also involved.


Subject(s)
Isoflavones/pharmacokinetics , Biological Transport , Caco-2 Cells , Diketopiperazines/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Intestinal Absorption , Multidrug Resistance-Associated Protein 2 , Propionates/pharmacology , Quinolines/pharmacology
15.
Mar Drugs ; 13(3): 1569-80, 2015 Mar 23.
Article in English | MEDLINE | ID: mdl-25806467

ABSTRACT

Nonfunctioning pituitary adenoma (NFPA) is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403) which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay) to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs) and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI) double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI) apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN) were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.


Subject(s)
Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Pituitary Neoplasms/drug therapy , Adenoma/drug therapy , Adenoma/pathology , Animals , Anthraquinones/isolation & purification , Antineoplastic Agents/isolation & purification , Ascomycota/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , China , Humans , Pituitary Neoplasms/pathology , Prolactinoma/drug therapy , Prolactinoma/pathology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Rats , Secondary Metabolism
16.
Radiol Med ; 120(8): 745-52, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25698301

ABSTRACT

PURPOSE: The purpose of this study was to review the clinical and imaging characteristics of giant cell tumour of tendon sheath (GCTTS) with bone invasion. MATERIALS AND METHODS: Radiography (n = 9), magnetic resonance imaging (MRI) (n = 7), computed tomography (CT) (n = 4) and clinical findings of nine patients with surgically and pathologically confirmed GCTTS with bone invasion were retrospectively reviewed. Specific imaging findings including tumour site, maximum tumour size, shape, margin, density or signal intensity, bone invasion, periosteal reaction, calcification, and cystic areas were documented. RESULTS: There were five males and four females, with median age of 34 years. Presenting symptoms were painless mass in five patients, painful mass in two, intermittent pain and swelling in one and pain without mass in one. Five tumours were in the ankle-foot region, two in the hand, one in the cubital fossa and one in the patellofemoral joint. The total symptom duration ranged from 5 months to 6 years (median 12 months). The maximum tumour size ranged from 1.0 to 6.8 cm (median 3.0 cm). Radiographically, all tumours appeared as cortical destruction with well-defined margins. Four patients underwent CT scanning that clearly showed an iso-attenuated mass with intraosseous soft tissue. MR scanning was performed in seven patients who demonstrated a round, oval, spindle-shaped or multilobular soft tissue mass near or inside the joint with cortical destruction and intraosseous soft tissue. Five lesions were homogeneous moderate signal on T1WI. Moderate (n = 1), slightly high or high (n = 2) and low (n = 2) signal intensities were evident on T2WI. Two lesions showed heterogeneous low-to-moderate signal intensities on T1WI and mixed low signal intensities on T2WI. CONCLUSIONS: GCTTS is a benign soft tissue mass that may present as an intraosseous lesion near extremity joints and frequently occurring in foot and hand on radiological examinations. GCTTS with bone invasion should be considered when MRI shows solid mass with characteristic low signal on T2-weighted images.


Subject(s)
Bone Neoplasms/secondary , Giant Cell Tumors/pathology , Lower Extremity/pathology , Tendons/pathology , Adult , Aged , Aged, 80 and over , Contrast Media , Female , Gadolinium DTPA , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Tumor Burden
17.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1119-22, 2015 Mar.
Article in Zh | MEDLINE | ID: mdl-26226756

ABSTRACT

OBJECTIVE: An accurate and reliable analytical method for-simultaneous determination of six active components (scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) in plants of Erycibe was developed. METHOD: Scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C in the samples were well separated in analytical HPLC by gradual elution with methanol-0.1% formic acid solution. The chromatographic condictions: Agilent Poroshell 120 EC-C18 column, flowing rate being 1 mL x min(-1), detecting wavelength at 345 nm. RESULT: Good linearities of scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C were in the range of 0.026 8-2.68, 0.027 0-2.70, 0.008 1-0.81, 0.018 8-1.88, 0.017 6-1.76, 0.019 6-1.96 µg, respectively (r > 0.999 6). The average recoveries of the six components were 98.1%, 98.7%, 100.8%, 100.4%, 99.7%, 101.1%; the relative standard deviations were 2.67%, 2.86%, 2.62%, 1.98%, 2.76%, 2.19%. CONCLUSION: The method is simple, feasible and reproducible and can be used for the quality control of plants of Erycibe.


Subject(s)
Chlorogenic Acid/analogs & derivatives , Chlorogenic Acid/analysis , Chromatography, High Pressure Liquid/methods , Convolvulaceae/chemistry , Coumarins/analysis , Drugs, Chinese Herbal/analysis , Glucosides/analysis , Scopoletin/analysis , China
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(9): 914-8, 2014 Sep.
Article in Zh | MEDLINE | ID: mdl-25229959

ABSTRACT

OBJECTIVE: To study the clinical characteristics of hospitalized infants with allergic proctocolitis, and to provide a scientific basis for early diagnosis and effective treatment of allergic proctocolitis. METHODS: The clinical data of 96 infants with allergic proctocolitis between September 2011 and March 2013 were reviewed retrospectively. Descriptive analysis was performed to assess the clinical characteristics of allergic proctocolitis. RESULTS: The most common clinical manifestation was diarrhea in the 96 infants. The electronic colonoscopy results indicated that 40% of the infants had multiple small nodules, 26% showed focal erythema and brittle mucous membranes, 25% showed multiple superficial erosion, and 9% showed ulcers with surface exudates. The affected areas included the sigmoid colon (87%), rectum (24%), descending colon (13%), and transverse colon ascending colon and ileocecal junction (8%). Histopathologic examination showed eosinophilic infiltration of mucosal layers, the condition of which was mild to moderate in 89% and severe and extremely severe in 12% of the infants. To treat the allergic proctocolitis, mothers and infants were suggested to avoid allergenic foods; 43% of them continued breastfeeding, 45% switched to highly hydrolyzed protein formula, and 13% were prescribed amino acid-based elemental formula. All infants were in complete remission at discharge. CONCLUSIONS: As the clinical manifestations of allergic proctocolitis in infants lack specificity, the electronic colonoscopy and mucosal histopathologic examination are helpful for early and differential diagnosis. The best treatment is to avoid allergenic foods. Formula-feeding infants should be prescribed highly hydrolyzed protein formula or amino acid-based elemental formula.


Subject(s)
Proctocolitis/pathology , Colonoscopy , Female , Humans , Infant , Male , Proctocolitis/diagnosis , Proctocolitis/therapy , Retrospective Studies
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(3): 230-3, 2014 Mar.
Article in Zh | MEDLINE | ID: mdl-24661511

ABSTRACT

OBJECTIVE: To evaluate the clinical effect of proton pump inhibitor-based triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori (Hp) infection among children in terms of Hp eradication rate and incidence of adverse events. METHODS: A prospective randomised controlled study was conducted on 240 children with a confirmed diagnosis of Hp infection. These patients were randomized into triple therapy (n=120) and probiotics groups (n=120). The triple therapy group received amoxicillin [40 mg/(kg·d), Tid], clarithromycin [15 mg/(kg·d), Bid] and omeprazole [0.7-0.8 mg/(kg·d), Qd], while the probiotics group received Saccharomyces boulardii (250 mg, Bid) in addition to triple therapy. The course of treatment was 14 days in both groups. The adverse events in subjects were recorded by their parents during treatment. Hp eradiation was evaluated by (13)C breath test at 4 weeks after treatment, and the eradication rate and incidence of adverse events were compared between the two groups. RESULTS: The Hp eradication rates were 75.8% (91/120) in the triple therapy group and 85% (102/120) in the probiotics group (P>0.05). Compared with the triple therapy group, the probiotics group had nonsignificantly lower incidence of nausea, vomiting, and abdominal pain (P>0.05) and significantly lower incidence of stomatitis, constipation and diarrhea (P<0.05). CONCLUSIONS: Triple therapy combined with Saccharomyces boulardii cannot significantly increase Hp eradication rate, but can significantly reduce the incidence of stomatitis, constipation, and diarrhea during treatment.


Subject(s)
Helicobacter Infections/therapy , Helicobacter pylori , Probiotics/administration & dosage , Saccharomyces , Amoxicillin/administration & dosage , Child , Child, Preschool , Clarithromycin/administration & dosage , Combined Modality Therapy , Drug Therapy, Combination , Female , Humans , Male , Omeprazole/administration & dosage , Prospective Studies
20.
Cancer Rep (Hoboken) ; 7(3): e2050, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38517478

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized as a globally prevalent malignancy. Immunotherapy is a promising therapy for HCC patients. Increasing evidence suggests that lncRNAs are involved in HCC progression and immunotherapy. AIM: The study reveals the mechanistic role of long non-coding RNA (lncRNA) FOXD1-AS1 in regulating migration, invasion, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), and immune escape in HCC in vitro. METHODS: This study employed real-time PCR (RT-qPCR) to measure FOXD1-AS1, miR-615-3p, and programmed death-ligand 1 (PD-L1). The interactions of FOXD1-AS1, miR-615-3p, and PD-L1 were validated via dual-luciferase reporter gene and ribonucleoprotein immunoprecipitation (RIP) assay. In vivo experimentation involves BALB/c mice and BALB/c nude mice to investigate the impact of HCC metastasis. RESULTS: The upregulation of lncRNA FOXD1-AS1 in malignant tissues significantly correlates with poor prognosis. The investigation was implemented on the impact of lncRNA FOXD1-AS1 on the migratory, invasive, and EMT of HCC cells. It has been observed that the lncRNA FOXD1-AS1 significantly influences the generation and metastasis of MCTC in vivo analysis. In mechanistic analysis, lncRNA FOXD1-AS1 enhanced immune escape in HCC via upregulation of PD-L1, which acted as a ceRNA by sequestering miR-615-3p. Additionally, lncRNA FOXD1-AS1 was found to modulate the EMT of CTCs through the activation of the PI3K/AKT pathway. CONCLUSION: This study presents compelling evidence supporting the role of lncRNA FOXD1-AS1 as a miRNA sponge that sequesters miR-655-3p and protects PD-L1 from suppression.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Animals , Mice , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/genetics , Liver Neoplasms/therapy , B7-H1 Antigen/genetics , Phosphatidylinositol 3-Kinases/genetics , RNA, Long Noncoding/genetics , Mice, Nude , Cell Line, Tumor , MicroRNAs/genetics , MicroRNAs/metabolism , Epithelial-Mesenchymal Transition/genetics , Forkhead Transcription Factors/genetics
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