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1.
Sci Data ; 11(1): 321, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548727

ABSTRACT

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Artificial Intelligence , Lung Neoplasms/diagnostic imaging , Thorax/diagnostic imaging , Anatomic Landmarks/diagnostic imaging
2.
J Nat Med ; 77(4): 928-938, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37294499

ABSTRACT

Plants of the Schisandra genus are commonly used in folk medicinal remedies. Some Schisandra species and their lignans have been reported to improve muscle strength. In the present study, four new lignans, named schisacaulins A-D, together with three previously described compounds ananonin B, alismoxide, and pregomisin were isolated from the leaves of S. cauliflora. Their chemical structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. Schisacaulin D and alismoxide significantly stimulated skeletal muscle cell proliferation by increasing the number of fused myotubes and expression of myosin heavy chain (MyHC) which may be good candidates for the treatment of sarcopenia.


Subject(s)
Lignans , Schisandra , Schisandra/chemistry , Lignans/chemistry , Plant Leaves/chemistry , Cell Proliferation , Muscle, Skeletal
3.
J Anal Methods Chem ; 2023: 2765508, 2023.
Article in English | MEDLINE | ID: mdl-36760655

ABSTRACT

The need for analytical methods that are fast, affordable, and ecologically friendly is expanding. Because of its low solvent consumption, minimal waste production, and speedy analysis, capillary electrophoresis is considered a "green" choice among analytical separation methods. With these "green" features, we have utilized the capillary electrophoresis method with capacitively coupled contactless conductivity detection (CE-C4D) to simultaneously determine glucosamine and Ca2+ in dietary supplements. The CE analysis was performed in fused silica capillaries (50 µm inner diameter, 40 cm total length, 30 cm effective length), and the analytical time was around 5 min. After optimization, the CE conditions for selective determination of glucosamine and Ca2+ were obtained, including a 10 mM tris (hydroxymethyl) aminomethane/acetic acid (Tris/Ace) buffer of pH 5.0 as the background electrolyte; separation voltage of 20 kV; and hydrodynamic injection (siphoning) at 25 cm height for 30 s. The method illustrated good linearity over the concentration range of 5.00 to 200 mg/L of for glucosamine (R 2 = 0.9994) and 1.00 to 100 mg/L for Ca2+ (R 2 = 0.9994). Under the optimum conditions, the detection limit of glucosamine was 1.00 mg/L, while that of Ca2+ was 0.05 mg/L. The validated method successfully analyzed glucosamine and Ca2+ in seven dietary supplement samples. The measured concentrations were generally in line with the values of label claims and with cross-checking data from reference methods (HPLC and ICP-OES).

4.
Z Naturforsch C J Biosci ; 78(1-2): 65-72, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36321958

ABSTRACT

Three sesquiterpene lactones (1-3) were isolated from the aerial part of Tithonia diversifolia (Hemsl.) A. Gray grown in the Hoa Binh province in Viet Nam. The structures of these three sesquiterpene lactones were identified as tagitinin A (1), 1ß-hydroxytirotundin 3-O-methyl ether (2), and tagitinin C (3) by analyzing spectroscopic data. For the first time, compound 2 was isolated from T. diversifolia growing in Viet Nam. Furthermore, contrary to existing literature, we determined that compound 1 was the major isolate. Compounds 1 and 3 significantly decreased numbers of acute myeloid leukemia OCI-AML3 cells by promoting apoptosis and causing cell cycle arrest at G0/G1 phase at concentrations as low as 2.5 µg/mL (compound 1) and 0.25 µg/mL (compound 3). Additionally, all three compounds showed cytotoxic activity against five human cancer cell lines (A549, T24, Huh-7, 8505, and SNU-1), with IC50 values ranging from 1.32 ± 0.14 to 46.34 ± 2.74 µM. Overall, our findings suggest that compounds 1 and 3 may be potential anti-cancer therapeutics and thus warrant further study.


Subject(s)
Asteraceae , Leukemia, Myeloid, Acute , Sesquiterpenes , Humans , Tithonia , Asteraceae/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Apoptosis , Leukemia, Myeloid, Acute/drug therapy , Cell Division , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Lactones/pharmacology , Lactones/chemistry
5.
Article in English | MEDLINE | ID: mdl-36174264

ABSTRACT

Vitamins and minerals are usually incorporated in pharmaceutical and nutraceutical products, but a simple, rapid, and inexpensive analytical method for their simultaneous determination is still lacking. In this study, we developed a quantification method for pyridoxine (vitamin B6) and magnesium (Mg) by using purpose-made capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) instrument. Main analytical conditions include: fused silica capillary (total length 55 cm, effective length 40 cm, inner diameter 50 µm); background electrolyte consisted of 10 mM L-arginine/acetic acid (pH 5) with 20% acetonitrile; separation voltage + 20 kV; hydrodynamic injection (siphoning at 20 cm in 25 s). Detection limits of vitamin B6 and Mg were 1 and 0.1 mg/L, respectively. Good linearity (R2 > 0.999) was observed for vitamin B6 and Mg calibration curves over concentration ranges of 3-100 and 0.3-200 mg/L, respectively. The method was applied to analyze vitamin B6 and Mg in several pharmaceutical and nutraceutical samples. The analytical results obtained by our method were in good agreement with reference methods (i.e., HPLC for vitamin B6 and ICP-OES for Mg). High-efficient and low-cost CE-C4D method can accordingly serve as a promising tool for concurrent analysis of inorganic and organic species in pharmaceutical and nutraceutical analysis.


Subject(s)
Magnesium , Vitamin B 6 , Acetonitriles , Arginine , Dietary Supplements , Electric Conductivity , Electrolytes , Electrophoresis, Capillary/methods , Pharmaceutical Preparations , Pyridoxine , Silicon Dioxide , Vitamins
6.
Chemosphere ; 306: 135527, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35780994

ABSTRACT

Membrane technology has rapidly gained popularity in wastewater treatment due to its cost-effectiveness, environmentally friendly tools, and elevated productivity. Although membrane performance in wastewater treatment has been reviewed in several past studies, the key techniques for improving membrane performance, as well as their challenges, and solutions associated with the membrane process, were not sufficiently highlighted in those studies. Also, very few studies have addressed hybrid techniques to improve membrane performance. The present review aims to fill those gaps and achieve public health benefits through safe water processing. Despite its higher cost, membrane performance can result in a 36% reduction in flux degradation. The issue with fouling has been identified as one of the key challenges of membrane technology. Chemical cleaning is quite effective in removing accumulated foulant. Fouling mitigation techniques have also been shown to have a positive effect on membrane photobioreactors that handle wastewater effluent, resulting in a 50% and 60% reduction in fouling rates for backwash and nitrogen bubble scouring techniques. Membrane hybrid approaches such as hybrid forward-reverse osmosis show promise in removing high concentrations of phosphorus, ammonium, and salt from wastewater. The incorporation of the forward osmosis process can reject 99% of phosphorus and 97% of ammonium, and the reverse osmosis approach can achieve a 99% salt rejection rate. The control strategies for membrane fouling have not been successfully optimized yet and more research is needed to achieve a realistic, long-term direct membrane filtering operation.


Subject(s)
Ammonium Compounds , Water Purification , Membranes, Artificial , Osmosis , Phosphorus , Sodium Chloride , Wastewater , Water Purification/methods
7.
Heliyon ; 8(3): e09070, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35287327

ABSTRACT

Balanophora laxiflora, a medicinal plant traditionally used to treat fever, pain, and inflammation in Vietnam, has been reported to possess prominent anti-inflammatory activity. This study examined the active constituents and molecular mechanisms underlying these anti-inflammatory effects using bioactivity-guided isolation in combination with cell-based assays and animal models of inflammation. Among the isolated compounds, the triterpenoid (21α)-22-hydroxyhopan-3-one (1) showed the most potent inhibitory effect on COX-2 expression in LPS-stimulated Raw 264.7 macrophages. Furthermore, 1 suppressed the expression of the inflammatory mediators iNOS, IL-1ß, INFß, and TNFα in activated Raw 264.7 macrophages and alleviated the inflammatory response in carrageenan-induced paw oedema and a cotton pellet-induced granuloma model. Mechanistically, the anti-inflammatory effects of 1 were mediated via decreasing cellular reactive oxygen species (ROS) levels by inhibiting NADPH oxidases (NOXs) and free radical scavenging activities. By downregulating ROS signalling, 1 reduced the activation of MAPK signalling pathways, leading to decreased AP-1-dependent transcription of inflammatory mediators. These findings shed light on the chemical constituents that contribute to the anti-inflammatory actions of B. laxiflora and suggest that 1 is a promising candidate for treating inflammation-related diseases.

8.
Nat Prod Res ; 36(13): 3381-3388, 2022 Jul.
Article in English | MEDLINE | ID: mdl-33350349

ABSTRACT

Reinvestigation of a methanol extract of Uraria crinita afforded a new 3- hydroxyisoflavanone, 3,5,7,2',4'-pentahydroxyisoflavanone (1), two new monoaryl glucosides, 3,4-dimethoxyphenyl 1-O-(6'-O-acetyl)-ß-D-glucopyranoside (2) and 3,4,5-trimethoxyphenyl 1-O-(6'-O-acetyl)-ß-D-glucopyranoside (3), in addition to three known compounds, 3'-O-methylorobol (4), robusflavone B (5), and apigenin (6). The structural elucidation of these compounds was achieved by analyses of their spectroscopic data (HR-ESI-MS, 1 D- and 2 D-NMR) and acidic hydrolysis. The U. crinita extracts and compounds 1-6 exhibited weak or no cytotoxic activity against KB, HepG2, Lu and MCF7 cell lines.


Subject(s)
Fabaceae , Fabaceae/chemistry , Glucosides/chemistry , Methanol/chemistry , Phenols/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology
9.
Nat Prod Res ; 36(9): 2341-2348, 2022 May.
Article in English | MEDLINE | ID: mdl-33078638

ABSTRACT

Phytochemical investigation of a methanolic extract of Sedum sarmentosum collected from Vietnam resulted in the isolation of a new megastigmane glucoside, named sedumoside K (1), together with 17 previously reported compounds (2-18). Structural elucidation of the new compound was achieved by HRFABMS, NMR spectroscopic analysis, acid hydrolysis and quantum ECD calculations. The absolute configuration of compounds 2-6 has been revised. The major isolates were tested for cytotoxic activity against HeLa human cervical cancer cells, and all showed moderate activities.


Subject(s)
Antineoplastic Agents , Drugs, Chinese Herbal , Sedum , Drugs, Chinese Herbal/chemistry , Humans , Norisoprenoids/chemistry , Phytochemicals , Sedum/chemistry
11.
Nat Prod Res ; 35(18): 3063-3070, 2021 Sep.
Article in English | MEDLINE | ID: mdl-31711303

ABSTRACT

Phytochemical investigation and chromatographic separation of extracts from the aerial parts of Dianella ensifolia (L.) DC. (synonym Dianella nemorosa Lam. Ex. Schiler f.) led to the isolation of 10 compounds, the structures of which were determined by HR-ESI-MS and 1 D- and 2 D-NMR spectroscopies, and by comparisons with published studies. Among the isolated compounds were three flavans, a biflavan, a biflavone, a tetralone, a naphthalen glycoside, an aromatic compound, and two steroids. Six of these were known chemicals, while three were identified as new compounds: 7-acetyl-4R,8-dihydroxy-6-methyl-1-tetralone, 2(S),2',4'-dihydroxy-7-methoxyflavan, and diaensi-biflavan. 2(S),7,4'-dimethoxy flavan was obtained for the first time as a natural product.


Subject(s)
Asphodelaceae/chemistry , Phenols , Molecular Structure , Phenols/isolation & purification , Phytochemicals/isolation & purification , Plant Components, Aerial/chemistry , Plant Extracts
12.
Nat Prod Res ; 33(6): 796-802, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29210295

ABSTRACT

This study describes the chemical constituents of Oldenlandia pinifolia (Wall. Ex G. Don) Kuntze (synonym Hedyotis pinifolia Wall. Ex G. Don) and discusses their anti-proliferative activities. Thirteen compounds were isolated from the n-hexane, ethyl acetate and n-butanol extracts of whole plants O. pinifolia by chromatography method. Their structures were elucidated using MS and NMR analysis and compared with reported data. They are three anthraquinones, a carotenoid, two triterpenes, four iridoid glycosides and three flavonoid glycosides. Among them, 2-methyl-1,4,6-trihydroxy-anthraquinone is a new one, and three compounds were found for the first time in this genus. MTT assay resulted that the n-butanol extract and four isolated compounds inhibited the proliferation of chronic myelogenous leukaemia cells. The results from Hoechst 33343 staining and caspase 3-inducing exhibited that those four tested compounds induced apoptosis and activated caspase 3 (p < 0.05). One of them, isorhamnetin-3-O-ß-rutinoside showed the most activity with IC50 value of 394.68 ± 25.12 µM.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Disaccharides/pharmacology , Flavonoids/pharmacology , Oldenlandia/chemistry , Plant Extracts/chemistry , Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Caspase 3/metabolism , Disaccharides/isolation & purification , Flavonoids/isolation & purification , Glycosides/isolation & purification , Glycosides/pharmacology , Humans , K562 Cells , KB Cells , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Triterpenes/isolation & purification , Triterpenes/pharmacology , Vietnam
13.
Nat Prod Res ; 33(21): 3065-3069, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30398364

ABSTRACT

Repeated column chromatography of the n-hexane extract of Ficus hirta leaves (Moraceae) led to isolation of a new oleanane triterpene, 3ß-hydroxy-11-oxo-olean-12-enyl-3-stearate (1) in addition to three known compounds, taraxerol (2), 3ß-acetoxy-11α-methoxy-12-ursene (3) and 3ß-acetoxy-11α-hydroxy-12-ursene (4). Their structures were elucidated by spectroscopic methods and by comparison with data reported in the literatures.


Subject(s)
Ficus/chemistry , Oleanolic Acid/analogs & derivatives , Triterpenes/isolation & purification , Molecular Structure , Oleanolic Acid/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Spectrum Analysis
14.
BMC Complement Altern Med ; 17(1): 191, 2017 Apr 04.
Article in English | MEDLINE | ID: mdl-28376775

ABSTRACT

BACKGROUND: The medicinal plant Siegesbeckia orientalis L. has been commonly used for the treatment of acute arthritis, rheumatism, and gout in Vietnam. However, pharmacological research of this plant associated with gout has not been reported. Anti-hyperuricemic and anti-inflammatory effects were evaluated and observed for the crude ethanol extract (CEE) of S. orientalis. Retention of these biological properties was found in a n-butanol-soluble fraction (BuOH fr.) of the extract, and therefore further biological and chemical investigations were undertaken on the BuOH fr. to support the medical relevance of this plant. METHODS: The aerial part of S. orientalis was obtained in the mountainous region of Vietnam. The crude ethanol extract (CEE) and its BuOH fr. were prepared from the plant materials. Anti-hyperuricemic activities of the CEE and BuOH fr. were tested in vivo using the model oxonate-induced hyperuricemia rats through determination of serum uric acid levels and inhibitory effects on xanthine oxidase (XO) in the rat liver. Anti-inflammatory activities of the BuOH fr. were also evaluated in vivo using carrageenan-induced paw edema and urate-induced synovitis in rats. Active components of the BuOH fr. were characterized by comparison of HPLC retention time (t R) and spectroscopic data (UV, 1H-NMR) with those of reference compounds. RESULTS: The CEE of S. orientalis displayed anti-hyperuricemic activity, and the BuOH fr. was found to be the most active portion of the extract. Further in vivo studies on this fraction showed 31.4% decrease of serum uric acid levels, 32.7% inhibition of xanthine oxidase (XO), 30.4% reduction of paw edema volume, symptomatic relief in urate-induced synovitis and significant analgesic effect at the dose of 120 mg/kg, as compared to the corresponding values of the control groups. Chemical analysis of the BuOH fr. revealed high phenolic content, identified as caffeic acid analogues and flavonones. CONCLUSIONS: This study suggested that anti-hyperuricemic and anti-inflammatory mechanism of S. orientalis is related to XO inhibitory effect of the phenolic components. Our findings support the use of this plant as the treatment of gout and other inflammatory diseases.


Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asteraceae/chemistry , Hyperuricemia/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Analgesics/isolation & purification , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Carrageenan , Disease Models, Animal , Hyperuricemia/chemically induced , Liver/drug effects , Liver/enzymology , Male , Phenols/chemistry , Phenols/isolation & purification , Plant Extracts/isolation & purification , Plants, Medicinal , Rats , Rats, Wistar , Uric Acid/blood , Vietnam , Xanthine Oxidase/antagonists & inhibitors
15.
Nat Prod Commun ; 12(4): 563-566, 2017 Apr.
Article in English | MEDLINE | ID: mdl-30520597

ABSTRACT

Chirita drakei Burtt (now accepted as Primzina drakei (B.L.Burtt) Mich.M61ler & A.Weber) is growing on limestone mountain slopes of Ha Long Bay islands in Vietnam. The chemical investigation of the aerial parts of C. drakei led to the isolation and structural elucidation of two new compounds named chiridrakoside A (1) and chiridrakoside B (2) besides twelve known compounds comprising five phenylethanoid glycosides (3-7), two lignans (8, 9), a phenyl propanoid (10), an anthraquinone (11), a furan derivative (12) and two triterpenes (13, 14). All described compounds, except 4, 5 and 11, were obtained for the first time from the genera Chirita or Primulina. The cytotoxic activity of the isolated compounds was evaluated against the four human cancer cell lines KB (mouth epidermal carcinoma), HepG2 (hepatocellular carcinoma), Lu (lung carcinoma) and MCF7 (breast carcinoma). Epoxyconiferyl alcohol (10) exhibited cytotoxic activity against the tested cell lines (IC50 from 46 to 128 µM).


Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Magnoliopsida/chemistry , Plant Extracts/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Humans , Lignans/chemistry , Lignans/isolation & purification , Lignans/pharmacology , Molecular Structure , Plant Extracts/isolation & purification , Plant Extracts/pharmacokinetics , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Vietnam
16.
Article in English | WPRIM | ID: wpr-820701

ABSTRACT

OBJECTIVE@#To screen Vietnamese medicinal plants for xanthine oxidase (XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant.@*METHODS@#The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR.@*RESULTS@#Three hundreds and eleven methanol extracts (CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 μg/mL with inhibition rates of over 50%. The extracts of Archidendron clypearia (A. clypearia), Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC values below 30 μg/mL. Chemical study performed on the extract of A. clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and (-)-7-O-galloyltricetiflavan. The compound (-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC value of 25.5 μmol/L.@*CONCLUSIONS@#From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC values of the methanol extracts below 30 μg/mL. Compound (-)-7-O- galloyltricetiflavan was identified as an XO inhibitor from A. clypearia with IC value of 25.5 μmol/L.

17.
Article in Chinese | WPRIM | ID: wpr-972610

ABSTRACT

Objective To screen Vietnamese medicinal plants for xanthine oxidase (XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. Methods The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. Results Three hundreds and eleven methanol extracts (CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 μg/mL with inhibition rates of over 50%. The extracts of Archidendron clypearia (A. clypearia), Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC

18.
BMC Cancer ; 15: 304, 2015 Apr 18.
Article in English | MEDLINE | ID: mdl-25900027

ABSTRACT

BACKGROUND: Angiogenesis plays a role in tumor growth and is partly mediated by factors in both the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) pathways. Durable clinical responses with VEGF tyrosine kinase inhibitors (TKIs) may be limited by intrinsic tumor resistance. We hypothesized that FGF signaling may impact clinical responses to sorafenib. METHODS: Nephrectomy material was available from 40 patients with metastatic renal cell carcinoma (RCC) enrolled in a phase II clinical trial of sorafenib ± interferon (ClinicalTrials.gov Identifier NCT00126594). Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor substrate 2 alpha (FRS2α) expression was assessed by in situ hybridization and immunofluorescence, respectively. The relationship between fibroblast growth factor pathway marker levels and progression-free survival (PFS) was analyzed using Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Univariate analysis indicated that more intense FGFR1 staining was associated with shorter PFS (log-rank P = 0.0452), but FRS2α staining was not significantly associated with PFS (log-rank P = 0.2610). Multivariate Cox proportional hazards regression models were constructed for FGFR1 and FRS2α individually, adjusting for baseline Eastern Cooperative Oncology Group performance status, treatment arm and anemia status. When adjusted for each of these variables, the highest intensity level of FGFR1 (level 3 or 4) had increased progression risk relative to the lowest intensity level of FGFR1 (level 1) (P = 0.0115). The highest intensity level of FRS2α (level 3 or 4) had increased progression risk relative to the lowest intensity level of FRS2α (level 1) (P = 0.0126). CONCLUSIONS: Increased expression of FGFR1 and FRS2α was associated with decreased PFS among patients with metastatic RCC treated with sorafenib. The results suggest that FGF pathway activation may impact intrinsic resistance to VEGF receptor inhibition.


Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/biosynthesis , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Receptor, Fibroblast Growth Factor, Type 1/biosynthesis , Aged , Aged, 80 and over , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/drug therapy , Female , Humans , Male , Middle Aged , Niacinamide/therapeutic use , Prospective Studies , Sorafenib , Treatment Outcome
19.
J Pharmacol Exp Ther ; 344(1): 41-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23033374

ABSTRACT

Raising high-density lipoprotein (HDL) levels is proposed as an attractive target to treat cardiovascular disease. However, a number of clinical studies examining the effect of HDL-raising therapies have been prematurely halted due to futility. Therefore there is a need for alternative therapies. Infusion of reconstituted HDL (rHDL) particles is still considered as a viable approach to increasing HDL levels. In this study we have profiled the anti-inflammatory effects of a trimeric-HDL particle. We show that trimeric apoA-I and rHDL particles promote cholesterol efflux to a similar rate as native apoA-I particles in both ABCA1-dependent and -independent pathways. Trimeric particles inhibited ICAM-1 and VCAM-1 expression and the ability of the endothelium to capture monocytes under shear flow. Monocyte activation, CD11b-dependent adhesion, and monocyte recruitment under shear flow conditions were perturbed by the trimeric particles. Our data suggest that trimeric rHDL particles can be constructed without any loss of function, preserving the anti-inflammatory effects of HDL that are key to its in vivo actions.


Subject(s)
Anti-Inflammatory Agents , Apolipoprotein A-I/chemistry , Apolipoprotein A-I/pharmacology , Lipoproteins, HDL/pharmacology , CD11b Antigen/biosynthesis , Cell Adhesion/drug effects , Cell Adhesion Molecules , Cell Separation , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flow Cytometry , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Immunohistochemistry , Intercellular Adhesion Molecule-1/drug effects , Liposomes , Monocytes/metabolism , Particle Size , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects
20.
J Biomed Biotechnol ; 2010: 290516, 2010.
Article in English | MEDLINE | ID: mdl-21318151

ABSTRACT

The exact molecular mechanism by which epigallocatechin gallate (EGCG) suppresses human pancreatic cancer cell proliferation is unclear. We show here that EGCG-treated pancreatic cancer cells AsPC-1 and BxPC-3 decrease cell adhesion ability on micro-pattern dots, accompanied by dephosphorylations of both focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) whereas retained the activations of mitogen-activated protein kinase and mammalian target of rapamycin. The growth of AsPC-1 and BxPC-3 cells can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 µM which completely abolishes activations of FAK and IGF-1R, EGCG suppresses more than 50% of cell proliferation without evidence of apoptosis analyzed by PARP cleavage. Finally, the MEK1/2 inhibitor U0126 enhances growth-suppressive effect of EGCG. Our data suggests that blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can be used in combination with other therapies, for pancreatic cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Catechin/analogs & derivatives , Focal Adhesion Kinase 1/antagonists & inhibitors , Pancreatic Neoplasms/metabolism , Receptor, IGF Type 1/antagonists & inhibitors , Tea , Antineoplastic Agents/therapeutic use , Antioxidants/metabolism , Antioxidants/pharmacology , Apoptosis/physiology , Catechin/metabolism , Catechin/pharmacology , Catechin/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Humans , Mitogen-Activated Protein Kinases/metabolism , Pancreatic Neoplasms/drug therapy
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