Publications by authors named "Hailun Li"

42 Publications

Circ_0023404 sponges miR-136 to induce HK-2 cells injury triggered by hypoxia/reoxygenation via up-regulating IL-6R.

J Cell Mol Med 2021 Jun 4;25(11):4912-4921. Epub 2021 May 4.

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

The significance of circular RNAs (circRNAs) is reported in various kidney diseases including acute kidney injury (AKI). Specific circRNAs have the capacity to function as novel indicators of AKI. Circ_0023404 exhibits an important role in several diseases. Nevertheless, the detailed biological role of circ_0023404 in AKI remains poorly known. The present study aimed to investigate the effect of circ_0023404 on renal ischaemia/reperfusion (I/R) injury in vitro. Here, we evaluated the function of circ_0023404 in HK-2 cells in response to hypoxia/reoxygenation (H/R). We established a cell AKI model induced by H/R in HK-2 cells. We found circ_0023404 was significantly increased in AKI. Then, we found loss of circ_0023404 increased cell growth, repressed apoptosis, reduced inflammatory factors secretion and oxidative stress generation in vitro. Besides, circ_0023404 sponged miR-136. miR-136 overturned the effects of circ_0023404 on HK-2 cell injury. We assumed IL-6 receptor (IL-6R) as a target of miR-136 and IL-6R was activated by circ_0023404 via sponging miR-136. In conclusion, we revealed circ_0023404 contributed to HK-2 cells injury stimulated by H/R via sponging miR-136 and activating IL-6R.
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http://dx.doi.org/10.1111/jcmm.15986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178261PMC
June 2021

Tremella fuciformis polysaccharides ameliorated ulcerative colitis via inhibiting inflammation and enhancing intestinal epithelial barrier function.

Int J Biol Macromol 2021 Jun 17;180:633-642. Epub 2021 Mar 17.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China. Electronic address:

The purpose of this paper was to explore the therapeutic effect and underlying mechanism of Tremella fuciformis polysaccharides (TFP) on ulcerative colitis (UC) based on dextran sodium sulfate (DSS)-induced mice UC model and lipopolysaccharide (LPS)-stimulated Caco-2 cells model. The results firstly indicated that TFP can significantly alleviate the symptoms and signs of the DSS-induced mice UC model, which manifests as improvement of body weight loss, increase of colon length, decrease of colon thickness and reduction of intestinal permeability. Then, results from histopathological and electron microscope analysis further implied that TFP could dramatically reduce inflammatory cells infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of LPS-stimulated Caco-2 cells model in vitro also further confirmed that TFP could markedly inhibit the expressions of pro-inflammatory cytokines and increase related genes or proteins expressions of intestinal barrier and mucus barrier. Taken together, these data suggested that TFP has a significant therapeutic effect on DSS-induced UC model, and its mechanisms are closely linked to the inhibition of inflammation and the restoration of intestinal barrier and mucus barrier function. These beneficial effects may make TFP a promising drug to be used in alleviating UC.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.083DOI Listing
June 2021

Bidirectional regulation of glial potassium buffering - glioprotection versus neuroprotection.

Elife 2021 Mar 1;10. Epub 2021 Mar 1.

Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, United States.

Glia modulate neuronal excitability and seizure sensitivity by maintaining potassium and water homeostasis. A salt inducible kinase 3 (SIK3)-regulated gene expression program controls the glial capacity to buffer K and water in , however upstream regulatory mechanisms are unknown. Here, we identify an octopaminergic circuit linking neuronal activity to glial ion and water buffering. Under basal conditions, octopamine functions through the inhibitory octopaminergic G-protein-coupled receptor (GPCR) OctβR to upregulate glial buffering capacity, while under pathological K stress, octopamine signals through the stimulatory octopaminergic GPCR OAMB1 to downregulate the glial buffering program. Failure to downregulate this program leads to intracellular glia swelling and stress signaling, suggesting that turning down this pathway is glioprotective. In the seizure model, the SIK3-mediated buffering pathway is inactivated. Reactivation of the glial buffering program dramatically suppresses neuronal hyperactivity, seizures, and shortened life span in this mutant. These findings highlight the therapeutic potential of a glial-centric therapeutic strategy for diseases of hyperexcitability.
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http://dx.doi.org/10.7554/eLife.62606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946421PMC
March 2021

Consumers' attention on identification, nutritional compounds, and safety in heavy metals of Canadian sea cucumber in Chinese food market.

Food Sci Nutr 2020 Nov 13;8(11):5962-5975. Epub 2020 Sep 13.

Clinical Medical College of Acupuncture Moxibustion and Rehabilitation School of Pharmaceutical Science Guangzhou University of Chinese Medicine Guangzhou China.

Background: Based on the consumers' attention issues of sea cucumbers, we aimed to complete comprehensive information of commercial Canadian sea cucumbers (CCSC), which sprang up extensively in Chinese food market.

Results: CCSC were identified as and characterized based on the characteristics, nutritional compositions, and heavy metals. The abdomen and five internal tendons of were special orange. The average of soaking degree and water content, which consumers paid great attention to, was 2.8 ± 0.3 and 0.46 ± 0.09%, respectively. Proteins (56.4 ± 9.1%) and polysaccharides (12.2 ± 14.7%) were the principal nutrient component. In addition, there was a variety of free amino acids, in which arginine (70.1 ± 50.0 mg/100 g), glutamate (42.6 ± 23.9 mg/100 g), and alanine (32.2 ± 21.0 mg/100 g) were the main components. Phosphorus (P, 0.26 ± 0.05%), magnesium (Mg, 0.19 ± 0.07%), and kalium (K, 0.17 ± 0.08%) were the major mineral elements. Amount of heavy metal was within the safety limitation (5.5 ± 1.4 mg/kg). Furthermore, the active ingredients were positively correlated with size.

Conclusion: The overall findings enriched the information of for consumers and suggested that the quality of was varied following commercial classification and size.
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http://dx.doi.org/10.1002/fsn3.1882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684582PMC
November 2020

Polydatin alleviates high-fat diet induced atherosclerosis in apolipoprotein E-deficient mice by autophagic restoration.

Phytomedicine 2021 Jan 23;81:153301. Epub 2020 Nov 23.

Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an 223003, Jiangsu, PR China.

Background: Polydatin has been reported to possess remarkable anti-atherosclerotic activities. However, there are different opinions on its regulatory mechanisms. It remains unclear whether the anti-atherosclerotic mechanism of polydatin is related to its autophagic restoration or not. The aim of this study was to explore the question.

Methods: Using atherosclerotic model induced by high-fat diet in apolipoprotein E-deficient mice, the investigation was performed with polydatin alone or in combination with autophagic inhibitor or inducer intervention. Inhibitory sites of polydatin to PI3K were identified by molecular docking.

Results: Polydatin can significantly inhibit PI3K/Akt/mTOR pathway proteins expression, improve autophagic dysfunction and reduce atherosclerotic lesions. These effects could be antagonized and reinforced by adding autophagic inhibitor and inducer, respectively. Inhibitory sites of polydatin to PI3K were found to be ASP-810, SER-854, VAL-851, LEU-807, SER-774, LYS-802, ASP-933, SER-919, ASN-920, PHE-930, MEF-922, GLN-859 of PI3Kα.

Conclusions: The mechanism of polydatin to alleviate atherosclerotic lesions was achieved by autophagic restoration.
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http://dx.doi.org/10.1016/j.phymed.2020.153301DOI Listing
January 2021

circ-AKT3 aggravates renal ischaemia-reperfusion injury via regulating miR-144-5p /Wnt/β-catenin pathway and oxidative stress.

J Cell Mol Med 2020 Nov 16. Epub 2020 Nov 16.

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China.

Renal ischaemia-reperfusion (RI/R) injury is one major pathological state of acute kidney injury (AKI) with a mortality rate ranking 50% to 80%. MiR-144-5p acts as a molecular trigger in various diseases. We presumed that miR-144-5p might be involved RI/R injury progression. We found that RI/R injury decreased miR-144-5p expression in rat models. MiR-144-5p downregulation promoted cell apoptosis rate and activated Wnt/β-catenin signal in RI/R injury rats. By performing bioinformatic analysis, RIP, RNA pull-down, luciferase reporter experiments, we found that circ-AKT3 sponged to miR-144-5p and decreased its expression in RI/R injury rats. Moreover, we found that circ-AKT3 promoted cell apoptosis rate and activated Wnt/β-catenin signal, and miR-144-5p mimic reversed the promotive effect of circ-AKT3 in rat models. We also found that circ-AKT3 increased the oxidative stress level in rat models. In conclusion, our study suggests that the circAKT3 is involved RI/R injury progression through regulating miR-144-5p/Wnt/β-catenin pathway and oxidative stress.
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http://dx.doi.org/10.1111/jcmm.16072DOI Listing
November 2020

Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874.

BMC Pharmacol Toxicol 2020 07 22;21(1):52. Epub 2020 Jul 22.

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, 223001, PR China.

Background: Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Novel therapeutic approaches slowing down its incidence is still lacking. Psoralen is the major active ingredient of Psoralea corylifolia Linn. (PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN using in vitro model.

Methods: Cell viability assay and immunofluorescence were used to evaluate the effect of psoralen on high glucose (HG)-stimulated human kidney HK-2 cells (48 h). RT-qPCR was used to detect the expressions of miRNA in cells. Cell transfection, apoptosis assay, inflammatory cytokines detection and Western blot were further performed to explore the underlying molecular mechanisms.

Results: HG-induced toxicity of HK-2 cells was alleviated by psoralen. Meanwhile, the secretion of inflammatory cytokines and extracellular matrix (ECM) accumulation induced by HG in HK-2 cells were also decreased by psoralen. In addition, the expression of miR-874 in HK-2 cells was significantly upregulated by psoralen. Western blot assays indicated that psoralen could reverse HG-induced increase of TLR-4/NF-κB and Smad2 via upregulation of miR-874.

Conclusion: This study demonstrated that psoralen could significantly alleviate HG-induced HK-2 cell injury via upregulation of miR-874. In addition, HG-induced increase of TLR-4/NF-κB and Smad2 was revered by psoralen. Therefore, psoralen might serve as an agent for the treatment of DN.
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http://dx.doi.org/10.1186/s40360-020-00434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376944PMC
July 2020

miR-195-5p alleviates acute kidney injury through repression of inflammation and oxidative stress by targeting vascular endothelial growth factor A.

Aging (Albany NY) 2020 06 3;12(11):10235-10245. Epub 2020 Jun 3.

Department of Nephrology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Acute kidney injury (AKI) is a common renal dysfunction. Renal ischemia-reperfusion (I/R) injury contributes to AKI progression. The microRNA miR-195-5p can act as a crucial tumor inhibitor in various cancers. However, the potential biological effects of miR-195-5p on AKI are not well-understood. We found that miR-195-5p levels were decreased in the serum samples of patients with AKI. Next, we determined miR-195-5p expression in the renal tissues of the rats and found that it was downregulated. Renal function was evaluated and confirmed using blood urea nitrogen and serum Cr levels. In parallel, the hypoxia-induced NRK-52E cell model was employed, and miR-195-5p was found to be markedly reduced under hypoxic conditions. Furthermore, miR-195-5p was modulated in NRK-52E cells. miR-195-5p induced NRK-52E cell proliferation and protected NRK-52E cells against hypoxia-triggered apoptosis. In an I/R mouse model, miR-195-5p alleviated renal injury triggered by I/R. In addition, oxidative stress and inflammatory factor concentrations were assessed using ELISA. The results showed that miR-195-5p mimicked attenuated oxidative stress induced by I/R injury and downregulated the protein expression of inflammatory factors. Moreover, we identified that vascular endothelial growth factor A (VEGFA) was a target gene of miR-195-5p, which could negatively regulate VEGFA expression in vitro. Inhibitors of miR-195-5p subsequently contributed to renal injury, which was reversed by VEGFA loss. In conclusion, miR-195-5p may repress AKI by targeting VEGFA.
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http://dx.doi.org/10.18632/aging.103160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346085PMC
June 2020

An effective method for extracting anthocyanins from blueberry based on freeze-ultrasonic thawing technology.

Ultrason Sonochem 2020 Nov 27;68:105192. Epub 2020 May 27.

National & Local Joint Engineering Research Center for Mineral Salt Deep Utilization, Huaiyin Institute of Technology, Huai'an 223003, Jiangsu, PR China. Electronic address:

The aim of this study was to develop an effective method for extracting anthocyanins from blueberry Vaccinium spp. (ABVS) using freeze-ultrasonic thawing technology (FUTE). Various parameters including freezing time, ultrasonic time, ultrasonic temperature and liquid-solid ratio were optimized by a single-factor design and multiple response surface methodology. The amounts of extracted anthocyanin and cyanidin-3-O-glucoside were measured by UV and HPLC respectively. The maximum yield of anthocyanins was achieved by freezing the samples for 5.43 min in liquid nitrogen at the liquid-solid ratio of 24.07:1 mL/g, followed by ultrasonic thawing at 41.64 °C for 23.56 min. The yield and antioxidant effects of ABVS extracted using FUTE, ultrasound-assisted extraction (UAE) and freeze-thawing extraction (FTE) were compared in order to determine the overall efficacy of FUTE. In addition to the higher content, FUTE extracted ABVS showed greater ability to scavenge DPPH·, ABTS and superoxide anions, and inhibit lipid peroxidation compared to the ABVS extracted by UAE or FTE. The reducing power of the FUTE-derived ABVS was intermediate between that of the UAE and FTE samples. Taken together, FUTE can rapidly and effectively extract ABVS and retain its antioxidant capacity.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105192DOI Listing
November 2020

Comparison of different extraction methods for polysaccharides from Crataegus pinnatifida Bunge.

Int J Biol Macromol 2020 May 9;150:1011-1019. Epub 2019 Nov 9.

Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an 223003, PR China. Electronic address:

In this study, different extraction methods of polysaccharides from Crataegus pinnatifida Bunge (CPP) were compared by studying the extraction yield, structural characteristics and antioxidant activities. Firstly, polysaccharides were obtained using hot water extraction (CPPh), ultrasound assisted extraction (CPPu), enzyme assisted extraction (CPPe) and enzyme-ultrasound assisted extraction (CPPc), respectively. Meanwhile, the optimum extraction conditions of enzyme-ultrasonic assisted extraction were determined by response surface method (RSM). The extraction yields, structural characteristics and antioxidant activities were investigated and compared by visual photos, gas chromatography, ultraviolet-visible and Fourier-transform infrared spectroscopy. The results clearly showed that enzyme-ultrasonic assisted extraction possessed the highest extraction yield (10.39 ± 0.04%). The molecular weight of CPPh was the highest while the other polysaccharides had no significant difference. Besides, the monosaccharide composition of CPPc, CPPh, CPPu and CPPe were similar but the molar percentages of monosaccharide were different. Finally, the results of antioxidant activities showed that CPPc exhibited the highest scavenging effect of superoxide radical and lipids inhibiting ability. In summary, enzyme-ultrasonic assisted extraction was a high-efficient and low-energy consumption method for CPP extraction.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.11.056DOI Listing
May 2020

SIK3 suppresses neuronal hyperexcitability by regulating the glial capacity to buffer K and water.

J Cell Biol 2019 12 23;218(12):4017-4029. Epub 2019 Oct 23.

Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO

Glial regulation of extracellular potassium (K) helps to maintain appropriate levels of neuronal excitability. While channels and transporters mediating K and water transport are known, little is understood about upstream regulatory mechanisms controlling the glial capacity to buffer K and osmotically obliged water. Here we identify salt-inducible kinase 3 (SIK3) as the central node in a signal transduction pathway controlling glial K and water homeostasis in Loss of SIK3 leads to dramatic extracellular fluid accumulation in nerves, neuronal hyperexcitability, and seizures. SIK3-dependent phenotypes are exacerbated by K stress. SIK3 promotes the cytosolic localization of HDAC4, thereby relieving inhibition of Mef2-dependent transcription of K and water transport molecules. This transcriptional program controls the glial capacity to regulate K and water homeostasis and modulate neuronal excitability. We identify HDAC4 as a candidate therapeutic target in this pathway, whose inhibition can enhance the K buffering capacity of glia, which may be useful in diseases of dysregulated K homeostasis and hyperexcitability.
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http://dx.doi.org/10.1083/jcb.201907138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891094PMC
December 2019

Protective activities of polysaccharides from Cipangopaludina chinensis against high-fat-diet-induced atherosclerosis via regulating gut microbiota in ApoE-deficient mice.

Food Funct 2019 Oct;10(10):6644-6654

Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an 223003, Jiangsu, China.

Sulfated polysaccharides (CCPS) obtained from Cipangopaludina chinensis have a certain protective effect on cardiovascular diseases, but whether they can slow down the development of atherosclerosis (AS) and how they work are still unclear. In this study, we aimed to determine the preventive effects of CCPS on high-fat-diet (HFD)-induced AS in mice and the underlying mechanism focusing on gut microbiota profile modulation. First, male apolipoprotein E knockout mice were fed HFD or normal diet and simultaneously intervened by a blank solvent, CCPS or atorvastatin to last for 12 weeks. Then, the histopathological characteristics, biochemical parameters and gut microbiota compositions of the experimental groups were compared. The results demonstrated that the CCPS supplementation significantly improved HFD-induced AS of the mice, which was mainly manifested by regulating the plasma lipid balance, decreasing the atherosclerotic index and reducing the atherosclerotic plaque area in a dose-dependent manner. Mechanistic analysis revealed that CCPS regulated the bacterial composition including reducing the ratio of Firmicutes/Bacteroidetes, decreasing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. Furthermore, through environmental factor correlation analysis, we found that the preventive effects of CCPS on AS in mice induced by HFD were closely related to reshaping the composition of gut microbiota.
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http://dx.doi.org/10.1039/c9fo01530bDOI Listing
October 2019

Dendrobium officinale polysaccharides alleviate colon tumorigenesis via restoring intestinal barrier function and enhancing anti-tumor immune response.

Pharmacol Res 2019 10 29;148:104417. Epub 2019 Aug 29.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, PR China; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, PR China. Electronic address:

Intact epithelial barrier and mucosal immune system are crucial for maintaining intestinal homeostasis. Previous study indicated that Dendrobium officinale polysaccharides (DOPS) can regulate immune responses and inflammation to alleviate experimental colitis. However, it remains largely unknown whether DOPS can suppress AOM/DSS-induced colorectal cancer (CRC) model through its direct impact on intestinal barrier function and intestinal mucosal immunity. Here, we demonstrated the therapeutic action of DOPS for CRC model and further illustrated its underlying mechanisms. Treatment with 5-aminosalicylic acid (5-ASA) and DOPS significantly improved the clinical signs and symptoms of chronic colitis, relieve colon damage, suppress the formation and growth of colon tumor in CRC mice. Moreover, administration of DOPS effectively preserved the intestinal barrier function via reducing the loss of zonula occludens-1 (ZO-1) and occludin in adjacent tissues and carcinomatous tissues. Further studies demonstrated that DOPS improved the metabolic ability of tumor infiltrated CD8 cytotoxic T lymphocytes (CTLs) and reduced the expression of PD-1 on CTLs to enhance the anti-tumor immune response in the tumor microenvironments (TME). Together, the conclusions indicated that DOPS restore intestinal barrier function and enhance intestinal anti-tumor immune response to suppress CRC, which may be a novel strategy for the prevention and treatment of CRC.
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http://dx.doi.org/10.1016/j.phrs.2019.104417DOI Listing
October 2019

Sulfated polysaccharide from Undaria pinnatifida stabilizes the atherosclerotic plaque via enhancing the dominance of the stabilizing components.

Int J Biol Macromol 2019 Nov 21;140:621-630. Epub 2019 Aug 21.

School of Pharmaceutical Science, Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, PR China. Electronic address:

The purpose of this study was to investigate the stable effect and mechanism of sulfated polysaccharide from Undaria pinnatifida (SPUP) on atherosclerotic plaque. The results showed that atherosclerotic plaques in the ApoE mice of high-fat diet model group increased significantly without drug intervention. The content of vulnerable components (lipid, inflammatory macrophage) increased significantly, and the content of stability components (smooth muscle cell, collagen) reduced significantly. However, it could find that atherosclerotic plaque areas were decreased in a dose-dependent manner after SPUP intervention. SPUP could enhance the dominance of the stability components in plaque, and reduce the content of vulnerable component. Furthermore, SPUP could significantly reduce the matrix metalloprotein-9 content in atherosclerotic plaque. These results suggested that SPUP could stabilize atherosclerotic plaque by enhancing the dominance of the stability components content, reducing the vulnerability components content, and lowering the vulnerability index value.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.08.173DOI Listing
November 2019

The longitudinal effect of subclinical hypothyroidism on urine microalbumin-to-urine creatinine ratio in patients with type 2 diabetes mellitus.

BMC Endocr Disord 2019 Aug 5;19(1):84. Epub 2019 Aug 5.

The Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian, 223002, Jiangsu, China.

Background: In patients with diabetes mellitus, the urinary microalbumin-to-urine creatinine ratio (UACR) can not only predict the occurrence of diabetic nephropathy but also can be a risk factor for cardiovascular disease and renal function damage. Current studies on subclinical hypothyroidism (SCH) and UACR are mainly cross-sectional studies, and the results suggest that SCH is an independent risk factor for UACR. To further explore the longitudinal effect of SCH on UACR, we carried out this study.

Methods: This was a retrospective cohort study including 46 patients with type 2 diabetes mellitus and SCH in the Department of Endocrinology, The Affiliated Huai'an Hospital of Xuzhou Medical University from January 2013 to April 2018. At the same time, 96 patients with type 2 diabetes mellitus and euthyroid were chosen according to 1:2 approximately matched with age, sex and duration of diabetes mellitus. Univariate analysis, stratified analysis, and multiple linear regression analysis were used to investigate the effect of SCH on ΔUACR(ΔUACR = UACR after 1 year - baseline UACR) in patients with type 2 diabetes mellitus.

Results: There was no significant difference between the baseline UACR, (p > 0.05). However, the ΔUACR was significantly higher in SCH group than euthyroid group, as shown by univariate analysis, stratified analysis and multiple linear regression analysis (β:-1.071, 95% CI: - 1.713--0.428), and the difference was statistically significant (all p < 0.05).

Conclusion: SCH is associated with an increased UACR in type 2 diabetes mellitus patients. It is necessary to screen for thyroid function in type 2 diabetes mellitus and increase the follow-up frequency of UACR in patients with SCH.
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http://dx.doi.org/10.1186/s12902-019-0405-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683563PMC
August 2019

Renoprotective effect and mechanism of polysaccharide from Polyporus umbellatus sclerotia on renal fibrosis.

Carbohydr Polym 2019 May 12;212:1-10. Epub 2019 Feb 12.

Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, PR China. Electronic address:

As a fungal polysaccharide, polysaccharide (PPUS) from Polyporus umbellatus sclerotia have showed remarkable anti-inflammatory activities. In view of the closely relationship between inflammation and renal fibrosis, and considering the significant role of other fungal polysaccharides on treatment of renal fibrosis, we speculated that PPUS may have therapeutic effects on renal fibrosis. However, there was not any reports about PPUS treatment this disease. The purpose of this paper is to investigate renoprotective effect and mechanism of PPUS on renal fibrosis. The results indicated that PPUS can improve renal function and ameliorate the degree of renal collagen deposition and further fibrosis. Its mechanism was found to be related with decreased inflammation, suppressive epithelial-mesenchymal transition, reconstructed the balance of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and pro-fibrotic and anti-fibrotic factors. The data implied that PPUS can serve as a clinical candidate on treatment of renal interstitial fibrosis.
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http://dx.doi.org/10.1016/j.carbpol.2019.02.026DOI Listing
May 2019

Therapeutic effect and mechanism of polysaccharide from Alpiniae oxyphyllae fructus on urinary incontinence.

Int J Biol Macromol 2019 May 30;128:804-813. Epub 2019 Jan 30.

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223001, Jiangsu, PR China. Electronic address:

The purpose of this paper was to investigate the effects and mechanism of polysaccharide (PAOF) from Alpiniae oxyphyllae fructus on urinary incontinence (UI) in old-age hydruric model rats (OHMR). Results suggested that PAOF can significantly reduce the urination volume, Na, Cl emission and increase K excretion of OHMR. In addition, PAOF can increase the content of aldosterone (ALD) and antidiuretic hormone (ADH) in blood of OHMR. The coefficients of spleen, thymus and adrenal of OHMR were improved by PAOF. Furthermore, PAOF can not only elevate significantly the expression of β3-adrenoceptor mRNA in bladder detrusor of OHMR, but also increase the content of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in bladder detrusor of OHMR. Meanwhile, PAOF can elevate significantly the expression of PKA protein in bladder detrusor of rats with polyuria. The data implied that PAOF may offer therapeutic potential against UI.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.01.193DOI Listing
May 2019

Effect of polysaccharide from Undaria pinnatifida on proliferation, migration and apoptosis of breast cancer cell MCF7.

Int J Biol Macromol 2019 Jan 18;121:734-742. Epub 2018 Oct 18.

School of Integrated Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shangdong, PR China. Electronic address:

Sulfated polysaccharide from Undaria pinnatifida (SPUP) has significant anti-breast cancer activity. However, its anticarcinogenic mechanism still remains unclear. The aim of this article is to observe the effect of SPUP on proliferation, migration and apoptosis of human breast cancer cell line MCF7. Firstly, the effect of SPUP on proliferation was evaluated through MTT assay, plate clonality assay and immunofluorescence test of PCNA. The results showed that SPUP could significantly reduce MCF7 cells proliferation in a time- and dose-dependent manner. Based on transwell and scratch wound healing assays, then, inhibitory action of SPUP for MCF7 cells migration was observed. Finally, apoptosis and cycle arrest of SPUP for MCF7 cells also were found by the results from both flow cytometry analysis and Hoechst 33342 staining of apoptotic cells. Overall, these results showed anti-breast cancer mechanism of SPUP could be possibly related to inhibit migration, proliferation and induce apoptosis of cancer cells.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.10.086DOI Listing
January 2019

Methods of extraction, separation, purification, structural characterization for polysaccharides from aquatic animals and their major pharmacological activities.

Crit Rev Food Sci Nutr 2020 4;60(1):48-63. Epub 2018 Oct 4.

Mathematical Engineering Academy of Chinese Medicine, and School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.

The further development of fishery resources is a hotspot in the development of the fishery industry. However, how to develop aquatic animal resources deeply is a key point to be solved in the fishery industry. Over the past decades, numerous aquatic animals have gained great attention in the development and utilization of their bioactive molecules which are of therapeutic applications as nutraceuticals and pharmaceuticals. Recent research revealed that aquatic animals are composed of many vital moieties, such as polysaccharides and proteins, which provide health benefits beyond basic nutrition. In particular, aquatic animal polysaccharides are gaining worldwide popularity owing to their high content, ease of extraction, specific structure, few side effects, prominent therapeutic potential and incorporation in functional foods and dietary supplements. Thus, tremendous research on the isolation, identification and bioactivities of polysaccharides has been carried out. This review presents comprehensive viewpoints on extraction, separation, purification, structural characterization and bioactivity of various polysaccharides from aquatic animals, such as sea cucumber, abalone, oyster and mussels. In addition, this review profiled a brief knowledge on both current challenges and future scope in aquatic animal polysaccharides field. The review will be a direction of deep processing in fishery resources, which is a hotspot, but technical bottleneck. Furthermore, the review could be served as a useful reference material for further investigation, production and application of polysaccharides from aquatic animals in functional foods and therapeutic agents.
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http://dx.doi.org/10.1080/10408398.2018.1512472DOI Listing
February 2020

Targeting Detection and Inhibition of Methicillin-Resistant Pneumonia with a Theranostic Mesoporous Silica-Based Platform.

J Biomed Nanotechnol 2018 Jul;14(7):1298-1307

In this study, non-invasive early stage diagnosis of methicillin-resistant Staphylococcus aureus-related pneumonia and related anti-inflammatory profiles with theranostic platforms were reported. Mesoporous silica NPs were first synthesized and chemically modified to bear an amino group and further covalently bind to amino-2,4,6-triiodoisophthalic acid and anti-methicillin-resistant S. aureus antibodies. The drug-loaded NPs were characterized by transmission electron microscopy, dynamic light scattering analysis and X-ray photoelectron spectra. MTT and broth dilution assays were used to investigate the biocompatibility and antibacterial potency of the platform. In vivo computed tomography analysis was performed in rats infected with different kinds of pneumonia, and anti-inflammatory studies such as bronchoalveolar lavage and pathological assays were used to test the capability of our nanomedicine as a theranostic platform. In addition, the long-term safety of the hybrid NPs was investigated via hematological and biochemical assays.
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http://dx.doi.org/10.1166/jbn.2018.2580DOI Listing
July 2018

Curcumin-Loaded Nanoparticles Protect Against Rhabdomyolysis-Induced Acute Kidney Injury.

Cell Physiol Biochem 2017 24;43(5):2143-2154. Epub 2017 Oct 24.

Department of Nephrology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai´an, China.

Background/aims: Rhabdomyolysis (RM) is a potentially life-threatening condition that results from the breakdown of muscle and consequent release of toxic compounds into circulation. The most common and severe complication of RM is acute kidney injury (AKI). This study aimed to evaluate the efficacy and mechanisms of action of curcumin-loaded nanoparticles (Cur-NP) for treatment of RM-induced AKI.

Methods: Curcumin-NP was synthesized using the nanocarrier distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to achieve a prolonged and constant drug release profile compared with the curcumin-free group. The anti-AKI effects of Curcumin-NP were examined both in vitro (myoglobin-treated renal tubular epithelial HK-2 cells) and in vivo (glycerol-induced AKI model).

Results: Our results indicated that Curcumin-NP reversed oxidative stress, growth inhibition and cell apoptosis accompanied with down-regulation of apoptotic markers Caspase-3 and GRP-78 in vitro. In vivo studies revealed enhanced AKI treatment efficacy with Curcumin-NP as characterized by reduced serum creatine phosphokinase (CPK), creatinine (Cr) and urea and less severe histological damage in renal tubules. In addition, kidney tissues from Curcumin-NP-treated AKI rats exhibited reduced oxidative stress, apoptosis, and cleaved Capase-3 and GRP-78 expression.

Conclusion: Our results suggest that nanoparticle-loaded curcumin enhances treatment efficacy for RM-induced AKI both in vitro and in vivo.
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http://dx.doi.org/10.1159/000484233DOI Listing
January 2018

Berberine nanoparticles protects tubular epithelial cells from renal ischemia-reperfusion injury.

Oncotarget 2017 Apr;8(15):24154-24162

Jiangsu College of Nursing, Huai'an, Jiangsu, China.

Renal ischemia-reperfusion (I/R) injury is one of the most common causes of acute renal failure, the prognosis of which remains poor and there still lacks of effective therapeutics available in the clinic. This study aimed at investigating the effects of Berberine nanoparticles (BBR-NP) on the ischemia-reperfusion injury of renal tubular epithelial cells and underlying the mechanisms. Our results showed that in a rat model of renal I/R injury, BBR and BBR-NP protected renal against injury both functionally (as assessed by serum urea nitrogen and creatinine level) and morphologically (as assessed by HE staining, transmission electron microscopy and TUNEL staining) in a dose-dependent manner, with the effects of BBR-NP superior to BBR alone. Mechanism investigation showed that BBR-NP reversed oxidative stress and subsequent apoptosis of renal cells, as demonstrated by the decreased expression of proteins involved in the oxidative stress and mitochondrial stress pathways. In conclusion, our study showed that BBR-NP is superior to BBR alone in protecting renal against I/R injury and explored the underlying mechanisms, which should be tested in further studies and might give impetus to the development of novel therapeutics based on BBR-NP against renal I/R.
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http://dx.doi.org/10.18632/oncotarget.16530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421835PMC
April 2017

Rituximab maintenance improves overall survival of patients with follicular lymphoma-Individual patient data meta-analysis.

Eur J Cancer 2017 05 21;76:216-225. Epub 2017 Mar 21.

Assuta Medical Center, Tel Aviv, Israel.

Background: Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis.

Methods: All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis. We obtained baseline patient and disease characteristics and time to progression and death for each patient. All analyses took into account the trial and original randomised treatment group. We analysed data in two ways: a two-stage analysis and a multivariate model including patient and disease characteristics.

Findings: Seven trials including 2315 patients were analysed. Overall survival of patients improved with MR compared with no MR (hazard ratio [HR] 0.79, 95% CI 0.66-0.96). We could not detect any patient or disease characteristics that were associated with a survival benefit with MR. In all of the models, MR had a beneficial effect on overall survival compared with observation for all types of patients, which was not shown in a particular subgroup in which the patient had already received rituximab in the induction phase and received first-line therapy. MR improved PFS compared with observation (HR 0.57, 95% CI 0.51-0.64). The risk of adverse events was higher with MR, specifically infection of any grade and grade 3-4 infections.

Interpretation: Based on IPD from randomised controlled trials, MR improves overall survival consistently in all patients, regardless of patient and disease characteristics when compared with observation, and should be prescribed after a successful induction with R-CVP or R-CHOP for patients with follicular lymphoma. It is still uncertain if that holds when the patient has already received rituximab in his/hers first induction. The effect of MR after bendamustine-rituximab induction compared with rituximab at progression should be further explored.
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http://dx.doi.org/10.1016/j.ejca.2017.01.021DOI Listing
May 2017

Acupuncture for Chemoradiation Therapy-Related Dysphagia in Head and Neck Cancer: A Pilot Randomized Sham-Controlled Trial.

Oncologist 2016 12 10;21(12):1522-1529. Epub 2016 Aug 10.

Head and Neck Oncology Program, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Introduction: Dysphagia is common in head and neck cancer patients after concurrent chemoradiation therapy (CRT). This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture.

Patients And Methods: Head and neck cancer (HNC) patients with stage III-IV squamous cell carcinoma were randomized to 12 sessions of either active acupuncture (AA) or sham acupuncture (SA) during and following CRT. Patients were blinded to treatment assignment. Swallowing-related quality of life (QOL) was assessed using the MD Anderson Dysphagia Inventory (MDADI) total and subscale scores.

Results: Multiple aspects of trial feasibility were confirmed. Forty-two of 196 patients screened (21%) were enrolled and randomized to receive AA (n = 21) or SA (n = 21); 79% completed at least 10 of 12 planned acupuncture sessions; 81% completed the study follow-ups. The majority of patients reported uncertainty regarding their treatment assignment, with no difference between the AA and SA groups. Audits confirmed both AA and SA treatments were delivered with high fidelity. No serious acupuncture-related side effects were observed. MDADI total scores significantly improved from baseline to 12 months post-CRT in both groups (AA: +7.9; SA +13.9; p = .044, p < .001). Similar patterns were observed for the MDADI global subscale (AA: +25.0; SA +22.7; p = .001, p = .002). Intent-to-treat analyses suggested no difference between the treatment groups (p = .17, p = .76 for MDADI total and global scores, respectively).

Conclusion: A sham-controlled randomized trial evaluating acupuncture in dysphagia-related QOL in HNC found the procedure to be feasible and safe. Further investigation is required to evaluate efficacy.

Implications For Practice: Dysphagia or swallowing difficulty is an important and common condition after concurrent chemoradiation therapy in head and neck cancer patients. In addition to current available supportive care, acupuncture may offer potential for treating dysphagia. This study demonstrated that both active acupuncture and sham acupuncture are safe and were associated with improved dysphagia-related quality of life from baseline to 12 months after concurrent chemoradiation therapy. This study was not designed to inform underlying specific versus nonspecific effects. Future larger-scale pragmatic clinical trials evaluating the effectiveness of acupuncture versus standard of care are warranted, and further mechanistic research is needed to understand how active versus purportedly sham acupuncture procedures affect dysphagia-related symptoms.
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http://dx.doi.org/10.1634/theoncologist.2015-0538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153334PMC
December 2016

Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496).

Cancer 2016 Oct 28;122(19):2996-3004. Epub 2016 Jun 28.

Washington University, St. Louis, Missouri.

Background: In an ECOG-ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression-free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long-term follow-up of the same patient cohort is presented.

Methods: Patients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m(2) × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.

Results: Of the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow-up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10-year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.

Conclusions: With long-term follow-up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B-cell lymphoma. Cancer 2016;122:2996-3004. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179PMC
October 2016

Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma.

Am J Hematol 2016 Feb 26;91(2):179-84. Epub 2015 Nov 26.

Centre National De La Recherche Scientifique (CNRS), Unite Mixte De Recherche (UMR), Université Claude Bernard, Lyon, France.

We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12-88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps.
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http://dx.doi.org/10.1002/ajh.24223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801345PMC
February 2016

Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era.

Br J Haematol 2015 Nov 7;171(4):530-8. Epub 2015 Sep 7.

Stanford University, Stanford, CA, USA.

The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.
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http://dx.doi.org/10.1111/bjh.13634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881845PMC
November 2015

Response-adapted therapy for aggressive non-Hodgkin's lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404).

Br J Haematol 2015 Jul 30;170(1):56-65. Epub 2015 Mar 30.

Stanford University Medical Center, Stanford, CA, USA.

A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B-cell lymphoma (DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received four cycles of R-ICE, PET-negative patients received two more cycles of R-CHOP. A ≥ 45% 2-year progression-free survival (PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% [90% confidence interval (CI), 19-63%] for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival (OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and -negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R-ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials.
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http://dx.doi.org/10.1111/bjh.13389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696544PMC
July 2015

Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405).

Blood 2014 Mar 23;123(11):1665-73. Epub 2014 Jan 23.

University of Wisconsin, Madison, WI;

Rituximab, bortezomib, modified hyper-cyclophosphamide, doxorubicin, vincristine, dexamethasone (VcR-CVAD) induction chemoimmunotherapy and maintenance rituximab (MR) were evaluated for efficacy and safety in Eastern Cooperative Oncology Group protocol E1405. Patients with previously untreated mantle cell lymphoma received VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years. Transplant-eligible patients had the option of autologous stem cell transplantation (ASCT) consolidation instead of MR. The primary end point was the complete response (CR) rate to VcR-CVAD. The secondary end points were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76) were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively. No substantial difference in PFS or OS was observed between patients treated with MR (n = 44) vs ASCT (n = 22). There were no unexpected toxicities. VcR-CVAD produced high ORR and CR rates in mantle cell lymphoma. MR after VcR-CVAD induction performed similarly to ASCT and may improve response duration. Randomized clinical trials comparing MR against ASCT should be considered and randomized clinical trials evaluating bortezomib's contribution to conventional therapy are under way. This study was registered at www.clinicaltrials.gov as #NCT00433537.
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http://dx.doi.org/10.1182/blood-2013-08-523845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954048PMC
March 2014

A phase II study of sorafenib (BAY 43-9006) in recurrent diffuse large B cell lymphoma: an eastern cooperative oncology group study (E1404).

J Hematol Oncol 2013 Jul 5;6:46. Epub 2013 Jul 5.

Stanford University, Stanford, CA, USA.

Patients with diffuse large B cell lymphoma (DLBCL) who are not candidates for or recur after autologous stem cell transplant have a poor overall prognosis. We conducted a phase II study of sorafenib (formerly BAY 43-9006) in the treatment of relapsed DLBCL. Fourteen patients were enrolled and assessed for response. Median number of cycles administered was 3 (range, 1-12). Common grade 3 toxicities included fatigue (29%), rash/desquamation (21%) and diarrhea (14%). One complete response (CR) was observed (the 14th patient enrolled). Response rate was 7% (90% CI, 0.4 - 30%). Duration of response was 6 months. Median progression-free survival (PFS) was 2 months (90% CI, 1 - 5 months). Median overall survival (OS) was 9 months (90% CI, 5 - 16 months). Although sorafenib has demonstrated activity in solid malignancies it demonstrated low single agent activity in treatment of DLBCL.
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http://dx.doi.org/10.1186/1756-8722-6-46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716977PMC
July 2013
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