Efficacy and safety of drug-eluting beads for transarterial chemoembolization in patients with advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has more recently become a leading cause of cancer-associated mortality worldwide. Particularly at an advanced stage, the prognosis is generally poor due to lack of effective treatments. Transarterial chemoembolization (TACE) is now a recognized therapy for advanced HCC, serving to deprive tumors of feeder arteries through induced ischemic necrosis. However, there is also a potential for undesired circulatory toxicity owing to drug reflux from tumor artery to surrounding healthy tissues. Although effective chemotherapeutic drug concentrations are thus lowered, the side effects of systemic chemotherapy are aggravated. The mid-2000 emergence of drug-eluting beads (DEB) loaded with anti-neoplastic drugs has proven particularly advantageous, enabling localized treatment and directed delivery of chemotherapeutics. DEB-TACE (dTACE) augments local infusion of anti-neoplastic agents to prolong agent/tumor contact, expanding upon conventional TACE. At present, data on DEB use in China are limited, particularly in terms of proprietary microspheres (CalliSpheres; Hengrui Medicine Co.). To explore the efficacy and safety of CalliSpheres, A total of 90 patients receiving this means of dTACE for advanced HCC were assessed in the present study. Clinical efficacy was evaluated based on tumor response and overall survival rates using the National Cancer Institute Common Terminology Criteria for Adverse Events to assess tolerability. The satisfactory tumor response and acceptable tolerability demonstrated in the follow-up confirm the promising utility of CalliSpheres in treating patients with advanced HCC.

Determination of citrus juice coumarins, furanocoumarins and methoxylated flavones using solid phase extraction and HPLC with photodiode array and fluorescence detection.

A synergistic combination of analytical techniques was developed for the simultaneous determination of the three most biologically active chemical families in citrus juices: methoxylated flavones, coumarins, and furanocoumarins. No rapid methodology has been available to determine them together. A solid phase extraction concentrated these groups and a ternary reverse phase HPLC gradient completely resolved them from other juice components. Two coumarins, isomeranzin and osthole, were identified in a sweet orange (C. sinensis) cultivar, Changyecheng, for the first time. Pummelo juice was characterized by coumarin and furanocoumarin epoxides such as meranzin and epoxybergamottin. No epoxides were observed in the more acidic juices. Added furanocoumarin epoxides hydrolyzed rapidly in the most acidic juices. The ratios of the UV peak areas at 320 nm to the fluorescence emission peaks as well as the ratio of fluorescence emission peaks at 450-400 nm could be used to identify chromatographic peaks.

Efficacy and Toxicity of Different Chemotherapy Regimens in the Treatment of Advanced or Metastatic Pancreatic Cancer: A Network Meta-Analysis.

Objective A network meta-analysis was conducted to compare the efficacy and toxicity of different chemotherapy regimens in treating advanced or metastatic pancreatic cancer (PC). PubMed, Cochrane Library and EMBASE databases from inception to June 2016 were searched. A combination of direct and indirect evidences was referred to for calculating the weighted mean difference (WMD) or the odds ratio (OR) and to establish surface under the cumulative ranking (SUCRA) curves, so as to evaluate the efficacy and toxicity of different chemotherapy regimens in treating advanced or metastatic PC. Twenty randomized controlled trials were enrolled. Twelve chemotherapy regimens included Gemcitabine, S-1 (Tegafur), Gemcitabine + Cisplatin, Gemcitabine + Capecitabine, Gemcitabine + S-1, Gemcitabine + 5-FU (5-fluorouracil), Gemcitabine + Exatecan, Gemcitabine + Irinotecan, Gemcitabine + Nab-paclitaxel, FOLFIRINOX (Oxaliplatin + Irinotecan + Fluorouracil + Leucovorin), Gemcitabine + Oxaliplatin, and Gemcitabine + Pemetrexed. Higher overall response rate (ORR) was observed in patients treated with the gemcitabine + S-1 and FOLFIRINO regimens. Thrombocytopenia reduced in patients treated with the S-1 regimen. The Gemcitabine + S-1 and FOLFIRINO regimens had better short- and long-term efficacies than the other regimens; S-1 regimen had the lowest hematologic toxicity, while Gemcitabine + Nab-paclitaxel, FOLFIRINOX, and Gemcitabine + Pemetrexed regimens had higher incidence of non-hematologic toxicity among twelve chemotherapy regimens. The efficacy of Gemcitabine + S-1 and FOLFIRINOX regimens may be better in treating patients with advanced or metastatic pancreatic cancer, while FOLFIRINOX and Gemcitabine + Pemetrexed regimens may have relatively higher incidence of toxicity than other regimens. J. Cell. Biochem. 119: 511-523, 2018. © 2017 Wiley Periodicals, Inc.

Preventive effects of the polysaccharide of Larimichthys crocea swim bladder on carbon tetrachloride (CCl4)-induced hepatic damage.

The aim of the present study was to determine the preventive effects of the polysaccharide of Larimichthys crocea swim bladder (PLCSB) on CCl4-induced hepatic damage in ICR mice. The in vitro preventive effects of PLCSB on CCl4-induced liver cytotoxic effect were evaluated in BRL 3A rat liver cells using the MTT assay. The serum levels of AST, ALT, and LDH in mice were determined using commercially available kits. The levels of IL-6, IL-12, TNF-α, and IFN-γ were determined using ELISA kits. The pathological analysis of hepatic tissues was performed with H and E staining, and the gene and protein expressions were determined by RT-PCR and Western blotting, respectively. PLCSB (20 µg·mL(-1)) could increase the growth of BRL 3A rat liver cells treated with CCl4. The serum levels of AST, ALT, and LDH were significantly decreased when the mice were treated with two doses of PLCSB, compared with the control mice (P < 0.05). PLCSB-treated groups also showed reduced levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ. PLCSB could decrease the liver weight, compared to the CCl4-treated control mice. The histopathology sections of liver tissues in the 100 mg·kg(-1) PLCSB group indicated that the animals were recovered well from CCl4 damage, but the 50 mg·kg(-1) PLCSB group showed necrosis to a more serious extent. The 100 mg·kg(-1) PLCSB group showed significantly decreased mRNA and protein expression levels of NF-κB, iNOS, and COX-2, and increased expression of IκB-α compared with the CCl4-treated control group. In conclusion, PLCSB prevented from CCl4-induced hepatic damage in vivo.

Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice.

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Preventive effect of Lactobacillus fermentum Lee on activated carbon-induced constipation in mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Lee (LF-Lee) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered lactic acid bacteria for nine days. Body weight, dietary and water intake, defecation status, gastrointestinal (GI) transit and defecation time, as well as levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were measured to evaluate the preventive effects of LF-Lee on constipation. Bisacodyl, a laxative drug, was administered as a positive control. The time taken until the first defecation of a black stool for normal, control, bisacodyl- (100 mg/kg, oral administration), Lactobacillus bulgaricus (LB)-, LF-Lee low dose (L)- and LF-Lee high dose (H)-treated mice was 90, 218, 117, 180, 161 and 151 min, respectively. Following the consumption of LB, LF-Lee (L) or LF-Lee (H), or the oral administration of bisacodyl, the GI transit was reduced to 55.2, 65.8, 73.1 and 94.6%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and those of SS were reduced in the mice treated with LF-Lee compared with those in the untreated control mice (P<0.05). These results demonstrate that lactic acid bacteria have preventive effects on constipation in mice and that LF-Lee has superior functional activity.

Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice.

The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-α and IFN-γ. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-κB, IκB-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-κB, iNOS and COX-2, but an increased expression level of IκB-α when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo.

Pu-erh tea has in vitro anticancer activity in TCA8113 cells and preventive effects on buccal mucosa cancer in U14 cells injected mice in vivo.

Pu-erh tea is a functional tea production in China. The functional effects should be proved. The oral cancer preventive and antimetastatic effects of Pu-erh tea in vitro and in vivo have been studied respectively. Pu-erh tea showed an inhibitory effect on human tongue carcinoma TCA8113 cells proliferation tested by 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyltetrazolium Bromide assay and induced TCA8113 apoptosis shown anticancer effect. The antimetastatic effect of Pu-erh tea in TCA8113 cells was proved by the decreasing of matrix metalloproteinases (MMPs) and increasing of tissue inhibitors of metalloproteinases (TIMPs) mRNA transcription. In the animal experiments, the tumor volumes and lymph node metastasis rates of Pu-erh tea-treated mice were smaller than control mice. Pu-erh tea reduced the levels of the serum proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor-α, and interferon-γ to a greater extent compared with the control mice, and the levels of 200 µg/mL treatment was more close to the normal mice than 100 µg/mL treated mice. Pu-erh tea also significantly induced apoptosis in tissues of mice (P < 0.05) by upregulating Bax and downregulating Bcl-2. These results demonstrate Pu-erh tea has cancer preventive and anti-metastatic effects on buccal mucosa cancer, the higher concentration get better efficiency.

Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice.

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-γ as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-κB, iNOS, and COX-2, and upregulating IκB-α. These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.

In vitro anticancer effects of insect tea in TCA8113 cells.

BACKGROUND: Insect tea is widely used a traditional drink or traditional Chinese medicine in China. This study was conducted with an aim to determine the in vitro anticancer effect of Insect tea in cancer cells. MATERIALS AND METHODS: The anticancer effects of Insect tea were evaluated in human tongue carcinoma TCA8113 cells using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry analysis, nuclear staining with 4,6-diamidino-2-phenylindole (DAPI), reverse transcription-polymerase chain reaction (RT-PCR) analysis, and western bolt assay. RESULTS: At 200 µg/mL, Insect tea inhibited the growth of TCA8113 cells by 80.7%, which was higher than the inhibition caused by 100 µg/mL Insect tea but lower than that of 200 µg/mL green tea. Compared to the control cancer cells, Insect tea significantly (P<0.05) induced apoptosis as determined by DAPI staining and flow cytometry analysis results. Insect tea significantly induced apoptosis in cancer cells by upregulating BAX, CASP3, CASP9 and downregulating BCL2. Genes encoding nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were significantly downregulated by Insect tea, demonstrating its anti-inflammatory properties. Insect tea also exerted a great anti-metastasis effect on cancer cells as demonstrated by decreased expression of matrix metalloproteinase (MMP) genes and increased expression of tissue inhibitors of metalloproteinases (TIMPs). CONCLUSION: The results showed that Insect tea has good in vitro anticancer effects in TCA8113 cells, like green tea.

Inhibitory effects of resistant starch (RS3) as a carrier for stachyose on dextran sulfate sodium-induced ulcerative colitis in C57BL/6 mice.

The aim of this study was to determine the effects of resistant starch 3 (RS3) as a carrier for stachyose on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. RS3 microspheres carrying stachyose (RS3 + stachyose) were produced and evaluated as a potentially improved colitis therapy for this study. The body weights of the mice treated with RS3 + stachyose were higher compared with those of DSS-treated control mice. RS3 + stachyose reduced the levels of the serum pro-inflammatory cytokines IL-6 and TNF-α to a greater extent compared with the same concentration of stachyose combined with ordinary starch (stachyose + starch). Histopathological examination of sections of colon tissues showed that the RS3 + stachyose group recovered well from colitis; however, the tissue sections of the stachyose + starch group presented necrosis to a more serious degree. These results suggest that stachyose with an RS3 carrier has better preventative effects on colitis than stachyose alone in mice.

Anti-inflammatory effects of kudingcha methanol extract (Ilex kudingcha C.J. Tseng) in dextran sulfate sodium-induced ulcerative colitis.

The present study aimed to investigate the anti­inflammatory effects of Ilex kudingcha C.J. Tseng methanol extracts (KME) on 3% dextran sulfate sodium (DSS)­induced ulcerative colitis (UC) in mice (C57BL/6J strain). Body weight, disease activity index (DAI), colon length, colon weight to length ratio, colonic myeloperoxidase (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were measured. Histological changes were observed by hematoxylin and eosin staining. Colonic levels of tumor necrosis factor­α (TNF­α), interleukin(IL)­1ß and IL­6 were measured with an enzyme­linked immunosorbent assay. The mRNA expression of TNF­α, IL­1ß, ­6, inducible nitric oxide synthase (iNOS) and cyclooxygenase­2 (COX-2) in the colon tissue, was quantified by RT­PCR. KME significantly suppressed DSS­induced body weight loss, colon length shortening and decreased the colon weight to length ratio. It also resulted in increased GSH and reduced MPO and MDA levels in the colon tissue. Histological observation suggested that KME prevented edema, mucosal damage and loss of crypts, which are induced by DSS. In addition, KME decreased the levels of TNF­α, IL­1ß and ­6 in the colon tissues, while inhibiting the mRNA expression of these cytokines, as well as iNOS and COX­2. The results of this study suggested that KME has anti­inflammatory effects on DSS­induced UC in mice (C57BL/6J strain) by reducing the colonic levels and inhibiting the mRNA expression of pro­inflammatory cytokines.

Sodium azide mutagenesis resulted in a peanut plant with elevated oleate content

Screening of peanut seeds resulting from 0.39 percent sodium azide treatment with NIRS calibration equation for bulk seed samples identified a plant with more than 60 percent oleate. Oleate content in individual seeds of the plant, as predicted by NIRS calibration equation for intact single peanut seeds, ranged from 50.05 percent ~ 68.69 percent. Three seeds with >60 percent oleate thus identified were further confirmed by gas chromatography. Multiple sequence alignments of the FAD2B gene from Huayu 22 (wild type) and peanut seeds with elevated oleate (mutant type) revealed a C281T transition in the coding region causing an I94T substitution in the oleoyl-PC desaturase, which may be responsible for reduction in the enzyme activity.