Clinical Study of Thalidomide Combined with Dexamethasone for the Treatment of Elderly Patients with Newly Diagnosed Multiple Myeloma

Chen, Hai-Fei,Li, Zheng-Yang,Tang, Jie-Qing,Shen, Hong-Shi,Cui, Qing-Ya,Ren, Yong-Ya,Qin, Long-Mei,Jin, Ling-Juan,Zhu, Jing-Jing,Wang, Jing,Ding, Jie,Wang, Ke-Yuan,Yu, Zi-Qiang,Wang, Zhao-Yue,Wu, Tian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Objective: To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). Methods: Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. Results: A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). Conclusions: The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.

Hepatic Re-resection Versus Transarterial Chemoembolization for the Treatment of Recurrent Hepatocellular Carcinoma after Initial Resection: a Systematic Review and Meta-analysis

Wang, Di-Ya,Liu, Lei,Qi, Xing-Shun,Su, Chun-Ping,Chen, Xue,Liu, Xu,Chen, Jiang,Li, Hong-Yu,Guo, Xiao-Zhong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Background: A systematic review and meta-analysis were performed to compare the post-recurrence survival with hepatic re-resection versus transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after initial resection. Materials and Methods: All relevant papers were searched via PubMed, EMBASE, and Cochrane Library databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analysis was performed according to country. Sensitivity analysis was performed in studies which clearly reported the recurrent regions, in moderate/high-quality studies, in studies published in full-text form, and in studies published after 2005. Results: In total, twelve papers were included in our study. Five and seven of them were of moderate- and poor-quality, respectively. The overall meta-analysis demonstrated a statistically significantly higher post-recurrence survival in the hepatic re-resection group than in those undergoing TACE (HR=0.64, 95%CI=0.52-0.79, P<0.0001). Heterogeneity was statistically significant and statistical significance remained in the subgroup analysis. Sensitivity analyses were also consistent with the overall analysis. Conclusions: Hepatic re-resection might provide a better post-recurrence survival than TACE for recurrent HCC after initial resection. However, considering the low quality of published studies and the potential bias of treatment selection, further randomized trials should be warranted to confirm these findings.

The Beneficial Effects of Electroacupuncture at PC6 Acupoints (Neiguan) on Myocardial Ischemia in ASIC3 / mice

Ying-Wang,Yi-guo Chen,Wan-shuang Zhao,Di Li,Ya-han Xu,Meng-di Li,Jin Chen,Zhi-jun Kou,Qi-ge Wang,Nsoa dimitri Joseph 사단법인약침학회 2018 Journal of Acupuncture & Meridian Studies Vol.11 No.3

This study aims to investigate the possible mechanisms of electroacupuncture (EA) at PC6to improve myocardial ischemia (MI) by regulating the cardiac transient outward potassiumcurrent channel (Ito). According to the random number table, the mice were dividedinto six groups of six mice each: control group, MI group, PC6, LU7 (Lieque-point), ST36(Zusanli-point), and nonacupoint group. Mice in the control group were injected with saline(20 mg/kg, 24 hours interval), and the other ASIC3 / mice were injected subcutaneouslytwice with isoproterenol (ISO) (20 mg/kg, 24 hours interval). In thepreexperiment, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg of ISO were used, andthe results showed that 5 mg/kg and 10 mg/kg of ISO both could induce acute MI, butshorter duration of sustained MI. On the other hand, an injection of 30 mg/kg can makethe mice experience arrhythmia or die immediately, and EA was operated at PC6, LU7,ST36 acupoints, and nonacupoint in the mice of PC6, LU7, ST36, and nonacupoint groups,respectively, after injecting twice. Then Western blotting techniques (Western Blot) wereused to analyze the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KchIP2. The results ofthis experiment showed that the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KChIP2 inMI group were significantly lower than those in the control group (p < 0.01). Comparedwith MI group, the results of PC6, LU7, and ST36 groups obviously increased (p < 0.05). Furthermore, the expressions of PC6 group were higher than LU7 group and ST36 group(p < 0.05). And electrocardiogram’s T-waves showed obvious pathological changes inthe MI group compared to the control group (p < 0.01). After EA, the abnormal T-waves voltage of ECG in PC6, LU7, and ST36 groups was improved (p < 0.05). In addition, therate change of PC6 group was larger than that of both LU7 and ST36 groups (p < 0.05). But the T-waves voltage of the nonacupoint group was not significantly different than thatof the MI group (p > 0.05).

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

IL-33/ST2 axis mediates hyperplasia of intrarenal urothelium in obstructive renal injury

Wei-Yu Chen,Jenq-Lin Yan,Yi-Hsiu Wu,Lung-Chih Li,Ru-Fang Li,Ya-Ting Chang,Lo-Hsin Dai,Wan-Chen Wang,Ya-Jen Chang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5- positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.

Development and Validation of Nomograms to Provide Individualized Predictions of Sur-vival Benefits from Surgery in Patients with Intermediate/Advanced Hepatocel-lular Carcinoma

( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.

Parkinson’s Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

Li-Jun Zuo,Shu-Yang Yu,Fang Wang,Yanghui Xia,Ying-Shan Piao,Yang Du,Teng-Hong Lian,Rui-Dan Wang,Qiu-Jin Yu,Ya-Jie Wang,Xiao-Min Wang,Piu Chan,Sheng-Di Chen,Yongjun Wang,Wei Zhang 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.2

Background and Purpose The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson’s disease (PD) patients who experience fatigue. Methods PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins—α-synuclein oligomer, β-amyloid (Aβ)1-42, and tau—were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. Results The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. Conclusions PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF

glyA Gene Knock-out in Escherichia coli Enhances L-serine Production without Glycine Addition

Ya Zhang,Pei Kang,Shuang Liu,Yujiao Zhao,Zhiwen Wang,Tao Chen 한국생물공학회 2017 Biotechnology and Bioprocess Engineering Vol.22 No.4

In E. coli, glyA encodes for serine hydroxymethyltransferase (SHMT), which converts L-serine to glycine. When engineering L-serine-producing strains, it is therefore favorable to inactivate glyA to prevent L-serine degradation. However, most glyA knockout strains exhibit slow cell growth because of the resulting lack of glycine and C1 units. To overcome this problem, we overexpressed the gcvTHP genes of the glycine cleavage system (GCV), to increase the C1 supply before glyA was knocked out. Subsequently, the kbl and tdh genes were overexpressed to provide additional glycine via the L-threonine degradation pathway, thus restoring normal cell growth independent of glycine addition. Finally, the plasmid pPK10 was introduced to overexpress pgk, serAΔ197, serC and serB, and the resulting strain E4G2 (pPK10) accumulated 266.3 mg/L of L-serine in a semi-defined medium without adding glycine, which was 3.18-fold higher than the production achieved by the control strain E3 (pPK10). This strategy can accordingly be applied to disrupt the L-serine degradation pathway in industrial production strains without causing negative side-effects, ultimately making L-serine production more efficient.

Establishment of Paclitaxel-resistant Breast Cancer Cell Line and Nude Mice Models, and Underlying Multidrug Resistance Mechanisms in Vitro and in Vivo

Chen, Si-Ying,Hu, Sa-Sa,Dong, Qian,Cai, Jiang-Xia,Zhang, Wei-Peng,Sun, Jin-Yao,Wang, Tao-Tao,Xie, Jiao,He, Hai-Rong,Xing, Jian-Feng,Lu, Jun,Dong, Ya-Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Background: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-${\pi}$ (GST-${\pi}$) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. Conclusion: The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-${\pi}$.

Metabolic engineering of erythritol production from glycerol by Yarrowia lipolytica

Ya-Ting Wang,Ling-Xuan Zhao,Liu-Jing Wei,Jun Chen,Zhijie Liu,Feng Liu,Qiang Hua 한국생물공학회 2024 Biotechnology and Bioprocess Engineering Vol.29 No.1

Erythritol as a four-carbon polyol has been widely used in food, pharmaceutical and daily chemical industries with characteristics of low caloric value and high chemical stability. Here, a system metabolic engineering strategy was used to increase the yield of erythritol from glycerol in Yarrowia lipolytica by enhancing the substrate transformation and restricting the by-product synthesis. Specifi cally, we determined that over-expression of a newly identifi ed erythrose reductase YPR1 was able to improve the erythritol production as same as the well-known erythrose reductase ER27. Instead of its up-regulation, knockout of erythrose reductase ER10 was eff ective to improve erythritol synthesis. Moreover, both over-expression of YPR1 and deletion of ER10 signifi cantly accelerated the glycerol utilization in response to high osmotic stress. To further decrease the by-product accumulation, a restriction and recycling strategy was implemented by knockout of mannitol dehydrogenase MDH2 and enhancement of arabitol dehydrogenase ADH1 and fructokinase HXK1. The engineered strain YL13 produced a titer of 25 g/L erythritol and less than 0.5 g/L mannitol and arabitol. By over-expression of transketolase TKL1, the fi nal strain YL14 produced 28.5 g/L erythritol and none of mannitol and arabitol. This study provides a new idea for reducing the production of by-products and improving the glycerol conversion to erythritol.