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Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9
<P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>
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Zhang, Xiao-Dan,Zhao, Qing-Yu,Fang, Yi,Chen, Guan-Xuan,Zhang, Hui-Fang,Zhang, Wen-Xiao,Yang, Xiao-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12
Objective: To assess the effects of perioperative comprehensive supportive care interventions on outcome of Chinese esophageal cancer patients in a prospective study. Methods: 60 patients with primary esophageal carcinoma were randomized into an intervention group (IG, n=31) and a control group (CG, n=29). The Chinese version of symptom checklist-90 (SCL-90) was adopted to assess their psychological status. The interventions, including health education, psychological support, stress management, coping strategies and behavior training, were carried out in 3 phases (preoperative, postoperative I and postoperative II), and psychological effects were thereafter evaluated accordingly before surgery, and 1 week, 4 weeks and 24 weeks post-surgery. Medical costs were estimated at discharge. Survival of patients was estimated each year post-surgery. General health status and satisfaction-with-hospital were surveyed by a follow-up questionnaire 4 years post-surgery. Results: All the subjects demonstrated higher scores in the preoperative phase than the normal range of Chinese population concerning 7 psychological domains including somatization, obsessive-compulsive, depression, anxiety, hostility, phobic anxiety and paranoid ideation. Although no significant difference was observed between the two groups at admission, the scores of IG, which tended to decrease at a faster rate, were generally lower than those of CG at weeks 1, 4 and 24 post-surgery. The length of hospital stay and medical costs of IG were significantly less than those of CG and satisfaction-with-hospital was better. However, there was no significant difference in 4-year survival or health status between two groups. Conclusions: Appropriate perioperative comprehensive supportive care interventions help to improve the psychological state of Chinese patients with esophageal carcinoma, to reduce health care costs and to promote satisfaction of patients and their families with hospital.
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Xuan, Zhu,Zhong, Zhao-Hui,Zhang, Xuan-Zhi,Zhang, Lei,Zhao, Xiao-Kun,Lv, Chen,Xu, Ran,Ren, Wei-Gang,Li, Song-Chao Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3
To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of $62{\pm}11$ years. Median duration of follow-up was $47{\pm}31$ months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ${\geq}70$ years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.
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Li, Fang-Xuan,Zhang, Ru-Peng,Liang, Han,Quan, Ji-Chuan,Liu, Hui,Zhang, Hui Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3
Background: The $7^{th}$ TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous. Methods: Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed. Results: Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors. Conclusions: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.
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Zhang, Chao,Hou, Wei-Hua,Ding, Xuan-Xi,Wang, Xiong,Zhao, Hui,Han, Xing-Wen,Wang, Wen-Ji Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.8
Background: Previous studies have assessed the association between the Cytotoxic T-lymphocyte Antigen-4(CTLA-4) polymorphism with the risk of malignant bone tumor, but the conclusions were inconsistent. We aimed to clarify association of cytotoxic T-lymphocyte antigen-4 polymorphisms with malignant bone tumors risk by performing a meta-analysis. Materials and Methods: The databases including PubMed, EMBase databases and the Cochrane Library were searched to identify the eligible studies prior to January 30 2016. Odds ratio (OR) with 95% confidence interval (95%CI) were used to estimate the strengths of the association between the CTLA-4 polymorphism and the malignant bone tumor risks. The meta-analysis was performed by STATA 12.0. Results: Four individual studies with a total of 1003 cases with malignant bone tumor and 1162 controls were included in our meta-analysis. The results of meta-analysis on those data demonstrated that CTLA-4 +49G>A polymorphism was associated with the risk of Ewing's sarcoma and osteosarcoma strongly (A vs. G: OR=1.36, 95%CI:1.20-1.54, p=0.000; AA+AG vs. GG: OR=1.35, 95%CI:1.14-1.61, p=0.001; AA vs. GG: OR=2.24, 95%CI:1.67-2.99, p=0.000; AA vs. AG+GG: OR=2.00, 95%CI:1.53-2.62, p=0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumor (C vs. T: OR=0.76, 95%CI:0.76-1.08, p= 0.262; CC+CT vs. TT: OR=0.70, 95%CI:0.41-1.20, p= 0.198; CC vs. TT: OR=0.69, 95%CI:0.40-1.19, p= 0.183; CC vs. CT+TT: OR=0.92, 95%CI:0.75-1.13, p= 0.419). Subgroup analysis showed that there are significantly positive correlations between CTLA-4 +49G>A polymorphism and increased risks of malignant bone tumors in large size of sample (A vs. G: OR=1.347, 95%CI: 1.172,1.548, p=0.000; AA vs. GG: OR=2.228, 95%CI: 1.608,3.085, p=0.000), Ewing's Sarcoma or Osteosarcoma (A vs. G: OR=1.361, 95%CI: 1.201,1.540, p=0.000; AA vs. GG: OR=2.236, 95%CI: 1.674,2.986, p=0.000), and PCR-RFLP or Sequencing(A vs. G: OR=1.361, 95%CI: 1.201,1.540, p=0.000; AA vs. GG: OR=2.236, 95%CI: 1.674,2.986, p=0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumors in diagnosis, genotype method, and sample size (all p>0.05). Conclusions: CTLA-4 +49A/G variant was associated with an increased risk of developing the malignant bone tumors, such as Ewing's sarcoma and osteosarcoma. However, it failed to show the association between CTLA-4 -318C/T polymorphism and the risk of malignant bone tumors. Future large-scale studies remain to be done to confirm our conclusions.
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Effects of Androgen Receptor Overexpression on Chondrogenic Ability of Rabbit Articular Chondrocytes
Hui Liu,Shoumei Xuan,Zhoujing Zhang,Kuang Gu,Duohong Zou,Jiacai He,Yong Zhou 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.4
Background: The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism. Methods: Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. The cell viability was determined using Cell Counting Kit-8, and cell apoptosis was assessed by flow cytometry analysis. The effects of AR overexpression on the expression of cartilage-specific proteins and some signalling molecules were evaluated by real-time PCR and Western blotting. Using 24 New Zealand rabbits, the regeneration of rabbit articular cartilage defects was further investigated in vivo and evaluated histologically. Results: The overexpression of AR significantly reduced the apoptosis rate of chondrocytes but did not affect their proliferation. The overexpression of AR also promoted the expression of Sry-related HMG box 9, collagen II and aggrecan, decreased the expression of matrix metalloproteinase-13, and downregulated p-S6 and RICTOR. The experimental group with AR-overexpressing chondrocytes exhibited superior regeneration of cartilage defects. Conclusion: AR overexpression can maintain the phenotype of chondrocytes and promote chondrogenesis in vitro and in vivo. mTOR-related signalling was inhibited. Background: The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism. Methods: Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. The cell viability was determined using Cell Counting Kit-8, and cell apoptosis was assessed by flow cytometry analysis. The effects of AR overexpression on the expression of cartilage-specific proteins and some signalling molecules were evaluated by real-time PCR and Western blotting. Using 24 New Zealand rabbits, the regeneration of rabbit articular cartilage defects was further investigated in vivo and evaluated histologically. Results: The overexpression of AR significantly reduced the apoptosis rate of chondrocytes but did not affect their proliferation. The overexpression of AR also promoted the expression of Sry-related HMG box 9, collagen II and aggrecan, decreased the expression of matrix metalloproteinase-13, and downregulated p-S6 and RICTOR. The experimental group with AR-overexpressing chondrocytes exhibited superior regeneration of cartilage defects. Conclusion: AR overexpression can maintain the phenotype of chondrocytes and promote chondrogenesis in vitro and in vivo. mTOR-related signalling was inhibited.
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The treatment effect of novel hGHRH homodimer to male infertility hamster
Zhang, Xu-Dong,Guo, Xiao-Yuan,Tang, Jing-Xuan,Yue, Lin-Na,Zhang, Juan-Hui,Liu, Tao,Dong, Yu-Xia,Tang, Song-Shan The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.6
Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.
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Gan Hui,Zhang Li,Chen Hui,Xiao Han,Wang Lu,Zhai Xuan,Jiang Ning,Liang Ping,Zheng Shuyue,Zhao Jing 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
The NLRC4 inflammasome, a member of the nucleotide-binding and oligomerization domain-like receptor (NLR) family, amplifies inflammation by facilitating the processing of caspase-1, interleukin (IL)–1β, and IL-18. We explored whether NLRC4 knockdown alleviated inflammatory injury following intracerebral hemorrhage (ICH). Furthermore, we investigated whether NLRC4 inflammasome activation can be adjusted by the regulator of G protein signaling 2/leucine-rich repeat kinase-2 pathway. Fifty microliters of arterial blood was drawn and injected into the basal ganglion to simulate the ICH model. NLRC4 small interfering RNAs (siRNAs) were utilized to knockdown NLRC4. An LRRK2 inhibitor (GNE7915) was injected into the abdominal cavity. Short hairpin (sh) RNA lentiviruses and lentiviruses containing RGS2 were designed and applied to knockdown and promote RGS2 expression. Neurological functions, brain edema, Western blot, enzyme-linked immunosorbent, hematoxylin and eosin staining, Nissl staining, immunoprecipitation, immunofluorescence assay and Evans blue dye extravasation and autofluorescence assay were evaluated. It was shown that the NLRC4 inflammasome was activated following ICH injury. NLRC4 knockdown extenuated neuronal death, damage to the blood-brain barrier, brain edema and neurological deficiency 3 days after ICH. NLRC4 knockdown reduced myeloperoxidase (MPO) cells as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-18 following ICH. GNE7915 reduced pNLRC4 and NLRC4 inflammasome activation. RGS2 suppressed the interaction of LRRK2 and NLRC4 and NLRC4 inflammasome activation by regulating pLRRK2. Our study demonstrated that the NLRC4 inflammasome may aggravate the inflammatory injury induced by ICH and that RGS2/LRRK2 may relieve inflammatory injury by restraining NLRC4 inflammasome activation.
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