Clinical Significance of SH2B1 Adaptor Protein Expression in Non-small Cell Lung Cancer

Zhang, Hang,Duan, Chao-Jun,Chen, Wei,Wang, Shao-Qiang,Zhang, Sheng-Kang,Dong, Shuo,Cheng, Yuan-Da,Zhang, Chun-Fang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.

Expression and Clinical Significance of REPS2 in Human Esophageal Squamous Cell Carcinoma

Zhang, Hang,Duan, Chao-Jun,Zhang, Heng,Cheng, Yuan-Da,Zhang, Chun-Fang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

Thermal pretreatment of poplar sawdust at 100 °C in water or with microwave heating impacts the pyrolysis behaviors

Chao Li,Baihong Li,Guoming Gao,Lijun Zhang,Shu Zhang,Lei Zhang,Jun Xiang,Song Hu,Yi Wang,Xun Hu 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.125 No.-

Drying at 100 C is a common practice for processing many biomasses for their further thermochemicalconversion via the routes such as pyrolysis. The drying temperature of 100 C is low, but might not be toolow to cause any impact on pyrolytic behaviors of a biomass feedstock. In this study, varied scenarios ofthermal pretreatment of poplar sawdust (oven-drying, boiling in water and microwave heating) at 100 Cwere screened for probing their potential influence on the pyrolytic behaviors at 500 and 750 C. Comparing with oven-drying, boiling in water (cooking) and microwave heating at 100 C could removesome oxygen-containing species, increasing carbon content of the pretreated sawdust and promotingcarbonization in pyrolysis. This enhanced formation of biochar, heavy p-conjugated organics in bio-oil,but suppressed generation of gas. The cooking or microwave heating pretreatment also promoted aromatizationto form the biochar of higher thermal stability, higher crystallinity, and higher aromatic degree,due to the enhanced deoxygenation reactions in the pyrolysis. The in-situ IR characterization suggestedthat microwave pretreatment promoted generation of unsaturated ketones and also the species with olefinicC = C, favoring their further aromatization. The cooking pretreatment impacted transformationroutes of the oxygen-containing organics, thus modifying pyrolysis behaviors of the pretreated sawdust.

Study of seismic performance and favorable structural system of suspension bridges

Xin-Jun Zhang,Chao Zhang 국제구조공학회 2016 Structural Engineering and Mechanics, An Int'l Jou Vol.60 No.4

By taking the Runyang Highway Bridge over the Yangtze River with 1490 m main span as example, structural response of the bridge under the horizontal and vertical seismic excitations is investigated by the response spectrum and time-history analysis of MIDAS/Civil software respectively, the seismic behavior and the influence of structural nonlinearity on the seismic response of the bridge are revealed. Considering the aspect of seismic performance, the suitability of employing the suspension bridge in super long-span bridges is investigated as compared to the cable-stayed bridge and cable-stayed-suspension hybrid bridge with the similar main span. Furthermore, the effects of structural parameters including the span arrangement, the cable sag to span ratio, the side to main span ratio, the girder height, the central buckle and the girder support system etc on the seismic performance of the bridge are investigated by the seismic response spectrum analysis, and the favorable earthquake-resistant structural system of suspension bridges is also discussed.

Original Article : A Disintegrin and Metalloprotease with Thrombospondin Motif 2 May Contribute to Cirrhosis in Humans through the Transforming Growth Factor-β/SMAD Pathway

( Chao Dong ),( Han Jun Li ),( Shi Chang ),( Hui Jun Liao ),( Zhi Peng Zhang ),( Peng Huang ),( Hui Huan Tang ) 대한간학회 2013 Gut and Liver Vol.7 No.2

Background/Aims: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-β1 (TGF-β1) in clinical human cirrhotic tissues. Methods: The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-β1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-β receptor II (TGFβRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed. Results: Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-β1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFβRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05). Conclusions: These findings suggested that ADAMTS-2 and TGF-β1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-β1 may induce the expression of ADAMTS-2 through the TGFβ/SMAD pathway. (Gut Liver 2013;7:213-220)

LETM1 Promotes Gastric Cancer Cell Proliferation, Migration, and Invasion via the PI3K/Akt Signaling Pathway

Zhang, Yunfeng,Chen, Lele,Cao, Yifan,Chen, Si,Xu, Chao,Xing, Jun,Zhang, Kaiguang The Korean Gastric Cancer Association 2020 Journal of gastric cancer Vol.20 No.2

Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells. Materials and Methods: The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting. Results: The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway. Conclusions: LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

Trans-arterial Chemo-Embolization in Treating Elderly Patients with Hepatocellular Carcinoma

Zhang, Jian-Feng,Liu, Jun-Mao,Zhang, Nin,Du, Chao,Zheng, Qin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: This analysis was conducted to evaluate the efficacy and safety of Trans-arterial Chemo-Embolization (TACE) in treating Elderly patients with Hepatocellular Carcinoma (EHPC). Methods: Clinical studies evaluating the efficacy and safety of TACE on response and safety for patients with EHPC were identified by using a predefined search strategy. Pooled response rate of treatment were calculated. Results: In TACE based regimen, clinical studies which including patients with EHPC were considered eligible for the evaluation of response. And, in these TACE based treatments, pooled analysis suggested that, in all 288 patients whose response could be assessed, the pooled reponse rate was 29.5%(85/288) in TACE based treatment. The most commonly encountered TACE-related morbidity was liver function impairment. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in EHPC patients with TACE based treatments. Conclusion: This evidence based analysis suggests that TACE based treatments are associated with mild response rate and accepted toxicities for treating patients with EHPC.

LETM1 Promotes Gastric Cancer Cell Proliferation, Migration, and Invasion via the PI3K/Akt Signaling Pathway

Yunfeng Zhang,Lele Chen,Yifan Cao,Si Chen,Chao Xu,Jun Xing,Kaiguang Zhang 대한위암학회 2020 Journal of gastric cancer Vol.20 No.2

Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells. Materials and Methods: The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting. Results: The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway. Conclusions: LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin

Chen, Jun,Zhong, Ming-Chao,Guo, Huaijian,Davidson, Dominique,Mishel, Sabrin,Lu, Yan,Rhee, Inmoo,Pé,rez-Quintero, Luis-Alberto,Zhang, Shaohua,Cruz-Munoz, Mario-Ernesto,Wu, Ning,Vinh, Donald C.,Si Nature Publishing Group 2017 Nature Vol. No.

<P>Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors(1,2). Phagocytosis by macrophages plays a critical role in cancer control(3-6). Therapeutic blockade of signal regulatory protein (SIRP)-alpha, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo(7-10), suggesting that blockade of the SIRP alpha-CD47 checkpoint could be useful in treating human cancer(11-14). However, the prophagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRP alpha-CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRP alpha-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions(15-17), SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18-20) and utilize signals involving immunoreceptor tyrosine-based activation motifs(21,22). These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRP alpha-CD47 blockade therapy.</P>

Synthesis of a Series of Zinc Porphyrins and Spectroscopic Changes upon Coordination Reaction with Imidazole Derivatives

Shu-Jun Wang,Yu-Ling Peng,Cheng-Gen Zhang,Yong-Bing Li,Chao Liu 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.11

Three metal-free porphyrins modified with Boc-l-threonine and their zinc analogs were synthesized and characterized by elemental analysis,1H NMR, UV/vis, and fluorescence spectroscopies. The binding of imidazole derivatives to these zinc porphyrins was studied, with emphasis on the binding mechanism in CH2Cl2 solution, by means of UV/vis spectroscopy and quantum chemical methods. Both experimental results and theoretical calculations showed that a coordination reaction occurred between the zinc porphyrins and imidazole derivatives. The association constants between the zinc porphyrins and imidazole derivatives decreased in the order N-MeIm>Im. Increasing the temperature disfavored the interaction. Thermodynamic parameters calculated by the van't Hoff equation showed that the driving force for the reaction was the enthalpy change. The fluorescence changes associated with the interaction between the zinc porphyrins and imidazole derivatives were also studied by fluorescence spectroscopy. The experimental results showed significant quenching between the various zinc porphyrins and imidazole derivatives.