G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy.

BACKGROUND: Colorectal cancer is the second most common malignant tumor worldwide. A deeper insight into the mechanisms underlying colorectal cancer metastasis is urgently needed. G-protein signaling modulator 1 and autophagy play critical roles in tumor migration and invasion. However, the biological functions and regulatory networks of G-protein signaling modulator 1 and autophagy have not yet been fully studied. METHODS: We performed immunohistochemistry and clinic-pathological characteristic analysis in 328 human colorectal cancer specimens to identify the clinical role of G-protein signaling modulator 1 in colorectal cancer. An in vitro coculture system and a tumor metastasis mouse model were used to explore the biological function of G-protein signaling modulator 1 on tumor metastasis. Autophagic flux detection like GFP-LC3B signal immunofluorescence and electron microscope observation of autophagic vesicles and confocal microscope detection were used to gain insights into the underlying role of G-protein signaling modulator 1 in autophagy. RESULTS: We found that G-protein signaling modulator 1 was abundantly expressed in colorectal cancer tissues and was associated with lymph node metastasis and poor prognosis. Furthermore, our bioinformatic and functional studies demonstrated that G-protein signaling modulator 1 significantly promoted cell migration and invasion, both in vitro and in vivo. Mechanistically, we demonstrated that G-protein signaling modulator 1 could promote colorectal cancer cell migration and invasion and inhibit autophagy and by activating the PI3K/AKT/mTOR pathway. CONCLUSIONS: We proposed that G-protein signaling modulator 1 promotes colorectal cancer metastasis by modulating autophagy through the PI3K/AKT/mTOR pathway.

Inflammatory mechanism of chlorpyrifos-induced lung injury in rats / 中国职业医学

OBJECTIVE: To investigate the inflammatory mechanism of chlorpyrifos-induced lung injury in rats. METHODS: Specific pathogen free SD rats were randomly divided into control and low-, medium-and high-dose groups, 8 rats in each group. Rats were exposed to 48% chlorpyrifos by continuous oral administration for 28 consecutive days, once a day, with the doses of 0.0, 4.1, 8.2 and 16.3 mg/kg body mass. After the exposure, the enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α) and interleukin-1(IL-1) in rat lung tissue. The expression of high mobility group protein-1(HMGB1) and nuclear transcription factor-κB(NF-κB) was detected by immunohistochemistry and Western blotting, respectively. RESULTS: The activity of the rats decreased after exposure in the low-, medium-and high-dose groups compared with the control group. The rats in the medium and high dose groups increased salivation, nasal secretions, and difficulty breathing. The rats in the high dose group also developed diarrhea, muscle tremor, unstable gait, as well as muscarinic and nicotinic symptoms. After the exposure, the lung tissues of rats in the low-, medium-and high-dose groups showed different degrees of inflammation, which increased in a dose-dependent manner; the body mass of rats in the 3 dose groups was lower than that in the control group(all P values were <0.05), and the body mass of rats decreased with the increase of chlorpyrifos dose(all P values were <0.05). The levels of TNF-α, IL-1 and the relative expression of HMGB1, NF-κB were higher in the 3 dose groups than those in the control group(all P values were <0.05), and the levels of TNF-α, IL-1 and the relative expression of HMGB1 increased with the increasing exposure dose(all P values were <0.05). CONCLUSION: Chlorpyrifos can activate the NF-κB signaling pathway and eventually induce the macrophages to secrete large amount of TNF-α and IL-1, resulting in lung inflammation and injury in rats. The effect of chlorpyrifos has a dose-effect relationship.

Prevention and treatment of perioperative pulmonary hypertensive crisis in patients with serious pulmonary arterial hypertension relevant with ventricular septal defect / 中国实用护理杂志

Objective To discuss key points of prevention and treatment of perioperative pulmonary hypertensive crisis in patients with serious pulmonary arterial hypertension associated with ventricular septal defect. Methods Retrospectively analyzed the nursing experience of perioperative pulmonary hypertensive crisis on 31 patients with serious pulmonary arterial hypertension associated with ventricular septal defect from March to December during 2016.Among these patients,7 patients occurred pulmonary hypertensive crisis.The prevention contained avoiding oxygen lack,keeping pH alkaloid in the body, application of pulmonary vasodilator, deep sedation. Results A total of 30 cases survived the perioperative period, and were discharged from the hospital, one died. Conclusions The patients with serious pulmonary arterial hypertension had more risks during the perioperative period,the main cause of death was pulmonary hypertensive crisis during this time.So prevention of pulmonary hypertension crisis is the key point of postoperative nursing.

Expression of TET2 and DNMT3A in peripheral T cell lymphoma and their significance / 临床与实验病理学杂志

Purpose To investigate the expression of TET2 and DNMT3A in patients with peripheral T cell lymphoma (PTCL) and the relationship to immunophenotypes of PTCL.Methods Using a panel of immunohistochemical markers (CD3,CD4,CD10,BCL-6,CXCL-13,CD30,ALK),all cases of PTCLs were further divided into four groups,including angioimmunoblastic T cell lymphoma (AITL),peripheral T cell lymphoma,not otherwise specified (PTCL-NOS),anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCL) and anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK + ALCL).The expression of TET2 and DNMT3A in 89 cases of PTCL was detected by immunohistochemical analysis.Results 89 cases were divide into four subtypes,AITL (36/89),PTCL-NOS (26/89),ALKALCL (18/89),and ALK + ALCL (9/89).Immunohistochemistry staining revealed higher cytoplasmic expression of TET2 and DNMT3A in AITL than that of in PTCL-NOS and ALCL (P ＜ 0.05).And the nuclear expression of DNMT3A in patients with AITL was higher than that of PTCL-NOS and ALCL (P ＜ 0.05).The cytoplasmic expression of TET2 was positively related with both cytoplasmic and nuclear expression of DNMT3A in patients with AITL (P ＜ 0.05).Conclusion TET2 combined with DNMT3A could be used as markers in AITL diagnosis,which could provide new strategy for AITL diagnosis.

Expression and significance of leptin receptor, p-STAT3 and p-AKT in diffuse large B-cell lymphoma.

We investigated the expression and clinical significance of leptin receptor (OBR), p-STAT3 and p-AKT in patients with diffuse large B-cell lymphoma (DLBCL) by immunohistochemical analysis. Immunohistochemistry revealed high expression of OBR, p-STAT3 and p-AKT in 45.0% (36/80), 28.8% (23/80) and 18.8% (15/80) cases of DLBCL, respectively, and minimal staining in 100% (20/20) cases of RLH (P<0.05). Compared with GCB group, the non-GCB group had higher p-STAT3 expression rate (21/57 vs. 2/23, P<0.01). The expression of OBR was positively related with that of p-STAT3 and p-AKT in DLBCL patients (P<0.05). Our data suggest that OBR stimulates the JAK/STAT and PI3K/AKT signaling pathway and induces the phosphorylation of STAT3 and AKT. This may be involved in carcinogenesis and prognosis of DLBCL. The specific inhibitions could interfere in the combination of leptin with OBR and obstruct the JAK/STAT and PI3K/AKT signaling pathways, which could lead to new research and treatment strategies for DLBCL treatment.

Expression and significance of leptin receptor and phosphorylation of signal transducer and activator of transcription 3 in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate the expression and clinical significance of leptin receptor (OBR) and phosphorylation of signal transducer and activator of transcription (p-STAT3) in patients with diffuse large B-cell lymphoma (DLBCL).Methods Immunohistochemical analysis was used to detect the expression of OBR and p-STAT3 in 80 patients with DLBCL and 10 patients with reactive lymphoid hyperplasia (RLH).Using a panel of immunohistochemical markers (CD10,bcl-6 and Mum-1),all cases of DLBCL were further divided into two groups,GCB (germinal center B-cell-like) or non-GCB.Results Immunohistochemistry revealed high expression of OBR and p-STAT3 in 45.0 ％ (36/80) and 28.8 ％ (23/80) cases of DLBCL,respectively,and minimal straining in 100.0 ％ (10/10) cases of RLH (P ＜ 0.05).Compared with GCB group (8.7 ％,2/23),non-GCB group had higher p-STAT3 high expression rate (36.8 ％,21/57) (P ＜ 0.05).There was no significant difference in the expression of OBR between these two groups.Compared with clinical stage Ⅰ-Ⅱ [46.2 ％ (18/39) and 25.6 ％ (10/39)],stage Ⅲ-Ⅳ had higher OBR and p-STAT3 high expression rate [61.9 ％ (13/21) and 38.1％ (8/21)] (P ＞ 0.05).The expression of OBR and p-STAT3 were not correlated with age,gender,extranodal infiltrations,LDH level,B-symptoms and IPI(international prognostic index)(P ＞ 0.05).The expression of OBR was positively related with that of p-STAT3 in DLBCL patients (r =0.232,P =0.039).Conclusion OBR could stimulate the JAK-STAT signaling pathway and induces the phosphorylation of STAT3.This may be involved in carcinogenesis and prognosis of DLBCL.

Relationship between expressions of CXCR4, MMP-2 and VGEF and biological behavior of pancreatic cancer / 中华胰腺病杂志

Objective To investigate the expressions of CXCR4,MMP-2 and VEGF in pancreatic carcinoma and the relationship with biological behavior of pancreatic carcinoma.Methods Immunohistochemical PV6000 technique was used to detect the expression of CXCR4,MMP-2 and VEGF in 47 cases of pancreatic carcinoma tissues,and the relationship between the expressions and pathologic parameters,and the relationship among the expressions of the 3 proteins were analysed.Results The expression rates of CXCR-4,MMP-2 and VEGF were 72.3%,66.O%and 61.7%in pancreatic carcinoma tissues,and all these proteins were correlated with metastasis,clinical staging and prognosis(X2=5.84～12.69;P＜0.05).The expression of CXCR-4,MMP-2 and VEGF was not correlated with sex,age,tumor size and differentiation(X2=0.03～4.27;P＞0.05).There was a positive relationship between the expression of CXCR-4 and MMP-2 or VEGF in pancreatic carcinoma(r=0.587,0.521;P＜0.01).Conclusions CXCR-4 could up-regulate the expression of MMP-2 and VEGF in pancreatic carcinoma,and they may contribute to metastasis and invasion of pancreatic carcinoma.

Differential proteomic analysis of liver in apoE/LDLR double-gene mutant mice / 中国病理生理杂志

5 fold) were noted.Six significant differential proteins in gel were identified by LTQ-ESI,e.g.endoplasmin precursor,acidic leucin-rich nuclear phosphoprotein 32 family member A,serotransferrin precursor,stress-70 protein precursor,fibronectin precursor,complement C3 precursor,fibrinogen gamma polypeptide.CONCLUSION: The protein profile of apoE-/-/LDLR-/-mouse liver exhibits significant difference compared to that of WT mice.The results imply that lipid metabolism relative polygenetic mutation contributes to the alteration of mouse liver protein expression profile,especially that lipid metabolism related perhaps participates in dysfunction in lipid metabolism during atherogenesis.