2.Clinical significance of expression and phosphorylation of FAK in human osteosarcoma
Ke REN ; Nan YAO ; Jun LU ; Xin SHI ; Sujia WU ; Jie MA ; Chen WANG
Chinese Journal of Clinical Oncology 2017;44(10):474-482
Objective: To examine expression patterns of focal adhesion kinase (FAK) and its activated form, phosphorylated FAK (pFAK),in human osteosarcoma and to investigate the correlation of FAK expression with clinicopathological parameters and prognosis. Functional consequence of manipulating FAK protein levels was also investigated in human osteosarcoma cell lines. Methods: Immunohistochemical staining was used to detect FAK and pFAK levels in pathologically archived materials from 113 patients with primary osteosarcoma. Kaplan-Meier survival and Cox regression analyses were used to evaluate prognoses. The role of FAK in cytological behavior of MG63 and 143B human osteosarcoma cell lines was studied via the FAK protein knockdown with siRNA. Cell proliferation, migration, invasiveness, and apoptosis were assessed using cell counting kit-8, Transwell, and Annexin V/PI staining methods. Results: Both FAK and pFAK were overexpressed in osteosarcoma patients. Tumor cells exhibited cytoplasmicity and occasional membranous immunoreactivity for FAK. A total of 42 cases (37.17%) mainly showed expressed pFAK in cytoplasm of osteosarcoma cells. No overexpression staining of anti-FAK and anti-pFAK antibodies was observed in normal cancellous bone tissues or negative controls. Significant differences were observed in overall survival between FAK-/pFAK- and FAK+/pFAK- groups (P=0.016), FAK+/pFAK- and FAK+/pFAK+ groups (P=0.012), and FAK-/pFAK- and FAK+/pFAK+ groups (P<0.001). All groups showed similar metastasis-free survival. Cox proportional hazard analysis showed that FAK expression profile is an independent indicator of both overall andmetastasis-free survival. siRNA-based knockdown of FAK significantly reducedmigration and invasion of MG63 and 143B cells and affected proliferation and apoptosis in osteosarcoma cells. Conclusion: Osteosarcoma malignancies in vitro and in vivo were correlated with overexpression and phosphorylation of FAK. These findings suggest that FAK plays an important biological role in osteosarcoma carcinogenesis. This study provides a better understanding of diagnostic and prognostic relevance of FAK overexpression and phosphorylation in osteosarcoma patients. Therefore, FAK and pFAK can be used as independent predictors of overall and metastasis-free survival in osteosarcoma patients.
3.Establishment and application of apparatus for the continued measurement of the oxygen consumption in mice
Yunsheng GAO ; Yongxiu QI ; Ke LI ; Yuyun ZHU ; Liyong HAO ; Jian MA ; Xiaoming XIN
Chinese Pharmacological Bulletin 2003;0(09):-
Aim To establish a set of apparatus and method for the continued measurement of the oxygen consumption in mice. Methods The apparatus consists of a bottle with broad-neck for mice, basic burette, beaker containing water and some tubes for connection. Twenty mice were divided randomly into two groups and administered intragestrically propranolol 20 mg?kg -1 or equal volume of normal saline, respectively. The survival time and oxygen consumption were measured in mice subjected to normobaric and hypoxia.Results The survival time was prolonged by 43.35% (P
4.Expression and variation of MIP-1β, MIP-2, and IL-12p70 in mouse models with bloodstream infection caused by different bacteria
Ming YANG ; Ya-Ting MA ; Shang HE ; Xin-Xin DUAN ; Jia-Nan WANG ; Ying JING ; Ke-Xin ZHANG ; Cheng-Bin WANG
Chinese Journal of Infection Control 2017;16(11):993-998
Objective To investigate the expression and variation of MIP 1β,MIP-2,and IL-12p70 in mice with bloodstream infection caused by 4 kinds of bacteria.Methods CD-1 (ICR) mouse models of bloodstream infection with Staphylococcus aureus (S.aureus),Enterococcus f aecalis (E.f aecalis),Escherichia coli (E.coli),and K lebsiella pneumoniae (K.pneumoniae) were established.After mice in each trial group and PBS control group were infected by bacteria for 0.5h,1h,3h,6h,12h,24h,and 48h,concentrations of MIP-1β,MIP-2,and IL-12p70 were detected by Luminex liquid suspension chip system.Results Concentrations of MIP-1β increased significantly 1h after bacteria was in blood,S.aureus,E.faecalis,E.coli,K.pneumoniae,and control groups were (134.5 ± 18.3),(61.5 ± 15.4),(3 354.0 ±809.0),(6 888.4 ± 1 100.2),and (28.9 ± 4.6) pg/mL respectively;the peak values of IL-12p70 were (389.3 ± 118.1),(127.6 ± 10.0),(42.2 ± 3.5),(62.8 ± 8.4),and (4.8 ± 0.3) pg/mL respectively.Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were significantly higher than other trial groups and control group (all P<0.01),while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than E.coli,K.pneumoniae,and control groups (all P<0.01).Conclusion Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were both significantly higher than those in S.aureus and E.faecalis groups,while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than those in E.coli and K.pneumoniae groups.The combination detection of multiple cytokines or chemokines are valuable in predicting gram-positive or gram-negative bacterial infection,and can provide basis for treatment of early infection.
5.Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized, controlled study.
Ke-ping CHEN ; Cong-xin HUANG ; De-jia HUANG ; Ke-jiang CAO ; Chang-sheng MA ; Fang-zheng WANG ; Shu ZHANG
Chinese Medical Journal 2012;125(24):4355-4360
BACKGROUNDNon-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).
METHODSA total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests.
RESULTSThe annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups.
CONCLUSIONIn Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.
Aged ; Aged, 80 and over ; Anticoagulants ; administration & dosage ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Warfarin ; administration & dosage ; therapeutic use
6.Protection of carbon monoxide intraperitoneal administration from rat intestine injury induced by lipopolysaccharide.
Shao-hua LIU ; Ke MA ; Bing XU ; Xin-rong XU
Chinese Medical Journal 2010;123(8):1039-1046
BACKGROUNDTreatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury in experimental animals induced by lipopolysaccharide (LPS) or ischemia-reperfusion. We hypothesized that CO intraperitoneal administration (i.p.) might provide similar protection to inhaled gas. This study aimed to investigate the effects of continuous 2 L/min of 250 ppm CO i.p. on rat intestine injury induced by LPS and to try to develop a more practical means of delivering the gas.
METHODSA total of 72 male Sprague-Dawley rats were randomly assigned to 4 groups: control group, CO i.p. group, LPS group and LPS+CO i.p. group. One hour after intravenously received 5 mg/kg LPS, the rats in LPS group and LPS+CO i.p. group were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively, and the rats of control group and CO i.p. group intravenously received an equal volume of 0.9% NaCl and 1 hour later, were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively. One, 3 and 6 hour of each group after treated with room air or CO i.p., the animals (n = 6 for each time point) were sacrificed and intestinal tissues were collected for determinating the levels of platelet activator factor (PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assays. The maleic dialdehyde (MDA) content and the myeloperoxidase (MPO) activity were determined with a chemical method. The phosphorylated p38 mitogen activated protein kinase (MAPK) expression was assayed with Western blotting and the cell apoptotic rate with flow cytometery. The arterial oxygenation was measured by blood gas analysis, and the pathology determined by light microscope.
RESULTSAfter treatment with 2 L/min of 250 ppm CO i.p., the increase of PAF, ICAM-1, MDA, MPO, and cell apoptotic rate induced by LPS was markedly reduced (P < 0.05 or 0.01), and accompanied by ameliorating intestine injury. Western blotting showed that these effects of CO i.p. were mediated by p38 MAPK pathway. There were no significant differences in all observed parameters between control group and CO i.p. group.
CONCLUSIONThe injury to the intestine via anti-oxidant, anti-inflammation and anti-apoptosis, which may involve the p38 MAPK pathway, was induced by 2 L/min of 250 ppm CO i.p. exerting potent protection against LPS.
Aldehydes ; metabolism ; Animals ; Blotting, Western ; Carbon Monoxide ; administration & dosage ; pharmacology ; therapeutic use ; Flow Cytometry ; Intercellular Adhesion Molecule-1 ; metabolism ; Intestines ; drug effects ; metabolism ; pathology ; Lipopolysaccharides ; toxicity ; Male ; Microscopy ; Peroxidase ; metabolism ; Platelet Activating Factor ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; chemically induced ; drug therapy ; p38 Mitogen-Activated Protein Kinases ; metabolism
7.39 cases of malignant tumors originated from external and middle ear.
Ying XIN ; Sen YAN ; Weiming SONG ; Tao PAN ; Huashun XIE ; Jia KE ; Lijuan LI ; Qingchuan DUAN ; Yu SONG ; Furong MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(14):1260-1263
OBJECTIVE:
To describe our experience in the clinical manifestation and treatment of malignant tumors of the external and middle ear.
METHOD:
The study reviewed 39 patients between 1994-2011 in our hospital, including 15 pinna tumors, 18 external canal tumors and 6 middle ear tumors. 23 males and 16 females were enrolled in this study. The mean age of patients at the time of surgery was 59. Radiotherapy or radiotherapy and chemotherapy were the only possible treatment in 6 cases. Thirty-three patients were treated surgically, and 9 patients also received radiotherapy after surgery.
RESULT:
All of the patients had been followed up over 3 years, except for 1 case of external canal and 1 case of middle ear tumor. The 3-year survival of pinna, external canal and middle ear tumors were 86.7%, 82.4% and 60.0% respectively. At the last follow up, the pinna tumors showed that the survival rate was 100% in T1, T2 and Tx stage, and 0% in T4 stage; the external canal tumors showed that the survival rate was 90% in T1 stage, and 66.7% in T2, T3 stage; the middle ear tumors showed that the survival rate was 100% in T1 and T2 stage, 0% in T3 stage.
CONCLUSION
The T staging system is for an important prognostic factor, and it is important for an early diagnosis and radical surgery to achieve a better therapeutical result.
Ear Auricle
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pathology
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Ear Canal
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pathology
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Ear Neoplasms
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pathology
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Ear, Middle
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pathology
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Female
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Humans
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Male
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Neoplasm Staging
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Retrospective Studies
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Survival Rate
8.Food Components and Risk of Esophageal Cancer in Chaoshan Region of China,a High-risk Area of Esophageal Cancer
Ke LI ; Ping YU ; Ge HUANG ; Xiao-Hong MA ; Zhi-Xin ZHANG ; Shao-Shan HUANG
Chinese Journal of Cancer 2001;20(2):160-163
Objective: The current study was designed to investigate the role of foods such as fish juice, pickles, bacon, salted fish, smoked food, fruit and vegetables in the etiology of esophageal cancer in Chaoshan region of China. Method: A large case-control study was conducted to investigate 1248 patients with squamous cell carcinoma of the esophagus and 1248 controls matched by sex and age. Results: After adjusting for the effects of occupation, areas of residence, income, alcohol, cigarette and tea, a strong association with a clear dose-response was observed between the frequencies of fish juice eating and esophageal cancer (P<0.01), and the relative risk for women was 23.5 and for men was 3.1, respectively. The results for pickles were similar to fish juice. A protective effect of fruits on esophageal cancer was observed both in women (OR=0.13) and in men (OR=0.46), and the risk was decreased (P< 0.01) as frequencies of fruits eating was increased. The risks were significantly higher in bacon and salted fish consumers than that in non-consumer, but the dose-response relationship was not significant. No significant effects, however, were detected in vegetables and smoked food consumption. Conclusions:To the authors' knowledge, this is the first report on relationship between the fish juice and high risk of esophageal cancer in population. Further epidemiological and experiment study are required to find a biological causal relationship between them.
9.The effect of iodine excess on bone metabolism in experimental autoimmune thyroiditis rats
Xin, ZHAO ; Ke-jun, CHEN ; Zhong-na, SANG ; Na, ZHAO ; Jin-xiang, ZHANG ; Zhai-xiao, YAO ; Wan-qi, ZHANG ; Xin-long, MA
Chinese Journal of Endemiology 2011;30(2):123-126
Objective To explore the effect of iodine excess on bone metabolism in experimental autoimmune thyroiditis (EAT) rats. Methods We selected 36 female Lewis rats with body weight of (131 ± 15)g,and divided them into 3 groups randomly: control group, EAT group and EAT + high iodine group, assuring 12 rats in every group. These rats were fed fodder with different concentration of iodine(0.9,0.9, 18.0 mg/kg), and rats in EAT group and EAT + high iodine group were immunized with pig thyroglobulin(pTG) and complete Freund's adjuvant(CFA) to create EAT model. After two weeks, the pathological changes of the thyroid tissues were observed,and the serum thyroid autoantibody[thyroglobulin antibody(TGAb) and thyroid microsomal antibody(TMAb)], the thyroid hormone levels[triiodo thyronine(T3) and thyrine(T4)] and some relevant data of bone metabolism[bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), C-terminal propeptide of type Ⅰ procollagen (PICP),C-terminal telopeptide of type Ⅰ collagen (ICTP), insulin-like growth factor- 1 ( IGF- 1 ), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL)] were measured. Results Inflammatory cell infiltration and local follicular structural damage were observed in the thyroid tissues of EAT rats in EAT group and EAT + high iodine group, and the pathological changes of EAT + high iodine group were mainly thyroid follicular expansion and integration. The level of serum TGAb, TMAb, T3 and T4 of EAT rats in EAT group and EAT + high iodine group[ (63.01 ± 12.36)%, (60.62 ± 11.24)%, (3.78 ± 1.43), (125.12 ± 16.00)pmol/L and (75.00 ± 15.44)%,(72.15 ± 15.00)%, (3.69 ± 0.91 ), (149.40 ± 20.67)pmol/L] were higher than those of the control group[ (4.47 ±1.04)%, (5.73 ± 1.01 )%, (0.75 ± 0.12), (76.91 ± 9.30)pmol/L, all P < 0.05], and the level of serum TGAb,TMAb and T4 of EAT rats in EAT + high iodine group were higher than those of the EAT group(all P < 0.05).The level of serum BGP, PICP and IGF- 1 in EAT group[ ( 1.70 ± 0.31 ), ( 11.31 ± 1.52) μg/L, (0.31 ± 0.06 ) mg/L]were lower than those of the control group[ (8.60 ± 0.33), (14.28 ± 3.10)μg/L, (1.16 ± 0.02)mg/L, all P <0.05], and the level of serum TRAP, ICTP, OPG and RANKL[ ( 19.88 ± 3.60)ng/L, (2.43 ± 0.82), (22.36 ± 2.80),( 1.35 ± 0.23 )μg/L] were higher than those of the control group[ ( 14.57 ± 3.56)ng/L, (0.50 ± 0.20), (1.61 ± 0.34),(0.10 ± 0.02)μg/L, all P < 0.05]; compared with EAT group, the level of PCIP and OPG in EAT + high iodine group [ (8.03 ± 1.84), ( 16.80 ± 3.79)μg/L] were obviously decreased(all P < 0.05). Conclusions The reinforcement of differentiation and maturation of osteoblast in the EAT rats results in the increasing of bone resorption. The activity of osteoblast and osteoclast of the EAT rats are inhibited by excessive iodine, showing a low conversion-type osteoporosis.
10.Quantity and distribution of CD44+/CD24- cells in breast cancer tissue and the cell lines.
Xin-quan LÜ ; Zhenhe SUO ; Chang-lu MA ; Ke-jia XU ; Yi-shan LIU ; Hui-xiang LI
Chinese Journal of Pathology 2009;38(7):441-444
OBJECTIVETo study the distribution and quantity of CD44+/CD24- cells in breast cancer tissue and the cell lines, and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma.
METHODSThe expression of CD44/CD24, estrogen receptor, progesterone receptor, HER2, human estrogen-induced protein PS2, bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining. The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) was also examined.
RESULTSThe quantity and distribution of CD44+/CD24- cells varied greatly and no specific patterns were identified. The percentage of CD44+/CD24- in breast cancer was 65%. The amount of CD44+/CD24- cells did not correlate with the age of patients, lymph node metastasis, tumor size, molecular subtypes and expression of various breast cancer markers in breast carcinoma. The proportion of CD44+/CD24- cells in MCF-7, MDA-MB-468, and MDA-MB-231 cell lines was <1%, 5% and >80%, respectively.
CONCLUSIONSCD44+/CD24- cells are demonstrated in certain breast cancer tissues and cell lines. However, there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer.
Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms ; classification ; metabolism ; pathology ; CD24 Antigen ; metabolism ; Carcinoma, Ductal, Breast ; classification ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Lymphatic Metastasis ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Progesterone ; metabolism ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; metabolism