Home Dust Mites Promote MUC5AC Hyper-Expression by Modulating the sNASP/TRAF6 Axis in the Airway Epithelium.

House dust mites (HDMs) are a common source of respiratory allergens responsible for allergic asthma and innate immune responses in human diseases. Since HDMs are critical factors in the triggering of allergen-induced airway mucosa from allergic asthma, we aimed to investigate the mechanisms of Toll-like receptors (TLR) in the signaling of the HDM extract that is involved in mucus hypersecretion and airway inflammation through the engagement of innate immunity. Previously, we reported that the somatic nuclear autoantigenic sperm protein (sNASP)/tumor necrosis factor receptor-associated factor 6 (TRAF6) axis controls the initiation of TLRs to maintain the homeostasis of the innate immune response. The present study showed that the HDM extract stimulated the biogenesis of Mucin 5AC (MUC5AC) in bronchial epithelial cells via the TLR2/4 signaling pathway involving MyD88 and TRAF6. Specifically, sNASP binds to TRAF6 in unstimulated bronchial epithelial cells to prevent the activation of TRAF6-depenedent kinases. Upon on HDMs' stimulation, sNASP is phosphorylated, leading to the activation of TRAF6 downstream of the p38 MAPK and NF-κB signaling pathways. Further, NASP-knockdown enhanced TRAF6 signaling and MUC5AC biogenesis. In the HDM-induced mouse asthma model, we found that the HDM extract promoted airway hyperresponsiveness (AHR), MUC5AC, and allergen-specific IgE production as well as IL-5 and IL-13 for recruiting inflammatory cells. Treatment with the PEP-NASP peptide, a selective TRAF6-blocking peptide, ameliorated HDM-induced asthma in mice. In conclusion, this study indicated that the sNASP/TRAF6 axis plays a regulatory role in asthma by modulating mucus overproduction, and the PEP-NASP peptide might be a potential target for asthma treatment.

Synthesis, crystal structures and DNA-cleaving activities of [Cemp]2[MCl4] (Cemp = N-carbethoxymethyl-1,10-phenanthrolinium, M = Cu(II), Zn(II), Co(II), Ni(II) and Mn(II)).

N-Carbethoxymethyl-1,10-phenanthrolinium bromide (CempBr) and its five ionic metal complexes, [Cemp]2[MCl4] where M = Cu(II) (1), Zn(II) (2), Co(II) (3), Ni(II) (4) and Mn(II) (5) were synthesized and fully characterized. Complexes 1-5 have similar structures, and consist of isolated [Cemp](+) cations and [MCl4](2-) anions in which there are no obvious interactions between the oxygen or nitrogen donor atoms in [Cemp](+) and the metal center in [MCl4](2-). Agarose gel electrophoresis studies on the cleavage of plasmid pBR322 DNA by complexes 1-5 indicated that complex 1 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanism. Kinetic assay of complex 1 afforded the maximal catalytic rate constant kmax of 0.55 h(-1) and Michaelis constant KM of 47.6 µM, respectively, which gives about 1.5×10(7)-fold rate acceleration over uncatalyzed cleavage of supercoiled DNA. Ethidium bromide displacement experiments indicated that complex 1 had a binding affinity of (1.58±1.12)×10(6) M(-1) toward calf-thymus DNA, 20-100-fold higher than those shown by CempBr and complexes 2-5. The high cleaving efficacy of complex 1 is thought to be due to the efficient catalysis of the copper(II)-coordinated center and the efficient binding of the quaternized 1,10-phenanthroline cation to DNA.

Synthesis, characterization and potent DNA-cleaving activity of copper(II)-complexed berberine carboxylate.

9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO(3))(2)·3H(2)O, and established as [Cu(CBB)(2)](NO(3))(2)·2H(2)O by means of (1)H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species. Kinetic assay afforded the maximal first-order rate constant k(max) of 2.41 h(-1) and Michaelis constant K(M) of 2.64 mM, respectively, representing ca. 10(8)-fold acceleration in the cleavage. This catalytic efficacy is attributed to the Cu(II)-assisted formation of dimeric species, in which the two berberine subunits cooperatively bind to DNA, whereas the carboxylate-coordinated Cu(II) moiety functions as the cleavage-active center.

[Serum Lipid Levels and Their Prognostic Significance in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the serum lipid levels and their prognostic significance in patients with multiple myeloma (MM). METHODS: A total of 87 newly diagnosed MM patients and 87 healthy controls in our hospital from January 2012 to April 2021 were selected. Serum lipid levels were compared between MM patients and healthy controls. The differences of serum lipid levels in patients among two groups of sex, age, hemoglobin (Hb), albumin (ALB), platelet (PLT), ß2-microglobulin (ß2-MG) and bone marrow plasma cell ratio (BMPC), different immune types, different ISS stages, before and after chemotherapy were analyzed. Univariate and COX multivariate regression analysis were used to analyze the influence of clinical parameters such as serum lipid indexes on prognosis of MM. RESULTS: The serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) in MM patients were significantly lower than those in healthy controls (P<0.05). Anemia, low protein and low PLT in patients were related to low cholesterol. The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with low Hb and ALB were significantly lower than those in patients with high Hb and ALB (P<0.05). The Apo B level of low PLT patients was significantly lower than that of high PLT patients (P<0.05). The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with different immune types were significantly different, the above indexes of IgA type were significantly lower than IgG type(P<0.05), IgG type were significantly lower than light chain type(P<0.05), double clone type were significantly lower than light chain type (P<0.05). The levels of TC, LDL-C, and Apo B in patients with different ISS stages were significantly different, stage Ⅱ were lower than those of stage Ⅰ (P>0.05), stage Ⅲ were significantly lower than those of stage Ⅱ and stageⅠ(P<0.05). The levels of TC, TG, LDL-C, HDL-C, Apo A1 and Apo B in patients after chemotherapy were significantly higher than those before chemotherapy (P<0.05). Univariate analysis showed that Hb, PLT, ß2-MG, BMPC, LDL-C and Apo B affected the prognosis of MM. Multivariate analysis showed that BMPC and Apo B were independent factors affecting the prognosis of MM. CONCLUSION: The serum cholesterol level is decreased in MM patients, and hypocholesterolemia is related to the classification and staging of the disease. With the improvement of the disease, the serum cholesterol level is increased, and low serum Apo B level predicts a poor prognosis.

Extracellular domain of semaphorin 5A serves a tumor­suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells.

Semaphorin 5A (SEMA5A), which was originally identified as an axon guidance molecule in the nervous system, has been subsequently identified as a prognostic biomarker for lung cancer in nonsmoking women. SEMA5A acts as a tumor suppressor by inhibiting the proliferation and migration of lung cancer cells. However, the regulatory mechanism of SEMA5A is not clear. Therefore, the purpose of the present study was to explore the roles of different domains of SEMA5A in its tumor­suppressive effects in lung adenocarcinoma cell lines. First, it was revealed that overexpression of full length SEMA5A or its extracellular domain significantly inhibited the proliferation and migration of both A549 and H1299 cells using MTT, colony formation and gap closure assays. Next, microarray analyses were performed to identify genes regulated by different domains of SEMA5A. Among the differentially expressed genes, the most significant function of these genes that were enriched was the 'Interferon Signaling' pathway according to Ingenuity Pathway Analysis. The activation of the 'Interferon Signaling' pathway was validated by reverse transcription­quantitative PCR and western blotting. In summary, the present study demonstrated that the extracellular domain of SEMA5A could upregulate genes in interferon signaling pathways, resulting in suppressive effects in lung adenocarcinoma cells.

Effects of methylthiouracil on the proliferation and apoptosis of rat bone marrow stromal cells.

The aim of the present study was to investigate the effects of methylthiouracil (MTU) on the proliferation and apoptosis of rat bone marrow stromal cells (BMSCs). Rat BMSCs were isolated, cultured in vitro and treated with various concentrations of MTU. Cell growth curves were determined using the Cell Counting Kit-8 method and the effect of MTU on BMSCs in a logarithmic growth phase was observed. BMSC apoptosis following MTU treatment was detected by flow cytometry. The experimental results demonstrated that the proliferation-inhibition effect was gradually enhanced with increasing MTU concentrations and the extension of treatment time. Statistically significant differences were observed between the treatment and the control groups (P<0.05). In addition, the BMSC apoptosis rate gradually increased with increasing drug concentrations and treatment time extension; statistically significant differences were observed between the treatment and the control groups (P<0.05). Therefore, the results of the present study demonstrated that MTU inhibited the proliferation of BMSCs and promoted apoptosis, indicating the cytotoxic effects of MTU on BMSCs.

[Effect of berberine on HL-60 cell proliferation, apoptosis and vascular endothelial growth factor receptor 2 expression].

This study was aimed to investigate the effect of berberine on the proliferation and apoptosis of HL-60 cells, and the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in HL-60 cells. Berberine (6 - 96 µg/ml) was added to the HL-60 cell line culture medium, the CCK-8 method was used to reveal the inhibitory effect on cell proliferation, the flow cytometry was used to determine the apoptosis rate and cell cycle in HL-60 cells treated with berberine. The expression of VEGFR2 mRNA and protein were examined by RT-PCR and Western blot respectively. The results showed that the berberine inhibited the proliferation of HL-60 cells and induced their apoptosis in dose- and time-dependent manners. With the increased concentration of berberine, the percentage of HL-60 cells in G(1) phase of cycle increased significantly, and the percentage of HL-60 cells in S phase decreased significantly. The expression of mRNA and protein of VEGFR2 decreased with the increased concentration of berberine. It is concluded that the berberine can inhibit HL-60 cell proliferation and induce HL-60 cell apoptosis. The expression of mRNA and proteins of VEGFR2 decreased after treatment with berberine.

Clinical analysis of treatment of airway stenosis caused by advanced central lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of Cisplatin (10 cases) / 中国内镜杂志

Objective To explore the clinical application value of bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer. Methods The clinical data of 10 cases of airway stenosis caused by advanced central lung cancer between Nov 2015 and Jan 2017 were analyzed retrospectively. Results 10 cases airway stenosis caused by advanced central lung cancer received EBUS guided intratumoral injection of Cisplatin treatment. Assessed by bronchoscopic, there were 8 cases of patients showed favorable effects after the treatment; Assessed by CT scan, 6 cases showed effects;And 8 cases relieved dyspnea. Conclusion EBUS guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer have some effect.

Value of non-real-time radial probe endobronchial ultrasound guided transbronchial lung biopsy in the diagnosis of peripheral lung cancer and analysis of false negative results / 中国内镜杂志

Objective To explore the diagnostic value of non-real-time radial probe endobronchial ultrasound (RP-EBUS) guided transbronchial lung biopsy (TBLB) for peripheral lung cancer and analysis of false negative results. Methods A retrospective analysis of the clinical and imaging data of 256 patients with peripheral lung cancer between March 2013 and December 2016, all the cases underwent non-real-time RP-EBUS guided TBLB, then evaluate its significance in the diagnosis of peripheral lung cancer and analyze the reasons of false negative results. Result In 256 patients who received non-real-time RP-EBUS examinations, 73.83% (189/256) of peripheral lung cancer were detected by RP-EBUS and the positive rate of RP-EBUS guided TBLB was 61.33% (157/256). The positive rate of non-real-time RP-EBUS guided TBLB was correlated with lesions >2 cm in diameter, lesions close to visceral pleura, ultrasonic image characteristics and the RP-EBUS probe surrounding by lesion (P < 0.05). The positive rate of non-real-time RP-EBUS guided TBLB was not correlated with RP-EBUS probe passed through lesions and times of biopsy (P > 0.05). Complications including bleeding, chest pain and pneumothorax recovered spontaneously. Conclusion Non-real-time RP-EBUS guided TBLB was a practical technology for diagnosis of peripheral lung cancer with high diagnostic rate and good safety. Lesion size, connection to visceral pleura, ultrasonic image characteristics and the RP-EBUS probe surrounding by lesion influenced the diagnostic yield. Improvement of operative skills can reduce false negative results.

[Inhibition of vegfr-2 gene expression by RNA interference].

This study was aimed to explore a novel potential gene target for therapy of malignant tumor. The recombinant expression plasmids of VEGF/VEGFR-2 were designed, constructed and then transfected into A549 cells by using lipofectamine. The expressions of VEGF/VEGFR-2 mRNA and protein were detected by RT-PCR and Western blot respectively. The cell proliferation was assayed by CCK-8 and the cell apoptosis was detected using Hoechst Staining. The results indicated that as compared with the blank control, pGenesil-1 and scramble groups, the interference effect of pGenesil-1-vegfr-2-shRNA-1 vector group was more obvious. As the expression of endogenous vegfr-2 mRNA decreased, the expression of VEGFR-2 protein decreased correspondingly. The proliferation of A549 cells was inhibited significantly by RNAi at 72 hours (p<0.01). The apoptosis of A549 cells was induced at 48 hours after being transfected with pGenesil-1-vegfr-2-shRNA-1 and the typical apoptosis morphology could be seen by fluorescence microscopy. It is concluded that the expression of vegfr-2 gene is inhibited effectively by vegfr-2 specific shRNA. The proliferation of A549 cells is inhibited significantly and the apoptosis of cells is induced. This result showed that VEGF/VEGFR-2 signaling pathway can be an effective target for the prevention and treatment of malignant tumor.

[Dynamic analysis of expression of VEGF and its receptor-2 in mouse model with acute myeloid leukemia].

The objective of study was to explore the role of vascular endothelial growth factor (VEGF) and its receptor-2 in pathogenesis of acute myeloid leukemia. The acute myeloid leukemia model was established on 20 mice with severe combined immunodeficiency (SCID) transplanted by HL-60 cells. The mice were divided into the normal control and test group randomly. The expression of VEGF was detected by enzyme linked immunosorbent assay (ELISA). The expression of VEGFR-2 mRNA was detected by RT-PCR. The results showed that the establishment of acute myeloid leukemia model was succeeded on all SCID mice by HL-60 cell transplantation. The expressions of VEGF and VEGFR-2 mRNAs could be determined on all mice. As compared with the normal control group, the expressions of VEGF and VEGFR-2 mRNAs in the test group significantly increased, but gradually increased during the course of disease. It is concluded that the abnormal expressions of VEGF and VEGFR-2 exist in mice with acute myeloid leukemia, which may be involved in the pathogenesis of AML.

[Effect of fas mRNA expression on cytochrome C-induced apoptosis of HL-60 cells in vitro].

The aim of this study was to investigate the effect of cytochrome C on apoptosis of HL-60 cells and to explore the mechanism of HL-60 cell apoptosis induced by cytochrome C. The HL-60 cells were treated with different concentrations of cytochrome C for 24 hours. The concentrations of cytochrome C were as follows: 0 (control group), 9.375 mg/L, 18.75 mg/L, 37.5 mg/L, 75 mg/L and 150 mg/L. The apoptosis was analyzed by flow cytometry (FCM) after HL-60 cells were treated with different concentrations of cytochrome C for 24 hours. The fas mRNA expression changes of relevant apoptotic genes were examined by reverse transcription-polymerase chain reaction (RT-PCR) after HL-60 cells were treated with different concentrations of cytochrome C for 24 hours and were analyzed half-quantitatively. The expressions of fas involved in HL-60 treated with different concentrations of cytochrome C for 24 hours were detected by Western blot. The results indicated that the flow cytometry (FCM) (PI straining) showed obvious hypo-diploid peak before G(1) phase in the treated group, and its apoptotic ratio increased in a dose-dependent manner. The fas mRNA expression levels of the relevant apoptotic genes could be detected by RT-PCR after HL-60 cells treated with different concentrations of cytochrome C for 24 hours, and the expression of fas mRNA in HL-60 cells was increased by cytochrome C in dose-dependent manner within range of 0-37.5 mg/L. It is concluded that the cytochrome C up-regulates expressions of fas mRNA and their protein so as to induce apoptosis of the HL-60 cells.

[Effect of cytochrome C on HL-60 cell apoptosis and its relationship with the relevant genes bcl-2 and bax].

To study the effect of cytochrome C on HL-60 cells in vitro and the mechanism of expression changes of relevant apoptotic genes, the inhibition rate of cytochrome C on HL-60 cells was detected by MTT, the morphology of HL-60 cells was observed by light microscopy and fluorescence microscopy, the changes of apoptosis rate and cell cycle were assayed by flow cytometry (FCM), DNA ladder was investigated on electrophoresis, the expression changes of bax and bcl-2 mRNA were examined by RT-PCR, when HL-60 cells were treated with different concentrations of cytochrome C for 24 hours. The results showed that the inhibition rate increased with increase of the cytochrome C concentration within 0 - 150 mg/L; when treated with 0 - 37.5 mg/L cytochtome C for 24 hours, the percentage of apoptotic HL-60 cells increased with the dose increasing, and the typical apoptotic cells and the apoptotic DNA ladder were observed. At the same time, within this range of concentration, the expression of bcl-2 mRNA decreased gradually and the expression of bax increased gradually. When the cytochrome C concentration was higher than 37.5 mg/L, the percentage of apoptotic HL-60 cells not increased, but decreased, while the cells necrosed. The above metioned results suggested that at certain range of concentration of cytochrome C, apoptosis or necrosis can be induced by cytochrome C, and cell cycle arrests at G(1) phase in HL-60 cells, the percentage of apoptotic cells and the changes of expression of bax and bcl-2 depend on the dose of cytochrome C. The mechanism that cytochtome C induced apoptosis in HL-60 cells may be related to the activation of bax and inhibition of bcl-2.

[Influence of cytochrome C on apoptosis induced by daunorubicine in acute myeloid leukemia (AML) cells].

The purpose was to study the responses of AML cell treated with cytochrome C and to explore the influence of cytochrome C on apoptosis of AML cell induced by daunorudicine (DNR). The differentiation of AML cell was detected by Wright-Giemsa staining and NBT test, the apoptosis of AML cell was assayed by flow cytometry and fluorescence microscopy. The results showed as follows: (1) different concentrations of cytochrome C could induce different effects on AML cells. Concentration of cytochrome C for differentiation was 10 microl/ml, for apoptosis was 20 microl/ml, and for necrosis was 40 microl/ml. (2) the apoptosis of AML cells decreased with the administration of cytochrome C in 10.0 microg/ml before treating AML cells with DNR (P < 0.01), but no change was shown with the administration of cytochrome C in 20.0 microg/ml (P > 0.05). (3) in reverse sequence, administrating of cytochrome C in 10 microl/ml and 20 microl/ml after treating AML cells with DNR, two different concentrations of cytochrome C could increase the apoptosis of AML cells (P < 0.01). It is suggested that cytochrome C may probably affect the apoptosis of AML cells induced by DNR.

[Effect of IL-15 on the proliferation and differentiation of CD34+ cells from MDS patients].

AIM: To explore the effect of IL-15 on proliferation and differentiation of CD34 (+) cells from MDS patients. METHODS: The CD34 (+) cells were separated by magnetic bead-activated cell sorter (MACS) system, and cultured in fluid or methylcellulose semisolid medium. MTT colorimetry was used to examine the inhibitory effect of IL-15 on the proliferation of MDS CD34(+) cells.The numbers of CD34(+)cells and colony formation of CFU-E, BFU-E, CFU-G, CFU-GEMM were counted. The expressions of CD33, CD13, CD71, CD19 and CD3 on cultured cells and the change of cell-cycle were analyzed by FCM. RESULTS: The recovery rate of CD34(+) cells was (75.4+/-5.2) %, the purity of CD34 (+) cells in positive fraction was (90.3+/-6.3) % and the enriched rate was (83.1+/-12.5) % in 11 MDS patients. MTT colorimetry detection showed that IL-15 could promote the proliferation of MDS CD34(+) cells. The optimal time of promotoing CD34(+) cell proliferation by IL-15 was 8 days and optimal dosage of IL-15 was 20 microg/L. After culture for 8 days with 0 microg/L IL-15 (control group) and 20 microg/L IL-15(experimental group), the number of CD34 (+) cells increased by 4.6-fold in control group and 6.3-fold in experimental group (P<0.05, n=5). The colony formation rates of experimental group were significantly higher than those of control group. The expression rates of the CD molecules (except for CD3) on CD34(+) in experimental group were notably higher than those in control group. As compared with control group, much more CD34(+) cells of experimental group were in G(2) and S phase of cell cycle(P<0.05, n=7). CONCLUSION: IL-15 can obviously promote the proliferation and differentiation of CD34(+) cells from MDS patients.

[Controlled pathological study and preoperative MRI evaluation of the consistency of pituitary adenomas].

BACKGROUND & OBJECTIVE: Consistency of pituitary adenoma may influence surgical remote of the tumor. Preoperative evaluation of tumor consistency will be useful in guiding the operative approach. This study was designed to investigate the relationship among pituitary adenoma consistency, collagen type I and MRI signal intensity. METHODS: Twenty pituitary adenoma patients received transsphenoidal surgery. Preoperative MRI, H-E stains and collagen type I immunohistochemistry(IHC)-autonomic image analysis for tumor specimens were performed RESULTS: Ten tumors were soft, mean T2WI tumor/while matter signal intensity ratio (TWSIR) is 17.38%; six were moderate, mean T2WI TWSIR was 2.01; and 4 were firm, mean T2WI TWSIR was 1.56. Mean collagen type I positive area ratio(CIPAR) of soft, moderate, and firm tumors was 17.38%, 27.30%, and 40.31%, respectively. Both C1PAR and T2WI TWSIR were significantly different among three types (P < 0.01) C1PAR was negatively correlated to T2WI TWSIR(P < 0.01). CONCLUSION: Collagen type I content relates with the consistency of pituitary adenomas. MRI can predict of pituitary consistency adenoma; and those show hypointensity in T2WI are firm.

[Microsurgical technique of brain glioma---a report of 183 cases].

BACKGROUND & OBJECTIVE: Prognosis of glioma is still poor, its main treatment is surgery. The extent of tumor resection relates with prognosis. This study was to evaluate the extent of resection, post-operative Karnofsky performance scale (KPS), and survival rate of the glioma patients received microsurgery. METHODS: Records of 183 glioma patients received microneurosurgery were retrospectively analyzed, the extent of resection, post-operative KPS, and survival rate of patients were evaluated. Different microsurgical techniques were applied according to the location of gliomas. En bloc resection was performed for gliomas in non-functional areas by dissecting the tumors along edema area with high-power bipolar electrocoagulation. The tumors in functional areas were separated along cortex sulcus, the central part of tumor was removed firstly, and residual part was resected with low-power electrocoagulation. Gliomas close to important vessels were sucked, and electrocoagulation seldom performed. RESULTS: Among 183 cases of glioma, 85 in non-functional area, 47 in functional area, and 51 close to important vessels. Total and sub-total resection was performed in 163 patients (89.1%). The average post-operative KPS was 74. The KPS was decreased in 23 patients, increased in 44 patients, and stable in 116 patients. Patients were followed up for 12-216 months with an average of 47.8 months. The follow-up rate was 100%. Among 113 patients with long-term follow-up (>/=5 years), 5-year survival rates of low-grade, and high-grade astrocytoma patients were 75.4% (52/69), and 18.2% (8/44). CONCLUSION: Using different microsurgical patterns according to location of glioma, maximal resection of tumor may achieve with protection of neurological function.

[Role of matrix metalloproteinases-9, 2 and their inhibitor-TIMP-1, 2 in invasive pituitary adenomas biological behavior].

BACKGROUND & OBJECTIVE: Usually pituitary adenomas are histological benign and grow slowly, but a proportion of them will become locally aggressive, and develop into invasive pituitary adenomas. The reasons for these differences in tumor behavior are poorly understood. Pituitary adenomas are abounding blood vessels. Angiogenesis and tumor invasion both require degradation of the extracellular matrix components to allow cell migration. The matrix metalloproteinases (MMPs) and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. The aggressive mechanism of pituitary adenomas was studied through investigating the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in both invasive and non-invasive adenomas. METHODS: Sixty-one surgical removed pituitary adenomas (forty-nine cases invasive and twelve non-invasive adenomas) were investigated. Immunohistochemistry staining (SP method) was used to detect the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in two groups. The results were treated with semi-quantitative method and analyzed by using non-parameter rank sum test. RESULTS: Immunohistochemical staining of tumor cells for MMP-9, TIMP-1, MMP-2, and TIMP-2 were noted 95.9% (47/49), 57.1% (28/49), 75.5% (37/49) and 89.8% (44/49) in invasive adenomas, and 100% (12/12), 91.7% (11/12), 66.7% (8/12), and 91.7% (11/12) in non-invasive adenomas, respectively. Invasive tumors were significantly less expressing TIMP-1 and TIMP-2 (P < 0.05). There was no significant difference for MMP-9 or MMP-2 between invasive and non-invasive groups (P > 0.05). CONCLUSIONS: TIMP-1 and TIMP-2 may play a key role in invasive pituitary adenomas to biological behavior.