BACKGROUND: Annexin A1 (ANXA1) is known to be involved in the progression and differentiation of various tumors. However, its significance and role in bladder carcinogenesis has not been fully elucidated. To determine the role ANXA1 plays in urothelial carcinoma (UC), we investigated the expression of ANXA1 protein in normal urothelial tissue, carcinoma in situ (CIS), and UC of the urinary bladder. METHODS: Protein expression level of ANXA1 and its subcellular localization were analyzed in 88 cases of UCs and corresponding 24 normal tissues and 24 CISs by immunohistochemistry. RESULTS: ANXA1 was significantly down-regulated at all subcellular localization in CIS and in the cytoplasm and membrane of cells of UC, compared to normal tissues. No significant correlation between ANXA1 expression level and tumor depth (pT), growth pattern, and recurrence was found. However, cytoplasmic and membranous ANXA1 were significantly up-regulated in high grade than in low grade UC (p=0.02 in cytoplasm and p=0.03 in membrane). CONCLUSIONS: These results suggest that ANXA1 dysregulation is involved in urothelial carcinogenesis and ANXA1 is potentially a marker for the pathologic differentiation of UC.
Annexin A1 ; Carcinoma in Situ ; Cytoplasm ; Membranes ; Recurrence ; Urinary Bladder

OBJECTIVETo observe the distribution of Annexin I and cytosolic phospholipose A2 (cPLA2) in the palatal process of dexamethasome teratogenerated mice.

METHODSCutting along the coronary plane of the heads of fetal mice to obtain palate in the 14th, 15th, 16th day of gestation by 10-week-old in-bred mice. The distribution of Annexin I and cPLA2 was checked by immunohistochemical staining.

RESULTSDuring the fusing of the palatal processes, the staining of Annexin I and cPLA2 was positive in the epithelial and mesenchymal cells of the palatal process, and the intensity of staining changed with time.

CONCLUSIONAnnexin I and cPLA2 can modulate the development of fetal palate to some extent, and they may be important mediators in the development of cleft palate induced by dexamethasone.

OBJECTIVES: To investigate the expression changes of annexin A1 （ANXA1） during the process of skin incision healing, and to explore its expression and function during skin injury repair. METHODS: The skin injury model of mice was prepared, and skin tissues of the controls and the injured group at 6 h, 12 h, 1 d, 3 d, 5 d, 7 d, 10 d and 14 d after injuries were taken. The morphological changes of the wound were observed by hematoxylin-eosin （HE） staining, and the expression of ANXA1 was detected by immunohistochemistry （IHC） and Western blotting. RESULTS: HE staining showed normal healing of skin wounds. IHC results revealed that ANXA1 was expressed in the epidermis, hair follicle, sebaceous gland and vascular endothelium. In the injured group, the expression of ANXA1 was enhanced in epidermis and skin appendages around the wound 6-12 h after injury, and ANXA1 was also highly expressed in neutrophils and a small number of mononuclear cells. ANXA1 was mainly positively expressed in monocytes, neovascular endothelial cells and fibroblasts, and small amount of fibroblasts at 1-3 d, 5-10 d, and 14 d after injury, respectively. Western blotting showed that, compared with the controls, the expression of ANXA1 was significantly increased at 6 h after injury, peaked at 1 d, and then decreased gradually in the injured group. CONCLUSIONS ANXA1 may be involved in the regulation of skin damage repair, with time-dependent expression during skin wound healing, and thus is expected to be a biological marker for inferring the wound formation time.
Animals ; Annexin A1/metabolism* ; Fibroblasts ; Mice ; Neutrophils ; Skin ; Wound Healing

Lipocortin 1 has been proposed as a putative mediator of anti-inflammatory actions of glucocorticoids. We investigated the role of lipocortin 1 in the effect of dexamethasone using rat splenic leukocytes. Concanavalin A(ConA; 1-microgram/ml) increased the leukocyte proliferation and nitric oxide(NO) generation, which were measured as (3H)-thymidine uptake by the cells and nitrite accumulation in the culture media, respectively. Dexamethasone suppressed CoNinduced cell proliferation, in a concentration-dependent manner with EC-50 around 50nM. The addition of anti-lipocortin 1 (Anti-LC1) reversed dexamethasone effects: 0.24, 1.2, 6 microgram/ml of Anti-LC1 reversed dexamethasone(50nM)-induced suppression of thymidine uptake by 9+/-3%, 16+/-3%, 36+/-5%, respectively; 0.24, 1.2, and 6-microgram/ml of Anti-LC1 reversed dexamethasone-induced decrease of nitrite concentration by 49 +/- 16%, 61 +/- 20%, 77 +/- 19 %, respectively. The present data indicate that lipocortin 1 mediates, at least in part, glucocorticoids-induced suppression of leukocyte proliferation and blockade of NO generation.
Animals ; Annexin A1* ; Annexins* ; Cell Proliferation ; Culture Media ; Dexamethasone* ; Glucocorticoids ; Leukocytes* ; Nitric Oxide* ; Rats* ; Thymidine

PURPOSE: The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. METHODS: Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. RESULTS: One hundred eighty-two cases were included and the mean age of the patients was 46.34 +/- 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p<0.001) and benign breast diseases (p<0.001). There was a significant alteration in ANXA1 expression according to hormone receptor status (p<0.001), cancer intrinsic type (p<0.001), and nuclear grade (p=0.004) in invasive cancer. In a univariate analysis, ANXA1 positivity tended to be related with poor breast cancer-related survival (p=0.062); however, the same results was not realized in multivariate results (p=0.406). HER2 overexpression and TNM staging were significantly associated with relapse-free survivals (RFS) in the multivariate analysis (p=0.037, p=0.048, respectively). In particular, in node-positive patients (p=0.048), HER2 overexpressed patients (p=0.013), and non-triple negative breast cancer patients (p=0.002), ANXA1 overexpression was correlated with poor RFS. CONCLUSION: Although significant loss of ANXA1 expression was noted in breast cancer including DCIS and invasive carcinoma, in cases of invasive cancer, overexpression of ANXA1 was related to unfavorable prognostic factors. And these results imply that ANXA1 plays dualistic roles and is involved in variable mechanisms related to cancer development and progression.
Annexin A1 ; Biopsy, Large-Core Needle ; Breast ; Breast Diseases ; Breast Neoplasms ; Carcinoma, Intraductal, Noninfiltrating ; Humans ; Multivariate Analysis ; Neoplasm Staging

OBJECTIVE: The aim of this study was to compare the expression of annexin I and thymosin beta4 in invasive cervical cancer including normal cervix and CIN. METHODS: In Ewha Womans University Mokdong Hospital, normal cervical tissues were obtained from healthy women (n=10), from patients with cervical intraepithelial neoplasia (CIN, n=10) and from patients with cervical cancer (n=33). The expressions of annexin I and thymosin beta4 mRNA and protein were examined by quantitative competitive-PCR and by western blot analysis. The expressions of annexin I and thymosin beta4 protein were measured by western blot analysis with thymosin beta4 peptides non treated and treated SiHa cells. RESULTS: The expression of thymosin beta4 mRNA and protein in cervical cancer were higher than that in normal cervix (p<0.05). The expression of annexin I mRNA and protein were higher than that in normal cervix and CIN (p<0.05). Thymosin beta4 and annexin I mRNA expressions were not significantly correlated with cervical cancer stage, or size of the tumor (p>0.05). But thymosin beta4 and annexin I protein expressions were increased according to the cancer stage. The expression of annexin I was slightly higher in thymosin beta4 treated SiHa cells than that in nontreated SiHa cells. CONCLUSIONS: Our results suggest that overexpression of thymosin beta4 and annexin I may play roles in progression of invasive cervical cancer. Thymosin beta4 upregulates expression of annexin I in invasive cervical cancer. Therefore, thymosin beta4 and annexin I may be biological markers in detecting the progression of invasive cervical cancer, and their interaction is important in invasive cervical cancer.
Annexin A1 ; Biomarkers ; Blotting, Western ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Female ; Humans ; Peptides ; RNA, Messenger ; Thymosin ; Uterine Cervical Neoplasms

OBJECTIVE: To investigate the correlation of Annexin A1 (ANXA1) expression with paclitaxel response and clinicopathological features of ovarian carcinoma. METHODS: The expression levels of ANXA1 in ovarian carcinoma SKOV3/Taxol-25 and SKOV3 cell lines were detected by Western blot and real time-PCR. The expression of ANXA1 protein in 42 specimens of ovarian carcinoma was examined by immunhistochemistry. The correlation of ANXA1 expression with paclitaxel response and clinicopathological features of ovarian carcinoma was analyzed. RESULTS: The expression level of ANXA1 was significantly lower in SKOV3/Taxol-25 cell line than that in SKOV3 cell line (P<0.05). The positive specimens of ANXA1 expression in paclitaxel-resistant tissues (14/20) were significantly lower than those in the sensitive ones (21/22, P<0.05), and there was also a significant difference between the mild and the strong positive specimens (P<0.01). The expression of ANXA1 protein showed no correlation with the type of mophology and histological grade of ovarian cancer (P>0.05), but it was correlated with the clinical stage(P<0.05). CONCLUSION ANXA1 expression is downregulated in paclitaxel-resistant ovarian carcinoma, which might be a valuable predictor for paclitaxel susceptibility of ovarian carcinoma.
Annexin A1 ; metabolism ; Blotting, Western ; Down-Regulation ; Drug Resistance, Neoplasm ; Female ; Humans ; Ovarian Neoplasms ; drug therapy ; metabolism ; Paclitaxel ; pharmacology

PURPOSE: The aim of this study was to investigate the effects of testosterone deprivation on urinary bladder in male rabbits by proteomic analysis. MATERIALS AND METHODS: New Zealand white male rabbits (2.5-3 kg) were divided into 2 group; control group with 5 rabbits and bilateral orchiectomized group, bilateral orchiectomized group was divided into post-operative 4 weeks group (group 1), and 8 weeks group (group 2) with 5 rabbits respectively. Bladder wall was excised partly at 4 or 8 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-D gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. We decided to consider 'significant' if protein had 50% decreasing or 200% increasing expression rate. RESULTS: Six proteins were significantly changed in orchiectomy group, compared to control group; serum albumin precursor, GABA transaminase, dimethylarginine dimethylaminohydrolase 2, serum/glucocorticoid regulated kinase and LOC304923 protein were over-expressed in both group 1 and group 2. Annexin A1 was significantly over-expressed in the group 2 only. CONCLUSION: An overexpression of Annexin A1 and GABA transaminase mean a processing of neuronal reactions to injury in orchiectomized rabbit bladder. Also an overexpression of dimethylarginine dimethylaminohydrolase 2 would increase NO synthesis and thereby promote re-endothelialization in the rabbit bladder after orchiectomy. Serum/glucocorticoid regulated kinase would relate to Na+ transport. Albumin precursor and LOC304923 protein are remained to further research. These data suggested that bilateral orchiectomy would make the urinary bladder unstable. However more information is needed in human bladder tissue.
4-Aminobutyrate Transaminase ; Annexin A1 ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Male ; Mass Spectrometry ; Neurons ; New Zealand ; Orchiectomy* ; Phosphotransferases ; Proteomics ; Rabbits ; Serum Albumin ; Testosterone ; Urinary Bladder*

Lipocortin represents a family of similar Ca++ depentent phospholipid-binding proteins capable of blocking the activity of phospholipase A2 (PLA2) in vitro. Generally, these proteins are believed to inhibit the release of arachidonic acid from photopholipids and the formation of lipid mediators such as prostaglandin, leukotriene, and platelet activating factor. Lipocortin 1, initially identified as a glucocorticoid- responsive protein in macrophages and neutrophils has been implicated in transmembrane signal transduction during growth factor-mediated cell proliferation and transformation. To define the synthesis and its regulation, we investigated the expression of lipocortin 1 in both the mRNA and protein level in U937 cell line in the presence of several differentiation factors. The results were as follows. 1. The expression of lipocortin 1 and its mRNA was increased during TPA-induced differentiation of U937 cells to maximum of 2-fold and 5-fold respectively. Both the protein and mRNA levels decreased after 48 hours. 2. With the treatment with IFN-gamma, the expression of CD16 was increased. However, the protein and mRNA levels of lipocortin 1 were, not changed significantly. 3. Neither the dexamethasone or hydrocortisone have any effects on the expression of lipocortin 1 in both TPA-differentiated and undifferentiated U937 cells. The results from this study would give a light on defining the functional role of lipocortin 1 in macro-moncycle cell lineage and possibly some informative clues for the pathogenic mechanisms of the inflammatory diseases.
Annexin A1* ; Annexins* ; Arachidonic Acid ; Cell Lineage ; Cell Proliferation ; Dexamethasone ; Humans ; Hydrocortisone ; Macrophages ; Neutrophils ; Phospholipases A2 ; Platelet Activating Factor ; RNA, Messenger ; Signal Transduction ; U937 Cells*

Splenic B-cell lymphomas (SBCLs) show characteristically pronounced splenomegaly without significant lymphadenopathy. Distinguishing hairy cell leukemia (HCL) from other SBCLs (splenic marginal zone lymphoma [SMZL], variant HCL [v-HCL], and splenic diffuse red pulp small B-cell lymphoma [SDRPL]) is essential to determine suitable treatments and prognoses. With advances in diagnostic modalities and therapies, splenectomy is not commonly performed, and thus diagnosis of HCL must be based on the results obtained using blood and bone marrow samples. Annexin A1 is known as the most specific marker for HCL. There has yet been no report of the assessment of annexin A1 immunostaining from Korea. In this study we analyzed samples from 13 Korean patients with SBCLs (three HCL, three v-HCL, six SMZL, and one SDRPL) from May 2001 to December 2016. Immunohistochemical analyses for annexin A1 and CD20 were performed using bone marrow sections; molecular analyses for detection of the BRAF V600E mutation were also performed. All HCL patients showed positive results for annexin A1 immunostaining and the presence of the BRAF V600E mutation, and negative results for other SBCLs. Our results confirmed the high specificity of annexin A1 and the BRAF V600E mutation as HCL markers. Molecular analysis requires expensive equipment and substantial manpower. Annexin A1 is a better alternative as an HCL marker than the BRAF V600E mutation in terms of cost-effectiveness.
Annexin A1 ; Bone Marrow ; Diagnosis ; Humans ; Korea ; Leukemia, Hairy Cell ; Lymphatic Diseases ; Lymphoma ; Lymphoma, B-Cell ; Prognosis ; Sensitivity and Specificity ; Splenectomy ; Splenomegaly