PURPOSE: CD10, a membrane-bound zinc-dependent metallopeptidase, is normally expressed in many tissues. Accordingly, the derangement of CD10 expression may be related to development or progression in a variety of tumors. The aim of this study is to examine any association between CD10 expression and clinicopathological parameters in bladder transitional cell carcinomas (TCCs) and the relationship between expression of E-cadherin and CD10. MATERIALS AND METHODS: Immunohistochemical staining was performed for CD10 and E-cadherin in tissues of 94 TCCs and 10 non-neoplastic bladder mucosa. RESULTS: Positive immunoreactivity for CD10 was observed in non-neoplastic urothelium at a proportion of 80% and TCCs were observed at a rate of 23%. A positive rate of CD10 expression was observed in 10% of total cases of a low grade tumor and in 35% of those of a high grade tumor. It was also observed in 15% of pTa tumors, 13% of pT1 tumors, and 48% of pT2 tumors. In addition, CD10 expression showed reciprocal correlation with expression of membranous E-cadherin in tumors. CONCLUSION: CD10 is again expressed at a certain stage during the neoplastic process of TCCs and could play some roles intheir carcinogenesis.
Cadherins ; Carcinoma, Transitional Cell ; Neprilysin ; Urinary Bladder ; Urothelium

BACKGROUND: The aim of this study was to examine the expression of CD10 and CD15 in tumor cells, stromal cells and infiltrating inflammatory cells during colorectal carcinoma (CRC) development and to investigate their expression levels between the tumor center and invasive front and compare them to clinicopathological parameters in invasive CRC. METHODS: We performed immunohistochemical staining for CD10, CD15, and E-cadherin in 42 cases of CRC, 49 of tubular adenoma, 15 of hyperplastic polyp, and 17 of non-neoplastic colon. RESULTS: CD10 was expressed in tumor cells (tCD10), stromal cells (sCD10) and infiltrating inflammatory cells (iCD10), and CD15 was expressed in tumor cells (tCD15) and infiltrating inflammatory cells (iCD15). Their expressions were progressively increased during CRC development and the iCD10 expression level was significantly correlated with the iCD15 expression level in invasive CRC. Invasive front revealed a higher expression level of iCD10 and iCD15 than the tumor center. Moreover, the iCD15 expression level of invasive front was significantly correlated with the degree of tumor budding and tCD15 in whole tissue sections was closely associated with tumor depth. CONCLUSIONS: The present study suggests that the expression of CD10 and CD15 is associated with the development and progression of CRC.
Adenoma ; Antigens, CD15 ; Cadherins ; Colorectal Neoplasms ; Neprilysin ; Polyps ; Stromal Cells

Angiotensin Receptor Antagonists ; Heart Failure ; Humans ; Neprilysin ; Receptors, Angiotensin

No abstract available.
Adult* ; Fetal Blood* ; Humans ; Neprilysin* ; Neutrophils* ; Respiratory Burst*

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC). METHODS: A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically. RESULTS: A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC. CONCLUSIONS: The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.
Carcinoma, Renal Cell ; Humans ; Keratin-7 ; Lymph Nodes ; Neoplasm Metastasis ; Neprilysin

PURPOSES: The cell surface metalloproteinase CD10/ neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. CD10/NEP has been recognized as modulating peptide-mediated proliferation of lung carcinomas and the normal airway epithelium. The purposes of this study are to evaluate the expression of CD10/NEP in human lung cancers, including non- small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), and to correlate its expression with several clinicopathologic parameters, including proliferative activity. MATERIALS AND METHODS: CD10/NEP expression and proliferative activity were evaluated by immunohisto chemistry in 55 formalin-fixed and paraffin-embedded NSCLC and SCLC specimens, using anti-Human CD10/ NEP and Ki-67 primary antibodies. The correlations between CD10/NEP expression and either Ki-67 proliferative activity or several clinicopathologic parameters were analyzed by chi-square test or Fisher's exact test. RESULTS: Most NSCLC (76%) and SCLC (80%) cases showed loss of CD10/NEP expression in the tumor cells, whereas the bronchial and alveolar epithelia and stromal fibroblasts in the adjacent healthy lung revealed strong expression of CD10/NEP. Its expression was not correlated with proliferative activity or any of the clinicopathologic parameters except for age. Only in terms of topographical expression was CD10/NEP expression found to be inversely correlated with Ki-67 proliferative activity. CONCLUSION: These results suggest that loss of CD10/ NEP expression may be important in the pulmonary carcinogenesis of both NSCLCs and SCLCs, which is topographically related to NSCLC proliferative activity, especially in the squamous cell type.
Antibodies ; Carcinogenesis* ; Chemistry ; Epithelium ; Fibroblasts ; Humans ; Lung ; Lung Neoplasms ; Neprilysin ; Peptide Hormones ; Small Cell Lung Carcinoma

Impaired angiogenesis is a common pathological characteristic of chronic wounds. Therefore, the regulation of angiogenesis is important for proper tissue repair. It was reported that substance P (SP) accelerates wound healing in a skin injury model. SP is degraded by neutral endopeptidase (NEP). Our study shows that systemic co-treatment of SP and thiorphan, an inhibitor of NEP synergically increased the number of α-smooth muscle actin positive-blood vessels in skin wounds. However, there was no synergic improvement in wound contraction and extracellular matrix deposition. Therefore, inhibition of endogenous NEP activity by thiorphan treatment might modulate the effects of SP treatment specifically on accelerating angiogenesis during wound healing. However, the molecular mechanism(s) of the synergic increase in angiogenesis by SP and thiorphan treatment is still unknown.
Actins ; Extracellular Matrix ; Neprilysin ; Skin ; Substance P* ; Thiorphan* ; Wound Healing* ; Wounds and Injuries*

Extracellular accumulation of amyloid beta protein (Abeta) plays a central role in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can affect the Abeta accumulation in the brain. However, the effect of mercury on Abeta accumulation in the brain is not clear. Thus, this study was proposed to estimate whether mercury concentration affects Abeta accumulation in PC12 cells. We treated 10, 100, and 1000 nM HgCl2 (Hg) or CH3HgCl2 (MeHg) for 48 hr in PC12 cells. After treatment, Abeta40 in culture medium increased in a dose- and time-dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is related to Abeta production. Neprilysin (NEP) levels in PC12 cells were decreased by Hg and MeHg treatment. These results suggested that Hg induced Abeta accumulation through APP overproduction and reduction of NEP.
Aluminum ; Alzheimer Disease ; Amyloid beta-Peptides ; Amyloid Precursor Protein Secretases ; Amyloid* ; Animals ; Brain ; Copper ; Mercuric Chloride ; Metals ; Neprilysin ; PC12 Cells*

OBJECTIVE: To investigate effects of benzo(a)pyrene (BaP) on expressions of insulin-degrading enzyme (IDE) and neprilysin (NEP) which have the ability to degrade β-amyloid (Aβ) in neuroglia cells. METHODS: Primary mix-neuroglia cells were cultured from newborn SD rats. After exposure to BaP, Aβ_1-42 oligomer or Aβ_1-42 fiber individually or jointly for 24 h, the cell survival rate was measured by cell counting kit-8 (CCK-8). Afterwards, the primary mix-neuroglia cells were divided randomly into six groups: Control group, BaP group (2.00 μmol/L), Aβ_1-42 oligomer group (20.00 mg/L), BaP plus Aβ_1-42 oligomer group, Aβ_1-42 fiber group (20.00 mg/L) and BaP plus Aβ_1-42 fiber group, of which BaP was pretreated for 12 h followed by cotreatment with different aggregated Aβ_1-42. The expressions of IDE and NEP were measured by quantitative real-time polymerase chain reaction (qRT-PCR) for mRNA level and Western blotting for protein level. RESULTS: The cell survival rate showed no significant differences after treatment with BaP (≤20.00 μmol/L), Aβ_1-42 oligomer (20.00, 40.00 mg/L), Aβ_1-42 fiber (20.00, 40.00 mg/L) or cotreatment with BaP and Aβ_1-42 oligomer or BaP and Aβ_1-42 fiber. Compared with the control group, expressions of IDE and NEP in BaP-treated alone group had no obvious change; however, exposure to Aβ_1-42 oligomer alone significantly increased the mRNA and protein level of IDE (P<0.05), and the BaP pretreatment could significantly inhibit the up-regulated expressions of IDE by Aβ_1-42 oligomer (P<0.05); on the other hand, exposure either to Aβ_1-42 fiber alone or under the BaP pretreatment did not change the mRNA and protein level of IDE and NEP obviously. CONCLUSION On the premise of no significant change of cell survival rate, BaP pretreatment inhibited the up-regulated expressions of IDE in primary mixed neuroglia cells under cotreatment with Aβ oligomer, indicating that BaP may disturb degradation of Aβ oligomer and cause deposition of β-amyloid and further induce cognitive decline and acceleration of Alzheimer.
Amyloid beta-Peptides ; Animals ; Benzo(a)pyrene ; Blotting, Western ; Insulysin/metabolism* ; Neprilysin/metabolism* ; Neuroglia/metabolism* ; Rats ; Rats, Sprague-Dawley

Aminobutyrates ; Angiotensin Receptor Antagonists ; China ; Consensus ; Drug Combinations ; Heart Failure/drug therapy* ; Humans ; Neprilysin ; Stroke Volume ; Tetrazoles ; Valsartan