OBJECTIVETo analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase (ALK) rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients.

METHODSClinicopathological data of 34 cases of ALK-positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistochemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method.

RESULTSAmong the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage IA in 5 patients, IB in one patient, IIA in two patients, IIIA in 16 patients, IIIB in 5 patients, IV in 4 patients, and one patient of unknown stage. ALK-positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with mucin production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet-ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation (L858R at exon 21). Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months (1.7-48.7 months).

CONCLUSIONSALK-positive tumors as a molecular subtype of lung adenocarcinoma have distinct clinicopathological features. The histological findings of ALK-positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet-ring cells and cribriform structures. They were rarely co-mutated with EGFR mutation.

Adenocarcinoma ; enzymology ; pathology ; therapy ; Exons ; Female ; Gene Rearrangement ; Genes, erbB-1 ; Humans ; Immunohistochemistry ; Lung Neoplasms ; enzymology ; pathology ; therapy ; Male ; Middle Aged ; Mucins ; biosynthesis ; Mutation ; Neoplasm Proteins ; genetics ; Polymerase Chain Reaction ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics ; Sequence Analysis, DNA

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the survival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR (RT-qPCR) and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC15 were significantly increased in glioma as compared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively correlated with the advanced clinical stages of glioam patients (P<0.01). Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma (P<0.001). Survival analysis indicated that glioma patients with higher MUC15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpression was an independent factor for prognosis (hazard risk: 3.216; P=0.009). It was concluded that MUC15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a potentially unfavorable prognostic factor for patients with glioma.
Adolescent ; Adult ; Aged ; Biomarkers, Tumor ; Brain Neoplasms ; Disease-Free Survival ; Female ; Glioma ; genetics ; pathology ; Humans ; Male ; Middle Aged ; Mucins ; biosynthesis ; genetics ; Prognosis ; RNA, Messenger ; biosynthesis

Aged ; Bile Duct Neoplasms ; diagnostic imaging ; mortality ; pathology ; surgery ; Cholangiopancreatography, Magnetic Resonance ; Female ; Humans ; Male ; Middle Aged ; Mucins ; biosynthesis ; Radiography

OBJECTIVETo determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pulmonary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function.

METHODSEighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the expression of MUC5AC in the paraffin's section was tested by immunohistochemistry.

RESULTSGoblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% +/- 0.10%) was significantly higher than that in the normal lung function group (0.13% +/- 0.06%, P < 0.05). The positive rate of MUC5AC expression in the COPD group (0.27% +/- 0.09%) was higher than that in the normal lung function group (0.20% +/- 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% +/- 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% +/- 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% +/- 6.44% and 10.88% +/- 7.10%, respectively).

CONCLUSIONFor COPD patients with declined lung function, there were goblet cell hyperplasia and increased expression of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.

Aged ; Bronchi ; pathology ; Cell Proliferation ; Epithelium ; pathology ; Exocrine Glands ; metabolism ; Goblet Cells ; pathology ; Humans ; Hyperplasia ; Middle Aged ; Mucin 5AC ; Mucins ; biosynthesis ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Smoking ; Up-Regulation

OBJECTIVETo explore the expression and clinical significance of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients.

METHODSThe expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients were detected with reverse transcription realtime PCR.

RESULTSExpression of MUC4 mRNA was not detected in the peripheral blood mononuclear cells of chronic pancreatitis patients and normal healthy people, but was observed in those of pancreatic cancer patients. The positive expression rate of MUC4 mRNA in pancreatic cancer patients was 60%, which was significantly higher than those of chronic pancreatitis patients and normal healthy people (P < 0.01). The positive expression rate of MUC4 mRNA increased with the development of clinical stage, and the positive expression rate in stage of II - IV (TNM system) was 76.92%, which was significantly higher than that of I - II stage (P < 0.01).

CONCLUSIONSExpression of MUC4 mRNA is highly correlated with the clinical stage in pancreatic cancer patients. Detecting the expression of MUC4 mRNA in peripheral blood mononuclear cells of pancreatic cancer patients may be helpful for the early diagnosis and differential diagnosis.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Female ; Humans ; Male ; Middle Aged ; Monocytes ; metabolism ; Mucins ; biosynthesis ; genetics ; Neoplasm Staging ; Pancreatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUND: Neutrophil elastase (NE) was found to increase the respiratory mucin gene, MUC5AC, although the molecular mechanisms of this process remain unknown. We attempted to determine the signal transduction pathway through which NE induces MUC5AC gene expression in bronchial epithelial cells. METHODS: A fragment of 1.3 Kb MUC5AC promoter which had been cloned into the pGL3-Basic luciferase vector was transfected to the A549 cells. By measuring the luciferase activity, we were able to evaluate the MUC5AC promoter activity in A549 cells. The involvement of mitogen-activated protein kinases (MAPK) was confirmed by Western blotting. To confirm the involvement of nuclear factor kappaB (NF-kB), we used site-directed mutagenesis and electrophoretic mobility shift assay (EMSA) autoradiogram. The MUC5AC mRNA expression was confirmed by RT-PCR. RESULTS: NE increased the transcriptional activity of the MUC5AC promoter in A549 cells. The increased transcriptional activity of the MUC5AC promoter by NE was found to be associated with increased NF-kB activity. Site-directed mutagenesis showed that the transfection of the mutated NF-kB binding sites from the PGL3-MUC5AC-3752 promoter luciferase reporter plasmid decreased the luciferase activity after NE stimulation. Among the MAPKs, only extracellular signal-regulated kinases (ERK) were involved in this NE-induced MUC5AC mucin expression. RT-PCR also showed that NE increased MUC5AC mRNA. An EMSA autoradiogram revealed that NE induced NF-kB: DNA binding. CONCLUSIONS: These results indicate that human NE induces MUC5AC mucin through the epidermal growth factor receptor (EGF-R), ERK, and NF-kB pathways in A549 cells.
Transcription, Genetic ; Signal Transduction ; Receptor, Epidermal Growth Factor/*metabolism ; NF-kappa B/*metabolism ; Mucins/*biosynthesis/genetics ; Leukocyte Elastase/*metabolism ; Humans ; Gene Expression Regulation ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Epithelial Cells ; Cell Line, Tumor ; Bronchi/cytology

OBJECTIVE: To explore the therapeutic effects and mechanisms of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers. METHODS: One hundred and twenty patients were randomly divided into 6 groups. Another 10 patients as the control group were confirmed with no peptic ulcers by endoscope, but had digestive tract symptoms. The clinical effects were compared among each group after the one month treatment. RESULTS: The clinical effects of the combination of Jianweiyuyang granules and ranitidine capsules were better than those of western medicine, with improvement in symptoms and syndrome (P < 0.01 to 0.05), but there was not significant difference with the rate of ulcer healing and the Hp clearance among the combination of Jianweiyuyang granules and ranitidine capsules, Jianweiyuyang granules, and ranitidine capsules (P > 0.05). The combination of Jianweiyuyang granules and ranitidine capsules could significantly upregulate the expression of MUCSAC mRNA (P < 0.01), while downregulate the expression of ETAR mRNA (P < 0.01). CONCLUSION There is obvious advantage in treating peptic ulcers by the combination of Jianweiyuyang granules and ranitidine capsules, and its mechanisms may be to protect the gastric mucosal barrier by up-regulating the expression of MUCSAC mRNA and to improve the gastric mucosal blood flow by down-regulating the expression of ETAR mRNA.
Adult ; Capsules ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Endothelin-1 ; biosynthesis ; genetics ; Female ; Gastric Mucosa ; metabolism ; Humans ; Male ; Middle Aged ; Mucin 5AC ; Mucins ; biosynthesis ; genetics ; Peptic Ulcer ; drug therapy ; Phytotherapy ; RNA, Messenger ; biosynthesis ; genetics ; Ranitidine ; therapeutic use ; Receptors, Endothelin ; biosynthesis ; genetics

To study the effects of glucocorticoid on the IL-13-induced Muc5ac expression in airways of mice, and investigate its role in mucus secretion of airways, 24 pathogen-free BALB/c mice were randomly divided into 3 groups. IL-13 group received an nasal instillation of 100 microg of recombinant murine IL-13 solution on days 1, 3 and 5. In dexamethasone group, dexamethasone (0.5 mg/kg) was administered intraperitoneally 24 h before and 1 h before the first instillation of IL-13 and on 4 consecutive days (day 0 to day 5, 6 consecutive days in total), while control group was not treated with IL-13 or dexamethasone. Bronchoalveolar lavage fluid (BALF) was collected and eosinophils were counted, and expression of Muc5ac mRNA and protein in lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) technology and immunohistochemical assay respectively. Our results showed that the number of mice, with positve Muc5ac protein expression, expression of Muc5ac mRNA and eosinophils in BALF after IL-13 treatment were all significantly higher than that of control group (all P<0.01). Despite eosinophils reduced (P<0.01), the number of mice with positive Muc5ac protein expression, expression of Muc5ac mRNA afterdexamethasone treatment didn't decreas significantly as compared with that of IL-13 group. It is concluded that IL-13 can up-regulate the expression of Muc5ac mRNA and protein, which may play a pivotal role in the mucus overproduction of airways. Dexamethasone can suppress IL-13-induced eosinophilic infiltration in lung but can't inhibit the mucus overproduction.
Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Dexamethasone ; pharmacology ; Interleukin-13 ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mucin 5AC ; Mucins ; biosynthesis ; genetics ; Mucus ; secretion ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Respiratory System ; metabolism

To study the effects of glucocorticoid on the IL-13-induced Muc5ac expression in airways of mice, and investigate its role in mucus secretion of airways, 24 pathogen-free BALB/c mice were randomly divided into 3 groups. IL-13 group received an nasal instillation of 100 microg of recombinant murine IL-13 solution on days 1, 3 and 5. In dexamethasone group, dexamethasone (0.5 mg/kg) was administered intraperitoneally 24 h before and 1 h before the first instillation of IL-13 and on 4 consecutive days (day 0 to day 5, 6 consecutive days in total), while control group was not treated with IL-13 or dexamethasone. Bronchoalveolar lavage fluid (BALF) was collected and eosinophils were counted, and expression of Muc5ac mRNA and protein in lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) technology and immunohistochemical assay respectively. Our results showed that the number of mice, with positve Muc5ac protein expression, expression of Muc5ac mRNA and eosinophils in BALF after IL-13 treatment were all significantly higher than that of control group (all P<0.01). Despite eosinophils reduced (P<0.01), the number of mice with positive Muc5ac protein expression, expression of Muc5ac mRNA afterdexamethasone treatment didn't decreas significantly as compared with that of IL-13 group. It is concluded that IL-13 can up-regulate the expression of Muc5ac mRNA and protein, which may play a pivotal role in the mucus overproduction of airways. Dexamethasone can suppress IL-13-induced eosinophilic infiltration in lung but can't inhibit the mucus overproduction.
Bronchoalveolar Lavage Fluid/cytology ; Dexamethasone/*pharmacology ; Interleukin-13/*pharmacology ; Mice, Inbred BALB C ; Mucins/*biosynthesis ; Mucins/genetics ; Mucus/secretion ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Random Allocation ; Respiratory System/*metabolism

OBJECTIVETo study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer.

METHODSMucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method.

RESULTSMUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001).

CONCLUSIONSThe expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.

Antigens, Neoplasm ; biosynthesis ; Dendritic Cells ; immunology ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Mucin-1 ; Mucins ; biosynthesis ; Prostatic Hyperplasia ; immunology ; metabolism ; pathology ; Prostatic Neoplasms ; immunology ; metabolism ; pathology