1.Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.
Ji Min JEON ; Hye Won LEE ; Ji Young PARK ; Hye Ra JUNG ; Ilseon HWANG ; Sun Young KWON ; Mi Sun CHOE ; Yu Na KANG ; Sang Pyo KIM ; Sang Sook LEE ; Won Il CHOI ; Kun Young KWON
Korean Journal of Pathology 2010;44(4):397-403
BACKGROUND: Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance. METHODS: We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray. RESULTS: We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128). CONCLUSIONS: MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.
Adenocarcinoma
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Carcinoma, Squamous Cell
;
Epithelial Cells
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Glycoproteins
;
Humans
;
Lung
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Molecular Weight
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Mucin-1
;
Mucin-4
;
Mucins
;
Prognosis
2.MUC4 research progress in tumor molecular markers.
Journal of Biomedical Engineering 2014;31(1):233-236
Mucin antigen 4 (MUC4) is a molecular marker for some malignant tumors for early tumor diagnosis, prognosis and targeted therapy. It provides a new research direction in tumor diagnosis and treatment that will have a wide application prospect. In recent years, there has been a large number of research reports on the basic and clini-a wide application prospect. In recent years, there has been a large number of research reports on the basic and clinical studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recentcal studies about MUC4, but the molecular imaging study about MUC4 is seldom reported. In this paper the recent research about MUC4 on basic and clinical studies is briefly reviewed, and it is expected to promote the development of tumor molecular imaging.
Biomarkers, Tumor
;
metabolism
;
Early Diagnosis
;
Humans
;
Mucin-4
;
metabolism
;
Neoplasms
;
metabolism
;
Prognosis
3.A Case of Human Herpes Virus-8 Unrelated Primary Effusion Lymphoma-Like Lymphoma Presented as Pleural Effusion.
Kyung Ho KIM ; Ji Hyun LEE ; Hye Cheol JEONG ; Gun Woo KIM ; Sang Hee SONG ; So Young JUNG ; Gwang Il KIM ; Eun Kyung KIM
Tuberculosis and Respiratory Diseases 2012;73(6):336-341
Primary effusion lymphoma (PEL) is a rare type of lymphoma that arises in the body cavity without detectable masses. It is associated with human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV). Recently, PEL unrelated to viral infection has been reported and it has been termed HHV-8 unrelated primary effusion lymphoma-like lymphoma (HHV-8 unrelated PEL-like lymphoma). Here, we report a case of HHV-8 unrelated PEL-like lymphoma in an 80-year-old woman. Chest X-ray and computed tomography revealed left-sided pleural effusion. Pleural effusion analysis and mediastinoscopic biopsy showed atypical cells that had originated from the B cells. The cells were positive for CD20 and bcl-2, but negative for CD3, CD5, CD21, CD30, CD138, epithelial membrane antigen, and HHV-8. Serological tests for HIV and EBV were negative. Considering the patient's age, further treatments were not performed. She has shown good prognosis without chemotherapy for more than 18 months.
B-Lymphocytes
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Biopsy
;
Female
;
Herpesvirus 4, Human
;
Herpesvirus 8, Human
;
HIV
;
Humans
;
Lymphoma
;
Lymphoma, Primary Effusion
;
Mucin-1
;
Pleural Effusion
;
Prognosis
;
Serologic Tests
;
Thorax
4.Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model.
Chin Hee SONG ; Nayoung KIM ; Sung Hwa SOHN ; Sun Min LEE ; Ryoung Hee NAM ; Hee Young NA ; Dong Ho LEE ; Young Joon SURH
Gut and Liver 2018;12(6):682-693
BACKGROUND/AIMS: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. METHODS: The effects of 17β-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. RESULTS: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p < 0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. CONCLUSIONS: E2 acts through the estrogen receptor β signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.
Animals
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Azoxymethane
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Blotting, Western
;
Claudin-4
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Colitis*
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Colitis, Ulcerative
;
Colon*
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Colonic Neoplasms
;
Cytokines
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Enzyme-Linked Immunosorbent Assay
;
Eosine Yellowish-(YS)
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Epithelial Cells
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Estradiol
;
Estrogens
;
Hematoxylin
;
Humans
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Inflammation*
;
Inflammatory Bowel Diseases
;
Male
;
Mice*
;
Mucin-2
;
Mucin-4
;
Occludin
;
Permeability*
;
Peroxidase
;
Real-Time Polymerase Chain Reaction
;
RNA, Messenger
;
Sodium
;
Tight Junctions
5.Clinicopathological Features of Low-Grade Thyroid-like Nasopharyngeal Papillary Adenocarcinoma.
Minhua LI ; Jiangguo WEI ; Xiaofei YAO ; Cheng WANG
Cancer Research and Treatment 2017;49(1):213-218
PURPOSE: Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid-like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)–encoded RNA. RESULTS: Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67–labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative. CONCLUSION: Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required.
Adenocarcinoma, Papillary*
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Adolescent
;
Asian Continental Ancestry Group
;
Epithelial Cells
;
Female
;
Glial Fibrillary Acidic Protein
;
Herpesvirus 4, Human
;
Humans
;
Immunohistochemistry
;
In Situ Hybridization
;
Keratins
;
Mucin-1
;
Nasopharynx
;
RNA
;
Thyroglobulin
;
Thyroid Gland
;
Transcription Factors
;
Vimentin
6.Pentamer guided HLA-restricted epitope identification for mucoprotein 4 antigen of pancreatic ductal adenocarcinoma.
Wen-tao GAO ; Jing-jing ZHANG ; Yi ZHU ; Ji-shu WEI ; Kai MENG ; Jian-min CHEN ; Jun-li WU ; Yi MIAO
Chinese Journal of Surgery 2010;48(18):1416-1424
OBJECTIVESTo identify HLA-restricted epitope of mucoprotein 4 (MUC4) antigen as a tumor associated antigen of pancreatic ductal adenocarcinoma (PDAC), and to validate its natural presentation in PDAC patient peripheral blood.
METHODSTwo epitope prediction databases (SYFPEITHI and ProPred-I) were used to predict HLA-A*0201 restricted MUC4 epitope, T2 cell assay was used to determine the peptide binding affinity with HLA-A*0201 molecule. Dendritic cells (DCs) were induced from the HLA-A* 0201-positive healthy individuals' peripheral blood mononuclear cells (PBMC). Mature DCs were pulsed with synthesized peptides. Autologous CD8(+) T cells from the HLA-A* 0201 healthy donor were stimulated with the peptide-pulsed DCs as CTL. CTL activity was assessed by lactate dehydrogenase release assay and IFN-γ released by enzyme-linked immunospot assay. Pentamer was synthesized for HLA-A* 0201 restricted epitope P1126, then was used to detect specific CTL in PBMC of PDAC patients.
RESULTSFive candidate HLA-A*0201 epitopes were predicted, LLLGVGTFV (P1125) and LLGVGTFVV (P1126) were determined as the two with more HLA-A*0201 affinity. Mature DCs could be induced from PBMCs. CTL induced by peptide P1126 could lyses T2 cells pulsed with peptide P1126 and HCT-116 cells [MUC4(+), HLA-A2(+)]. The number of CTL induced by peptide P1126 which could secret IFN-γ (130.3 ± 6.6) was obviously higher than that in the negative group. By Pentamer assay, P1126-pentamer and CD8 double positive CTL could be detected in PBMC of PDAC patients with MUC4(+) than patients with MUC4(-), but no significant difference of CTL frequency between patients with HLA-A2(+) and with HLA-A2(-) in MUC4(+) PDAC patients.
CONCLUSIONSTumor associated antigen MUC4-derived HLA-A* 0201-restrictive cytotoxic T lymphocyte (CTL) epitope P1126 can induce CTL reaction. The CTL can secret immunologic active material to induce the specific target cells lysis. P1126 epitope can be naturally presented in PBMC of PDAC patients, but its HLA-restriction may not be perfect.
Antigens, Neoplasm ; immunology ; Cells, Cultured ; Dendritic Cells ; immunology ; Epitopes, T-Lymphocyte ; immunology ; HLA-A Antigens ; immunology ; HLA-A2 Antigen ; immunology ; Humans ; Mucin-4 ; immunology ; Pancreatic Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology
7.Murine calcium-activated chloride channel family member 3 induces asthmatic airway inflammation independently of allergen exposure.
Li MEI ; Li HE ; Si-Si WU ; Bo ZHANG ; Yong-Jian XU ; Zhen-Xiang ZHANG ; Jian-Ping ZHAO ; Hui-Lan ZHANG
Chinese Medical Journal 2013;126(17):3283-3288
BACKGROUNDExpression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.
METHODSmCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated. Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed. The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and interleukin-13 (IL-13) were determined quantitatively.
RESULTSmCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway epithelium. The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group. The level of IL-13, but not IL-4, IL-5, IFN-γ, CCL2, CCL5 or CCL11, was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung tissue, the number of eosinophils in BALF, and the content of IL-13 protein in BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.
CONCLUSIONThese findings suggest that increased expression of a single-gene, mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3 overexpression up-regulating IL-13 expression.
Allergens ; Animals ; Asthma ; Chloride Channels ; Female ; Inflammation ; chemically induced ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; genetics ; metabolism ; Interleukin-5 ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Mucin 5AC ; genetics ; metabolism ; Ovalbumin ; pharmacology
8.Alteration of cytokines and mucin in lower respiratory tract in allergic rhinitis model in rats.
Fei HAN ; Yun-Fang AN ; Chang-Qing ZHAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(5):339-342
OBJECTIVETo investigate the relationship between allergic rhinitis (AR) and asthma as well as the mechanisms related with it.
METHODSSixty healthy rats were randomly divided into AR group and control group. AR model was established by intraperitoneal injection of ovalbumin (OVA) and nasal challenge with OVA. Nasal mucosa and lung tissue from both groups were stained with hematoxylin-eosin (HE), alcian-blue and periodic acid-schiff (AB-PAS), respectively. At the same time, the lung tissue was studied by transmission electron microscopy (TEM). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to examine the level of interleukin-4 (IL-4) in bronchial alveolus lavage fluid (BALF) and the expression of intercellular adhesion molecule-1 (ICAM-1) and MUC5AC in nasal and lung tissue, respectively.
RESULTSInfiltration of inflammatory cells in nasal mucosa and lung tissue of AR model in rat was evident. Cilia destruction of bronchial epithelial cells of AR model was found. The level of IL4 in BALF of AR group (58.10 +/- 7.92) pg/ml was significant higher compared with that in control group (24.66 +/- 2.07) pg/ml. The expression of ICAM-1 (0.66 +/- 0.24) and MUC5AC (0.71 +/- 0.10) in lung tissue were both significantly higher than that in control group (0.23 +/- 0.02, 0.29 +/- 0.03).
CONCLUSIONSAllergic inflammation in nasal mucosa not only leads to changes in both histopathology and immunology, but also initiates the inflammation in lower respiratory tract mainly causing the change of cytokines and mucin.
Animals ; Bronchoalveolar Lavage Fluid ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-4 ; metabolism ; Mucin 5AC ; metabolism ; Mucins ; metabolism ; Nasal Mucosa ; metabolism ; pathology ; Rats ; Rhinitis, Allergic, Perennial ; chemically induced ; metabolism ; pathology
9.Effect of Yifei Jianpi Recipe on Airway Inflammation and Airway Mucus Hypersecretion of Chronic Obstructive Pulmonary Disease Model Rats.
Sheng WANG ; Ling-ling XIONG ; Wei REN ; Chun-dong ZHU ; Chun-ying LI ; Qun ZHOU
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(8):993-999
OBJECTIVETo observe preventive and therapeutic effect of Yifei Jianpi Recipe (YJR) on chronic obstructive pulmonary disease (COPD) model rats and to explore its mechanism from the way of airway inflammation and airway mucus hypersecretion.
METHODSThe COPD rat model was established by using cigarette smoking combined with intratracheal injection of lipopolysaccharide (LPS). Male SD rats were randomly divided into the blank control group (control group), the model group, the YJR group, 6 in each group. Forced vital capacity (FVC), forced expiratory volume in 0. 1 second (FEV0. 1), FEVO. 1/FVC, peak expiratory flow (PEF) was tested by lung function device. Pathological changes of bronchi and lung tissues were observed by HE staining. Airway Goblet cells were observed using AB-PAS staining. Contents of IL-8, IL-17, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Protein expressions of intercellular cell adhesion molecule-1 (ICAM-1), nuclear factor KB (NF-KB), mucin 5AC (Muc5AC), and Toll-like receptor 4 (TLR4) in rat airway were detected by immunohistochemical assay. mRNA expressions of TLR4 and Muc5AC in bronchi and lung tissues were detected by real-time quantitative PCR (RT qPCR).
RESULTSChanges of bronchi and lung tissues in the model group rats were consistent with typical pathological manifestations of COPD. Compared with the model group, the degree of lung injury was significantly alleviated in the YJR group. Compared with the control group, FVC, FEV0. 1, FEVO. I/FVC, and PEF were decreased (P <0. 01), contents of IL-8, IL-17, and TNF-α in BALF were significantly increased (P <0. 01), protein expressions of ICAM-1, NF-KB, Muc5AC, and TLR4, mRNA expression levels of Muc5AC and TLR4 in bronchi and lung tissues were also significantly increased in the model group (P <0. 01). Compared with the model group, FVC, FEV0. 1, FEV0. 1/FVC, and PEF were significantly increased in the YJR group (P <0. 01, P <0. 05), but the rest indices were significantly lowered (P <0. 01, P <0. 05).
CONCLUSIONYJR could decrease contents of IL-8, IL-17, and TNF-α in BALF of COPD model rats, inhibit protein expression levels of ICAM-1, NF-κB, Muc5AC, and TLR4.in airway and lung tissues, thus playing preventive and therapeutic roles by reducing airway inflammation and airway mucus hypersecretion.
Animals ; Bronchi ; Bronchoalveolar Lavage Fluid ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Inflammation ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-17 ; metabolism ; Interleukin-8 ; metabolism ; Lipopolysaccharides ; Lung ; Male ; Models, Animal ; Mucin 5AC ; metabolism ; Mucus ; metabolism ; NF-kappa B ; metabolism ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
10.Study on anti-tumor effect of cyanidin-3-glucoside on ovarian cancer.
Linchai ZENG ; Jie GAO ; Rui ZHANG
China Journal of Chinese Materia Medica 2012;37(11):1651-1654
OBJECTIVETo investigate the effect and the mechanism of cyanidin-3-glucoside (C3G) in the growth inhibition of ovarian cancer in vitro and in vivo.
METHODAfter human ovarian cancer cell line HO-8910PM was treated with C3G, cell growth was determined by the Cell Counting Kit-8 (CCK-8) assay and apoptosis was evaluated by flow cytometry analysis stained with Annexin V-FITC/PI. The protein expression in HO-8910PM cells was analyzed by Western blot assay. HO-8910PM cells were injected subcutaneously into nude mice to establish xenograft model. After 3 weeks of implantation, mice were randomized into 2 groups (n = 8): control group, feed with 0.2 mL double distilled water; C3G group, feed with C3G at a dose of 5 mg x kg(-1). All treatment lasted for two weeks, thrice per week. Eight weeks after implantation, tumor weight and inhibition rate were evaluated respectively after the mice were sacrificed. Immunohistochemistry was used to detect the positive expression of Ki-67 and Mucin-4 in the tumors.
RESULTThe proliferation of ovarian cancer cells was inhibited significantly by C3G with IC50 being 13.82 mg x L(-1). Apoptosis rate induced by C3G was markedly highter than that of control. The expression of Mucin4 was down-regulated in HO-8910PM cells after treatment of C3G. C3G inhibited the growth of ovarian xenograft tumors in nude mice. Furthermore, the positive expression of Ki-67 and Mucin-4 were both decreased in tumors after administration of C3G.
CONCLUSIONC3G exerts anti-tumor activity in ovarian cancer both in vitro and in vivo, which may be related to down-regulation of Mucin-4 protein.
Animals ; Anthocyanins ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Glucosides ; pharmacology ; Humans ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Inbred BALB C ; Mucin-4 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Xenograft Model Antitumor Assays