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1.
Exp Oncol ; 30(1): 81-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18438347

ABSTRACT

UNLABELLED: Anion exchanger 2 (AE2), which mediates exchange of Cl(-)/HCO3(-) across the plasma membrane, is widely expressed in body tissues. It is most abundantly expressed in stomach and is responsible for the uptake of Cl(-) ions that are destined to become HCl molecules. AIM: To determine whether AE2 expression was altered in gastric tumors. METHODS: We have studied AE2 expression in normal human gastric tissues (n =16) and in gastric tumors (n = 33) using immunohistochemistry and immunofluorescent labeling. RESULTS: In normal gastric tissue positive staining was observed in gastric fundus gland, suggesting parietal cell-related expression of AE2, and AE2 expression was localized in the nuclear membrane and even in cell nuclei. For assay of cancerous gastric tissues, specimens of human gastric cancer arising from the region of the fundus (2 cases), the body (14 cases) and the antrum (17 cases) were randomly selected. Immunohistochemical staining has showed that AE2 was down-regulated in all 14 cancerous gastric body specimens, whereas staining for AE2 in cancerous antrum was less intense and had a diffuse profile. CONCLUSIONS: The data suggest that AE2 might be associated with gastric carcinogenesis and the achlorhydria experienced by gastric cancer patients.


Subject(s)
Adenocarcinoma/metabolism , Anion Transport Proteins/metabolism , Antiporters/metabolism , Stomach Neoplasms/metabolism , Achlorhydria/etiology , Achlorhydria/metabolism , Adenocarcinoma/complications , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Down-Regulation , Female , Follow-Up Studies , Gastric Mucosa/metabolism , Humans , Male , Middle Aged , Retrospective Studies , SLC4A Proteins , Stomach Neoplasms/complications , Stomach Neoplasms/pathology
2.
Ann Oncol ; 19(9): 1584-91, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18436522

ABSTRACT

BACKGROUND: The vesicular stomatitis virus matrix protein (VSVMP) has been receiving attention as an anticancer agent because of its ability of inducing apoptosis. MATERIALS AND METHODS: Nude mice bearing A2780s and A2780cp ovarian tumors were treated twice weekly with i.v. administration of 50 microg VSVMP/250 mug liposome complex, 50 microg empty plasmid/250 microg liposome complex, 0.9% NaCl solution or weekly with i.p. administration of cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. TUNEL assay and CD34 vessel staining were conducted in tumor tissue. Antiangiogenesis in vivo were determined by sponge assay. Antiproliferative and apoptosis-inducing activities of VSVMP in vitro were tested on MS1 murine endothelial cells and four human ovarian cancer cell lines: A2780s, A2780cp, HO8910 and COC1. RESULTS: Administration of VSVMP resulted in significant inhibition (87%-98% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts, and prolonged the survival of the treated mice. Complete tumor regression happened in VSVMP-treated mice in both tumor models. These antitumor responses were associated with marked increases in tumor apoptosis and reductions in intratumoral microvessel density. CONCLUSIONS: Our data indicate that VSVMP may provide an effective approach to inhibit both cisplatin-sensitive and -resistant human ovarian cancer growth with minimal side-effects.


Subject(s)
Cisplatin/pharmacology , Genetic Therapy/methods , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Vesiculovirus , Analysis of Variance , Animals , Apoptosis/genetics , Apoptosis/physiology , Cell Division/drug effects , Cell Division/physiology , Disease Models, Animal , Drug Resistance, Neoplasm , Female , Gene Transfer Techniques , Humans , Kaplan-Meier Estimate , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Ovarian Neoplasms/pathology , Probability , Random Allocation , Sensitivity and Specificity , Survival Rate , Tumor Cells, Cultured , Viral Matrix Proteins/genetics , Xenograft Model Antitumor Assays
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