ABSTRACT
BACKGROUND: Long-lived somatic cells such as stem/progenitor cells may progressively accumulate oncogenic mutations and cause cancer. Some evidence suggests that pre-menopausal administration of progesterone confers a long-term increased risk of breast cancer. AIM: To clarify the effect of progesterone on long-lived mammary epithelial cells in rats. MATERIALS AND METHODS: Female Sprague- Dawley rats (3 and 7 weeks of age) were implanted sc with 14-day slow-release pellets of 5-bromo-2'-deoxyuridine (BrdU) and were sacrificed every 2 weeks between 0 and 10 weeks after the release period. Some rats at 7 weeks of age were also implanted with progesterone and sacrificed 0 or 10 weeks after the release period. Mammary glands were examined by immunohistochemistry and immunofluorescence for BrdU, proliferative cell nuclear antigen (PCNA) and progesterone receptor (PR). RESULTS: After BrdU labeling of 3- and 7-week-old rats, the BrdU index decreased gradually over 10 weeks and resulted in small fractions (1-3%) of label-retaining epithelial cells (LREC) 10 weeks after BrdU labeling in both mammary lobules and ducts. Treatment with progesterone during labeling significantly increased the fraction of long-lived LREC in lobules and ducts by 9- and 4-fold, respectively. The long-lived LREC population in the ducts was enriched for PCNA- and PR-positive cells, but the percentage of positive cells was not affected by progesterone in either lobules or ducts. CONCLUSIONS: Progesterone stimulates proliferation of a long-lived epithelial cell population in the mammary lobules and ducts of rats. Such cells in the duct are characterized by a high proliferation rate and PR expression.
Subject(s)
Cell Proliferation , Epithelial Cells/drug effects , Mammary Glands, Animal/drug effects , Progesterone/pharmacology , Progestins/pharmacology , Stem Cells/drug effects , Animals , Bromodeoxyuridine/metabolism , Cells, Cultured , Epithelial Cells/cytology , Epithelial Cells/metabolism , Female , Fluorescent Antibody Technique , Immunoenzyme Techniques , Mammary Glands, Animal/cytology , Mammary Glands, Animal/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Progesterone/metabolism , Stem Cells/cytology , Stem Cells/metabolismABSTRACT
BACKGROUND AND AIMS: Although regenerating gene (REG) Ialpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ialpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. METHODS: Expression of REG Ialpha mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ialpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ialpha protein on growth and H(2)O(2) induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. RESULTS: REG Ialpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ialpha mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ialpha promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG Ialpha protein promoted cell growth and conferred resistance to H(2)O(2) induced apoptosis in LoVo cells. REG Ialpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. CONCLUSIONS: The REG Ialpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.
Subject(s)
Colitis, Ulcerative/genetics , Colonic Neoplasms/genetics , Lithostathine/genetics , Adenoma/genetics , Adult , Aged , Aged, 80 and over , Apoptosis/genetics , Cell Division/genetics , Cell Line, Tumor , Colitis, Ulcerative/metabolism , Colonic Neoplasms/metabolism , Cytokines/genetics , Female , Gene Expression Regulation/genetics , Humans , Immunohistochemistry/methods , Intestinal Mucosa/physiology , Lithostathine/metabolism , Male , Middle Aged , Neoplasm Proteins/analysis , Proliferating Cell Nuclear Antigen/analysis , RNA, Messenger/analysis , RNA, Neoplasm/analysisABSTRACT
The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.
Subject(s)
Th2 Cells/immunology , Vaccination/methods , Vaccines/administration & dosage , Administration, Oral , Administration, Rectal , Animals , Antibody Formation , CD4-Positive T-Lymphocytes/immunology , Cytokines/genetics , Female , Immunoglobulin A, Secretory/biosynthesis , Mice , Mice, Inbred BALB C , Microspheres , Ovalbumin/administration & dosage , Ovalbumin/immunology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Churg-Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systematic vasculitis occurring in individuals with bronchial asthma. We present a case of 24-year-old woman with CSS diagnosed by and followed with gastrointestinal fiberscopic examination and electroneuromyography. The duodenal biopsy showed granulomatous angiitis with eosinophilic infiltration, and the electroneuromyography showed peripheral nerve dysfunction. After steroid treatment, the duodenal erosion and ulcer were almost completely resolved. There was no improvement in electroneuromyography, but the patient was able to walk independently after intensive rehabilitative training.
