{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:44:58Z","timestamp":1791233098546,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,5,12]],"date-time":"2005-05-12T00:00:00Z","timestamp":1115856000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Urol"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Current models of the mechanism by which intravesical BCG induces an anti-tumor effect in urothelial carcinoma propose a secondary cellular immune response as principally responsible. Our group has demonstrated that BCG mediated cross-linking of \u03b15\"Equation missing\"1 integrin receptors present on the tumor surface elicits a complex biologic response involving AP1 and NF-\u03baB signaling as well as the transactivation of immediate early genes. This study evaluated the direct biologic effect of cross-linking \u03b15\u03b21 integrin on cell cycle progression and apoptosis in two human urothelial carcinoma cell lines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Two independent assays (MTT and Colony forming ability) were employed to measure the effect of \u03b15\u03b21 cross-linking (antibody mediated or BCG) on cellular proliferation. Flow cytometry was employed to measure effect of BCG and \u03b15\u03b21 antibody mediated cross-linking on cell cycle progression. Apoptosis was measured using assays for both DNA laddering and Caspase 3 activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Results demonstrate that integrin cross-linking by BCG, or antibody mediated crosslinking of \u03b15\u03b21 resulted in a decrease in proliferating cell number. BCG treatment or \u03b15\u03b21 cross-linking increased the percentage of cells in G0\/G1, in both 253J and T24 cell lines. Peptide mediated blockade of integrin binding site using RGDS reversed the effect BCG on both proliferation and cell cycle arrest. Apoptosis in response to BCG was not identified by either DNA laddering or Caspase 3 activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These findings show that BCG exerts a direct cytostatic effect on human urothelial carcinoma cell lines. Cell cycle arrest at the G1\/S interface is a mechanism by which BCG inhibits cellular proliferation. This effect is duplicated by antibody mediated cross-linking of \u03b15\u03b21 and likely occurs as a consequence of crosslink-initiated signal transduction to cell cycle regulatory genes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2490-5-8","type":"journal-article","created":{"date-parts":[[2005,5,13]],"date-time":"2005-05-13T06:13:25Z","timestamp":1115964805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["BCG directly induces cell cycle arrest in human transitional carcinoma cell lines as a consequence of integrin cross-linking"],"prefix":"10.1186","volume":"5","author":[{"given":"Fanghong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"See","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,5,12]]},"reference":[{"issue":"4","key":"45_CR1","first-page":"280","volume":"18","author":"SB Malkowicz","year":"2000","unstructured":"Malkowicz SB: Intravesical therapy for superficial bladder cancer. 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