{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:18:46Z","timestamp":1779121126988,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T00:00:00Z","timestamp":1533600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["AIRC IG 18853"],"award-info":[{"award-number":["AIRC IG 18853"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>The efficacy of therapeutic regimens incorporating weekly or every\u20103\u2010weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose\u2010dense\u2010equi (every other day to the conventional cumulative dose), or dose\u2010dense\u2010high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time\u2010windows in two patient\u2010derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short\u2010term effects on cell cycle, tumor cell proliferation\/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose\u2010dense (with\/without DDP) was superior to the conventional scheme in a dose\u2010dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP\/PTX dose\u2010dense\u2010high (only chemotherapy) was at least as active as DDP\/PTX conventional plus bevacizumab. DDP\/PTX dose\u2010dense\u2010high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule\u2010dose of the treatment and help to explain the unclear benefits after bevacizumab.<\/jats:p>","DOI":"10.1002\/ijc.31596","type":"journal-article","created":{"date-parts":[[2018,5,12]],"date-time":"2018-05-12T05:31:20Z","timestamp":1526103080000},"page":"2187-2199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tumor progression and metastatic dissemination in ovarian cancer after dose\u2010dense or conventional paclitaxel and cisplatin plus bevacizumab"],"prefix":"10.1002","volume":"143","author":[{"given":"Francesca","family":"Bizzaro","sequence":"first","affiliation":[{"name":"Laboratory of Biology and Treatment of Metastasis, Department of Oncology IRCCS\u2010Istituto di Ricerche Farmacologiche Mario Negri Milan 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