21 research outputs found
Paraneoplastic thrombocytosis in ovarian cancer
<p>Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that
platelets play in abetting cancer growth are unclear.</p>
<p>Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse
models of epithelial ovarian cancer were used to explore the underlying mechanisms
of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.</p>
<p>Results: Thrombocytosis was significantly associated with advanced disease and shortened
survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated
in patients who had thrombocytosis as compared with those who did not. In mouse
models, increased hepatic thrombopoietin synthesis in response to tumor-derived
interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis
in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in
tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In
addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of
paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet
antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor
growth and angiogenesis.</p>
<p>Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic
thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have
therapeutic potential. </p>
Primary peritoneal carcinoma presenting as a Sister Mary Joseph's nodule: A case report and review of the literature
Sister Mary Joseph's nodule is sometimes the first sign of an internal malignancy, including gastrointestinal, gynecological, or malignancy of unknown primary. It is rarely the sole presentation of a primary peritoneal cancer. In this report, we present the case of a 70-year-old female with umbilical drainage and a computed tomography scan consistent with solitary umbilical nodule. Excision of the nodule revealed adenocarcinoma of likely müllerian origin. Surgical staging did not show any evidence of malignancy with the exception of pelvic washings. She was considered to have primary peritoneal adenocarcinoma and was treated with adjuvant chemotherapy