General: Trombocytose, elevated platelets increase chance of dying from ovarian cancer, significantly. It shows an important predictive factor trombocytose on survival and chances of relapse. Article posted 21 February 2012
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21 February 2012: N Engl J Med. Source: 2012; 366: 610-618
Increase chance of Trombocytose, elevated platelets, dying from ovarian cancer significantly. It shows an important predictive factor for trombocytose patients with ovarian cancer on the survival time and chances of a relapse. Overall, one in three women with ovarian cancer trombocytose-too many platelets.-and thus a significant increased risk of dying from the disease, faster this will be apparent from the results of a prospective study with 619 women with ovarian cancer, conducted in four hospitals in America and published in the New England Journal of Medicine.
From the study with 619 patients with ovarian cancer showed that 192 (31%) patients had trombocytose ...For women with trombocytose was the median survival for patients with 2.62 years, a normal platelet count was that 4.65 years (P <. 001). In a multivariate analysis corrected for age, disease stage, tumor stage, type of the tumor and the extent of a surgical procedure-tumor reduction, trombocytose remained an independent Predictor of poor survival (P <. 001).
According to the researchers platelet as fuel depot for tumors seem to function by providing them with growth factors. "The idea that platelets play an important role in the growth of cancer and uitzaaiïngen has long been subject of investigation but never are the mechanisms and biological significance of this increase in platelets really understand," the researchers write.
The researchers discovered that in mice with ovarian cancer, inflammatory cytokine interleukin (IL-6) ensures that platelets are rising and apparently stimulates the growth of the tumor. Research by the insights from their pre-clinical researchers came to the conclusion that ' trombocytose ' might not be just a paraneoplastic uitting of cancer progression is,
but precisely also an active contribution.
In a phase I/II study, the researchers found that treatment with an antibody against IL-6 siltuximab, every 2 weeks during 12 weeks resulted in a significant and sustained reduction in the number of platelets (P = 0,009), the researchers said
In the prospective study trombocytose was defined as the platelet count was more than 450,000/ML3. Of the 192 women in the study with trombocytose, only a fraction (2%) had a shortage of iron or a benign inflammation, which common causes of elevated concentrations of platelets, notify the authors. Thus showed that clearly relates to the ovarian cancer trombocytose, according to the researchers.
In addition to a worse survival rate in patients with duideljke trombocytose there was also significantly more likely to have a more severe stage of the disease, more prone to vascular thromboembolic complications and a higher level of Antigen measured 125 for the operation, compared with people who have a normal platelet level. Women with significantly shorter median time to trombocytose also had a progression of the disease than people with a normal number of platelets.
Here is the abstract of the study. The full study report, you can see if you click here
One in 3 women with ovarian cancer have thrombocytosis, or high platelet counts, and are consequently at a significantly increased risk for reduced disease-specific survival
Paraneoplastic Thrombocytosis in Ovarian Cancer
N Engl J Med 2012; 366: 610-618February 16, 2012
Background
The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.
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 of genesis were ascertained.
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 tumor-derived thrombopoietin synthesis in response to interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived hepatic interleukin-6 and were also linked to thrombopoietin thrombocytosis in patients. Thrombopoietin and interleukin-6 in Silencing tumor-bearing mice thrombocytosis abrogated. 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 in mouse models of epithelial ovarian cancer or paclitaxel. The use of an antiplatelet antibody to tumor-bearing mice significantly half platelet counts in reduced tumor growth and angiogenesis genesis.
Conclusions
These findings support the existence of a paracrine circuit wherein increased production of cytokines in tumor and host tissue thrombopoietic paraneoplastic thrombocytosis, which fuels leads to tumor growth. We speculate that either directly or indirectly by targeting paraneoplastic thrombocytosis countering these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.)
Supported in part by a Gail MacNeil KOH Research Award from the Gynecologic Cancer Foundation; grants (CA109298, CA098258, CA128797, CA083639, P50 P50, RC2GM092599, CA140933, CA151668, and CA016672 U54 R01CA104825) from the National Institutes of Health; a Program Project Development Grant from the Ovarian Cancer Research Fund; grants (W81XWH-OC073399, 10-1-0158, and BC085265) from the Department of Defense; the Baylor College of Medicine and M.D. Anderson Cancer Center Multidisciplinary Research Program; the Zarrow Foundation; the Marcus Foundation; the Estate or c.g. Johnson, Jr.; the United Kingdom Medical Research Council; the Blanton-Davis Ovarian Cancer Research Program; the Laura and John Arnold Foundation; the RGK Foundation; the Murray Distinguished Professorship Bettyann Asche; and training grants (T32 CA101642 supported Drs. Stone, Nick, T32 CA009666 Bottsford-Miller, and King and supported Dr. Pecot) from the National Cancer Institute. The siltuximab trial was funded by the United Kingdom Medical Research Council and sponsored and monitored by Queen Mary, University of London.
Dr. Stone reports being listed as one of the inventors on a U.S. patent entitled "Use Selective Adenosine A1 Receptor Allosteric Enhancers to Manipulate or Angiogenesis genesis." No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank Donna Reynolds, Robert Langley, Ph.d. (Department of Cancer Biology, M.D. Anderson Cancer Center), De-Yu Shen, and Nicholas b. Jennings for their technical assistance and helpful discussions, as well as Bueso-Ramos, M.D., Ph.d. (Department of Hematopathology, M.D. Anderson Cancer Center), for his hematopathology expertise.
Source Information
Gynecologic Oncology and Reproductive Medicine From the Departments or (A.M.N., H.D.H., R.L.S., J.B.-m., W.H., H.G., K.M., M.M.K.S., E.R.K., A.K.S.), Cancer Biology (r.r., G.L.-b., A.K.S.), Experimental Therapeutics (G.N.A.-p., I.T., Bo, G.L.-b.), Hematology and Oncology (C.V.P.)Benign Hematology, Pathology (M.T.D), (H.G.V., v.a.-k.), Biostatistics (D.U.), and Leukemia (F.g.9), and the Center for RNA Interference and Non-Coding RNA (H.D.H., G.L.-b., A.K.S.), University of Texas M.D. Anderson Cancer Center, the Department of Biochemistry and Molecular Biology, Baylor College of Medicine (r.w., W.C.), and the Department of Bioengineering and Nanomedicine, UT Health (G.L.-b.) — all in Houston; the Barts Cancer Institute, Queen Mary, University of London, London (I.A.M., F.B., J.C.); the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama, Birmingham (C.N.L.); the Department of Obstetrics and Gynecology, University of Maryland, Baltimore (E.H.A., V.K.B.); the Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati (A.F.D.); and the Departments of Psychology (K.C., S.K.L.), Urology (S.K.L.), and Obstetrics and Gynecology (K.D., S.K.L.), and the Holden Comprehensive Cancer Center (K.D., S.K.L.), University of Iowa, Iowa City.
Address reprint requests to Dr. Sood at the Department of Gynecologic Oncology and Reproductive Medicine, M.D. Anderson Cancer Center, Unit 1362, P.O. Box 301439 77230-1439, Houston, TX, or at asood@mdanderson.org.
