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South San Francisco, CA, United States

Ridker P.M.,Harvard University | MacFadyen J.G.,Harvard University | Wolfert R.L.,diaDexus | Koenig W.,University of Ulm
Clinical Chemistry | Year: 2012

BACKGROUND: Although lipoprotein-Associated phospholipase A2 (Lp-PLA2) levels are associated with cardiovascular events, L p-PLA2 is physically linked to LDL cholesterol (LDL-C). Whether measures of Lp-PLA2 mass or activity continue to predict risk after LDL-C reduction by statin therapy is uncertain. METHODS: L p-PLA2 mass concentration and activity were evaluated at baseline and after treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin 20 mg to placebo among 17 802 men and women without cardiovascular disease or diabetes at study entry. The relationships of L p-PLA2 mass and activity with risk of future vascular events were evaluated in the placebo and rosuvastatin groups. RESULTS: Before randomization, levels of Lp-PLA2 mass and activity correlated moderately with each other and with LDL-C. The magnitude of these correlations increased after statin therapy. Rosuvastatin reduced Lp-PLA 2 mass by 33.8%, Lp-PLA2 activity by 33.2%, and LDL-C by 48.7% (all P < 0.0001). Among those study participants allocated to placebo, increasing quartiles of Lp-PLA2 activity (Ptrend<0.04) but not Lp-PLA2 mass (Ptrend < 0.92) were associated with incident cardiovascular events after adjustment for LDL-C and conventional risk factors. Comparable analyses conducted among those allocated to rosuvastatin revealed no significant relationship between L p-PLA2 levels and subsequent vascular events. The ability of rosuvastatin to reduce vascular events was not significantly modified by baseline Lp-PLA2 level. CONCLUSIONS: Among JUPITER trial participants allocated to placebo, levels of Lp-PLA2 activity, but not mass, were associated with cardiovascular risk. However, Lp-PLA2 no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin. © 2012 American Association for Clinical Chemistry.


The present invention provides a new method for detecting, diagnosing, monitoring, staging, prognosticating, imaging and treating selected cancers including gynecologic cancers such as breast, ovarian, uterine and endometrial cancer and lung cancer.


Patent
diaDexus | Date: 2011-12-16

The invention provides isolated anti-ovarian, pancreatic, lung or breast cancer antigen (Pro104) antibodies that bind to Pro104 on a mammalian cell in vivo. The invention also encompasses compositions comprising an anti-Pro104 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Pro104 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Pro104 antibodies. The invention encompasses a method of producing the anti-Pro104 antibodies. Other aspects of the invention are a method of killing a Pro104-expressing cancer cell, comprising contacting the cancer cell with an anti-Pro104 antibody and a method of alleviating or treating a Pro104-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the anti-Pro104 antibody to the mammal.


Patent
diaDexus | Date: 2012-05-08

The invention provides isolated anti-PCan065 antibodies that bind to PCan065. The invention also encompasses compositions comprising an anti-PCan065 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-PCan065 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-PCan065 antibodies. The invention encompasses a method of producing the anti-PCan065 antibodies. Other aspects of the invention are a method of killing an PCan065-expressing cancer cell, comprising contacting the cancer cell with an anti-PCan065 antibody and a method of alleviating or treating an PCan065-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the anti-PCan065 antibody to the mammal.


The invention provides isolated anti-Lp-PLA2 antibodies that bind to Lp-PLA2. The invention also encompasses compositions comprising an anti-Lp-PLA2 antibody. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Lp-PLA2 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Lp-PLA2 antibodies. The invention encompasses a method of producing the anti-Lp-PLA2 antibodies. Other aspects of the invention are a method of detecting an Lp-PLA2 in a subject.

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