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Drugs and antibodies that interrupt vascular endothelial growth factor (VEGF) signaling pathways improve outcomes in patients with a variety of cancers by inhibiting tumor angiogenesis. A major adverse effect of these treatments is hypertension, suggesting a critical role for VEGF in blood pressure (BP) regulation. However, the physiological mechanisms(More)
AIM This study was designed to determine the efficacy and tolerability of capecitabine, oxaliplatin and bevacizumab in combination with cetuximab as first-line therapy for advanced colorectal cancer. PATIENTS AND METHODS Patients with previously untreated advanced colorectal cancer received oxaliplatin 130 mg/m² and bevacizumab 7.5 mg/kg every three(More)
The newly defined eicosatetraenoates (ETEs), 5-oxoETE and 5-oxo-15(OH)-ETE, share structural motifs, synthetic origins, and bioactions with leukotriene B4 (LTB4). All three eicosanoids stimulate Ca2+ transients and chemotaxis in human neutrophils (PMN). However, unlike LTB4, 5-oxoETE and 5-oxo-15(OH)-ETE alone cause little degranulation and no superoxide(More)
The enzyme CoA-independent transacylase (CoA-IT) has been proposed to mediate the movement of arachidonate between specific phospholipid subclasses, and we have shown that two inhibitors of CoA-IT (SK&F 98625 and SK&F 45905) block this movement. In this report, we use these inhibitors to further characterize the role of CoA-IT in the production of lipid(More)
Impairment of dendritic cells (DC), the most effective activators of anticancer immune responses, is one mechanism for defective antitumor immunity, but the causes of DC impairment are incompletely understood. We evaluated the association of impaired DC differentiation with angiogenesis-associated molecules D-dimer, vascular endothelial growth factor(More)
Cancers subvert the host immune system to facilitate disease progression. These evolved immunosuppressive mechanisms are also implicated in circumventing immunotherapeutic strategies. Emerging data indicate that local tumor-associated DC populations exhibit tolerogenic features by promoting Treg development; however, the mechanisms by which tumors(More)
Pathologic angiogenesis creates an abnormal microenvironment in solid tumors, characterized by elevated interstitial fluid pressure (IFP) and hypoxia. Emerging theories suggest that judicious downregulation of proangiogenic signaling pathways may transiently "normalize" the vascular bed, making it more suitable for drug delivery and radiotherapy. In this(More)
PURPOSE Formalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis-related genes to identify prognostic or predictive biomarkers for cetuximab treatment. PATIENTS AND METHODS Patients (238 total) with first-line metastatic colorectal cancer (mCRC) were randomized to FOLFOX or FOLFIRI chemotherapy ±(More)
The type III transforming growth factor β (TGF-β) receptor (TβRIII), also known as betaglycan, is the most abundantly expressed TGF-β receptor. TβRIII suppresses breast cancer progression by inhibiting migration, invasion, metastasis, and angiogenesis. TβRIII binds TGF-β ligands, with membrane-bound TβRIII presenting ligand to enhance TGF-β signaling.(More)
Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-β receptor (TβRIII) mediates BMP signaling. While TβRIII expression is lost during breast cancer progression, the role of TβRIII in regulating BMP signaling in normal(More)