[A case of cecum colon cancer with lymph node metastasis successfully treated with XELOX plus bevacizumab].

A 65-year-old woman with a history of constipation presented at our hospital and was subsequently diagnosed with advanced cecum cancer. We performed laparoscopic right hemicolectomy in January 2009, with pathological findings reveal- ing the presence of Stage III b (pT3, pN3, cM0, Cur A) disease. The patient was treated with a uracil/tegafur plus Leucovorin (UFT/LV) adjuvant chemotherapy regimen for six months. In June 2010, bold examination indicated an elevated level of tumor marker CA19-9. Computed tomography (CT) and positron emission tomography (PET)/CT revealed Virchow's and para-aortic lymph node metastasis. Therapy with XELOX and bevacizumab (Bmab) was administered and continued for 10 cycles. Capecitabine+Bmab treatment was also administered for 11 courses due to an adverse event of peripheral neuropathy. Follow-up revealed both the Virchow's and para-aortic lymph node metastasis had disappeared upon completion of treatment. In November, 2011 the patient was considered to have achieved a clinical complete response (CR) and continues to be followed with no further disease progression.

Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice.

Plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of a major fibrinolytic factor, tissue-type plasminogen activator, can both promote and inhibit angiogenesis. However, the physiologic role and the precise mechanisms underlying the angiogenic effects of PAI-1 remain unclear. In the present study, we report that pharmacologic inhibition of PAI-1 promoted angiogenesis and prevented tissue necrosis in a mouse model of hind-limb ischemia. Improved tissue regeneration was due to an expansion of circulating and tissue-resident granulocyte-1 marker (Gr-1(+)) neutrophils and to increased release of the angiogenic factor VEGF-A, the hematopoietic growth factor kit ligand, and G-CSF. Immunohistochemical analysis indicated increased amounts of fibroblast growth factor-2 (FGF-2) in ischemic gastrocnemius muscle tissues of PAI-1 inhibitor-treated animals. Ab neutralization and genetic knockout studies indicated that both the improved tissue regeneration and the increase in circulating and ischemic tissue-resident Gr-1(+) neutrophils depended on the activation of tissue-type plasminogen activator and matrix metalloproteinase-9 and on VEGF-A and FGF-2. These results suggest that pharmacologic PAI-1 inhibition activates the proangiogenic FGF-2 and VEGF-A pathways, which orchestrates neutrophil-driven angiogenesis and induces cell-driven revascularization and is therefore a potential therapy for ischemic diseases.