We have isolated and characterized a novel growth factor for endothelial cells,

SummaryVEGF-C is a recently characterised endothelial growth factor structurally related to vascular endothelial growth factor (VEGF). We studied the expression of VEGF-C and VEGF in the cells of peripheral blood and in the umbilical cord blood CD 34+ cells, representing haematopoietic progenitor cells. Expression of VEGF-C was detected in the CD34+ cells. In peripheral blood VEGF-C mRNA was restricted to platelets and T-cells. In contrast to the expression pattern of VEGF-C, VEGF mRNA was detected in all peripheral blood cell fractions studied, and also in CD34+ cells. VEGF-C mRNA was also detected in fresh bone marrow samples of acute leukaemia patients, but the expression did not show lineage specificity. VEGF-C and VEGF polypeptides were present in platelets and they were released from activated platelets together with the release of β-thromboglobulin, suggesting that VEGF-C and VEGF reside in the α-granules of platelets. VEGF-C and VEGF, released from activated platelets, may have a role in angiogenesis during wound healing, and possibly also in other pathological conditions, such as atherosclerosis, tumour growth, and metastasis formation.

Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next-generation sequencing now allows rapid identification of patient-specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays for rearrangements could detect a single copy of the tumor genome in plasma without false positives. Disease status, drug responsiveness, and incipient relapse could be serially assessed. In future, this strategy could be readily established in diagnostic laboratories, with major impact on monitoring of disease status and personalizing treatment of solid tumors.

Expression of LPH mRNA in the intestinal mucosa in individuals with T(-13910) A(-22018) alleles is several times higher than that found in individuals with C(-13910), G(-22018) alleles. These findings suggest that the two SNPs, C/T(-13910) and G/A(-22018), associated with adult-type hypolactasia, are associated with the transcriptional regulation of the LPH gene. The presence of the T(-13910) A(-22018) allele also shows significant elevation of the L/S ratio.

High serum concentrations of vascular endothelial growth factor (S-VEGF) and basic fibroblast growth factor (S-bFGF) are associated with unfavorable clinical characteristics in cancer. The combined effect of S-VEGF and S-bFGF on the survival of 200 patients with non-Hodgkin lymphoma (NHL) was studied. High S-VEGF and S-bFGF at diagnosis were associated with poor survival with the medians, the highest tertiles, or the highest quartiles as the cutoff values. The highest prognostic power was obtained when S-VEGF and S-bFGF were examined as a combination. Patients who had both S-VEGF and S-bFGF within the highest quartiles had only a 21% 5-year survival rate in contrast to a 64% 5-year survival rate among patients with both factors within the 3 lowest quartiles (P < .0001). Simultaneous elevation of S-VEGF and S-bFGF was associated with poor survival in different grades of lymphomas and in the largest histologic subgroup, the large-cell diffuse and immunoblastic lymphomas. S-VEGF (relative risk [RR], 1.83; P = .019) and S-bFGF (RR, 2.02; P = .0049) had independent influences on survival in multivariate models when tested together with the components of the International Prognostic Index (IPI). Patients with both S-VEGF and S-bFGF within the highest quartiles had nearly 3 times higher risk for death (RR, 2.90; 95% confidence interval [CI], 1.56-5.40;P = .0008) than the rest of the patients. This RR was higher than the relative risks associated with any of the components of the IPI in the same model. The authors conclude that the combination of S-VEGF and S-bFGF is a powerful prognostic variable in NHL.