Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF), a protein isolated from serum of patients with liver failure, is a potent mitogen for hepatocytes and is thought to play a role in liver regeneration. Here we present structural and functional evidence that human SF and human HGF (and also the human lung fibroblast-derived mitogen) are identical proteins encoded by a single gene, since (a) no major difference could be found by protein sequencing, by cDNA analysis, and by immunological comparison and (ii) SF in fact acts as a hepatocyte growth factor-i.e., stimulates DNA synthesis of primary hepatocytes-whereas HGF exhibits scatter factor activity-i.e., dissociates and induces invasiveness of various epithelial cells. The human SF/HGF gene was localized to chromosome bands 7q11.2-21. These results have important consequences for further studies on the involvement of SF/HGF as a modulator of cellular growth and motility in embryonal, malignant, and regenerative processes.
The BCR-ABL fusion, the molecular equivalent of the Philadelphia translocation, gains importance for treatment stratification in adult acute lymphoblastic leukemia (ALL). In this prospective study, samples from 478 patients with CD10
Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.
Key Points• Largest prospective trial for adult Burkitt lymphoma/ leukemia patients. • Substantial cure rates and high treatment-realization rates in all age groups.This largest prospective multicenter trial for adult patients with Burkitt lymphoma/ leukemia aimed to prove the efficacy and feasibility of short-intensive chemotherapy combined with the anti-CD20 antibody rituximab. From 2002 to 2011, 363 patients 16 to 85 years old were recruited in 98 centers. Treatment consisted of 6 5-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years old received a reduced regimen. Rituximab was given before each cycle and twice as maintenance, for a total of 8 doses. The rate of complete remission was 88% (319/363); overall survival (OS) at 5 years, 80%; and progression-free survival, 71%; with significant difference between adolescents, adults, and elderly patients (OS rate of 90%, 84%, and 62%, respectively). Full treatment could be applied in 86% of the patients. The most important prognostic factors were International Prognostic Index (IPI) score (0-2 vs 3-5; P 5 .0005), age-adjusted IPI score (0-1 vs 2-3; P 5 .0001), and gender (male vs female; P 5 .004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, even in elderly patients. This trial was registered at www.clinicaltrials.gov as #NCT00199082. (Blood. 2014;124(26):3870-3879)
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