The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation.

Metnase is a human SET and transposase domain protein that methylates histone H3 and promotes DNA double-strand break repair. We now show that Metnase physically interacts and co-localizes with Topoisomerase IIalpha (Topo IIalpha), the key chromosome decatenating enzyme. Metnase promotes progression through decatenation and increases resistance to the Topo IIalpha inhibitors ICRF-193 and VP-16.

Phase II studies of antiangiogenic four drug regimens for the treatment of advanced renal cell carcinoma: FUNIL-retinoid and the FUNIL-thalidomide protocols.

Background And Purpose: The objective of these studies was to determine the activity of two alternative 4- drug combinations using cis-retinoic acid or thalidomide administered with a previously developed combination of 5 fluorouracil, interferon-alpha, and interleukin 2 (FUNIL), for patients with metastatic renal cell carcinoma (RRC).

Methods: Patients enrolled in these studies had progressive measurable metastatic renal cell cancer and signed an informed consent. Treatments included continuous infusions of 5-fluorouracil, interferon-alpha, 6 MIU/m2 given subcutaneous on days 1, 3, and 5 every week, interleukin-2 6 MIU/m2/day given by continuous infusion days 2 to 5 every week, and either cis-retinoic acid at a dose of 1 mg/kg/day orally in two divided doses or thalidomide given at an initial dose of 200 mg per day.

The chemokine CXCL14 (BRAK) stimulates activated NK cell migration: implications for the downregulation of CXCL14 in malignancy.

Objective: The primary function of chemokines is the regulation of leukocyte trafficking by stimulating directional chemotaxis. The chemokine CXCL14 (BRAK) is highly expressed in all normal tissues, but is not expressed in most malignant tissues. The chemotactic activity of CXCL14 has been difficult to characterize.

The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair.

The molecular mechanism by which foreign DNA integrates into the human genome is poorly understood yet critical to many disease processes, including retroviral infection and carcinogenesis, and to gene therapy. We hypothesized that the mechanism of genomic integration may be similar to transposition in lower organisms. We identified a protein, termed Metnase, that has a SET domain and a transposase/nuclease domain.