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Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma.

BACKGROUND The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. RESULTS The median age of the pa...

Seasonal and annual trends in forage fish mercury concentrations, San Francisco Bay.

San Francisco Bay is contaminated by mercury (Hg) due to historic and ongoing sources, and has elevated Hg concentrations throughout the aquatic food web. We monitored Hg in forage fish to indicate seasonal and interannual variations and trends. Interannual variation and long-term trends were determined by monitoring Hg bioaccumulation during September-November, for topsmelt (Atherinops affinis...

Phase I Clinical and Pharmacokinetic Study of Protein Kinase C- Antisense Oligonucleotide ISIS 3521 Administered in Combination with 5-Fluorouracil and Leucovorin in Patients with Advanced Cancer

The present study was designed to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein kinase Cantisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc., Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21-day co...

Type 1 diabetes mellitus at very high altitude. The summit of Mount Damāvand (5670 m) safely reached by 18 patients with type 1 diabetes mellitus.

A randomized phase II and pharmacokinetic study of the antisense oligonucleotides ISIS 3521 and ISIS 5132 in patients with hormone-refractory prostate cancer.

PURPOSE Protein kinase C (PKC)-alpha and Raf-1 are important elements of proliferative signal transduction pathways in both normal and malignant cells. Abrogation of either Raf-1 or PKC-alpha function can both inhibit cellular proliferation and induce apoptosis in several experimental cancer models including prostate cancer cell lines. ISIS 3521 and ISIS 5132 are antisense phosphorothioate olig...