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View the Table of Contents for the November 1 issue of Clinical Cancer Research.
Carson-Walter et al. Page 7643
In this study, Carson-Walter et al. demonstrate that plasmalemmal vesicle associated protein-1 (PV-1) is selectively expressed in the endothelium of clinical high-grade central nervous system tumors, such as glioblastoma and metastatic carcinoma, but not in the endothelium of nonneoplastic brain. PV-1 is induced in vitro by exposure to glioma-conditioned media or to exogenous growth factors such as VEGF, linking PV-1 induction to well described proangiogenic pathways. Most importantly, RNAi inhibited expression of PV-1 and blocked endothelial migration and tubulogenesis in vitro, implicating PV-1 as a critical factor in CNS angiogenesis. PV-1 may, therefore, represent a novel and selective target for antiangiogenesis brain tumor therapies.
Hung et al. Page 7749
Previous studies demonstrated that mesenchymal stem cells (MSCs) can migrate and engraft into the stroma of tumors and can be used as vectors for therapy. From a clinical perspective, it is critical to show that such an approach is not limited to radiologically detectable tumors, but can be used to target micro-metastatic tumors. To explore this, Hung et al. used clinically applicable PET imaging with 18F-FHBG in mice bearing microscopic tumors that had been intravenously administered with MSCs expressing the HSV1-TK gene. These MSCs migrated and engrafted into the microscopic tumor lesions and participated in formation of a significant portion of the developing tumor stroma.
Ebbinghaus et al. Page 7807
Tasidotin (ILX651) is a third-generation depsipeptide that inhibits cancer cell growth by disrupting spindle microtubule organization necessary for cell division. Ebbinghaus et al. report on a Phase 1 study (n = 36) using tasidotin administered intravenously daily for 5 days every 3 weeks in patients with advanced refractory solid tumors. The maximum tolerated dose was 27.3 mg/m2/day with neutropenia being the dose-limiting toxicity. Notably absent were the cardiovascular toxicities seen with cemadotin and infusion pain seen with TZT-1027, other dolastatin depsipeptides. One patient with melanoma metastatic to liver and bone experienced a complete response; 9 patients had stable disease.
Yaccoby et al. Page 7599
Yaccoby et al. isolated CD138 myeloma cells from patients and cultured them to further deplete CD45-expressing cells. The cells were cocultured with osteoclasts for up to 20 weeks. The pre-cultured myeloma cell phenotype, which typically was CD45low CD38high CD19- CD34-, shifted to cells expressing CD45intermediate/high CD19low CD34low. In contrast to precultured cells, myeloma cells recovered from cocultures were resistant to spontaneous and drug-induced apoptosis. This study indicates that myeloma cells have plasticity expressed by their ability to reprogram, dedifferentiate, and acquire autonomous survival properties. The investigator questions whether these cells are responsible for relapses among patients.
Caballero et al. Page 7757
B-cell chronic lymphocytic leukemia (B-CLL) has been considered an incurable disease. Recently two articles have reported that allogeneic transplant may overcome this dismal prognosis. In this study, Caballero et al., evaluated efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor prognosis molecular characteristics. This study confirms the efficacy of RIC allogeneic transplant in CLL with adverse biological prognostic factors such as unmutated status and, for the first time, additional efficacy in patients with 11q- and 17 p- aberrations.