No abstract

Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.

The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases. Here, we show that oral NaHCO 3 selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by 31 P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO 3 therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO 3 therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease.

The effectiveness of prehospital interventions for out-of-hospital cardiac arrest may be estimated from their influence on collapse to CPR and collapse to defibrillation intervals. A model derived from combined data from two geographically distinct populations did not identify site as a predictor of survival if clinically relevant predictor variables were controlled for. This model can be generalized to other US populations and used to project the local effectiveness of interventions to improve cardiac arrest survival.

As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.