Characterization of the CXCR4 Signaling in Pancreatic Cancer Cells

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.     

The KDOQI clinical practice guidelines and clinical practice recommendations for treating anemia in patients with chronic kidney disease: implications for nurses.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative recently published revised clinical practice guidelines and recommendations for the treatment of anemia. This article provides an overview of the new guidelines and recommendations, with a focus on the hemoglobin treatment range, iron status, use of erythropoiesis-stimulating agents, and adjuvant therapies.     

Prenatal screening and diagnosis of handicaps: Current state of the art

Current medical procedures used in prenatal screening and diagnosis of handicapping conditions are reviewed. These strategies include ultrasound, amniocentesis, chorionic villus biopsy, restriction enzyme analysis, maternal serum analysis, fetoscopy, and fetal serum analysis. Along with an explanation of each method, advantages, disadvantages, and risks involved with each are provided. An understanding of these procedures by medical and educational personnel is encouraged, and the potential benefits of prenatal identification of handicapping conditions are emphasized.     

Facilitating Perinatal Grieving Between the Mother and the Father

Society often expects mothers and fathers to share equally in the perinatal grief process because the child was a common bond between them. Unfortunately, in perinatal grief, this is not always the case. The mother and the father can experience incongruent grieving and use discordant coping mechanisms. It is important to evaluate these differences to facilitate communication between the distraught parents. Improved communication can in turn facilitate the grieving process.     

Exercise in the prevention and treatment of chronic disorders

The Defense Women's Health Research Initiative commissioned a review of the literature of women's health issues. This was performed and published by the Institute of Medicine. In this publication it was noted that health promotion and disease prevention in women should be an area of high priority for military medicine. This article details some of the ways in which exercise may make substantial contributions to this goal.

The available evidence indicates that there is an inverse association between physical activity and a variety of chronic diseases. Moreover, physical activity appears to influence psychological well-being. Aerobic exercise is the mode most frequently studied, and appears to confer positive changes, but other forms of exercise may prove to be equally beneficial. However, the appropriate duration, intensity, and frequency of the exercise have not been determined for any of these chronic health problems and must be considered before global recommendations can be offered. Efforts to promote physical activity within the community, schools, and homes must be initiated to achieve the goals set forth in Healthy People 2000, so the health of our women can improve. Future studies will be required to identify mechanisms whereby physical activity confers benefit.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182