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Multiple genetic alterations occur in melanoma, a lethal skin malignancy of increasing incidence. These include mutations that activate Ras and two of its effector cascades, Raf and phosphoinositide 3-kinase (PI3K). Induction of Ras and Raf can be caused by active N-Ras and B-Raf mutants as well as by gene amplification. Activation of PI3K pathway(More)
Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. No current treatments substantially enhance patient survival once metastasis has occurred. This review focuses on(More)
The problem of underwater positioning is increasingly crucial due to the emerging importance of sub-sea activities. At the surface, positioning problems have been resolved by extended use of GPS, which is straightforward and effective. Unfortunately, GPS in the sub-sea environment is impossible and positioning requires special systems. These are all(More)
Parathyroid hormone (PTH) is a potent stimulator of osteoblastic cell function in vitro and bone resorption and formation in vivo; however, the details of the molecular mechanism(s) responsible for PTH action and the regulation of gene expression in response to PTH remain unknown. In this study, we employed an mRNA differential display (DRD) approach to(More)
The tumor necrosis factor alpha receptor (TNFR1) activates downstream effectors that include the mitogen-activated protein kinase kinase 7 (MKK7)/c-Jun-NH(2)-kinase (JNK)/activator protein 1 (AP1) cascade. Here, we report that JNK is activated in a majority of spontaneous human squamous cell carcinomas (SCC). JNK pathway induction bypassed cell cycle(More)
Pharmacologic blockade of TNFalpha has been a highly effective approach to treating several immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. 1,2,3 Both etanercept, the recombinant extracellular domain of the tumor necrosis factor receptor 2 (TNFR2), and infliximab, a humanized murine antibody, bind(More)
Direct mapping of the interface between parathyroid hormone (PTH) and its receptor (hPTH1-Rc) was carried out by photoaffinity scanning studies. Photoreactive analogs of PTH singularly substituted with a p-benzoylphenylalanine (Bpa) at each of the first six N-terminal positions have been prepared. Among these, the analog(More)
PTH maintains blood calcium concentrations within the physiological range by acting on a G protein-coupled heptahelical receptor (PTH1 Rc) located primarily in cells in bone and kidney. We have undertaken a photoaffinity cross-linking approach to elucidate the nature of the bimolecular interaction of PTH with the human (h) PTH1 Rc. Specifically, we have(More)
Commitment of members of the monocyte/macrophage family to the bone resorptive phenotype, in vitro, requires contact, of these osteoclast precursors, with osteoblasts or related stromal cells. The osteoclast-inductive properties of these stromal cells are typically expressed, however, only in the presence of steroid hormones such as 1,25 dihydroxyvitamin D(More)
Identification and treatment of involved axillary lymph nodes is important in the planning of strategies for adjuvant treatments of breast cancer. With the advent of the National Health Service Screening Programme, an increasing number of women with the disease are detected at an early stage, when the lymph nodes are not involved. In whom, therefore, is it(More)