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Biotech / Medical : Techniclone (TCLN) -- Ignore unavailable to you. Want to Upgrade?

To: Maurice Winn who wrote (2408)	8/12/1998 11:04:00 PM
From: Maurice Winn	Respond to of 3702

Message 5451661 Coulter stream Rick Harmon and others on Techniclone. Maybe somebody who has some technical oomph can answer his questions. Read the next few posts after that one. Also, the original comments by golfdad97 in the post linked to Rick Harmon's: Message 5446462 Meanwhile, thanks Terry for the Vitamin D reference: upci.upmc.edu University of Pittsburgh Cancer Institute. Part way through that page you can read that Vitamin D, [cod liver oil by another name, but without the nifty Vitamin A component nor the lovely oils which you get with cod liver oil] does in fact do some damage to some cancer cells. Read all about it. ------------------------------------------------------------------ New Agents. The biologically active metabolite of vitamin D, 1,25-dihydroxycholecalciferal or calcitriol, regulates calcium and phosphate transport in the intestine and the mobilization of mineral from the bone. Evidence from receptor studies demonstrates that besides the classic target organs, vitamin D receptors are present on a wide variety of human normal and cancer cell lines and fresh tissues. In addition, calcitriol can inhibit cell proliferation and differentiation in vitro and in vivo can inhibit the growth and prolong survival in murine myeloid leukemia models and murine syngeneic and human xenograft solid tumor models. Studies to extend these observations into the clinic, however, have been limited due to hypercalcemia. As a result, a number of vitamin D analogues have been developed that produce significant anti-tumor effects without hypercalcemia. One such vitamin D analogue, 1,25 dihydroxy-16-ene-23-yne cholecalciferol (Ro23-7553), has been shown to inhibit leukemic cell growth in vitro and in vivo, promote differentiation of myeloid leukemia cells and to have minimal effect on intestinal calcium absorption and bone calcium mobilization. Studies in Dr. Candace S. Johnson's laboratory have demonstrated that both calcitriol and the analogue, Ro23-7553, were capable of significantly inhibiting the growth and proliferation of a variety of tumor cell line in vitro. In vivo, using a murine squamous cell carcinoma model system (SCCVII/SF), both calcitriol and the analogue significantly inhibited the growth of established tumors as well as the initiation of tumor induction. These effects were dose-dependent and at high doses, treatment with calcitriol was associated with hypercalcemia, whereas the analogue resulted in significant tumor growth inhibition without inducing hypercalcemia. In addition, a significant increase in anti-tumor activity was observed when calcitriol was combined with dexamethasone with a diminished hypercalcemic effect. As a result of these pre-clinical studies, Drs. Candace S. Johnson and Donald L. Trump have implemented a phase I clinical trial to assess the toxicities associated with calcitriol and determine the MTD of parenteral calcitriol alone and with concurrent steroid therapy (Phase I trial of subcutaneous calcitriol and prednisone in advanced solid tumors, PCI #94-60). Specifically, these studies 1) determine the toxicities and MTD of subcutaneous calcitriol alone and in combination with prednisone, 2) examine the effect of repeated therapy on the pharmacokinetics of calcitriol, 3) determine the effect of prednisone on the pharmacokinetics of calcitriol, 4) assess the relationship between the toxicities of this regimen and the pharmacokinetics of calcitriol, and 5) monitor changes in immunologic status associated with the administration of calcitriol alone and in combination with prednisone. Concurrent to this trial, pre-clinical studies continue and focus on the relationship between vitamin D receptor expression in vivo, state of differentiation and/or therapeutic efficacy with both calcitriol and the analogue. In addition, studies examine whether these activities can be enhanced with glucocorticoids, what effects these agents have on T cell and macrophage function, and how schedule and dose parameters can be optimized. As these investigators have done in the past, should pre-clinical studies suggest, for example, that vitamin D receptor status correlated with therapeutic efficacy or a more malignant phenotype, the clinical studies would be modified to examine vitamin D receptor status in patient samples. ------------------------------------------------------------------ Unfortunately, eating about 200IU Vitamin D each day for many years does not prevent the intitiation of lymphoma, at least in one 21 year old person. So don't give up on the monoclonal antibodies to corner the market on cod liver oil just yet. Maurice