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G B Boder

Publications and source records attributed to G B Boder.

32 records · Page 2Linked to original sources
PubMed1977

Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don). 38. 4'-Dehydrated derivatives.

A series of 4'-dehydrated derivatives of various dimeric Vinca alkaloids has been synthesized to further define the structure-activity relationships of Vinca alkaloids with onolytic potency. The concentrated sulfuric acid dehydration in most cases gave mixtures of the 3',4'-and two isomeric 4',20'-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compound tested for antitumor activity include the three dehydro isomers of 4'-deacetylvinblastine, 4-deacetylvincristine, and 4-deacetylvinblastine-23-amide and some4'-dehydrated derivatives epimeric at C-18'. Generally, the decrease in toxicity imparted by the new double bond was accompained by a decrease in potency. An exception was 3',4'-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least one tumor in which vincristine itself has little effect.

Adenocarcinoma↗
PubMed1977

Changes in the islets of langerhans in the obese Zucker rat.

Pancreatic islet tissue from lean and obese Zucker rats was investigated with histologic and immunocytochemical techniques, and the changes in cytologic composition were correlated with levels of serum glucose, lipids, and insulin. The insular changes in obese rats progressed in severity with increasing age. Changes consisted of pronounced insulin cell hyperplasia, disarrangement of islet architecture, and disappearance (degranulation?) of a new islet cell type, the pancreatic polypeptide cell. High levels of free fatty acids, triglyceride, and insulin were detected in serum of obese rats. Upon diet restriction, these parameters decreased and islet morphology became normalized. When obese Zucker rats were treated with streptozotocin, high levels of serum free fatty acids and triglycerides remained but there was a great reduction in serum insulin levels to near normal levels. Pancreatic polypeptide cells werenot found in the islets. It is suggested that high free fatty acid and triglyceride levels in obese rats may be related to the inability to demonstrate pancreatic polypeptide cells in the islets of 100- to 300-day-old obese Zucker rats.

Animals↗
PubMedDate not supplied

Effect of albumin on antitumor activity of diarylsulfonylureas.

Several diarylsulfonylureas (DSU), including Sulofenur (LY186641) and LY181984, have been described that exhibit wide spectrum and high therapeutic activity against murine solid tumors and human tumor xenografts. The mechanism for antitumor activity is poorly understood. Moreover, in vitro cytotoxic activity in serum-containing medium is not predictive of in vivo antitumor activity for DSU. Since DSU are extensively bound to serum albumin (> 99%), we sought to determine the effect of albumin on tumor cytotoxicity. We adapted human CCRF-CEM leukemia and GC3 colon carcinoma cells for growth in UltraCHO serum- and albumin-free medium. In comparisons between normal growth medium (RPMI-1640 with 10% fetal bovine serum) and UltraCHO medium, the unbound fraction of drug correlated better with cytotoxic activity than did the total drug. Tumor cytotoxicity by DSU required > 24 h and was markedly enhanced in UltraCHO medium. For example, LY181984 and Sulofenur had IC50 values of 7.4 and 12.1 micrograms/ml against CCRF-CEM in normal growth medium and 0.6 and 0.2 microgram/ml in UltraCHO. Moreover, DSU with the lowest IC-50s in albumin-free medium displayed the most potent in vivo antitumor activity in the 6C3HED lymphosarcoma. A Sulofenur-resistant CCRF-CEM cell line was developed by culturing the cells for > 20 passages in UltraCHO medium containing LY186641 at 2 micrograms/ml (10X IC-50). This line showed approximately 18-fold resistance to LY186641, but did not show cross-resistance to vinblastine, actinomycin D, or doxorubicin. The albumin-free conditions may be useful for further mechanistic studies on the antitumor action by DSU. Further studies are underway to determine whether DSU structural requirements for cytotoxicity an albumin binding are intrinsically linked.

Animals↗