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Research on Tumor Growth Factors May Yield Clues for New Drugs
Research on Tumor Growth Factors May Yield Clues for New Drugs Although there is still some lingering doubt about the role of administered estrogens in the initial causation of breast cancer, endogenous estrogen does seem to be an essential factor for the growth of these cancers-but, for some unknown reason, only in the initial phase of many malignancies. Estrogen, though usually associated with a limited number of re. ceptor sites, is capable of entering all the cells of the body. On the surfaces of these cells, it unites with a receptor protein. This steroid-receptor complex binds to various loci on cell DNA, thereby quantitatively altering the amount of gene products elaborated via the affected loci.
Unraveling the Mechanism In one cancerous cell line, estra. diol in postmenopausal concentrations stimulates DNA synthesis as well as the incorporation of macromolecules, resulting in accelerated cell growth and division. Marc Lippmann, head, Medical Breast Cancer Section, National Cancer Institute, is working to unravel the precise mechanism by which estradiol influences cell growth, and under what conditions.
Lippmann began a search for the particular enzyme associated with cell growth whose action was stim-' ulated by estradiol. He found that the action of thymidine kinase was increased 2-6 times; but then so was the activity of eleven other enzymes. Therefore, two possibilities seemed likely. First, estradiol could have been simultaneously stimulating all of the enzymes necessary for growth. However, since this hypothesis necessitated a corollary theory that estradiol itself worked by an unpredictable shotgun approach, this line of thinking was unsatisfactory. So instead, Lippmann speculated tha t some key growth factor was serving as the intermediary messenger of estradiol's stimulatory effect. Such a theory would also explain how malignant tissue might be capable of becoming independent of stimulation by estrogen: once it had "learned" how to make the growth factor necessary for its rapid replication, further stimulation by estrogen would become unnecessary. Evidence for this putative growth factor came from several kinds of experiments. For example, it was found
Smith Kline & French Researching New Class of Anti--Ulcer Drugs Through an agreement with the West German pharmaceutical group Altana, Smith Kline & French Laboratories has acquired the rights to a new class of anti-ulcer drugs, the H + K + ATPase inhibitors, or proton pump inhibitors. Proton pump inhibitors are distinguishable from compounds of the H 2antagonist class by their different mode and site of action. Proton pump inhibitors work within the stomach's acid-secreting cells, preventing the action of the catalyst that
causes acid production: H + K + ATPase. One hundred compounds of this new class were acquired by SK&F through their recent agreement with Altana. Of these, two are currently in the development stage in the United States; the lead compound is presently undergoing Phase I pharmacology studies in humans. The two firms plan to collaborate on all remaining research and development activities for agents of this type.
that, as the numbers of malignant cells in a culture dish increased, so did their growth rate, suggesting that they were producing some substance that enhanced their growth.
Identifying Factors In another study, mice were implanted with malignant NCF-7 cells. Some of the mice were given estradiol, while others were given a supernatant liquid derived from malignant cell cultures, which contained the suspected estrogen-induced growth factors (but no estrogen). In both experimental conditions, tumors grew, although those induced by the growth factor were smaller. the specific growth factors involved in tumorigenesis have been identified for certain, it may well be possible to develop new drugs that contain antibodies to them, which can impede tumor growth rate, while at the same time leaving unhindered the normal actions of estrogen.
---Once
DRY MOUTH (continued from page 23)
tablet, alleviation of the pain of angina was considerably delayed. Robbins then verified the patient's report under the Plore controlled conditions of his office. The patient took a single O.6-mg sublingual nitroglycerin tablet, from a newly opened bottle, and placed it under his tongue. After five minutes, no visible dissolution of the tablet had occurred. The patient commented that he had been able to partially overcome this problem by chewing gum to increase salivation at times when angina was likely to occur. In this case, the patient decidedafter consulting with his psychiatrist-to discontinue taking the imipramine, and after two months, dry mouth had disappeared, and nitroglycerin dissolved satisfactorily.
Unraveling the Mechanism In one cancerous cell line, estra. diol in postmenopausal concentrations stimulates DNA synthesis as well as the incorporation of macromolecules, resulting in accelerated cell growth and division. Marc Lippmann, head, Medical Breast Cancer Section, National Cancer Institute, is working to unravel the precise mechanism by which estradiol influences cell growth, and under what conditions.
Lippmann began a search for the particular enzyme associated with cell growth whose action was stim-' ulated by estradiol. He found that the action of thymidine kinase was increased 2-6 times; but then so was the activity of eleven other enzymes. Therefore, two possibilities seemed likely. First, estradiol could have been simultaneously stimulating all of the enzymes necessary for growth. However, since this hypothesis necessitated a corollary theory that estradiol itself worked by an unpredictable shotgun approach, this line of thinking was unsatisfactory. So instead, Lippmann speculated tha t some key growth factor was serving as the intermediary messenger of estradiol's stimulatory effect. Such a theory would also explain how malignant tissue might be capable of becoming independent of stimulation by estrogen: once it had "learned" how to make the growth factor necessary for its rapid replication, further stimulation by estrogen would become unnecessary. Evidence for this putative growth factor came from several kinds of experiments. For example, it was found
Smith Kline & French Researching New Class of Anti--Ulcer Drugs Through an agreement with the West German pharmaceutical group Altana, Smith Kline & French Laboratories has acquired the rights to a new class of anti-ulcer drugs, the H + K + ATPase inhibitors, or proton pump inhibitors. Proton pump inhibitors are distinguishable from compounds of the H 2antagonist class by their different mode and site of action. Proton pump inhibitors work within the stomach's acid-secreting cells, preventing the action of the catalyst that
causes acid production: H + K + ATPase. One hundred compounds of this new class were acquired by SK&F through their recent agreement with Altana. Of these, two are currently in the development stage in the United States; the lead compound is presently undergoing Phase I pharmacology studies in humans. The two firms plan to collaborate on all remaining research and development activities for agents of this type.
that, as the numbers of malignant cells in a culture dish increased, so did their growth rate, suggesting that they were producing some substance that enhanced their growth.
Identifying Factors In another study, mice were implanted with malignant NCF-7 cells. Some of the mice were given estradiol, while others were given a supernatant liquid derived from malignant cell cultures, which contained the suspected estrogen-induced growth factors (but no estrogen). In both experimental conditions, tumors grew, although those induced by the growth factor were smaller. the specific growth factors involved in tumorigenesis have been identified for certain, it may well be possible to develop new drugs that contain antibodies to them, which can impede tumor growth rate, while at the same time leaving unhindered the normal actions of estrogen.
---Once
DRY MOUTH (continued from page 23)
tablet, alleviation of the pain of angina was considerably delayed. Robbins then verified the patient's report under the Plore controlled conditions of his office. The patient took a single O.6-mg sublingual nitroglycerin tablet, from a newly opened bottle, and placed it under his tongue. After five minutes, no visible dissolution of the tablet had occurred. The patient commented that he had been able to partially overcome this problem by chewing gum to increase salivation at times when angina was likely to occur. In this case, the patient decidedafter consulting with his psychiatrist-to discontinue taking the imipramine, and after two months, dry mouth had disappeared, and nitroglycerin dissolved satisfactorily.