594 THE BIOCHEMISTRY OF B VITAMINS 



in cancer tissues regardless of the host organism or site of appearance or 

 means of induction, the general patterns of the metabolism of cancer 

 tissues appear to be related. 158 



The folic acid from livers of rats bearing Walker tumor transplants is 

 liberated by autolysis either in phosphate-sodium chloride or acetate 

 buffer, whereas maximal release of folic acid from livers of normal rats 

 requires both Clarase and phosphate-sodium chloride buffer. The acetate 

 buffer does not replace the phosphate buffer. 



Pteroyldi-y-glutamylglutamic Acid. The first direct effect on growth of 

 cancer by a member of the folic acid group was reported by Leuchten- 

 berger, et al., 100 who found that the growth of Sarcoma 180 in female 

 Rockland mice was reduced to approximately 35 per cent of the controls 

 by intravenous injection of 5 y of a concentrate containing members of 

 the folic acid group, or by the same number of injections of 0.4 y of 

 fermentation Lactobacillus casei factor (pteroyldi-y-glutamylglutamic 

 acid) . Complete regressions of spontaneous breast cancers in mice were 

 observed in 38 among 89 (43 per cent) animals treated with daily injec- 

 tions of 5 y of the pteroyltriglutamate. The incidence of the development 

 of new tumors was decreased from 14 out of 60 mice in the controls to 1 

 out of 89 mice treated with the triglutamate. 161 The liver Lactobacillus 

 casei factor (pteroylglutamic acid) is inactive in effecting this inhibitory 

 action on the tumors. 161 Additional data on the inhibition of transplanted 

 tumors and of spontaneous tumors have been reported by this group. 162 

 However, failures in attempts to confirm these results using sarcoma 180 

 or spontaneous breast cancer of mice have been reported. 163-166 



Preliminary clinical reports of the use of pteroyldi-y-glutamylglutamic 

 acid (teropterin) in the treatment of cancer have indicated that it is 

 nontoxic and in 500-mg doses relieves pain in most cases, if not all, 

 thereby allowing a reduction in amount of sedation or analgesia required 

 and in some cases obviating the necessity for use of opiates. The patients, 

 after treatment with the compound, are cheerful, exhibit a sense of well- 

 being and are more mentally alert. Although some patients with advanced 

 malignancy have shown considerable improvement on treatment with 

 the compound, the results in most instances cannot be evaluated objec- 

 tively because other treatments known to have desirable effects preceded 

 or were concurrent with the administration of the triglutamate. 167-169 



Effect of Folic Acid and Related Compounds on Rous Chicken Sarcoma. 

 Folic acid and related compounds have a profound effect on the avian 

 neoplasm first described by Rous. 170 The Rous chicken sarcoma, which 

 is transmitted by a filtrable agent, can be controlled either by regulation 

 of the amount of folic acid in the diet of the chicks or by administration 

 of certain folic acid antagonists. 77, 170-172 Thus, injection of a sterile, 



