254 LOCAL TISSUE REACTIVITY 



edly uncler<>() coinplete regression within the sec:ond week f()ll()\v- 

 ing- tiic injection of the filtrate. 'Miis comse of events is also illus- 

 trated by histologic sedions. Ihe reaction lour hoius after the 

 injection is that of an abundant hemorrhage into the tumor tissue 

 with disruption oi the tumor. Most of the tumor (ells, ho\ve\'er, 

 are viable. T^venty-foin- hours alter the injection, there appears 

 extensive necrosis of the timior. The necrotic zone begins to he 

 sharply delimited from zones of active growth within the follo\ving 

 fe^v days. Approximately one week after the intravenous injec- 

 tion, there is observed a small residtial mass of ttimor tnrderooino- 

 necrosis and regression. Three vveeks after injection of the filtrate, 

 the healed site shows a small area of grantdation tissue. No tumor 

 cells can be discovered microscopically. No lesions were noted in 

 any other organs of the mice treated. 



The apjiearance of the reaction suggests a close resemblance to 

 the phenomenon of local skin reactivity to l)acterial filtrates and 

 is decidedly different from the spontaneous hemorrhagic and 

 necrotic lesions and lesions prodticed in chemically treated 

 timiors. The consj^icuous differentiating featines are prompt 

 hemorrhage extending throughout the entire tumor, necrosis ac- 

 companied by comparatively insignihcant cell infiltration and the 

 absence of thrombosis. 



In 193.S, Duran-Reynals sttidied the effect of active principles 

 of the phenomenon upon a variety of tinnors of rats and mice. 

 As a soince of the active principles, he irsed filtrates of a six day 

 old broth cidtine of B. coli and injected them into the peritoneunr 

 or intravenously in a dose of 0.5 c.c. for mice and 0.1 c.c. for rats. 

 The tumors tested by Duran-Reynals were divided into the posi- 

 tively and negatively reacting timiors. 



Positively reacting tumors : 



This group consisted of 20^^ mice and rats bearing rapidly grow- 

 ing malignant and transplantaljle tumors which ordinarily give a 

 high percentage of takes and regress only rarely (sarcoma S/37, 

 sarconra 180, adeirocarcinoma M/63, Twort adenocarcinoma and 

 Walker sarcoma) . The timiors diflfered in aoe, size and deoree of 

 necrosis prior to the injection of the bacterial filtrate. The in- 

 tensity of the phenomenon seemed to bear a direct relationship 

 to the age and size of the tumors. ^VHiile very yoinig, perfectly 

 healthy tumors often gave no reaction, larger tumors gave prac- 

 tically 100 per cent positive results. Dman-Reynals was also im- 



