Potentiation of tumour growth by endotoxin in serum from syngeneic tumour-bearing mice

Abstract

Summary.-The subcutaneous growth of 2 antigenically distinct syngeneic methylcholanthrene-induced murine fibrosarcomas, designated HI and H7, were significantly augmented by the concomitant administration of E. coli endotoxin (LPS).Amounts as little as 0*02 ,-g i.p. potentiated tumour growth. The weakly antigenic tumour, Hi, was more susceptible to provocation by LPS than the more strongly antigenic H7. Maximum provocation of HI tumour growth occurred when LPS was injected 1 day before the administration of 5000 tumour cells. In contrast, significant anti-tumour resistance resulted if LPS was administered 6 days before the inoculation of tumour cells. Preliminary evidence indicates that low doses of LPS can facilitate the "sneaking through" phenomenon. Enhancement of tumour growth could not be demonstrated with sera or plasma from tumour-bearing mice, unless the samples were contaminated with endotoxin. The results illustrate the importance of excluding endotoxin from solutions used in studies of experimental tumours.

Negative impact of leakage on survival of patients undergoing curative resection for advanced gastric cancer

“…Host inflammation associated with leakage, perhaps in response to viable exfoliated cancer cells, may play an important role in patient outcomes. Previous studies have suggested that various mediators of the systemic inflammatory response caused by leakage may facilitate the growth of circulating or implanted cancer cells 8, 28, 29. Cytokines, such as tumor necrosis factor α, interleukin 1β, and interleukin 6, are powerful stimulators of tumor‐cell proliferation and survival, and may promote local recurrence or distant metastasis of tumors.…”

Modulation of anti‐tumour immunity induced by syngeneic mitomycin C‐treated murine tumour cells

“…more than 0.5 X lo6 cells. Fewer H7 tumour cells are completely rejected (Nelson and Nelson, 19786;Kearney and Harrop, 1980). In contrast to the H1 tumour, it is also noteworthy that the H7 tumour does not exhibit a "sneak-through'' effect (Kearney, unpublished observation).…”

“…In the present study, the down-regulation of such resistance by the "weakly" antigenic tumour, together with the previous findings that Tc cells are not produced (Nelson et al, 1978;Hopper et al, 1979) are likely to be important factors in the establishment of such tumours. In addition, since the "weakly" antigenic H1 tumour is exquisitely sensitive to the tumour-augmenting effects of bacterial endotoxin (Kearney and Harrop, 1980) and to the presence of tissue debris (Wu and Kearney, 1979), then small foci of such "weakly" antigenic tumours are more likely to become established following surgical procedures.…”

“…Two 3-methylcholanthrene-induced tumours designated H1 and H7 were used as described previously (Kearney and Harrop, 1980). A third methylcholanthrene-induced tumour designated MC-2 of BALB/c origin was kindly provided by Dr. Findlay-Jones of the School of Medicine, Hinders University, South Australia.…”

“…A third methylcholanthrene-induced tumour designated MC-2 of BALB/c origin was kindly provided by Dr. Findlay-Jones of the School of Medicine, Hinders University, South Australia. Tumour cells were obtained by disaggregating tumour fragments with pronase as described earlier (Kearney and Harrop, 1980) except that foetal calf serum (FCS) was not added to the tumour-cell suspensions. Washed tumour cells were suspended in 0.2 ml serum-free Dulbecco's modified Eagle's medium (DME) and injected subcutaneously (s.c.) along the midline of the abdominal wall.…”