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The effects of a biological response modifier, OK-432, on tumor-induced alterations in the host metabolism
Y Noguchi1, A Tsuburaya, T Makino
1First Department of Surgery, Yokohama City University School of Medicine, Japan.
Abstract:
The effects of multicytokine inducer, OK-432, on tumor-induced metabolic alterations were studied by assessing three key regulatory enzymes of gluconeogenesis, de novo fatty acid synthesis and the triglyceride clearance pathways. Two Klinish Einheit (KE) of OK-432 was subcutaneously injected on alternate days, for 10 days, into Fischer 344 rats with or without methylcholanthrene-induced sarcoma. At the time of sacrifice, the tumors accounted for approximately 23% of their total body weight. The injections of OK-432 did not affect the amount of food intake in either the tumor bearers or the controls. The tissue lipoprotein lipase activities in the epididymal fat pads of the tumor bearers were significantly decreased compared with the controls (P < 0.01). Phosphoenolpyruvate carboxykinase activity in the liver was significantly increased (P < 0.01), while malic enzyme activity tended to be decreased in the tumor bearers compared with the controls. However, there were no significant differences in those activities depending on the OK-432 injections, even though OK-432 induced tumor necrosis factor (TNF) and increased cytotoxic activities in the mesenteric lymph nodes as well as in the spleen. Thus, although the role of monokines in inducing cancer cachexia is not yet clearly understood, OK-432 was not able to revert the tumor-induced metabolic alterations which lead to tissue wasting and cancer cachexia.
Insights
The multicytokine inducer OK-432 did not reverse tumor-induced metabolic changes in rats, failing to prevent cancer cachexia despite increasing cytotoxic activity.
Area of Science:
- Biochemistry
- Oncology
- Immunology
Background:
- Cancer cachexia involves complex metabolic alterations contributing to tissue wasting.
- Multicytokine inducers like OK-432 are explored for their potential to modulate anti-tumor responses.
- Understanding metabolic pathways affected by cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the impact of OK-432 on tumor-induced metabolic alterations in a rat model.
- To assess the effects of OK-432 on key enzymes involved in gluconeogenesis, fatty acid synthesis, and triglyceride clearance.
- To determine if OK-432 can mitigate metabolic disturbances associated with cancer cachexia.
Main Methods:
- Fischer 344 rats with methylcholanthrene-induced sarcoma were injected with OK-432.
- Activity of key metabolic enzymes (lipoprotein lipase, phosphoenolpyruvate carboxykinase, malic enzyme) was measured.
- Tumor weight, food intake, and immune cell cytotoxic activity were assessed.
Main Results:
- Tumor bearers showed decreased lipoprotein lipase activity and increased liver phosphoenolpyruvate carboxykinase activity.
- OK-432 administration did not alter food intake or significantly change the measured enzyme activities.
- OK-432 did induce tumor necrosis factor (TNF) and increased cytotoxic activities in lymphoid organs.
Conclusions:
- OK-432 did not revert tumor-induced metabolic alterations in rats.
- The study suggests OK-432 is ineffective in preventing cancer cachexia-related metabolic changes.
- Further research is needed to understand the role of monokines in cancer cachexia.