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A 4-year survey is presented on the alpha-ketoglutarate (KG) values in whole blood of 200 patients with malignant neoplasms mainly of the gastroinstestinal tract and the female breast. A group of patients with benign surgical diseases served as control. KG showed an association with the extent of the primary tumor classified according to the TNM-scheme. The percentages of single values above the 2s-range of the control were as follows: T2:18%, T3: 41%, and T 4: 64%. The mean value of KG had highly significantly increased already in stage T 2 as compared to the control group. Rats bearing the Yoshida sarcoma showed a significant correlation between the tumor size and the daily excretion of KG into urine during the early stage of tumor growth. The results suggested that KG cannot be regarded as an early tumor marker in humans, but may be of some value as an aid for the differential diagnosis in advanced tumor stages. [ABSTRACT FROM AUTHOR]

The continuous administration of physiological doses of the branched-chain amino acids leucine, isoleucine, and valine (Leu-Ile-Val) to Yoshida sarcoma-bearing rats caused a significant increase in the survival time by 32% and a significant reduction of tumor size after 3 weeks of growth by 33%. The shift of the nitrogen balance to negative values during the cachectic stage was delayed but not prevented. On the average, less nitrogen (-47 mg/day) were lost by Leu-Ile-Val treated rats compared with untreated tumor-bearing animals (-91 mg N/day). It appeared that Leu-Ile-Val increased the synthesis of carcass proteins, while it left the proteolysis rate unchanged, since the excretion of urea and creatinine was unaffected by these amino acids. The daily excretion of α-ketoglutarate, which is correlated with tumor size during the early stage of growth, was decreased during the first 2 weeks by Leu-Ile-Val, but remained for a longer period on a high level than in untreated tumor bearers. The results point to an improvement of the metabolic resistance against carcass protein depletion of the tumor-bearing host by the administration of branched-chain amino acids. [ABSTRACT FROM AUTHOR]

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Referring to the increased α-ketoglutarate (I) concentration in blood of cancer-bearing humans, the concentration of (I) in blood and of albumin (II) in serum were measured in 85 tumor-bearing and control rats by fluorimetry and cellulose acetate electrophoresis, respectively. (I) was elevated on the average by a factor of 1.82 and (II) was decreased by a factor of 0.73 in rats bearing the solid Rhabdomyosarcoma BA 1112 and the ascitic or solid forms of Walker-carcinoma 256 and Yoshida-sarcoma compared with tumor-free animals. All deviations were found to be statistically significant for the different tumor types, with the exception of the increase of (I) in Walker-ascites tumor-bearing rats. For rats bearing the ascitic and solid Yoshida-sarcoma and the ascitic Walker-carcinoma 256 and for tumor-free rats a negative correlation could be observed between increase of (I) and decrease of (II). The increase of (I) in blood was paralleled by an increased excretion rate of (I) into urine. In rats bearing the solid Yoshida-sarcoma the daily excreted amount of (I) was significantly increased by a factor of 1.86 compared with tumor-free animals. The excretion of (I) was already increased in the first week after tranplantation, remained constant for two more weeks and decreased sharply below normal values prior to death. The results suggest that rats bearing the inquested tumors are suitable models for metabolic studies on causes of pathological concentrations of (I) in blood of cancer patients. [ABSTRACT FROM AUTHOR]