The diagnostic and prognostic value of pretreatment serum creatine kinase bb levels in patients with neuroblastoma

Abstract

The serum levels of the BB isozyme of creatine kinase (CK-BB) and neuron-specific enolase (NSE) were measured before therapy in 35 patients with neuroblastoma. Sixty percent (21 of 35) of neuroblastoma patients had CK-BB levels higher than 11 ng/ml. The extent of disease was associated with an increased incidence of elevated serum CK-BB levels. The highest pretreatment serum CK-BB titers were found in patients with Stage IV disease. A strong correlation between the pretreatment CK-BB level and the outcome in patients with neuroblastoma was observed. Eleven (79%) of 12 patients who had a serum CK-BB level greater than 15 ng/ml died, and eight of ten (80%) who had a serum level less than 11 ng/ml were alive and tumor free after 2 years. A positive linear correlation between the pretreatment CK-BB and NSE (n = 35, r = 0.695) levels was found.

Progressive decrease of phosphocreatine, creatine and creatine kinase in skeletal muscle upon transformation to sarcoma

“…Here, a special mention is needed about the BCK isoform in relation to malignancy. In many tumors, although not all, BCK activity had been found to be considerably higher than in the tissue of origin [9–14]. Its elevated activity had been suggested as a marker for several malignancies such as small‐cell lung carcinoma [12] and neuroblastoma [13].…”

“…In many tumors, although not all, BCK activity had been found to be considerably higher than in the tissue of origin [9–14]. Its elevated activity had been suggested as a marker for several malignancies such as small‐cell lung carcinoma [12] and neuroblastoma [13]. However, estrogen and other hormones and growth factors had been found to stimulate BCK activity in target cells [24].…”

“…Because creatine metabolism is intimately connected with ATP requirements, its role in malignant cells is of prime importance. However, there are conflicting results on the role of the CK ⁄ creatine system in tumor growth and malignancy [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Here we analyze whether changes in the phosphocreatine ⁄ creatine system are related to the progression of sarcoma malignancy, a question that has not been studied systematically to date.…”

“…Some comparative studies on the activities of different CK isoforms in some normal and malignant cells also indicate mixed results. Some studies report upregulation of some form(s) of CK in malignant cells [9][10][11][12][13][14]. By contrast, there have been reports of decreased levels of creatine and an increased choline ⁄ creatine ratio, and a decrease in the activity of CK and some of its isoforms in several different forms of cancer [15][16][17][18][19][20].…”

Inhibition of rate of tumor growth by creatine and cyclocreatine.

“…Increased CK activity has been observed in regenerating rat liver (3), and CK has been implicated in spindle activity during normal cell division (4). In many tumors, although not all, CK-BB activity is considerably higher than in the tissue of origin (3,5); its elevated activity has been used as a diagnostic marker and prognostic indicator for small-cell lung carcinoma (6) and neuroblastoma (7). Recently it has been reported that CK-BB may be induced by the oncogenic products of the Ela region of adenovirus type 5 (8), and the intriguing possibility that induction of CK-BB may be related to metabolic events following oncogenic activation was suggested.…”