Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: Relation to methylation status of the CKB promoter

Ishikawa, Jinko; Taniguchi, Terumi; Takeshita, Akira; Maekawa, Masato

doi:10.1016/j.cccn.2005.05.028

Cited by 10 publications

(11 citation statements)

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“…In tumorigenesis, increased localization of CK-BB to nuclear matrix was observed in colon cancer (Balasubramani M et al, 2006). Besides, unmethylation of the CK-BB promotor and therefore higher CK-BB mRNA expression in hematological cancer cell lines was identified (Ishikawa J et al, 2005). It was also reported that CK-BB contributed to increasing the number of cancer cell in pre-and mitotic phases, but was not associated with the cell proliferation (Mooney SM et al, 2011).…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies also demonstrated the phenomenon was associated with increased activity of CK-BB (Huddleston et al, 2005;Ishikawa et al, 2005). Based on the analysis employing the technologies of microarray and quantitative proteomics, it was suggested that CK-BB could therefore serve as a potential biomarker for early diagnosis of certain malignancies (Huddleston et al, 2005;Zeng et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang¹,

Liou²,

Su³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Chang¹,

Liou²,

Su³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…The corresponding gene that is expressed in muscle, CKM , shows no difference in transcript abundance between these three species. Because CKB expression positively correlates with CKB protein activity (Ishikawa et al, 2005), higher CKB transcript abundance in humans may allow for more efficient ATP regeneration during energy utilization, helping support the increased metabolic demands of the human brain (Wallimann et al, 1992; Wallimann and Hemmer, 1994). The reaction catalyzed by CKB provides energy for a diverse set of enzymatic activities in the cytoplasm (Figure 1E-F), potentially providing humans with the ability to support a greater number of simultaneous enzymatic reactions in the brain than either chimpanzee or rhesus macaque.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to bear in mind, however, that these methods are generally underpowered, and are unable to identify selection on single point mutations, any other kind of mutation, or epigenetic modifications, any of which could influence gene expression. (In fact, expression of CKMT1 , CKM , and CKB can be influenced by epigenetic regulation [Caretti et al, 2004; Ishikawa et al, 2005; Uzawa et al, 2006])…”

Section: Discussionmentioning

confidence: 99%

Comparative expression analysis of the phosphocreatine circuit in extant primates: Implications for human brain evolution

Pfefferle

Warner

Wang

et al. 2011

Journal of Human Evolution

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While the hominid fossil record clearly shows that brain size has rapidly expanded over the last ~2.5 M.yr., the forces driving this change remain unclear. One popular hypothesis proposes that metabolic adaptations in response to dietary shifts supported greater encephalization in humans. An increase in meat consumption distinguishes the human diet from that of other great apes. Creatine, an essential metabolite for energy homeostasis in muscle and brain tissue, is abundant in meat and was likely ingested in higher quantities during human origins. Five phosphocreatine circuit proteins help regulate creatine utilization within energy demanding cells. We compared the expression of all five phosphocreatine circuit genes in cerebral cortex, cerebellum, and skeletal muscle tissue for humans, chimpanzees, and rhesus macaques. Strikingly, SLC6A8 and CKB transcript levels are higher in the human brain, which should increase energy availability and turnover compared to non-human primates. Combined with other well-documented differences between humans and non-human primates, this allocation of energy to the cerebral cortex and cerebellum may be important in supporting the increased metabolic demands of the human brain.

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“…However, further epidemiological analyses in larger human sample sets are required before confirming its clinical utility as a marker of PCD or PNS. Furthermore, CKB expression has been reported to be high in the sera of patients with malignant lymphoma . The results of our immunohistochemical analysis showed that CKB is also expressed at higher levels in Hodgkin's cells.…”

Section: Discussionmentioning

confidence: 49%

Antibodies to a brain‐type creatine kinase associated with paraneoplastic neurological syndromes

Tetsuka

Yamasawa

Ikeguchi

et al. 2015

Neurology & Clinical Neurosc

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Background Previously, we identified a brain‐type creatine kinase antibody to be associated with paraneoplastic cerebellar degeneration using a proteomic approach. Immunohistochemistry showed that this antibody reacted with both mouse cerebellar neurons and bladder cancer tissues. Furthermore, we detected this antibody in sera from two paraneoplastic cerebellar degeneration patients with small cell lung cancer and one lymphoma patient. In total, we detected four paraneoplastic cerebellar degeneration patients. Aim To confirm the new onconeural antibody, we investigated whether this autoantigen is expressed in both human cerebellum and cancer tissues (small cell lung cancer of lymphoma). Methods We examined sera from two paraneoplastic cerebellar degeneration patients with small cell lung cancer, one lymphoma patient and a patient with sensory‐motor neuropathy as paraneoplastic neurological syndrome by western blotting and enzyme‐linked immunosorbent assay to explore creatine kinase brain‐type antibody expressions in these cancer cells as well as in the human cerebellum. Sera from the patients without paraneoplastic cerebellar degeneration were used as controls. In addition, we examined the serum from a patient with sensory‐motor neuropathy as paraneoplastic neurological syndrome by western blot. Results The mean serum values of creatine kinase brain‐type antibodies in paraneoplastic cerebellar degeneration patients with small cell lung cancer were significantly higher than those of small cell lung cancer patients without paraneoplastic cerebellar degeneration. Immunohistochemistry detected this autoantigen expression in both abovementioned specimens. We also detected this antibody in the serum in sensory‐motor neuropathy as paraneoplastic neurological syndrome. Conclusion Our study showed that this antibody was produced in four paraneoplastic cerebellar degeneration patients, and that this autoantigen expression was evident in human cerebellum and cancer. These findings show that creatine kinase brain‐type antibody might be a novel antibody associated with paraneoplastic neurological syndrome.

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Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: Relation to methylation status of the CKB promoter

Cited by 10 publications

References 10 publications

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Comparative expression analysis of the phosphocreatine circuit in extant primates: Implications for human brain evolution

Antibodies to a brain‐type creatine kinase associated with paraneoplastic neurological syndromes

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