Polyamine profiles in the urine of patients with leukemia

Lee, Seon Hwa; Suh, Ja Won; Chung, Bong Chul; Kim, Soon Ok

doi:10.1016/s0304-3835(97)00399-6

Cited by 22 publications

(17 citation statements)

References 12 publications

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“…The prognosis of patients was generally good when the diacetylpolyamine level was normal or nearly normal, whereas the prognosis was poor when the diacetylpolyamine level remained far above the normal limit after apparently effective treatment (3). DiAcSpm in urine was also reported to be increased in patients with leukemia (8,9). The present results together with these previous observations strongly suggest that DiAcSpm may be useful to detect a wide variety of neoplastic diseases and that more extensive and detailed analyses of the usefulness of DiAcSpm as a diagnostic and prognostic marker for these as well as other types of cancer are warranted.…”

Section: Discussionsupporting

confidence: 78%

N 1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers

Hiramatsu

Takahashi²,

Yamaguchi³

et al. 2005

Clinical Cancer Research

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-diacetylspermine (DiAcSpm) in the urine of colorectal and breast cancer patients was examined to establish its usefulness as a novel diagnostic tool for detecting these cancers at clinically early stages. Experimental Design: Urine samples from 248 colon cancer patients and 83 breast cancer patients as well as 51patients with benign gastrointestinal diseases treated inTokyo Metropolitan Komagome Hospital during the period of August1999 toJanuary 2004 were collected. DiAcSpm was analyzed by ELISA and its sensitivity for malignant conditions was compared with that of serum carcinoembryonic antigen (CEA), CA19-9, and CA15-3. Results: The sensitivity of urinary DiAcSpm for colon cancer patients (n = 248) was 75.8% (mean F 2 SD for 52 healthy controls as a cutoff value), which was markedly higher than the sensitivities of serum CEA (39.5%, P < 0.0001) and CA19-9 (14.1%, P < 0.0001). DiAcSpm was elevated in 60% of tumor-node-metastasis cancer stage 0 + I patients, whereas only 10% (P < 0.0001) and 5% (P < 0.0001) of these patients were CEA-and CA19-9^positive, respectively.The sensitivity of urinary DiAcSpm for 83 cases of breast cancer (60.2%) was higher than the sensitivities of CEA (37.3%, P = 0.0032) and CA15-3 (37.3%, P = 0.0032). DiAcSpm was elevated in 28% of tumor-node-metastasis stage I + II patients, whereas only 3% (P = 0.0064) and 0% (P = 0.001) of these patients were CEA-and CA15-3^positive, respectively. Conclusion:The observations indicate that urinary DiAcSpm is a more sensitive marker than CEA, CA19-9, and CA15-3 and that it can efficiently detect colorectal and breast cancers at early stages.We reported previously that N 1 ,N 12 -diacetylspermine (DiAcSpm) is excreted in the urine of healthy persons, with small individual variations in the amount (1). We devised a high-performance liquid chromatography separation system connected to an in-line enzymatic detection system for DiAcSpm and carried out precise analyses of urinary DiAcSpm in healthy persons as well as patients with malignant diseases.Our analysis revealed that DiAcSpm may be useful as a novel diagnostic and prognostic tumor marker in that its excretion in urine is elevated significantly and frequently in patients with urogenital malignancies and tends to recover to the normal level on remission (2, 3). At the same time, we noted that monoacetylpolyamines that constitute a major part of urinary polyamines, including N-acetylputrescine, N 1 -acetylspermidine, and N 8 -acetylspermidine, were much less sensitive as markers for these urogenital malignancies than DiAcSpm and could not be considered practical tumor markers. The part of our observations concerning conventional monoacetylpolyamines was very well in accord with the popular evaluation of urinary polyamines at that time (4), but our results on DiAcSpm analysis were radically different from those on other polyamine derivatives and looked highly promising (2, 3).Although the biochemistry and clinical chemistry of DiAcSpm remain largely obscure at present because of the lack of intensiv...

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Section: Discussionsupporting

confidence: 78%

N 1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers

Hiramatsu

Takahashi²,

Yamaguchi³

et al. 2005

Clinical Cancer Research

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“…The most significant metabolite is N-acetylputrescine. N-Acetylputrescine is the most abundant of all polyamines both in normal individuals and in patients with leukemia [ 26 ]. Currently, the role of plasma N-acetylputrescine may play in glioma tumorigenesis is unclear.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes

Zhao

Heimberger

et al. 2016

Oncotarget

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BackgroundTumor-based molecular biomarkers have redefined in the classification gliomas. However, the association of systemic metabolomics with glioma phenotype has not been explored yet.MethodsIn this study, we conducted two-step (discovery and validation) metabolomic profiling in plasma samples from 87 glioma patients. The metabolomics data were tested for correlation with glioma grade (high vs low), glioblastoma (GBM) versus malignant gliomas, and IDH mutation status.ResultsFive metabolites, namely uracil, arginine, lactate, cystamine, and ornithine, significantly differed between high- and low-grade glioma patients in both the discovery and validation cohorts. When the discovery and validation cohorts were combined, we identified 29 significant metabolites with 18 remaining significant after adjusting for multiple comparisons. Those 18 significant metabolites separated high- from low-grade glioma patients with 91.1% accuracy. In the pathway analysis, a total of 18 significantly metabolic pathways were identified. Similarly, we identified 2 and 6 metabolites that significantly differed between GBM and non-GBM, and IDH mutation positive and negative patients after multiple comparison adjusting. Those 6 significant metabolites separated IDH1 mutation positive from negative glioma patients with 94.4% accuracy. Three pathways were identified to be associated with IDH mutation status. Within arginine and proline metabolism, levels of intermediate metabolites in creatine pathway were all significantly lower in IDH mutation positive than in negative patients, suggesting an increased activity of creatine pathway in IDH mutation positive tumors.ConclusionOur findings identified metabolites and metabolic pathways that differentiated tumor phenotypes. These may be useful as host biomarker candidates to further help glioma molecular classification.

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“…According to this study, colonic bacteria utilize polyamines to build biofilms (producing DAS), and this biofilm formation induces pro-inflammatory and pro-carcinogenic effects in the host tissues, increasing the risk of tumour formation. Interestingly, some metabolomic studies have associated DAS with other cancers, including cancers of the lung 72 , breast 73 , blood 74 and bladder 75 , as well as identifying it as a dietary metabolite 76 . Thus, further studies assessing the roles of diet and bacteria in cancers are of the utmost importance.…”

Section: Novel Biological Insightsmentioning

confidence: 99%

Metabolomics: beyond biomarkers and towards mechanisms

Johnson

Ivanišević

Siuzdak

2016

Nat Rev Mol Cell Biol

1,904

1,362

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Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases.

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Polyamine profiles in the urine of patients with leukemia

Cited by 22 publications

References 12 publications

N 1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers

N 1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers

Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes

Metabolomics: beyond biomarkers and towards mechanisms

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