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Kyoko Hiramatsu

Publications and source records attributed to Kyoko Hiramatsu.

9 recordsLinked to original sources
PubMed2006

Diacetylated derivatives of spermine and spermidine as novel promising tumor markers.

N1,N12-diacetylspermine (DiAcSpm) and N1,N8-diacetylspermidine (DiAcSpd) are minor components of human urinary polyamine to which little attention has been paid until recently. HPLC analysis of urinary polyamines has revealed that the excretion of these diacetylpolyamines, in particular, into urine was frequently and markedly increased in association with every type of cancer so far examined. Remission was usually accompanied by recovery of urinary diacetylpolyamines to the normal level. DiAcSpm was more sensitive than CEA for detecting colorectal cancer patients, while DiAcSpd was highly specific for malignant conditions in that the excretion of the latter was scarcely elevated in cases of benign urogenital diseases. An ELISA procedure for rapid determination of DiAcSpm was developed to promote the clinical application of these new tumor markers, and subsequent studies indicated that DiAcSpm was elevated in 60% of colorectal cancer patients at early stages (stage 0 + I), whereas only 10% of these patients were CEA-positive. DiAcSpm may also be useful as a follow-up marker that is efficient for detecting recurrence and sensitive to changes in the clinical condition of patients. The evidence accumulated so far indicates that DiAcSpm and DiAcSpd are promising novel tumor markers. They deserve more intensive studies, including studies of their biochemistry and metabolism.

Animals↗
PubMed2005

N(1),N(12)-Diacetylspermine as a sensitive and specific novel marker for early- and late-stage colorectal and breast cancers.

PURPOSE: N(1),N(12)-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 51 patients with benign gastrointestinal diseases treated in Tokyo Metropolitan Komagome Hospital during the period of August 1999 to January 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 +/- 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.

Adult↗
PubMed2005

Interaction of N1,N12-diacetylspermine with polyamine transport systems of polarized porcine renal cell line LLC-PK1.

LLC-PK(1) cells grown on porous membrane filters were employed as a model system to explore the renal transport of polyamines. The polarity of LLC-PK(1) monolayers was confirmed by the exclusive appearance of a Na(+)-dependent alpha-methylglucoside transport system on the apical surface. The uptake of free polyamines from the basolateral side of monolayers was consistent with the existence of a single class of transport system, while the existence of two kinetically distinct polyamine transport systems with higher and lower affinities on apical membranes was suggested. The results of competition studies indicated that each of these transporters was able to interact with putrescine, spermidine and spermine. LLC-PK(1) cells incorporated monoacetylspermine from the apical surface of monolayers at about half the rate of spermine uptake. Monoacetylspermine inhibited spermidine uptake, indicating that free polyamine transport systems also recognized the monoacetylated derivative. In contrast, N(1),N(12)-diacetylspermine did not inhibit spermidine uptake, nor was it incorporated into the cells, indicating the absence of transport systems that recognize N(1),N(12)-diacetylspermine on the apical membranes of LLC-PK(1) cells. These results may be relevant as to our previous observation that the content of diacetylpolyamines in urine is relatively constant, and may explain the excellence of N(1),N(12)-diacetylspermine as a tumor marker.

Animals↗
PubMed2005

[Urinary diacetylspermine: its analysis and performance as a novel tumor marker].

N1,N12-Diacetylspermine (DiAcSpm) is excreted in the urine of healthy persons as a minor component of urinary polyamine. It is a promising tumor marker, since its excretion is frequently elevated in patients with various types of cancers. DiAcSpm was first detected and characterized by HPLC fractionation followed by enzymatic detection, but more recently, antibodies highly specific for DiAcSpm was prepared, and an ELISA system applicable to determination of urinary DiAcSpm was established. Measurement of urinary DiAcSpm using this ELISA system revealed that DiAcSpm is able to detect early stage (m and sm) colon cancers which CEA and CA19-9 cannot detect. DiAcSpm may also serve as a prognostic indicator and a marker for recurrence of colon cancer. Urinary DiAcSpm is elevated in metastatic and primary brain tumors including grade 3 and 4 gliomas and primary central nervous system lymphoma. In these primary brain tumors changes in urinary DiAcSpm were well correlated with the efficacy of treatments, recurrence of disease and increased malignancy of a tumor. DiAcSpm may be useful as a comprehensive indicator of the activeness of a brain tumor lesion in a patient. DiAcSpm was elevated in hepatocellular carcinoma, but patients with liver cirrhosis also showed considerably elevated levels of DiAcSpm.

Biomarkers, Tumor↗
PubMed2004

[Clinical usefulness of urinary diacetylpolyamines as novel tumor markers].

N1,N12-Diacetylspermine(DiAcSpm) and N1,N8-diacetylspermidine(DiAcSpd) are excreted in the urine of healthy persons as minor components of urinary polyamine, with small individual variations in amount. They are promising tumor markers, since their excretion is frequently elevated in patients with various types of cancers. DiAcSpm is sensitive in cancer detection, while DiAcSpd is highly specific for cancer. Diacetylpolyamines were initially characterized and determined by HPLC fractionation, followed by enzymatic detection. More recently, antibodies highly specific for DiAcSpm and DiAcSpd were developed, and an ELISA system applicable to the determination of urinary DiAcSpm was established. Measurement of urinary DiAcSpm using this ELISA system revealed that DiAcSpm is a more sensitive tumor marker than CEA, CA19-9 and CA15-3 for colon and breast cancers. More importantly, DiAcSpm efficiently detects patients at early stages. On the other hand, CEA, CA19-9 and CA15-3 are quite insensitive for early stage cancers. The urinary DiAcSpm level tends to remain low even in tumor-bearing individuals when their cancerous lesions remain static, while it rises rapidly concomitant with recurrence. DiAcSpm may serve as a prognostic indicator and marker for recurrence of prostate and colon cancers. Diacetylpolyamines may turn out to be general tumor markers, since active proliferation of any cancer tissues would likely be accompanied by activation of polyamine metabolism.

Biomarkers, Tumor↗
PubMed2004

[The significance of urine di-acetyl spermine level as a cancer marker for colorectal cancer].

We analyzed the significance of the measurement of urine di-acetyl spermine (DiAcSpm) as a cancer marker for colorectal cancer treatment. We measured both the urine DiAcSpm(ELISA, normal range: 0-0.25 mumol/creatinine) and serum CEA (normal range: 0-5.0 ng/ml) of preoperative and postoperative colorectal cancer patients every month. We compared the positive rate from the cancer stage and the power of prognostic prediction. We divided the colorectal cancer patients into 4 groups: Group A: both levels were high; Group B: only the CEA level was high; Group C: only the DiAcSpm level was high; Group D: both levels were within a normal range. The positive rates of DiAcSpm and CEA from cancer staging were as follows: Stage 0: 62% and 9.5%, Stage I: 60% and 10%, Stage II: 70% and 42%, Stage III: 82% and 47%, and Stage IV: 88% and 63%, respectively. There was a significant difference (p < 0.0001) between both levels, especially for early-stage cases. The two-year survival rate was 0% in Group A, 100% in Group B, 72.7% in Group C and 100% in Group D. The difference among the 4 groups was significant (p < 0.0001). This showed that urine DiAcSpm predicted the prognosis after colorectal cancer surgery more exactly than serum CEA.

Biomarkers, Tumor↗
PubMed2002

Two enzyme-linked immunosorbent assay (ELISA) systems for N1,N8-diacetylspermidine and N1,N12-diacetylspermine using monoclonal antibodies.

We obtained monoclonal antibodies against N(1),N(12)-diacetylspermine (DiAcSpm) and N(1),N(8)-diacetylspermidine (DiAcSpd), and developed two systems of competitive ELISA that utilize the antibodies and a common enzyme-labeled antigen to measure these di-acetylpolyamines. Cross-reactions with N(1)-acetylspermidine in the assay of DiAcSpm and with N8-acetylspermidine in the assay of DiAcSpd were as low as 0.26 and 0.6%, respectively, and were judged to be insignificant in clinical use for measuring urinary diacetylpolyamines. These assays were used to assess diurnal variations in diacetylpolyamine excretion in urine to show that the excretion of diacetylpolyamines after normalization for the concentration of creatinine is stable over a day with only minimal diurnal variation.

Antibodies, Monoclonal↗
PubMed2002

Mass spectrometric separation and determination of N1,N12-diacetylspermine in the urine of cancer patients.

An ionspray ionization mass-spectrometric method for the determination of N1,N12-diacetylspermine (Ac2Spm) was developed using 15N-labeled Ac2Spm as the internal standard. Concentrations of Ac2Spm in the urine obtained from 17 cancer patients measured by the present method correlated well with those measured by ELISA, showing the usefulness of the two methods.

Enzyme-Linked Immunosorbent Assay↗