The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies.

Polyamines are essential biomolecules for normal cellular metabolism in humans. The roles of polyamines in cancer development have been widely discussed in recent years. Among all, spermine alongside with its acetylated derivative, N1, N12-Diacetylspermine, demonstrate a relationship with the diagnosis and staging of various cancers, including lung, breast, liver, colorectal and urogenital. Numerous studies have reported the level of spermine in different body fluids and organ tissues in patients with different types of cancers. Currently, the role and the underlying mechanisms of spermine in cancer development and progression are still under investigation. This review summarized the roles of spermine in cancer development and as a diagnostic, prognostic and therapeutic tool in various cancers.

Urinary N1,N12-diacetylspermine as a biomarker for pediatric cancer: a case-control study.

PURPOSE: Minimally invasive examinations are particularly important in pediatric patients. Although the significance of urinary N1,N12-diacetylspermine (DiAcSpm) as a tumor marker (TM) has been reported in many types of adult cancers, its usefulness in pediatric cancers has not been reported. This may be due to urinary DiAcSpm level variations with age. This study aims to measure the normal levels of urinary DiAcSpm in healthy individuals and investigate its usefulness as a TM in childhood cancer. METHODS: Urinary samples were collected from pediatric patients with and without cancer. The urinary DiAcSpm levels were measured, and the values were compared. RESULTS: A total of 32 patients with cancer and 405 controls were enrolled in the study. Of the 32 patients, 13 had neuroblastoma, 9 had malignant lymphoma (ML), and 10 had leukemia. In the control group, the urinary DiAcSpm values markedly fluctuated among those with young age, especially infants; meanwhile, the values converged among those aged roughly 10 years and above. The sensitivity of DiAcSpm was significantly different among the three types of cancers: neuroblastoma (30.8%), ML (77.8%), and leukemia (40%). CONCLUSION: The urinary DiAcSpm value is a useful TM for both screening and follow-up of ML.

Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.

Rapid LC-MS/MS quantification of cancer related acetylated polyamines in human biofluids.

Increased urinary acetylated polyamines (APs) are reported as cancer biomarkers in many studies. N1,N12-diacetylspermine has been proposed as a biomarker indicative of different cancers in urine and plasma. N1-Acetylspermine has previously been found to be increased in the saliva of patients with breast cancer; however, in plasma this metabolite was too low abundant to be detected by previous analytical methods. In addition, no method has been reported to perform AP analysis on the level of speed, robustness and sensitivity required for daily clinical routines. Here we describe a high-throughput sample preparation and LC-MS/MS method for the fast, accurate and precise quantification of three APs: N8-acetylspermidine, N1-acetylspermine, and N1,N12-diacetylspermine in plasma, urine and saliva. Stable isotope labeled N1,N12-diacetylspermine was used as internal standard. Robustness was validated by intra- and inter-day reproducibility. Precision and accuracy of the method were tested at six concentration levels from 0.0375 to 750 ng/mL resulting in less than 15% relative standard deviation and less than 15% percent error in quantification. Using 96-well plates, the assay described herein allows for preparing, analyzing, and quantifying 240 samples per day for a single researcher to quantify three APs commonly related to cancer status.

Prognostic significance of urine N1, N12-diacetylspermine in patients with non-small cell lung cancer.

BACKGROUND: Recently N(1),N(12)-diacetylspermine, a diacetylated polyamine derivative, was recognized as a tumor marker in patients with several kinds of cancers. However, the significance of its levels in urine as a prognostic factor has not been elucidated. In the present study, we examined whether the urine N(1),N(12)-diacetylspermine levels can be used as a prognostic factor in patients with NSCLC. PATIENTS AND METHODS: Urine samples from 251 patients with NSCLC were collected prior to surgery and the urinary N(1),N(12)-diacetylspermine concentration was measured. Thereafter, all 251 patients underwent curative surgery and the analysis of prognosis was performed for over 10 years. Out of the 251 patients, 91 had recurrent disease. The significance of the urinary N(1),N(12)-diacetylspermine level as a prognostic factor among all 251 patients and among the 91 patients with recurrence was evaluated. RESULTS: Univariate analysis of all 251 patients showed that the level of urinary N(1),N(12)-diacetylspermine was a significant prognostic factor for disease-free survival and overall survival; however, multivariate analysis showed it had no significance. Conversely, the univariate and multivariate analyses of post-recurrent survival of the 91 patients with recurrence showed that urinary N(1),N(12)-diacetylspermine was an independent prognostic factor for post-recurrent survival. CONCLUSION: Patients with recurrence with positive urinary N(1),N(12)-diacetylspermine should undergo more intensive care and determination of urinary N(1),N(12)-diacetylspermine may contribute to improvement of prognosis of NSCLC.

Excretion of N(1), N(12)-diacetylspermine in the urine of healthy individuals.

BACKGROUND: Urinary N(1),N(12)-diacetylspermine (DiAcSpm) is a novel tumour marker that can be used to detect early cancers. In this study, we examined whether spot urine samples could represent the daily excretion of DiAcSpm after creatinine normalization and which factors should be taken into account in determining reference values for this biomarker. METHODS: We collected the following urine samples: (1) samples from seven healthy volunteers collected on each day of two 2-day sessions to examine the circadian variation of DiAcSpm excretion; (2) samples from 3952 male and 1782 female volunteers to estimate the DiAcSpm concentrations in apparently healthy adults and (3) samples from 16 female volunteers collected every morning over a 3-month period to examine the menstruation-related variation in DiAcSpm excretion. The DiAcSpm concentrations were determined by enzyme-linked immunosorbent assay or a colloidal gold aggregation procedure using DiAcSpm-specific antibodies. RESULTS: (1) The circadian variation of DiAcSpm in the urine was greatly diminished after creatinine normalization. (2) DiAcSpm was higher in females than in males, and the creatinine-normalized medians (95th percentile) of the urinary DiAcSpm concentrations were 149 (305) and 100 (192) nmol/g creatinine for females and males, respectively. (3) The mean concentrations of urinary DiAcSpm were lower after menstruation than before menstruation by approximately 30 nmol/g creatinine. CONCLUSION: Spot urine samples obtained at any time of a day may be used to estimate the daily excretion of DiAcSpm in nmol DiAcSpm per gram creatinine. Sex, age and menstrual condition should be considered when determining the reference values for urinary DiAcSpm.