The first protocol of stable isotope ratio assessment in tumor tissues based on original research

Abstract

Thanks to proteomics and metabolomics, for the past several years there has been a real explosion of information on the biology of cancer, which has been achieved by spectroscopic methods, including mass spectrometry. These modern techniques can provide answers to key questions about tissue structure and mechanisms of its pathological changes. However, despite the thousands of spectroscopic studies in medicine, there is no consensus on issues ranging from the choice of research tools, acquisition and preparation of test material to the interpretation and validation of the results, which greatly reduces the possibility of transforming the achieved knowledge to progress in the treatment of individual patients. The aim of this study was to verify the utility of isotope ratio mass spectrometry in the evaluation of tumor tissues. Based on experimentation on animal tissues and human neoplasms, the first protocol of stable isotope ratio assessment of carbon and nitrogen isotopes in tumor tissues was established.

The first investigation of Wilms' tumour atomic structure-nitrogen and carbon isotopic composition as a novel biomarker for the most individual approach in cancer disease

“…They were placed in 12.5 × 5 mm tin capsules, and dried in a vacuum for five hours at room temperature. Around 1 mg of vanadium pentoxide was added to each sample as a sulphur oxidation catalyst, and capsules were folded carefully the same way as described by Taran [9]. Next, the isotope ratios of nitrogen 15 N/ 14 N and carbon 13 C/ 12 C were measured in triplicate for each tumour case with the use of a Sercon 20–22 Continuous Flow Isotope Ratio Mass Spectrometer (CF-IRMS) coupled with a Sercon SL Elemental Analyzer for simultaneous carbon-nitrogen-sulphur (NCS) analysis as described by Fry [43].…”

“…It may also represent a potential source of data needed for the assessment of the most individual characteristics of cancer and complements those at the microscopic or molecular levels. Recently, a few preliminary studies have examined isotope ratios directly in tumour tissues [9, 10, 11, 12] with promising indications that isotopic composition may facilitate the classification of patients into risk groups [11, 12]. However, these previous studies have not covered all the prognostic parameters appropriate to the cancer type, which constitute the existing base for the choice of treatment protocol and prognosis in individual cases.…”

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies

“…However, interpretation of the data is contingent on prior knowledge of the isotope discriminations associated with the relevant reactions and processes. Moreover, variations in natural abundance isotope ratios are far less pronounced than in isotope labelling studies, requiring extremely precise measurement of the isotope ratios (e.g., [ 14 , 18 ]).…”

“…With the improvement and automation of analysis methods, discussed below, there has been a recent blossoming of natural abundance stable isotope studies in the medical sciences [ 1 , 3 , 6 ]. This work has focused variously on healthy metabolism [ 19 – 22 ], cancer [ 14 – 18 , 23 – 27 ], and other diseases [ 4 , 13 ]. Of particular interest here is the recent focus on metabolic interactions in the tumor environment [ 17 , 23 , 28 – 33 ].…”

“…This work promises to advance our understanding of cancer metabolism as well as to offer new diagnostic approaches. However, in some cases, such as in stable isotope studies of nitrogen (N), the sample size required for natural abundance isotopic analysis has stood as an impediment (e.g., [ 14 , 17 ]).…”