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Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholineproducing enzymes, and uptake of [methyl-14 C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcholine metabolites contributing to the 1 H NMR total choline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 F 0.9 and 5.2 F 2.4 nmol/10 6 cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 F 0.93 in EONT cells; average [phosphocholine] was 3-to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phosphatidylcholine metabolite, whereas average glycerophosphocholine/phosphocholine values decreased significantly to V0.2. Two-dimensional {phosphocholine/total choline, [total choline]} and {glycerophosphocholine/total choline, [total choline]} maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline kinase activity in EOC cells were 12-to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 F 0.1 nmol/10 6 cells/h), accounting for a consistently elevated (5-to 15-fold) [methyl-14 C]-choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher (f5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phosphatidylcholine cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvasive clinical tools for EOC diagnosis and treatment follow-up. (Cancer Res 2005; 65(20): 9369-76)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. Patients and methods:After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out.Results: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. Conclusion:Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

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BackroundThe number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full range of issues relevant to disease-free cancer survivors. The objectives of this project are: 1) to develop a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire that captures the full range of physical, mental and social HRQOL issues relevant to disease-free cancer survivors; and 2) to determine at which minimal time since completion of treatment the questionnaire should be used.MethodsWe reviewed 134 publications on cancer survivorship and interviewed 117 disease-free cancer survivors with 11 different types of cancer across 14 countries in Europe to generate an exhaustive, provisional list of HRQOL issues relevant to cancer survivors. The resulting issue list, the EORTC core questionnaire (QLQ-C30), and site-specific questionnaire modules were completed by a second group of 458 survivors.ResultsWe identified 116 generic survivorship issues. These issues covered body image, cognitive functioning, health behaviors, negative and positive outlook, health distress, mental health, fatigue, sleep problems, physical functioning, pain, several physical symptoms, social functioning, and sexual problems. Patients rated most of the acute symptoms of cancer and its treatment (e.g. nausea) as no longer relevant approximately one year after completion of treatment.ConclusionsCompared to existing cancer survivorship questionnaires, our findings underscore the relevance of assessing issues related to chronic physical side effects of treatment such as neuropathy and joint pain. We will further develop a core survivorship questionnaire and three site-specific modules for disease-free adult cancer survivors who are at least one year post-treatment.Electronic supplementary materialThe online version of this article (10.1186/s12955-018-0920-0) contains supplementary material, which is available to authorized users.