Purpose: colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and detection of new prognostic markers is mandatory for patients to receive optimal oncological treatment. The aim of the study was to assess clinical and prognostic value of red cell distribution width (RDW) in patients with CRC. Methods: RDW values in 90 patients with CRC undergoing surgery for primary disease were analyzed in pre- and postoperative setting, and correlated with clinical and hematological parameters. Results: Both pre- and postoperative RDW measurements were found to be associated with features of iron deficiency anemia, inflammatory response to tumor, advanced age and depth of tumor invasion. Optimal cutoff points were calculated to be 14% for preoperative and 13.6% for postoperative RDW measurements. Elevations in both pre- and postoperative RDW values had significant effects on survival in univariate and multivariate analyses. Effects were found to be independent of tumor related features, stage of the disease, development of anemia and aberrant inflammatory response to tumor. Conclusions: RDW is an integrative parameter reflecting tumor specific features and shows significant association with overall survival in patients with CRC. This is especially important in patients with stage 2 disease where elevation in preoperative RDW values can contribute to recognition of higher risk patients.

The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD⁺) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H₂O₂. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD⁺-consuming enzymes poly–adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD⁺ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT’s positive effect on cellular NAD⁺ flux by stalling liberation of NAM and reducing NAD⁺ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD⁺ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.

Background: The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Patients and methods: This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients’ hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. Results: After a median follow-up of 23.0 (12.0–38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11–0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89–108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627–0.791). HT occurred in 13 (20.0%) patients with a score < 7.1 and in 57 (62.6%) patients with a score > 7.1. Conclusions: The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism.