Determination of copper and other trace elements in serum samples from patients with biliary tract cancers: prospective noninterventional nonrandomized clinical study protocol.

BACKGROUND: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS). PATIENTS AND METHODS: In this prospective, noninterventional, nonrandomized study 20 patients and 20 healthy volunteers will be enrolled to identify serum Cu, Zn and Fe levels, Cu isotopic fractionation as a predictive biomarker of response to systemic therapy of BTCs, which will be evaluated by computed tomography. Newly developed analytical methods based on ICP-MS will be applied to metal-based biomarker research in oncology. CONCLUSIONS: In the study the comparison of the total concentration of selected trace elements, the proportion of free Cu and Cu bound to Cp and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients will be conducted to provide the foundation for the development of a BTC cancer screening methodology and the data on their usability as a potential predictive biomarker for BTCs of response to systemic therapy.

Quantitative profiling and baseline intervals of trace elements in healthy lung tissues.

BACKGROUND: Human lung tissue, as an interface with the environment, is susceptible to various environmental pollutants, including trace metals. However, quantitative data on trace metals in human lung tissues remain poorly described. METHODS: This study aimed to characterize the elemental composition of histologically healthy, unaffected parts of human lung tissues, associated with non-infective, non-infiltrative, and non-malignant diseases (n = 60) for essential (Cr, Mn, Fe, Co, Cu, Zn, and Se) and toxic trace elements (Sr, Ni, As, Cd, and Pb). Additionally, we investigated the influence of personal factors (sex, age, and smoking habits) on the examined trace element profiles, as well as between the trace elements correlations in the healthy human lungs. RESULTS: Among the analyzed trace elements, Fe was the most prevalent, while As was the least prevalent in healthy lung tissues. Stratifying by age revealed significantly higher Cr and Co (less Sr, Ni, and Pb) and lower Se levels in older individuals (above 65 years) compared to their younger counterparts. Sex-based differences were also notable, with Cu and Co 1.2- and 2.3-fold higher levels in females than in males. Exploring the impact of smoking habits revealed a striking 10-fold increase in Cd levels in the lung tissues of smokers compared to non-smokers. Correlation analyses showed significant positive associations between concentrations of certain toxic and essential trace elements in healthy lung tissues. CONCLUSIONS: This study could contribute to the establishment of baseline intervals for essential and toxic trace elements, valuable for toxicological and clinical assessment, in healthy, unaffected human lungs, and indicates the influence of sex, age, and smoking. However, further larger-scale studies are needed to make more stable conclusions.

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin - an in vitro study.

BACKGROUND: Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 µs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT. MATERIALS AND METHODS: We performed in vitro experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay. RESULTS: We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2-7 × 107 per cell. CONCLUSIONS: High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.