Vitamin D supplementation in cancer prevention and the management of cancer therapy.

Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g.

Slow Sulfide Donor GYY4137 Increased the Sensitivity of Two Breast Cancer Cell Lines to Paclitaxel by Different Mechanisms.

Paclitaxel (PTX) is a chemotherapeutic agent affecting microtubule polymerization. The efficacy of PTX depends on the type of tumor, and its improvement would be beneficial in patients' treatment. Therefore, we tested the effect of slow sulfide donor GYY4137 on paclitaxel sensitivity in two different breast cancer cell lines, MDA-MB-231, derived from a triple negative cell line, and JIMT1, which overexpresses HER2 and is resistant to trastuzumab.

5-Fluorouracil Induced Hypertriglyceridemia During the Colorectal Cancer Treatment in a Patient With Multifactorial Chylomicronemia Syndrome: A Case Report.

Purpose: The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly.

Methods: Based on laboratory tests and clinical evaluations, treatment was suggested by specialists.

Role of the 3-mercaptopyruvate sulfurtransferase in colon/colorectal cancers.

The 3-mercaptopyruvate sulfurtransferase (MPST) is a protein persulfidase, occurring mainly in mitochondria. Although function of this protein in cancer cells has been already studied, no clear outcome can be postulated up to now. Therefore, we focused on the determination of function of MPST in colon (HCT116 cells)/colorectal (DLD1 cells) cancers.

Chronic venous insufficiency and venous leg ulcers: Aetiology, on the pathophysiology-based treatment.

The chronic venous disease covers a wide spectrum of venous disorders that are characterized by severely impaired blood return that primarily affects veins in the lower extremities. Morphological and functional abnormalities of the venous system led to chronic venous insufficiency (CVI), and present as leg heaviness/achiness, edema, telangiectasia, and varices. The term 'chronic venous insufficiency' (CVI) refers to a disease of greater severity.

Cystathionine β-synthase affects organization of cytoskeleton and modulates carcinogenesis in colorectal carcinoma cells.

Background: Cystathionine β-synthase (CBS), one of three enzymes that endogenously produce hydrogen sulfide, is extensively studied for its relevance in the cells of various tumors. In our previous work, we observed that the immunofluorescence pattern of CBS is very similar to that of tubulin and actin. Therefore, we focused on the potential interaction of CBS with cytoskeletal proteins β-actin and β-tubulin and the functional relevance of the potential interaction of these proteins in colorectal carcinoma cell lines.

Signaling pathways in cutaneous wound healing.

Wound healing is a very complex process, where variety of different pathways is activated, depending on the phase of healing. Improper or interrupted healing might result in development of chronic wounds. Therefore, novel approaches based on detailed knowledge of signalling pathways that are activated during acute or chronic cutaneous wound healing enables quicker and more effective healing.

Camptothecin, triptolide, and apoptosis inducer kit have differential effects on mitochondria in colorectal carcinoma cells.

Mitochondrial fission and fusion are required for cell survival, and several studies have shown an imbalance between fission and fusion in cancer. High levels of mitochondrial fusion are observed in drug-resistant tumor cells, whereas mitochondrial fission may be important in sensitizing tumor cells to chemotherapy drugs. Based on current knowledge, we hypothesized that different chemotherapeutics might differentially affect mitochondrial dynamics and energy production.

Slow sulfide donor GYY4137 potentiates effect of paclitaxel on colorectal carcinoma cells.

Although paclitaxel (PTX) is potent chemotherapeutic agent commonly used in variety of cancers, in colorectal carcinoma its usage is excluded because of low effectivity. Up to now, some experimental attempts were utilized to improve sensitivity of colorectal carcinoma to PTX. We used a slow sulfide donor GYY4137 to increase sensitivity of colorectal carcinoma cells to PTX.

Involvement of calcium signaling in different types of cell death in cancer.

Programmed cell death is a basic feature of chemotherapeutic (and also radiotherapeutic) intervention. Induction of cell death in tumor cells aims to kill preferentially the tumor cells, with minimal impact on the normal cells. Although apoptosis is the most obvious type of cell death induced by chemotherapeutics, several other types can also be activated, especially in conditions, where cells are resistant to apoptosis induction.

Role of Sodium/Calcium Exchangers in Tumors.

The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted-calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans.

Calcium signaling affects migration and proliferation differently in individual cancer cells due to nifedipine treatment.

Several papers have reported that calcium channel blocking drugs were associated with increased breast cancer risk and worsened prognosis. One of the most common signs of breast tumors is the presence of small deposits of calcium, known as microcalcifications. Therefore, we studied the effect of dihydropyridine nifedipine on selected calcium transport systems in MDA-MB-231 cells, originating from triple negative breast tumor and JIMT1 cells that represent a model of HER2-positive breast cancer, which possesses amplification of HER2 receptor, but cells do not response to HER2 inhibition treatment with trastuzumab.

Type 1 Sodium Calcium Exchanger Forms a Complex with Carbonic Anhydrase IX and Via Reverse Mode Activity Contributes to pH Control in Hypoxic Tumors.

Hypoxia and acidosis are among the key microenvironmental factors that contribute to cancer progression. We have explored a possibility that the type 1Na/Ca exchanger (NCX1) is involved in pH control in hypoxic tumors. We focused on changes in intracellular pH, co-localization of NCX1, carbonic anhydrase IX (CA IX), and sodium proton exchanger type 1 (NHE1) by proximity ligation assay, immunoprecipitation, spheroid formation assay and migration of cells due to treatment with KB-R7943, a selective inhibitor of the reverse-mode NCX1.

Sodium/calcium exchanger is involved in apoptosis induced by HS in tumor cells through decreased levels of intracellular pH.

We explored possibility that sodium/calcium exchanger 1 (NCX1) is involved in pH modulation and apoptosis induction in GYY4137 treated cells. We have shown that although 10 days treatment with GYY4137 did not significantly decreased volume of tumors induced by colorectal cancer DLD1 cells in nude mice, it already induced apoptosis in these tumors. Treatment of DLD1 and ovarian cancer A2780 cells with GYY4137 resulted in intracellular acidification in a concentration-dependent manner.

Type 3 inositol 1,4,5-trisphosphate receptor has antiapoptotic and proliferative role in cancer cells.

Although the involvement of type 1 (IPR1) and type 2 (IPR2) inositol 1,4,5-trisphosphate receptors in apoptosis induction has been well documented in different cancer cells and tissues, the function of type 3 IPR (IPR3) is still elusive. Therefore, in this work we focused on the role of IPR3 in tumor cells in vitro and in vivo. We determined increased expression of this receptor in clear cell renal cell carcinoma compared to matched unaffected part of the kidney from the same patient.

Endogenous HS producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma.

Background: Knowledge about the expression and thus a role of enzymes that produce endogenous HS - cystathionine-β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient's samples, microarray and immunohistochemistry was used.

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells.

Background/aims: Melatonin is a hormone transferring information about duration of darkness to the organism and is known to modulate several signaling pathways in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status of the cells, etc.

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells.

Aims: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP receptors (IPR1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IPR1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats.

Polysulfides and products of HS/S-nitrosoglutathione in comparison to HS, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of HO.

Exogenous and endogenously produced sulfide derivatives, such as HS/HS/S, polysulfides and products of the HS/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox.

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IPR1 Complex.

Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IPRs). Aim of this work was to investigate possible changes in IPRs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.

Effect of Hyperhomocysteinemia on Redox Balance and Redox Defence Enzymes in Ischemia-Reperfusion Injury and/or After Ischemic Preconditioning in Rats.

Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0.

Nilotinib induces ER stress and cell death in H9c2 cells.

Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9c2 cells as a suitable cell model.

Athymic nude mice as an experimental model for cancer treatment.

Athymic nude mice, a murine strain bearing spontaneous deletion in the Foxn1 gene that causes deteriorated or absent thymus (which results in inhibited immune system with reduction of number of T cells), represent a widely used model in cancer research having long lasting history as a tool for preclinical testing of drugs. The review describes three models of athymic mice that utilize cancer cell lines to induce tumors. In addition, various methods that can be applied in order to evaluate activity of anticancer agents in these models are shown and discussed.

Mathematical relationships and their consequences between rat pulse waveform parameters and blood pressure during decreasing NO bioavailability.

What is the central question of this study? We wanted to find out whether the relationship between rat arterial pulse waveform (APW) parameters and blood pressure could be described by known mathematical functions and find mathematical parameters for conditions of hypertension resulting from decreased NO bioavailability. What is the main finding and its importance? We found mathematical functions and their parameters that approximate the relationships of 12 APW parameters to systolic and diastolic blood pressure in conditions of decreased NO bioavailability. The results may assign APW parameters to decreased NO bioavailability, which may have predictive or diagnostic value.