Effect of combined action of doxorubicin and calcifediol on MCF-7 breast cancer cells

Introduction: Breast cancer is one of the most common cancers in women. Current recommendations for combination therapy in patients with breast cancer are still being developed and new therapies with greater success are sought. A relatively new approach is the administration of cytostatics in combination with vitamins. Hence, the study aimed to clarify whether the combination of calcifediol [25(OH)D3] with doxorubicin affects the response of the MCF-7 breast cancer cell line to the cytostatic. Material and methods: In the MCF-7 cell line, the authors assessed cytotoxicity using the MTT assay, analysed the cell cycle and cell death mechanism using flow cytometry, and examined the structure of the cytoskeleton and cell morphology. Results: The results showed that doxorubicin in combination with calcifediol in a 1:1 ratio showed a synergistic effect resulting in a dose-dependent decrease in cell survival. Further studies have shown that this is due to the pro-apoptotic and necrotic effects of the combination of these compounds. There were also changes in the organization of the cytoskeleton and cell morphology. In addition, features of entosis were noted in MCF-7 cells. Conclusion: The synergistic effect of doxorubicin and calcifediol significantly reduced the viability of MCF-7 breast cancer cells. Inducing the desired effect by lowering the cytostatic dose is of great clinical importance, taking into account the cardiotoxicity of doxorubicin. Another very interesting aspect is the entosis process induced in the present research, which may have a dual nature

‘To grasp Paris, one has to live with Paris for a long time’. French impressions from journeys of Łucja Rautenstrauch from the ducal family of Giedroyć

The article is a short attempt to present the reader with a profile of the now-forgotten Łucja Rautenstrauch from the ducal family of Giedroyć, a nineteenth century writer and traveller, who gained her fame and appreciation in the epoch thanks to her travel writings. Two of Łucja Rautenstrauch’s works deserve special attention: My memories of France [Wspomnienia moje o Francyi] and The last journey to France [Ostatnia podróż do Francyi], where she gave an impartial description of Paris. The author depicts the city pointing both to its good and bad sides. Her memories distinguish themselves from among other travel writings because of the author’s unusual sense of perception and the accuracy of her remarks. One will not find any instances of artificial admiration nor unnecessary humility in front of the people who meant more than her. On the contrary, an image of an educated aristocrat who does not feel the obligation to uphold the rules of the world she did not appreciate emerges for My memories of France. In the same work Łucja Rautenstrauch focuses on the description of the visible and external world: the customs, fashion, the French street, the salon and the history of the visited places

„…i jeśli mi pozwolą tragedie moje, chcęż jeszcze Panią widzieć”. Łucja Rautenstrauch’s decade with Norwid

Artykuł stanowi próbę rekonstrukcji relacji Łucji Rautenstrauchowej z Cyprianem Norwidem. Na podstawie analizy biografii pisarki oraz znanej korespondencji Cypriana Norwida autorka podejmuje próbę odtworzenia początków znajomości z poetą, która została zawarta we Włoszech w latach 40. XIX w. a także dalszego przebiegu relacji, kontynuowanej w trakcie wizyt pisarki w Paryżu w latach 50. i 60. XIX wieku.This article attempts to reconstruct Łucja Rautenstrauch’s relation to Cyprian Norwid. Based on an analysis of the writer’s biography and her known correspondence with Cyprian Norwid, the author of the article attempts to reconstruct the beginnings of their acquaintance, which started in Italy in the 1840s, as well as the further course of their relationship, which continued during the writer’s visits to Paris in the 1850s and 1860s

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility, Ca2+ fluxes, induction of endoplasmic reticulum stress, and autophagy. Our findings indicate that bortezomib treatment leads to left ventricular contractile dysfunction manifested by a significant drop in left ventricle ejection fraction. Dramatic ultrastructural abnormalities of cardiomyocytes, especially within mitochondria, were accompanied by decreased ATP synthesis and decreased cardiomyocyte contractility. Monitoring of cardiac function in bortezomib-treated patients should be implemented to evaluate how frequently cardiotoxicity develops especially in patients with pre-existing cardiac conditions, as well as when using additional cardiotoxic drugs