Dietary Phytochemicals Targeting Cancer Stem Cells

There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. Moreover, we evaluate and summarize studies dealing with effects of dietary phytochemicals on CSCs of various malignancies in preclinical and clinical research. Dietary phytochemicals have a significant impact on CSCs which may be applied in cancer prevention and treatment. However, anticancer effects of plant derived compounds have not yet been fully investigated in clinical research

Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma In Vivo and In Vitro

Naturally-occurring mixtures of phytochemicals present in plant foods are proposed to possess tumor-suppressive activities. In this work, we aimed to evaluate the antitumor effects of Thymus vulgaris L. in in vivo and in vitro mammary carcinoma models. Dried T. vulgaris (as haulm) was continuously administered at two concentrations of 0.1% and 1% in the diet in a chemically-induced rat mammary carcinomas model and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular analyses of rodent mammary carcinomas were performed. In addition, in vitro evaluations using MCF-7 and MDA-MB-231 cells were carried out. In mice, T. vulgaris at both doses reduced the volume of 4T1 tumors by 85% (0.1%) and 84% (1%) compared to the control, respectively. Moreover, treated tumors showed a substantial decrease in necrosis/tumor area ratio and mitotic activity index. In the rat model, T. vulgaris (1%) decreased the tumor frequency by 53% compared to the control. Analysis of the mechanisms of anticancer action included well-described and validated diagnostic and prognostic markers that are used in both clinical approach and preclinical research. In this regard, the analyses of treated rat carcinoma cells showed a CD44 and ALDH1A1 expression decrease and Bax expression increase. Malondialdehyde (MDA) levels and VEGFR-2 expression were decreased in rat carcinomas in both the T. vulgaris treated groups. Regarding the evaluations of epigenetic changes in rat tumors, we found a decrease in the lysine methylation status of H3K4me3 in both treated groups (H3K9m3, H4K20m3, and H4K16ac were not changed); up-regulations of miR22, miR34a, and miR210 expressions (only at higher doses); and significant reductions in the methylation status of four gene promoters—ATM serin/threonine kinase, also known as the NPAT gene (ATM); Ras-association domain family 1, isoform A (RASSF1); phosphatase and tensin homolog (PTEN); and tissue inhibitor of metalloproteinase-3 (TIMP3) (the paired-like homeodomain transcription factor (PITX2) promoter was not changed). In vitro study revealed the antiproliferative and proapoptotic effects of essential oils of T. vulgaris in MCF-7 and MDA-MB-231 cells (analyses of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS); 5-bromo-20-deoxyuridine (BrdU); cell cycle; annexin V/PI; caspase-3/7; Bcl-2; PARP; and mitochondrial membrane potential). T. vulgaris L. demonstrated significant chemopreventive and therapeutic activities against experimental breast carcinoma

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper

Flavonoids as an efective sensitizer for anti‑cancer therapy: insights into multi‑faceted mechanisms and applicability towards individualized patient profles

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are: - Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects; - Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities

Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers

Privacy and internet services

Práce se zabývá soukromím při používání internetových služeb. Cílem práce je zjistit povědomí uživatelů o tom, jak je přistupováno k jejich soukromí při používání internetových služeb. Podle zjištěných výsledků navrhnout postup, jak zlepšit toto povědomí, nebo doporučit postupy které umožní lepší kontrolu nad soukromím při používání internetových služeb. V teoretické části je rozebrán obecný i legislativní přístup k soukromí. Její součástí je analýza chování uživatelů a poskytovatelů internetových služeb. Předmětem této analýzy je mimo jiné použití cookies pro sledování uživatelů internetových služeb a možný dopad tohoto sledování na jejich soukromí. Praktickou částí je dotazníkově šetření, které slouží k samotnému zjištění úrovně povědomí uživatelů o tom, jak je přistupováno k jejich soukromí při používání internetových služeb a doporučení některých prostředků sloužících k ochraně soukromíThis thesis is focused on internet services user privacy. Goal of this thesis is to determine level of user awareness of how is their privacy approached while using internet services. Then suggest procedure to improve this awareness, or that will lead to better control of individual privacy. In theoretical part I analyze general and legislative approach to privacy, followed by analysis of behaviour of internet service users and providers. Part of this analysis deals with usage of web cookies for user tracking purposes and its possible impact on user privacy. Practical part consists of survey which is used to determine true level of user awareness of how is their privacy approached while using internet services, and of suggestion of measures to improve protection of privacy

System of assistance for homeless people and low income citizen groups modelled by process approach.

Práce prezentuje návrh systému pomoci lidem bez domova a nízko příjmovým skupinám obyvatel. Návrh je vytvořen s použitím procesní analýzy a zahrnuje zajištění potravin, oblečení, hygieny a systém pro podporu tvorby pracovních příležitostí. Systém je navržen na základě zkušeností lidí, či organizací pohybujících se v oblasti sociálních služeb, informačních technologií. Byli osloveni lidé ze zkušeností s neziskovým sektorem a ale také bezdomovci a chudí. Informace pro vypracování analýzy byly získány na základě osobních setkání či elektronické komunikace. Práce se zaměřuje především na organizace a služby působící v ČR, konkrétně v Praze. Teoretickou částí práce je získání potřebných informací a podkladů k vytvoření návrhu sytému. Informace k analýze získám rozborem podobných projektů, od osob či organizací zabývajících se touto problematikou ale také od lidí, kterým má projekt pomoci - bezdomovcům a chudým. Praktickou část tvoří návrh procesního modelu systému a zapracování případné zpětné vazby po jeho zveřejnění na kolaborační platformě GitHub.This thesis presents system for assistance to homeless people and low-income citizen groups. Design is created using process analysis and includes assurance of food, clothes, hygiene and system for the support of creation of jobs. System is designed based on experience of people and organizations in area of non-profit sector and also of homeless and low-income citizens themselves. Information for analysis were acquired by personal meetings, visits and electronic communication. Above all thesis is focuses on organizations offering their services in Czech Republic, particularly in Prague. Theoretic part of thesis is to obtain necessary information and base for creation of the assistance system. I gain information by analysing similar project from persons and organizations focused on this issue, but also from people, for which this system should be helpful -- homeless and poor. Practical part consists of process model design of the system and implementation of feedback after its publication if there will be an

Privacy and internet services

This thesis is focused on internet services user privacy. Goal of this thesis is to determine level of user awareness of how is their privacy approached while using internet services. Then suggest procedure to improve this awareness, or that will lead to better control of individual privacy. In theoretical part I analyze general and legislative approach to privacy, followed by analysis of behaviour of internet service users and providers. Part of this analysis deals with usage of web cookies for user tracking purposes and its possible impact on user privacy. Practical part consists of survey which is used to determine true level of user awareness of how is their privacy approached while using internet services, and of suggestion of measures to improve protection of privacy

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism