The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer:Targets for Effective Therapy with 3-Bromopyruvate

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development

The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer:Targets for Effective Therapy with 3-Bromopyruvate

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development

Fungi present in home and their impact on human health-A short review

It is estimated that even up to 30% of buildings worldwide may be the subject of complaints connected with the quality of indoor air. Potential sources of air pollution can be both organic and inorganic particles. This article focuses on biological air pollutants from living and dead biological sources, especially those connected with fungi. Fungi found in the indoor air of domestic dwellings in a large extent are similar in their species composition to those found on the outside of the building. Microorganisms enters into the buildings during the airing of rooms or through the different slots and can develop on the surfaces of various materials. Intensively develops in a poorly ventilated, damp and dusty environments. For this reason the exposure to the indoor air pollution might be stranger for inhabitants than the expose to the impurities of the outdoor air. Presence of fungi in domestic dwellings can be very danger because of most often is associated with allergic reactions, mycotoxins, volatile organic compounds or even with fungal infections

Update on Stachybotrys chartarum—Black Mold Perceived as Toxigenic and Potentially Pathogenic to Humans

In nature, there are many species of fungi known to produce various mycotoxins, allergens and volatile organic compounds (VOCs), as well as the commonly known etiological agents of various types of mycoses. So far, none of them have provoked so much emotion among homeowners, builders, conservators, mycologists and clinicians as Stachybotrys chartarum. This species compared to fungi of the genera Fusarium and Aspergillus is not as frequently described to be a micromycete that is toxigenic and hazardous to human and animal health, but interest in it has been growing consistently for three decades. Depending on the authors of any given review article, attention is focused either on the clinical aspects alongside the role of this fungus in deterioration of biomaterials, or aspects related to its biology, ecology and taxonomic position. On the one hand, it is well established that inhalation of conidia, containing the highest concentrations of toxic metabolites, may cause serious damage to the mammalian lung, particularly with repeated exposure. On the other hand, we can find articles in which authors demonstrate that S. chartarum conidia can germinate and form hyphae in lungs but are not able to establish an effective infection. Finally, we can find case reports that suggest that S. chartarum infection is linked with acute pulmonary hemorrhage, based on fungal structures recovered from patient lung tissue. New scientific reports have verified the current state of knowledge and note that clinical significance of this fungus is exceedingly controversial. For these reasons, understanding S. chartarum requires reviewing the well-known toxigenic features and harmful factors associated with this fungus, by gathering the newest ones into a coherent whole. The research problem related to this fungus seems to be not overly publicized, and there is still a demand to truthfully define the real threats of S. chartarum and phylogenetically related species. The most important problem, which should be fully elucidated as soon as possible, remains the clarification of the pathogenicity of S. chartarum and related species. Maybe it is urgent time to ask a critical question, namely what exactly do we know 28 years after the outbreak of pulmonary hemorrhage in infants in Cleveland, Ohio, USA most likely caused by S. chartarum

Diversity of Species and Susceptibility Phenotypes toward Commercially Available Fungicides of Cultivable Fungi Colonizing Bones of Ursus spelaeus on Display in Niedźwiedzia Cave (Kletno, Poland)

Underground ecosystems are one of the most inhospitable places for microorganism development and function. Therefore, any organic matter located in these areas can stimulate fungal growth. The main purpose of this study was to find the best solution to effectively preserve (without relapses) paleolithic bones of cave bear (Ursus spelaeus) exhibited in cave without any negative influence on the cave environment. To achieve this aim, unambiguous identification of fungal species and its susceptibility tests toward fungicidal preparations were performed. Fungi were identified based on phenotypic tests and the internal transcribed spacer (ITS) region analysis. The antifungal activity of three preparations (Pufmax, Boramon and Devor Mousse) was evaluated by microdilution assay (protocol M38-A2) and spot tests assay. Phenotypic and molecular research showed that bones were colonized by 11 fungal species: Absidia glauca, Aspergillus fumigatus, Chrysosporium merdarium, Fusarium cerealis, Mortierella alpina, Mucor aligarensis, M. plumbeus, Penicillium chrysogenum, P. expansum, Sarocladium strictum and Scopulariopsis candida. All of the tested preparations were the most active against C. merdarium. In turn, M. plumbeus, M. aligarensis, M. alpina and A. glauca were the least susceptible. The highest antifungal activity was shown for Pufmax (minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values were in the range of 0.16–0.63% and 1.25–2.50%, respectively). The lowest fungicidal effect was observed for Boramon (MICs and MFCs in the range of 2.5–10% and 5–20%, respectively). Devor Mousse and Pufmax preparations showed fungicidal activity at the concentrations in the range of 1.25–5%. Susceptibility profiles were also confirmed based on spot tests assay. Our study allows for unambiguously identifying isolated fungi and assessing their susceptibility to commercially available fungicides, to prevent fungal outbreak