The gut microbiota is a complex component of humans that depends on diet, host genome, and lifestyle. The background: The study purpose is to find relations between nutrition, intestinal lactic acid bacteria (LAB) from various environments (human, animal intestine, and yogurt) and sulfate-reducing microbial communities in the large intestine; to compare kinetic growth parameters of LAB; and to determine their sensitivity to different concentration of hydrogen sulfide produced by intestinal sulfate-reducing bacteria. METHODS: Microbiological (isolation and identification), biochemical (electrophoresis), molecular biology methods (DNA isolation and PCR analysis), and statistical processing (average and standard error calculations) of the results were used. THE RESULTS: The toxicity of hydrogen sulfide produced by sulfate-reducing bacteria, the survival of lactic acid bacteria, and minimal inhibitory concentrations (MIC) were determined. The measured hydrogen sulfide sensitivity values were the same for L. paracasei and L. reuteri (MIC > 1.1 mM). In addition, L. plantarum and L.fermentum showed also a similar sensitivity (MIC > 0.45 mM) but significantly (p < 0.05) lower than L.reuteri and L. paracasei (1.1 > 0.45 mM). L. paracasei and L. reuteri are more sensitive to hydrogen sulfide than L. fermentum and L. plantarum. L. pentosus was sensitive to the extremely low concentration of H2S (MIC > 0.15 mM). CONCLUSIONS: The Lactobacillus species were significantly sensitive to hydrogen sulfide, which is a final metabolite of intestinal sulfate-reducing bacteria. The results are definitely helpful for a better understanding of complicated interaction among intestinal microbiota and nutrition.

• MeSH
• Bacteria klasifikace   izolace a purifikace   metabolismus   MeSH
• feces mikrobiologie   MeSH
• idiopatické střevní záněty mikrobiologie   MeSH
• Lactobacillus účinky léků   růst a vývoj   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mikrobiální viabilita účinky léků   MeSH
• myši MeSH
• střeva mikrobiologie   MeSH
• střevní mikroflóra účinky léků   MeSH
• sulfan metabolismus   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• cílená molekulární terapie MeSH
• karcinogeneze účinky léků   genetika   MeSH
• lidé MeSH
• nádorové mikroprostředí účinky léků   genetika   MeSH
• nádory farmakoterapie   genetika   prevence a kontrola   MeSH
• patologická angiogeneze farmakoterapie   genetika   prevence a kontrola   MeSH
• proliferace buněk účinky léků   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

• MeSH
• karcinogeneze chemicky indukované   MeSH
• lidé MeSH
• nádorové mikroprostředí účinky léků   MeSH
• nádory chemicky indukované   MeSH
• nebezpečné látky škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.

• MeSH
• lidé MeSH
• nádory chemicky indukované   etiologie   MeSH
• nebezpečné látky škodlivé účinky   MeSH
• signální transdukce účinky léků   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.

• MeSH
• antitumorózní látky fytogenní terapeutické užití   MeSH
• chemorezistence genetika   MeSH
• cílená molekulární terapie * MeSH
• genetická heterogenita * MeSH
• individualizovaná medicína * MeSH
• lidé MeSH
• nádorové mikroprostředí genetika   MeSH
• nádory genetika   patologie   prevence a kontrola   terapie   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

• MeSH
• karcinogeneze chemicky indukované   MeSH
• karcinogeny životního prostředí škodlivé účinky   MeSH
• lidé MeSH
• nádory chemicky indukované   etiologie   MeSH
• nebezpečné látky škodlivé účinky   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH