Energy, macronutrients and laryngeal cancer risk

BACKGROUND: A role for diet in laryngeal carcinogenesis has been suggested, but only a few studies have examined the potential relationship with a wide variety of macronutrients. PATIENTS AND METHODS: A case-control study was conducted between 1992 and 2000 in Italy and Switzerland, including 527 incident cases of laryngeal cancer, and 1297 controls hospitalized for acute, non-neoplastic conditions. The subjects' usual diet was investigated through a validated food frequency questionnaire, including 78 foods and beverages. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. RESULTS: Cases reported higher energy intake than controls. The continuous OR for 100 kcal/day was 1.16 (95% CI 1.12-1.21) for alcohol energy, and 1.02 (95% CI 1.01-1.04) for non-alcohol energy. A significantly increased risk of laryngeal cancer was observed for animal protein (continuous OR = 1.21, 95% CI 1.03-1.41), polyunsaturated fats other than linoleic and linolenic fatty acids (OR = 1.43, 95% CI 1.19-1.70), and cholesterol intake (OR = 1.43, 95% CI 1.19-1.71). Laryngeal cancer risk was slightly reduced with increasing vegetable protein (OR = 0.75, 95% CI 0.62-0.91), sugar (OR = 0.84, 95% CI 0.71-1.00) and monounsaturated fatty acid intake (OR = 0.83, 95% CI 0.70-0.99). CONCLUSIONS: Laryngeal cancer cases have a higher energy intake than control subjects, and report a higher intake of animal protein and cholesterol. [authors]]]> eng https://serval.unil.ch/resource/serval:BIB_26D8787AF96A.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_26D8787AF96A3 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_26D8787AF96A3 info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_26D8AFEA3D4D 2022-05-07T01:13:16Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_26D8AFEA3D4D Symbiose et sénescence: étude du cycle glyoxylique chez le soja (Glycine max. L., var. Maple arrow) et Bradyrhizobium japonicum Fargeix, C. Université de Lausanne, Faculté des sciences info:eu-repo/semantics/doctoralThesis phdthesis 2001 fre oai:serval.unil.ch:BIB_26D955FDA835 2022-05-07T01:13:16Z openaire documents <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_26D955FDA835 New emerging tasks for microRNAs in the control of β-cell activities info:doi:10.1016/j.bbalip.2016.05.003 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbalip.2016.05.003 info:eu-repo/semantics/altIdentifier/pmid/27178175 Guay, Claudiane Regazzi, Romano info:eu-repo/semantics/review article 2016-12 Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, vol. 1861, no. 12, pp. 2121-2129 info:eu-repo/semantics/altIdentifier/pissn/1388-1981 urn:issn:1879-2618 <![CDATA[MicroRNAs are key regulators of β-cell physiology. They participate to the differentiation of insulin-producing cells and are instrumental for the acquisition of their unique secretory properties. Moreover, they contribute to the adaptation of β-cells to conditions of increased insulin demand and, if expressed at inappropriate levels, certain microRNAs cause β-cell dysfunction and promote the development of different forms of diabetes mellitus. While these functions are increasingly better understood, additional tasks for these small non-coding RNAs have been recently unveiled. Thus, microRNAs are emerging as signaling molecules of a novel exosome-mediated cell-to-cell communication mode permitting a coordinated response of the β-cells to inflammatory conditions and to modifications in the insulin demand. These discoveries raise a number of important issues that once addressed promise to shed new light on the molecular mechanism governing the functions of the β-cells under normal and disease states. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez

Selected themes of histology, cytology and embryology core

CYTOLOGYEMBRYOLOGYHISTOLOGYГИСТОЛОГИЯУЧЕБНЫЕ ПОСОБИЯЦИТОЛОГИЯЭМБРИОЛОГИЯThe study manual includes topics on histology, cytology and embryology core

X-ray structure of the mature ectodomain of phogrin

Phogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel β-strands packed against two α-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes

Nutrient-sensing mechanisms and pathways

The ability to sense and respond to fluctuations in environmental nutrient levels is a requisite for life. Nutrient scarcity is a selective pressure that has shaped the evolution of most cellular processes. Different pathways that detect intracellular and extracellular levels of sugars, amino acids, lipids and surrogate metabolites are integrated and coordinated at the organismal level through hormonal signals. During food abundance, nutrient-sensing pathways engage anabolism and storage, whereas scarcity triggers homeostatic mechanisms, such as the mobilization of internal stores through autophagy. Nutrient-sensing pathways are commonly deregulated in human metabolic diseases.National Institutes of Health (U.S.) (Grant R01 CA129105)National Institutes of Health (U.S.) (Grant R01 CA103866)National Institutes of Health (U.S.) (Grant R01 AI047389)National Institutes of Health (U.S.) (Grant R21 AG042876)American Federation for Aging ResearchStarr FoundationDavid H. Koch Institute for Integrative Cancer Research at MIT (Frontier Research Program)Ellison Medical FoundationCharles A. King TrustAmerican Cancer Society (Ellison Medical Foundation Postdoctoral Fellowship PF-13-356-01-TBE

Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics

Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells

In addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca2+)-mediated secretion of pleiotropic paracrine and endocrine factors, including those produced in bone. Influx of Ca2+ through VSCCs activates intracellular signaling pathways to modulate a variety of cellular processes that include cell proliferation, differentiation, and bone adaptation in response to mechanical stimuli. Less well understood is the role of VSCCs in the control of bone and calcium homeostasis mediated through secreted factors. In this review, we discuss the various functions of VSCCs in skeletal cells as regulators of Ca2+ dynamics and detail how these channels might control the release of bioactive factors from bone cells. Because VSCCs are druggable, a better understanding of the multiple functions of these channels in the skeleton offers the opportunity for developing new therapies to enhance and maintain bone and to improve systemic health

Studies on the mechanisms of sorafenib-induced cell death

In 2008, 26% of all deaths were cancer-related, making this group of diseases the second leading cause of death in the EU countries. Derailment of tyrosine kinase signaling is one important pre-requisite towards tumorigenesis. Small molecular inhibitors of receptor tyrosine kinases (RTKs) are a new type of targeted therapy and they are increasingly used as a core component of personalized cancer therapy. The main aim of this thesis is to investigate the anti-cancer effects of the multi tyrosine kinase inhibitor (TKI) sorafenib in hematological and solid tumors. In the first study, we found that sorafenib is particularly effective in inducing cell death in a panel of human myeloma cell lines. We investigated the mode of cell death induced by sorafenib and found that this TKI induces both caspase dependent and caspase independent cell death. Furthermore, sorafenib induces autophagy in some human myeloma cell lines, myeloma patient samples and mouse myeloma cells and co-treatment of myeloma cells with sorafenib and autophagy inhibitors potentiates the cytotoxic efficacy of sorafenib. Importantly, sorafenib induced cell death in freshly isolated CD138+ multiple myeloma cells from newly diagnosed patients chemotherapy naïve as well as bortezomib resistant patient samples. We investigated the efficacy of sorafenib in the 5T33MM mouse myeloma model and found that this TKI lead to significantly increased survival, reduced tumor growth and decreased serum M component. In the pertaining studies we investigated the efficacy of sorafenib against prostate cancer cell lines. In the second study we demonstrated that sorafenib caused a dose-dependent decrease in cell viability in two hormone refractory and one hormone responsive prostate cancer cell lines. In the third study we further investigated the signaling cascades inhibited by sorafenib leading to cell death in prostate cancer cell lines (22Rv1 and PC3). Activation of caspases and downregulation of Mcl-1 are seen in both cell lines. However we found that distinct upstream signaling cascades are activated in these two prostate cancer cell lines which are differentially affected upon treatment with sorafenib. In 22Rv1, ERK1/2 is constitutively phosphorylated and active whereas in PC3 cells it is not active. In contrast, Src and AKT were constitutively active in PC3 cells but not in 22Rv1 and treatment with sorafenib could inhibit these kinases in PC3 cells. In both cell lines, sorafenib induces autophagy and inhibition of autophagy potentiates the cytotoxic efficacy of sorafenib. PC3 and 22Rv1 cells could further be rescued from sorafenib-induced cell death when co-cultured with cancer associated fibroblasts. This protection could be overcome by co-treatment with ABT737 (a Bcl-2/Bcl-xL inhibitor), suggesting that these anti-apoptotic proteins are, at least in part, responsible for the rescuing phenotype observed upon co-culture with cancer associated fibroblasts. In a fourth study we found that even though DU145 cells do not express ATG5 they undergo autophagy upon treatment with sorafenib or bafilomycin A1. Interestingly, we showed that sorafenib-induced autophagy in DU145 cells is cytotoxic and the cell death observed could be inhibited by the exogenous re-constitution of Atg5 expression. We found that treatment with molecular or chemical inhibitors of RIPK1 suppressed the observed cell death. Collectively our data suggest that in Atg5-deficient cells autophagy is cytotoxic and the ensuing cell death is executed by the necroptotic program. In summary, these data identify some molecular mechanisms and requirements for the successful usage of sorafenib as a putative anti-cancer treatment against multiple myeloma and prostate cance

Does microRNA perturbation control the mechanisms linking obesity with diabetes? Implications for cardiovascular risk.

Metabolic disorders such as obesity and type 2 diabetes (T2D) are considered the major risk factors for the development of cardiovascular diseases (CVD). Although the pathological mechanisms underlying the mutual development of obesity and T2D are difficult to define, a better understanding of the molecular aspects is of utmost importance to identify novel therapeutic targets. Recently, a class of non-coding RNAs, called microRNAs (miRNAs), are emerging as key modulators of metabolic abnormalities. There is increasing evidence supporting the role of intra-and extracellular miRNAs as determinants of the crosstalk between adipose tissues, liver, skeletal muscle and other organs, triggering the paracrine communication among different tissues. miRNAs may be considered as risk factors for CVD due to their correlation with cardiovascular events, and in particular, may be related to the most prominent risk factors. In this review, we describe the associations observed between miRNAs expression levels and the most common cardiovascular risk factors. Furthermore, we sought to depict the molecular aspect of the interplay between obesity and diabetes, investigating the role of microRNAs in the interorgan crosstalk. Finally, we discussed the fascinating hypothesis of the loss of protective factors, such as antioxidant defense systems regulated by such miRNAs

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin