63 research outputs found
Assessment of histone acetylation levels in relation to cell cycle phase
No full textHistone acetylation affects chromatin structural organization, thus regulating gene expression and DNA-related cellular events. Levels of histone acetylation are tightly modulated in normal cells and frequently altered in tumors. Consequently, histone deacetylase inhibitors are currently being tested in clinical trials as anticancer drugs. Presented here is a protocol for measuring the degree of cellular histone tail acetylation, alone or in combination with DNA content to simultaneously evaluate cell ploidy and/or cell cycle progression. The procedure can also be employed to stain peripheral blood samples in order to assess mean histone acetylation levels in patients treated with histone deacetylase inhibitor
Synthesis of Pyrazoles by 1,3-Dipolar Cycloaddition under Aqueous Micellar Catalysis
No full textEthyl diazoacetate (EDA), which is easily prepared from ethyl glycinate and NaNO2, reacts in situ with alkynes in a water micelle environment without organic solvent to form pyrazoles. The reaction is pH dependent, as in the presence of protic catalysis (H2SO4 4%, pH 3.5) a mixture of 3,5- and 4,5-disubstituted pyrazoles was obtained, while, at pH 5.5, only the 3,5-disubstituted isomer was obtained. The presence of the surfactant TPGS-750-M was crucial to secure clean crude reaction mixtures and high yields of the products. The same protocol was successfully applied to the synthesis of substituted pyrazolines. © 2022 The Author
Comparison of fetal and neonatal growth curves in detecting growth restriction
No full textOBJECTIVE:: To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. METHODS:: We analyzed 53 pregnancies with severe IUGR classified as group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age (appropriate for gestational age [AGA] group). Differences were analyzed with the χ test and the Student t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P<.05 was considered significant. RESULTS:: At delivery, using the neonatal standards, 25 of 53 (47%) IUGR showed a birth weight above the 10th percentile (IUGRAGA), whereas in 28, birth weight was below the 10th percentile (IUGR small for gestational age [SGA]-IUGRSGA). All body size measurements were significantly higher in AGA than in IUGRAGA and IUGRSGA. Forty-nine of 79 (62%) AGA and 49 of 53 (92%) IUGR were admitted to the neonatal intensive care unit (P<.001). One of 79 (1%) AGA and 6 of 53 (11%) IUGR newborns died within 28 days (P<.02). Major and minor morbidity was not different. CONCLUSION:: This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birth weight infants and should be used only when obstetric data are unavailable
Life is not a camping trip - on the desirability of Cohenite socialism
No full textIn Why Not Socialism?, GA Cohen defines socialism as the combined application of two moral principles: the egalitarian principle and the principle of community. The desirability of a social order organized around these two principles is illustrated by the 'camping trip' example. After describing the fundamental features of the camping trip scenario at reasonable length, Cohen argues that the desirability of such a social model is nearly self-explanatory, concluding therefore that the most significant challenges to socialism lie in its feasibility. This article argues that the desirability of the camping trip model as an appropriate ideal for society is less obvious than Cohen acknowledges. To argue my point, I shall compare the camping trip with another social practice that is equally small sized and characterized by strong emotional ties among its members, but in which the conditions of what I shall call 'goal-monism' and discontinuity in time do not hold, namely, the family. © The Author(s) 2011
Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway
No full textHistone deacetylases (HDACs) regulate transcription and specific cellular functions, such as tumor suppression by p53, and are frequently altered in cancer. Inhibitors of HDACs (HDACIs) possess antitumor activity and are well tolerated, supporting the idea that their use might develop as a specific strategy for cancer treatment. The molecular basis for their selective antitumor activity is, however, unknown. We investigated the effects of HDACIs on leukemias expressing the PML-RAR or AML1-ETO oncoproteins, known to initiate leukemogenesis through deregulation of HDACs. Here we report that: (i) HDACIs induce apoptosis of leukemic blasts, although oncogene expression is not sufficient to confer HDACI sensitivity to normal cells; (ii) apoptosis is p53 independent and depends, both in vitro and in vivo, upon activation of the death receptor pathway (TRAIL and Fas signaling pathways); (iii) TRAIL, DR5, FasL and Fas are upregulated by HDACIs in the leukemic cells, but not in normal hematopoietic progenitors. These results show that sensitivity to HDACIs in leukemias is a property of the fully transformed phenotype and depends on activation of a specific death pathway
The Tumor Suppressor p53 Regulates Polarity of Self-Renewing Divisions in Mammary Stem Cells
No full textSummaryStem-like cells may be integral to the development and maintenance of human cancers. Direct proof is still lacking, mainly because of our poor understanding of the biological differences between normal and cancer stem cells (SCs). Using the ErbB2 transgenic model of breast cancer, we found that self-renewing divisions of cancer SCs are more frequent than their normal counterparts, unlimited and symmetric, thus contributing to increasing numbers of SCs in tumoral tissues. SCs with targeted mutation of the tumor suppressor p53 possess the same self-renewal properties as cancer SCs, and their number increases progressively in the p53 null premalignant mammary gland. Pharmacological reactivation of p53 correlates with restoration of asymmetric divisions in cancer SCs and tumor growth reduction, without significant effects on additional cancer cells. These data demonstrate that p53 regulates polarity of cell division in mammary SCs and suggest that loss of p53 favors symmetric divisions of cancer SCs, contributing to tumor growth
Lipopolysaccharide or Whole Bacteria Block the Conversion of Inflammatory Monocytes into Dendritic Cells In Vivo
No full textMonocytes can develop into dendritic cells (DCs) that migrate to lymph nodes (LNs) and present antigens to T cells. However, we find that this differentiation is blocked when monocytes accumulate subcutaneously in response to bacteria or lipopolysaccharide (LPS). The inhibition of DC differentiation is mediated by the bacteria and in conjunction with inflammatory cells recruited at the site of injection. Inhibition of migratory DC development was reversed in Toll-like receptor (TLR)4-mutated mice when LPS, but not whole bacteria, was injected, suggesting that TLR4 is one but not the only mediator of the inhibition. The block imposed by bacteria was partly relieved by the absence of interleukin (IL)-12 p40, but not by individual absence of several cytokines involved in DC differentiation or in inflammation, i.e., IL-6, IL-10, IL-12 p35, and interferon γ. Consistent with the inability of monocytes to yield migrating DCs, and the finding that other DCs had limited access to particulate or bacterial antigens, these antigens were weakly presented to T cells in the draining LN. These results illustrate that bacteria-associated signals can have a negative regulatory role on adaptive immunity and that local innate responses for containment of infectious bacteria can at least initially supersede development of adaptive responses
Correction to: Unprescribed cannabinoids and multiple sclerosis: a multicenter, cross-sectional, epidemiological study in Lombardy, Italy (Journal of Neurology, (2024), 10.1007/s00415-024-12472-4)
No full textIn the original version of this article, affiliation details for author Riccardo Giossi were incorrectly given as 2Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy but should have been 1Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy and 2Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy The original article has been corrected
Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content
No full textSummaryPathways that govern stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SCs (hNMSCs), from cultured mammospheres, on the basis of their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we prospectively isolated SCs from the normal gland and from breast tumors. Poorly differentiated (G3) cancers displayed higher content of prospectively isolated cancer SCs (CSCs) than did well-differentiated (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in CSCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their CSC content
Differential cytogenomics and miRNA signature of the Acute Myeloid Leukaemia Kasumi-1 cell line CD34+38− compartment
No full textThe t(8;21) Acute Myeloid Leukaemia (AML) Kasumi-1 cell line with N822K KIT mutation, is a model system for leukemogenesis. As AML initiating cells reside in the CD34+CD38− fraction, we addressed the refined cytogenomic characterization and miRNA expression of Kasumi-1 cell line and its FACS-sorted subpopulations focussing on this compartment. By conventional cytogenetics, Spectral-Karyotyping and array-CGH the cytogenomic profile of Kasumi-1 cells evidenced only subtle regions differentially represented in CD34+CD38− cells. Expression profiling by a miRNA platform showed a set of miRNA differentially expressed in paired subpopulations and the signature of miR-584 and miR-182 upregulation in the CD34+CD38− fraction
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