186 research outputs found
Demonstration of a gastric bioptic specimen mix-up by laser capture microdissection (LCM) and DNA fingerprinting
No full textWe demonstrate here the successful use of laser capture microdissection (LCM) and DNA fingerprinting in the identification of a case of gastric bioptic specimen mix-up. A 70-year-old man, suffering from chronic atrophic gastritis, underwent to a gastric biopsy and received a diagnosis of gastric cancer. In the absence of any clinical evidence of gastric cancer, a specimen mix-up was suspected. LCM was used to retrieve gastric cells from the histologic slide, classified as gastric carcinoma, and suspected to be mislabelled. DNA was extracted from microdissected cells, and a total of 16 different genetic loci were analyzed, using an identity test. Comparison of the results with those obtained using DNA extracted from a control slide, and from patient's saliva, demonstrated a distinct DNA fingerprint pattern in all genetic markers examined, clearly indicating the occurrence of a specimen mix-up. The combined use of LCM and DNA fingerprinting represents the most accurate and sophisticated method available for the identification of specimen mix-up, especially when only the tissue on the suspected slide is available
O2/3 exposure inhibits cell progression affecting cyclin B1/cdk 1 activity in SK-N-SH while induces apoptosis in SK-N-DZ neuroblastoma cells
No full textIn search for innovative therapeutic agents for children neuroblastoma, the oxygen therapy could be considered an alternative antitumoral
treatment. Given the physiochemical properties ofO2/3 gas mixture including fairly low aqueous solubility and spreading, and the
interesting perspective of hyperoxia, we analyzed the inhibitory effect ofO2/3 treatment on two human neuroblastoma cell lines (SK-N-SH
and SK-N-DZ). In this study, we demonstrated thatO2/3 treatment was able to induce cell growth inhibition and cell cycle perturbation in
both cell lines. We observed an arrest at G2 phase, accompanied by an alteration in the expression and localization of cyclin B1/cdk1
complex and a reduction in its activity in SK-N-SH cells. This reduction was consistent with the increase in both Wee1 and chk1 protein
levels. On the contrary, O2/3 induced apoptosis in SK-N-DZ cells via caspase 3 activation and Poly ADP-ribose polymerase-1 (PARP)
cleavage, associated with an increase in the pro-apoptotic Bax protein. Consequently, we considered the possibility of improving the
responsiveness to chemotherapeutic agents such as Cisplatin, Etoposide, and Gemcitabine in combination with O2/3 treatment. The
combined treatments produced a stronger cell inhibitory effect than Cisplatin and Etoposide used alone in SK-N-SH cells.Onthe contrary,
the combination data were not significantly different from O2/3 treatment alone in SK-N-DZ cells, thus suggesting that the obtained
changes in cell growth inhibition were due to the effect of O2/3 alone
Enrico IV ovvero il potere salvifico dell’immaginazione
No full textAmong the writings published by Umberto Artioli a year before his sudden death in July 2004, there is a study on Luigi Pirandello’s Enrico IV. Abandoning the usual realistic interpretation of the text, the scholar highlights the allegorical path underneath its conception and a number of references related to the evangelical Last Supper. The core of Pirandello’s hero teachings identifies in the theatrical imagination the way to salvation. Although the initiation of his disciples fails, the Author outlines the characteristics of a new type of artist and his ideal relationship with the public; a figure that will inspire Bontempelli’s ideas on an extremely versatile and eclectic interpreter to be driven on stage like a puppet
3,3',5-Triiodo-L-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy.
No full textThe pancreatic adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression, and profound resistance to actual treatments, including chemotherapy and radiotherapy. At the moment, surgical resection provides the best possibility for long-term survival, but is feasible only in the minority of patients, when advanced disease chemotherapy is considered, although the effects are modest. Several studies have shown that thyroid hormone, 3,3',5-triiodo-l-thyronine (T(3)) is able to promote or inhibit cell proliferation in a cell type-dependent manner. The aim of the present study is to investigate the ability of T(3) to reduce the cell growth of the human pancreatic duct cell lines chosen, and to increase the effect of chemotherapeutic drugs at conventional concentrations. Three human cell lines hPANC-1, Capan1, and HPAC have been used as experimental models to investigate the T(3) effects on pancreatic adenocarcinoma cell proliferation. The hPANC-1 and Capan1 cell proliferation was significantly reduced, while the hormone treatment was ineffective for HPAC cells. The T(3)-dependent cell growth inhibition was also confirmed by fluorescent activated cell sorting analysis and by cell cycle-related molecule analysis. A synergic effect of T(3) and chemotherapy was demonstrated by cell kinetic experiments performed at different times and by the traditional isobologram method. We have showed that thyroid hormone T(3) and its combination with low doses of gemcitabine (dFdCyd) and cisplatin (DDP) is able to potentiate the cytotoxic action of these chemotherapic drugs. Treatment with 5-fluorouracil was, instead, largely ineffective. In conclusion, our data support the hypothesis that T(3) and its combination with dFdCyd and DDP may act in a synergic way on adenopancreatic ductal cells
3,5,3 '-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis
No full text3,5,3'-triiodothyronine (T-3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T-3 has largely been demonstrated and the pathways via which T-3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T-3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T-3 promotes cell proliferation in islet beta-cell lines (rRINm5F and hCM) provoking an increment in cell number (up to 55%: rRINm5F and 45%: hCM), cell viability, and BrdU incorporation, and regulating the cell cycle-related molecules (cyc A, D1, E, and p27(kip1)). T-3 inhibited the apoptotic process induced by streptozocin, S-Nitroso-N-Acetylpenicylamine (SNAP), and H2O2 via regulation of the pro- and anti-apoptotic factors Bcl-2, Bcl-X-L, Bad, Bax, and Caspase 3. The T-3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAkt(Thr308). Thus, T-3 could be considered a survival factor protecting islet beta-cells from apoptosis
Modulation of proteomic profile in H295R adrenocortical cell line induced by mitotane
No full textMitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chloro-phenyl) ethane (o,p'-DDD), is a compound that represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. In this type of cancer, the biological mechanism induced by this treatment remains still unknown. In this study, we have already shown a greater impairment in the first steps of the steroidogenesis and recognized a little effect on cell cycle. We also evaluated the variation of proteomic profile of the H295R ACC cell line, either in total cell extract or in mitochondria-enriched fraction after treatment with mitotane. In total cell extracts, triose phosphate isomerase, alpha-enolase, D-3-phosphoglycerate dehydrogenase, peroxiredoxin II and VI, heat shock protein 27, prohibitin, histidine triad nucleotide-binding protein, and profilin-1 showed a different expression. In the mitochondrial fraction, the following proteins appeared to be down regulated: aldolase A, peroxiredoxin 1, heterogenous nuclear ribonucleoprotein A2/B1, tubulin-beta isoform II, heat shock cognate 71 kDa protein, and nucleotide diphosphate kinase, whereas adrenodoxin reductase, cathepsin D, and heat shock 70 kDa protein 1 A were positively up-regulated. This study represents the first proteomic study on the mitotane effects on ACC. It permits to identify some protein classes affected by the drug involved in energetic metabolism, stress response, cytoskeleton structure, and tumorigenesis
Thyroid Hormones (T3 and T4): Dual Effect on Human Cancer Cell Proliferation
No full textSeveral findings suggest that the patient's hormonal context plays a crucial role in determining cancer outcome. The exact nature of thyroid hormone action on tumour growth has not been established yet, in fact contrasting data show thyroid hormones have a promotory or an inhibitory action on cancer cell proliferation depending on the case. We hypothesized that not only tissue specificity, but also specific mutations occurring during tumoral development in different thyroid hormone cellular targets are responsible for this dual effect. To test our hypothesis we analysed, by time-course and bromodeoxyuridine assay, thyroid hormone effects on the proliferation of six cancer cell lines originating from the same tissue or organ but carrying different mutations (in phospho-inositide 3 kinase or β-catenin genes). The data obtained in this study show how mutations that affect the balance between degradation and stabilization of β-catenin assume a remarkable importance in determining the cell-specific thyroid hormone effect on cell growth
The Fractal Structure of the Universal Steenrod Algebra: An Invariant-theoretic Description
No full textAs recently observed by the second author, the mod2 universal
Steenrod algebra Q has a fractal structure given by a system of nested
subalgebras Qs, for s > N, each isomorphic to Q. In the present paper
we provide an alternative presentation of the subalgebras Qs through
suitable derivations s, and give an invariant-theoretic description of
them
Thyroid hormone receptor TRβ1 mediates Akt activation by T3 in pancreatic β cells
No full textIt has recently been recognized that thyroid hormones may rapidly generate biological responses by non-genomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways underlying these effects are just beginning to be defined. We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic b cells rRINm5F and hCM via thyroid hormone receptor (TR) b1. The phosphorylation of Akt was T3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the phosphatidylinositol 3 kinase (PI3K) p85a subunit and the thyroid receptor b1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a ‘cytoplasmic TRb1’ was implicated. Moreover, we evidenced that T3 treatment was able to induce kinase activity of the TRb1-associated PI3K. The silencing of TRb1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt. This action involved a T3-induced nuclear translocation of activated Akt, as demonstrated by confocal immunofluorescence. In summary, T3 is able to specifically activate Akt in the islet b cells rRINm5F and hCM through the interaction between TRb1 and PI3K p85a, demonstrating the involvement of TRb1 in this novel T3 non-genomic action in islet b cells
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