p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time.

B-cell high-grade lymphomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. As bcl-2 and p53 gene deregulations are frequently involved in several types of lymphoid malignancies, we aimed our investigation at the study of the relation between bcl-2 and p53 expression and survival probability in a group of 119 patients with B-cell high-grade lymphoma. These were obtained from the Virgen de la Salud Hospital, Toledo, Spain (73 cases), John Radcliffe Hospital, Oxford, UK (31 cases), and the Istituto Nazionale dei Tumori, Milan, Italy (15 cases). The relation between bcl-2 protein expression and survival was small, depending on the primary localisation of the tumour (in lymph node of mucosae), and lacked a significant correlation with overall survival. In contrast with this, p53 expression was related to survival probability in our series, this relation being both significant and independent of histological diagnosis. p53-positive patients showed a sudden decrease in life expectancy in the first months after diagnosis. Multivariant regression analysis confirmed that the only parameters significantly related with survival were extranodal origin, which is associated with a better prognosis, and p53 expression, which indicates a poor prognosis. Simultaneous expression of bcl-2 and p53 was associated with a poorer prognosis than p53 alone. This is particularly significant for large B-cell lymphomas presenting in lymph nodes. The cumulative poor effect of both p53 and bcl-2 in large B-cell lymphomas, which is more significant in nodal tumours, could confirm the existence of a multistep genetic deregulation in non-Hodgkin's lymphoma. This indicates that the genetic mechanisms controlling apoptosis and their disregulation are critical steps in the progression of lymphomas

Regular black hole in three dimensions

We find a new black hole in three dimensional anti-de Sitter space by introducing an anisotropic perfect fluid inspired by the noncommutative black hole. This is a regular black hole with two horizons. We compare thermodynamics of this black hole with that of non-rotating BTZ black hole. The first-law of thermodynamics is not compatible with the Bekenstein-Hawking entropy.Comment: 15 pages, 16 figures, 3D noncommutative black hole included as Sec 4, a version to appear in EPJ

Lifshitz black holes in Brans-Dicke theory

We present an exact asymptotically Lifshitz black hole solution in Brans-Dicke theory of gravity in arbitrary $n(\ge 3)$ dimensions in presence of a power-law potential. In this solution, the dynamical exponent $z$ is determined in terms of the Brans-Dicke parameter $\omega$ and $n$. Asymptotic Lifshitz condition at infinity requires $z>1$, which corresponds to $-(n-1)/(n-2) \le \omega < -n/(n-1)$. On the other hand, the no-ghost condition for the scalar field in the Einstein frame requires $0<z \le 2(n-2)/(n-3)$. We compute the Hawking temperature of the black hole solution and discuss the problems encountered and the proposals in defining its thermodynamic properties. A generalized solution charged under the Maxwell field is also presented.Comment: 32 pages, no figure. v2: revised version. Section 3.1 and Appendix B improved. The argument in Appendix A clarified. v3: References added. v4: analysis on the black hole thermodynamical properties corrected. Final version to appear in JHE

Phase transitions for the Lifshitz black holes

We study possibility of phase transitions between Lifshitz black holes and other configurations by using free energies explicitly. A phase transition between Lifshitz soliton and Lifshitz black hole might not occur in three dimensions. We find that a phase transition between Lifshitz and BTZ black holes unlikely occurs because they have different asymptotes. Similarly, we point out that any phase transition between Lifshitz and black branes unlikely occurs in four dimensions since they have different asymptotes. This is consistent with a necessary condition for taking a phase transition in the gravitational system, which requires the same asymptote.Comment: 19 pages, 7 figures, a revised version to appear in EPJ

Black holes with a null Killing vector in three-dimensional massive gravity

We investigate solutions of new massive gravity with two commuting Killing vectors, one of which is null, with a special emphasis on black hole solutions. Besides extreme BTZ black holes and, for a special value of the coupling constant, massless null warped black holes, we also obtain for a critical coupling a family of massive "log" black holes. These are asymptotic to the extreme BTZ black holes in the sense of log gravity.Comment: 16 pages; v2: title changed; v3: section 4 reworked; version to be published in Classical and Quantum Gravit

p27(Kip1 )is expressed in proliferating cells in its form phosphorylated on threonine 187

BACKGROUND: G1/S cell cycle progression requires p27(Kip1 )(p27) proteolysis, which is triggered by its phosphorylation on threonine (Thr) 187. Since its levels are abundant in quiescent and scarce in cycling cells, p27 is an approved marker for quiescent cells, extensively used in histopathology and cancer research. METHODS: However here we showed that by using a specific phosphorylation site (pThr187) antibody, p27 is detectable also in proliferative compartments of normal, dysplastic and neoplastic tissues. RESULTS: In fact, whereas un-phosphorylated p27 and MIB-1 showed a significant inverse correlation (Spearman R = -0.55; p < 0,001), pThr187-p27 was positively and significantly correlated with MIB-1 expression (Spearman R = 0.88; p < 0,001). Thus proliferating cells only stain for pThr187-p27, whereas they are un-reactive with the regular p27 antibodies. However increasing the sensitivity of the immunocytochemistry (ICH) by the use of an ultra sensitive detection system based on tiramide signal amplification, simultaneous expression and colocalisation of both forms of p27 was shown in proliferating compartments nuclei by double immunofluorescence and laser scanning confocal microscopy studies. CONCLUSION: Overall, our data suggest that p27 expression also occurs in proliferating cells compartments and the combined use of both regular and phospho- p27 antibodies is suggested

DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos

DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of ?H2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells ?H2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of ?H2AX-only cells increases after caspase inhibition while the relative number of TUNELonly cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration

An A91V SNP in the perforin gene is frequently found in NK/T-cell lymphomas

NK/T-cell lymphoma (NKTCL) is the most frequent EBV-related NK/T-cell disease. Its clinical manifestations overlap with those of familial haemophagocytic lymphohistiocytosis (FHLH). Since PERFORIN (PRF1) mutations are present in FHLH, we analysed its role in a series of 12 nasal and 12 extranasal-NKTCLs. 12.5% of the tumours and 25% of the nasal-origin cases had the well-known g.272C>T(p.Ala91Val) pathogenic SNP, which confers a poor prognosis. Two of these cases had a double-CD4/CD8-positive immunophenotype, although no correlation was found with perforin protein expression. p53 was overexpressed in 20% of the tumoral samples, 80% of which were of extranasal origin, while none showed PRF1 SNVs. These results suggest that nasal and extranasal NKTCLs have different biological backgrounds, although this requires validation