CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 ...expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in‐transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10−8). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker.
In insects, extra-molting has been viewed as a compensatory mechanism for nymphal growth that contributes to optimize body weight for successful reproduction. However, little is known on the capacity ...of extra-molting to evolve in natural populations, which limits our understanding of how selection acts on nymphal growth. We used a multi-generational pedigree, individual monitoring and quantitative genetics models to investigate the evolution of extra-molting and its impact on nymphal growth in a solitarious population of the desert locust, Schistocerca gregaria. Growth compensation via extra-molting was observed for 46% of the females, whose adult weight exceeded by 4% that of other females, at a cost of a 22% longer development time. We found a null heritability for body weight threshold only, and the highest and a strongly female-biased heritability for extra molting. Our genetic estimates show that (1) directional selection can act on growth rate, development time and extra-molting to optimize body weight threshold, the target of stabilizing selection, (2) extra-molting can evolve in natural populations, and (3) a genetic conflict, due to sexually antagonistic selection on extra-molting, might prevent its fixation. Finally, we discuss how antagonistic selection between solitarious and gregarious environments and/or genetic correlations between growth and phase traits might also impact the evolution of extra-molting in locusts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Leptospirosis After a Stay in Madagascar Pagès, Frédéric; Kuli, Barbara; Moiton, Marie‐Pierre ...
Journal of travel medicine,
03/2015, Letnik:
22, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We report a case of polymerase chain reaction (PCR)‐confirmed leptospirosis in a patient who recently traveled to Madagascar, a country where only two cases have been reported since 1955. Although ...laboratory and clinical presentations were atypical and despite leptospirosis not being a documented disease in Madagascar, blood and urine tests for leptospirosis enabled retrospective confirmation of the diagnosis.
In metastatic colorectal cancer, KRAS and NRAS genotyping is mandatory before prescription of panitumumab or cetuximab. In order to perform such molecular tests, the French National Cancer Institute ...has set up a nationwide network of molecular centers. We report here the percentage of these mutations according to a prospective nonselected cohort of incident metastatic colorectal carcinoma patients. A total of 6,803 patients were tested between July 1, 2013, and December 31, 2013. Overall, 49.06% of patients harbored a mutation in either KRAS or NRAS. Mutations of NRAS exons 3 and 4 were very rare. No NRAS exon 3 at c.59 or exon 4 at c.117 mutations were retrieved, and only 1 NRAS exon 4 at c.146 mutation was detected. This present cohort is likely to represent most of the incident cases of metastatic colorectal adenocarcinomas arising in France over 6 months and is to our knowledge the largest population set genotyped for these genes in this condition. This is a unique opportunity to observe the frequency of RAS mutations regardless of most inclusion bias.
Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011-January 2013 in Reunion. ...Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The capacity of mesenchymal stem cells (MSCs) to differentiate into functional osteoblasts is tightly controlled by transcription factors that trigger osteoblast commitment and differentiation. The ...role of Twist1, a basic helix‐loop‐helix (bHLH) transcription factor, in osteogenic differentiation of MSCs remains unclear. Here we investigated the role of Twist1 in the osteogenic differentiation program of murine C3H10T1/2 mesenchymal cells. We showed that molecular silencing of Twist1 using short hairpin RNA (shRNA) expression moderately increased C3H10T1/2 cell proliferation and had no effect on cell survival. In contrast, Twist1 silencing enhanced osteoblast gene expression and matrix mineralization in vitro. Biochemical analyses revealed that Twist1 silencing increased the expression of FGFR2 protein level, which was reduced by a mutant Runx2. Consistent with this finding, Twist1 silencing increased ERK1/2 and PI3K signaling. Moreover, molecular or pharmacological inhibition of FGFR2 or of ERK1/2 and PI3K signaling partly abolished the increased osteoblast gene expression induced by Twist1 silencing in C3H10T1/2 cells. These results reveal that Twist1 silencing upregulates osteoblast differentiation of murine mesenchymal cells in part via activation of FGFR2 expression and downstream signaling pathways, which provides novel insights into the molecular signals by which this transcription factor regulates the osteogenic differentiation program in MSCs. J. Cell. Biochem. 110: 1147–1154, 2010. Published 2010 Wiley‐Liss, Inc.
AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia ...characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total “bulk leukemic cells” we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS HR = 2.8(1.02-7.73), P = 0.04 and OS HR = 2.65(1.09-6.43), P = 0.03.CONCLUSION Taken together, these results show that a CD34/CD38 “backbone” for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.
Objectives: Patients with near‐tetraploid (karyotype: 81 – 103 chromosomes) acute lymphoblastic leukemia (NT‐ALL) constitute about 1% of childhood ALL and data reported on them are limited and ...controversial. The aim of the study was to enlarge the knowledge on these rarely occurring ALL.
Methods: The members of the European Group for Immunophenotyping of Leukemias (EGIL) searched retrospectively their databases for NT‐ALL patients.
Results: We collected data of 36 European children from seven European countries with NT‐ALL diagnosed since 1992. All patients reached complete remission (CR) after induction chemotherapy. Their blasts were negative for peroxidase and BCR‐ABL1. Ten children were diagnosed as T‐cell ALL (T‐ALL) EGIL categories (T‐I n = 2, T‐II n = 2, T‐III n = 3, T‐IV n = 3) and four displayed various structural chromosomal abnormalities. Eight of 10 T‐ALL remained in 1st CR; one died in CR from sepsis and one is alive in 2nd CR. Median survival was 88 (7–213) months. B‐cell precursor (BCP) ALL was diagnosed in 26 children. Thirteen were positive for ETV6‐RUNX1 and are alive in 1st CR for 32–147 months. Ten children were ETV6‐RUNX1 negative and remained in 1st CR for 16–163 months. One girl with hypodiploid and NT metaphases and ETV6‐RUNX1‐negative BCP‐ALL and one of two boys with NT‐BCP‐ALL not examined for ETV6‐RUNX1 died of infection after stem cell transplantation in 2nd/3rd CR. Secondary myelodysplastic syndrome developed in two patients with NT‐BCP‐ALL.
Conclusions: Our data demonstrate immunophenotypic, cytogenetic, and molecular heterogeneity of NT‐ALL and favorable prognosis of most NT‐ALL across different immunophenotypic and/or genetic ALL subtypes.
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