Journals
2014 EN
Island Joshua O. · Buscema Michele · Barawi Mariam
+7 more
TiS 3 nanoribbons with thickness down to 15 nm are isolated by viscoelastic mechanical exfoliation. Field‐effect transistors are fabricated and their electrical characteristics are studied in the dark state and upon illumination. An ultrahigh photoresponse up to 3000 A/W, a bandgap of 1 eV, and response times of about 4 ms are found making TiS 3 a state‐of‐the‐art material in photodetection.
Journals
2014 EN
Mizuno Hitoshi · Maeda Takuro · Yanagi Hisao
+8 more
Room temperature optically pumped lasing is achieved for a new n‐type molecular crystal of 2,5‐bis(4′‐cyanobiphenyl‐4‐yl)thiophene (BP1T‐CN). Efficient stimulated emission in the Fabry–Pérot crystal cavity is supported with a high group refractive index (4.18–4.98), Q factor (910–1860), material gain coefficient (120 cm ‐1 ), and a high stimulated emission rate demonstrated by pump–probe measurements.
Journals
2014 EN
Malagola Michele · Breccia Massimo · Skert Cristina
+29 more
Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty‐seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow‐up, the BCR‐ABL transcripts level was available in 96/101 living patients (95%) The BCR‐ABL:ABL ratio was between 0.1 and 0.01% (MR 3.0 ) in 17%, and less than 0.01% (MR 4.0 ) in 81% of patients. No patient was completely molecular negative (MR 4.5 or MR 5.0 ). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR 4.0 . Complete molecular response (MR 4.5 or MR 5.0 ) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα. Am. J. Hematol. 89:119–124, 2014. © 2013 Wiley Periodicals, Inc.
Journals
2014 EN
Morabito Fortunato · Bringhen Sara · Larocca Alessandra
+31 more
Novel agents in combination with melphalan and prednisone (MP) significantly improved progression‐free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty‐six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2‐microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients ( P = 0.007). After a median follow‐up of 34 months (range, 1–92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52–0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32–0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control‐case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT. Am. J. Hematol. 89:355–362, 2014. © 2013 Wiley Periodicals, Inc.
Journals
2014 EN
Montanaro Marco · Latagliata Roberto · Cedrone Michele
+17 more
To identify prognostic factors affecting thrombosis‐free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real‐life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow‐up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years ( P 60 years ( P 15 × 10 9 /l ( P = 0.0370) were independent risk factors. Previous thrombotic events in ET patients are crucial for TFS but their importance seems related not to the occurrence per se but mainly to the interval between the event and the diagnosis. Am. J. Hematol. 89:542–546, 2014. © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Sahin Ilyas · Azab Feda · Mishima Yuji
+9 more
The phosphatidylinositol‐3 kinase (PI3K) pathway is activated in multiple myeloma (MM) and Waldenstrom Macroglobulenima (WM), and plays a crucial role in tumor progression and drug resistance. In this study, we characterized the role of pan‐class I PI3K inhibition on cell trafficking and survival of MM and WM cells. We tested the effect of pan‐class I PI3K inhibition by siRNA silencing or pharmacologic inhibition with buparlisib on MM cell survival, apoptosis and cell cycle in vitro and tumor growth and mobilization of MM cells in vivo. We then evaluated buparlisib‐dependent mechanisms of induced MM cell mobilization. Moreover, the effect of buparlisib on cell survival, apoptosis, and adhesion of WM cells to bone marrow stromal cells (BMSCs) has been evaluated. We showed that buparlisib induced toxicity in MM cells, supported by induction of apoptosis and cell cycle arrest. Buparlisib was also found to reduce tumor progression in vivo. Importantly, buparlisib enhanced MM cell mobilization in vivo which was driven by decreased adhesion of MM cells to BMSCs and increased chemotaxis via up‐regulation of CXCR4 expression. Similar to its effects on MM cells, buparlisib also induced cell survival and apoptosis, and decreased adhesion in WM cells. These data highlight the critical contribution of class I PI3K signaling to the regulation of survival and cell dissemination in B‐cell malignancies. Am. J. Hematol. 89:1030–1036, 2014. © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Mitchell William Beau · Pinheiro Mariana P. · Boulad Nayla
+8 more
Platelet survival depends upon mediators of apoptosis e.g., Bcl‐x L, Bax, and Bak, which are regulated by thrombopoietin (TPO)‐mediated AKT signaling. Thrombopoietin receptor (TPO‐R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti‐apoptotic effects of TPO‐R‐agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl‐x L inhibitor assay; Bcl‐x L Western blot; and flow cytometric (FACS) analysis of the AKT‐signaling pathway. Eight/ten patients had platelet responses to eltrombopag and all three to romiplostim. Platelet sensitivity to apoptosis by Bcl‐xL inhibition was greater in pretreatment patients than controls. This sensitivity normalized after one week of therapy, but surprisingly returned to pretreatment levels at week two. FACS analysis revealed increased AKT‐pathway signaling after one week, followed by a decrease at week two. Platelet counts correlated with the Bcl‐x L /Bak ratio. Platelet survival may be enhanced by TPO‐R‐agonists as a transient decrease in platelet sensitivity to apoptosis was accompanied by transient activation of AKT. However, this mechanism has only a short‐lived effect. Megakaryocytes and platelets already present at the start of TPO‐R‐agonist treatment appear to respond differently than those generated de novo. Am. J. Hematol. 89:E228–E234, 2014. © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Tacchetti Paola · Terragna Carolina · Galli Monica
+17 more
A subanalysis of the GIMEMA‐MMY‐3006 trial was performed to characterize treatment‐emergent peripheral neuropathy (PN) in patients randomized to thalidomide‐dexamethasone (TD) or bortezomib‐TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). A total of 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade ≥2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed in 120 VTD‐treated patients. The incidence of grade ≥2 PN was 35% in the VTD arm and 10% in the TD arm ( P < 0.001). PN resolved in 88 and 95% of patients in VTD and TD groups, respectively. Rates of complete/near complete response, progression‐free and overall survival were not adversely affected by emergence of grade ≥2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis, and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD‐induced PN. Am. J. Hematol. 89:1085–1091, 2014. © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Casale Maddalena · Citarella Serena · Filosa Aldo
+10 more
Iron overload in β‐thalassemia major (TM) typically results in iron‐induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long‐term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion‐dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% ( P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism ( n = 5) and hypoparathyroidism ( n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly ( P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased ( P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre‐exisisting was observed in a real clinical practice setting. Am. J. Hematol. 89:1102–1106, 2014. © 2014 Wiley Periodicals, Inc.
Journals
2014 EN
Bleuze Michele M. · Wheeler Sandra M. · Williams lana J.
+1 more
Objectives The purpose of this study is to document the appearance of adult patterns in intralimb indices during ontogeny in a skeletal sample from the Kellis 2 cemetery, Dakhleh Oasis, Egypt. In addition, this study explores evolvability in intralimb indices to understand relative differences in sensitivity to ecogeographic variables. Methods Brachial and crural indices were compared across age cohorts with Welch's ANOVA tests and post‐hoc Dunnett‐Tukey‐Kramer (DTK) pairwise multiple comparison tests. Spearman's rank correlation coefficients were used to examine developmental conservation and evolvability in intralimb proportions. Results Brachial and crural indices are greatest in the fetus/perinate cohort as compared to all other cohorts, decrease during infancy and early childhood, and increase during middle/late childhood. The adult pattern in the brachial index is first evident in infancy, but is not maintained throughout development. Conversely, the adult pattern in the crural index appears during early childhood and is maintained throughout development. The brachial index shows a higher degree of evolvability than the crural index in utero . Conclusions The shifting pattern in intralimb proportions during development in the Kellis 2 sample is similar to that previously reported from globally diverse samples, which likely reflects the differential growth acceleration of proximal and distal intralimb skeletal elements during ontogeny. The brachial index may be more responsive to climatic conditions while the crural index may be more conserved due to functional demands. The data indicate that Kellis 2 juveniles were under strong selective pressures from climatic factors. Am. J. Hum. Biol. 26:221–228, 2014. © 2014 Wiley Periodicals, Inc.