Sub-second infrared variability from the archetypal accreting neutron star 4U 1728−34

We report on the first simultaneous high-time resolution X-ray and infrared (IR) observations of a neutron star low mass X-ray binary in its hard state. We performed ≈ 2 h of simultaneous observations of 4U 1728−34 using HAWK-I@VLT, XMM– Newton, and NuSTAR. The source displayed significant X-ray and IR variability down to sub-second time-scales. By measuring the cross-correlation function between the IR and X-ray lightcurves, we discovered a significant correlation with an IR lead of ≈ 30–40 ms with respect to the X-rays. We analysed the X-ray energy dependence of the lag, finding a marginal increase towards higher energies. Given the sign of the lag, we interpret this as possible evidence of Comptonization from external seed photons. We discuss the origin of the IR seed photons in terms of cyclo-synchrotron radiation from an extended hot flow. Finally, we also observed the IR counterpart of a type-I X-ray burst, with a delay of ≈ 7.2 s. Although some additional effects may be at play, by assuming that this lag is due to light travel time between the central object and the companion star, we find that 4U 1728−34 must have an orbital period longer than 3 h and an inclination higher than 8◦

Papel de la cirugía en el tratamiento del linfoma gástrico primario

Primary gastric lymphoma's optimum management remains controversial. We reviewed our series of 23 patients with primary gastric lymphoma treated in our hospital between 1976 and 1998 with surgery as main therapy. Ten patients underwent surgical resection alone, whereas 13 also received postoperative adjuvant therapy, depending on the oncologist-haematologist's recommendations. No differences were found between treatments regarding mortality and morbidity. Clinical-histological features and patients, follow-up are analyzed. No patient died because of lymphoma and there wasn't either local or distant recurrence. We consider that surgery remains a valid option for the primary gastric lymphoma treatment. The introduction of combined modalities of radiation therapy and chemotherapy will depend on the final stage, the tumor histological features, and the feasibility of getting a radical resection

RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation

Identification of TNF-α and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array

BACKGROUND: Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. METHODS: We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. RESULTS: Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-alpha, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-alpha and MMP-9 baseline levels were significantly increased in non-responders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-alpha and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. CONCLUSION: Baseline levels of TNF-alpha and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response

P53 expression is significantly correlated with high risk of malignancy and epithelioid differentiation in GISTs. An immunohistochemical study of 104 cases

<p>Abstract</p> <p>Background</p> <p>Molecular analyses of the <it>c-kit </it>and <it>PDGFRα </it>genes have contributed greatly to our understanding of the development of gastrointestinal stromal tumors (GISTs), but little is known about their malignant potential. The aim of our study was to evaluate cell cycle regulators as potential prognostic markers in GISTs.</p> <p>Methods</p> <p>We investigated 104 KIT positive GISTs from various tumor sites in immunoassays on CD34, Ki67 and particularly on P53, BCL-2 and Cyclin D1. The results were compared with tumor size, mitotic rate, proliferative activity, histological subtype, nuclear atypia and risk assessment according to Fletcher and Miettinen. Occurrence of metastases and survival were also taken into account.</p> <p>Results</p> <p>The expression of P53 was significantly correlated with high risk criteria towards malignancy and epithelioid differentiation in GISTs. Likewise P53 label correlated significantly with the established prognostic indicators: tumor size, mitotic rate, nuclear atypia and proliferative activity. Regarding the site of tumor presentation, P53 was not a decisive factor. BCL-2 and Cyclin D1 expression was not related to any of the prognostic indicators.</p> <p>Conclusion</p> <p>The present data identified P53 being a recommendable marker for predicting the risk of malignancy in GISTs. In addition, we found P53 significantly correlated with epithelioid tumor differentiation, independent of tumor site. BCL-2 and Cyclin D1, however, did not prove to be deciding markers for diagnosis and prognosis.</p

Pasado, presente y futuro de la vacunación anti-idiotipo

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients

Device complications with addition of defibrillation to cardiac resynchronisation therapy for primary prevention

Objective: In patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection. // Methods: Observational multicentre European cohort study of 3008 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias, undergoing CRT implantation with (CRT-D, n=1785) or without (CRT-P, n=1223) defibrillator. Using propensity score and competing risk analyses, we assessed the risk of significant device-related complications requiring surgical reintervention. Inappropriate shocks were not considered except those due to lead malfunction requiring lead revision. // Results: Acute complications occurred in 148 patients (4.9%), without significant difference between groups, even after considering potential confounders (OR=1.20, 95% CI 0.72 to 2.00, p=0.47). During a mean follow-up of 41.4±29 months, late complications occurred in 475 patients, giving an annual incidence rate of 26 (95% CI 9 to 43) and 15 (95% CI 6 to 24) per 1000 patient-years in CRT-D and CRT-P patients, respectively. CRT-D was independently associated with increased occurrence of late complications (HR=1.68, 95% CI 1.27 to 2.23, p=0.001). In particular, when compared with CRT-P, CRT-D was associated with an increased risk of device-related infection (HR 2.10, 95% CI 1.18 to 3.45, p=0.004). Acute complications did not predict overall late complications, but predicted device-related infection (HR 2.85, 95% CI 1.71 to 4.56, p<0.001). // Conclusions: Compared with CRT-P, CRT-D is associated with a similar risk of periprocedural complications but increased risk of long-term complications, mainly infection. This needs to be considered in the decision of implanting CRT with or without a defibrillator