Hematopoetic stem cell transplantation for solid tumors in Europe

Background: Hematopoetic stem cell transplants (HSCT) are discussed as treatment options for patients with solid tumors. Transplant numbers have changed substantially over the last decade, few controlled studies are available and different opinions prevail. Objective information on current practice is needed. Patients and methods: Data from 27 902 HSCT for solid tumors (2% allogeneic, 98% autologous), collected by the European Group for Blood and Marrow Transplantation (EBMT) activity survey from 1991 to 2002 were used to assess trends, transplant rates and coefficient of variation of transplant rates in Europe. Results: Transplant numbers increased from 536 in 1991 to 4154 in 1997 and decreased to 1913 in 2002. Indications were neuroblastoma (2504 HSCT; 9%), glioma (662 HSCT; 2%), soft tissue sarcoma (1253 HSCT; 4%), germ cell cancer (3291 HSCT; 12%), breast cancer (13 524 HSCT; 48%), Ewing's sarcoma (1896 HSCT; 7%), lung cancer (387 HSCT; 1%), ovarian cancer (845 HSCT; 3%) and other solid tumors (3540 HSCT; 14%). Allogeneic cells were used in <20 cases up to 1997; since then allogeneic HSCT increased to 159 in 2002, mainly for renal cell carcinoma. Low coefficients of variation in transplant rates (<60%) are observed for Ewing's sarcoma (<56.5%), suggesting consensus for this indication. Conclusions: These data give an overview on current practice of HSCT for solid tumors in Europe. They provide objective information for health-care providers and patient counsellin

Seismic data reveal eastern Black Sea Basin structure

Rifted continental margins are formed by progressive extension of the lithosphere. The development of these margins plays an integral role in the plate tectonic cycle, and an understanding of the extensional process underpins much hydrocarbon exploration. A key issue is whether the lithosphere extends uniformly, or whether extension varies\ud with depth. Crustal extension may be determined using seismic techniques. Lithospheric extension may be inferred from the waterloaded subsidence history, determined from\ud the pattern of sedimentation during and after rifting. Unfortunately, however, many rifted margins are sediment-starved, so the subsidence history is poorly known.\ud To test whether extension varies between the crust and the mantle, a major seismic experiment was conducted in February–March 2005 in the eastern Black Sea Basin (Figure 1), a deep basin where the subsidence history is recorded\ud by a thick, post-rift sedimentary sequence. The seismic data from the experiment indicate the presence of a thick, low-velocity zone, possibly representing overpressured sediments. They also indicate that the basement and\ud Moho in the center of the basin are both several kilometers shallower than previously inferred. These initial observations may have considerable impact on thermal models of the petroleum system in the basin. Understanding\ud the thermal history of potential source rocks is key to reducing hydrocarbon exploration risk. The experiment, which involved collaboration between university groups in the United Kingdom, Ireland, and Turkey, and BP and\ud Turkish Petroleum (TPAO), formed part of a larger project that also is using deep seismic reflection and other geophysical data held by the industry partners to determine the subsidence history and hence the strain evolution of\ud the basin

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

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Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience

Background: Results of second-line chemotherapy in patients with extragonadal non-seminomatous germ cell tumor (NSGCT) appear inferior to results in testicular NSGCT. Patients with retroperitoneal NSGCT achieve a comparable long-term survival rate of 30%, but the salvage rates of patients with mediastinal primary are less than 10%. We conducted a retrospective analysis on patients with mediastinal and retroperitoneal NSGCT treated with second-line high-dose chemotherapy (HDCT) registered with the European Group for Blood and Marrow Transplantation (EBMT). Patients and methods: Between 1987 and 1999, 59 registered patients with retroperitoneal (n=37) and mediastinal (n=22) primary NSGCT, median age 28 years (range 18-60), were treated with second-line HDCT. All had received cisplatin-containing chemotherapy as first-line treatment. Results: Toxic death occurred in three cases (5%). With a median follow-up of 58 months (range 14-114), 18/59 patients (30%) continue to be disease-free. Of three patients who had a disease recurrence after HDCT, one patient achieved a disease-free status with further chemotherapy and surgery. In total, 19 patients (32%) are currently disease-free. Sixteen of 37 patients (43%) with retroperitoneal NSGCT, and three of 22 patients (14%) with mediastinal NSGCT are currently alive and disease-free. Conclusions: Second-line HDCT might represent a possible option for patients with retroperitoneal primary NSGCT. New salvage strategies are needed for patients with mediastinal NSGC

Nanoparticle‐Templated Molecular Recognition Platforms for Detection of Biological Analytes

Molecular recognition of biological analytes with optical nanosensors provides both spatial and temporal biochemical information. A recently developed sensing platform exploits near-infrared fluorescent single-wall carbon nanotubes combined with electrostatically pinned heteropolymers to yield a synthetic molecular recognition technique that is maximally transparent through biological matter. This molecular recognition technique is known as corona phase molecular recognition (CoPhMoRe). In CoPhMoRe, the specificity of a folded polymer toward an analyte does not arise from a pre-existing polymer-analyte chemical affinity. Rather, specificity is conferred through conformational changes undergone by a polymer that is pinned to the surface of a nanoparticle in the presence of an analyte and the subsequent modifications in fluorescence readout of the nanoparticles. The protocols in this article describe a novel single-molecule microscopy tool (near-infrared fluorescence and total internal reflection fluorescence [nIRF TIRF] hybrid microscope) to visualize the CoPhMoRe recognition process, enabling a better understanding of synthetic molecular recognition. We describe this requisite microscope for simultaneous single-molecule visualization of optical molecular recognition and signal transduction. We elaborate on the general procedures for synthesizing and identifying single-walled carbon nanotube-based sensors that employ CoPhMoRe via two biologically relevant examples of single-molecule recognition for the hormone estradiol and the neurotransmitter dopamine. © 2016 by John Wiley &amp; Sons, Inc

Autologous hematopoietic stem cell transplantation for breast cancer in Europe: Critical evaluation of data from the European Group for Blood and Marrow Transplantation (EBMT) Registry 1990-1999

The aim of this study was to identify trends in high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (ASCT) and to assess survival in a large cohort of breast cancer (BC) patients receiving this therapy in Europe from 1990 to 1999. A total of 7471 patients who received HDC with ASCT between January 1, 1990 and December 31, 1999 were reported to the European Group for Blood and Marrow Transplantation Registry. Data required for demographics and survival analysis were available for 2679 patients with high-risk primary BC; 921 patients with inflammatory BC (IBC), and 2295 patients with metastatic disease. The main evaluation parameters were progression-free survival (PFS) and overall survival (OS). Between 1990 and 1998, autotransplants for BC increased 30-fold. Significant trends included use of blood-derived rather than marrow-derived stem cells, increment of reporting centers and decrease of mortality within 100 days from transplantation. The 5-year PFS and OS probabilities were 53 and 68% for high-risk disease and 42 and 53% for IBC, respectively. For metastatic disease 5-year PFS and OS probabilities in the whole cohort were 18 and 27%, respectively, while for women transplanted in complete remission the 5-year PFS was 29%. In conclusion, HDC with ASCT has been increasingly used until 1998 and the 100-day mortality rate has been constantly less than 2% from 1995 to date. The 5-year survival of high-risk BC is related to the number of axillary nodes involved at surgery. Outcome of patients with IBC is encouraging, suggesting the need for randomized trials. Patients with metastatic disease responding to pretransplant chemotherapy and harboring ER+ tumors have a better outcome

Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations

High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg−1), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 μg h ml−1) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 μg h ml−1). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. 1999 Cancer Research Campaig

Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients

Fried foods: a risk factor for laryngeal cancer?

The role of fried foods on laryngeal cancer risk was investigated in a case–control study from Italy and Switzerland on 527 cases and 1297 hospital controls. A significant increased risk was found for high consumption of fried meat, fish, eggs and potatoes, with odds ratios of 1.6, 3.1, 1.9 and 1.9, respectively

Oil prices and stock returns : nonlinear links across sectors

We present evidence of an asymmetric relationship between oil prices and stock returns. The two regime multivariate Markov switching vector autoregressive (MSVAR) model allow us to capture the state shifts in the relationship between regional stock markets and sectors. Results suggest that oil price risk is significantly priced in the sample used. The impact is asymmetric with respect to market phases, and regimes have been associated with world economic, social and political events. Our study also suggests asymmetric responses of sector stock returns to oil price changes and different transmission impacts depending on the sector analyzed. There is a high causality from oil to sectors like Industrials and Oil & Gas. Companies inside the Utilities sector were more able to hedge against oil price increases between 2007 and 2012. Historical crisis events between 1992–1998 and 2003–2007 do not seem to have affected the relationship between oil and sector stock returns, given the higher probability of remaining smoother. For all sectors there seems to be a turn back to stability from 2012 onwards. Finally, investors gain more through portfolio diversification benefits built across, rather than within sectors.info:eu-repo/semantics/publishedVersio