2,827 research outputs found
Treatment of Breast Cancer Cells by IGF1R Tyrosine Kinase Inhibitor Combined with Conventional Systemic Drugs
Nitrogen deposition shows no consistent negative nor positive effect on the response of forest productivity to drought across European FLUXNET forest sites
Atmospheric reactive nitrogen (N) deposition is an important driver of carbon (C) sequestration in forest ecosystems. Previous studies have focused on N-C interactions in various ecosystems; however, relatively little is known about the impact of N deposition on ecosystem C cycling during climate extremes such as droughts. With the occurrence and severity of droughts likely to be exacerbated by climate change, N deposition—drought interactions remain one of the key uncertainties in process-based models to date. This study aims to contribute to the understanding of N deposition-drought dynamics on gross primary production (GPP) in European forest ecosystems. To do so, different soil water availability indicators (Standardized Precipitation Evapotranspiration Index (SPEI), soil volumetric water) and GPP measurements from European FLUXNET forest sites were used to quantify the response of forest GPP to drought. The computed drought responses of the forest GPP to drought were linked to modelled N deposition estimates for varying edaphic, physiological, and climatic conditions. Our result showed a differential response of forest ecosystems to the drought indicators. Although all FLUXNET forest sites showed a coherent dependence of GPP on N deposition, no consistent or significant N deposition effect on the response of forest GPP to drought could be isolated. The mean response of forest GPP to drought could be predicted for forests with Pinus trees as dominant species (R2 = 0.85, RMSE = 8.1). After extracting the influence of the most prominent parameters (mean annual temperature and precipitation, forest age), however, the variability remained too large to significantly substantiate hypothesized N deposition effects. These results suggest that, while N deposition clearly affects forest productivity, N deposition is not a major nor consistent driver of forest productivity responses to drought in European forest ecosystems
Adolescents and Young Adults Living With an Uncertain or Poor Cancer Prognosis:The "New" Lost Tribe
Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a "lost tribe" without a medical "home"; neither pediatric nor adult oncology services were able to provide ageappropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of longterm disease control, AYA care programs should address the unique palliative care needs of this "new" lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group
99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein.
99mTc-sestamibi (99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99mTc-MIBI alone. 99mTc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR150x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR150x vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR150x. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this gamma-rays-emitting complex is tested for tumour efflux measurements
Ultra-thin corrugated metamaterial film as large-area transmission dynode
Large-area transmission dynodes were fabricated by depositing an ultra-thin
continuous film on a silicon wafer with a 3-dimensional pattern. After removing
the silicon, a corrugated membrane with enhanced mechanical properties was
formed. Mechanical materials, such as this corrugated membrane, are engineered
to improve its strength and robustness, which allows it to span a larger
surface in comparison to flat membranes while the film thickness remains
constant. The ultra-thin film consists of three layers (AlO
/TiN/AlO) and is deposited by atomic layer deposition (ALD). The
encapsulated TiN layer provides in-plane conductivity, which is needed to
sustain secondary electron emission. Two types of corrugated membranes were
fabricated: a hexagonal honeycomb and an octagonal pattern. The latter was
designed to match the square pitch of a CMOS pixel chip. The transmission
secondary electron yield was determined with a collector-based method using a
scanning electron microscope. The highest transmission electron yield was
measured on a membrane with an octagonal pattern. A yield of 2.15 was achieved
for 3.15 keV incident electrons for an AlO /TiN/AlO tri-layer
film with layer thicknesses of 10/5/15 nm. The variation in yield across the
surface of the corrugated membrane was determined by constructing a yield map.
The active surface for transmission secondary electron emission is near 100%,
i.e. a primary electron generates transmission secondary electrons regardless
of the point of impact on the corrugated membrane
Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2.
In a phase I trial the toxicity and immunomodulatory effects of combined treatment with intravenous (i.v.) bispecific monoclonal antibody BIS-1 and subcutaneous (s.c.) interleukin 2 (IL-2) was studied in renal cell cancer patients. BIS-1 combines a specificity against CD3 on T lymphocytes with a specificity against a 40 kDa pancarcinoma-associated antigen, EGP-2. Patients received BIS-1 F(ab')2 fragments intravenously at doses of 1, 3 and 5 micrograms kg-1 body weight during a concomitantly given standard s.c. IL-2 treatment. For each dose, four patients were treated with a 2 h BIS-1 infusion in the second and fourth week of IL-2 therapy. Acute BIS-1 F(ab')2-related toxicity with symptoms of chills, peripheral vasoconstriction and temporary dyspnoea was observed in 2/4 and 5/5 patients at the 3 and 5 micrograms kg-1 dose level respectively. The maximum tolerated dose (MTD) of BIS-1 F(ab')2 was 5 micrograms kg-1. Elevated plasma levels of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were detected at the MTD. Flow cytometric analysis showed a dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes. Peripheral blood mononuclear cells (PBMCs), isolated after treatment with 3 and 5 micrograms kg-1 BIS-1, showed increased specific cytolytic capacity against EGP-2+ tumour cells as tested in an ex vivo performed assay. Maximal killing capacity of the PBMCs, as assessed by adding excess BIS-1 to the assay, was shown to be decreased after BIS-1 infusion at 5 micrograms kg-1 BIS-1 F(ab')2. A BIS-1 F(ab')2 dose-dependent disappearance of circulating mononuclear cells from the peripheral blood was observed. Within the circulating CD3+ CD8+ lymphocyte population. LFA-1 alpha-bright and HLA-DR+ T-cell numbers decreased preferentially. It is concluded that i.v. BIS-1 F(ab')2, when combined with s.c. IL-2, has a MTD of 5 micrograms kg-1. The treatment endows the T lymphocytes with a specific anti-EGP-2-directed cytotoxic potential
Financial outcomes of adolescent and young adult cancer survivors:A longitudinal population-based registry study
Background: The patterns and determinants of long-term income among adolescent and young adult (AYA) cancer survivors, and the differences compared with peers, have not yet been fully explored. This study investigated the long-term effects of cancer on the income of AYA cancer survivors. Methods: The Netherlands Cancer Registry identified all AYA cancer patients (aged 18-39 years) diagnosed in 2013 and alive 5 years postdiagnosis. Clinical data of the selected AYA patients were linked to individual, administrative real-world labor market data of Statistics Netherlands. The control group consisted of a random sample of individuals of the same age, sex, and migration background without cancer. Data on 2434 AYA cancer patients and 9736 controls were collected annually from 2011 until 2019. Changes in income level were measured and compared with the control group using difference-in-difference regression models. Results: AYA cancer survivors experience, on average, an 8.5% decrease in annual earnings, relative to the control population. The effects are statistically significant and permanent (P < .01). Younger AYAs (those aged 18-25 years 15.5% income reduction), married cancer survivors (12.3%), females (11.6%), those diagnosed with stage IV disease (38.1%), and central nervous system (15.7%) cancer patients experienced the largest decline in income, on average, relative to controls, all else constant. Conclusion: Although dependent on the sociodemographic and clinical characteristics, a cancer diagnosis at AYA age has significant implications on the income of cancer patients. Awareness of vulnerable groups and the development of policies to mitigate the financial impact of cancer are critical
A new in vitro assay for quantitation of chemotherapy-induced mucositis.
Patients receiving high-dose chemotherapy (HD-CT) are at risk of severe mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this study was to develop an objective in vitro assay of chemotherapy-induced mucositis. Twelve patients with locally advanced breast carcinoma received HD-CT followed by peripheral stem cell reinfusion. Before and twice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity grading; furthermore, blood leucocyte levels were determined. For the oral washings, the percentage of viable epithelial cells was determined by trypan blue dye exclusion and leucocytes were counted by fluorescence microscopy after incubation with acridine orange. Maturity of buccal cells was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunteers served as controls. The mean percentage (+/- s.e.m.) of viable oral epithelial cells was stable in controls (44 +/- 2%). In patients, they increased after HD-CT, which was significant after day 7 compared with pretreatment (P < or = 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observed. Oral leucocyte levels were closely correlated with the blood leucocyte counts. The WHO score followed the results of these other evaluations with some delay. The viability of buccal cells obtained by oral washings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more immature cells. These data can be quantitated, and this assay may therefore be useful in studies aimed at prevention of mucositis
Prediction of Cardiovascular Events by Using Non-Vascular Findings on Routine Chest CT
Background: Routine computed tomography (CT) examinations contain an abundance of findings unrelated to the diagnostic question. Those with prognostic significance may contribute to early detection and treatment of disease, irrelevant findings can be ignored. We aimed to assess the association between unrequested chest CT findings in lungs, mediastinum and pleura and future cardiovascular events. Methods: Multi-center case-cohort study in 5 tertiary and 3 secondary care hospitals involving 10410 subjects who underwent routine chest CT for non-cardiovascular reasons. 493 cardiovascular hospitalizations or deaths were recorded during an average follow-up time of 17.8 months. 1191 patients were randomly sampled to serve as a control subcohort. Hazard ratios and annualized event rates were calculated. Results: Abnormalities in the lung (26–44%), pleura (14–15%) and mediastinum (20%) were common. Hazard ratios after adjustment for age and sex were for airway wall thickening 2.26 (1.59–3.22), ground glass opacities 2.50 (1.72–3.62), consolidations 1.97 (1.12–3.47), pleural effusions 2.77 (1.81–4.25) and lymph-nodes 2.04 (1.40–2.96). Corresponding annual event rates were 5.5%, 6.0%, 3.8%, 10.2 % and 4.4%. Conclusions: We have identified several common chest CT findings that are predictive for future risk of cardiovascular events and found that other findings have little utility for this. The added value of the non-vascular predictors to establishe
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