| 1. |
- Bidleman, Terry F., et al.
(författare)
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Air-water exchange of brominated anisoles in the northern baltic sea
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:11, s. 6124-6132
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Tidskriftsartikel (refereegranskat)abstract
- Bromophenols produced by marine algae undergo O-methylation to form bromoanisoles (BAs), which are exchanged between water and air. BAs were determined in surface water of the northern Baltic Sea (Gulf of Bothnia, consisting of Bothnian Bay and Bothnian Sea) during 2011-2013 and on a transect of the entire Baltic in September 2013. The abundance decreased in the following order: 2,4,6-tribromoanisole (2,4,6-TBA) > 2,4-dibromoanisole (2,4-DBA) ≫ 2,6-dibromoanisole (2,6-DBA). Concentrations of 2,4-DBA and 2,4,6-TBA in September were higher in the southern than in the northern Baltic and correlated well with the higher salinity in the south. This suggests south-to-north advection and dilution with fresh riverine water enroute, and/or lower production in the north. The abundance in air over the northern Baltic also decreased in the following order: 2,4,6-TBA > 2,4-DBA. However, 2,6-DBA was estimated as a lower limit due to breakthrough from polyurethane foam traps used for sampling. Water/air fugacity ratios ranged from 3.4 to 7.6 for 2,4-DBA and from 18 to 94 for 2,4,6-TBA, indicating net volatilization. Flux estimates using the two-film model suggested that volatilization removes 980-1360 kg of total BAs from Bothnian Bay (38000 km(2)) between May and September. The release of bromine from outgassing of BAs could be up to 4-6% of bromine fluxes from previously reported volatilization of bromomethanes and bromochloromethanes.
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| 3. |
- Hultman, Bo, 1964-, et al.
(författare)
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Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy
- 2014
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Background The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.Methods Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.Results The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.Conclusion Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.
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| 4. |
- Händel, Peter, et al.
(författare)
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Smartphone-Based Measurement Systems for Road Vehicle Traffic Monitoring and Usage-Based Insurance
- 2014
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Ingår i: IEEE Systems Journal. - : IEEE Press. - 1932-8184 .- 1937-9234. ; 8:4, s. 1238-1248
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Tidskriftsartikel (refereegranskat)abstract
- A framework is presented to deploy a smartphone-based measurement system for road vehicle traffic monitoring and usage-based insurance (UBI). Through the aid of a hierarchical model to modularize the description, the functionality is described as spanning from sensor-level functionality and technical specification to the topmost business model. The designer of a complex measurement system has to consider the full picture from low-level sensing, actuating, and wireless data transfer to the topmost level, including enticements for the individual smartphone owners, i.e., the end users who are the actual measurement probes. The measurement system provides two data streams: a primary stream to support road vehicle traffic monitoring and a secondary stream to support the UBI program. The former activity has a clear value for a society and its inhabitants, as it may reduce congestion and environmental impacts. The latter data stream drives the business model and parts of the revenue streams, which ensure the funding of the total measurement system and create value for the end users, the service provider, and the insurance company. In addition to the presented framework, outcome from a measurement campaign is presented, including road vehicle traffic monitoring (primary data stream) and a commercial pilot of UBI based on the driver profiles (secondary data stream). The measurement system is believed to be sustainable due to the incitements offered to the individual end users, in terms of favorable pricing for the insurance premium. The measurement campaign itself is believed to have an interest in its own right, as it includes smartphone probing of road traffic with a number of probes in the vicinity of the current state of the art, given by the Berkeley Mobile Millennium Project. During the ten-month run of the project, some 4500 driving h/250 000 km of road vehicle traffic data were collected.
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| 5. |
- Kashif, Muhammad, et al.
(författare)
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A Pragmatic Definition of Therapeutic Synergy Suitable for Clinically Relevant In Vitro Multicompound Analyses
- 2014
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 13:7, s. 1964-1976
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Tidskriftsartikel (refereegranskat)abstract
- For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS.
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| 6. |
- Månsson, Christopher, et al.
(författare)
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Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer
- 2014
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 34:1A, s. 289-293
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Tidskriftsartikel (refereegranskat)abstract
- Background:Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase I study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC).Patients and Methods:Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation.Results:No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound.Conclusion: IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.
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| 8. |
- Pettersson, Anna, et al.
(författare)
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Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy : Long-term results from a randomized controlled trial
- 2014
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 113:2, s. 240-247
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:To evaluate the long-term effects of dietary intervention on gastrointestinal symptoms after highly dose-escalated radiotherapy for localized prostate cancer, using boost with protons or high-dose-rate brachytherapy.MATERIALS AND METHODS:Patients were randomized to an intervention group (n=64) advised to reduce insoluble dietary fiber and lactose intake, or to a standard care group (n=66) advised to continue their usual diet. Gastrointestinal symptoms, other domains of health-related quality of life (HRQOL), and dietary intake were evaluated for ⩽24months post-radiotherapy with the European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-C30 and QLQ-PR25, Gastrointestinal Side Effects Questionnaire, and Food Frequency Questionnaire. The effect of the intervention on gastrointestinal symptoms was evaluated using generalized estimating equations.RESULTS:Dietary intervention had no obvious effect on long-term gastrointestinal symptoms or HRQOL. The intervention group markedly reduced their dietary fiber and lactose intake during radiotherapy, but adherence tended to decline over time. The vast majority of long-term gastrointestinal symptoms were reported as 'a little', with a noticeable difference from pre-treatment only for unintentional stool leakage, limitations on daily activities, and mucus discharge.CONCLUSION:Long-term gastrointestinal symptoms were predominantly mild, and dietary intervention was not superior to a usual diet in preventing these symptoms.
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| 9. |
- von Heideman, Anne, et al.
(författare)
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Chemotherapeutic drug sensitivity of primary cultures of epithelial ovarian cancer cells from patients in relation to tumour characteristics and therapeutic outcome
- 2014
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:2, s. 242-250
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Tidskriftsartikel (refereegranskat)abstract
- Background. A number of chemotherapeutic drugs are active in epithelial ovarian cancer (EOC) but so far choice of drugs for treatment is mostly empirically based. Testing of drug activity in tumour cells from patients might provide a rationale for a more individualised approach for drug selection. Material and methods. Sensitivity of EOC to chemotherapeutic drugs was analysed in 125 tumour samples from 112 patients using a short-term primary culture assay based on the concept of total cell kill. Sensitivity was related to tumour histology, treatment status and clinical tumour response. Results. For most EOC standard drugs serous high grade and clear cell EOC were the most sensitive subtypes and the mucinous tumours the most resistant subtype. Docetaxel, however, tended to show the opposite pattern. Samples from previously treated patients tended to be more resistant than those from treatment naive patients. The activity of cisplatin correlated with that of other drugs with the exception of docetaxel. Tumour samples from two sites in the same patient at the same occasion showed similar cisplatin sensitivity in contrast to samples taken at different occasions. Samples from patients responding in the clinic to treatment were more sensitive to most drugs than samples from non-responding patients. At the individual patient level, drug sensitivity in vitro compared with clinical response showed sensitivities and specificities in the 83-100% and 55-83% ranges, respectively. Conclusions. Assessment of EOC tumour cell drug sensitivity in vitro provides clinically relevant and potentially useful information for the optimisation of drug treatment.
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| 10. |
- Zhang, Xiaonan, et al.
(författare)
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Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3295-
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal vascularization of solid tumours results in the development of microenvironments deprived of oxygen and nutrients that harbour slowly growing and metabolically stressed cells. Such cells display enhanced resistance to standard chemotherapeutic agents and repopulate tumours after therapy. Here we identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to bioenergetic catastrophe and tumour cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Importantly, VLX600 displays tumour growth inhibition in vivo. Our findings suggest that tumour cells in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function, and suggest a strategy for targeting the quiescent populations of tumour cells for improved cancer treatment.
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