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| 2. |
- Karlsson, S. C. Hannah, et al.
(författare)
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Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy
- 2013
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Ingår i: Cancer Gene Therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 20:7, s. 386-393
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Tidskriftsartikel (refereegranskat)abstract
- B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) has entered clinical trials. Gene engineered chimeric antigen receptor (CAR) T cells also show promise in B-cell malignancy, and as they induce apoptosis via the extrinsic pathway, we hypothesized that small-molecule inhibitors of the Bcl-2 family may potentiate the efficacy of CAR T cells by engaging both apoptosis pathways. CAR T cells targeting CD19 were generated from healthy donors as well as from pre-B-ALL (precursor-B acute lymphoblastic leukemia) patients and tested together with ABT-737 to evaluate apoptosis induction in five B-cell tumor cell lines. The CAR T cells were effective even if the cell lines exhibited different apoptosis resistance profiles, as shown by analyzing the expression of apoptosis inhibitors by PCR and western blot. When combining T-cell and ABT-737 therapy simultaneously, or with ABT-737 as a presensitizer, tumor cell apoptosis was significantly increased. In conclusion, the apoptosis inducer ABT-737 enhanced the efficacy of CAR T cells and could be an interesting drug candidate to potentiate T-cell therapy.
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| 3. |
- Linnarsson, M K, et al.
(författare)
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Precipitate formation in heavily Al-doped 4H-SiC layers
- 2001
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Ingår i: Materials Science Forum, Vols. 353-356. ; , s. 583-586, s. 583-586
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Konferensbidrag (refereegranskat)abstract
- Epitaxially grown 4H-SiC structures with several heavily Al doped layers were used. The samples were annealed in Ar atmosphere in a RF-heated furnace between 1500 and 2900 degreesC for 0.5 to 3h. Secondary ion mass spectrometry (SIMS) was used to measure the aluminum concentration versus,depth as well as the lateral distribution (ion images). Transmission electron microscopy (TEM) was employed to study the crystallinity and determine phase composition after heat treatment. A solubility limit of 2x10(20) Al/cm(3) at 2000 degreesC is extracted. Ion images of the lateral Al distribution reveal a pronounced dependence on the Al content. Precipitate formation occurs after heat treatment at 1700 - 2000 degreesC when the Al concentration exceeds 2x10(20) cm(-3) and energy-filtered TEM (EFTEM) shows that the precipitates contain Al.
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| 4. |
- Linnarsson, Margareta K., et al.
(författare)
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Solubility limit and precipitate formation in Al-doped 4H-SiC epitaxial material
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 79:13, s. 2016-2018
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Tidskriftsartikel (refereegranskat)abstract
- Heavily Al-doped 4H-SiC structures have been prepared by vapor phase epitaxy. Subsequent anneals have been carried out in an Ar atmosphere in a rf-heated furnace between 1500 degreesC and 2000 degreesC for 0.5 to 3 h. Secondary ion mass spectrometry has been utilized to obtain Al concentration versus depth as well as lateral distributions (ion images). Transmission electron microscopy (TEM) has been employed to study the crystallinity and determine phase composition after heat treatment. A solubility limit of similar to 2x10(20) Al/cm(3) (1900 degreesC) is extracted. Three-dimensional ion images show that the Al distribution does not remain homogeneous in layers heat treated at 1700 degreesC or above when the Al concentration exceeds 2x10(20) cm(-3). Al-containing precipitates are identified by energy-filtered TEM.
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| 5. |
- Spetz, Anna-Clara, et al.
(författare)
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Change in testosterone concentrations over time is a better predictor than the actual concentrations for symptoms of late onset hypogonadism
- 2011
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Ingår i: The Aging Male. - : Informa Healthcare. - 1368-5538 .- 1473-0790. ; 14:4, s. 249-256
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Tidskriftsartikel (refereegranskat)abstract
- Background. Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier. less thanbrgreater than less thanbrgreater thanMethods. In 2008, 282 men, aged 60-82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the Androgen Decline in Aging Males (ADAM)-questionnaire. Blood samples were analysed for concentrations of T and calculations were made for BT. less thanbrgreater than less thanbrgreater thanResults. A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p andlt; 0.05). Both T and BT concentrations decreased during the 5 years (p andlt; 0.05) but only the symptom less strong erections changed significantly (p andlt; 0.05). Men reporting one of the four specific symptoms from the ADAM-questionnaire for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003. less thanbrgreater than less thanbrgreater thanConclusions. The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom.
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