| 1. |
- Schmidt, Henning, et al.
(författare)
-
DESIREE as a new tool for interstellar ion chemistry
- 2008
-
Ingår i: International Journal of Astrobiology. - 1473-5504 .- 1475-3006. ; 7:3-4, s. 205-208
-
Tidskriftsartikel (refereegranskat)abstract
- A novel cryogenic electrostatic storage device consisting of two ion-beam storage rings with a common straight section for studies of interactions between oppositely charged ions at low and well-defined relative velocities is under construction at Stockholm University. Here we consider the prospect of using this new tool to measure cross-sections and rate coefficients for mutual neutralization reactions of importance in interstellar ion chemistry in general and specifically in cosmic pre-biotic ion chemistry.
|
|
| 2. |
|
|
| 3. |
- Bernhard, Jürg, et al.
(författare)
-
Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone : a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001
- 2008
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:22, s. 3695-3701
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.
|
|
| 4. |
- Herrmann, Richard, et al.
(författare)
-
Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer : a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
- 2007
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 25:16, s. 2212-2217
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. Patients and Methods: Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Kamofsky performance score (KPS), presence of pain, and disease extent. Results: A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. Conclusion: GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
|
|
| 5. |
- Hoffmann, Thomas K, et al.
(författare)
-
A novel mechanism for anti-EGFR antibody action involves chemokine-mediated leukocyte infiltration.
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:11, s. 2589-96
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). Monoclonal antibodies (mAbs) against EGFR are currently used for therapy of recurrent or metastatic disease; however, their mode of action is not completely understood. To investigate the immunological effects of anti-EGFR mAb, we generated a three-dimensional spheroid model of EGFR-expressing SCCHN and used this model to study the effect of anti-EGFR mAb on leukocyte migration toward tumors. Pretreatment with the blocking anti-EGFR mAb EMD 72000, its F(ab')2 fragments or an EGFR tyrosine kinase inhibitor led to substantially increased leukocyte infiltration into EGFR overexpressing tumor spheroids, but not into those with low EGFR expression. Nonblocking anti-EGFR mAb or fibroblast-specific mAb did not affect leukocyte infiltration, suggesting that the observed increase in leukocyte infiltration depends on interference with EGFR activation. Using a human cytokine macroarray, we demonstrated that the blockade of EGFR by anti-EGFR mAb in EGFR-overexpressing SCCHN cells leads to differential expression of several cytokines and chemokines, including the chemokine MCP-1/CCL-2. The significant upregulation of MCP-1/CCL2 on exposure to anti-EGFR mAb was confirmed by quantitative PCR and enzyme-linked immunospot analyses. Moreover, blocking anti-MCP-1 antibody inhibited leukocyte migration toward tumor cells induced by anti-EGFR mAb, pointing to an important role of MCP-1/CCL2 in anti-EGFR mAb-induced leukocyte migration. Our findings demonstrate that anti-EGFR mAb induces leukocyte infiltration to tumor spheroids by upregulating chemokine expression. This novel mechanism for anti-EGFR mAb action may contribute to the antitumor effects of anti-EGFR mAb in vivo.
|
|
| 6. |
- Huth, Cornelia, et al.
(författare)
-
Joint analysis of individual participants' data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index.
- 2009
-
Ingår i: Annals of medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 41:2, s. 128-38
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have investigated associations between the -174G>C single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results. AIMS: This joint analysis aimed to clarify whether IL6 -174G>C was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI). METHODS: Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P>0.1), they were combined by using the inverse-variance fixed-effect model. RESULTS: The main analysis included 9440, 7398, 24,117, or 5659 non-diabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI, or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (-0.091 mmol/L, P=0.014). There was no evidence for association between IL6 -174G>C and BMI or interleukin-6 levels, except in some subgroups. CONCLUSIONS: Our data suggest that C-allele carriers of the IL6 -174G>C polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.
|
|
| 7. |
- Karger, Stefan, et al.
(författare)
-
FOXO3a : a novel player in thyroid carcinogenesis?
- 2009
-
Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 16:1, s. 189-99
-
Tidskriftsartikel (refereegranskat)abstract
- The forkhead box transcription factor FOXO3a has recently been identified as central mediator of the cellular response to oxidative stress inducing cell cycle arrest or apoptosis. The aim of our study was to investigate the regulation of FOXO3a in the thyroid and to determine whether alterations in FOXO3a activity occur in thyroid carcinogenesis. In vitro, we demonstrate that FOXO3a activity is negatively regulated by the PI3K/Akt cascade promoting increased phosphorylation and cytoplasmatic accumulation of FOXO3a with decreased transcription of the target genes p27kip (CDKN1B) and Bim (BCL2L11), but increased expression of GADD45A. By contrast, we show that H(2)O(2) exposure activates FOXO3a in thyrocytes with JNK (MAPK8)-mediated nuclear accumulation of FOXO3a and increased expression of the cell cycle arrest genes p27kip and GADD45A. In vivo, we observed a marked cytoplasmatic accumulation of FOXO3a in differentiated thyroid cancers versus an exclusive nuclear accumulation in follicular adenoma and normal thyroid tissue. Moreover, this cytosolic accumulation of FOXO3a correlated with an increased phospho-Akt expression in thyroid malignancies and was accompanied by decreased expression of the FOXO targets p27kip and Bim and an increase in GADD45A mRNA expression in the thyroid cancers. Our data suggest FOXO3a as a novel player of cellular stress response in the thyroid, mediating the thyrocyte's fate either to survive or to undergo apoptosis. Furthermore, PI3K-dependent FOXO3a inactivation may be a novel pathomechanism for the escape from apoptosis in thyroid cancer cells, in particular in follicular thyroid carcinoma.
|
|
| 8. |
- Krause, Kerstin, et al.
(författare)
-
Evidence for a role of the amyloid precursor protein in thyroid carcinogenesis.
- 2008
-
Ingår i: The Journal of endocrinology. - 1479-6805. ; 198:2, s. 291-9
-
Tidskriftsartikel (refereegranskat)abstract
- We have recently found an increased expression of amyloid precursor protein (APP) in cold thyroid nodules that are difficult to classify as a truly benign thyroid neoplasm or a lesion with the potential for further dedifferentiation. Since differences in APP activity have been found in other human cancers, we asked whether thyroid carcinogenesis might be associated with an altered APP expression and function. APP regulation was studied in vitro in differentiated (FRTL-5) and dedifferentiated follicular thyroid carcinomas (FTC-133) thyroid cells after specific inhibition or activation of the cAMP-PKA, the PI3K/AKT or the protein kinase c (PKC) cascades. In vivo analysis of APP expression and downstream signalling was performed in benign and malignant thyroid tissues. We found that upregulation of APP expression and sAPP secretion is induced by TSH in differentiated thyroid cells and by insulin in thyroid cancer cells. PKC is a strong activator of APP cleavage and in FTC-133 confers prolonged release of the APP ectodomain. FTC-133 but not FRTL-5 cells show a prominent cell surface expression of the APP ectodomain, which has been suggested to function as an autocrine growth factor. Thyroid cancers are characterized by APP upregulation, increased membrane targeting of the APP ectodomain and significantly increased mRNA levels of the APP scaffold proteins JIP1, ShcA and Fe65.
|
|
| 9. |
- Lyra, Wladimir, 1981-
(författare)
-
Turbulence-Assisted Planetary Growth : Hydrodynamical Simulations of Accretion Disks and Planet Formation
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The current paradigm in planet formation theory is developed around a hierarquical growth of solid bodies, from interstellar dust grains to rocky planetary cores. A particularly difficult phase in the process is the growth from meter-size boulders to planetary embryos of the size of our Moon or Mars. Objects of this size are expected to drift extremely rapid in a protoplanetary disk, so that they would generally fall into the central star well before larger bodies can form.In this thesis, we used numerical simulations to find a physical mechanism that may retain solids in some parts of protoplanetary disks long enough to allow for the formation of planetary embryos. We found that such accumulation can happen at the borders of so-called dead zones. These dead zones would be regions where the coupling to the ambient magnetic field is weaker and the turbulence is less strong, or maybe even absent in some cases. We show by hydrodynamical simulations that material accumulating between the turbulent active and dead regions would be trapped into vortices to effectively form planetary embryos of Moon to Mars mass.We also show that in disks that already formed a giant planet, solid matter accumulates on the edges of the gap the planet carves, as well as at the stable Lagrangian points. The concentration is strong enough for the solids to clump together and form smaller, rocky planets like Earth. Outside our solar system, some gas giant planets have been detected in the habitable zone of their stars. Their wakes may harbour rocky, Earth-size worlds.
|
|
| 10. |
- Mustafa, Tarek, et al.
(författare)
-
Expression of the epidermal growth factor seven-transmembrane member CD97 correlates with grading and staging in human oral squamous cell carcinomas
- 2005
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 14:1, s. 108-119
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The oral squamous cell carcinoma (OSCC) is the sixth most common malignant tumor worldwide. No significant better progress has been made in the treatment of OSCCs during the last decades. The heterodimeric CD97 protein is a epidermal growth factor seven-transmembrane family member and was identified as a dedifferentiation marker in thyroid carcinomas. Nothing is known about CD97 in OSCCs. Material andMETHODS: Employing UV-laser microdissection, CD97 and its ligand CD55 were investigated in normal oral mucosa and OSCCs (n = 78) by multiplex reverse transcription-PCR. Frozen sections were investigated by immunohistochemistry. The effects of retinoic acid and sodium butyrate on the CD97/CD55 expression in OSCC cell lines were determined by quantitative PCR, immunocytochemistry, and flow cytometry.RESULTS: Weak CD97 transcripts were expressed in normal mucosa and normal basal epithelial cells revealed specific CD97 immunostaining. Strong CD97 transcripts were detected in pT(3)/T(4) and G3/G4 OSCC tissues, whereas pT(1)/T(2) and G1/G2 carcinomas revealed weak CD97 transcript levels. A weak CD97 immunostaining was observed in pT(1)/T(2) and G1/G2 tumors. By contrast, intensive CD97 immunostaining was detected in pT(3)/T(4) OSCCs and G3/G4 lesions. CD55 gene expression was low in normal mucosa. All OSCCs, irrespective of stage and grading, displayed strong CD55 immunostaining. Sodium butyrate and retinoic acid inhibited CD97 mRNA and protein in OSCC cell lines. Interestingly, CD55 was up-regulated by both substances.CONCLUSION: We identified CD97 as a novel marker of dedifferentiated OSCC. Interaction of CD97 and CD55 may facilitate adhesion of OSCC cells to surrounding surfaces that would result in metastases and bad prognosis.
|
|
