| 1. |
|
|
| 2. |
- Zor, K., et al.
(author)
-
A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection
- 2014
-
In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 4:109, s. 63761-63771
-
Journal article (peer-reviewed)abstract
- Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.
|
|
| 3. |
|
|
| 4. |
- Stangegaard, M., et al.
(author)
-
A biocompatible micro cell culture chamber (microCCC) for the culturing and on-line monitoring of eukaryote cells
- 2006
-
In: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 6:8, s. 1045-1051
-
Journal article (peer-reviewed)abstract
- We have previously shown that a polymeric (PMMA) chip with medium perfusion and integrated heat regulation provides sufficiently precise heat regulation, pH-control and medium exchange to support cell growth for weeks. However, it was unclear how closely the cells cultured in the chip resembled cells cultured in the culture flask. In the current study, gene expression profiles of cells cultured in the chip were compared with gene expression profiles of cells cultured in culture flasks. The results showed that there were only two genes that were differently expressed in cells grown in the cell culture chip compared to cell culture flasks. The cell culture chip could without further modification support cell growth of two other cell lines. Light coming from the microscope lamp during optical recordings of the cells was the only external factor identified, that could have a negative effect on cell survival. Low grade light exposure was however compatible with optical recordings as well as cell viability. These results strongly indicate that a cell culture chip could be constructed that allowed for on-line optical recording of cellular events without affecting the cell culturing condition compared to cell cultured in culture flasks incubated in a dark and CO 2 conditioned incubator. © The Royal Society of Chemistry 2006.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Huuhtanen, Jani, et al.
(author)
-
IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
- 2022
-
In: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
-
Journal article (peer-reviewed)abstract
- In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
|
|
| 14. |
|
|
| 15. |
- Piehl, F., et al.
(author)
-
Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis The RINOMAX Randomized Clinical Trial
- 2022
-
In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
-
Journal article (peer-reviewed)abstract
- IMPORTANCE Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. OBJECTIVE To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. INTERVENTIONS Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. MAIN OUTCOMES AND MEASURES Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. RESULTS Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. CONCLUSIONS AND RELEVANCE A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.
|
|
