Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans. Also, perspectives for further improvement of tolerogenic cell preparation towards enhanced suppressive activity and stability of the cells will be discussed.
- MeSH
- Autoimmunity drug effects immunology MeSH
- Cell- and Tissue-Based Therapy methods MeSH
- Diabetes Mellitus, Type 1 immunology therapy MeSH
- Immune Tolerance drug effects immunology MeSH
- Immunosuppressive Agents administration & dosage MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Organic Chemicals administration & dosage MeSH
- T-Lymphocytes, Regulatory drug effects immunology MeSH
- Arthritis, Rheumatoid immunology therapy MeSH
- Multiple Sclerosis immunology therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Seminars in oncology, ISSN 0093-7754 vol. 26, no. 5, suppl. 16, October 1999
77 s. : il., tab. ; 28 cm
BACKGROUND: Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. PATIENTS AND METHODS: The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. RESULTS: Median progression-free and overall survival were 12.9 (95% confidence interval(CI)=11.0-14.8) months and 33.2 (95% CI=29.9-36.4) months, respectively. Overall response rate and disease control rate were 25.1% and 57.4%, respectively. Adverse events led to discontinuation of treatment in 37 (12.1%) patients. CONCLUSION: The results confirm that pazopanib is an effective and safe first-line targeted treatment in patients with mRCC. Both the International mRCC Database Consortium and the Memorial Sloan Kettering models were valid predictors of prognosis and nephrectomy was associated with improved survival.
- MeSH
- Databases, Factual MeSH
- Adult MeSH
- Indoles therapeutic use MeSH
- Angiogenesis Inhibitors adverse effects therapeutic use MeSH
- Carcinoma, Renal Cell drug therapy pathology surgery MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms drug therapy pathology surgery MeSH
- Nephrectomy MeSH
- Disease-Free Survival MeSH
- Proto-Oncogene Proteins c-kit antagonists & inhibitors MeSH
- Pyrimidines adverse effects therapeutic use MeSH
- Pyrroles therapeutic use MeSH
- Receptors, Platelet-Derived Growth Factor antagonists & inhibitors MeSH
- Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors MeSH
- Registries MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sulfonamides adverse effects therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Metabolic flux investigations of cells and tissue samples are a rapidly advancing tool in diverse research areas. Reliable methods of data normalization are crucial for an adequate interpretation of results and to avoid a misinterpretation of experiments and incorrect conclusions. The most common methods for metabolic flux data normalization are to cell number, DNA and protein. Data normalization may be affected by a variety of factors, such as density, healthy state, adherence efficiency, or proportional seeding of cells. The mussel-derived adhesive Cell-Tak is often used to immobilize poorly adherent cells. Here we demonstrate that this coating strongly affects the fluorescent detection of DNA leading to an incorrect and highly variable normalization of metabolic flux data. Protein assays are much less affected and cell counting can virtually completely remove the effect of the coating. Cell-Tak coating also affects cell shape in a cell line-specific manner and may change cellular metabolism. Based on these observations we recommend cell counting as a gold standard normalization method for Seahorse metabolic flux measurements with protein content as a reasonable alternative.
- MeSH
- DNA * MeSH
- Membrane Proteins * MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Biosensing Techniques * methods instrumentation MeSH
- Equipment Design MeSH
- Electrochemical Techniques instrumentation MeSH
- Carbamazepine MeSH
- Lab-On-A-Chip Devices MeSH
- Microelectrodes MeSH
- Microfluidic Analytical Techniques * methods instrumentation MeSH
- Neurons MeSH
- Neurotoxins analysis MeSH
- Drinking Water analysis MeSH
Cell immunocapture microfluidic devices represent a rapidly developing field with many potential applications in medical diagnostics. The core of such approach lies in the cell binding to antibody coated surfaces through their surface receptors. Here we show, that the small recombinant protein binders (PBs) can be used for this purpose as well, with the advantage of their constructional flexibility, possibility of fusion with range of tags and cheap mass production. For this purpose, two different PBs derived from Albumin Binding Domain (ABDwt) of streptococcal protein G, so called REX and ARS ligands with proved high affinity and selectivity to the human interleukin-23 (IL-23R) and IL-17 receptor A were used. Four PBs variants recognizing two different epitopes on two different receptors and two PBs variants binding to the same epitope on one receptor but having different peptide spacer with Avitag sequence necessary for their immobilization on sensor surface were tested for cell-capture efficiency. The glass microfluidic Y-system with planar immunocapture channel working in so-called stop-flow dynamic regime was designed. Up to 60-74% immunocapture efficiency of model THP-1 cells on REX/ARS surfaces and practically no cell binding on control ABDwt surfaces was achieved. Moreover, the specific immunocapture of THP-1 cells from mixture with IL-17RA negative DU-145 cells was demonstrated. We discuss the role of the epitope, affinity and immobilization spacer of PBs as well as the influence of stop-flow dynamic regime on the effectivity of THP-1 cell immunocapture. Results can be further exploited in design of microfluidic devices for rare cells immunocapture.
- MeSH
- Biosensing Techniques * MeSH
- Humans MeSH
- Microfluidics MeSH
- Neoplastic Cells, Circulating * MeSH
- Receptors, Interleukin-17 MeSH
- Recombinant Proteins genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
PURPOSE: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS: Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P < .001), relative to cryoablation. Of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P = .5) relative to cryoablation. CONCLUSIONS: Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.
- MeSH
- Carcinoma, Renal Cell * surgery MeSH
- Humans MeSH
- Kidney Neoplasms * surgery MeSH
- Hot Temperature MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
