| 1. |
- Ankerst, Jaro, et al.
(author)
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Cross‐reacting tstas in adeno 7 and 12 tumors demonstrated by 51CR‐Cytotoxicity and isograft rejection tests
- 1969
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 4:3, s. 279-287
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Journal article (peer-reviewed)abstract
- Antisera of mice hyperimmunized against syngeneic X‐irradiated adeno 12 tumor cells were tested for complement‐dependent cytotoxicity against an adeno 7 and an adeno 12 hamster tumor by a 51Cr‐cytotoxic test, developed to work on non‐lymphoid target cells. Significant isotope release above the level of release obtained after exposure to control sera was recorded with both tumors. There was no similar release from BHK‐C13 control hamster cells. The cytotoxic effect on hamster adeno 7 tumor cells was confirmed by the colony inhibition technique. Furthermore, it was demonstrated by transplantation tests in mice that the hamster adeno 7 tumor cells were immunogenic, causing an isograft immunity to adeno 12 tumors similar to that induced by adeno 12 hamster and mouse tumor cells.
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| 2. |
- Ankerst, Jaro, et al.
(author)
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Demonstration of two group‐specific TSTAs in adenovirus‐induced tumors
- 1970
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 6:1, s. 84-92
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Journal article (peer-reviewed)abstract
- Infection of mice and rats with any one of five tested human adenovirus types belonging to groups A and B (types 3, 7, 12, 18 and 31) induced an immunity to the TSTAs of type 12 tumors as detected by the colony inhibition (CI) test. No immunity was found against an adenovirus type 1 tumor. Two adenovirus types belonging to group C (types 1 and 5) were similarly tested and found to induce a clear‐cut immunity to the adenovirus type 1 tumor but not to tumors induced by adenovirus of groups A and B. The only tested virus type of group D (type 4) did not induce any clear‐cut immunity to either adenovirus 12 tumors or the adenovirus 1 tumor. Immunization of rats with rat adenovirus 12 tumor cells induced a cellular immunity to adenovirus 12 mouse tumor cells but not to a mouse polyoma tumor. Adenovirus 1 rat tumor cells induced no such immunity. Immunization of rats with syngenic adenovirus 12 tumor cells induced a cellular immunity to adenovirus 12 rat and mouse tumors and an adenovirus 7 hamster tumor, but not to an adenovirus 1 rat tumor or BHK‐C13 control hamster cells. The result of a tumor prevention experiment is consistent with the existence of a common TSTA induced by types 7 and 12 and a different TSTA induced by type 5 virus. It is concluded that the highly oncogenic group A and the weakly oncogenic group B adeno virus types all induce a common TSTA. Another TSTA is induced by the group C viruses, while no evidence has been obtained for the existence of any TSTA induced by a group D virus type.
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| 3. |
- Ankerst, Jaro, et al.
(author)
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Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in rats
- 1982
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 29:6, s. 707-710
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Journal article (peer-reviewed)abstract
- Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 μg per ml of drinking water) on tumorigenesis of adenovirus‐type‐9‐induced breast fibroadenomas and on 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (I) resulted in inhibition of DMH‐induced large‐bowel carcinogenesis; (2) facilitated induction of small‐bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH‐induced largebowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.
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| 4. |
- Huang, Yi Shu, et al.
(author)
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Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:19
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Journal article (peer-reviewed)abstract
- Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.
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| 5. |
- Kjellman, Christian, et al.
(author)
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Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma
- 2000
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In: International Journal of Cancer. - 0020-7136. ; 89:3, s. 251-258
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Journal article (peer-reviewed)abstract
- Human gliomas express TGF-beta but, so far the expression of downstream mediators has been investigated in only a few cell lines. We have examined tissue specimens of 23 gliomas: 3 astrocytomas grade II (AST), 8 anaplastic astrocytomas grade III (AAST), and 12 glioblastoma multiforme grade IV (GBM). We analyzed the mRNA expression of TGF-beta1, TGF-beta2, TGF-beta3, the TGF-beta receptors type I (TbetaR-I) and type II (TbetaR-II), Smad2, Smad3, and Smad4. mRNA expression of IL-10 and CD95 (FAS/APO-1) were also studied. We detected increased mRNA levels of the 3 TGF-beta isoforms, correlating with the degree of malignancy. TGF-beta3 mRNA was increased, particularly in AST and AAST, while TGF-beta1 and TGF-beta2 mRNAs were strongly expressed in GBM. TGF-beta normally up-regulates the TGF-beta receptors, and TbetaR-I and TbetaR-II showed stronger expression in all gliomas when compared to normal tissues. However, the mRNA expression of Smad2, Smad3, and Smad4 was decreased in GBM. IL-10 mRNA expression was detected in glioma tissues but not in glioma cell lines. No marked increase in the expression of soluble CD95 splicing variants was found in the gliomas compared with normal tissue. However, total CD95 mRNA was elevated among GBM tissues.
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| 6. |
- Paulsson, Kajsa M, et al.
(author)
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Association of tapasin and COPI provides a mechanism for the retrograde transport of major histocompatibility complex (MHC) class I molecules from the Golgi complex to the endoplasmic reticulum
- 2002
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In: Journal of Biological Chemistry. - 1083-351X. ; 277:21, s. 18266-18271
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Journal article (peer-reviewed)abstract
- Tapasin is a subunit of the transporter associated with antigen processing (TAP). It associates with the major histocompatibility complex (MHC) class I. We show that tapasin interacts with beta- and gamma-subunits of COPI coatomer. COPI retrieves membrane proteins from the Golgi network back to the endoplasmic reticulum (ER). The COPI subunit-associated tapasin also interacts with MHC class I molecules suggesting that tapasin acts as the cargo receptor for packing MHC class I molecules as cargo proteins into COPI-coated vesicles. In tapasin mutant cells, neither TAP nor MHC class I are detected in association with the COPI coatomer. Interestingly, tapasin-associated MHC class I molecules are antigenic peptide-receptive and detected in both the ER and the Golgi. Our data suggest that tapasin is required for the COPI vesicle-mediated retrograde transport of immature MHC class I molecules from the Golgi network to the ER.
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| 7. |
- Sjögren, Erik, 1977-, et al.
(author)
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Optimal experimental design for assessment of enzyme kinetics in a drug discovery screening environment
- 2011
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In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 39:5, s. 858-863
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Journal article (peer-reviewed)abstract
- A penalized ED-optimal design with a discrete parameter distribution was used to find an optimal experimental design for assessment of enzyme kinetics in a screening environment. A data set for enzyme kinetic data (Vmax and Km) was collected from previously reported studies and every Vmax/Km pair (n=76) was taken to represent a unique drug compound. The design was restricted to 15 samples, an incubation time of up to 40 min and starting concentrations (C0) for the incubation between 0.01 and 100 µM. The optimization was performed by finding the sample times and C0 returning the lowest uncertainty (SE) of the model parameter estimates. Individual optimal designs (I-OD), one general optimal design (G-OD) and one for laboratory practice pragmatically modified design (OD) were obtained. In addition, a standard design (STD-D), representing a commonly applied approach for metabolic stability investigations, was constructed. Simulations were performed for OD and STD-D using the Michaelis-Menten (MM) equation and enzyme kinetic parameters were estimated both with MM and a mono exponential (EXP) decay. OD generated a better result (RSE) for 99% of the compounds and an equal or better result (RMSE) for 78% of the compounds. Furthermore, high-quality estimates (RMSE <30%) of both Vmax and Km could be obtained for a considerable number (26%) of the investigated compounds. The results presented in this study demonstrate that the output could generally be improved when compared to that obtained from the standard approaches used today.
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| 8. |
- Sjögren, Hans O., et al.
(author)
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Effect of BCG and allogeneic tumour cells on adenovirus type 12 tumorigenesis in mice
- 1969
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 221:5183, s. 863-864
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Journal article (peer-reviewed)abstract
- HAMSTERS and mice inoculated at birth with tumour viruses have been used in studies of the prophylactic effects of various treatments during the latent period. The incidence of primary tumours in hamsters infected at birth with SV40 is reduced if the virus is inoculated during the latent period1-3. Similar administration of adenovirus type 12 also inhibited the induction of tumours by SV404; this was taken as an indication of a cross-reaction between the tumour-specific transplantation antigens (TSTA) of SV40 and adeno 12 virus tumours. X-irradiated SV40 tumour cells which did not contain infectious virus were also effective in reducing the frequency of primary SV40 tumours when given at various times before tumour development2,5.
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