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- Femel, Julia, 1986-, et al.
(författare)
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Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer.
- 2014
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:23, s. 12418-12427
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic vaccination targeting self-molecules is an attractive alternative to monoclonal antibody-based therapies for cancer and various inflammatory diseases. However, development of cancer vaccines targeting self-molecules has proven difficult. One complicating factor is that tumor cells have developed strategies to escape recognition by the immune system. Antigens specifically expressed by the tumor vasculature can therefore provide alternative targets. The alternatively spliced extra domain-A and B (ED-A and ED-B) of fibronectin are expressed during vasculogenesis in the embryo, but essentially undetectable under normal conditions in the adult. However, these domains are re-expressed during tumor angiogenesis and matrix remodeling, which renders them highly interesting for targeted cancer therapies. Using the MMTV-PyMT transgenic model of metastatic mammary carcinoma, we show that tumor burden can be significantly decreased by immunization against ED-A in a therapeutic setting. Furthermore, we found that in mice carrying anti-ED-A antibodies the number of metastases was reduced. ED-A immunization increased infiltration of macrophages and compromised tumor blood vessel function. These findings implicate an attack of the tumor vasculature by the immune system, through a polyclonal antibody response. We conclude that tumor vascular antigens are promising candidates for development of therapeutic vaccines targeting growth of primary tumors as well as disseminated disease.
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- Lundgren, Markus, et al.
(författare)
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Reduced morbidity at diagnosis and improved glycemic control in children previously enrolled in DiPiS follow-up
- 2014
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 15:7, s. 494-501
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Children participating in longitudinal type 1 diabetes prediction studies were reported to have less severe disease at diabetes diagnosis. Our aim was to investigate children who from birth participated in the Diabetes Prediction in Skane (DiPiS) study for metabolic status at diagnosis and then continued to be followed for 2 yr of regular clinical care. Methods: Children, followed in DiPiS before diagnosis, were compared to children in the same birth cohort, who did not participate in follow-up. Metabolic status, symptoms at diagnosis as well as hemoglobin A1c (HbA1c) and doses of insulin at 3, 6, 12, and 24 months after diagnosis were compared. Results: Children, followed in DiPiS and diagnosed at 2-12 yr of age, had 0.8% (9 mmol/mol) lower HbA1c at diagnosis than those who were not followed (p=0.006). At diagnosis, fewer DiPiS children had symptoms (p=0.014) and ketoacidosis at diagnosis were reduced (2% compared to 18%, p=0.005). During regular clinical care, HbA1c levels for the DiPiS children remained lower both at 12 (0.4% (4 mmol/mol); p=0.009) and 24 months (0.8% (9 mmol/mol) p < 0.001) after diagnosis, despite no difference in total daily insulin between the two groups. Conclusions: Participation in prospective follow-up before diagnosis of type 1 diabetes leads to earlier diagnosis with fewer symptoms, decreased incidence of ketoacidosis as well as better metabolic control up to 2 yr after diagnosis. Our data indicate that metabolic control at the time of diabetes diagnosis is important for early metabolic control possibly affecting the risk of long-term complications.
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