| 11. |
|
|
| 12. |
- Mattila, Mirjami M., et al.
(author)
-
Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells
- 2006
-
In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 253:1-2, s. 36-43
-
Journal article (peer-reviewed)abstract
- In the search for androgen target genes responsible for malignant growth in S115 mouse mammary tumor cells we found that thrombospondin 1 (TSP1) expression was strongly downregulated by testosterone (Te). Experiments with cycloheximide suggested that Te repression of TSP1 was dependent on de novo protein synthesis. TSPI repression by Te was preceded by the induction of fibroblast growth factor 8 (FGF8) expression. FGF8 has previously been shown to mediate androgen effects on proliferation of S 115 cells by autocrine/paracrine mechanisms. It has also been shown to increase breast cancer cell growth as tumors in nude mice and to stimulate tumor angiogenesis. We studied here the possibility that FGF8 belonged to the Te-induced de novo synthesized proteins that mediate the effect of Te on TSP1 expression in these cells. We found that addition of FGF8b to in vitro cultures or ectopic expression of FGF8b in S115 cells repressed TSP1 expression at mRNA and protein levels even in the absence of Te. FGF2, another angiogenic member of FGF family, also downregulated TSPI mRNA level in the in vitro cultures of S115 cells. The antisense oligonucleotides for FGF8 did not, however, prevent Te-repression of TSP1 mRNA expression and a neutralizing anti-FGF8b antibody only partially opposed Te induced downregulation of TSP1. These results suggest that both androgen and FGF8 inhibit TSP1 expression independently. They also suggest that opposite to many other androgen-induced responses in S115 cells, the effect of Te on the expression TSP1 is not mediated by FGF8.
|
|
| 13. |
- Sentenac, M, et al.
(author)
-
Maternal education and language development at 2 years corrected age in children born very preterm: results from a European population-based cohort study
- 2020
-
In: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 74:4, s. 346-353
-
Journal article (peer-reviewed)abstract
- Socioeconomic factors influence language development in the general population, but the association remains poorly documented in children born very preterm (VPT). We assessed the impact of maternal education on language development in children born VPT and effect modification by perinatal risk.MethodsData were from the Effective Perinatal Intensive Care in Europe (EPICE) population-based cohort of children born <32 weeks’ gestational age (GA) in 2011/2012. Regions from six countries (Estonia, France, Germany, Italy, Sweden and UK) used a validated short form MacArthur Developmental Communicative Inventories Checklist to assess language at 2 years corrected age. Perinatal variables were collected from clinical records. We assessed expressive language delay (ELD), defined as (a) not combining words; and (b) expressive vocabulary <10th percentile of norms for age and sex. Perinatal risk (low, moderate and high) was determined using GA, small for GA and neonatal morbidities. We estimated adjusted risk ratios (aRR) of ELD by maternal education with inverse weighting to account for non-response bias.ResultsOf 2741 children, 24.6% were not combining words and 39.7% had a low expressive vocabulary. Low maternal education (lower secondary or less compared with a bachelor’s degree or more) increased risks of ELD: not combining words: aRR=1.52 (95% CI 1.36 to 1.69); low expressive vocabulary: aRR=1.25 (1.04 to 1.51). For children with low perinatal risk, the aRR were 1.88 (1.26 to 2.80) and 1.44 (1.06 to 1.95), respectively, compared with those with high perinatal risks: 1.36 (1.10 to 1.67) and 1.11 (0.97 to 1.27), respectively.ConclusionLow maternal education affects ELD for children born VPT, although the association appears attenuated among those with highest perinatal risk.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Elo, Teresa D., et al.
(author)
-
Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice
- 2010
-
In: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 12:11, s. 94-915
-
Journal article (peer-reviewed)abstract
- Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelial morphology progressing from atypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.
|
|
| 17. |
|
|
| 18. |
- Johansson, BL, et al.
(author)
-
C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients
- 2004
-
In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:1, s. E14-E19
-
Journal article (peer-reviewed)abstract
- Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.
|
|
| 19. |
- Keskitalo, S, et al.
(author)
-
Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
- 2019
-
In: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
-
Journal article (other academic/artistic)abstract
- Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
|
|
| 20. |
|
|
