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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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- Helminen, O, et al.
(författare)
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Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett's esophagus: a matched case-control study
- 2022
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 481:3, s. 467-476
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Tidskriftsartikel (refereegranskat)abstract
- Barrett’s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett’s metaplasia and low-grade dysplasia. This was a retrospective matched case–control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett’s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett’s metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett’s metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett’s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd’s ratio 6.7, 95% CI 1.8–24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case–control study, p53 expression associated with a high risk of malignant progression in Barrett’s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.
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- Helminen, O, et al.
(författare)
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Preoperative esophageal stenting and short-term outcomes of surgery for esophageal cancer in a population-based study from Finland and Sweden
- 2019
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Ingår i: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. - : Oxford University Press (OUP). - 1442-2050. ; 32:11
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Tidskriftsartikel (refereegranskat)abstract
- Population-based studies examining whether preoperative esophageal stenting influences the short-term outcomes after esophagectomy for esophageal cancer are lacking. This nationwide cohort combining data from Finland and Sweden was conducted to cover this gap. Patients with locally advanced esophageal cancer (T ≥ 3 and/or N ≥ 1, M0) who underwent esophagectomy between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. The study exposure was preoperative stenting. The primary outcomes were 30- and 90-day mortality. Secondary outcomes were length of hospital stay and 30- and 90-day readmission rates. Multivariable Cox and linear regression analyses provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, comorbidity, tumor histology, year of surgery, and country. Of all 1029 participating patients who underwent surgery for locally advanced esophageal cancer, 127 (12.3%) had an esophageal stent inserted preoperatively. The absolute 30-day mortality rates were higher in stented patients (3.9%) than in those without a stent (1.6%), but the HR was not statistically significantly increased (HR 2.42; 95% CI 0.85–6.92). Similarly, the absolute 90-day mortality rates were increased after preoperative stenting (11.8%) compared to no stenting (7.0%), but again the HR was not statistically significantly increased (HR 1.68; 95% CI 0.95–2.98). Preoperative stenting did not influence length of hospital stay or readmission rates. The possibly increased short-term mortality after preoperative stenting in patients who undergo esophagectomy for esophageal cancer indicated in this study suggests a cautious approach to preoperative stenting until future research or meta-analyses provide a more definite answer.
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- Kemi, N, et al.
(författare)
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Immune Cell Infiltrate and Prognosis in Gastric Cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine and compare the prognostic value of immune cell score (ICS) and Klintrup–Mäkinen (KM) grade in gastric cancer. Methods: Gastric adenocarcinoma tissues from samples of 741 patients surgically treated in two hospitals in Finland were assessed for ICS and KM grade. Cox regression with adjustment for confounders provided hazard ratios (HRs) and 95% CIs. Subgroup analyses were performed in intestinal and diffuse type subgroups. The primary outcome was 5-year overall survival. Results: High ICS was associated to longer 5-year survival (adjusted HR 0.70, 95% CI 0.52–0.94), compared to low ICS. The difference was significant in intestinal type subgroup (adjusted HR 0.54, 95% CI 0.36–0.81) but not in diffuse type subgroup (adjusted HR 0.92, 95% CI 0.58–1.46). High KM grade was an independent prognostic factor for longer 5-year overall survival (adjusted HR 0.59, 95% CI 0.45–0.77) in both intestinal (adjusted HR 0.61, 95% CI 0.44–0.85) and diffuse subgroups (adjusted HR 0.52, 95% CI 0.31–0.86). ICS and KM grade were moderately correlated (ρ = 0.425). When both immune cell score and KM grade were included in the regression analysis, only KM grade remained prognostic. Conclusions: Both ICS and KM grade are prognostic factors in gastric adenocarcinoma, but immunohistochemistry-based ICS might not have additional prognostic value over hematoxylin–eosin-based KM grade.
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- Uimonen, M, et al.
(författare)
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Reply to Li et al
- 2024
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - 1873-734X. ; 65:5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 42. |
- Vasara, Anna I, et al.
(författare)
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Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation.
- 2006
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Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584 .- 1522-9653. ; 14:10, s. 1066-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.
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