| 1. |
- Kauppila, Joonas H, et al.
(författare)
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Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. Results: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0–3.1). MTCO1 expression was not correlated to clinicopathological variables or survival. Materials and Methods: MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated. Conclusions: Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.
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| 2. |
- Kauppila, Joonas H, et al.
(författare)
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Tenascin-C and fibronectin in normal esophageal mucosa, Barrett's esophagus, dysplasia and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. RESULTS: Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin. METHODS: Tenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated. CONCLUSIONS: Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett's esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
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| 3. |
- Mäkelä, Olli, et al.
(författare)
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Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate.
- 2003
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 62:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits.METHODS: The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([(166)Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [(35)]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples.RESULTS: Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [(166)Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [(166)Ho]FHMA radiosynovectomy.CONCLUSIONS: [(166)Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen--for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.
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| 4. |
- Mäkelä, Olli, et al.
(författare)
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Effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate on adult equine cartilage.
- 2004
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 31:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate (166Ho-FHMA) on articular cartilage in 6 adult horses.METHODS: Arthritic changes and mechanical properties of articular cartilage were evaluated with arthroscopy and postmortem microscopic analyses. Glycosaminoglycan content was measured by safranin-O staining combined with digital densitometry, uronic acid analyses, and dimethylene blue binding assay. 35S-sulfate labeling and autoradiography were used to localize proteoglycan synthesis and to characterize proteoglycan structures using SDS-agarose gel electrophoresis. Northern hybridizations were performed to measure the mRNA levels for aggrecan and pro-a1(II) collagen in cartilage samples.RESULTS: Histological signs of degeneration were present in the articular cartilage of both control and radiosynovectomized equine joints. Radiosynovectomy did not aggravate degenerative changes or significantly alter the matrix glycosaminoglycan content. A slightly decreased size of proteoglycan monomers was observed 2 months after 166Ho-FHMA radiosynovectomy. Tissue analysis of extracted proteoglycans revealed lower 35S incorporation after radiosynovectomy, but corresponding changes could not be observed in aggrecan mRNA levels. Transient downregulation of pro-a1(II) collagen mRNA transcription was observed 5 days after 166Ho-FHMA radiosynovectomy.CONCLUSION: 166Ho-FHMA treatment did not markedly affect the composition or morphology of adult articular cartilage showing mild degeneration. However, minor degradation of proteoglycan monomers and transient downregulation of pro-a1(II) collagen mRNA were observed.
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