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- Cesano, A, et al.
(författare)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II-practical challenges
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated with the infrastructure, technology, workforce, and sustainability required for clinical biomarker data sharing. To provide guidance and assist in the navigation of these challenges, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to outline the challenges that researchers currently face, both at the conceptual level (Volume I) and at the technical level (Volume II). The committee also suggests possible solutions to these problems in the form of professional standards and harmonized requirements for data sharing, assisting in continued progress toward effective, clinically relevant biomarkers in the IO setting.
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- Rutella, S, et al.
(författare)
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Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I-conceptual challenges
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I—conceptual challenges and Volume II—practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting.
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- Sennström, Maria B., et al.
(författare)
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Human cervical ripening, an inflammatory process mediated by cytokines
- 2000
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:4, s. 81-375
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Tidskriftsartikel (refereegranskat)abstract
- An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.
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- Falconer, C, et al.
(författare)
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Different organization of collagen fibrils in stress-incontinent women of fertile age
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 77, s. 87-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to test the hypothesis that stress urinary incontinence in women is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in women of fertile age with stress urinary incontinence and in matched continent controls. All the stress-incontinent women were characterized with urodynamic investigation. In the biopsies, collagen concentration, measured as hydroxyproline, and the degree of extraction by pepsin digestion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organization was examined with transmission electron microscopy and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: The biochemical and morphological analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women. Also the organization of the collagen fibrils differed, with considerably higher cross-linking. A higher level of mRNA for collagen I and III in the incontinent group indicates that the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resulting in a significantly lower proteoglycan/collagen ratio in the incontinent group of women.CONCLUSION: Stress urinary incontinence in fertile women is associated with a change in collagen metabolism resulting in an increased concentration of collagen and larger collagen fibrils. These alterations should result in a more rigid form of extracellular matrix, suggesting a connective tissue with impaired mechanical function.
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- Falconer, C, et al.
(författare)
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Paraurethral connective tissue in stress-incontinent women after menopause
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 77:1, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group.CONCLUSION: The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.
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