| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Kårehed, Karin, et al.
(author)
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Fibrinogen and histidine-rich glycoprotein in early-onset preeclampsia
- 2010
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 89:1, s. 131-139
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. DESIGN: The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. SETTING: Uppsala University Hospital, Uppsala. METHODS: Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. RESULTS: Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). CONCLUSIONS: HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.
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| 3. |
- Bolin, Marie, et al.
(author)
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Prediction of Preeclampsia by Combining Serum Histidine-Rich Glycoprotein and Uterine Artery Doppler
- 2012
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In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 25:12, s. 1305-1310
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Journal article (peer-reviewed)abstract
- BackgroundPreeclampsia is associated with both maternal and perinatal morbidity and mortality. Histidine-rich glycoprotein (HRG) is a protein interacting with angiogenesis, coagulation, and inflammatory responses, processes known to be altered in preeclamptic pregnancies. Significantly lower levels of HRG have been demonstrated as early as in the first trimester in women later developing preeclampsia compared with normal pregnancies. The aim of this study was to investigate whether the combination of HRG and uterine artery Doppler ultrasonography can be used as a predictor of preeclampsia.MethodsA total of 175 women were randomly selected from a case-control study; 86 women had an uncomplicated pregnancy and 89 women later developed preeclampsia. Blood samples and pulsatility index (PI) were obtained from both cases and controls in gestational week 14.ResultsHRG levels were significantly lower in women who developed preterm preeclampsia compared with controls, but not for women developing preeclampsia in general. PI was significantly higher in the preeclampsia group compared with controls, especially in preterm preeclampsia. The combination of HRG and PI revealed a sensitivity of 91% and a specificity of 62% for preterm preeclampsia.ConclusionsThe combination of HRG and uterine artery Doppler may predict preterm preeclampsia in early pregnancy.
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| 4. |
- de Peppo, Giuseppe Maria, et al.
(author)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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In: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Journal article (peer-reviewed)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 5. |
- Femel, Julia, 1986-, et al.
(author)
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Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer.
- 2014
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:23, s. 12418-12427
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Journal article (peer-reviewed)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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| 6. |
- Harbst, Katja, et al.
(author)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Journal article (peer-reviewed)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 7. |
- Hultgren, Frances, et al.
(author)
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Forskningsprojektet KUMBA och Barnens kulturrum
- 2011
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In: Mötesplats Borås: Profession, Forskning. 19-20 oktober 2011, Högskolan i Borås. - : Högskolan i Borås: Institutionen Biblioteks- och informationsvetenskap.
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Conference paper (other academic/artistic)abstract
- Barn och unga framhålls i handlingsprogram och styrdokument ofta som prioriterade grupper, där inte minst rättigheterna för barn med funktionshinder och med annan bakgrund än den svenska framhålls. Barnbibliotek, museer och kulturskolor finns i alla kommuner och erbjuder verksamheter och upplevelser för barn. Men det sker få utvärderingar och uppföljningar av dessa verksamheter och projekt. Det saknas i stor utsträckning forskning om barn och unga som kulturkonsumenter och kulturskapare, något som uppmärksammats av såväl forskare och praktiker som politiker på regional och kommunal nivå (Rydsjö & Elf 2007). I regionala och kommunala handlingsprogram framhålls vikten av barns och ungas tillgång till kulturupplevelser och att unga ska ha verklig möjlighet till inflytande och delaktighet. (VGR 2008; 2009; Borås Stad 2004). Barns delaktighet utgör ett nytt och snabbt växande forskningsområde (Christensen & James 2000; Mayall 2002; Brembeck et al., 2010), men ännu saknas studier om barns och ungas delaktighet i kulturverksamheter (Maceviciute et al., 2009).
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| 8. |
- Olsson, Anna-Karin, 1966, et al.
(author)
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Occupational Therapists' Experience Concerning Occupational Performance in Adults With Asperger Syndrome
- 2013
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In: Occupational Therapy in Mental Health. - 0164-212X .- 1541-3101. ; 29:1, s. 42-59
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Journal article (peer-reviewed)abstract
- Persons with Asperger Syndrome often seem to have difficulty performing everyday occupations. This study aimed to describe occupational therapists’ experience concerning abilities to occupational performance among adults with Asperger Syndrome. Data were collected in interviews with eight occupational therapists and analyzed using a qualitative method. Results showed that clients with Asperger Syndrome often possess abilities but seem to have difficulties knowing when, where, and how they should use them. The ability to adapt behavior in accordance with cues from the environment was identified as the core category. Environment plays a major role in how these persons interact in different situations.
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| 9. |
- Strand, Carina, et al.
(author)
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The combination of Ki67, histological grade and estrogen receptor status identifies a low-risk group among 1,854 chemo-naive women with N0/N1 primary breast cancer
- 2013
-
In: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 2
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Journal article (peer-reviewed)abstract
- Background: The aim was to confirm a previously defined prognostic index, combining a proliferation marker, histological grade, and estrogen receptor (ER) in different subsets of primary N0/N1 chemo-naive breast cancer patients. Methods/design: In the present study, including 1,854 patients, Ki67 was used in the index (KiGE), since it is the generally accepted proliferation marker in clinical routine. The low KiGE-group was defined as histological grade 1 patients and grade 2 patients which were ER-positive and had low Ki67 expression. All other patients made up the high KiGE-group. The KiGE-index separated patients into two groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001). Discussion: We have confirmed a prognostic index based on a proliferation marker (Ki67), histological grade, and ER for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group constituting 57% of the patients, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided.
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| 10. |
- Söderlund, Karin, et al.
(author)
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Inflammation Induced by MMP-9 Enhances Tumor Regression of Experimental Breast Cancer
- 2013
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In: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:8, s. 4420-4430
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Journal article (peer-reviewed)abstract
- Matrix metalloproteinases (MMPs) have been suggested as therapeutic targets in cancer treatment, but broad-spectrum MMP inhibitors have failed in clinical trials. Recent data suggest that several MMPs including MMP-9 exert both pro-and antitumorigenic properties. This is also the case of the natural inhibitors of MMPs, tissue inhibitor of metalloproteinases (TIMPs). The inhibitor of MMP-9 is TIMP-1, and high levels of this enzyme have been associated with decreased survival in breast cancer. Inflammation is one hallmark of cancer progression, and MMPs/TIMPs may be involved in the local immune regulation. We investigated the role of MMP-9/TIMP-1 in regulating innate antitumor immunity in breast cancer. Breast cancers were established in nude mice and treated with intratumoral injections of adenoviruses carrying the human TIMP-1 or MMP-9 gene (AdMMP-9). In vivo microdialysis for sampling of cancer cell-derived (human) and stroma-derived (murine) proteins, immunostainings, as well as cell cultures were performed. We report a dose-dependent decrease of tumor growth and angiogenesis after AdMMP-9 treatment. In addition to increased generation of endostatin, AdMMP-9 promoted an antitumor immune response by inducing massive neutrophil infiltration. Neutrophil depletion prior to gene transfer abolished the therapeutic effects of AdMMP-9. Additionally, AdMMP-9 activated tumor-infiltrating macrophages into a tumor-inhibiting phenotype both in vivo and in vitro. AdMMP-9 also inhibited tumor growth in immune-competent mice bearing breast cancers. Adenoviruses carrying the human TIMP-1 gene had no effect on tumor growth or the immune response. Our novel data identify MMP-9 as a potent player in modulating the innate immune response into antitumor activities. The Journal of Immunology, 2013, 190: 4420-4430.
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