| 1. |
- Augustsson, Anna, et al.
(författare)
-
Challenges in assessing the health risks of consuming vegetables in metal-contaminated environments
- 2018
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 113, s. 269-280
-
Tidskriftsartikel (refereegranskat)abstract
- A great deal of research has been devoted to the characterization of metal exposure due to the consumption of vegetables from urban or industrialized areas. It may seem comforting that concentrations in crops, as well as estimated exposure levels, are often found to be below permissible limits. However, we show that even a moderate increase in metal accumulation in crops may result in a significant increase in exposure. We also highlight the importance of assessing exposure levels in relation to a regional baseline. We have analyzed metal (Pb, Cd, As) concentrations in nearly 700 samples from 23 different vegetables, fruits, berries and mushrooms, collected near 21 highly contaminated industrial sites and from reference sites. Metal concentrations generally complied with permissible levels in commercial food and only Pb showed overall higher concentrations around the contaminated sites. Nevertheless, probabilistic exposure assessments revealed that the exposure to all three metals was significantly higher in the population residing around the contaminated sites, for both low-, medianand high consumers. The exposure was about twice as high for Pb and Cd, and four to six times as high for As. Since vegetable consumption alone did not result in exposure above tolerable intakes, it would have been easy to conclude that there is no risk associated with consuming vegetables grown near the contaminated sites. However, when the increase in exposure is quantified, its potential significance is harder to dismiss - especially when considering that exposure via other routes may be elevated in a similar way.
|
|
| 2. |
- Adman, Per, et al.
(författare)
-
171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
|
|
| 3. |
- Karlsson, Terese, 1979-, et al.
(författare)
-
LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease
- 2018
-
Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 174-184
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.
|
|
| 4. |
- Karlsson, Terese, 1979-
(författare)
-
The expression and molecular functions of LRIG proteins in cancer and psoriasis
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The leucine-rich repeats and immunoglobulin-like domains (LRIG) family consists of three integral membrane proteins that are important in human cancer. LRIG1 is a negative regulator of growth factor signaling. Its expression is associated with longer survival in several cancer types, and the gene has been shown to function as a tumor suppressor. The roles of LRIG2 and LRIG3 are less well known. The aim of this thesis was to improve our understanding of the expression and function of the LRIG protein family in psoriasis and cancer.To investigate their expression in psoriasis, the mRNA levels and subcellular localization of the LRIG proteins were analyzed and compared between normal and psoriatic human skin. There were no differences in the LRIG mRNA levels between psoriatic and normal skin samples. However, the subcellular localization of all three LRIG proteins differed between psoriatic and normal skin.To study the physiological and molecular functions of Lrig2, we generated Lrig2E12-/- mice. These mice were viable and born at a Mendelian rate, but Lrig2E12-/- mice had an increased rate of spontaneous mortality and a transient reduction in growth rate compared to Lrig2 wild-type (wt) mice. In an orthotopic platelet-derived growth factor (PDGF)B-driven brain tumor mouse model, we studied the effect of Lrig2 on gliomagenesis. All Lrig2 wt mice developed tumors; 82% developed grade II/III tumors, and 18% developed grade IV tumors. Only 77% of the Lrig2E12-/- mice developed tumors, and they were all grade II/III tumors. Thus, Lrig2 increased the incidence and malignancy rates of PDGFB-driven gliomas. We then analyzed the effect of Lrig2 on Pdgf receptor (Pdgfr) signaling. Lrig2 had no effect on Pdgfr steady-state levels, the starvation-induced up-regulation of Pdgfrs, the phosphorylation of Pdgfrs, primary cilium formation or the PDGFBB-induced phosphorylation of Akt or Erk1/2. However, the kinetics of induction of the immediate-early genes Fos and Egr2 were altered, resulting in a more rapid induction in Lrig2E12-/- cells.We then analyzed the clinical and biological importance of LRIG1 in lung cancer. In a human lung cancer tissue micro-array (TMA), LRIG1 expression was found to be an independent positive prognostic factor for adenocarcinoma. To study the importance of Lrig1 regarding lung cancer development in vivo, we used an inducible EGFRL858R-driven mouse lung cancer model. The mice developed diffuse lung adenocarcinoma, and the tumor burden was greater in Lrig1-/- mice than in Lrig1+/+ mice (p = 0.025) at 60 days. The human lung cancer cell line H1975, with either normal or Tet-induced expression of LRIG1, was injected into the flanks of Balb/cA nude mice. Tumors formed by LRIG1-overexpressing cells were smaller than those formed by parental cells, further indicating that LRIG1 is important during lung tumor formation or growth. In vitro, LRIG1 suppressed the proliferation of H1975 cells and down-regulated the phosphorylation of MET and RET.To investigate the molecular functions of LRIG proteins further, we performed a yeast two-hybrid (YTH) screen using a peptide from the cytosolic tail of LRIG3 as bait. This screen identified LMO7 and LIMCH1 as prominent interaction partners for LRIG3. Proximity ligation assays showed that LMO7 interacted with all of the LRIG proteins at endogenous expression levels. LMO7 and LIMCH1 were expressed in all human tissues analyzed. Their expression was dramatically decreased in lung cancer compared to normal lung tissue. The expression of LMO7 was analyzed in a human lung cancer TMA. LMO7 was expressed in respiratory epithelial cells in normal lungs. However, LMO7 was only expressed in a quarter of the lung tumors. LMO7 expression was found to be an independent negative prognostic factor for lung cancer.In summary, we found that the LRIG proteins were redistributed in psoriatic skin. In a mouse glioma model, Lrig2 promoted oligodendroglioma genesis. LRIG1 was an independent positive prognostic factor in human lung cancer. Lrig1 ablation increased the tumor size in an EGFRL858R-driven lung cancer mouse model. LRIG1 expression decreased the tumor growth of human lung cancer cells in a xenograft mouse model. LMO7 interacted with all three LRIG proteins and was an independent negative prognostic factor in human lung cancer. These data demonstrate the importance of LRIG proteins in human disease.
|
|
| 5. |
- Kvarnbrink, Samuel, et al.
(författare)
-
LRIG1 is a prognostic biomarker in non-small cell lung cancer
- 2015
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 1651-226X .- 0284-186X. ; 54:8, s. 1113-1119
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins are involved in the regulation of cellular signal transduction. LRIG1 is an endogenous inhibitor of receptor tyrosine kinases (RTKs) and an emerging tumor suppressor. In the lung epithelium, the expression of LRIG1 is downregulated by tobacco smoking, and further downregulated in lung squamous cell carcinoma. Material and methods. The expression of LRIG proteins were analyzed in 347 cases of non-small cell lung cancer (NSCLC) by immunohistochemistry, and LRIG1 mRNA expression was evaluated in 807 lung cancer samples in silico in the Oncomine database. Potential associations between the expression data and the clinical parameters, including patient survival, were investigated. Results. Expression of the LRIG1 protein was found to be an independent prognostic factor in NSCLC, whereas expression of LRIG2 or LRIG3 did not correlate with patient survival. The levels of LRIG1 mRNA also correlated with the survival of NSCLC patients. Conclusion. These findings demonstrate that LRIG1 is an independent prognostic factor in patients with NSCLC that could be important in future decision-making algorithms for adjuvant lung cancer treatment.
|
|
