| 1. |
- Dello, Nishte, et al.
(author)
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Effect of Antioxidant rA1M on Expression of Apoptosis and Oxidative-Stress-Related Genes during 177Lu-Octreotate Treatment of GOT1 Neuroendocrine Tumours
- 2021
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In: 5th European Radiation Protection Week. Book of Abstracts. Vienna, Austria, 2021, 22-25 November, p. 58.
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Conference paper (other academic/artistic)abstract
- Kidney radiotoxicity during targeted radionuclide therapy with 177Lu-octreotate in patients with neuroendocrine tumours (NETs) limits the administered activity and thereby the therapeutic response. Reducing renal side effects of radiation could allow for higher activity amounts and better tumour control, increasing the cure rate. Co-treatment with the human recombinant antioxidant α1– microglobulin (rA1M) protects against short and long-termed radiation-induced renal damage in mice treated with 177Lu-octreotate. Furthermore, co-treatment with rA1M does not affect the therapeutic effects on tumour volume in human NET GOT1-bearing mice. Purpose: The aim of this work was to investigate transcriptional regulation of genes related to apoptosis and oxidative stress in GOT1 tumours in mice at one and seven days after administration of rA1M and after treatment with 177Lu-octreotate with or without co-administration with rA1M. Methods: Adult female Balb/c mice with s.c. GOT1 tumours were i.v. injected with either 177Luoctreotate (30 MBq, n=6), rA1M (5mg/kg, n=6) or co-treatment with both (n=6). A control group was sham-treated with NaCl (n=4). RNA was extracted from tumours sampled at one or seven days after injection. Gene expression of 84 apoptosis and 84 oxidative stress-related genes were evaluated using RNA array plates and RT-qPCR. Results: RT-qPCR analysis showed higher and similar expression of apoptotic genes in the irradiated groups than rA1M administration alone on day one after injection. Corresponding result after seven days was similar but less prominent. The most affected pro-and anti-apoptotic genes were GADD45A, TNFRS10B, FADD, FAS, CASP4,6,3, BAX and BAG3, BIRC2, BIRC3, BIRC5, XIAP, NAIP, BCL2L10, BCL2L2, IGF-1R, IL-10, CFLAR, respectively. Overall, most oxidative stress genes were not significantly regulated. APOE, DUOX1, HMOX and FOXM1 were some of the most regulated genes in the oxidative stress array. The results were more similar between the irradiated groups than those in the A1M group. CYBG and MB, related to oxygen transportation, were significantly upregulated after 177Lu-octreotate and coadministration, but not after rA1M alone. Conclusions: The transcriptional regulation of the analyzed apoptosis-related genes may suggest a similar apoptotic response in irradiated and co-treated groups compared to administration of rA1M alone. Antioxidant genes were generally downregulated, indicating that antioxidant defense mechanisms were less prioritized in damaged cells.
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| 2. |
- El-Sayed, Najib M., et al.
(author)
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The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.
- 2005
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5733, s. 409-15
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
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| 3. |
- Fjellström, Daniella, et al.
(author)
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The Role of Digitalization in SMEs’ Strategy Development : The Case of Sweden
- 2020. - 1
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In: The Changing Role of SMEs in Global Business. - Cham : Palgrave Macmillan. - 9783030458317 - 9783030458300 ; , s. 65-88
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Book chapter (peer-reviewed)abstract
- The diffusion of digital technologies has enabled a notable transformation in firms’ boundaries, processes, structures, roles, and interactions. This digital revolution affects a company as a whole, thereby redefining its strategies, entrepreneurial processes, and governance mechanisms or structures. The aim of this study is to understand how digitalization affects small and medium-sized enterprises’ (SMEs’) marketing strategy. The study uses a qualitative approach with semi-structured interviews. The findings demonstrate that digital marketing tools demand few resources and have a positive effect on competitive advantage. The study contributes to our knowledge on how small enterprises develop strategy, showing that they focus on customer preferences. It also shows the benefits of SME digital marketing where digitalizing an enterprise’s marketing activities helps to reduce costs and increase dynamic capabilities to maintain competitive advantage.
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| 4. |
- Johansson, Daniella, 1983, et al.
(author)
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Comparative study of Fischer-Tropsch production and post-combustion CO2 capture at an oil refinery: Economic evaluation and GHG (greenhouse gas emissions) balances
- 2013
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In: Energy. - : Elsevier BV. - 0360-5442. ; 59, s. 387-401
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Journal article (peer-reviewed)abstract
- The impact on CO2 emissions of integrating new technologies (a biomass-to-Fischer-Tropsch fuel plant and a post-combustion CO2 capture plant) with a complex refinery has previously been investigated separately by the authors. In the present study these designs are integrated with a refinery and evaluated from the point-of-view of economics and GHG (greenhouse gas emissions) emissions and are compared to a reference refinery. Stand-alone Fischer-Tropsch fuel production is included for comparison. To account for uncertainties in the future energy market, the assessment has been conducted for different future energy market conditions. For the post-combustion CO2 capture process to be profitable, the present study stresses the importance of a high charge for CO2 emission. A policy support for biofuels is essential for the biomass-to-Fischer-Tropsch fuel production to be profitable. The level of the support, however, differs depending on scenario. In general, a high charge for CO2 economically favours Fischer-Tropsch fuel production, while a low charge for CO2 economically favours Fischer-Tropsch fuel production. Integrated Fischer-Tropsch fuel production is most profitable in scenarios with a low wood fuel price. The stand-alone alternative shows no profitability in any of the studied scenarios. Moreover, the high investment costs make all the studied cases sensitive to variations in capital costs. (C) 2013 Elsevier Ltd. All rights reserved.
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| 5. |
- Larsson, Peter, et al.
(author)
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Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.
- 2022
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22
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Journal article (peer-reviewed)abstract
- The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types. External validation was performed using a breast cancer cohort and KM plotter with four cancer types.The PSM genetic alteration frequency was high in certain cancer types (e.g. 67%; esophageal adenocarcinoma), with DNA amplification being most common. Compared with normal tissue, most PSM genes were predominantly overexpressed in cancer. Survival analysis also established a relationship with PSM gene expression and adverse clinical outcome, where PSMA1 and PSMD11 expression were linked to more unfavorable prognosis in≥30% of cancer types for both overall survival (OS) and relapse-free interval (PFI). Interestingly, PSMB5 gene expression was associated with OS (36%) and PFI (27%), and OS for PSMD2 (42%), especially when overexpressed.These findings indicate that several PSM genes may potentially be prognostic biomarkers and novel therapeutic targets for different cancer forms.
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| 6. |
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| 7. |
- Rassol, Nishte, et al.
(author)
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Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors
- 2023
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In: Scientific Reports. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the 177Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of 177Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq 177Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after 177Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of 177Lu-octreotate in GOT1 tumors.
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| 8. |
- Romiani, Arman, 1991, et al.
(author)
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Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice
- 2024
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In: Heliyon. - 2405-8440. ; 10:10
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Journal article (peer-reviewed)abstract
- Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177Lu-octreotate and 177Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177Lu-octreotate or 177Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177Lu-octreotide compared to 177Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177Lu-octreotate, respectively. 177Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8, TNSFS10, and TRADD were regulated after administration with 177Lu-octreotate. Treatment with 177Lu-octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD, and of the anti-apoptotic gene IL10 as well as the apoptosis-related gene TNF. Conclusion: 177Lu-octreotide gave somewhat better anti-tumor effects than 177Lu-octreotate. The similar effect observed in the treated groups with 177Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.
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| 9. |
- Werner Rönnerman, Elisabeth, 1970, et al.
(author)
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Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma.
- 2022
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In: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Journal article (peer-reviewed)abstract
- Ovarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior. However, the origin and molecular pathogenesis of MC are not yet fully understood. Therefore, identification of novel diagnostic markers could potentially facilitate early diagnosis of OC, particularly the MC histotype, thereby leading to the development of histotype-specific treatment regimens and improved survival rates.In the present study, Trefoil factor gene family members (TFF1, TFF2 and TFF3) were identified as MC histotype-specific biomarkers using RNA sequencing (RNA-seq) data for 95 stage I-II OCs. The diagnostic value of TFF1, TFF2 and TFF3 was then evaluated by immunohistochemistry on 206 stage I-II OCs stratified by histotype (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], clear cell carcinoma [CCC], and MC).We showed significantly elevated intracytoplasmic protein expression levels for TFF1, TFF2 and TFF3 in MC samples, thereby revealing an association between expression of Trefoil factor gene family members and the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype.Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Moreover, these novel histotype-specific diagnostic biomarkers may not only improve patient stratification of early-stage ovarian carcinomas but may also be candidates for the development of molecular targeted therapies.
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