| 1. |
- Bergh Thorén, Fredrik, 1976, et al.
(author)
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Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation immunotherapy in acute myeloid leukemia.
- 2009
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In: Expert opinion on biological therapy. - : Informa Healthcare. - 1744-7682 .- 1471-2598. ; 9:9, s. 1217-23
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Research review (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Although most patients achieve complete remission (CR) after chemotherapy, the majority suffer from subsequent leukemic relapse, which is associated with poor long-term survival. Thus, new therapies to maintain CR are highly warranted. After the completion of chemotherapy, AML patients have a minimal burden of leukemic cells, which are reportedly susceptible to cytotoxic lymphocytes such as NK cells and T cells. A therapy that boosts the function of these effector cells therefore has the potential to eradicate the malignant clone in AML and prevent relapse, Here, we briefly review the literature on the role of the immune system in AML and introduce the rationale for the use of histamine dihydrochloride (HDC) in conjuction with low-dose IL-2 as relapse-preventive immunotherapy for this disease.
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| 2. |
- Berglund, S., et al.
(author)
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Advances in umbilical cord blood cell therapy : the present and the future
- 2017
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In: Expert Opinion on Biological Therapy. - : Taylor & Francis. - 1471-2598 .- 1744-7682. ; 17:6, s. 691-699
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Research review (peer-reviewed)abstract
- Introduction: Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy. Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI. It also provides an overview regarding the progress in adoptive cellular therapy using UCB. Expert opinion: UCB has been established as an important source of stem cells for HSCT. Successful strategies to overcome the limitations of UCBT, such as the limited cell numbers and naivety of the cells, are being developed, including novel methods to perform in vitro expansion of progenitor cells, and to improve their homing to the bone marrow. Promising early clinical trials of adoptive therapies with UCB cells, including non-immunological cells, are currently performed for viral infections, malignant diseases and in regenerative medicine.
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| 3. |
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| 4. |
- Borrebaeck, Carl
(author)
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Antibody microarray-based oncoproteomics
- 2006
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In: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 6:8, s. 833-838
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Journal article (peer-reviewed)abstract
- The driving force behind oncoproteomics is the belief that certain protein signatures or patterns exist that are associated with a particular malignancy. if so, the correlation of clinical parameters with defined protein expression patterns would allow us to predict disease progression and perhaps even postulate improved therapeutic modalities. The technological challenges to achieve these goals are significant, as the human proteome is not defined. No general methodological approach exists today, and human cancer can, furthermore, be divided into several disease subgroups. One potential solution to finding cancer-associated protein signatures is the emerging technology of affinity proteomics. This approach addresses some of the shortcomings of traditional proteomics and combines it with the power of microarrays. The present review focuses on the role of antibody microarrays in oncoproteomics and its potential to provide a truly proteome-wide analytical approach.
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| 5. |
- Brännström, Mats, 1958
(author)
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Womb transplants with live births: an update and the future
- 2017
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 17:9, s. 1105-1112
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Journal article (peer-reviewed)abstract
- Introduction: Absolute uterine factor infertility, with a uterine absence or presence of a nonfunctional uterus, has during the last decades been the only remaining, major group of female infertility. Uterus transplantation (UTx) has now emerged as the first therapy for these women that have traditionally been regarded as unconditionally infertile.Areas covered: This review summarizes the research preparations in several experimental animal species that paved the way for the clinical introduction of UTx. The article also describes the human UTx attempts that have been reported up until today and the several live births that have occurred after the initial UTx baby was born in 2014. Future developments in human UTx and efforts to create a bioengineered uterus are also discussed.Expert opinion: UTx has already at this early phase of experimental introduction in the human setting proved to be a highly effective treatment for absolute uterine factor infertility. The UTx procedure has now been introduced at several centers worldwide within clinical research studies and with variations in techniques. The outcome and data from these studies will further optimize the UTx procedure to become a safe and highly effective infertility treatment.
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| 6. |
- Di Giuseppe, D., et al.
(author)
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Uptake of rheumatology biosimilars in the absence of forced switching
- 2018
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 18:5, s. 499-504
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Journal article (peer-reviewed)abstract
- Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.
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| 7. |
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| 8. |
- Enell Smith, Karin, et al.
(author)
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Rationale and clinical development of CD40 agonistic antibodies for cancer immunotherapy
- 2021
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 21:12, s. 1635-1646
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Research review (peer-reviewed)abstract
- Introduction: CD40 signaling activates dendritic cells leading to improved T cell priming against tumor antigens. CD40 agonism expands the tumor-specific T cell repertoire and has the potential to increase the fraction of patients that respond to established immunotherapies. Areas covered: This article reviews current as well as emerging CD40 agonist therapies with a focus on antibody-based therapies, including next generation bispecific CD40 agonists. The scientific rationale for different design criteria, binding epitopes, and formats are discussed. Expert opinion: The ability of CD40 agonists to activate dendritic cells and enhance antigen cross-presentation to CD8+ T cells provides an opportunity to elevate response rates of cancer immunotherapies. While there are many challenges left to address, including optimal dose regimen, CD40 agonist profile, combination partners and indications, we are confident that CD40 agonists will play an important role in the challenging task of reprogramming the immune system to fight cancer.
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| 9. |
- Fishman, JM, et al.
(author)
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Airway tissue engineering
- 2011
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In: Expert opinion on biological therapy. - : Informa Healthcare. - 1744-7682 .- 1471-2598. ; 11:12, s. 1623-1635
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Journal article (peer-reviewed)
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| 10. |
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| 11. |
- Kurrikoff, Kaido, et al.
(author)
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Status update in the use of cell-penetrating peptides for the delivery of macromolecular therapeutics
- 2021
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 21:3, s. 361-370
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Research review (peer-reviewed)abstract
- Introduction In this review, recent developments and applications with cell-penetrating peptides (CPP) are discussed. CPPs are widely used tools for the delivery of various macromolecular therapeutics, such as proteins and nucleic acids. Areas covered The current review focuses on recent important advances and reports that demonstrate high clinical and translational potential. Most important clinical developments have occurred with the CPP-drug conjugate approaches that target various protein-protein interactions, and these have been highlighted subsequently. Most of the applications are targeting cancer, but recently, noteworthy advances have taken place in the field of antisense oligonucleotides and muscular dystrophies, lung targeting, and trans-BBB targeting. Expert opinion Successful applications and clinical development with the drug conjugate approaches are discussed. On the other hand, the reasons of why the nanoparticle approaches are not as far in development are analyzed.
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| 12. |
- Larsson, Olivia, et al.
(author)
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Novel strategies for the treatment of grass pollen-induced allergic rhinitis
- 2016
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 16:9, s. 1143-1150
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Research review (peer-reviewed)abstract
- Introduction: Allergic rhinitis (AR) affects over 20% of the population of Europe and the United States. Allergen immunotherapy (AIT) is currently the only form of treatment that affects symptoms and modifies the progression of disease. Established forms of AIT include subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and are widely effective, yet only 2-9% of eligible patients undergo therapy, likely due to the long duration of treatment. As a result, novel, faster forms of AIT are currently under development. Areas covered: This article provides an overview of AR and summarises the efficacy and mechanisms of established forms of AIT, highlighting the current drawbacks. We discuss novel strategies of AIT that have been developed in an attempt to tackle these limitations, including epicutaneous, intradermal and intralymphatic immunotherapy (ILIT), focusing on ILIT, the treatment that has been most comprehensively assessed. Expert opinion: Current strategies to treat AR suffer from a poor safety profile and, importantly, lack of adherence. ILIT is a faster and safer form of AIT, with a treatment regime of only 12 weeks. Further validation is required, but ILIT, with its short and comparatively inexpensive protocol, has the potential to offer disease-modifying therapy to a larger number of patients.
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| 13. |
- Ludvigsson, Johnny
(author)
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GAD-alum (Diamyd) - a new concept for preservation of residual insulin secretion
- 2010
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In: EXPERT OPINION ON BIOLOGICAL THERAPY. - : Ashley Publications. - 1471-2598 .- 1744-7682. ; 10:5, s. 787-799
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Journal article (peer-reviewed)abstract
- Importance of the field: Type 1 diabetes is a common and very serious disease. There has been very active research going on for a long time aiming at preservation of the residual insulin secretion by some kind of intervention to stop the destructive autoimmune process. This review covers a new type of immune intervention using auto-antigen treatment. Areas covered in this review: Immune interventions in type 1 diabetes have been tried during the last 30 years, this review mentions some of them, but the main topic is the use of the auto-antigen glutamic acid decarboxylase ( GAD) to create tolerance to stop the autoimmune process. The clinical trials have been performed during the last 15 years and are all covered. What the reader will gain: This review will give the reader a picture of the research behind treatment with GAD as an immune intervention in type 1 diabetes. Take home message: The key finding so far is that treatment with Diamyd (R) has not only been shown to preserve residual beta cell function in type 1 diabetes, but this treatment may be the proof in humans of a new concept of treating and perhaps even preventing autoimmune diseases.
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| 14. |
- Ludvigsson, Johnny
(author)
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GAD65: a prospective vaccine for treating Type 1 diabetes?
- 2017
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In: Expert Opinion on Biological Therapy. - : TAYLOR & FRANCIS LTD. - 1471-2598 .- 1744-7682. ; 17:8, s. 1033-1043
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Research review (peer-reviewed)abstract
- Introduction: In spite of modern techniques, the burden for patients with type 1 diabetes (T1D) will not disappear and T1D remains a life-threatening disease causing severe complications and increased mortality. We have to learn how to preserve residual insulin secretion or even increase beta cell regeneration. This would give a milder disease, simpler treatment and perhaps even cure. Thus, there are good reasons to try therapies that may preserve beta cell function.Areas covered: In this review the author reviews the literature and registered ongoing trials using GAD-alum put in relation to the high number of published different immune interventions.Expert opinion: GAD-alum treatment is safe, tolerable and easy for the patients and healthcare. It seems probable that treatment with GAD65-alum 20 mu g sc can preserve residual beta cell function in T1D, but efficacy needs to be improved. This may be achieved by the use of combination therapies and new approaches for administration.
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| 15. |
- Lässer, Cecilia, 1981
(author)
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Exosomal RNA as biomarkers and the therapeutic potential of exosome vectors.
- 2012
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 12:Sup1
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Journal article (peer-reviewed)abstract
- Introduction: Exosomes are nano-sized (40 – 100 nm), extracellular vesicles, of endosomal origin. They are released by cells and found in many body fluids, including plasma. Exosomes contain proteins, microRNAs (miRNAs), and messenger RNAs (mRNAs) that can be transferred between cells. The discovery that exosomes contain RNA, and that this encapsulated RNA could potentially be transferred over distances in vivo, reinforced the importance of exosomes in cell-to-cell communication. Areas covered: The existence of exosomes, as a naturally occurring delivery system of RNA, enables their use as both biomarkers and vectors in gene therapy. This review provides an overview of studies reporting that exosomal miRNA and mRNA in plasma can serve as a diagnostic marker in various types of cancers. In addition, the recent finding that exosomes can be used as vectors for delivery of small interfering RNA (siRNA) in mice, with therapeutic effects, is also reviewed. Expert opinion: The data reviewed here suggest that exosomal RNA has the potential to play an important role in the diagnosis, prognosis, and treatment of diseases in the future.
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| 16. |
- Lässer, Cecilia, 1981
(author)
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Exosomes in diagnostic and therapeutic applications: biomarker, vaccine and RNA interference delivery vehicle
- 2015
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 15:1, s. 103-117
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Research review (peer-reviewed)abstract
- Introduction: Cells release extracellular vesicles to their surroundings to communicate with each other. Exosomes are a subgroup of 30 – 100-nm-sized extracellular vesicles, originating from the endocytic pathway. They contain RNA molecules, proteins and lipids that can be transferred between cells. Exosomes have been found in several body fluids, indicating that this is a frequently used and tolerated system for cells to communicate RNA molecules and proteins over distances. Areas covered: It has been shown that patients with cancer have higher concentrations of exosomes in their blood and that these exosomes can carry tumor-specific molecules. Exosomes are, therefore, currently being evaluated for their potential use as biomarkers. Additionally, exosomes have been demonstrated to have the capacity to modulate immune responses. Therefore, exosomes are believed to be beneficial as a cell-free vaccine for cancer and infections. Further, as exosomes are the body’s endogenous system for transport RNA, exosomes are also evaluated for their potential use as a therapeutic RNA delivery system. This review provides an overview of studies reporting diagnostic and therapeutic potential for exosomes. Expert opinion: The data reviewed here suggest that exosomes have the potential to be used for both diagnosis and therapy for several diseases in the future.
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| 17. |
- Magalhaes, Isabelle, et al.
(author)
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Facing the future : challenges and opportunities in adoptive T cell therapy in cancer
- 2019
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In: Expert Opinion on Biological Therapy. - : Taylor & Francis Group. - 1471-2598 .- 1744-7682. ; 19:8, s. 811-827
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Journal article (peer-reviewed)abstract
- INTRODUCTION: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain.AREAS COVERED: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed.EXPERT OPINION: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. The heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.
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| 18. |
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| 19. |
- Mazzini, Letizia, et al.
(author)
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Advances in stem cell therapy for amyotrophic lateral sclerosis
- 2018
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In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 18:8, s. 865-881
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Research review (peer-reviewed)abstract
- Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies. Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies. Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.
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| 20. |
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| 21. |
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| 22. |
- Parodis, Ioannis, et al.
(author)
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Smoking reduces the efficacy of belimumab in mucocutaneous lupus.
- 2018
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In: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 18:8, s. 911-920
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Recently, we demonstrated a negative impact of smoking on belimumab efficacy in patients with systemic lupus erythematosus (SLE). Here, we particularly investigated clinical effects of belimumab and a potential impact of smoking in mucocutaneous and articular SLE.METHODS: We surveyed 62 SLE patients treated between 2011 and 2017. Evaluation included the mucocutaneous descriptors of SLEDAI-2K (rash, alopecia, mucosal ulcers; mcSLEDAI-2K), CLASI, the arthritis SLEDAI-2K descriptor (arSLEDAI-2K) and the 28-joint count.RESULTS: mcSLEDAI-2K and CLASI activity decreased from baseline to month 6 and 12 (P<0.001 for all). No worsening in CLASI damage was observed. Current or previous smokers displayed a higher probability of unchanged/worsened mcSLEDAI-2K compared to never smokers (OR: 6.4; 95% CI: 1.5-27.4; P=0.012), also after adjustment for antimalarial agents. arSLEDAI-2K scores had decreased at month 6 (P<0.001) and 12 (P<0.001). Likewise, tender and swollen 28-joint counts had improved at month 6 (P=0.010 and P<0.001, respectively) and 12 (P=0.001 for both). We observed no impact of smoking on belimumab efficacy in articular SLE.CONCLUSION: We observed a negative impact of smoking on the efficacy of belimumab in mucocutaneous SLE. In contrast, no impact of smoking on belimumab efficacy was seen in patients with articular manifestations.
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| 23. |
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| 24. |
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| 25. |
- Taylor, DA, et al.
(author)
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Ethics of bioengineering organs and tissues
- 2014
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In: Expert opinion on biological therapy. - : Informa Healthcare. - 1744-7682 .- 1471-2598. ; 14:7, s. 879-882
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Journal article (other academic/artistic)
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| 26. |
- Tolmachev, Vladimir, et al.
(author)
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Affibody molecules : potential for in vivo imaging of molecular targets for cancer therapy
- 2007
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In: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 7:4, s. 555-568
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Research review (peer-reviewed)abstract
- Targeting radionuclide imaging of tumor-associated antigens may help to select patients who will benefit from a particular biological therapy. Affibody molecules are a novel class of small (approximately 7 kDa) phage display-selected affinity proteins, based on the B-domain scaffold of staphylococcal protein A. A large library (3 x 10(9) variants) has enabled selection of high-affinity (up to 22 pM) binders for a variety of tumor-associated antigens. The small size of Affibody molecules provides rapid tumor localization and fast clearance from nonspecific compartments. Preclinical studies have demonstrated the potential of Affibody molecules for specific and high-contrast radionuclide imaging of HER2 in vivo, and pilot clinical data using indium-111 and gallium-68 labeled anti-HER2 Affibody tracer have confirmed its utility for radionuclide imaging in cancer patients.
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| 27. |
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| 28. |
- Yalcin, Arzu Didem, et al.
(author)
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Omalizumab is effective in treating severe asthma in patients with severe cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25-hydroxyvitamin D and IL-1 beta levels
- 2013
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In: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 13:9, s. 1335-1341
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Journal article (peer-reviewed)abstract
- Background: There have been concerns about the cardiovascular safety of omalizumab. less thanbrgreater than less thanbrgreater thanObjectives: In this study, the clinical status of the omalizumab receiving severe asthma patients and the cytokine expressions patterns were investigated. less thanbrgreater than less thanbrgreater thanMaterials and methods: In a pilot study described below we examined the levels of serum eosinophil cationic peptid (ECP), CD200, d-dimer, 25-hydroxyvitamin D (25(OH) D), CXCL8 and IL-1 beta in asthma patients treated with anti-IgE therapy, to explore their relationship with disease activity, and the impact of anti-IgE therapy impact on those levels. Exercise stress testing and blood samples were taken at all follow up visits from the time of first diagnosis and after 20 months of treatment during the disease remission. less thanbrgreater than less thanbrgreater thanResults: Fractional exhaled nitric oxide concentrations and serum levels of sTRAIL, sCD200, D-dimer, ECP, total IgE, IL-1 beta and Hs-CRP were decreased while CXCL8, 25(OH) D were increased after starting the treatment of anti-IgE. Our first case of a patient, who had both protein C and S deficiency and hence a high risk for thromboembolism, documents for the first time the safety of omalizumab for asthmatic patients with concurrent risk factors contributing to arteriothrombotic events. less thanbrgreater than less thanbrgreater thanConclusion: Omalizumab might be used carefully in patients with cardiovascular diseases.
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| 29. |
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| 30. |
- Andersson, Hampus, et al.
(author)
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Next-generation CD40 agonists for cancer immunotherapy
- 2024
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In: Expert Opinion on Biological Therapy. - 1471-2598. ; 24:5, s. 351-363
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Research review (peer-reviewed)abstract
- Introduction: There is a need for new therapies that can enhance response rates and broaden the number of cancer indications where immunotherapies provide clinical benefit. CD40 targeting therapies provide an opportunity to meet this need by promoting priming of tumor-specific T cells and reverting the suppressive tumor microenvironment. This is supported by emerging clinical evidence demonstrating the benefits of immunotherapy with CD40 antibodies in combination with standard of care chemotherapy. Areas covered: This review is focused on the coming wave of next-generation CD40 agonists aiming to improve efficacy and safety, using new approaches and formats beyond monospecific antibodies. Further, the current understanding of the role of different CD40 expressing immune cell populations in the tumor microenvironment is reviewed. Expert opinion: There are multiple promising next-generation approaches beyond monospecific antibodies targeting CD40 in immuno-oncology. Enhancing efficacy is the most important driver for this development, and approaches that maximize the ability of CD40 to both remodel the tumor microenvironment and boost the anti-tumor T cell response provide great opportunities to benefit cancer patients. Enhanced understanding of the role of different CD40 expressing immune cells in the tumor microenvironment may facilitate more efficient clinical development of these compounds.
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| 31. |
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| 32. |
- Magnusson, Kristina, 1979-, et al.
(author)
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ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer
- 2016
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In: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 16
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Journal article (peer-reviewed)abstract
- Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. Conclusions: ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.
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| 33. |
- Lood, Rolf, et al.
(author)
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Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes
- 2008
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In: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 8
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Journal article (peer-reviewed)abstract
- Background: Propionibacterium acnes is a commensal of human skin but is also known to be involved in certain diseases, such as acne vulgaris and infections of orthopaedic implants. Treatment of these conditions is complicated by increased resistance to antibiotics and/or biofilm formation of P. acnes bacteria. P. acnes can be infected by bacteriophages, but until recently little has been known about these viruses. The aim of this study was to identify and characterize inducible phages from P. acnes on a genetic and morphological basis. Results: More than 70% (65/92) of P. acnes isolates investigated have inducible phages, classified morphologically as Siphoviruses. The phages have a head of 55 nm in diameter and a tail of 145 155 nm in length and 9-10 nm in width. There was no difference in carriage rate of phages between P. acnes isolates from deep infections and isolates from skin. However, there was a significant lower carriage rate of phages in P. acnes biotype IB, mostly attributed to the low carriage rate of inducible phages in biotype IB isolated from deep tissue. Most phages have a strong lytic activity against all P. acnes isolates with inducible phages, but have less lytic activity against isolates that have no prophages. Phages only infected and lysed P. acnes and not other closely related propionibacteria. All phages could infect and lyse their non-induced parental host, indicating that these prophages do not confer superinfection immunity. The phages have identical protein pattern as observed on SDS-PAGE. Finally, sequencing of two phage genes encoding a putative major head protein and an amidase and showed that the phages could be divided into different groups on a genetic basis. Conclusion: Our findings indicate that temperate phages are common in P. acnes, and that they are a genetically and functionally homogeneous group of Siphoviruses. The phages are specific for P. acnes and do not seem to confer superinfection immunity.
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