| 1. |
- Agathangelidis, Andreas, et al.
(author)
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High-Throughput immunogenetics for precision medicine in cancer
- 2022
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In: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 84, s. 80-88
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Journal article (peer-reviewed)abstract
- Cancer is characterized by an extremely complex biological background, which hinders personalized therapeutic interventions. Precision medicine promises to overcome this obstacle through integrating information from different 'subsystems', including the host, the external environment, the tumor itself and the tumor microenvironment. Immunogenetics is an essential tool that allows dissecting both lymphoid cancer ontogeny at both a cell-intrinsic and a cell-extrinsic level, i.e. through characterizing micro-environmental interactions, with a view to precision medicine. This is particularly thanks to the introduction of powerful, high-throughput approaches i.e. next generation sequencing, which allow the comprehensive characterization of immune repertoires. Indeed, NGS immunogenetic analysis (Immune-seq) has emerged as key to both understanding cancer pathogenesis and improving the accuracy of clinical decision making in oncology. Immune-seq has applications in lymphoid malignancies, assisting in the diagnosis e.g. through differentiating from reactive conditions, as well as in disease monitoring through accurate assessment of minimal residual disease. Moreover, Immune-seq facilitates the study of T cell receptor clonal dynamics in critical clinical contexts, including transplantation as well as innovative immunotherapy for solid cancers. The clinical utility of Immune-seq represents the focus of the present contribution, where we highlight what can be achieved but also what must be addressed in order to maximally realize the promise of Immune-seq in precision medicine in cancer.
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| 2. |
- Agathangelidis, Andreas, et al.
(author)
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Unlocking the secrets of immunoglobulin receptors in mantle cell lymphoma : Implications for the origin and selection of the malignant cells
- 2011
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In: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X .- 1096-3650. ; 21:5, s. 299-307
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Research review (peer-reviewed)abstract
- Immunogenetic analysis of mantle cell lymphoma (MCL) has offered important evidence helping to decipher the immune pathways leading to its development and also prompting a reappraisal of the views about its ontogeny. In particular, older and more recent studies have demonstrated that MCL is characterized by a highly distinctive immunoglobulin gene repertoire with remarkable predominance of the IGHV3-21 and IGHV4-34 genes; restricted associations of IGHV,IGHD and IGHJ genes, culminating in the creation of quasi-identical ("stereotyped") heavy complementarity-determining region 3 sequences in roughly 10% of cases; and, very precisely targeted and, probably, functionally driven somatic hypermutation, ranging from minimal (in most cases) to pronounced. Furthermore, comparison to other entities, in particular CLL, revealed that several of these immunogenetic features are "MCL-biased". On these grounds, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases.
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| 3. |
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| 4. |
- Alzrigat, Mohammad, et al.
(author)
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Epigenetics in multiple myeloma : From mechanisms to therapy
- 2018
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In: Seminars in Cancer Biology. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1044-579X .- 1096-3650. ; 51, s. 101-115
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Research review (peer-reviewed)abstract
- Multiple myeloma (MM) is a tumor of antibody producing plasmablasts/plasma cells that resides within the bone marrow (BM). In addition to the well-established role of genetic lesions and tumor-microenvironment interactions in the development of MM, deregulated epigenetic mechanisms are emerging as important in MM pathogenesis. Recently, MM sequencing and expression projects have revealed that mutations and copy number variations as well as deregulation in the expression of epigenetic modifiers are characteristic features of MM. In the past decade, several studies have suggested epigenetic mechanisms via DNA methylation, histone modifications and non-coding RNAs as important contributing factors in MM with impacts on disease initiation, progression, clonal heterogeneity and response to treatment. Herein we review the present view and knowledge that has accumulated over the past decades on the role of epigenetics in MM, with focus on the interplay between epigenetic mechanisms and the potential use of epigenetic inhibitors as future treatment modalities for MM.
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| 5. |
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| 6. |
- Axelson, Håkan, et al.
(author)
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Renal stem cells and their implications for kidney cancer.
- 2013
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In: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 23:1, s. 56-61
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Research review (peer-reviewed)abstract
- The renal cell carcinomas (RCC) denote a diverse set of neoplasias with unique genetic and histological features. The RCCs emanate from the renal tubule, a highly heterogeneous epithelial structure, and depending on which cell is malignified the resulting cancer displays unique characteristics. Notwithstanding this, the cells of origin for the RCC forms are far from established, and only inferred by the accumulated weight of marker similarities, not always providing an unequivocal picture. The tubular epithelium is normally mitotically quiescent, but demonstrates a considerable regenerative capacity upon renal injury. Recently the hypothesis that regeneration is driven by adult stem cells has been added experimental support, providing further complexity to the issue of renal carcinogenesis. Whether these cells are linked to RCC is an open question. In the present review we therefore present the prevailing theories regarding kidney regeneration, since a better understanding of this process might be of relevance when considering the different malignancies that arise from kidney epithelium. Our own results show that papillary renal cell carcinoma displays considerable similarities to proximal tubular progenitor cells and we suggest that this tumor form may develop in a multi-step fashion via benign renal adenomas. The putative connection between renal stem cells and carcinomas is, however, not clarified, since the current understanding of the renal stem cell system is not complete. It is clear that the efforts to isolate and characterize renal progenitor/stem cells suffer from numerous technical limitations and that it remains likely that the kidney harbors different stem cell pools with a restricted differentiation potential.
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| 7. |
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| 8. |
- Baecklund, Eva, et al.
(author)
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Lymphoma development in patients with autoimmune and inflammatory disorders : What are the driving forces?
- 2014
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In: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X .- 1096-3650. ; 24, s. 61-70
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Research review (peer-reviewed)abstract
- For decades, it has been known that patients with certain autoimmune and inflammatory disorders, such as rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS), have an increased risk of developing malignant lymphoma. Although the clinico-biological reasons for this association remain largely unknown, our knowledge has improved and new insights have been obtained. First, the direct link between autoimmunity and lymphomagenesis has been strengthened by large epidemiological studies showing a consistent risk increase of lymphoma associated with certain autoimmune/inflammatory conditions in independent cohorts from different countries. Second, a number of local and systemic disease-related risk factors in these diseases have been repeatedly linked to lymphoma development, with the prime examples being disease severity and the degree of inflammatory activity. Considering the key role of B- and T-cell activation in the pathogenesis of both autoimmunity and lymphoma, it is perhaps not surprising that longstanding chronic inflammation and/or antigen stimulation have emerged as major predisposing factors of lymphoma in patients with active autoimmune disease. Finally, increasing evidence suggests that lymphomas associated with autoimmunity constitute a different spectrum of entities compared to lymphomas arising in patients without any known autoimmune or inflammatory conditions, pointing to a different pathobiology. In this review, we summarize the recent literature that supports a direct or indirect link between immune-mediated disease and lymphoma and describe the characteristics of lymphomas developing in the different diseases. We also discuss molecular, genetic and microenvironmental factors that may come into play in the pathobiology of these disorders.
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| 9. |
- Berg, Tracy J, et al.
(author)
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Radiotherapy-induced remodeling of the tumor microenvironment by stromal cells
- 2022
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In: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 86:Part 3, s. 846-856
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Research review (peer-reviewed)abstract
- Cancer cells reside amongst a complex milieu of stromal cells and structural features known as the tumor microenvironment. Often cancer cells divert and co-opt functions of stromal cells of the microenvironment to support tumor progression and treatment resistance. During therapy targeting cancer cells, the stromal cells of the microenvironment receive therapy to the same extent as cancer cells. Stromal cells therefore activate a variety of responses to the damage induced by these therapies, and some of those responses may support tumor progression and resistance. We review here the response of stromal cells to cancer therapy with a focus on radiotherapy in glioblastoma. We highlight the response of endothelial cells and the vasculature, macrophages and microglia, and astrocytes, as well as describing resulting changes in the extracellular matrix. We emphasize the complex interplay of these cellular factors in their dynamic responses. Finally, we discuss their resulting support of cancer cells in tumor progression and therapy resistance. Understanding the stromal cell response to therapy provides insight into complementary therapeutic targets to enhance tumor response to existing treatment options.
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| 10. |
- Bjerkvig, Rolf, et al.
(author)
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Cancer stem cells and angiogenesis
- 2009
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In: Seminars in Cancer Biology. - London : Academic Press. - 1044-579X .- 1096-3650. ; 19:5, s. 279-284
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Research review (peer-reviewed)abstract
- Most cancers contain tumor cells that display stem cell-like characteristics. How and when such cells appear in tumors are not clear, but may involve both stochastic as well as hierarchical events Most. likely, tumor cells that display stem cell-like characteristics can undergo asymmetric cell division giving rise to tumor cells that trigger angiogenic programs. As normal stem cells the cancer stem-like cells seem to adapt to hypoxic environments and will use metabolic pathways that involve increased conversion of glucose to pyruvate and lactate, and a concomitant decrease in mitochondrial metabolism and mitochondrial mass. The molecular pathways responsible for inducing glycolysis are now being explored. These pathways seem to mediate multiple metabolic functions in cancer stem-like cells, leading to a highly migratory and angiogenesis-independent phenotype. Future challenges will be to identify and validate molecular targets involved in anaerobic metabolic pathways active in cancer stem-like cells and to determine how these pathways differ from regulatory pathways involved in normal stem cell function.
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