| 1. |
- Cedervall, Jessica, et al.
(författare)
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Tumor-Induced NETosis as a Risk Factor for Metastasis and Organ Failure
- 2016
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 76:15, s. 4311-4315
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Forskningsöversikt (refereegranskat)abstract
- A large proportion of cancer-related deaths are caused by thrombosis and general organ failure. One example is acute renal failure, a major cause of morbidity and mortality in cancer patients. Surprisingly, however, little is known about the situation in organs that are not targets for metastasis or affected by the primary tumor. Recently, neutrophil extracellular traps (NET) were implicated in tumor-induced effects on distant organs unaffected by the actual tumor cells. Formation of NETs (NETosis) was identified a decade ago as amechanismby which the innate immune system protects us from infections, especially in situations with sepsis. NETs are formed when neutrophils externalize their nuclear DNA together with antimicrobial granule proteins and form a web-like structure that can trap and kill microbes. It is now becoming increasingly clear that NETs also form under noninfectious inflammatory conditions like cancer, thrombosis, autoimmunity, and diabetes and significantly contribute to disease development. The existence of NET-dissolving drugs like heparin and DNase I, already in clinical use, and recent development of specific inhibitors of proteinarginine deiminase 4 (PAD4), an enzyme required for NET formation, should enable clinical targeting of NETosis. Preventing NETosis in cancer could provide a strategy to counteract tumor-induced thrombosis and organ failure as well as to suppress metastasis.
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| 2. |
- Soussi, Thierry
(författare)
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Benign SNPs in the Coding Region of TP53 : Finding the Needles in a Haystack of Pathogenic Variants
- 2022
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 82:19, s. 3420-3431
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Forskningsöversikt (refereegranskat)abstract
- With the recent explosion in high-throughput genotyping tech-nology, the amount and quality of SNP data have increased expo-nentially, facilitating the discovery of multiple uncommon SNPs in the human population. To provide unified and centralized resources for the scientific community, several repositories have been devel-oped that aggregate numerous population studies and serve widely as references to filter natural variants in genetic analyses. However, they are largely biased toward European populations. TP53 gene is the most frequently mutated gene in human cancer, and pathogenic germline TP53 variants are associated with several cancer suscep-tibility disorders such as Li-Fraumeni syndrome. For these reasons, it is essential that TP53 SNPs are rigorously evaluated to avoid misclassifications that could impair patient management. The recent discovery of numerous benign SNPs within the coding region of TP53 can be attributed to surveillance of both global repositories and population-specific databases, with the latter enabling the recognition of additional TP53 SNPs in Japanese, African, and Indian populations. This review summarizes the body of evidence behind the identification of 21 TP53 variants and the information defining them as bona fide SNPs. This illustrates the need to include populations of different ethnic origins in genetic studies and the substantial benefits that can be derived from the information.
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| 3. |
- Vardi, Anna, et al.
(författare)
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Immunogenetic Studies of Chronic Lymphocytic Leukemia : Revelations and Speculations about Ontogeny and Clinical Evolution
- 2014
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:16, s. 4211-4216
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Forskningsöversikt (refereegranskat)abstract
- Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes associated with a different clinical course that drew attention. As the years ensued, this not only continued to hold strong, but also revealed an unprecedented BcR restriction (aptly coined as "stereotypy"), thus cementing the idea that antigenic elements select the leukemic clones. With all this in mind, in the present review, we focus on the CLL BcR IG, a molecule that clearly lies at the heart of disease pathogenesis, and attempt to distil from past and emerging biologic knowledge the most relevant aspects in the context of the immunogenetics of CLL, while at the same time provoking questions that remain unanswered. We juxtapose CLL with mutated BcR IGs against CLL with unmutated BcR IGs due to their striking clinicobiologic differences; however, when considering ontogeny, common derivation of the two mutational subtypes cannot be excluded. The issue of stereotypy is intertwined throughout and we also raise the subject of isotype-switched CLL, which, despite its rarity, contributes intriguing ontogenetic hints.
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| 4. |
- Zackrisson, Sophia, et al.
(författare)
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Light in and sound out: emerging translational strategies for photoacoustic imaging.
- 2014
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Ingår i: Cancer Research. - 1538-7445. ; 74:4, s. 979-1004
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Forskningsöversikt (refereegranskat)abstract
- Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique. Cancer Res; 74(4); 979-1004. ©2014 AACR.
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