| 491. |
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| 492. |
- 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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| 493. |
- Zarrizi, Reihaneh, et al.
(författare)
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Deubiquitination of γ-tubulin by BAP1 prevents chromosome instability in breast cancer cells.
- 2014
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Ingår i: Cancer Research. - 1538-7445. ; 74:22, s. 6499-6508
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Tidskriftsartikel (refereegranskat)abstract
- Microtubule nucleation requires the γ-tubulin ring complex, and during the M phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The post-translational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the present study, we identified BRCA1 associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared to non-cancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of breast cancer patients. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Importantly, rescue experiments including expression of full length but not the catalytic mutant of BAP1 reduced ubiquitination of γ-tubulin and prevented mitotic defects. Our study uncovers a new mechanism for BAP1 involved in deubiquitination of γ-tubulin, which is required to prevent abnormal mitotic spindle formation and genome instability.
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| 494. |
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| 495. |
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| 496. |
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| 497. |
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| 498. |
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| 499. |
- Zhang, Yanyu, et al.
(författare)
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Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis
- 2020
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 80:16, s. 3345-3358
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor b-positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. Here, we show that tumor vascular function, as well as pericyte coverage is significantly impaired in mice with conditional knockout of PDGFB in platelets. A lack of PDGFB in platelets led to enhanced hypoxia and epithelial-to-mesenchymal transition in the primary tumors, elevated levels of circulating tumor cells, and increased spontaneous metastasis to the liver or lungs in two mouse models. These findings establish a previously unknown role for platelet-derived PDGFB, whereby it promotes and maintains vascular integrity in the tumor microenvironment by contributing to the recruitment of pericytes. Significance: Conditional knockout of PDGFB in platelets demonstrates its previously unknown role in the maintenance of tumor vascular integrity and host protection against metastasis.
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| 500. |
- Zhao, Chunyan, et al.
(författare)
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Estrogen receptor beta 2 negatively regulates the transactivation of estrogen receptor alpha in human breast cancer cells
- 2007
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:8, s. 3955-3962
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens, by binding to and activating two estrogen receptors (ER alpha and ER beta), are critically involved in the development of the mammary gland and breast cancer. An isoform of ER beta, ER beta 2 (also called ER beta cx), with an altered COOH-terminal region, is coexpressed with ER alpha. in many human breast cancers. In this study, we generated a stable cell line from MCF7 breast cancer cells expressing an inducible version of ER beta 2, along with endogenous ER alpha, and examined the effects of ER beta 2 on the ER alpha protein levels and function. We showed that ER beta 2 inhibited ER alpha-mediated transactivation via estrogen response element and activator protein-1 sites of reporter constructs as well as the endogenous genes pS2 and MMP-1. Chromatin immunoprecipitation assays revealed that ER beta 2 expression caused a significant reduction in the recruitment of ER alpha to both the pS2 and MMP-1 promoters. Furthermore, ER beta 2 expression induced proteasome-dependent degradation of ER alpha. The inhibitory effects of ER beta 2 on ER alpha activity were further confirmed in HEK293 cells that lack functional endogenous ER alpha. We also showed that ER beta 2 can interact with ER alpha both in vitro and in mammalian cells' which is compatible with a model where ER beta 2/ER alpha heterodimers are targeted to the proteasome. Finally, in human breast cancer samples, we observed that expression of ER beta 2 significantly correlated with ER alpha-negative phenotype. Our data suggest that ER beta 2 could influence ER alpha-mediated effects relevant for breast cancer development, including hormone responsiveness.
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