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Inhibition of the i...
Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects of castration in a rat model for prostate cancer growth in bone
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- Nordstrand, Annika (författare)
- Umeå universitet,Onkologi
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- Halin Bergström, Sofia (författare)
- Umeå universitet,Patologi
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- Thysell, Elin (författare)
- Umeå universitet,Patologi
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- Bovinder-Ylitalo, Erik (författare)
- Umeå universitet,Patologi
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- Lerner, Ulf H (författare)
- Umeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Institutionen för odontologi,Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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- Widmark, Anders (författare)
- Umeå universitet,Onkologi
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- Bergh, Anders (författare)
- Umeå universitet,Patologi
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- Wikström, Pernilla (författare)
- Umeå universitet,Patologi
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(creator_code:org_t)
- 2017-04-26
- 2017
- Engelska.
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Ingår i: Clinical & Experimental Metastasis. - : Springer Science and Business Media LLC. - 0262-0898 .- 1573-7276. ; 34:3-4, s. 261-271
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Abstract
Ämnesord
Stäng
- Prostate cancer (PCa) patients with bone metastases are primarily treated with androgen deprivation therapy (ADT). Less pronounced ADT effects are seen in metastases than in primary tumors. To test if acute effects of ADT was enhanced by concurrent inhibition of pro-survival insulin-like growth factor 1 (IGF-1), rats were inoculated with Dunning R3327-G tumor cells into the tibial bone marrow cavity and established tumors were treated with castration in combination with IGF-1 receptor (IGF1R) inhibitor NVP-AEW541, or by each treatment alone. Dunning R3327-G cells were stimulated by androgens and IGF-1 in vitro. In rat tibia, Dunning R3327-G cells induced bone remodeling, identified through increased immunoreactivity of osteoblast and osteoclast markers. Tumor cells occasionally grew outside the tibia, and proliferation and apoptotic rates a few days after treatment were evaluated by scoring BrdU-and caspase-3-positive tumor cells inside and outside the bone marrow cavity, separately. Apoptosis was significantly induced outside, but unaffected inside, the tibial bone by either castration or NVP-AEW541, and the maximum increase (2.7-fold) was obtained by the combined treatment. Proliferation was significantly reduced by NVP-AEW541, independently of growth site, although the maximum decrease (24%) was observed when NVP-AEW541 was combined with castration. Tumor cell IGF1R immunoreactivity was evaluated in clinical PCa bone metastases (n = 61), and positive staining was observed in most cases (74%). In conclusion, IGF-1R inhibition may be evaluated in combination with ADT in patients with metastatic PCa, or in combination with therapies for the subsequent development of castration-resistant disease, although diverse responses could be anticipated depending on metastasis site.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Bone metastasis
- IGF-1R
- Apoptosis
- Proliferation
- Immune response
- RUNX2
- TRAP
- androgen ablation
- cell-lines
- tumors
- expression
- metastases
- matrix
- tissue
- mice
- Oncology
- Bone metastasis
- Oncology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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