#RUNX2 Antibody | Explore Tumblr Posts and Blogs

bostorbio · 3 years

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For transcriptional regulation, this gene encodes a nuclear protein with the Runt DNA-binding domain, which is part of the RUNX (RUNX2 Antibody) family.

#RUNX2 Antibody

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tumimmtxpapers · 5 years

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A Novel Sulforaphane-Regulated Gene Network in Suppression of Breast Cancer-Induced Osteolytic Bone Resorption.

Related Articles A Novel Sulforaphane-Regulated Gene Network in Suppression of Breast Cancer-Induced Osteolytic Bone Resorption. Mol Cancer Ther. 2019 Nov 29;: Authors: Pore SK, Hahm ER, Kim SH, Singh KB, Nyiranshuti L, Latoche JD, Anderson CJ, Adamik J, Galson DL, Weiss KR, Watters RJ, Lee B, Kumta PN, Singh SV Abstract Bone is the most preferred site for colonization of metastatic breast cancer cells for each subtype of the disease. The standard of therapeutic care for breast cancer patients with bone metastasis include bisphosphonates (e.g., zoledronic acid), which have poor oral bioavailability, and a humanized antibody (denosumab). However, these therapies are palliative and a subset of patients still develop new bone lesions and/or experience serious adverse effects. Therefore, a safe and orally bioavailable intervention for therapy of osteolytic bone resorption is still a clinically unmet need. This study demonstrates suppression of breast cancer-induced bone resorption by a small molecule (sulforaphane, SFN) that is safe clinically and orally bioavailable. In vitro osteoclast differentiation was inhibited in a dose-dependent manner upon addition of conditioned media from SFN-treated breast cancer cells representative of different subtypes. Targeted microarrays coupled with interrogation of TCGA dataset revealed a novel SFN-regulated gene signature involving cross-regulation of runt-related transcription factor 2 (RUNX2) and nuclear factor-κB and their downstream effectors. Both RUNX2 and p65/p50 expression were higher in human breast cancer tissues compared to normal mammary tissues. RUNX2 was recruited at the promotor of NFKB1. Inhibition of osteoclast differentiation by SFN was augmented by doxycycline-inducible stable knockdown of RUNX2. Oral SFN administration significantly increased the percentage of bone volume/total volume of affected bones in the intracardiac MDA-MB-231-Luc model indicating in vivo suppression of osteolytic bone resorption by SFN. These results indicate that SFN is a novel inhibitor of breast cancer induced osteolytic bone resorption in vitro and in vivo. PMID: 31784454 [PubMed - as supplied by publisher] http://dlvr.it/RKTkqJ

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battybat-boss · 6 years

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The present study indicates that benzyl isothiocyanate has the ability to inhibit breast cancer-induced osteolytic bone resorption in vivo.

PMID: Carcinogenesis. 2018 Feb 9 ;39(2):134-145. PMID: 29040431 Abstract Title: Prevention of breast cancer-induced osteolytic bone resorption by benzyl isothiocyanate. Abstract: Osteolytic bone resorption is the primary cause of pain and suffering (e.g. pathological bone fracture) in women with metastatic breast cancer. The current standard of care for patients with bone metastasis for reducing the incidence of skeletal complications includes bisphosphonates and a humanized antibody (denosumab). However, a subset of patients on these therapies still develops new bone metastasis or experiences adverse effects. Moreover, some bisphosphonates have poor oral bioavailability. Therefore, orally-bioavailable and non-toxic inhibitors of breast cancer-induced osteolytic bone resorption are still clinically desirable. We have shown previously that benzyl isothiocyanate (BITC) decreases the incidence of breast cancer in a transgenic mouse model without any side effects. The present study provides in vivo evidence for inhibition of breast cancer-induced osteolytic bone resorption by BITC. Plasma achievable doses of BITC (0.5 and 1μM) inhibited in vitro osteoclast differentiation induced by co-culture of osteoclast precursor cells (RAW264.7) and breast cancer cells representative of different subtypes. This effect was accompanied by downregulation of key mediators of osteoclast differentiation, including receptor activator of nuclear factor-κB ligand and runt-related transcription factor 2 (RUNX2), in BITC-treated breast cancer cells. Doxycycline-inducible knockdown of RUNX2 augmented BITC-mediated inhibition of osteoclast differentiation. Oral administration of 10 mg BITC/kg body weight, 5 times per week, inhibited MDA-MB-231-induced skeletal metastasis multiplicity by ~81% when compared with control (P = 0.04). The present study indicates that BITC has the ability to inhibit breast cancer-induced osteolytic bone resorption in vivo.

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cancersfakianakis1 · 7 years

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Trabectedin Overrides Osteosarcoma Differentiative Block and Reprograms the Tumor Immune Environment Enabling Effective Combination with Immune Checkpoint Inhibitors

Purpose: Osteosarcoma, the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested.

Experimental Design: We have developed immunocompetent osteosarcoma models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human osteosarcoma. These models have been used to test the efficacy of trabectedin, a chemotherapeutic drug utilized clinically for sarcomas and ovarian cancer.

Results: Trabectedin, as monotherapy, significantly inhibited osteosarcoma primary tumor growth and lung metastases by both targeting neoplastic cells and reprogramming the tumor immune microenvironment. Specifically, trabectedin induced a striking differentiation of tumor cells by favoring the recruitment of Runx2, the master genetic regulator of osteoblastogenesis, on the promoter of genes involved in the physiologic process of terminal osteoblast differentiation. Differentiated neoplastic cells, as expected, showed reduced proliferation rate. Concomitantly, trabectedin enhanced the number of tumor-infiltrating T lymphocytes, with local CD8 T cells, however, likely post-activated or exhausted, as suggested by their high expression of the inhibitory checkpoint molecule PD-1. Accordingly, the combination with a PD-1–blocking antibody significantly increased trabectedin efficacy in controlling osteosarcoma progression.

Conclusions: These results demonstrate the therapeutic efficacy of trabectedin in osteosarcoma treatment, unveiling its multiple activities and providing a solid rationale for its combination with immune checkpoint inhibitors. Clin Cancer Res; 23(17); 5149–61. ©2017 AACR.

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#Oncology-Sfakianakis

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tumimmtxpapers · 7 years

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TRABECTEDIN OVERRIDES OSTEOSARCOMA DIFFERENTIATIVE BLOCK AND REPROGRAMS THE TUMOR IMMUNE ENVIRONMENT ENABLING EFFECTIVE COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS.

Related Articles TRABECTEDIN OVERRIDES OSTEOSARCOMA DIFFERENTIATIVE BLOCK AND REPROGRAMS THE TUMOR IMMUNE ENVIRONMENT ENABLING EFFECTIVE COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS. Clin Cancer Res. 2017 Jun 09;: Authors: Ratti C, Botti L, Cancila V, Galvan S, Torselli I, Garofalo C, Manara MC, Bongiovanni L, Valenti CF, Burocchi A, Parenza M, Cappetti B, Sangaletti S, Tripodo C, Scotlandi K, Colombo MP, Chiodoni C Abstract Purpose: Osteosarcoma (OS), the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested. Experimental Design: We have developed immuno-competent OS models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human OS. These models have been used to test the efficacy of trabectedin, a chemotherapeutic drug utilized clinically for sarcomas and ovarian cancer. Results: Trabectedin, as monotherapy, significantly inhibited OS primary tumor growth and lung metastases by both targeting neoplastic cells and reprogramming the tumor immune microenvironment. Specifically, trabectedin induced a striking differentiation of tumor cells by favoring the recruitment of Runx2, the master genetic regulator of osteoblastogenesis, on the promoter of genes involved in the physiologic process of terminal osteoblast differentiation. Differentiated neoplastic cells, as expected, showed reduced proliferation rate. Concomitantly, trabectedin enhanced the number of tumor-infiltrating T lymphocytes, with local CD8 T cells, however, likely post-activated or exhausted, as suggested by their high expression of the inhibitory checkpoint molecule PD-1. Accordingly, the combination with a PD-1-blocking antibody significantly increased trabectedin efficacy in controlling OS progression. Conclusion: These results demonstrate the therapeutic efficacy of trabectedin in OS treatment, unveiling its multiple activities and providing a solid rationale for its combination with immune checkpoint inhibitors. PMID: 28600479 [PubMed - as supplied by publisher] http://dlvr.it/PLQjyX

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cancersfakianakis1 · 7 years

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TRABECTEDIN OVERRIDES OSTEOSARCOMA DIFFERENTIATIVE BLOCK AND REPROGRAMS THE TUMOR IMMUNE ENVIRONMENT ENABLING EFFECTIVE COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS

Purpose: Osteosarcoma (OS), the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested. Experimental Design: We have developed immuno-competent OS models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human OS. These models have been used to test the efficacy of trabectedin, a chemotherapeutic drug utilized clinically for sarcomas and ovarian cancer. Results: Trabectedin, as monotherapy, significantly inhibited OS primary tumor growth and lung metastases by both targeting neoplastic cells and reprogramming the tumor immune microenvironment. Specifically, trabectedin induced a striking differentiation of tumor cells by favoring the recruitment of Runx2, the master genetic regulator of osteoblastogenesis, on the promoter of genes involved in the physiologic process of terminal osteoblast differentiation. Differentiated neoplastic cells, as expected, showed reduced proliferation rate. Concomitantly, trabectedin enhanced the number of tumor-infiltrating T lymphocytes, with local CD8 T cells, however, likely post-activated or exhausted, as suggested by their high expression of the inhibitory checkpoint molecule PD-1. Accordingly, the combination with a PD-1-blocking antibody significantly increased trabectedin efficacy in controlling OS progression. Conclusion: These results demonstrate the therapeutic efficacy of trabectedin in OS treatment, unveiling its multiple activities and providing a solid rationale for its combination with immune checkpoint inhibitors.

http://ift.tt/2snRCkb

#Oncology-Sfakianakis

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