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You searched for subject:(AURKB). Showing records 1 – 3 of 3 total matches.

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University of Minnesota

1. Chang, Xiaoyu. Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis.

Degree: PhD, Biomedical Informatics and Computational Biology, 2020, University of Minnesota

Melanoma is an aggressive tumor of the skin. Although BRAF V600E inhibitors have been developed to treat melanoma, drug resistance and metastasis are still the major problems in melanoma therapy. Novel targets and effective agents to overcome drug resistant melanoma and reduce metastasis are urgently needed in clinical therapy. In this study, AURKB was defined as the target for melanoma therapy in an effort to overcome drug resistance. Notably, HI-511, a novel dual-target inhibitor for AURKB and BRAF V600E, inhibits development of both drug-sensitive and drug-resistant melanoma. We analyzed the Gene Expression Omnibus (GEO) database, utilized gene editing, and a xenograft mouse model to show AURKB is crucial for development of both drug-sensitive and drug-resistant melanoma. Inhibition of AURKB suppresses the cell growth and the rate of induced apoptosis in melanoma. Knocking down expression of AURKB decreased activation of the BRAF/MEK/ERKs and PI3K/AKT signaling pathways. Notably, a novel AURKB and BRAF V600E dual-target inhibitor HI-511 was developed. HI-511 strongly suppresses development of vemurafenib-sensitive and vemurafenib-resistant melanoma in vitro and in vivo, which is evidenced by in vitro kinase assays, cell base studies, xenograft mouse models and the BRAF V600E/PTEN-loss melanoma mouse model. Moreover, we also analysis the metastatic melanoma database and utilized the wound healing assay and a luciferase-linked xenograft mouse model to demonstrate HI-511 could reduce melanoma metastasis. Overall, AURKB could be a potential target for melanoma treatment and could overcome the resistance to BRAF V600E inhibitor and reduce melanoma metastasis. HI-511 is a novel dual-target inhibitor for both AURKB and BRAF V600E and could achieve durable suppression of melanoma, even drug-resistant melanoma and metastatic melanoma.

Subjects/Keywords: AURKB; BRAF V600E; HI-511; melanoma; metastasis; vemurafenib-resistant melanoma

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chang, X. (2020). Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/216163

Chicago Manual of Style (16th Edition):

Chang, Xiaoyu. “Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis.” 2020. Doctoral Dissertation, University of Minnesota. Accessed March 04, 2021. http://hdl.handle.net/11299/216163.

MLA Handbook (7th Edition):

Chang, Xiaoyu. “Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis.” 2020. Web. 04 Mar 2021.

Vancouver:

Chang X. Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis. [Internet] [Doctoral dissertation]. University of Minnesota; 2020. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/11299/216163.

Council of Science Editors:

Chang X. Hi-511 Inhibits Both BRAF and AURKB To Overcome Malignant Melanoma Drug Resistance and Metastasis. [Doctoral Dissertation]. University of Minnesota; 2020. Available from: http://hdl.handle.net/11299/216163

2. D. Corbani. MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1).

Degree: 2013, Università degli Studi di Milano

Reproductive efficiency in dairy cows is decreasing worldwide. The root cause of the declining fertility is probably a combination of a variety of physiological and management factors that have an additive effect on reproductive efficiency. These factors include increasing in milk production and herd size, greater use of confinement housing, labor shortages and higher inbreeding percentages. In addition, the reproductive physiology of dairy cattle has also changed in response to genetic selection for milk production. Compared with traditional dairy cows, modern dairy cows have longer intervals to first ovulation, a higher incidence of anestrus and abnormal luteal phases, lower blood progesterone and IGF-I concentrations, higher incidence of multiple ovulations and twinning rates as well as greater embryonic loss. Declining fertility represents an obstacle in maintaining profitability of dairy farms. It has been estimated that a slight increase in pregnancy rates results in a significant increase in profitability that could make the difference in whether a family farm remains in operation. These findings suggest that defining the factors and mechanisms that contribute to oocyte and embryo quality is essential for improving female fertility. In particular, basic knowledge of which proteins within the oocyte regulate meiosis, oocyte fertilizability and developmental potential would be advantageous. Starting from these observations, our studies were conducted to test the hypothesis that PGRMC1 is one of the key factors that regulate mammalian oocyte quality and therefore female fertility. Initial indications that PGRMC1 participates in progesterone signaling in the reproductive system come from studies in which PGRMC1 expression was silenced using siRNA in ovarian cells. These experiments demonstrated that Progesterone’s ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1, indicating that PGRMC1 plays an essential role in promoting the survival of ovarian cell in vitro. This led us to start our investigations on the function of PGRMC1 in bovine fertility. Initial experiments were conducted to determine the presence and localization of PGRMC1 in various compartments of the bovine female reproductive organs, during the follicular and luteal phases of the estrous cycle. Importantly, these studies revealed the presence of PGRMC1 in the nucleus of bovine oocytes. Further studies revealed that PGRMC1 is present in both GV- and MII-stage oocyte, is associated with male and female pronuclei in the zygote and is highly expressed in the blastocysts, with typical localization at each of these stages. Since fertilization and embryonic development are mainly dependent on the completion of oocyte maturation, we focused our attention on PGRMC1’s role during this important step. Our localization as well as our functional data suggest an important role of PGRMC1 in oocyte maturation that may be specifically related to the mechanism by which chromosomes segregate and the first polar body… Advisors/Committee Members: tutor: A.M. Luciano, coordinator: F. Gandolfi, LUCIANO, ALBERTO MARIA, GANDOLFI, FULVIO.

Subjects/Keywords: PGRMC1; AURKB; oocyte; meiosis; premature ovarian failure; antral follicle count; ovary; infertility; Settore VET/01 - Anatomia degli Animali Domestici

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Corbani, D. (2013). MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1). (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/216690

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Corbani, D.. “MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1).” 2013. Thesis, Università degli Studi di Milano. Accessed March 04, 2021. http://hdl.handle.net/2434/216690.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Corbani, D.. “MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1).” 2013. Web. 04 Mar 2021.

Vancouver:

Corbani D. MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1). [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2434/216690.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Corbani D. MOLECULAR DETERMINANTS OF MAMMALIAN FERTILITY: ROLE OF PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1 (PGRMC1). [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/216690

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Queensland

3. Bokhari, Fawzi Faisal A. siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer.

Degree: UQ Diamantina Institute, 2014, University of Queensland

HPV oncogenes disable a number of tumour suppressor pathways, including p53 and Rb, contributing to the transformed phenotype. Loss of these critical host cell functions may also provide an opportunity to selectively target the destruction of HPV-transformed cells. We have performed an siRNA screen using the kinome (779 genes) library to identify genes that when depleted are synthetically lethal with HPV transformation. The primary and validations screens have confirmed Aurora A kinase (AURKA) as a potential synthetic lethal target selective for HPV transformed cells. AURKA has been further investigated using the selective small molecule inhibitor MLN8237. We found that MLN8237 was significantly more potent towards the HPV transformed cells. The effect was not a consequence of targeting mitosis as two other mitotic inhibitors, PLK1 inhibitor (BI2536) and taxol, demonstrated no selectivity. Analysis of the nuclear structure and DNA content showed that Aurora A inhibition promoted a high level of polyploidy in non-HPV treated cells whilst this same degree of polyploidy was associate with apoptosis in the HPV-transformed cell lines. Whereas Bcl-2 over expression in HeLa cells had no effect on sensitivity to MLN8237, Mcl-1 overexpressing HeLa cells were less sensitive to the MLN8237 in comparison to the parental cell line, which may suggests the involvement of Noxa or Puma pro-apoptotic proteins in the induction of the apoptosis in the HPV-transformed cells. The transfection of the non-HPV C33A cervical cancer and SCC25 squamous cell carcinoma cell lines with the HPV16 oncogenic E7 increased sensitivity to MLN8237 between 3 >10 fold suggesting that the sensitivity to MLN8237-dependent killing was a direct consequence of HPV E7 expression. Xenograft experiments with cervical cancer cell lines in immunodeficient mice showed MLN8237 inhibited growth of HPV and non-HPV xenografts during treatment with 30mg/kg MLN8237 once a day for 10 consecutive days. However, outgrowth of tumour was noticed from the second day post-treatment in the non-HPV tumour group whereas the HPV-induced tumour group did not show cancer recurrence for 50 days post-treatment. These findings suggest that MLN8237 represent a promising novel therapeutic targeted agent against HPV-transformed cervical cancer.

Subjects/Keywords: siRNA; AURKA; AURKB; Haspin; GSG2; cervical cancer; HPV; synthetic lethality; 0601 Biochemistry and Cell Biology; 0604 Genetics; 1112 Oncology and Carcinogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bokhari, F. F. A. (2014). siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer. (Thesis). University of Queensland. Retrieved from http://espace.library.uq.edu.au/view/UQ:341649

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Bokhari, Fawzi Faisal A. “siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer.” 2014. Thesis, University of Queensland. Accessed March 04, 2021. http://espace.library.uq.edu.au/view/UQ:341649.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Bokhari, Fawzi Faisal A. “siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer.” 2014. Web. 04 Mar 2021.

Vancouver:

Bokhari FFA. siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer. [Internet] [Thesis]. University of Queensland; 2014. [cited 2021 Mar 04]. Available from: http://espace.library.uq.edu.au/view/UQ:341649.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bokhari FFA. siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer. [Thesis]. University of Queensland; 2014. Available from: http://espace.library.uq.edu.au/view/UQ:341649

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.