In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers

Breast cancer is a heterogeneous disease with a wide variety of clinical, pathological, and molecular characteristics, the most commonly diagnosed cancer among females and the leading cause of women cancer death. Hormone receptor studies such as estrogen receptor (ER), progesterone receptor (PgR), a...

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Main Author:	Jaffar, Nurul Fathiyatul Nabila
Format:	Thesis
Language:	English
Published:	2020
Subjects:	R Medicine
Online Access:	http://eprints.usm.my/48889/1/NURUL%20FATHIYATUL%20NABILA%20BINTI%20JAFFAR-FINAL%20THESIS%20P-UM000918%28R%29%20PWD_-24%20pages.pdf
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spelling	my-usm-ep.488892021-04-14T04:29:09Z In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers 2020-10 Jaffar, Nurul Fathiyatul Nabila R Medicine Breast cancer is a heterogeneous disease with a wide variety of clinical, pathological, and molecular characteristics, the most commonly diagnosed cancer among females and the leading cause of women cancer death. Hormone receptor studies such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) are routinely done in prognosis of breast carcinoma and helps in deciding the best treatment. Sirolimus is a natural macrocyclic lactone drug from bacteria with immunosuppressive and anti-proliferative properties by inhibiting mechanistic target of rapamycin (mTOR). Sunitinib is a tyrosine kinase inhibitor (TKI) with antiangiogenic properties. Therefore, it will be interesting to analyse the effect of Sirolimus and Sunitinib in blocking the growth of breast cancer from responding to hormone stimulation. In this study, invasive mammary carcinoma was induced by using 70mg/kg body weight N-Nitroso-N-Methylurea (NMU) in 32 young female Sprague Dawley rats. The gene and protein expressions of ER, PgR and HER2/neu markers were evaluated by using semi-quantitative immunohistochemistry analysis and quantitative real-time PCR assay. Findings from the untreated-control group demonstrated that all mammary lesions are 100% malignant, histopathological characterized with invasive breast carcinoma (IBC) of three major patterns; cribriform, papillary and no special type (NST). Sirolimus treatment showed significant inhibition of mammary tumour progression and downregulate the protein expressions of ER and PgR. However, high expressions of ER and PgR genes expressed on mRNA level might due to Sirolimus cause post-transcriptional regulation in gene. Meanwhile, tumour treated with Sunitinib reduced in diameter after first treatment, but the diameter increased after second treatment, and consequently showed no significant downregulation of ER and PgR. Histologically, Sunitinib treated tumour did not show any aggressive ductal NST histological subtypes. All NMU-induced tumours were HER2/neu-negative scoring. Tumour regression in combination treatment shown was predicted due to Sirolimus predominantly showed anticancer effect rather than Sunitinib. Thus, present findings suggested that Sirolimus is neither synergistic nor additive with Sunitinib. 2020-10 Thesis http://eprints.usm.my/48889/ http://eprints.usm.my/48889/1/NURUL%20FATHIYATUL%20NABILA%20BINTI%20JAFFAR-FINAL%20THESIS%20P-UM000918%28R%29%20PWD_-24%20pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Kesihatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R Medicine
spellingShingle	R Medicine Jaffar, Nurul Fathiyatul Nabila In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
description	Breast cancer is a heterogeneous disease with a wide variety of clinical, pathological, and molecular characteristics, the most commonly diagnosed cancer among females and the leading cause of women cancer death. Hormone receptor studies such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) are routinely done in prognosis of breast carcinoma and helps in deciding the best treatment. Sirolimus is a natural macrocyclic lactone drug from bacteria with immunosuppressive and anti-proliferative properties by inhibiting mechanistic target of rapamycin (mTOR). Sunitinib is a tyrosine kinase inhibitor (TKI) with antiangiogenic properties. Therefore, it will be interesting to analyse the effect of Sirolimus and Sunitinib in blocking the growth of breast cancer from responding to hormone stimulation. In this study, invasive mammary carcinoma was induced by using 70mg/kg body weight N-Nitroso-N-Methylurea (NMU) in 32 young female Sprague Dawley rats. The gene and protein expressions of ER, PgR and HER2/neu markers were evaluated by using semi-quantitative immunohistochemistry analysis and quantitative real-time PCR assay. Findings from the untreated-control group demonstrated that all mammary lesions are 100% malignant, histopathological characterized with invasive breast carcinoma (IBC) of three major patterns; cribriform, papillary and no special type (NST). Sirolimus treatment showed significant inhibition of mammary tumour progression and downregulate the protein expressions of ER and PgR. However, high expressions of ER and PgR genes expressed on mRNA level might due to Sirolimus cause post-transcriptional regulation in gene. Meanwhile, tumour treated with Sunitinib reduced in diameter after first treatment, but the diameter increased after second treatment, and consequently showed no significant downregulation of ER and PgR. Histologically, Sunitinib treated tumour did not show any aggressive ductal NST histological subtypes. All NMU-induced tumours were HER2/neu-negative scoring. Tumour regression in combination treatment shown was predicted due to Sirolimus predominantly showed anticancer effect rather than Sunitinib. Thus, present findings suggested that Sirolimus is neither synergistic nor additive with Sunitinib.
format	Thesis
qualification_level	Master's degree
author	Jaffar, Nurul Fathiyatul Nabila
author_facet	Jaffar, Nurul Fathiyatul Nabila
author_sort	Jaffar, Nurul Fathiyatul Nabila
title	In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
title_short	In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
title_full	In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
title_fullStr	In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
title_full_unstemmed	In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
title_sort	in vivo effects of sirolimus and sunitinib of breast cancer prognostic markers
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Kesihatan
publishDate	2020
url	http://eprints.usm.my/48889/1/NURUL%20FATHIYATUL%20NABILA%20BINTI%20JAFFAR-FINAL%20THESIS%20P-UM000918%28R%29%20PWD_-24%20pages.pdf
_version_	1747821971447480320

In vivo effects of sirolimus and sunitinib of breast cancer prognostic markers

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