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  1. The association between phenotype and size of breast tumors induced by 1-methyl-1-nitrosourea (MNU) injection in rats
    Jaafar H, Mohamad Idris F, Mohd Nafi SN
    Med Sci Monit, 2009 May;15(5):BR129-34.
    PMID: 19396029
    Administration of 1-methyl-1-nitrosourea (MNU) is considered a simple and rapid method for inducing breast tumors in rats. While most studies focus on the time frame of tumor development, there are little data on the development of breast tumor in relation to tumor size. Thus the current study was carried out to analyze the phenotype of MNU-induced tumors in relation to tumor size.
    Matched MeSH terms: Methylnitrosourea/toxicity*
  2. Fulltext Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth
    Jaffar NFN, Muhammad Sakri MS, Jaafar H, Wan Abdul Rahman WF, Tengku Din TADA
    Asian Pac J Cancer Prev, 2020 Oct 01;21(10):2919-2925.
    PMID: 33112549 DOI: 10.31557/APJCP.2020.21.10.2919
    OBJECTIVE: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib.

    METHODS: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis.

    RESULTS: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring.

    CONCLUSION: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
    .

    Matched MeSH terms: Methylnitrosourea/toxicity*
  3. Cellular and Molecular Changes in MNU-Induced Breast Tumours Injected with PF4 or bFGF
    Mohd Nafi SN, Idris F, Jaafar H
    Asian Pac J Cancer Prev, 2017 Dec 28;18(12):3231-3238.
    PMID: 29281877
    Background: Angiogenic activity has been considered to reflect important molecular events during breast tumour
    development. The present study concerned cellular and molecular changes of MNU-induced breast tumours subjected
    to promotion and suppression of angiogenesis. Methods: Female Sprague Dawley rats at the age of 21 days received
    MNU at the dose 70 mg/kg of body weight by intraperitoneal injection. Three months post-carcinogen initiation,
    mammary tumours were palpated and their growth was monitored. When the tumour diameter reached 1.0 ± 0.05 cm,
    rats were given bFGF or PF4 intratumourally at a dose of 10 μg/tumour. Entire palpable tumour were subsequently
    excised and subjected to histology examination, IHC staining, and RT-PCR. Results: No critical morphological changes
    were observed between pro-angiogenic factor, bFGF, and control groups. However, increase of tumour size with more
    necrotic and diffuse areas was notable in tumours after anti-angiogenic PF4 intervention. ER and PR mRNA expression
    was significantly up- and down-regulated in bFGF and PF4 groups, respectively. The trends were significantly associated
    with peri- and intratumoural MVD counts. However, irrespective of whether we promoted or inhibited angiogenesis,
    the expression of EGFR and ERBB2 continued to be significantly increased but this was not significantly associated
    with the MVD score. No significant differences in E-cadherin and LR gene expression were noted between intervention
    and control groups. Conclusion: ER and PR receptor expression shows consistent responses when tumour angiogenesis
    is manipulated either positively or negatively. Our study adds to current understanding that not only do we need to
    target hormonal receptors, as presently practiced, but we also need to target endothelial receptors to successfully treat
    breast cancer.
    Matched MeSH terms: Methylnitrosourea/toxicity*
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