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Fulltext Andrographolide is an Alternative Treatment to Overcome Resistance in ER-Positive Breast Cancer via Cholesterol Biosynthesis Pathway

Rajaratinam H, Nafi SNM

Malays J Med Sci, 2019 Sep;26(5):6-20.
PMID: 31728115 MyJurnal DOI: 10.21315/mjms2019.26.5.2

Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to anti-oestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.
Immunohistochemical expression of apolipoprotein B and 4-hydroxynonenal proteins in colorectal carcinoma patients: a retrospective study

Ng PY, Nafi SNM, Jalil NAC, Kueh YC, Lee YY, Zin AAM

Croat Med J, 2023 Feb 28;64(1):29-36.
PMID: 36864816

AIM: To assess the association of the expression of apolipoprotein B (apoB) and 4-hydroxynonenal (4HNE) with the clinicopathological data of patients with colorectal cancer (CRC).
METHODS: We obtained 80 CRC histopathological specimens sent to the Pathology Laboratory of Hospital Universiti Sains Malaysia from 2015 to 2019. Data on demographic factors, body mass index (BMI), and clinicopathological characteristics were also collected. Formalin-fixed paraffin-embedded tissues were stained by using an optimized immunohistochemical protocol.
RESULTS: Patients were mostly older than 50 years, male, Malay, and overweight or obese. A high apoB expression was observed in 87.5% CRC samples (70/80), while a high 4HNE expression was observed in only 17.5% (14/80) of CRCs. The expression of apoB was significantly associated with the sigmoid and rectosigmoid tumor sites (p =0.001) and tumor size 3-5 cm (p =0.005). 4HNE expression was significantly associated with tumor size 3-5 cm (p =0.045). Other variables were not significantly associated with the expression of either marker.
CONCLUSION: ApoB and 4HNE proteins may play a role in promoting CRC carcinogenesis.
Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models

Arshad M, Azad A, Chan PYK, Vigneswara V, Feldinger K, Nafi SNM, et al.

Br J Cancer, 2024 Apr 10.
PMID: 38600326 DOI: 10.1038/s41416-024-02665-z

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear.
METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays.
RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab.
CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.
Unraveling Roles of miR-27b-3p as a Potential Biomarker for Breast Cancer in Malay Women via Bioinformatics Analysis

Jusoh AR, Al-Astani Bin Tengku Din TAD, Abdullah-Zawawi MR, Abdul Rahman WFW, Nafi SNM, Romli RC, et al.

Int J Mol Cell Med, 2023;12(3):257-274.
PMID: 38751652 DOI: 10.22088/IJMCM.BUMS.12.3.257

Abnormal miRNA expression has been associated with breast cancer. Knowing miRNA and its target genes gives a better understanding of the biological mechanism behind the development of breast cancer. Here, we evaluated the potential prognostic and predictive values of miRNAs in breast cancer development by analyzing Malay women with breast cancer expression profiles. Seven differentially expressed miRNAs (DEMs) were subjected to miRNA‒target interaction network analysis (MTIN). A comprehensive MTIN was developed by integrating the information on miRNA and target gene interactions from five independent databases, including DIANA-TarBase, miRTarBase, miRNet, miRDB, and DIANA-microT. To understand the role of miRNAs in the progress of breast cancer, functional enrichment analysis of the miRNA target genes was conducted, followed by survival analysis to assess the prognostic values of the miRNAs and their target genes. In total, 1416 interactions were discovered among seven DEMs and 1274 target genes with a confidence score (CS) > 0.8. The overall survival analysis of the three most DEMs revealed a significant association of miR-27b-3p with poor prognosis in the TCGA breast cancer patient cohort. Further functional analysis of 606 miR-27b-3p target genes revealed their involvement in cancer-related processes and pathways, including the progesterone receptor signaling pathway, PI3K-Akt pathway, and EGFR transactivation. Notably, six high-confidence target genes (BTG2, DNAJC13, GRB2, GSK3B, KRAS, and UBR5) were discovered to be associated with worse overall survival in breast cancer patients, underscoring their essential roles in breast cancer development. Thus, we suggest that miR-27b-3p has significant potential as a biomarker for detecting breast cancer and can provide valuable understanding regarding the molecular mechanisms of the disease.