Displaying publications 1 - 20 of 348 in total

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  1. See MH, Sinnadurai S, Lai LL, Tan KL, Teh MS, Teoh LY, et al.
    Surgery, 2021 12;170(6):1604-1609.
    PMID: 34538341 DOI: 10.1016/j.surg.2021.08.001
    BACKGROUND: Although immediate breast reconstruction is increasingly becoming popular worldwide, evidence from resource-limited settings is scarce. We investigated factors associated with immediate breast reconstruction in a multiethnic, middle-income Asian setting. Short-term surgical complications, timing of initiation of chemotherapy, and survival outcomes were compared between women undergoing mastectomy alone and their counterparts receiving immediate breast reconstruction.

    METHODS: This historical cohort study included women who underwent mastectomy after diagnosis with stage 0 to stage IIIa breast cancer from 2011 to 2015 in a tertiary hospital. Multivariable regression analyses were used to assess factors associated with immediate breast reconstruction and to measure clinical outcomes.

    RESULT: Out of 790 patients with early breast cancer who had undergone mastectomy, only 68 (8.6%) received immediate breast reconstruction. Immediate breast reconstruction was independently associated with younger age at diagnosis, recent calendar years, Chinese ethnicity, higher education level, and invasive ductal carcinomas. Although immediate breast reconstruction was associated with a higher risk of short-term local surgical complications (adjusted odds ratio: 3.58 [95% confidence interval 1.75-7.30]), there were no significant differences in terms of delay in initiation of chemotherapy, 5-year disease-free survival, and 5-year overall survival between both groups in the multivariable analyses.

    CONCLUSION: Although associated with short-term surgical complications, immediate breast reconstruction after mastectomy does not appear to be associated with delays in initiation of chemotherapy, recurrence, or mortality after breast cancer. These findings are valuable in facilitating shared surgical decision-making, improving access to immediate breast reconstruction, and setting priorities for surgical trainings in middle-income settings.

    Matched MeSH terms: Breast Neoplasms/pathology
  2. Poh Yen K, Stanslas J, Zhang T, Li H, Wang X, Kok Meng C, et al.
    Bioorg Med Chem, 2021 11 01;49:116442.
    PMID: 34600241 DOI: 10.1016/j.bmc.2021.116442
    Acquired paclitaxel (PTX) chemoresistance in triple-negative breast cancer (TNBC) can be inferred from the overexpression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) proteins and the activation of the TLR4/MyD88 cascading signalling pathway. Finding a new inhibitor that can attenuate the activation of this pathway is a novel strategy for reducing PTX chemoresistance. In this study, a series of small molecule compounds were synthesised and tested in combination with PTX against TNBC cells. The trimethoxy-substituted compound significantly decreased MyD88 overexpression and improved PTX activity in MDA-MB-231TLR4+ cells but not in HCCTLR4- cells. On the contrary, the trifluoromethyl-substituted compound with PTX synergistically improved the growth inhibition in both TNBC subtypes. The fluorescence titrations indicated that both compounds could bind with MD2 with good and comparable binding affinities. This was further supported by docking analysis, in which both compounds fit perfectly well and form some critical binding interactions with MD2, an essential lipid-binding accessory to TLR4 involved in activating the TLR-4/MyD88-dependent pathway.
    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology
  3. Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG
    Invest New Drugs, 2021 10;39(5):1232-1241.
    PMID: 33768386 DOI: 10.1007/s10637-021-01106-5
    Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.
    Matched MeSH terms: Breast Neoplasms/pathology*; Triple Negative Breast Neoplasms/pathology
  4. Maniam S, Maniam S
    Int J Mol Sci, 2021 Sep 08;22(18).
    PMID: 34575883 DOI: 10.3390/ijms22189722
    Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.
    Matched MeSH terms: Breast Neoplasms/pathology
  5. Almoustafa HA, Alshawsh MA, Chik Z
    Anticancer Drugs, 2021 Aug 01;32(7):745-754.
    PMID: 33675612 DOI: 10.1097/CAD.0000000000001065
    Poly lactic-co-glycolic acid (PLGA) nanoparticles are intensively studied nanocarriers in drug delivery because of their biodegradability and biochemical characteristics. Polyethylene glycol (PEG) coating for nanocarriers gives them long circulation time in blood and makes them invisible to the reticuloendothelial system. Breast cancer cells have greater uptake of hyaluronic acid compared to normal cells as it binds to their overexpressed CD44 receptors. Since hypoxia plays an important role in cancer metastasis; we formulated PEG-PLGA nanoparticles coated with hyaluronic acid as targeted delivery system for doxorubicin (DOX) using nanoprecipitation method, and characterized them for chemical composition, size, surface charge, shape, and encapsulation efficiency. Then we tested them in vitro on hypoxia-optimized metastatic breast cancer cells. The nanoparticles were spherical with an average size of about 106 ± 53 nm, a negative surface charge (-15 ± 3 mV), and high encapsulation efficiency (73.3 ± 4.1%). In vitro investigation with hypoxia-elevated CD44 MDA-MB-231 cells showed that hyaluronic acid-targeted nanoparticles maintained their efficacy despite hypoxia-induced drug resistance unlike free DOX and nontargeted nanoparticles. In conclusion, this study revealed a simple third generation nanoparticle formulation for targeted treatment of hypoxia-induced drug resistance in breast cancer metastatic cells. Further, optimization is needed including In vivo efficacy and nanoparticle-specific pharmacokinetic studies.
    Matched MeSH terms: Breast Neoplasms/pathology
  6. Ameli F, Ghafourina Nassab F, Masir N, Kahtib F
    Asian Pac J Cancer Prev, 2021 Aug 01;22(8):2603-2609.
    PMID: 34452576 DOI: 10.31557/APJCP.2021.22.8.2603
    INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

    MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

    RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

    CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.

    Matched MeSH terms: Breast Neoplasms/pathology*
  7. Mohamed M, Mohd Nafi SN, Jaafar H, Paiman NM
    Asian Pac J Cancer Prev, 2021 Jul 01;22(7):2043-2047.
    PMID: 34319025 DOI: 10.31557/APJCP.2021.22.7.2043
    OBJECTIVE: The role of HMG-CoA reductase (HMGCR) in relation to prognostic and treatment predictive information of HER2 positive breast cancer has been newly explored. In this study, we aimed to determine the expression of HMGCR in HER2 immunohistochemistry (IHC) scores of 2+ and 3+ breast cancer and to correlate with the patients' outcomes.

    METHODOLOGY: Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar. IHC staining for HMGCR was performed on paraffin-embedded tissues at the Pathology Laboratory, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian using the standard staining procedure. The results were correlated with the patient's demographic and clinicopathological data.

    RESULTS: A total of 59 cases of HER2 IHC 2+ and 3+ invasive breast carcinoma were identified. The cases were predominant in young Malay women with tumours smaller than 50mm, higher grade and positive for lymphovascular invasion, axillary lymph nodes involvement and ER/PR expressions. HMGCR was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong. Majority of the cases were scored 1+ for HMGCR expression. A low-positive HMGCR was more likely to be associated with less favourable outcomes of patients with HER2 IHC 2+ and 3+. However, the associations were statistically not significant.

    CONCLUSION: A study in a larger cohort of tumour samples is needed to further validate HMGCR expression as a potential prognostic biomarker for HER2 positive breast cancer. It is also suggested that all the HER2 IHC 2+ and 3+ cases need to be gene amplified using FISH analysis.  
    .

    Matched MeSH terms: Breast Neoplasms/pathology*
  8. Yin Lee JP, Thomas AJ, Lum SK, Shamsudin NH, Hii LW, Mai CW, et al.
    Surg Oncol, 2021 Jun;37:101536.
    PMID: 33677364 DOI: 10.1016/j.suronc.2021.101536
    INTRODUCTION: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers.

    METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas.

    RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy.

    CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.

    Matched MeSH terms: Breast Neoplasms/pathology*
  9. Wong YP, Vincent James EP, Mohammad Azhar MAA, Krishnamoorthy Y, Zainudin NA, Zamara F, et al.
    Diagn Cytopathol, 2021 Jun;49(6):718-726.
    PMID: 33629823 DOI: 10.1002/dc.24731
    BACKGROUND: The International Academy of Cytology (IAC) Yokohama reporting system was recently proposed to serve as a standardized diagnostic platform for the cytological interpretation of breast fine needle aspiration biopsy (FNAB). Five cytological categories were suggested, linked to a certain risk of malignancy (ROM). The aim of this study was to assess the potency of this newly proposed reporting guideline, with a review of literatures.

    METHODS: This is a retrospective study over 8-year duration in which all the breast FNABs performed in our institution were recategorized in accordance to the IAC Yokohama reporting system. Kappa coefficient was used to evaluate the agreement between the proposed cytological category and corresponding histological diagnosis, with the level of significance set at 5%. Cyto-histopathological correlation and its diagnostic performance were also assessed.

    RESULTS: A total of 1136 breast FNABs were analyzed, including 31 repeat FNABs. Of these, 521 (47.1%) cases had matched histopathological results. Respective ROM for each category was: "insufficient" 13.6%, "benign" 0.4%, "atypical" 25.0%, "suspicious" 85.7%, and "malignant" 100%. There was substantial agreement (κ=0.757) between cytology and histopathological results. Our data revealed a high-diagnostic specificity, sensitivity, positive and negative predictive value of 99.3% (95% CI: 97.6%-99.9%), 94.2% (95% CI: 87.9%-97.9%), 98.0% (95% CI: 92.5%-99.5%), 98.0% (95% CI: 96.1%-99.1%) respectively when both the "suspicious" and "malignant" cases were considered as positive tests, with area under the curve of 0.993.

    CONCLUSIONS: The IAC Yokohama system is a reliable, evidence-based, and standardized reporting system that helps to facilitate communication among cytopathologists, radiologists, and surgeons toward individualized patient management.

    Matched MeSH terms: Breast Neoplasms/pathology*
  10. Mohd Fisall UF, Ismail NZ, Adebayo IA, Arsad H
    Mol Biol Rep, 2021 May;48(5):4465-4475.
    PMID: 34086162 DOI: 10.1007/s11033-021-06466-y
    Moringa oleifera is a well-known medicinal plant which has anti-cancer and other biological activities. This research aims to determine the cytotoxic and apoptotic effect of M. oleifera leave extract on the breast cancer (MCF7) cells. The extracts were prepared using hexane, dichloromethane, chloroform and n-butanol by fractionating the crude 80% methanol extract of the plant leaves. The cytotoxic effect of the extracts on MCF7 cells were determined using CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay. The apoptosis study was conducted using Annexin V-FITC analysis and confirmed by Western blotting using selected proteins, which are p53, Bax, cytochrome c and caspase 8. Our results showed that the dichloromethane (DF-CME-MOL) extract was selectively cytotoxic to MCF7 cells (5 μg/mL) without significantly inhibiting the non-cancerous breast (MCF 10A) cells. It had the highest selectivity index (SI) value of 9.5 among the tested extracts. It also induced early apoptosis and increased the expressions of pro-apoptotic proteins Bax, caspase 8 and p53 in MCF7 cells. Gas chromatography-mass spectrometry analysis (GC-MS) analysis showed that the major compounds found in DF-CME-MOL were benzeneacetonitrile, 4-hydroxy- and benzeneacetic acid, 4-hydroxy-, methyl ester among others that were detected. Thus, DF-CME-MOL extract was found to inhibit the proliferation of MCF7 cells by apoptosis induction, which is likely due to the activities of the detected phytochemical compounds of the extract.
    Matched MeSH terms: Breast Neoplasms/pathology
  11. Fadzli F, Rahmat K, Ramli MT, Rozalli FI, Hooi TK, Fadzli AN, et al.
    Medicine (Baltimore), 2021 Apr 23;100(16):e25297.
    PMID: 33879660 DOI: 10.1097/MD.0000000000025297
    To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P 
    Matched MeSH terms: Breast Neoplasms/pathology
  12. Hossan MS, Break MKB, Bradshaw TD, Collins HM, Wiart C, Khoo TJ, et al.
    Molecules, 2021 Apr 09;26(8).
    PMID: 33918814 DOI: 10.3390/molecules26082166
    Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.
    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology*
  13. Morra A, Jung AY, Behrens S, Keeman R, Ahearn TU, Anton-Culver H, et al.
    Cancer Epidemiol Biomarkers Prev, 2021 Apr;30(4):623-642.
    PMID: 33500318 DOI: 10.1158/1055-9965.EPI-20-0924
    BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

    METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

    RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

    CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

    IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

    Matched MeSH terms: Breast Neoplasms/pathology*
  14. Siddig A, Tengku Din TADA, Mohd Nafi SN, Yahya MM, Sulong S, Wan Abdul Rahman WF
    Genes (Basel), 2021 03 05;12(3).
    PMID: 33807872 DOI: 10.3390/genes12030372
    Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
    Matched MeSH terms: Breast Neoplasms/pathology*
  15. Chong ZX, Yeap SK, Ho WY
    Pathol Res Pract, 2021 Mar;219:153326.
    PMID: 33601152 DOI: 10.1016/j.prp.2020.153326
    MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are capable of regulating gene expression post-transcriptionally. Since the past decade, a number of in vitro, in vivo, and clinical studies reported the roles of these non-coding RNAs (ncRNAs) in regulating angiogenesis, an important cancer hallmark that is associated with metastases and poor prognosis. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signalling pathways regulated by these ncRNAs will be discussed in this review. In light of the recent trend in exploiting ncRNAs as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agent against angiogenesis was also discussed.
    Matched MeSH terms: Breast Neoplasms/pathology*
  16. Baraya YS, Yankuzo HM, Wong KK, Yaacob NS
    J Ethnopharmacol, 2021 Mar 01;267:113522.
    PMID: 33127562 DOI: 10.1016/j.jep.2020.113522
    ETHNOPHARMACOLOGICAL RELEVANCE: Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and β-sitosterol.

    AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.

    MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).

    RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.

    CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

    Matched MeSH terms: Breast Neoplasms/pathology
  17. Yeap SK, Mohd Ali N, Akhtar MN, Razak NA, Chong ZX, Ho WY, et al.
    Molecules, 2021 Feb 26;26(5).
    PMID: 33652854 DOI: 10.3390/molecules26051277
    (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.
    Matched MeSH terms: Breast Neoplasms/pathology
  18. Hod R, Maniam S, Mohd Nor NH
    Molecules, 2021 Feb 19;26(4).
    PMID: 33669783 DOI: 10.3390/molecules26041105
    Equol is a soy isoflavone metabolite that can be produced by intestinal bacteria. It is lipophilic and resembles natural oestrogens with an affinity to oestrogen receptors. This review is focused on how equol affects breast cancer, as evidenced by in vivo and in vitro studies. Equol is considered chemoprotective in specific endocrine-related pathologies, such as breast cancer, prostate cancer, cardiovascular diseases, and menopausal symptoms. In humans, not everyone can produce equol from gut metabolism. It is postulated that equol producers benefit more than non-equol producers for all the endocrine-related effects. Equol exists in two enantiomers of R-equol and S-equol. Earlier studies, however, did not specify which enantiomer was being used. This review considers equol's type and concentration variations, pathways affected, and its outcome in in vivo and in vitro studies.
    Matched MeSH terms: Breast Neoplasms/pathology*
  19. Sabtu SN, Sani SFA, Looi LM, Chiew SF, Pathmanathan D, Bradley DA, et al.
    Sci Rep, 2021 Feb 05;11(1):3250.
    PMID: 33547362 DOI: 10.1038/s41598-021-81426-x
    The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600-1800 cm-1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey's multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.
    Matched MeSH terms: Breast Neoplasms/pathology*
  20. Daud SM, Yaacob NS, Fauzi AN
    Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):59-65.
    PMID: 33576213 DOI: 10.31557/APJCP.2021.22.S1.59
    OBJECTIVE: The persistent activation of aerobic glycolysis in cancer cells results in accumulation of lactate and other metabolic intermediates that contribute to tumorigenesis. Increased glycolysis is frequently dysregulated in triple-negative breast cancer (TNBC), which promotes tumor growth and immune escape. This study was conducted to investigate the effect of 2-methoxy-1, 4-naphthoquinone (MNQ), compound extracted from Impatiens balsamina on glycolytic activities in human breast adenocarcinoma, MDA-MB-231 cells.

    METHODS: Initially, MTT proliferation assay was used to test the cell viability with various doses of MNQ (5-100 µM). As the half maximal inhibitory concentration (IC50) was obtained, glucose uptake and lactate assays of the cells were tested with IC50 dose of MNQ. The treated cells were also subjected to gene and protein analysis of glycolysis-related molecules (GLUT1 and Akt).

    RESULTS: The results showed that MNQ decreased the percentage of MDA-MB-231 cell viability in a dose-dependent manner with the IC50 value of 29 µM. The percentage of glucose uptake into the cells and lactate production decreased significantly after treatment with MNQ as compared to untreated cells. Remarkably, the expressions of GLUT1 and Akt molecules decreased in MNQ-treated cells, suggesting that the inhibition of glycolysis by MNQ is GLUT1-dependent and possibly mediated by the Akt signaling pathway.

    CONCLUSION: Our findings indicate the ability of MNQ to inhibit the glycolytic activities as well as glycolysis-related molecules in MDA-MB-231 cells, suggesting the potential of MNQ to be further developed as an effective anticancer agent against TNBC cells.

    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology
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