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  1. Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
    Matched MeSH terms: Breast Neoplasms
  2. Abdelgawad MA, Bakr RB, Ahmad W, Al-Sanea MM, Elshemy HAH
    Bioorg. Chem., 2019 Nov;92:103218.
    PMID: 31536956 DOI: 10.1016/j.bioorg.2019.103218
    To enhance the cytotoxicity of benzimidazole and/or benzoxazole core, the benzimidazole/benzoxazole azo-pyrimidine were synthesized through diazo-coupling of 3-aminophenybenzimidazole (6a) or 3-aminophenylbenzoxazole (6b) with diethyl malonate. The new azo-molanates 6a&b mixed with urea in sodium ethoxide to afford the benzimidazolo/benzoxazolopyrimidine 7a&b. The structure elucidation of new synthesized targets was proved using spectroscopic techniques NMR, IR and elemental analysis. The cytoxicity screening had been carried out against five cancer cell lines: prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), pancreas cancer (PaCa-2) and colon cancer (HT-29). Furthermore, the antioxidant activity, phospholipase A2-V and cyclooxygenases inhibitory activities of the target compounds 7a&b were evaluated and the new compounds showed potent activity (cytotoxicity IC50 range from 4.3 to 9.2 µm, antioxidant activity from 40% to 80%, COXs or LOX inhibitory activity from 1.92 µM to 8.21 µM). The docking of 7a&b was made to confirm the mechanism of action.
    Matched MeSH terms: Breast Neoplasms
  3. Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, et al.
    EBioMedicine, 2019 Oct 16.
    PMID: 31629678 DOI: 10.1016/j.ebiom.2019.09.006
    BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

    METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

    FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

    Matched MeSH terms: Breast Neoplasms
  4. Mutazah R, Hamid HA, Mazila Ramli AN, Fasihi Mohd Aluwi MF, Yusoff MM
    Food Chem. Toxicol., 2019 Oct 15.
    PMID: 31626839 DOI: 10.1016/j.fct.2019.110869
    Clinacanthus nutans has attracted Malaysian public interest due to its high medicinal value in the prevention of cancer. Currently, the specific compound or compounds giving rise to the anticancer potential of C. nutans has not been investigated thoroughly. The extraction was carried out by MeOH at room temperature using the powdered bark of C. nutans, while chromatography was carried out on a silica gel RP-18 column using the crude methanolic extract. Six fractions collected from column chromatography were evaluated by MTT assay against two breast cancer cell lines: MDA-MB-231 and MCF-7. Amongst the fractions, A12 and A17 were shown to exhibit the highest activity. Two sulphur-containing compounds, viz., entadamide C (1) and clinamide D (2), were isolated from these fractions. Molecular docking simulation studies revealed that entadamide C and clinamide D could bind favourably to the caspase-3 binding site with the binding energy of -4.28 kcal/mol and -4.84 kcal/mol, respectively. This study provides empirical evidence for the presence of sulphur-containing compounds in the leaves of C. nutans that displayed anticancer effects which explains its ethnomedicinal application against breast cancer. The docking simulation study showed that both compounds could serve as important templates for future drug design and development.
    Matched MeSH terms: Breast Neoplasms
  5. Loh HY, Norman BP, Lai KS, Rahman NMANA, Alitheen NBM, Osman MA
    Int J Mol Sci, 2019 Oct 06;20(19).
    PMID: 31590453 DOI: 10.3390/ijms20194940
    MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
    Matched MeSH terms: Breast Neoplasms
  6. Schliemann D, Su TT, Paramasivam D, Somasundaram S, Ibrahim Tamin NSB, Dahlui M, et al.
    Transl Behav Med, 2019 Oct 04.
    PMID: 31583402 DOI: 10.1093/tbm/ibz134
    Increasingly, policy and research attention is being directed toward improving global health in low- and middle-income countries. This study investigated the cultural adaptation of a UK-designed and developed evidence-based mass media campaign with the aim of improving colorectal cancer and breast cancer awareness in Malaysia. Guided by the heuristic framework of cultural adaptation, a multidisciplinary team adapted the UK Be Cancer Aware programme for implementation in the Malaysian context. The approach included five steps: (a) information gathering and needs assessment; (b) preliminary design; (c) preliminary testing; (d) refinement; and (e) final trial. Key findings from the information gathering stage related to the need to take into account differences in ethnicity, religion, and beliefs about cancer. Discussions with experts indicated that particular words were not acceptable in Malay culture and that specific aspects were "taboo" (e.g., showing pictures of breasts in relation to breast cancer on TV). Stage 3 of the analysis revealed that the presentation of cancer survivors rather than health professionals on programme materials was preferred by Malaysians and that there was a poor level of awareness about colorectal cancer. The results were used systematically to adapt two culturally suitable cancer awareness mass media campaigns for implementation in Malaysia. The developed materials were in line with government priorities and took into account the local health care system structure. The establishment of a partnership with key stakeholders (e.g., the Ministry of Health and the lead patient advocacy organization) and the application of a systematic approach to address cultural factors and resource constraints contribute to the successful implementation of public health programmes in global health settings.
    Matched MeSH terms: Breast Neoplasms
  7. Cheong PCH, Yong YS, Fatima A, Ng ST, Tan CS, Kong BH, et al.
    IUBMB Life, 2019 Oct;71(10):1579-1594.
    PMID: 31190445 DOI: 10.1002/iub.2101
    A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with a predicted molecular mass of 22.8 kDa, was overexpressed in water-soluble form without signal peptide and purified via native affinity chromatography Ni-NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin-related plant lectin. In its native form, Rhinocelectin exists as a homo-tetramer predicted with four chains of identical proteins consisting of 11 beta-sheet structures with only one alpha-helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA-MB-231 and breast cancer MCF-7 are 36.52 ± 13.55 μg mL-1 and 53.11 ± 22.30 μg mL-1 , respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 μg mL-1 . The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 μg mL-1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 μg mL-1 . The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 μg mL-1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 μg mL-1 and 6.250 μg mL-1 , respectively.
    Matched MeSH terms: Triple Negative Breast Neoplasms
  8. Chan JY, Ahmad Kayani AB, Md Ali MA, Kok CK, Ramdzan Buyong M, Hoe SLL, et al.
    Electrophoresis, 2019 Oct;40(20):2728-2735.
    PMID: 31219180 DOI: 10.1002/elps.201800442
    This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.
    Matched MeSH terms: Breast Neoplasms
  9. Famurewa AC, Ekeleme-Egedigwe CA, David EE, Eleazu CO, Folawiyo AM, Obasi NA
    PMID: 31532279 DOI: 10.1080/15376516.2019.1669243
    Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1β, (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.
    Matched MeSH terms: Breast Neoplasms
  10. Mohamed Amin Z, Che Ani MA, Tan SW, Yeap SK, Alitheen NB, Syed Najmuddin SUF, et al.
    Sci Rep, 2019 Sep 30;9(1):13999.
    PMID: 31570732 DOI: 10.1038/s41598-019-50222-z
    The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 29. Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine.
    Matched MeSH terms: Breast Neoplasms
  11. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, et al.
    JAMA Oncol, 2019 Sep 27.
    PMID: 31560378 DOI: 10.1001/jamaoncol.2019.2996
    Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

    Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

    Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

    Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

    Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

    Matched MeSH terms: Breast Neoplasms
  12. Mohamad Hanif EA
    Mol. Biol. Rep., 2019 Sep 24.
    PMID: 31552595 DOI: 10.1007/s11033-019-05079-w
    FEC chemo-resistance in triple negative breast cancer (TNBC) remains a challenge. Therefore it is crucial to determine the right treatment regime by understanding molecular mechanisms of driver regulators involved in the progression of TNBCs. This study aims to understand SETD1A mechanisms in TNBC development in two TNBC cell lines. SETD1A was transiently transfected in MDA-MB-468 (FEC good prognosis) and Hs578T (FEC poor prognosis). Regulation of potential targets miR205, EMT marker ZEB1 and LRG1 and proliferative marker Ki-67 were tested by RqPCR to elucidate SETD1A interactions. This study displayed significant recovery of miR205 with SETD1A depletion and reduction of ZEB1 in MDA-MB-468. However, ZEB1 remained unchanged in Hs578T indicating ZEB1 regulation may be outcompeted by other mechanisms associated with aggressive cell line characteristics and the expression of endogenous ZEB1 was relatively high in Hs578T. Elevation of LRG1 and declined Ki-67 were observed by SETD1A knocked down. Enhanced expression was observed by LRG1 in Hs578T and not in MDA-MB-468 suggesting LRG1 contributed to distinct poor FEC outcome in TNBCs. The underlying mechanism of SETD1A in miR205/ZEB1/Ki-67/LRG1 axis needs further evaluation. Whether abrogation of the pathway is indeed associated with transcriptional or post-transcriptional activation in TNBC cell lines models, clearly validation in clinical samples is warranted to achieve its prognostic and therapeutic values in TNBCs.
    Matched MeSH terms: Triple Negative Breast Neoplasms
  13. Dinesh BJ, Hayati F, Azizan N, Abdul Rashid NF
    BMJ Case Rep, 2019 Sep 18;12(9).
    PMID: 31537599 DOI: 10.1136/bcr-2019-231516
    Florid papillomatosis (FP) of the nipple, or nipple adenoma, is a rare breast tumour, affecting middle-aged group population. A 46-year-old woman presented to us with a cauliflower-like FP of the right nipple with no blood stained discharge or breast lump. FP can be mistaken clinically for Paget's disease and occasionally misinterpreted as invasive ductal or intraductal carcinoma. Extensive intervention, correct diagnosis and prompt treatment are essential. Any breast pathology requires triple assessment including FP of the nipple. Once the diagnosis of ductal carcinoma is excluded, simple complete excision can be undertaken. This is to ensure complete obliteration of disease recurrence and preservation of cosmetic result. We discuss the pathology and psychosocial aspects of FP.
    Matched MeSH terms: Breast Neoplasms
  14. Nigjeh SE, Yeap SK, Nordin N, Rahman H, Rosli R
    Molecules, 2019 Sep 05;24(18).
    PMID: 31492037 DOI: 10.3390/molecules24183241
    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females globally. The tumorigenic activities of cancer cells such as aldehyde dehydrogenase (ALDH) activity and differentiation have contributed to relapse and eventual mortality in breast cancer. Thus, current drug discovery research is focused on targeting breast cancer cells with ALDH activity and their capacity to form secondary tumors. Citral (3,7-dimethyl-2,6-octadienal), from lemon grass (Cymbopogoncitrates), has been previously reported to have a cytotoxic effect on breast cancer cells. Hence, this study was conducted to evaluate the in vivo effect of citral in targeting ALDH activity of breast cancer cells. BALB/c mice were challenged with 4T1 breast cancer cells followed by daily oral feeding of 50 mg/kg citral or distilled water for two weeks. The population of ALDH+ tumor cells and their capacity to form secondary tumors in both untreated and citral treated 4T1 challenged mice were assessed by Aldefluor assay and tumor growth upon cell reimplantation in normal mice, respectively. Citral treatment reduced the size and number of cells with ALDH+ activity of the tumors in 4T1-challenged BALB/c mice. Moreover, citral-treated mice were also observed with smaller tumor size and delayed tumorigenicity after reimplantation of the primary tumor cells into normal mice. These findings support the antitumor effect of citral in targeting ALDH+ cells and tumor recurrence in breast cancer cells.
    Matched MeSH terms: Breast Neoplasms
  15. Liaw YY, Loong FS, Tan S, On SY, Khaw E, Chiew Y, et al.
    Breast J, 2019 Sep 04.
    PMID: 31486157 DOI: 10.1111/tbj.13520
    Women with a positive family history of breast cancer are greatly predisposed to breast cancer development. From January 2007 to December 2016, 1101 patients with a histologically confirmed breast cancer were divided into two groups: patients with and without a positive family history of breast cancer. Variables including age at presentation, ethnicity, tumor size, age at menarche, age at menopause, oral contraceptive pill (OCP) use, hormone replacement therapy (HRT), alcohol intake, smoking, body mass index (BMI), diabetes mellitus, parity, and breastfeeding were recorded. One hundred and fifty-nine out of 1101 (14.4%) of the patients had a family history of breast cancer. There was no significant difference in the incidence of breast cancer among Malays, Chinese, and Indians. Both patient groups presented at a mean age of about 60 years (+FH 60; -FH 61.2 P-value = .218). Significantly higher prevalence of history of benign breast disease (11.3%, P .018), nulliparity (13.2%, P .014), tumor size at presentation of more than 5 cm (47.3%, P 0.001), and bilateral site presentation (3.1%, P 0.029) were noted among respondents with a positive family history of breast cancer compared to those with a negative family history of breast cancer. The odds of having a tumor size larger than 5cm at presentation were almost two times higher in patients with a positive family history as compared to those without a family history (adjusted OR = 1.786, 95% CI 1.211-2.484) (P-value .003). Women in Malaysia, despite having a positive family history of breast cancer, still present late at a mean age of 60 with a large tumor size of more than 5 cm, reflecting a lack of awareness. Breastfeeding does not protect women with a family history from developing breast cancer.
    Matched MeSH terms: Breast Neoplasms
  16. Kwong SC, Abd Jamil AH, Rhodes A, Taib NA, Chung I
    J. Lipid Res., 2019 Sep 04.
    PMID: 31484694 DOI: 10.1194/jlr.M092379
    Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentivirus particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231 cells. FABP7-overexpressing Hs578T cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signalling, despite the lack of fatty acids in culture media, as it attempts to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signalling.
    Matched MeSH terms: Triple Negative Breast Neoplasms
  17. Fatemian T, Moghimi HR, Chowdhury EH
    Pharmaceutics, 2019 Sep 03;11(9).
    PMID: 31484456 DOI: 10.3390/pharmaceutics11090458
    : Pharmacotherapy as the mainstay in the management of breast cancer suffers from various drawbacks, including non-targeted biodistribution, narrow therapeutic and safety windows, and also resistance to treatment. Thus, alleviation of the constraints from the pharmacodynamic and pharmacokinetic profile of classical anti-cancer drugs could lead to improvements in efficacy and patient survival in malignancies. Moreover, modifications in the genetic pathophysiology of cancer via administration of small nucleic acids might pave the way towards higher response rates to chemotherapeutics. Inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized in this study to efficiently deliver various classes of therapeutics into cancer cells. Co-delivery of drugs and genetic materials was successfully attained through a carbonate apatite delivery device. On 4T1 cells, siRNAs against AKT and ERBB2 plus paclitaxel or docetaxel resulted in the largest increase in anti-cancer effects compared to CA/paclitaxel or CA/docetaxel. Therefore, these ingredients were selected for further in vivo investigations. Animals receiving injections of CA/paclitaxel or CA/docetaxel loaded with siRNAs against AKT and ERBB2 possessed significantly smaller tumors compared to CA/drug-treated mice. Interestingly, synergistic interactions in target protein knock down with combinations of CA/AKT/paclitaxel, CA/ERBB2/docetaxel were documented via western blotting.
    Matched MeSH terms: Breast Neoplasms
  18. Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, et al.
    Hum. Mutat., 2019 Sep;40(9):1557-1578.
    PMID: 31131967 DOI: 10.1002/humu.23818
    The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.
    Matched MeSH terms: Breast Neoplasms
  19. Walters K, Cox A, Yaacob H
    Genet. Epidemiol., 2019 Sep;43(6):675-689.
    PMID: 31286571 DOI: 10.1002/gepi.22212
    The default causal single-nucleotide polymorphism (SNP) effect size prior in Bayesian fine-mapping studies is usually the Normal distribution. This choice is often based on computational convenience, rather than evidence that it is the most suitable prior distribution. The choice of prior is important because previous studies have shown considerable sensitivity of causal SNP Bayes factors to the form of the prior. In some well-studied diseases there are now considerable numbers of genome-wide association study (GWAS) top hits along with estimates of the number of yet-to-be-discovered causal SNPs. We show how the effect sizes of the top hits and estimates of the number of yet-to-be-discovered causal SNPs can be used to choose between the Laplace and Normal priors, to estimate the prior parameters and to quantify the uncertainty in this estimation. The methodology can readily be applied to other priors. We show that the top hits available from breast cancer GWAS provide overwhelming support for the Laplace over the Normal prior, which has important consequences for variant prioritisation. This work in this paper enables practitioners to derive more objective priors than are currently being used and could lead to prioritisation of different variants.
    Matched MeSH terms: Breast Neoplasms
  20. Majeed Alneamy JS, A Hameed Alnaish Z, Mohd Hashim SZ, Hamed Alnaish RA
    Comput. Biol. Med., 2019 Sep;112:103348.
    PMID: 31356992 DOI: 10.1016/j.compbiomed.2019.103348
    Accurate medical disease diagnosis is considered to be an important classification problem. The main goal of the classification process is to determine the class to which a certain pattern belongs. In this article, a new classification technique based on a combination of The Teaching Learning-Based Optimization (TLBO) algorithm and Fuzzy Wavelet Neural Network (FWNN) with Functional Link Neural Network (FLNN) is proposed. In addition, the TLBO algorithm is utilized for training the new hybrid Functional Fuzzy Wavelet Neural Network (FFWNN) and optimizing the learning parameters, which are weights, dilation and translation. To evaluate the performance of the proposed method, five standard medical datasets were used: Breast Cancer, Heart Disease, Hepatitis, Pima-Indian diabetes and Appendicitis. The efficiency of the proposed method is evaluated using 5-fold cross-validation and 10-fold cross-validation in terms of mean square error (MSE), classification accuracy, running time, sensitivity, specificity and kappa. The experimental results show that the efficiency of the proposed method for the medical classification problems is 98.309%, 91.1%, 91.39%, 88.67% and 93.51% for the Breast Cancer, Heart Disease, Hepatitis, Pima-Indian diabetes and Appendicitis datasets, respectively, in terms of accuracy after 30 runs for each dataset with low computational complexity. In addition, it has been observed that the proposed method has efficient performance compared with the performance of other methods found in the related previous studies.
    Matched MeSH terms: Breast Neoplasms
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