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Fulltext Concurrent massive breast enlargement, myasthenia gravis and dermopathy as manifestations of penicillamine toxicity in a Wilson's disease patient

Tan SS, Latif SA, Poh WY

Med J Malaysia, 2012 Jun;67(3):323-5.
PMID: 23082426 MyJurnal

Penicillamine toxicity in Wilson's disease has been well reported but rarely seen now as newer agents are being used. We present a case who developed multiple rare complications of Penicillamine concurrently. Our patient is one of three siblings on Penicillamine, she was the only one who developed massive breast enlargement four months after commencing Penicillamine therapy, as well as dermatological adverse reactions and myasthenia gravis three more months later. All the adverse effects improved soon after substitution of the offending agent with Trientine.

Matched MeSH terms: Breast/drug effects
Anti-proliferation effect of Hevea brasiliensis latex B-serum on human breast epithelial cells

Lee YK, Lay LK, Mahsufi MS, Guan TS, Elumalai S, Thong OM

Pak J Pharm Sci, 2012 Jul;25(3):645-50.
PMID: 22713955

The rubber tree (Hevea brasiliensis) extracts are becoming increasingly visible in pharmaceutical and therapeutical research. The present study is aimed at examining the specific anti-proliferation property of H. brasiliensis latex B-serum sub-fractions against human breast cancer epithelial cell lines MCF-7 and MDA-MB231. The results showed that the latex whole B-serum and DBP sub-fraction exerted a specific anti-proliferation activity against cancer-origin cells MDA-MB231 but had little effect on non-cancer-origin cells. On the other hand, the anti-proliferative activity was diminished in the pre-heated B-serum fractions. With the low toxicity that the B-serum demonstrated previously in Brine Shrimp Lethality Test (BSLT), the present results suggest the potential use of the B-serum sub-fractions in cancer treatment.

Matched MeSH terms: Breast/drug effects*
Fulltext Cell viability and electrical response of breast cancer cell treated in aqueous graphene oxide solution deposition on interdigitated electrode

Ramli MM, Rosman AS, Mazlan NS, Ahmad MF, Halin DSC, Mohamed R, et al.

Sci Rep, 2021 10 19;11(1):20702.
PMID: 34667216 DOI: 10.1038/s41598-021-00171-3

Breast cancer is one of the most reported cancers that can lead to death. Despite the advances in diagnosis and treatment procedures, the possibility of cancer recurrences is still high in many cases. With that in consideration, researchers from all over the world are showing interest in the unique features of Graphene oxide (GO), such as its excellent and versatile physicochemical properties, to explore further its potential and benefits towards breast cancer cell treatment. In this study, the cell viability and electrical response of GO, in terms of resistivity and impedance towards the breast cancer cells (MCF7) and normal breast cells (MCF10a), were investigated by varying the pH and concentration of GO. Firstly, the numbers of MCF7 and MCF10a were measured after being treated with GO for 24 and 48 h. Next, the electrical responses of these cells were evaluated by using interdigitated gold electrodes (IDEs) that are connected to an LCR meter. Based on the results obtained, as the pH of GO increased from pH 5 to pH 7, the number of viable MCF7 cells decreased while the number of viable MCF10a slightly increased after the incubation period of 48 h. Similarly, the MCF7 also experienced higher cytotoxicity effects when treated with GO concentrations of more than 25 µg/mL. The findings from the electrical characterization of the cells observed that the number of viable cells has corresponded to the impedance of the cells. The electrical impedance of MCF7 decreased as the number of highly insulating viable cell membranes decreased. But in contrast, the electrical impedance of MCF10a increased as the number of highly insulating viable cell membranes increased. Hence, it can be deduced that the GO with higher pH and concentration influence the MCF7 cancer cell line and MCF10a normal breast cell.

Matched MeSH terms: Breast/drug effects
Fulltext Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth

Khoo BY, Miswan N, Balaram P, Nadarajan K, Elstner E

Int J Mol Sci, 2012;13(5):5607-27.
PMID: 22754319 DOI: 10.3390/ijms13055607

In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

Matched MeSH terms: Breast/drug effects
Fulltext Novel sesquiterpene lactone analogues as potent anti-breast cancer agents

Nakagawa-Goto K, Chen JY, Cheng YT, Lee WL, Takeya M, Saito Y, et al.

Mol Oncol, 2016 06;10(6):921-37.
PMID: 27055598 DOI: 10.1016/j.molonc.2016.03.002

Triple-negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti-TNBC agent has been a challenge in oncology. In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. DETD-35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA-MB-231 cells in a concentration-dependent manner. Comparative study of DETD-35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time-dependent G2/M cell-cycle arrest, while DETD-35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD-35 was evaluated using a lung metastatic MDA-MB-231 xenograft mouse model. DETD-35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX-2 in SCID mice. DETD-35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD-35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.

Matched MeSH terms: Breast/drug effects*
Fulltext Long-term exposure to insulin and volumetric mammographic density: observational and genetic associations in the Karma study

Borgquist S, Rosendahl AH, Czene K, Bhoo-Pathy N, Dorkhan M, Hall P, et al.

Breast Cancer Res, 2018 08 09;20(1):93.
PMID: 30092829 DOI: 10.1186/s13058-018-1026-7

BACKGROUND: Long-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants.
METHODS: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes.
RESULTS: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively).
CONCLUSIONS: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.

Matched MeSH terms: Breast/drug effects
Fulltext Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies

Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.

Int J Mol Sci, 2014 Apr 25;15(5):7225-49.
PMID: 24776765 DOI: 10.3390/ijms15057225

Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.

Matched MeSH terms: Breast/drug effects
Fulltext Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-β, PDGF-BB, c-Kit and SCF genes

Kadivar A, Kamalidehghan B, Akbari Javar H, Karimi B, Sedghi R, Noordin MI

Drug Des Devel Ther, 2017;11:469-481.
PMID: 28260860 DOI: 10.2147/DDDT.S124102

Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2-10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer.

Matched MeSH terms: Breast/drug effects