Displaying publications 1 - 20 of 29 in total

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  1. Madden SF, Cremona M, Farrelly AM, Low WH, McBryan J
    Cancer Gene Ther, 2023 Feb;30(2):324-334.
    PMID: 36266450 DOI: 10.1038/s41417-022-00548-0
    To prevent the development of endocrine-resistant breast cancer, additional targeted therapies are increasingly being trialled in combination with endocrine therapy. The molecular mechanisms facilitating cancer cell survival during endocrine treatment remain unknown but could help direct selection of additional targeted therapies. We present a novel proteomic timecourse dataset, profiling potential drug targets in a population of MCF7 cells during 1 year of tamoxifen treatment. Reverse phase protein arrays profiled >70 proteins across 30 timepoints. A biphasic response to tamoxifen was evident, which coincided with changes in growth rate. Tamoxifen strongly impeded cell growth for the first 160 days, followed by gradual growth recovery and eventual resistance development. The growth-impeded phase was distinguished by the phosphorylation of Stat3 (y705) and Src (y527). Tumour tissue from patients treated with neo-adjuvant endocrine therapy (<4 months) also displayed increased Stat3 and Src signalling. Inhibitors of Stat3 (napabucasin) and Src (dasatinib), were effective at killing tamoxifen-treated MCF7 and T47D cells. Sensitivity to both drugs was significantly enhanced once tamoxifen had induced the growth-impeded phase. This novel proteomic resource identifies key mechanisms enabling cell survival during tamoxifen treatment. It provides valuable insight into potential drug combinations and timing that may prevent the development of endocrine resistance.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology; Antineoplastic Agents, Hormonal/therapeutic use
  2. Othman NH, Othman MS, Ismail AN, Mohammad NZ, Ismail Z
    Aust N Z J Obstet Gynaecol, 1996 May;36(2):216-8.
    PMID: 8798320
    A 30-year old female who initially had typical endometriosis treated according to a standard regimen later developed numerous highly vascular endometrial polyps on the vagina, cervix, ureter, serosal surfaces of the uterus, pouch of Douglas (POD) and other areas of pelvic peritoneum as well as the endometrium 8 months after withdrawal of treatment with Zoladex gonadotrophin releasing hormone (GnRH) agonist used for treatment of this disease. We postulate that these polyps developed as a rebound phenomenon upon withdrawal of Zoladex. We believe this is the first report of this complication following use of GnRH analogue.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/adverse effects*; Antineoplastic Agents, Hormonal/therapeutic use
  3. Abubakar MB, Wei K, Gan SH
    Pharmacogenet Genomics, 2014 Dec;24(12):575-81.
    PMID: 25203739 DOI: 10.1097/FPC.0000000000000092
    Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/adverse effects; Antineoplastic Agents, Hormonal/pharmacokinetics*
  4. Kong WY, Leedman P, Irish A
    Intern Med J, 2014 Sep;44(9):932-4.
    PMID: 25201428 DOI: 10.1111/imj.12022
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage; Antineoplastic Agents, Hormonal/adverse effects*
  5. Teh LK, Mohamed NI, Salleh MZ, Rohaizak M, Shahrun NS, Saladina JJ, et al.
    AAPS J, 2012 Mar;14(1):52-9.
    PMID: 22183189 DOI: 10.1208/s12248-011-9313-6
    CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacokinetics; Antineoplastic Agents, Hormonal/pharmacology; Antineoplastic Agents, Hormonal/therapeutic use
  6. Ho WY, Yeap SK, Ho CL, Rahim RA, Alitheen NB
    PLoS One, 2012;7(9):e44640.
    PMID: 22970274 DOI: 10.1371/journal.pone.0044640
    In comparison to monolayer cells, MCTS has been claimed as more suitable candidate for studying drug penetration due to the high resemblance to solid tumors. However, the cultivation of MCTS is cumbersome, time consuming, and most technique fail to generate spheroids with uniform sizes. Therefore, the application of spheroid cultures in high throughput screening has been rather limiting. Besides, the lack of a well established screening protocol method that is applicable to spheroid could also be attributed to this limitation. Here we report a simple way of cultivating homogenous MCTS cultures with compact and rigid structure from the MCF-7 cells. Besides, we had also made some modifications to the standard MTT assay to realize high throughput screening of these spheroids. Using the modified protocol, tamoxifen showed cytotoxicity effect towards MCTS cultures from MCF-7 with high consistency. The results correlated well with the cultures' response assessed by LDH release assay but the latter assay was not ideal for detecting a wide range of cytotoxicity due to high basal background reading. The MTT assay emerged as a better indicator to apoptosis event in comparison to the LDH release assay. Therefore, the method for spheroid generation and the modified MTT assay we reported here could be potentially applied to high throughput screening for response of spheroid cultures generated from MCF-7 as well as other cancer cell lines towards cytotoxic stimuli.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology
  7. Lim SS, Sockalingam JK, Tan PC
    Int J Gynaecol Obstet, 2008 May;101(2):178-83.
    PMID: 18164303 DOI: 10.1016/j.ijgo.2007.10.020
    To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage*
  8. Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A
    Drug Des Devel Ther, 2017;11:771-782.
    PMID: 28352153 DOI: 10.2147/DDDT.S123939
    Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage*; Antineoplastic Agents, Hormonal/metabolism; Antineoplastic Agents, Hormonal/pharmacokinetics; Antineoplastic Agents, Hormonal/pharmacology
  9. Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Zainal Z, Hakim MN
    Int J Nanomedicine, 2011;6:3099-111.
    PMID: 22163163 DOI: 10.2147/IJN.S24510
    A new simple preparation method for a hippurate-intercalated zinc-layered hydroxide (ZLH) nanohybrid has been established, which does not need an anion-exchange procedure to intercalate the hippurate anion into ZLH interlayers.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology*; Antineoplastic Agents, Hormonal/chemistry
  10. Lim IL, Loo AVP, Subrayan V, Khang TF, See MH, Alip A, et al.
    Breast, 2018 Jun;39:117-122.
    PMID: 29660599 DOI: 10.1016/j.breast.2018.04.003
    It is now increasingly common for breast cancer patients to receive adjuvant tamoxifen therapy for a period of up to 10 years. As survival rate increases, managing tamoxifen ocular toxicities is important for patients' quality of life. Macular pigments in photoreceptor cells protect against free radical damage, which can cause macular degeneration. By reducing macular pigment concentration, tamoxifen may increase the risk of macular degeneration. Here, we compared macular pigment optical density (MPOD) and central macular thickness between breast cancer patients on tamoxifen adjuvant therapy (n = 70), and a control group (n = 72). Multiple regression analysis indicated that MPOD decreases with increasing tamoxifen dosage, up to a threshold of about 20 g, after which MPOD plateaus out. Mean MPOD in the treatment group (mean = 0.40) was significantly lower (p-value = 0.02) compared to the control group (mean = 0.47) for the left eye, and for the right eye (treatment mean = 0.39; control mean = 0.48; p-value = 0.009). No significant difference in mean central macular thickness was found between the treatment and the control group (p-values > 0.4). In the control group, MPOD and central macular thickness showed significant correlation (r∼0.30; p-values 
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage; Antineoplastic Agents, Hormonal/adverse effects*
  11. Mohamad NV, Soelaiman IN, Chin KY
    Endocr Metab Immune Disord Drug Targets, 2017 Nov 16;17(4):276-284.
    PMID: 28925899 DOI: 10.2174/1871530317666170919112757
    BACKGROUND AND OBJECTIVE: Prostate cancer is the most prevalent non-cutaneous cancer in men, which causes significant mortality among the patients. Since prostate cancer cells are stimulated by androgen, effective androgen ablation in men is one of the essential strategies in the management of prostate cancer.

    DISCUSSION: Several treatment options are available for different stages of prostate cancer. Hormone therapy known as androgen deprivation therapy (ADT) is the first line treatment used to treat advanced prostate cancer. Chemical castration by gonadotropin-releasing hormone agonists suppresses lutenizing hormone production, which in turn inhibits the production of testosterone and dihydrotestosterone. This will prevent the growth of prostate cancer cells. However, ADT causes deleterious effects on bone health because the androgens are essential in preserving optimal bone health in men.

    CONCLUSION: Various observational studies showed that long-term ADT for advanced or metastatic prostate cancer was associated with decreased bone mineral density, as well as altered body composition that might affect bone health. Considering the potential impact of osteoporotic fracture, interventions to mitigate these skeletal adverse effects should be considered by physicians when initiating ADT on their patients.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology; Antineoplastic Agents, Hormonal/therapeutic use*
  12. Love RR, Hossain SM, Hussain MM, Mostafa MG, Laudico AV, Siguan SS, et al.
    Eur J Cancer, 2016 06;60:107-16.
    PMID: 27107325 DOI: 10.1016/j.ejca.2016.03.011
    PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes.

    METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase.

    RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%.

    CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

    Study site: Bangladesh, The Philippines, China, Nigeria,
    Indonesia, Malaysia, Taiwan, Morocco, and Vietnam
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
  13. Bhoo-Pathy N, Balakrishnan N, See MH, Taib NA, Yip CH
    World J Surg, 2016 12;40(12):2913-2921.
    PMID: 27456497 DOI: 10.1007/s00268-016-3658-z
    BACKGROUND: Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting.

    METHODS: All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities.

    RESULTS: One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients.

    CONCLUSION: While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.

    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use*
  14. Bhoo-Pathy N, Verkooijen HM, Taib NA, Hartman M, Yip CH
    Br J Surg, 2011 Nov;98(11):1566-72.
    PMID: 21858791 DOI: 10.1002/bjs.7650
    Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  15. D'Souza UJ
    Asian J Androl, 2003 Sep;5(3):217-20.
    PMID: 12937805
    To evaluate the effect of tamoxifen citrate on male reproductive system of rat.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/toxicity*
  16. Jennings CJ, Zainal N, Dahlan IM, Kay EW, Harvey BJ, Thomas W
    Anticancer Res, 2016 11;36(11):5905-5913.
    PMID: 27793915
    Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology*
  17. Ngoo KS, Rohaizak M, Naqiyah I, Shahrun Niza AS
    Singapore Med J, 2009 May;50(5):519-21.
    PMID: 19495524
    Breast cancer is a rare condition among men with a reported incidence of about one percent. Nevertheless, it is thought to behave similarly in both genders. Due to its rarity, male breast cancer is not widely reported, especially in the Asian population.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/therapeutic use
  18. Sivalingam N, Pathmalingam A
    Singapore Med J, 1999 Jun;40(6):402-4.
    PMID: 10489508
    Endometrial changes have been observed when tamoxifen is used as an adjuvant therapy for carcinoma of the breast in postmenopausal women with positive estrogen receptors status.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/adverse effects*
  19. Hassan F, El-Hiti GA, Abd-Allateef M, Yousif E
    Saudi Med J, 2017 Apr;38(4):359-365.
    PMID: 28397941 DOI: 10.15537/smj.2017.4.17061
    OBJECTIVES: To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells. Methods: This is a prospective study. Anastrozole's mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research's, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research  and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016. Results: The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control. Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/pharmacology*
  20. How CW, Rasedee A, Manickam S, Rosli R
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
    PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009
    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage; Antineoplastic Agents, Hormonal/pharmacokinetics
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