【Abstract】 Objective To study the effects of different levels estradiol on inhibitory of tamoxifen on human mammary cancer cells(ER+) in vitro. Methods Estrogen receptor (ER) positive MCF7 human breast cancer cell line was treated by the same level of tamoxifen and different levels of estradiol in vitro. Cell proliferation was evaluated by MTT assay. Results E2 at concentrations between 1 × 10-12 mol/L to 1× 10-7 mol / L significantly stimulated the growth of MCF 7 . TAM (10 μmol/ L) inhabited the growth of MCF7 significantly. E2 at different levels may influence inhibitory of tamoxifen on MCF7 cell lines. E2 (1×10-8 mol/L) makes inhibitory of tamoxifen on MCF7 cell lines valueless.Conclusion E2 is the risk factor of breast cancer, and the concentration around breast cancer cells may influence the effects of TAM.
Objective To observe the influences of estradiol (E2), basic fibroblast growth factor (bFGF), and tamoxifen (TAM) on the proliferation of hemangioma vascular endothelial cell (HVEC). Methods Two strawberry hemangioma from 2 infants (case 1 and case 2) were prepared for HVEC culture. The HVEC on passage 3 were cultured in estrogenfree improved minimum essential medium (IMEM) and subjected to various treatments with 100 pg/ml 17-β-E2, 10 ng/ml bFGF, and 1×10-6 mol/L 4-OH-tamoxifen(4-OH-TAM). The experiment was divided into 5 groups: group 1(IMEM, control group), group 2(17-β-E2), group 3(bFGF), group 4(17-β-E2／bGFG) and group 5(17-β-E2／bGFG／4-OH-TAM). The cell count(CC) and DNA proliferation index (PI) were determined. Results Two cases of HVEC were successfully cultured in vitro. The HVEC showed cobblestoneslike under microscopy and factor Ⅷrelated antigen(also named as von Willebrand factor，vWF) was positive by immunochemical staining. At 9 days in case 1: CC and PI remained unchanged in the control group; CC and PI were slightly increased in group 2, being 1.4 and 1.6 times as much as those in the control group respectively (P＜0.05); CC and PI significantly increased in group 3, being2.6 and 2.3 times as much as those in the control group respectively (P＜0.01); CC and PI increased remarkably in group 4, being 3.7 and 2.9 times as much as those in thecontrol group respectively (P＜0.01); CC and PI were down to the levels of controls in group 5(P＞0.05). The results in case 2 were similar to those in case 1. Conclusion In vitro, the promoting effect of bFGF on HVEC proliferation is much ber than that of estrogen. Estrogen and bFGF enhance this proliferation in a synergistic manner, which can be inhibited by tamoxifen.
Objective To study the effects on MCF-7 breast cancer cells with combination of tamoxifen（TAM） and antisense oligonucleotide （ASODN） targeting survivin mRNA. Methods MCF-7 breast cancer cells were treated with a 20 mer ASODN targeting survivin mRNA and TAM, which were divided into three groups: TAM group (treated by TAM only), ASODN group (by ASODN only), and TAM+ASODN combined group (by TAM+ASODN combination). The growth inhibition of MCF-7 cells, the changes of cell cycles and apoptotic rate, the positive rate of survivin mRNA expression, and the activity of caspase-3 were tested by MTT, flow cytometry, hybridization in situ, and spectrophotometric method, respectively.Results The rate of growth inhibition of MCF-7 cells in the TAM+ASODN combined group was (62.26±3.92)%, which was significantly higher than that in the TAM group 〔(42.30±6.63)%〕 or ASODN group 〔(54.77±9.99)%〕, Plt;0.05. The apoptotic rate of MCF-7 cells was (28.08±4.32)% in the TAM+ASODN combined group, which was significantly higher than that in the TAM group 〔(18.94±4.01)%〕 or ASODN group 〔(21.12±3.95)%〕, Plt;0.01. The effect of arresting MCF-7 cells in G0/G1 phase in the TAM+ASODN combined group was ber than that in the TAM or ASODN group (Plt;0.05, Plt;0.01). The positive rate of survivin mRNA in the TAM+ASODN combined group was (13.38±3.45)%, which was significantly lower than that in the TAM group 〔(39.67±7.42)%〕 or ASODN group 〔(27.50±5.80)%〕, Plt;0.01. The activity of caspase-3 in the TAM+ASODN combined group （0.93±0.13） was significantly higher than that in the TAM group (0.50±0.09) or ASODN group (0.64±0.08), Plt;0.01. Conclusion The ASODN targeting survivin mRNA can promote the apoptosis of MCF-7 breast cancer cells, and make MCF-7 cells more sensitive to tamoxifen.
ObjectiveTo explore the role of toremifene in postmenopausal operable patients with luminal subtype of breast cancer in China. MethodsA total of 618 eligible patients diagnosed with luminal subtype of breast cancer from January 2000 to December 2009 in the Cancer Center of Sun Yat-sen University were analyzed. One hundred and fifteen patients were treated with toremifene(toremifene group) and 503 patients were treated with tamoxifen(tamoxifen group) as adjuvant endocrine therapy. Survival was compared by Kaplan-Meier with log-rank test in two groups. Cox analysis was used to compare different prognostic factors. ResultsThe general clinical data had no significant differences between the toremifene group and tamoxifen group (P > 0.05). After a median follow-up of 76 months, there was no statistical difference in the 5-year disease free survival rate and 5-year overall survival rate between the toremifene group and the tamoxifen group (5-year disease free survival rate:78.5% versus 85.5%, P=0.083;5-year overall survival rate:86.4% versus 92.0%, P=0.334). Univariated analysis showed that the histological grade, tumor size, lymph node status, TNM stage, HER-2 positive expression were associated with the disease free survival rate and overall survival rate(P < 0.05). Multivariated analysis showed that the tumor size and lymph node status were the independent risk factors of disease free survival rate and overall survival rate for postmenopausal operable patients with luminal subtype of breast cancer(P < 0.05). HER-2 positive expression was the independent risk factor in predicting disease free survival rate for patients with tamoxifen or toremifene. There was no grade 3 or 4 toxicity for all the patients according to CTC AE 4.0 grade. ConclusionsSimilar benefit is found in disease free survival rate and overall survival rate in Chinese postmenopausal patients with operable luminal subtype of breast cancer between patients receiving toremifene and tamoxifen with tolerable adverse effects. HER-2 status is associated with disease free survival rate.
ObjectiveTo summarize the relevant studies of pharmacological mechanism of tamoxifen and its influence on ovary function in order to provide information and evidence for the therapy of breast cancer. MethodsPapers published from January 1950 to January 2014, were retrieved in MedLine, OVID, CBM, CNKI databases using the keywords on tamoxifen, drug metabolism, ovary, sex hormone, etc, 1286 papers were retrieved in English literatures, and 621 in Chinese literatures. Criteria of paper adoption:①The clinical and basic studies about metabolism of tamoxifen, metabolic effect of tamoxifen, and gene polymorphism of CYP2D6.②The role played by estrogen receptor and protein cofactors in tamoxifen effect.③The clinical and basic studies about tamoxifen induced ovulation, caused endometrial thickening, changed sex hormone levels. According to the above criteria, 152 papers were selected, and 77 papers out of them were finally analyzed and reviewed. Results①The tamoxifen metabolite 4-OH-N-tamoxifen was the main working component, the decreased levels could predict the poor prognosis.②The CYP2D6 gene polymorphism could affect the metabolic effect of tamoxifen and the therapeutic effect of patients with breast cancer.③The metabolic effect of tamoxifen needed the participation of the estrogen receptors and protein cofactors.④Tamoxifen could affect the reproductive system function through the estrogen receptor of H-P-O axis, ovary, and endometrium. ConclusionsMetabolic effect of tamoxifen is regulated by gene, it could affect reproductive system functions through estrogen receptor. the mechanism that tamoxifen cowld affect the hormone levels and wherther it could reflect the ovarian function by monitering the hormone levels continuously for patients with breast cancer need to be researched.
ObjectiveTo investigate the efficacy and safety of using tamoxifen sequential with the third generation aromatase inhibitors versus the third generation aromatase inhibitors or tamoxifen alone for postmenopausal hormone receptor-positive breast cancer patients.MethodsThe Cochrane Library (Issue 10, 2016), PubMed, EMbase, CNKI, and WanFang Data were searched to collect randomized controlled trials on using tamoxifen sequential with the third generation aromatase inhibitors versus the third generation aromatase inhibitors or tamoxifen alone for postmenopausal hormone receptor-positive breast cancer patients from inception to October, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 9 studies involving 22 005 patients were included. The results of meta-analysis showed that the sequential therapy group was superior to the tamoxifen monotherapy group on overall survival (HR=0.71, 95%CI 0.52 to 0.98, P=0.04) and recurrence-free survival (HR=0.60, 95%CI 0.46 to 0.79, P=0.000 3). However, no significant difference was found in overall survival and disease free survival between the sequential therapy group and the aromatase inhibitors monotherapy group. As to adverse events, compared with the tamoxifen monotherapy group, the sequential therapy group could reduce the incidence of endometrial hyperplasia (OR=0.22, 95%CI 0.11 to 0.45, P<0.000 01), death (OR=0.74, 95%CI 0.66 to 0.84, P<0.000 01) and metastasis (OR=0.79, 95%CI 0.68 to 0.91, P=0.001); however, the incidence of bone fracture was higher in sequential therapy group compared with intamoxifen monotherapy group (OR=1.31, 95%CI 1.13 to 1.51, P=0.000 3).ConclusionThe sequential therapy using tamoxifen and the third generation of aromatase inhibitors is better than tamoxifen monotherapy for postmenopausal hormone receptor-positive breast cancer patients. However, there is no significant difference in survival benefit between the sequential therapy and aromatase inhibitors monotherapy.
Immunoglobulin G4-related disease (IgG4-RD) is a new disease entity recognized at the start of this century noted to be involving many organ systems including endocrine system and thyroid in particular. It represents an immune mediated fibro inflammatory condition with characteristic histopathological appearance affecting single or multiple organs. In general, immunoglobulin G4-related thyroid disease (IgG4-RTD) is rarely considered and it may be isolated or with other organ involvement. Four subcategories of IgG4-RTD have been identified so far: Riedel thyroiditis, fibrosing variant of Hashimoto thyroiditis, immunoglobulin G4-related Hashimoto thyroiditis, and Graves disease with elevated immunoglobulin G4 levels. The diagnostic approach is complex and the work up relies on the coexistence of clinical features, histological features and serological evidence. Demonstration of the classic histopathological features is vital to diagnose IgG4-RD in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. The treatments for IgG4-RTD include medical and surgical options. Steroids are first line treatment though it may need further evaluation. Tamoxifen and rituximab are second line treatment for steroid resistant patients. Surgical excision of thyroid gland in presence of compression symptoms is the surgical option. Inspite of pathophysiology of the disease being poorly understood till now, early and prompt diagnosis and an early treatment initiation can improve the outcomes.
ObjectiveTo observe the multimodal imaging characteristics of tamoxifen retinopathy. MethodsA retrospective case study. From January 2019 to December 2021, 4 patients (8 eyes) with tamoxifen retinopathy diagnosed in Tangshan Eye Hospital were included in the study. All patients were female, with sick binoculus. The age was 59.5±4.6 years. After breast cancer resection, tamoxifen 20 mg/d was taken orally consecutively, including 1, 1, and 2 cases who took tamoxifen orally for 5, 7, and ≥10 years. All eyes were examined by fundus color photography, optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and fundus autofluorescence (AF). The multi-mode image features of the fundus of the affected eyes were observed. ResultsThe yellow white dot crystal like material deposition in the macular area was observed in all eyes. In fundus AF examination, macular area showed patchy strong AF. FFA examination showed telangiectasia and fluorescein leakage in macular area at late stage. OCT showed that punctate strong reflexes could be seen between the neuroepithelial layers in the macular region with the formation of a space between the neuroepithelial layers, the interruption of the elliptical zone (EZ), and the formation of a hole in the outer lamella including 4, 5 and 3 eyes; The thickness of ganglion cells in macular region decreased in 7 eyes. OCTA showed that the blood flow density of the superficial retinal capillary plexus around the arch ring was decreased, and the retinal venules were dilated in 2 eyes; Deep capillary plexus (DCP) showed telangiectasia. ConclusionDeposition of yellowish white dot like crystals can be seen in the macular region of tamoxifen retinopathy; dotted strong reflex between neuroepithelial layers, cavity formation, thinning of ganglion cell layer, EZ middle fissure and outer lamellar fissure; DCP capillaries and venules around the arch were dilated; telangiectasia in macular region; flaky strong AF in macular region.