جستجوی مقالات مرتبط با کلیدواژه « Tamoxifen » در نشریات گروه « پزشکی »

One of the major challenges in gastric cancer (GC) chemotherapy is the phenomenon of multi-drug resistance (MDR). The epithelial-mesenchymal transition (EMT) and its key molecules, transforming growth factor-β (TGFβ) and SMAD2, play a central role in MDR occurrence.  Tamoxifen (TAM), a triphenylethylene derivative, can overcome MDR in human gastric cancers. The aim of this study was to investigate the effect of TAM on 5-FU resistance of GC by suppressing the TGFβ1/SMAD2 signaling pathway and EMT. The MKN-45 cell line was subjected to treatment with 5-FU, TAM and a combination of both. The MTT assay was used to investigate the cytotoxic effects of 5-FU and TAM, and the DNA laddering technique was used to assess DNA fragmentation and apoptosis. Real-time RT-PCR examined the change in gene expression in EMT-related genes (SNAI2, VIM, TGFβ1 and SMAD2). The results of the present study indicated that not only TAM treatment significantly decreased the IC50 of 5-FU (P≤0.05), but also the addition of TAM to 5-FU induced apoptosis in the MKN-45 cell line. Treatment with TAM and 5-FU significantly inhibited TGFβ1 and TGFβ1-induced expression of EMT markers (VIM and SNAI2) in MKN-45 cells (P≤0.05). The reduction of TGFβ1 targets downstream of the SMAD2 signaling pathway reversed the process of EMT and significantly increased the sensitivity of MKN-45 cells to 5-FU. The results of the present study suggested that reversal of EMT-mediated MDR via the TGFβ1/SMAD signaling pathway using TAM may be a potential new therapeutic strategy to overcome chemoresistance to 5-FU during GC chemotherapy.

Carbon nanotubes (CNTs) serve as molecular carriers for in vivo and in vitro delivery. Initial studies have suggested that nanotubes in drug delivery can enhance the therapeutic response to anti-cancer drugs. The present study intended to investigate the effect of CNTs carrying tamoxifen (TAM-CNTs) on the induction of apoptosis in the MDA-MB-231 cell line.

The cells were treated with various concentrations of TAM and TAM-CNTs. The IC50 for these compounds was determined using a MTT assay. The cells were then treated with a lower concentration of IC50. The BAX and BCL-2 genes expression were evaluated by Real-Time PCR and Western blot. Flow cytometry was employed for evaluating apoptosis induction by TAM and TAM-CNTs.

The IC50 value of TAM and TAM-CNTs in a 48-hour period was 66.19 mg/mL and 36.59 mg/mL, respectively. The results demonstrated that BAX in the cells treated with TAM and TAM-CNTs was upregulated 3.64 and 7.88 times, respectively (P <0.05). Conversely, BCL-2 was downregulated 3.98 and 5.31 times (P <0.05). Furthermore, Western blot experiments confirmed the expression of BAX and BCL-2 proteins based on their gene expression. Flow cytometry results indicated that the viability of MDA-MB-231 cells in the control group, TAM-treated, and TAM-CNTs-treated cells was 95.3%, 64.9%, and 13.75%, respectively. This suggests that TAM-CNTs significantly diminishes cell viability compared to TAM (P <0.001).

The findings revealed that TAM accompanied by CNTs exhibits a greater cytotoxic and apoptotic effect on MDA-MB-231 cells.

Breast cancer is an important women’s malignancy with high cancer-related deaths worldwide. Drug resistance lowers the treatment efficacy in this malignancy. This study aimed to explore the underlying mechanisms of histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to overcome resistance to tamoxifen in breast cancer cells.

Tamoxifen-resistance in MCF-7 breast cancer cells was simulated. MTT assay was used to detect the cytotoxic effects of HDAC inhibitor and PI3K inhibitor on the cancer cells. Trans-well assay was applied to evaluate the invasion and migration of the treated cancer cells. Flow cytometer assay was also applied to evaluate cell cycle phases in the treated cancer cells. Finally, expression of vascular endothelial growth factor (VEGF), E-cadherin, Vimentin, phosphorylated phosphatidylinositol kinase (p-PI3k), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target protein of rapamycin (p-mTOR) was evaluated by western blotting.

The obtained results indicated that HDAC inhibitor treatments significantly decreased viability, migration, and invasion in the cancer cells. Furthermore, the frequency of the treated cancer cells significantly increased in the S phase as well as significantly decreasing in the G2/M phase of the cell cycle. Moreover, HDAC inhibitor modified levels of VEGF, E-cadherin, Vimentin, p-PI3k, p-AKT, and p-mTOR proteins. However, HDAC inhibitor combined with PI3K inhibitor exerts more profound effects on the cancer cells as compared to HDAC inhibitor monotherapy.

HDAC inhibitors inhibited the survival of breast cancer drug-resistant cells, invasion, migration, and angiogenesis by inhibiting the PI3k/Akt/mTOR signaling pathway.

Background &  The administration of tamoxifen to post-menopausal patients with breast cancer may lead to vaginal bleeding, necessitating a thorough understanding of associated factors. Our objective was to investigate sonographic, hysteroscopic, and pathologic findings in breast cancer patients experiencing vaginal bleeding following tamoxifen use.Materials &  In this cross-sectional study, we evaluated women with post-menopausal breast cancer reporting vaginal bleeding while undergoing tamoxifen treatment for more than six months. Data collection involved a checklist encompassing ultrasonographic, hysteroscopic, and pathologic findings. The study included 100 patients with a mean age of 56.2 ± 2.9 years and a mean endometrial thickness of 14.5 ± 3.4 mm. Notably, 25% of the patients exhibited abnormally large uterine size. Ultrasonography revealed polyps and myomas in 36% and 15% of cases, respectively. Positive hysteroscopy findings were observed in 72%, comprising polyps in 36%, hyperplasia in 32%, and atrophy in 4%. Pathological assessment identified abnormal features in 31% as polyps, 34% as hyperplasia, 4% as atrophy, and 5% as cancerous lesions. Patients who received tamoxifen had high endometrial thickness due to endometrial polyp, it seems that clinicians can consider using hysteroscopy with dilation and curettage in these patients.

Invasive angiomyxoma as a mesenchymal tumor with a high recurrence rate has been reported mainly in reproductive age according to its association with the estrogenic level of plasma. Above that, it seems there is a need for further treatment despite complete resection of the tumor, to eliminate the hormonal state. In the present study, we sought to introduce a rare case of invasive angiomyxoma in a post-menopausal but high-risk woman, discuss the relativity of risk factors in all hormonal-dependent gynecological malignancy, and intend to seek help from colleagues' opinions and experiences about treatment. It is clearly of great importance to emphasize the role of individualized medicine in such a rare case, in conclusion, there is not any debate on the role of surgical resection but the necessity of changing in lifestyle or adjuvant systemic or local therapy, and the needed duration is doubtful.

Pulmonary cryptococcosis (PC) of the lungs is a fungal infection often occurring in immunocompromised patients, which is most commonly contracted by inhalation. Here, we report the case of a 44-year-old woman who had undergone modified radical surgery for stage I intraductal carcinoma of the left breast one year earlier and had been undergoing endocrine therapy with tamoxifen. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings indicated multiple pulmonary nodules, which was highly suspicious of lung metastasis from breast cancer. However, the pathological results suggested cryptococcus infection. The patient was subsequently treated with itraconazole antifungal therapy. However, a chest computed tomography (CT) examination one month later revealed that both lung lesions were still present. Her clinician suspected they were due to her intake of the estrogen receptor inhibitor tamoxifen and asked her to stop temporarily taking the drug. One month later, chest CT reexamination revealed that the lung lesions had disappeared. So far, there have been no reports of pulmonary cryptococcosis caused by tamoxifen after breast cancer surgery. Our case study suggests that PC infection may be one of the rare side effects of tamoxifen and should be considered in the differential diagnosis of multiple nodules in both lungs in patients with a history of cancer surgery and taking estrogen receptor inhibitors. Therefore, the etiology of infections should be considered in the differential diagnosis, especially in patients taking estrogen receptor inhibitors after tumor surgery.

Controlled drug delivery using nanotechnology enhances drug targeting at the site of interest and prevents drug dispersal throughout the body. This study focused on loading a poorly water-soluble drug Tamoxifen (TMX) into silica nanoparticles (SNPs) and amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15).  SNPs were prepared according to the Stöber method and functionalized with an amine group using 3-aminopropyl triethoxysilane (APTES) through a one-pot synthesis method to produce amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15). Characterization of both nanoparticles was performed using FT-IR, FE-SEM, CHN analysis, porosity tests (BET), and dynamic light scattering (DLS).  The results showed an average particle size of 103.7 nm for SNPs and 225.9 nm for NH2-SBA-15. Based on the BET results, the pore size of NH2-SBA-15 was about 5.4 nm. In both silica nanoparticles, drug release at pH=5.7 was greater than that of pH=7.4. However, Tamoxifen-loaded NH2-SBA-15 (TMX@NH2-SBA-15) indicated the highest drug release in the acidic medium among TMX-loaded SNPs (TMX@SNPs), perhaps due to the high columbic repulsion in the functionalized NH2-SBA-15 nanoparticles. Regarding cytotoxicity results against MCF-7 breast cancer cell lines, both TMX@SNPs and TMX@NH2-SBA-15 nanoparticles exhibited greater cytotoxicity compared to the free TMX as a positive control. Although TMX@SNPs had a small size and high loading capacity, the cytotoxic effects were higher than those of TMX@NH2-SBA-15. Amine functionalization of SNPs can improve the potential activity of these nanoparticles for target therapy.

Consumption of a high-fat diet (HFD) is associated with an increased incidence of inflammatory diseases and metabolic disorders. Also, these disorders will increase in women with aging and menopause, which is probably due to the reduced role of estradiol (E2). Selective estrogen modulators including tamoxifen (TAM), which acts through estrogen receptors, have important metabolic effects. This study aimed to determine whether TAM and E2 have protective effects on inflammation caused by HFD in young and aged mice. Four-month-old (Sham and ovariectomized [OVX]) and 20-month-old female C57BL/6J mice were used in this study. After feeding them with HFD for 12 weeks, they were divided into nine groups consisting of Sham + Oil, Sham +TAM, Sham + E2, OVX + Oil, OVX +TAM, OVX + E2, Aged + Oil, Aged +TAM, and Aged + E2. TAM and E2 were injected subcutaneously every four days for four weeks. At the end of the experiments, the mice’s blood was sampled. The serum cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were also determined using ELISA kits. The results revealed that HFD increased inflammation by reducing IL-10 and increasing TNF-a/IL-10 and IL-6/IL-10 ratio in young and aged mice, and TAM and E2 therapy resulted in a significant decrease in TNF-α and IL-6, and an increase in IL-10 in young and aged mice. In conclusion, the results of this study indicated that TAM, in addition to being used as an anticancer drug, can reduce HFD-induced inflammation in both young and aged mice. Therefore, probably it is a good candidate to substitute E2.

In 1980, tamoxifen was introduced as an effective adjuvant endocrine therapy for breast cancer, resulting in a significant increase in overall survival. Nevertheless, the development of acquired resistance limited the efficacy of tamoxifen therapy. Several molecular mechanisms have been proposed to explain the probable process of tamoxifen resistance. In vitro studies have suggested that alterations in the expression of cytoplasmic growth cascades such as insulin-like growth factor receptor (IGFR) and epidermal growth factor receptor (EGFR) along with associated downstream signaling pathways such as ERK1, ERK2, and ERK6 are the main cause of resistance to tamoxifen. In this review, we investigated the role of estrogen receptor-α (ER-α), EGFR, IGFR, and their downstream signaling pathways in tamoxifen resistance. The present study attempted to find out possible culprits of tamoxifen resistance to improve treatment efficacy in breast cancer patients.

Due to the side effects of drugs, the development of nanoscale drug delivery systems has led to a significant improvement in medicinal therapies due to drug pharmacokinetics changes, decreased toxicity, and increased half-life of the drug. This study aimed to synthesize tamoxifen (TMX)-loaded L-lysine coated magnetic iron oxide nanoparticles as a nano-carrier to investigate its cytotoxic effects and anti-cancer properties against MCF-7 cancer cells.

Magnetic Fe3O4 nanoparticles were synthesized and coated with L-lysine (F-Lys NPs). Then, TMX was loaded onto these NPs. The characteristics of synthesized nanoparticles (F-Lys-TMX NPs) were evaluated by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). The drug release was analyzed at pH 5.8 and pH 7.4. The MCF-7 cells were exposed to F-Lys-TMX NPs, F-Lys NPs, and TMX for 24, 48, and 72 hours. To evaluate the cytotoxic potential of designed nanoparticles, MTT and apoptosis assays, real-time PCR, and cell cycle analysis was carried out.

The F-Lys-TMX NPs had spherical morphology with a size ranging from 9 to 30 nm. By increasing the nanoparticles concentration and treatment time, more cell proliferation inhibition and apoptosis induction were observed in F-Lys-TMX NPs-treated cells compared to the TMX. The expression levels of ERBB2, cyclin D1, and cyclin E genes were down-regulated and expression levels of the caspase-3 and caspase-9 genes were up-regulated. Studies on the drug release revealed a slow and controlled pH-dependent release of the nanoparticles. Cell cycle analysis indicated that F-Lys-TMX NPs could arrest the cells at the G0/G1 phase.

The findings suggest that F-Lys-TMX NPs are more effective and have the potential for cell proliferation inhibition and apoptosis induction compared to the TMX. Hence, F-Lys-TMX NPs can be considered as an anti-cancer agent against MCF-7 breast cancer cells.

Berberine, an isoquinoline alkaloid purified from Chinese herbs, was verified to have antitumor effects. It has also been reported that berberine can enhance the anticancer effect of tamoxifen (TAM) in estrogen receptor (ER)-positive breast cancer cells; however, the involved underlying mechanism is still unclear. In the present study, the role of one variant of ER-α, ER-α36, in the TAM sensitizing effect of berberine was explored in TAM-resistant breast cancer cells. This study demonstrated that berberine potently sensitized TAM-resistant breast cancer cells, including TAM-resistant MCF7 and BT-474 cells, to TAM treatment. Additionally, this study showed that berberine could simultaneously suppress ER-α36 expression in TAM-resistant cells. However, when ER-α36 was knocked down in TAM-resistant cells, there was no significant TAM-sensitizing effect by berberine. Therefore, this study indicated that ER-α36 is involved in berberine’s TAM-sensitizing effect on ER-positive breast cancer cells, which provided supporting data for the application of berberine in cancer therapy as an adjuvant agent for TAM treatment.

Breast cancer is a heterogeneous disease in which many factors and receptors are effective in the disease process and response to treatment. Currently, estrogen, progesterone, and HER2 receptors are among the most important factors in choosing a treatment regimen. Other metabolic factors that may affect the treatment outcome include diabetes and hyperinsulinemia. In order to evaluate the role and complexity of cross-talk between different pathways initiating from various receptors, value the most common drugs in the treatment of breast cancer are investigated on different cell lines in this manuscript at the cell culture level. The result of different doses of Tamoxifen and estradiol on the cells with various levels of the estrogenic, progesterone, and HER2 receptors is examined alone, or in combinations, and the presence or absence of insulin. The effects of these variables on the cells’ growth pattern and survival in various breast cancer cells are investigated using cell counting, colony counting, and MTT assays. Our results have further confirmed the complexity of deciding on the outcome of treatment for breast cancer with such a wide variability in the kind of receptors and biochemical agents present in the body of a cancer patient.

Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells.

A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis.

Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis.

Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.

Tamoxifen (TAM) is the main treatment of estrogen receptor (ER)-positive breast cancer, however; its adverse effects and development of resistance hinder its use. Concanavalin A (Con A) is a mannose/glucose-binding lectin that has been reported to induce apoptosis in a variety of cell lines.

The effects of Con A on TAM-induced cell death in ERα positive cell line (MCF-7) were elucidated to identify the potential underlying molecular mechanisms using in silico (molecular docking) and in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and reverse transcription and quantitative real time-PCR) techniques as well.

The results demonstrated that combined treatment with Con A and TAM reduced the expression of ERα, which showed clear synergistic effects on inhibiting the cell viability of MCF- 7 cells. Interestingly, the combined treatment induces G1 phase arrest and reduces cyclin D1 activity while increasing apoptosis and autophagy as indicated by decreasing the expression level of anti-apoptosis gene BCl-2 and increased apoptosis/autophagic gene BNIP3. Molecular docking was conducted to evaluate the binding affinity of Con A towards ERα, and it revealed its potential activity as an ERα antagonist. Our data further indicated that Con A administration increased the drug reduction index of TAM.

Overall, our findings suggested that Con A could be used as an adjuvant agent with TAM to improve its effectiveness as an anticancer agent.

The purpose of this study was to compare the efficacy of tamoxifen and clomiphene citrate in induction of ovulation in women with PCOS and anovulation.

In this prospective cohort study, 104 women with PCOS and primary infertility were enrolled after fulfilling the inclusion and exclusion criteria. The patients were allocated in two groups; group A (n=54) received tamoxifen 40 mg once daily (Days 3-7) and group B (n=50) received clomiphene citrate 100 mg once daily (Days 3-7). Serial ultrasounds were done till the administration of human chorionic gonadotropin (hCG). The ovulation and pregnancy rates in both groups were compared. The number of dominant follicles, estradiol levels, and endometrial thickness were also studied. Comparison was done using chi-square and student’s t-test and a p-value of less than 0.05 was considered statistically significant.

The number of dominant follicles and serum estradiol levels were significantly higher in group B (p<0.05), whereas the endometrial thickness was significantly more in group A (p<0.05). The ovulation rates were similar in both groups (66.6% vs. 70%, p=0.715). Pregnancy rate per treatment cycle and per ovulatory cycle was marginally higher in group A (14.81% and 22.22%, respectively), as compared to group B (14% and 20%, respectively), but the difference was not statistically significant (p>0.05).

Tamoxifen and clomiphene citrate are both equally effective in induction of ovulation and achieving a pregnancy in women with PCOS.

 Tamoxifen (TAM) is an effective agent for the treatment of breast cancer and has antifungal activity against various fungi. However, the antifungal effects of TAM in-vivo and in patients under treatment remain unclear.

 The present study aimed to investigate the antifungal effects of TAM on yeast oral flora in-vitro and in breast cancer patients.

 In this case-control study, the antifungal effects of TAM were assessed on 50 breast cancer patients receiving TAM treatment, 50 breast cancer patients without TAM treatment, and 50 healthy controls. The disc-diffusion method was used to determine the antifungal effects of TAM on six clinical yeast isolates in-vitro.

 The number and species count of the yeasts were extremely low in the patients undergoing TAM treatment compared to the other subjects. On the other hand, the absence of the isolates was more evident in the patients receiving TAM treatment (96%). Candida albicans was frequently isolated from all the subjects. In the in-vitro tests, all the yeasts were susceptible to the two concentrations of TAM (5 and 10 µg/mL) at varying degrees. In addition, C. intermedia was the most susceptible yeast species to TAM with a low minimal inhibitory concentration (3.8 µg/mL).

 According to the results, TAM exerted significant antifungal effects on the yeasts of the oral cavity in the breast cancer patients, showing superior inhibitory effects compared to clotrimazole. Therefore, TAM is recommended as a promising antifungal, while further investigation is required regarding its safety.