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Breast Cancer (Tokyo, Japan) Jan 2018In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In patients with hormone receptor-positive postmenopausal of early stage breast cancer, adjuvant endocrine monotherapies include letrozole, anastrozole, exemestane, toremifene and tamoxifen. But the optimum regimen remains controversial.
METHODS
PubMed, Cochrane Database and ClinicalTrials.gov were systematically reviewed of abstract for randomized-controlled trials (RCTs) to assess the efficacy of tamoxifen, letrozole, exemestane, anastrozle and toremifene for postmenopausal patients with hormone-receptor positive (HR+), who have not received prior therapy for early stage breast cancer. The outcomes were measured by disease-free survival (DFS) and overall survival (OS). We evaluated relative hazard ratios (HRs) for death of different therapies by combination hazard ratios for death of included trials. The SUCRA values were used to evaluate the rankings of efficacy for these monotherapies.
RESULTS
A total of fourteen studies including 19,517 patients in our research were absorbed and estimated. The superiority of efficacy for DFS were 5-year letrozole and 10-year tamoxifen (SUCRA values 0.743/0.657) in all comparisons. A more efficient SUCRA values for OS were 5-year Exemestane, 5-year letrozole and 10-year tamoxifen (0.756/0.677/0.669).
CONCLUSIONS
Clinically important differences exist between commonly prescribed different adjuvant endocrine monotherapy regimens for both efficacy and acceptability in favor of exemestane and letrozole. 10-year tamoxifen for early breast cancer patients is noninferior to 5-year anastrozle, and might be the best choice where aromatase inhibitors (AIs) are not easy to acquire.
Topics: Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Network Meta-Analysis; Postmenopause; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 28755088
DOI: 10.1007/s12282-017-0794-8 -
Endocrinology Oct 2021Cancer-induced skeletal muscle defects show sex-specific differences in severity with men performing poorly compared to women. Hormones and sex chromosomal differences...
Cancer-induced skeletal muscle defects show sex-specific differences in severity with men performing poorly compared to women. Hormones and sex chromosomal differences are suggested to mediate these differences, but the functional skeletal muscle markers to document these differences are unknown. We show that the myogenic microRNA miR-486 is a marker of sex-specific differences in cancer-induced skeletal muscle defects. Cancer-induced loss of circulating miR-486 was more severe in men with bladder, lung, and pancreatic cancers compared to women with the same cancer types. In a syngeneic model of pancreatic cancer, circulating and skeletal muscle loss of miR-486 was more severe in male mice compared to female mice. Estradiol (E2) and the clinically used selective estrogen receptor modulator toremifene increased miR-486 in undifferentiated and differentiated myoblast cell line C2C12 and E2-inducible expression correlated with direct binding of estrogen receptor alpha (ERα) to the regulatory region of the miR-486 gene. E2 and toremifene reduced the actions of cytokines such as myostatin, transforming growth factor β, and tumor necrosis factor α, which mediate cancer-induced skeletal muscle wasting. E2- and toremifene-treated C2C12 myoblast/myotube cells contained elevated levels of active protein kinase B (AKT) with a corresponding decrease in the levels of its negative regulator PTEN, which is a target of miR-486. We propose an ERα:E2-miR-486-AKT signaling axis, which reduces the deleterious effects of cancer-induced cytokines/chemokines on skeletal muscle mass and/or function.
Topics: Animals; Cell Differentiation; Cell Line, Tumor; Estradiol; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Muscle, Skeletal; Muscular Diseases; Myostatin; Neoplasms; Sex Factors; Signal Transduction; Toremifene; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 34265069
DOI: 10.1210/endocr/bqab142 -
Frontiers in Microbiology 2021Deep learning significantly accelerates the drug discovery process, and contributes to global efforts to stop the spread of infectious diseases. Besides enhancing the... (Review)
Review
Deep learning significantly accelerates the drug discovery process, and contributes to global efforts to stop the spread of infectious diseases. Besides enhancing the efficiency of screening of antimicrobial compounds against a broad spectrum of pathogens, deep learning has also the potential to efficiently and reliably identify drug candidates against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Consequently, deep learning has been successfully used for the identification of a number of potential drugs against SARS-CoV-2, including Atazanavir, Remdesivir, Kaletra, Enalaprilat, Venetoclax, Posaconazole, Daclatasvir, Ombitasvir, Toremifene, Niclosamide, Dexamethasone, Indomethacin, Pralatrexate, Azithromycin, Palmatine, and Sauchinone. This mini-review discusses recent advances and future perspectives of deep learning-based SARS-CoV-2 drug discovery.
PubMed: 34777286
DOI: 10.3389/fmicb.2021.739684 -
Acta Pharmacologica Sinica Aug 2021To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry...
To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC = 0.95 ± 0.83 µM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.
Topics: Antiviral Agents; Cell Line; Drug Approval; Drug Repositioning; High-Throughput Screening Assays; Humans; Microbial Sensitivity Tests; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33116249
DOI: 10.1038/s41401-020-00556-6 -
Cancers Jan 2018Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor... (Review)
Review
Androgen deprivation therapy (ADT) has been widely prescribed for patients with advanced prostate cancer (PC) to control key signaling pathways via androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs; estrogen receptors (ERs; ERα and ERβ); and estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as , , , , , , and of PC, via ERs and ERRs. Selective ER modulators (SERMs) have been developed. Recently, estrogen and androgen blockade (EAB) using a combination of toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a "personalized medicine" or "precision medicine". In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and SERMs as candidates for advanced PC treatment.
PubMed: 29360794
DOI: 10.3390/cancers10020029 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Mar 2022To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against .
OBJECTIVES
To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against .
METHODS
The minimum inhibitory concentration of 426 Food and Drug Administration (FDA)-approved small-molecule drugs against was determined using the microdilution method, and the target of SERMs acting on was explored by employing a random transposon mutant library.
RESULTS
Among the 426 FDA-approved SERMs, toremiphene, tamoxifen, clomiphene, and raloxifene exhibited excellent antibacterial effects against . Results of mutant library screening showed that the two mutant strains were resistant to clomiphene. The gene sequence of the resistant strains showed that the transposon insertion sites were located in the genes of and .
CONCLUSIONS
SERMs, such as toremifene, tamoxifen, clomiphene, and raloxifene, exerted obvious antibacterial effects on , and their targets may be proteins expressed by and gene.
PubMed: 38597056
DOI: 10.7518/hxkq.2022.02.014 -
Journal of the Advanced Practitioner in... Mar 2017DE, a 31-year-old premenopausal woman with a nonsignificant medical history, noticed a right breast mass after playing basketball in September 2011. She initially... (Review)
Review
DE, a 31-year-old premenopausal woman with a nonsignificant medical history, noticed a right breast mass after playing basketball in September 2011. She initially attributed the mass to slight trauma, but after 2 weeks, she realized the mass was increasing in size. Her primary care physician ordered a bilateral screening mammogram and ultrasound. Mammography revealed no evidence of malignancy in the left breast. In the right breast, at the 7 o'clock position, a loose cluster of faint calcifications spanned a 2.2-cm area. Ultrasound confirmed an irregular hypoechoic mass in the right breast measuring 3.5 × 2.7 × 2.8 cm. Ultrasound of the right axilla identified two enlarged right axillary lymph nodes. Ultrasound core-needle biopsy of the suspicious right breast mass confirmed invasive ductal carcinoma, nuclear grade 2, Ki67 index of 55%, estrogen receptor-positive (H score of 180), progesterone receptor-positive (H score of 135), HER2-positive (3+ on immunohistochemistry). Utilizing the TNM (tumor, node, metastasis) staging system, she was clinically staged with a stage IIB (cT2, cN1, M0) invasive breast tumor. The computerized axial tomography (CT) scan of the chest, abdomen, and pelvis demonstrated the known right breast mass and two enlarged right axillary lymph nodes; however, no metastatic disease was noted. Nuclear bone scan revealed no bone metastases. Her medical oncologist recommended she receive neoadjuvant chemotherapy. The patient was treated with 6 cycles of neoadjuvant docetaxel at 75 mg/m², carboplatin at an AUC (area under the curve) of 6, and trastuzumab (Herceptin) at 6 mg/kg (TCH), which she tolerated well. She then underwent a right segmental mastectomy with axillary lymph node dissection and was found to have a residual 1.0-cm invasive ductal carcinoma, representing a 60% tumor volume reduction. None of 13 axillary lymph nodes were positive for disease. Pathologic staging confirmed a stage IA (ypT1, ypN0, M0) tumor. DE completed 33 fractions of radiation therapy to the right breast. She initiated endocrine therapy with tamoxifen at 20 mg daily and received 1 year of maintenance trastuzumab (6 mg/kg). Due to vaginal discharge and weight gain, endocrine therapy was switched from tamoxifen to toremifene (Fareston), which she tolerated relatively well. She continued routine follow-up, with no evidence of disease. In September 2014, DE presented to her primary care physician complaining of left hip pain. Magnetic resonance imaging (MRI) of the left hip revealed T2 hyperintense masses within the right anterior superior iliac crest, right sacrum, and left iliac body consistent with skeletal metastases. She was referred back to her medical oncologist, and per National Comprehensive Cancer Network (NCCN) guidelines, a biopsy of the suspicious lesion was obtained. The bone biopsy of the lytic lesion was consistent with metastatic breast cancer, which was estrogen receptor-positive, progesterone receptor-positive, and HER2-positive (3+ on immunohistochemistry). Restaging CT scan of the chest, abdomen, and pelvis revealed new 4- to 6-mm pulmonary nodules, hilar and mediastinal lymphadenopathy, new liver lesions, and bone lesions. Nuclear bone scan confirmed multiple bone metastases of the right and left iliac bones and sternum. Complete blood cell count with differential and complete metabolic panel were within normal ranges. The CA 27-29 tumor marker for breast cancer was elevated at 495 U/mL (normal range, < 37 U/mL). DE was understandably devastated by the new diagnosis. She questioned how the treatment plan was to be established. Her medical oncologist struck a somewhat optimistic tone. He explained that metastatic breast cancer was not yet considered to be curable, but periods of disease stability and chronicity were possible. He explained that the HER2 positivity was perhaps the most important factor in delineating her treatment options. He told her that current treatment options were numerous and increasing in number.
PubMed: 29900024
DOI: No ID Found -
Asia-Pacific Journal of Clinical... Apr 2022To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy.
PURPOSE
To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy.
METHODS
Estrogen receptor-positive breast cancer patients were selected and CYP2D6*10 genotypes (C/C, C/T, and T/T) were determined by Sanger sequencing. Patients were divided into tamoxifen, toremifene, or tamoxifen + toremifene groups according to prior therapy. The correlation between CYP2D6*10 genotype and disease-free survival was analyzed.
RESULTS
In total, 293 estrogen receptor-positive breast cancer patients treated with tamoxifen or toremifene between 2008 and 2017 were studied. Median follow-up was 39 months (10-141). Of these, 107 (36.52%), 112 (38.23%), and 74 (25.26%) patients had C/C, C/T, and T/T genotypes, respectively. Genotype was significantly associated with disease-free survival in tamoxifen patients. Patients with C/T and T/T genotypes showed worse disease-free survival than patients with a C/C genotype. Genotype and disease-free survival in toremifene and tamoxifen+toremifene patients were not correlated. Of patients with a C/T genotype, toremifene or tamoxifen+toremifene groups showed better disease-free survival than tamoxifen patients. Although disease-free survival of patients with a T/T genotype in the three groups was not statistically different, tamoxifen patients showed worse disease-free survival. There was no correlation between different treatments and disease-free survival in patients with a C/C genotype. Cox proportional hazard analysis revealed toremifene patients had a better prognosis than tamoxifen patients; toremifene was an independent protective factoremifene for disease-free survival.
CONCLUSIONS
Tamoxifen was less effective in patients with CYP2D6*10 C/T and T/T genotypes. Estrogen receptor-positive breast cancer patients with a CYP2D6*10 mutation genotype have a better prognosis with toremifen than tamoxifen.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; China; Cytochrome P-450 CYP2D6; Female; Genotype; Humans; Prognosis; Receptors, Estrogen; Tamoxifen; Toremifene
PubMed: 34196110
DOI: 10.1111/ajco.13571 -
BMC Cancer Jul 2021Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been...
BACKGROUND
Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been proved to affect serum lipid profiles and cause fatty liver disease. The study aimed to compare the effects of TAM and TOR on fatty liver development and lipid profiles.
METHODS
This study performed a retrospective analysis of 308 SERMs-treated early breast cancer patients who were matched 1:1 based on propensity scores. The follow-up period was 3 years. The primary outcomes were fatty liver detected by ultrasonography or computed tomography (CT), variation in fibrosis indexes, and serum lipid profiles change.
RESULTS
The cumulative incidence rate of new-onset fatty liver was higher in the TAM group than in the TOR group (113.2 vs. 67.2 per 1000 person-years, p < 0.001), and more severe fatty livers occurred in the TAM group (25.5 vs. 7.5 per 1000 person-years, p = 0.003). According to the Kaplan-Meier curves, TAM significantly increased the risk of new-onset fatty liver (25.97% vs. 17.53%, p = 0.0243) and the severe fatty liver (5.84% vs. 1.95%, p = 0.0429). TOR decreased the risk of new-onset fatty liver by 45% (hazard ratio = 0.55, p = 0.020) and showed lower fibrotic burden, independent of obesity, lipid, and liver enzyme levels. TOR increased triglycerides less than TAM, and TOR increased high-density lipoprotein cholesterol, while TAM did the opposite. No significant differences in total cholesterol and low-density lipoprotein cholesterol are observed between the two groups.
CONCLUSIONS
TAM treatment is significantly associated with more severe fatty liver disease and liver fibrosis, while TOR is associated with an overall improvement in lipid profiles, which supports continuous monitoring of liver imaging and serum lipid levels during SERM treatment.
Topics: Adult; Breast Neoplasms; Fatty Liver; Female; Humans; Lipids; Middle Aged; Retrospective Studies; Tamoxifen; Toremifene
PubMed: 34246237
DOI: 10.1186/s12885-021-08538-5 -
Cleveland Clinic Journal of Medicine Jun 2020To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment...
To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options for COVID-19. We discuss one treatment strategy that combines anti-inflammatory (melatonin) and antiviral (toremifene) agents for patients infected with SARS-CoV-2 from network medicine-based findings. We also describe the pathobiology and immunologic characteristics of COVID-19 and highlight the rationale of combination drug treatment to rescue the pulmonary and cardiovascular conditions resulting from COVID-19. A preliminary analysis reveals a high potential for the synergistic effects of melatonin and toremifene to reduce viral infection and replication, and the aberrant host inflammatory responses, offering strong biologic plausibility as an effective therapy for COVID-19.
PubMed: 32606050
DOI: 10.3949/ccjm.87a.ccc037