Search Results (165)

Breast cancer remains a leading cause of global mortality. According to international cancer data, significant progress has been made in treating breast cancer; however, metastasis and drug resistance continue to be the primary causes of mortality for many patients. This study investigated the modulation of apoptosis-related genes in response to ionizing radiation and estrogen exposure based on a human breast epithelial cell model (MCF-10F and its transformed variants: Estrogen, Alpha3, Alpha5, Tumor2) previously established, where cells were treated with high linear energy transfer alpha particles, with or without 17β-estradiol. Gene expression profiling was performed using an Affymetrix U133A microarray, and bioinformatic analyses assessed differential expression, estrogen receptor status, and correlations with overall survival. Distinct gene expression patterns emerged across cell lines and tumor subtypes. TP53 expression correlated positively with TP63, BIK, CFLAR, BIRC3, and BCLAF1. TP63, PERP, CFLAR, BCLAF1, GULP1, and BIRC3 were elevated in normal tissue, whereas BIK, PHLDA2, and BBC3 were upregulated in tumors. ER-positive tumors exhibited higher TP63, BIK, BCLAF1, and BBC3 expression, while ER-negative tumors showed increased PERP, CFLAR, BIRC3, and PHLDA2. Notably, elevated BCLAF1 expression was associated with poorer survival in Luminal A patients, and high PHLDA2 expression correlated with reduced survival in Luminal B cases. These findings indicate that resistance to apoptosis is a fundamental mechanism in breast cancer progression and therapeutic evasion. Breast tumors selectively alter the expression of key genes to promote growth, evade apoptosis, and develop therapeutic resistance. The differential expression and correlations of these apoptosis-related genes highlight their potential as molecular targets for future personalized cancer therapies and as valuable biomarkers for prognostic stratification and predicting therapeutic response. Full article

Tamoxifen is a well-established selective estrogen receptor modulator (SERM) widely used in breast cancer treatment, yet its efficacy varies across tumor types. To enhance its antitumor potential, we previously synthesized and investigated novel ferrocene-linked (T5, T15) derivatives. This publication is a close continuation of this work, introducing a new indene-based (T6) derivative. Objectives: The main aim of this study was to further broaden our knowledge of the mechanism behind the increased antitumor effect of the ferrocene-linked drugs (T5 and T15) and compare it with a new, indene-based tamoxifen derivative, T6. The indene moiety was selected as a rigid, hydrophobic aromatic unit to probe pharmacological effects independent of ferrocene’s redox activity. Methods: The compounds were tested on MCF7, MDA-MB231 and PANC1 cells. Cell viability was assessed with the AlamarBlue assay and the xCELLigence SP system. Reactive oxygen species (ROS) production was measured with the ROS Glo assay. Flow cytometry and RT-qPCR experiments were conducted to assess apoptosis and ROS regulation as well. Results: The modified compounds demonstrated an increased cell-viability-decreasing effect in breast (MCF7, MDA-MB-231) and pancreatic (PANC1) cancer cell lines, influencing both estrogen-receptor-dependent and -independent pathways. T6 led to G2/M phase arrest in PANC1 cells. Beyond cell cycle disruption, these derivatives significantly elevated ROS levels, contributing to apoptosis. Conclusions: Our findings suggest that these structural modifications retain tamoxifen’s pharmacophore properties while expanding its mechanism of action, particularly through universal interactions independent of the ER status of tumor cells. The enhanced antitumor effects highlight the potential of these derivatives as promising candidates for improved cancer therapies. Full article

Background/Objectives: With the growing number of cancer survivors receiving long-term endocrine therapy, understanding its potential effects on oral and periodontal health is of increasing clinical relevance. This systematic review aimed to synthesize current evidence on the impact of hormone therapies used in cancer treatment on periodontal status. Methods: A comprehensive literature search was conducted across the Medline, Web of Science, and Scopus databases to identify observational studies published up to June 2025 that evaluated the effects of endocrine therapy on periodontal parameters and tooth loss in cancer patients. Results: Thirteen studies met the inclusion criteria, twelve involving breast cancer patients and one prostate cancer. Third-generation aromatase inhibitors (AIs) were the most frequently studied agents, either alone or in comparison with tamoxifen. Most studies reported that AI therapy was associated with a higher prevalence of severe periodontitis, increased bleeding on probing and more severe alveolar bone loss compared to healthy controls. In contrast, tamoxifen appeared to have a comparatively milder impact on periodontal health. The single study on prostate cancer patients undergoing androgen deprivation therapy similarly indicated a higher prevalence of periodontitis with respect to controls. Conclusions: These findings suggest a potential link between endocrine therapy and periodontal status deterioration, particularly with AIs. This review highlights an important yet often neglected aspect of survivorship care and emphasizes the need for routine periodontal assessment and interdisciplinary collaboration in the management of patients undergoing hormone therapy for cancer. Full article

Background: Hormonal fluctuations significantly influence skin physiology, affecting collagen production, sebum regulation, pigmentation, and tissue repair. Hormonal therapies are increasingly used in cosmetic dermatology to address age-related and hormone-dependent skin changes. Methods: This narrative review synthesizes the current literature on the mechanisms, clinical applications, and future directions of hormonal therapies in dermatologic aesthetics. Studies were selected through a comprehensive search on PubMed, Scopus, and Web of Science. Results: Estrogens, androgens, progesterone, and other hormones act on skin through specific receptors, modulating fibroblast, sebocyte, and melanocyte activity. Clinical applications include hormone-based strategies for anti-aging, acne, melasma, alopecia, and postmenopausal atrophy. Both systemic (e.g., HRT) and topical (e.g., clascoterone, phytoestrogens) approaches are discussed. Safety concerns, including systemic absorption and off-label use, require careful evaluation. Emerging technologies such as SERMs, nanocarriers, and regenerative combinations suggest promising future avenues. Conclusions: Hormonal therapies offer a biologically rational and increasingly evidence-based tool in cosmetic dermatology. Responsible integration into clinical practice depends on personalized approaches, ethical prescribing, and further research on long-term safety and efficacy. Full article

Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as hot flashes and osteoporosis, the neurocognitive consequences of hormonal fluctuations during the menopausal transition and the subsequent sustained estrogen loss after menopause have received less focus. Estrogen receptors (ERs), specifically ERα and ERβ, play a critical role in maintaining brain health, influencing mood, memory, and cognition. This review explores the connection between estrogen receptor signaling and mental health during menopause, focusing on mood disorders such as depression and anxiety, as well as cognitive decline and dementia. We discuss the molecular mechanisms by which ERs modulate brain function, including their effects on neuroplasticity, neurotransmitter systems, and gene expression. The review also examines current clinical approaches to managing menopausal cognitive and mental health issues, including hormone replacement therapy and selective ER modulators, while emphasizing the need for further research into alternative therapies and individualized treatments. The importance of estrogen receptors in the menopausal brain and their potential as therapeutic targets is critically evaluated, aiming to shed light on this often-overlooked aspect of menopause and aging. Full article

Background/Objectives: Cancer ranks as the second most prevalent cause of death worldwide, according to the World Health Organization. Approximately one in six global deaths is attributed to cancer. Among females, breast cancer stands out as the most frequent type of tumor. Raloxifene (RLX), recognized as a selective estrogen receptor modulator, has been employed as a therapeutic option in treating breast cancer among postmenopausal women. The objective of this study was to investigate the anticancer potential of raloxifene-loaded hexosomes, nanoliposomes, and nanoniosomes to identify the most effective formulation. Methods: The particle size, zeta potential, entrapment efficiency, and structural elucidation of the various nanovesicle formulations was validated; Results: Each nanocarrier exhibited a negative surface charge, nanometric size, and a reasonable encapsulation efficiency. Cytotoxicity of the different raloxifene-loaded nanovesicles on MCF-7 breast cancer cell lines and MCF10 non tumorigenic cells revealed the substantial cytotoxic activity of the hexosomal nanocarrier compared to the other nanovesicles, exhibiting the lowest IC50 = 45.3 ± 1.10 µM. Conclusions: The RLX-loaded hexosomal formulation showed superior cytotoxic activity, indicating its potential as a highly effective therapeutic agent. To fully understand its capabilities and mechanisms, further in vitro characterization studies are necessary. Full article

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Breast cancer is the leading cause of death among women, and its treatment often involves chemotherapy and hormone therapy, which can compromise bone mineral density (BMD). Tamoxifen, a selective estrogen receptor modulator, has different effects depending on the patient’s hormonal status. On the one hand, in postmenopausal women, it has a protective effect on BMD; on the other hand, in premenopausal women, it can accelerate bone loss, increasing the risk of osteoporosis and fractures. The reduction in estrogen levels during treatment is a key factor in this bone loss. This review underscores the importance of early risk assessment and regular monitoring of bone mineral density, along with the adoption of individualized pharmacological and non-pharmacological strategies, such as calcium and vitamin D supplementation and physical exercise, to preserve bone health in premenopausal women with breast cancer undergoing endocrine therapy. Full article

The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and the possible mechanisms involving the RAS. Female Wistar rats were divided into the following groups: sham (SHAM), ovariectomized (OVX), OVX and treated with 17β-estradiol (E2) (OE₂), OVX and treated with E2 and drospirenone (OE₂ + DRSP), and OVX and treated with medroxyprogesterone (MPA). Hormonal treatment was delivered via gavage for 28 days. Vascular responses to Ang-(1-7) were assessed in isolated aortic rings, and a Western blot of the thoracic aorta was used to determine the protein levels of angiotensin II (Ang II) type-1 receptor (AT₁R), Ang II type-2 receptor (AT₂R), Ang-(1-7) receptor (Mas), angiotensin-converting enzyme 2 (ACE2), and endothelial nitric oxide synthase (eNOS). The results showed impaired vascular reactivity caused by ovariectomy. Ang-(1-7) induced vasodilation in the OE₂, OE₂ + DRSP, and MPA-treated groups, while the administration of the AT₂R antagonist (PD123319) or the selective Mas antagonist (A779) increased the extent of vasorelaxation induced by Ang-(1-7) in the OVX + MPA group. There were no differences in the aortic levels of AT₁R or ACE2 between the groups, but the MPA group showed significantly increased levels of AT₂R and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters. Full article

Background and Objectives: Osteoporosis is a common chronic condition after menopause that increases the risk of fractures. In South Korea, the prevalence of osteoporosis among adults aged 50 and older is 22.4%, with 94.4% of treated patients being women, highlighting its significant impact on postmenopausal health. In this study, we examine the sales trends of osteoporosis medications in Korea from 2018 to 2023 to understand current usage patterns and market dynamics. Materials and Methods: This study is a retrospective analysis based on pre-recorded sales data from Intercontinental Marketing Services (IMS). Data covering a five-year period (2018–2023) were analyzed to examine the sales trends of osteoporosis medications, including bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone analogs, denosumab, romosozumab, and others. Romosozumab, approved in November 2019, was included in the analysis. Given the nature of this study, no direct patient data or clinical interventions were involved. Results: The total market size for osteoporosis medications in South Korea reached USD 285.42 million in 2023, reflecting a 15.3% increase from 2022. Bisphosphonates, previously the dominant therapy, experienced an 11% decline in market share over five years. Meanwhile, denosumab, a receptor activator of the nuclear factor-κB ligand inhibitor, showed a remarkable growth rate of 957.6% from 2018 to 2023, surpassing bisphosphonates in their market share. Romosozumab, a newly introduced anabolic agent, accounted for 7.4% of the market, with sales increasing by 59% in 2023. Conclusions: This analysis revealed major shifts in treatment preferences, with newer drugs like denosumab and romosozumab gaining prominence over traditional bisphosphonates. These trends highlight the increasing clinical adoption of anabolic agents for high-risk patients and the impact of expanded reimbursement policies on osteoporosis management. Given the increasing use of advanced therapies, it is essential to monitor treatment access, patient adherence, and long-term clinical outcomes. Understanding these sales trends can aid healthcare professionals and policymakers in optimizing osteoporosis treatment strategies and ensuring better patient care. Full article

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic and ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling and other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth and endocrine resistance. Emerging research highlights the role of prebiotics in modulating gut microbiota, which may influence estrogen metabolism, immune function, and therapeutic responses in BC. This review explores the impact of prebiotics on estrogen receptor modulation, gut microbiota composition, immune regulation, and metabolic pathways in breast cancer. The potential of prebiotics as adjunctive therapies to enhance treatment efficacy and mitigate chemotherapy-related side effects is discussed. A comprehensive analysis of recent preclinical and clinical studies was conducted, examining the role of prebiotics in gut microbiota modulation, immune regulation, and metabolic reprogramming in breast cancer. The impact of short-chain fatty acids (SCFAs) derived from prebiotic fermentation on epigenetic regulation and endocrine resistance was also evaluated. Prebiotics were found to modulate the gut microbiota-estrogen axis, reduce inflammation, and influence immune responses. SCFAs demonstrated selective estrogen receptor downregulation and metabolic reprogramming, suppressing tumor growth. Synbiotic interventions mitigate chemotherapy-related side effects, improving the quality of life in breast cancer patients. Prebiotics offer a promising avenue for breast cancer prevention and therapy by modulating estrogen metabolism, immune function, and metabolic pathways. Future clinical trials are needed to validate their efficacy as adjunctive treatments in breast cancer management. Full article

Approximately 70–80% of breast cancers are estrogen receptor-positive (ER+), with 65% of these cases also being progesterone receptor-positive (ER+PR+). In most cases of ER+ advanced breast cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These include tamoxifen, a selective estrogen receptor modulator (SERM); fulvestrant, a selective estrogen receptor degrader (SERD); and aromatase inhibitors (AIs), which block estrogen synthesis. However, intrinsic or acquired hormone resistance eventually develops, leading to disease progression. The combination of ET with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) has been shown to significantly increase progression-free survival (PFS) and, in some cases, overall survival (OS). CDK4/6is works by arresting the cell cycle in the G1 phase, preventing DNA synthesis, and enhancing the efficacy of ET. This review highlights the key mechanisms of resistance to ET, whether used alone or in combination with biological agents, as well as emerging therapeutic strategies aimed at overcoming resistance. Addressing ET resistance remains a work in progress, and in the near future, better patient selection for different therapeutic approaches is expected through the identification of more precise biological and genetic markers. In particular, liquid biopsy may provide a real-time portrait of the disease, offering insights into mechanisms driving ET resistance and cancer progression. Full article

Breast cancer is the most common malignancy among women globally, with incidence rates continuing to rise. A comprehensive understanding of its risk factors and the underlying biological mechanisms that drive tumor initiation is essential for developing effective prevention strategies. This review examines key non-modifiable risk factors, such as genetic predisposition, demographic characteristics, family history, mammographic density, and reproductive milestones, as well as modifiable risk factors like exogenous hormone exposure, obesity, diet, and physical inactivity. Importantly, reproductive history plays a dual role, providing long-term protection while temporarily increasing breast cancer risk shortly after pregnancy. Current chemoprevention strategies primarily depend on selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, which have demonstrated efficacy in reducing the incidence of estrogen receptor-positive breast cancer but remain underutilized due to adverse effects. Emerging approaches such as aromatase inhibitors, RANKL inhibitors, progesterone antagonists, PI3K inhibitors, and immunoprevention strategies show promise for expanding preventive options. Understanding the interactions between risk factors, hormonal influences, and tumorigenesis is critical for optimizing breast cancer prevention and advancing safer, more targeted chemopreventive interventions Full article