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Functional genomics for breast cancer drug target discovery.

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechani

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… Current endocrine-based treatments targeting estrogen (E2)-ERα signaling (selective estrogen receptor modulators, selective estrogen receptor downregulation, aromatase inhibitors) [ 6 , 7 ] as well as some molecular target drugs, such as mTOR inhibitors [ 8 , 9 ], PI3K inhibitors [ 10 ], and CDK4/6 inhibitors …

Воздействие лечения на стероидом у женщин с множественным склерозом.

Множественный склероз (MS) — хроническое воспалительное нейродегенеративное заболевание центральной нервной системы. Происхождение MS связано с стероидными изменениями во время менструального цикла и беременности. Поскольку данных о воздействии лечения противомоскитных препаратов на стероидом недостаточно, мы провели оценку стерейдомичных изменений (79 стероидов) у 61 женщины-психолога репродуктивного возраста 39 лет (29, 47 лет) после лечения с помощью антимиосных препаратов на платформе GC-MS/MS и иммуномассы (кортизол и эстрадиол). Эти изменения были оценены с использованием уровней стероид

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, V

Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to i

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… Among the compounds that share those miRNAs that are targeted by the reference compound, hesperidin, we find a group of heterogeneous molecules of different types, such as corticosteroids, diarylheptanoids, antivirals, nucleoside analogs, oncology drugs, purine derivatives, estrogen receptor modulators … receptor modulator Vorinostat | 5311 | 0.387 | 3 | 8.21 × 10 4 | Histone deacetylase inhibitor (3R,5S)-Atorvastatin | 46780495 | 0.212 | 12 | 0.013398551 | HMG-CoA reductase inhibitor Atorvastatin, (3S,5R)- | 6093359 | 0.212 | 10 | 0.007799482 | HMG-CoA reductase inhibitor ent-Atorvastatin | 62976 | …

Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility.

Denosumab is a breakthrough biological drug approved by the Food and Drug Administration and European Medicines Agency for the treatment of osteoporosis in 2010. It is a fully human monoclonal antireceptor activator of nuclear factor kappa-B ligand antibody, which inhibits the activity of osteoclasts, resulting in an antiresorptive effect with a significant increase in bone mineral density. The FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial, comparing denosumab with no treatment in 7868 women with postmenopausal osteoporosis, showed an important reduc

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… receptor modulator are needed to evaluate the prevention of osteoporotic fractures, breast cancers, endometrial cancers, and cardiovascular events. … When treating patients with osteoporosis, estrogens and selective estrogen receptor modulators have effects not only on bone metabolism, but also on the breast, endometrium, and lipid metabolism. …

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

The Interplay between Immune System and Microbiota in Osteoporosis.

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becom

GPER1 Активация Антитуморной активности в Множестве миелом.

G белковый рецептор эстрогена. 1 Активация (GPER1) становится перспективной терапевтической стратегией борьбы с различными видами рака. Несмотря на то, что в контексте твердых опухолей широко изучался вопрос о адресации GPER, его воздействие на гематологию еще предстоит понять в полной мере. Здесь мы показываем, что GPER1 mRNA понижается в плазменных клетках от открытой множественной миэломы (MM) и лейкемии от плазмы по сравнению с нормальными спонсорами или преднасыщенными условиями (моноклональная гаммопатия неопределённого значения и удушающая MM); кроме того, более низкое выражение GPER1 а

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigeneti

Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance.

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathw

Associations of Bone Mineral Density with RANKL and Osteoprotegerin in Arab Postmenopausal Women: A Cross-Sectional Study.

Background and objective: There is limited information as to the association of several key bone markers with bone mineral density (BMD) in understudied ethnic groups. This study investigated the relationship between circulating levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) with BMD in Arab postmenopausal women. Materials and methods: In this cross-sectional study, a total of 617 Saudi postmenopausal women from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases were included. Anthropometric data, BMD, and biochemical data

Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.

Osteoclastic bone diseases represent a significant health burden, especially in an aging population, due to imbalances in bone homeostasis that result in postmenopausal osteoporosis, inflammatory arthritis, malignancy-induced bone disease and secondary metabolic conditions, which result in fragility fractures, disability and death. Although advances in imaging and pharmacology have enhanced management, existing diagnostic strategies have poor sensitivity in detecting early-stage pathological changes or fracture risk. The NF-kappaB/receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin

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… Other antiresorptive and anabolic therapies Bisphosphonates, selective estrogen receptor modulators, calcitonin, and anabolic agents such as parathyroid hormone analogs exert their skeletal effects through indirect modulation of osteoblast-osteoclast coupling and remodeling dynamics[ 144 ]. …

Disproportionality analysis of sex-stratified adverse event signals in growth impairment: Insights from the FDA adverse event reporting system.

This study aimed to examine sex-disaggregated adverse event signals associated with growth impairment in pediatric patients, utilizing data from the FDA adverse event reporting system, with a particular focus on growth hormone and related therapeutic agents. A disproportionality analysis was performed on FDA adverse event reporting system data spanning 2004 Q1 to 2025 Q1. The analysis encompassed 3281 growth impairment-related reports, disaggregated by gender, employing Reporting Odds Ratios (ROR) and proportional reporting ratios for signal detection, with temporal patterns assessed via Weibu

Osteoporosis: the current status of mesenchymal stem cell-based therapy.

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves

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… Hormone therapy, such as therapy with estrogen [ 114 ] and with selective estrogen receptor modulators (SERMs) acting as estrogen agonists, such as raloxifene [ 115 ], has been used in postmenopausal women to slow the bone breakdown process, maintain bone density, and reduce fracture risk. … receptor modulator; SNPs, single nucleotide polymorphisms; SOST, sclerostin; SP7, Sp7 transcription factor 7; TCF/LEF, T cell factor/lymphoid enhancer factor; TGF-β, transforming growth factor beta; TNFRSF, tumor necrosis factor receptor superfamily; UC, umbilical cord-derived; UCB, umbilical cord blood …

The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.

Purpose of reviewIn this review, we describe the interaction between B cells and bone during development, aging, and disease. RECENT FINDINGS: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted

Sex Differences in Cancer and Cardiotoxicity: Mechanisms, Outcomes, and Clinical Implications Across Solid and Hematological Malignancies.

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women-particularly premenopausal or with specific genotypes-may be at increased risk for cardiotoxicity after treatment

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… Exogenous hormonal therapies, such as selective estrogen receptor modulators can significantly alter the clinical penetrance of cardiac arrhythmias, prolonging the QT interval by interacting with cardiac ion channels [ 120 ]. …

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

IntroductionPesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.MethodsAnalyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

Hormone therapy use and cancer survivorship.

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Использование динамики моноцитов для лечения множественных склерозов; анализ результатов экспериментальных исследований моделей.

Моноциты играют центральную роль в реакции врожденной иммунной системы на инфекцию или травму. В мурине эти клетки подразделяются на отдельные подмножества: классические моноциты, определяемые повышенным выражением Ly6C (Ly6Chi), промежуточные моноциты (Ly6Cint) и неклассические подстрекательские моноциты, характеризующиеся низким выражением Ly6C (Ly6Clow). Моноциты, набираемые для производства тканей, проводят различие между макрофагами, которые могут быть провоспалительными или противовоспалительными, оказывая тем самым влияние на процессы и результаты заболеваний. Основной функцией классиче