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The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… ER targeting can be performed using classical drugs, such as raloxifene and tamoxifen, which are collectively called selective estrogen receptor modulators (SERMs) and are effectively applied in pre-and post-menopausal women [ 235 ]. …

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.

Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RAN

Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

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… Selective estrogen receptor modulators (SERMs) regulate bone metabolism and the immune response by mimicking the bone-protective effects of estrogens. …

Effects of three flavonoids from an ancient traditional Chinese medicine Radix puerariae on geriatric diseases.

As the worldwide population ages, the morbidity of neurodegenerative, cardiovascular, cerebrovascular, and endocrine diseases, such as diabetes and osteoporosis, continues to increase. The etiology of geriatric diseases is complex, involving the interaction of genes and the environment, which makes effective treatment challenging. Traditional Chinese medicine, unlike Western medicine, uses diverse bioactive ingredients to target multiple signaling pathways in geriatric diseases. Radix puerariae is one of the most widely used ancient traditional Chinese medicines and is also consumed as food. T

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases.

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, an

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… Most commonly used are bisphosphonates (e.g., alendronate, risedronate, ibandronate and zoledronic acid) [ 1 ] and selective estrogen receptor modulators (SERMs; e.g., tamoxifen, raloxifene, and toremifene) [ 2 ]. …

The Multifaceted Roles of Myrrha in the Treatment of Breast Cancer: Potential Therapeutic Targets and Promises.

BackgroundBreast cancer is a critical threat to human health, and effective targeted agents showing lower systemic toxicity are still lacking. Therefore, exploring new potent therapeutic candidates with a broader safety margin is warranted. Alternative medicine, which has historically been used in traditional Chinese medicine, has played an increasingly prominent role in this area of research. This study introduces Commiphora myrrha (or myrrh) as a potential therapeutic candidate for treating breast cancer patients. Myrrh bioactive extracts have been used traditionally for decades to treat num

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

Perturbing Enhancer Activity in Cancer Therapy.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation.

Снижение уровня эстрогена лимфатического узла вызывает неиспускающее заболевание аутоиммунной энцефаломиелита.

Эстроген, стероидный гормон, синтезированный как гонадальными, так и негональными тканями, играет ключевую роль в модуляции иммунной реакции, включая снижение частоты рецидивов при повторном излучающем многократном склерозе (МС). В этом исследовании изучалось выражение ароматазы, фермента, ответственного за синтез эстрогенов, в лимфатических узлах (ЛН) и его потенциальная роль в патогенезе MS с использованием модели мыши. Мы использовали мыши Cyp19-RFP, где клетки, которые выражают или ранее выражали ген Cyp19 (кодирование ароматазы), обозначаются красным флуоресцентным белком (RFP). RPF был о

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

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… These agents include estrogens, selective estrogen receptor modulators (SERMs), bisphosphonates and monoclonal antibodies [ 103 ]. Bone resorption is highly determined by hormone levels, such us estrogens. … Selective Estrogen Receptor Modulators Asian Spine J. 2016 10 787 791 10.4184/asj.2016.10.4.787 27559463 PMC4995266 107. Martinkovich S. Shah D. Planey S.L. Arnott J.A. Selective estrogen receptor modulators: Tissue specificity and clinical utility Clin. Interv. …

Gut-Bone Axis: A Non-Negligible Contributor to Periodontitis.

Periodontitis is a polymicrobial infectious disease characterized by alveolar bone loss. Systemic diseases or local infections, such as diabetes, postmenopausal osteoporosis, obesity, and inflammatory bowel disease, promote the development and progression of periodontitis. Accumulating evidences have revealed the pivotal effects of gut microbiota on bone health via gut-alveolar-bone axis. Gut pathogens or metabolites may translocate to distant alveolar bone via circulation and regulate bone homeostasis. In addition, gut pathogens can induce aberrant gut immune responses and subsequent homing o

Bone Effects of Anti-Cancer Treatments in 2024.

Considerable progress has been made in the management of cancer patients in the last decade with the arrival of anti-cancer immunotherapies (immune checkpoint inhibitors) and targeted therapies. As a result, a broad spectrum of cancers, not just hormone-sensitive ones, have seen several patients achieve profound and prolonged remissions, or even cures. The management of medium- and long-term side-effects of treatment and quality of life of patients are essential considerations. This is especially true for bone, as bone fragility can lead to increased fractures and loss of autonomy, ultimately

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease.

The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environment

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… SERMs A distinct class of medications known as selective estrogen receptor modulators (SERMs) exhibits high affinity for the estrogen receptor, manifesting varying estrogen agonist and antagonist properties according to the specific target organ. …

E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer.

Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestan

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… Several therapeutic options exist and include selective estrogen receptor modulators (e.g., tamoxifen), the aromatase inhibitors (AIs; anastrozole, letrozole, exemestane) and selective estrogen receptor down-regulators (e.g., fulvestrant). …

Sex Differences in Cancer Immunotherapy-Clinical Evidence and Mechanisms With a Focus on NSCLC.

Accumulating evidence suggests that the immune system shows subtle but relevant differences between men and women. These differences may have an impact on cancer development and TME composition as well as responses to and adverse events elicited by immunotherapies. Several, albeit not all, clinical trials indicate a greater benefit from mono-immunotherapies over chemotherapies for male patients than for female patients, especially in non-small cell lung cancer and melanoma. Vice versa, female patients might benefit more from chemo-immunotherapies. In human as well as animal models, sex differe

Нацеливаюсь на гормональное лечение мозга в менопаузе.

Эстрогены являются нейрозащитными, и менопауза может способствовать нейродегенерации. Эстриол преимущественно связывает бета-рецептор эстрогена (ERβ) в мозге для обеспечения нейрозащиты. Ранее пероральный эстриол повышал скорость когнитивной обработки и уменьшил атрофию коры головного мозга в месяц лечения twelve в случае женщин с множественным склерозом (МС). В данном случае лечение с помощью волдыря, предназначенного для здоровых менопаузальных женщин, содержащих эстриол и прогестерон (Pearlpak), оценивалось с точки зрения его воздействия на когнитивные симптомы, характерные для домена, в ря

Translational Strategies to Target Metastatic Bone Disease.

Metastatic bone disease is a common and devastating complication to cancer, confounding treatments and recovery efforts and presenting a significant barrier to de-escalating the adverse outcomes associated with disease progression. Despite significant advances in the field, bone metastases remain presently incurable and contribute heavily to cancer-associated morbidity and mortality. Mechanisms associated with metastatic bone disease perpetuation and paralleled disruption of bone remodeling are highlighted to convey how they provide the foundation for therapeutic targets to stem disease escala

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… Selective estrogen receptor modulators (SERMs) (i.e., raloxifene, toremifene, and tamoxifen) are unique molecules that bind estrogen receptors (ER) although lack the steroidal component found in estrogens. … Selective Estrogen-Receptor Modulators—Mechanisms of Action and Application to Clinical Practice. N. Engl. J. Med. 2003;348:618–629. doi: 10.1056/NEJMra022219. 56. Lu J. Palbociclib: A first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. J. …

Current and emerging therapeutic options in adrenocortical cancer treatment.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p'DDD (ortho-, para'-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment f

Clinically proven natural products against breast cancer, with mechanistic insights.

BackgroundBreast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14% of all female cancer-related deaths worldwide. This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.MethodologyRequired data for this review article was retrieved employing several readily obtainable search databases, including Web of Science® (Thomson Reuters, USA), PubMed® (U.S. National Library of Medicine, USA), and SciVerse Scopus® (Elsevier Properties S.A., USA), takin