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Cancer metastasis to the bone: Mechanisms and animal models (Review).

The majority of cancer-related deaths result from tumor metastasis, with bone metastasis occurring in almost all types of malignant tumors. Understanding the mechanism by which tumors metastasize to bone is critical for the identification of novel therapeutic targets. A large amount of research has been carried out using animal models, and these models have been crucial in advancing the fundamental understanding of cancer. However, current models are limited; although they can mimic specific stages of the metastatic process, they are not able to replicate the entire process from tumorigenesis

Safety of solid oncology drugs in older patients: a narrative review.

The older population represents ∼50%-60% of the population of newly diagnosed patients with cancer. Due to physiological and pathological aging and the increased presence of comorbidities and frailty factors, this population is at higher risk of serious toxicity from anticancer drugs and, consequently, often under-treated. Despite the complexity of these treatments, a good knowledge of the pharmacology of anticancer drugs and potentially risky situations can limit the emergence of potentially lethal toxicities in this population. This review focuses on optimizing systemic oncology treatments f

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

BACKGROUND: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the complement C3a activates osteoclasts to participate in the pathogenesis of MBD; however, its mechanism of action is diverse and complex. Studies have shown that the Sirtuin (Sirt) family of proteins (i.e., Sirt1-7) are expressed in human bone and cartilage, and participate in bone metabolic balance. METHODS AND RESULTS: We measured the levels of complement C3a, Sirt1, osteoclast-related genes, and bone disease-related biological indicators using enzyme-linked imm

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment.

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs' safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

Gene regulation by non-Coding RNAs in infertility: a mechanistic review.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remode

Blood hypercoagulability and thrombosis mechanisms in cancer patients -A brief review.

Patients with malignant tumors are prone to present hypercoagulability of blood and form thrombosis, and its pathogenesis is complex involving various factors from clinical and histopathological to genetic influences. Current studies on the potential mechanism of blood hypercoagulability in patients with malignant tumors focus on the following aspects but are not limited: (1) tumor cells release coagulant-promoting substances, (2) tumor cells interact with the fibrinolytic system, (3) tumor cell-mediated platelet activation, (4) tumor-associated complement activation, and (5) genetic factors a

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemothera

Oxidative Stress Linking Obesity and Cancer: Is Obesity a 'Radical Trigger' to Cancer?

Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer

Recent advances in development of CDK7 inhibitors and their clinical trials: a narrative review.

Background and objectiveCDK7, a member of the CDK-activating kinase (CAK) family, plays a key role in cell cycle, transcriptional regulation and in regulating the proliferation and apoptosis of tumor cells. Some evidence suggests that CDK7 is a promising target for cancer treatments, so it is of great significance to develop an efficient and highly selective CDK7 inhibitor. CDK7 inhibitors have not yet been marketed. This review focuses on some selective CDK7 inhibitors currently in clinical research, and introduces their targets, indications, and the latest clinical trial progress in detail.M

Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy.

Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed and tested in clinical trials in patients with osteoporosis. In the last years, the role of osteocytes in the development of osteolytic bone lesions that occurs in multiple myeloma, have been underlined. Myeloma cells increase osteocyte death through the up-regulation of both apop

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively.

LOX-1 and cancer: an indissoluble liaison.

Recently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on metabolic targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for the recognition, binding, and internalization of ox-LDL. In the past, several studied, aimed to clarify the role of LOX-1 receptor in atherosclerosis, shed light on its role in the stimulation of the expression of adhesion molecules, pro-inflammatory signaling pathways, and pro-angiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macroph

Нейрогенная желудочно-кишечная, мочевая и сексуальная дисфункция при множественном склерозе: многодисциплинарная основа для клинической практики.

Нейрогенные желудочно-кишечные, мочевые и сексуальные симптомы широко распространены у людей с множественным склерозом и существенно ухудшают качество жизни, повседневное функционирование и психосоциальное благополучие. Несмотря на их частотность и клиническую актуальность, управление по-прежнему носит разрозненный характер по различным специальностям, тесная взаимосвязь между этими симптомами зачастую игнорируется, а у клинических работников отсутствует прагматическая основа, адаптированная к различным условиям здравоохранения. Этот обзор преобразует нынешние данные в прагматичную модель уход

Систематический обзор потенциального ускорения нееврокогнитивного старения пожилых лиц, переживших рак.

По мере роста показателей выживаемости больше внимания стало уделяться возможным когнитивным сиквелам у пожилых больных раком, что можно объяснить ускоренным старением мозга. В этом обзоре мы представляем полный обзор исследований, посвященных нейроимации, нейрокогнитивным и нейродегенеративным расстройствам у пожилых выживших жертв рака (см.>65 лет), на основе three базы данных (Pubmed, Web of Science and Medline). Ninety-six В него были включены исследования. Были обнаружены данные о функциональных и структурных изменениях в мозге (фронтальные области, базальная ганглиа, серые и белые вещест

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer.

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulati

The Rise of Oncoendocrinology: How Modern Cancer Therapies Are Reshaping Endocrine Practice.

The emergence of immune checkpoint inhibitors, targeted therapies, CAR T-cell therapy, and antibody-drug conjugates has transformed modern oncology, significantly improving survival across a wide range of malignancies. However, these advances have also introduced a growing spectrum of endocrine and metabolic complications, redefining the scope of endocrine practice. Therapy-induced endocrinopathies, including thyroid dysfunction, hypophysitis, adrenal insufficiency, diabetes, pancreatitis, dyslipidemia, gonadal dysfunction, and metabolic syndrome, are recognized as clinically significant and o

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… These biological insights underpin endocrine-based therapeutic strategies, including aromatase inhibitors, selective estrogen receptor modulators, anti-androgens, and gonadotropin-releasing hormone agonists, which remain central to the management of hormone-driven malignancies [ 23 ]. …