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From laboratory to clinic: opportunities and challenges of functional food active ingredients in cancer therapy.

This review provides a comprehensive analysis of the potential of functional food active ingredients in cancer prevention and therapy. It outlines the multifaceted anticancer mechanisms of bioactive compounds-such as polyphenols, carotenoids, omega-3 fatty acids, phytosterols, alkaloids, isothiocyanates, polysaccharides, phenolic acids, flavonols, and amide-bearing compounds-which include antioxidant and anti-inflammatory activities, induction of apoptosis and autophagy, modulation of the tumor microenvironment, interference with cell cycle regulation and signaling pathways, and regulation of

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… In breast and oral carcinoma cells, capsaicin treatment has been shown to cause a G1-phase arrest by downregulating cyclin D/CDK4/6 and upregulating the CDK inhibitor p21, whereas in other models (e.g., KB nasopharyngeal carcinoma, MCF-7 breast cancer), it induced a G2/M arrest associated with reduced …

Unraveling the Anticancer Effect of Curcumin and Resveratrol.

Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unr

Tackling mantle cell lymphoma (MCL): Potential benefit of allogeneic stem cell transplantation.

Mantle cell lymphoma (MCL) is a type of non-Hodgkins lymphoma (NHL) associated with poor progression-free and overall survival. There is a high relapse rate with conventional cytotoxic chemotherapy. Intensive combination chemotherapy including rituximab, dose intense CHOP- (cyclophosphamide-doxorubicin-vincristine-prednisone) like regimens, high dose cytarabine, and/or consolidation with autologous stem cell transplant (autoSCT) have shown promise in significantly prolonging remissions. Data from phase II studies show that even in patients with chemotherapy refractory MCL, allogeneic stem cell

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… MCL has recently emerged as a separate clinicopathologic entity critically dependent on the dysregulation of cyclin D. …

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/RANK … with the RANK receptor. The new generation of both anti- and mesoprogestins that inhibit the NF-κB-cyclin D1 axis and blocks the binding of RANKL to RANK can be considered as a potential source of new RANK receptor ligands with anti-RANKL function, which may provide a new perspective into osteoporosis treatment itself as well as limit the osteoporosis ris …

Advancement of NF-κB Signaling Pathway: A Novel Target in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and is the third highest among cancer related deaths. Despite modest success with therapy such as gemcitabine, pancreatic cancer incidence remains virtually unchanged in the past 25 years. Among the several driver mutations for PDAC, Kras mutation contributes a central role for its development, progression and therapeutic resistance. In addition, inflammation is implicated in the development of most human cancer, including pancreatic cancer. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is recogniz

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connec

miR‑140‑5p inhibits the proliferation of multiple myeloma cells by targeting VEGFA.

MicroRNA (miR)‑140‑5p is associated with the growth and metastasis of various tumor cell types, yet its role in multiple myeloma (MM) remain … rated that transfection with miR‑140‑5p mimic significantly reduced the expression levels of Ki‑67, cyclin D1, vimentin, Snail, matrix metalloproteinase (MMP)‑2 and MMP‑3. Moreover, as predicted by TargetScan7.2 and verified by luciferase activity assay, it was demonstrated that vascular endothelial growth factor A (VEGFA) was targeted by miR‑140‑5p. Furth …

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

Advances in the mechanism and therapies of achondroplasia.

Achondroplasia (ACH), is the prevailing type of genetic dwarfism in humans, caused by mutations in fibroblast growth factor receptor 3 (FGFR3) that are inherited in an autosomal dominant manner. FGFR3 is mainly expressed in condensed mesenchyme, chondrocytes, and mature osteoblasts and osteoclasts, in which it regulates the formation, development, growth, and remodeling of the skeletal system. Mutations in FGFR3 causing ACH result in enhanced FGFR3 signaling through combined mechanisms including enhancing FGF dimerization and tyrosine kinase activity and stabilizing FGF receptors. In ACH, supp

Recent advancement in the anticancer efficacy of the natural flavonoid scutellarin: a comprehensive review.

Scutellarin (SC), a natural flavonoid, has been expansively employed in treating innumerable inflammation-related diseases due to its antitumor, antiinflammatory, anticancer, and antioxidant potential. Scutellarin can inhibit significant inflammatory cell signaling pathways, comprisingPI3K/Akt, NF-κB, and MAPK, and while activating antioxidant-related pathways such as Nrf2 and ARE. Numerous reviews have outlined scutellarin's pharmacological effects and associated mechanisms in inflammation-related diseases. Several studies have elucidated the mechanisms of anticancer activity by inhibiting va

Nucleo-cytoplasmic transport as a therapeutic target of cancer.

Shuttling of specific proteins out of the nucleus is essential for the regulation of the cell cycle and proliferation of both normal and malignant tissues. Dysregulation of this fundamental process may affect many other important cellular processes such as tumor growth, inflammatory response, cell cycle, and apoptosis. It is known that XPO1 (Exportin-1/Chromosome Region Maintenance 1/CRM1) is the main mediator of nuclear export in many cell types. Nuclear proteins exported to the cytoplasm by XPO1 include the drug targets topoisomerase IIα (topo IIα) and BCR-ABL and tumor suppressor proteins s

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting p

Фульминантный внематочный рецидив множественной миэломы с редким сердцем, сосудистым и многовизорным участием: отчет о деле.

Множественная миелома (ММ) — плазменная злокачественная клетка, которая, как правило, проходит длительный клинический курс. Внешняя болезнь (ЭМД) представляет собой агрессивное проявление MM с относительно низким уровнем заболеваемости, которое традиционно затрагивает кожу и мягкие ткани. В то время как MM, как правило, безжалостно прогрессирует, мощное развитие болезней, характеризующееся обширной многовизорной и сосудистой инфильтрацией, является исключительно редким явлением и редко документируется в медицинской литературе. Этот случай иллюстрирует 64-летнюю женщину, у которой были обнаруже

A Systematic Review of the Effects of Bisphosphonates on Osteoblasts In Vitro.

Bisphosphonates (BPs) are widely used to treat bone disorders, prevent skeletal-related events, and manage bone metastasis. These drugs are synthetic analogs of pyrophosphate and primarily function by inhibiting osteoclast activity. However, increasing evidence suggests that they also have an effect on osteoblasts. This systematic review aims to evaluate how bisphosphonates affect osteoblasts by summarizing findings from in vitro studies on the impact of BPs on osteoblast lineage cells, addressing the following question: "Do bisphosphonates affect osteoblast cell lineage function?". For this p

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… Despite this, CL can increase cyclin D expression [ 54 ] but does not affect MSX1 and MSX2 [ 55 ]. Only 4 studies evaluated the effects of IB on OB-like cells. …

miR-135b: A key role in cancer biology and therapeutic targets.

miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting cancer progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as cancer growth, apoptosis, migration, invasion, drug resistance, and angiogenesis, establishing it as a critical driver of cancer progression. Additionally, miR-135b is regulated by various oncogenes and therapeutic drugs, highlighting its complexity and therapeutic potential. Significant progress has been made in understanding miR-135b's impact on cancer cell behavior, establishing it as a promising b

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.

Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma.

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Rece

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… Interestingly, as MM-BMSCs are able to suppress miR-15a expression, they provide survival support and protect MM cells from bortezomib-induced apoptosis, as they block repression of bortezomib downstream targets (VEGF, cyclin D, Bcl-2; Fig. 5 ) [ 69 ]. … However, expression of miR-15a is suppressed by bone marrow stromal cells (BMSCs) that protect multiple myeloma (MM) cells from bortezomib-induced apoptosis, as they block repression of bortezomib downstream targets (VEGF, cyclin D, Bcl-2-B-cell lymphoma, Sp1–transcription factor Specificity protein …

IgM Myeloma: Всеобъемлющий обзор и практический подход к хемапаевому управлению.

IgM mieloma — редкий подтип множественной миэломы (MM). 0.5% из всех его дел. Она характеризуется нерегулируемым распространением плазменных клеток ИгМ в костном мозге. Фундаментальный патогенез предполагает регулирование изотипной рекомбинации переключателей, что приводит к различным транслокациям хромосом, таким, как 11q13 и 4p16. Обычно у пациентов возникают симптомы гипервизорного синдрома, инфильтрации костного мозга и органомегалия. Диагностика включает в себя клиническую оценку, лабораторные тесты (электропорез, биопсия костного мозга, цитогенетика, иммунохимия) и съемку. Варианты лечен

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

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… So far, research on cellular senescence has been hindered by our lack a universal, specific and widely applicable marker of cellular senescence Here, we discuss the most commonly used markers of senescence: p16 INK4a : This member of the INK4a family is a cyclin D-dependent kinase CDK4 and CDK6 inhibitor … A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704–707. doi: 10.1038/366704a0. 79. Sharpless N.E., Sherr C.J. Forging a signature of in vivo senescence. Nat. Rev. Cancer. 2015;15:397–408. doi: 10.1038/nrc3960. 80. …