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Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-2

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… The synthesis of UCP1 protein is highly regulated by the PRDM16 protein [ 90 ] , PPARγ and PPARα proteins [ 91 ] , C/EBP-α [ 91 ] , CREB-binding protein [ 92 ] , and PGC-1α [ 93 , 94 ] . … In addition, lipolysis in adipocytes could be stimulated by the treatment with LLC-derived EVs enriched in the eukaryotic translation initiation factor 5A (EIF5A) via CREB-binding protein activation [ 109 ] . …

The Eph/Ephrin system in primary bone tumor and bone cancer pain.

The family of Eph receptor tyrosine kinases and their Ephrin ligands system constitutes a bidirectional signaling pathway. Eph/Ephrin system coordinate a wide spectrum of pathologic processes during development, metastasis, prognosis, drug resistance and angiogenesis in carcinogenesis. Chemotherapy, surgery and radiotherapy are the most commonly used clinical treatments for primary bone tumors. Therefore, surgical resection is often unable to completely eliminate the tumor, and this is the main cause of metastasis and postoperative recurrence. A growing body of literature has been published la

A New Paradigm for Pediatric AML: Improving the Pipeline for Treatments Targeting Cytogenetic and Molecular Alterations.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where "one-size-fits-all" chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on s

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

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

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… HAT-Mediated Regulation of the DNA Damage Response The HAT p300/CREB-binding protein-associated factor (PCAF) acetylates H4K8 in BRCA-deficient TNBC, thereby promoting replication fork degradation [ 76 ]. … Activation of Stat3 sequence-specific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation J. Biol. Chem. 2005 280 11528 11534 10.1074/jbc.M413930200 15649887 47. Sakaguchi K. Herrera J.E. Saito S. Miki T. Bustin M. Vassilev A. Anderson C.W. Appella E. …

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

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… Their binding to PPAR-γ leads to recruitment of CREB-binding protein (CBP) and p300. By possessing histone acetyltransferase activity, these proteins modify chromatin by adding acetyl groups to histones. … AMP-activated protein kinase AP1 activator protein 1 BAX BCL2-associated X protein Bcl B-cell lymphoma proteins (Bcl-2 and Bcl-xL) BRAF B-rapidly accelerated fibrosarcoma BRCA1 breast cancer gene 1 cAMP cyclic adenosine monophosphate CAF cancer-associated fibroblasts CASP1 caspase 1 CAT catalase CBP CREB-binding …

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that t

Leptin, Leptin Receptor, KHDRBS1 (KH RNA Binding Domain Containing, Signal Transduction Associated 1), and Adiponectin in Bone Metastasis from Breast Carcinoma: An Immunohistochemical Study.

Breast cancer patients are at a high risk of complications from bone metastasis. Molecular characterization of bone metastases is essential for the discovery of new therapeutic targets. Here, we investigated the expression and the intracellular distribution of KH RNA binding domain containing, signal transduction associated 1 (KHDRBS1), leptin, leptin receptor (LEPR), and adiponectin in bone metastasis from breast carcinoma and looked for correlations between the data. The expression of these proteins is known in breast carcinoma, but it has not been investigated in bone metastatic tissue to d

Эффективность Куркумина в нейродегенеративных болезнях: от фармакокинетических барьеров до передовых систем доставки.

Предыстория и цели: Основные нейродегенеративные заболевания (НД) - болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS) - создают растущее бремя для здоровья людей во всем мире при отсутствии доступных методов лечения, позволяющих вести борьбу с заболеваниями. Куркумин, полифенол из Curcuma longa, является многообещающим кандидатом из-за его плейотропного антиоксиданта, антивоспалительного и нейрозащитного профиля, наблюдаемого главным образом в доклинических моделях, но плохой оральной биодоступности ().<1%) и незначительное пр

The protective and chemotherapeutical role of amygdalin in induced mammary cancer in experimental mice and upregulation of related genes.

Breast cancer is a prominent health issue among oncological diseases in emerging nations. The study sought to assess the significant function of amygdalin as a protective and chemotherapeutical substance in combating this lethal condition, either independently or in conjunction with tamoxifen therapy. Breast cancer in mice was induced by 7,12-Dimethylbenz(a)anthracene (DMBA). Mice were divided into six groups, 15 mice in each group. (i) control group, (ii) carcinogenic group, (iii) tamoxifen-treated group, (iv) Amygdalin-treated group, (v) (Amygdalin + tamoxifen) group, (vi) Amygdalin protecti

Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt/β-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt/β-catenin pathway is still not targeted in routine clinical practice for cancer mana

Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate

A Route for Investigating Psoriasis: From the Perspective of the Pathological Mechanisms and Therapeutic Strategies of Cancer.

Psoriasis is an incurable skin disease that develops in about two-thirds of patients before the age of 40 and requires lifelong treatment; its pathological mechanisms have not been fully elucidated. The core pathological process of psoriasis is epidermal thickening caused by the excessive proliferation of epidermal keratinocytes, which is similar to the key feature of cancer; the malignant proliferation of cancer cells causes tumor enlargement, suggesting that there is a certain degree of commonality between psoriasis and cancer. This article reviews the pathological mechanisms that are common

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… Annotation: CDK7: cyclin-dependent kinase 7; TYK2: tyrosine protein kinase 2; IL-23: interleukin-23; IL-17: interleukin-17; BRD4: bromo domain-containing protein 4; p300/CBP: histone acetyltransferase paralogues/ CREB-binding protein; HDACs: histone deacetylases; DNMTs: DNA methyltransferases; GLUT1: …

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility gr

The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.

As a multi-substrate transmembrane protease, γ-secretase exists widely in various cells. It controls multiple important cellular activities through substrate cleavage. γ-secretase inhibitors (GSIs) play a role in cancer inhibition by blocking Notch cleavage, and are considered as potential therapeutic strategies for cancer. Currently, GSIs have encouraging performance in preclinical models, yet this success does not translate well in clinical trials. In recent years, a number of breakthrough discoveries have shown us the promise of targeting γ-secretase for the treatment of cancer. Here, we in

Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.

INTRODUCTION: Chemoresistance and disease relapses in epithelial ovarian cancer (EOC) highlight the need for novel therapeutic strategies. Here, we investigated phosphodiesterase 7A (PDE7A) as a potential target in ovarian cancer treatment. METHODS: Gene expression was performed by RNA sequencing data comparing high-grade serous ovarian carcinoma (HGSOC) and fallopian tube samples. The PDE7 inhibitor BRL 50481, alone or combined with paclitaxel (PTX), was tested in drug-sensitive A2780 and multi-resistant OVCAR3 cells by Diphenyltetrazolium bromide (MTT) assay. To validate data from the high

Resveratrol and Curcumin for Chagas Disease Treatment-A Systematic Review.

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage-characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease's progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Re

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… Curcumin, a Novel P300/CREB-Binding Protein-Specific Inhibitor of Acetyltransferase, Represses the Acetylation of Histone/Nonhistone Proteins and Histone Acetyltransferase-Dependent Chromatin Transcription. J. Biol. Chem. 2004;279:51163–51171. doi: 10.1074/jbc.M409024200. 80. …

Мелатонин улучшает астроглиоз и микроглиоз в мышечной модели купризоны.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛЬ: В ряде исследований сообщалось, что мелатонин участвует в совершенствовании подстрекательского процесса, совершенствовании функции миелина и регенерации центральной нервной системы (ЦНС). Нынешнее исследование направлено на оценку защитного воздействия мелатонина в кустарной зоне (КХЗ) в результате повреждения миелина в корпусе каллосум (КЦ) и изучение вероятных основополагающих механизмов способности к ремиелинации и/или нейрозащиты.Мы управляли кухонной зоной в чау в одиночестве каждый день. 6 Мы изучали демиэлизацию с помощью пятна LFB, пятна олигодендроцита с

Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-gamma agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARgamma agonists in the treatment and prevention of