Update on Adipose Tissue and Cancer

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 44(6), P. 961 - 974

Published: June 1, 2023

Adipose tissue is the largest endocrine organ and an accepted contributor to overall energy homeostasis. There strong evidence linking increased adiposity development of 13 types cancer. With comes metabolic dysfunction insulin resistance, systemic glucose support growth many cancers, including those colon endometrium. also important direct crosstalk between adipose various organs. For instance, healthy function mammary gland, as well development, growth, progression breast cancer, are heavily impacted by in which epithelial cells embedded. Cells responsive external stimuli, overfeeding, leading remodeling changes secretion factors known drive cancers. Loss like adiponectin production leptin, endotrophin, steroid hormones, inflammatory mediators have been determined be obesity-cancer link. Obesity associated with a structural tissue, localized fibrosis disrupted angiogenesis that contribute Furthermore, tumor feed off where lipolysis within adipocytes leads release fatty acids stromal cell aerobic glycolysis lactate. Both hypothesized higher energetic demands cancer cells. Here, we aim provide update on state literature revolving around role initiation progression.

Language: Английский

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Targeting inflammation as cancer therapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: March 22, 2024

Abstract Inflammation has accompanied human beings since the emergence of wounds and infections. In past decades, numerous efforts have been undertaken to explore potential role inflammation in cancer, from tumor development, invasion, metastasis resistance tumors treatment. Inflammation-targeted agents not only demonstrate suppress cancer but also improve efficacy other therapeutic modalities. this review, we describe highly dynamic complex inflammatory microenvironment, with discussion on key mediators including cells, cytokines, their downstream intracellular pathways. addition, especially address development highlight action mechanisms inflammation-targeted therapies antitumor response. Finally, summarize results both preclinical clinical studies up date illustrate translation therapies.

Language: Английский

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KK-LC-1 as a therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 5, 2023

Abstract Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) a marker (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstream targets control ALDH + may facilitate TNBC suppression. Here, we show that KK-LC-1 determines the stemness via binding FAT1 subsequently promoting ubiquitination degradation. This compromises Hippo pathway leads nuclear translocation YAP1 ALDH1A1 transcription. These findings identify KK-LC-1-FAT1-Hippo-ALDH1A1 in as therapeutic target. To reverse malignancy due expression, employ computational approach discover Z839878730 (Z8) an small-molecule inhibitor which disrupt binding. We demonstrate Z8 suppresses growth mechanism reactivates decreases cell viability.

Language: Английский

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Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4646 - 4687

Published: May 13, 2024

This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in human body. The biochemical processes occurring are described, ranging from nonspecific, first glance, strictly hormone-induced reactions, genetic epigenetic regulation, which allows for a broader deeper understanding principles oncogenesis, as well maintaining viability cells mammary gland. Specific pathways activation stress have studied response overproduction hormones estrogens, specific ways reduce its negative impact described. diversity participants that trigger reactions different sides is considered more fully: glycolytic activity cancer, nature consumption amino acids metals. role metals discussed detail. They can act both co-factors direct stress, since they either mechanism lipid peroxidation or capable activating signaling tumorigenesis. Special attention paid regulation tumors. A complex cascade mechanisms explained, made it possible reconsider existing opinion triggers launching oncological process, survival their ability localize.

Language: Английский

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Combined Gadolinium and Boron Neutron Capture Therapies for Eradication of Head-and-Neck Tumor Using Gd¹⁰B₆ Nanoparticles under MRI/CT Image Guidance

JACS Au, Journal Year: 2023, Volume and Issue: 3(8), P. 2192 - 2205

Published: Aug. 4, 2023

Eradication of head-and-neck (H&N) tumors is very difficult and challenging because the characteristic feature frequent recurrence difficulty in killing cancer stem cells. Neutron capture therapy (NCT) emerging as a noninvasive potential modality for treatments various types tumors. Herein, we report that 98.5% 10B-enriched anti-EGFR-Gd10B6 nanoparticles can not only deliver large doses 158 μg 10B/g tumor tissues well 56.8 157Gd/g with high tumor-to-blood (T/B) 10B ratio 4.18, but also exert effective CT/MRI image-guided combined GdBNCT effects on cells eradication recurrent This leads to long average half-lifespan 81 days H&N tumor-bearing mice, which record-making result, surpasses best result reported literature using radiotherapy T cell-mediated immunotherapy (70 d).

Language: Английский

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Disaggregation‐Activated pan‐COX Imaging Agents for Human Soft tissue Sarcoma

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(24)

Published: April 12, 2024

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly heterogeneous malignancies like adult soft tissue sarcomas, where conventional inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker CSCs sarcoma clinical pathology. Based on their structures, BD-IMC-1 showcased higher susceptibility to compared BD-IMC-2, consistent with selective interaction COX. Notably, the revealed positive cooperativity binding COX-2 at sub-micromolar ranges. Both showed significant turn-on upon LPS or PMA triggered upregulation live RAW264.7, HeLa, human cell line (Saos-LM2) up 2-fold increase negligible toxicity. More importantly, demonstrated practical imaging paraffin-fixed tissue. Considering fixed tissues most practiced pathological sample, our finding suggests of activated chemosensor applications.

Language: Английский

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Cancer and Autoimmune Diseases as Two Sides of Chronic Inflammation and the Method of Therapy

Current Cancer Drug Targets, Journal Year: 2024, Volume and Issue: 24(11), P. 1089 - 1103

Published: Jan. 29, 2024

Chronic inflammation is associated with a prolonged increase in various inflammatory factors. According to clinical data, it can be linked both cancer and autoimmune diseases the same patients. This raises critical question of how chronic relates seemingly opposing - tumors, which there immunosuppression, diseases, over-activation immune system. In this review, we consider as prerequisite for suppression an increased likelihood damage. We also discuss potential disease-modifying therapies targeting inflammation, helpful autoimmunity. On one hand, pro-inflammatory factors persisting areas stimulate production anti-inflammatory due negative feedback loop, eliciting suppression. other bring baseline immunity closer threshold level required triggering response using bystander activation cells. Focusing on role may open prospects more intensive drug discovery inflammation.

Language: Английский

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Tumor Regulatory Effect of 15-Hydroxyprostaglandin Dehydrogenase (HPGD) in Triple-Negative Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1912 - 1912

Published: Feb. 23, 2025

Prostaglandin regulation is known to play a pivotal role in tumorigenesis; however, the contributions of prostaglandin-metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) cancer development remain poorly understood. In this study, we investigate effects HPGD on cell viability, proliferation, anchorage-independent growth, and migration triple-negative breast (TNBC), an aggressive subtype cancer. Overexpression human TNBC cells resulted both positive negative proliferation colony formation, with these occurring independent prostaglandin E2 (PGE2). contrast, overexpression mouse homolog, Hpgd, murine led consistent but modest reduction viability indicating that activity varies depending species line context. Notably, expressing mutant form Hpgd (Hpgdmut), which lacks ability bind PGE2, exhibited similar functional outcomes formation as those wild-type (HpgdWT). These findings suggest may exert its tumorigenic through non-enzymatic mechanisms, potentially by involving modulation KRAS signaling cells. Our results highlight diverse roles biology, particularly context TNBC, point pathways significant aspect activity.

Language: Английский

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A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Sept. 26, 2022

Breast cancer (BC) is the most common in women worldwide. This highly heterogeneous disease molecularly stratified into luminal A, B, HER2, triple-negative/basal-like, and normal-like subtypes. An important aspect BC progression activation of inflammatory processes. The CD8+/Th1, NK, M1 tumor associated macrophages (TAMs), leads to destruction. In contrast, an anti-inflammatory response mediated by CD4+/Th2 M2 TAMs will favor progression. Inflammation also stimulates production mediators like reactive oxygen species (ROS). chronic inflammation, ROS activates oxidative stress endothelial dysfunction. cancer, plays a dual role with anti-tumorigenic pro-tumorigenic effects cell signaling pathways that control proliferation, survival, apoptosis, inflammation. MicroRNAs (miRNAs), which are known be involved can regulated ROS. At same time, miRNAs regulate expression genes modulating stress. this review, we discuss interplay between ROS, as anticancer promoter molecules BC. A clear understanding regulation may lead new opportunities for therapy

Language: Английский

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α-chaconine increases the sensitivity of HER2+ breast cancer cells to trastuzumab by targeting acetylcholinesterase

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 188, P. 109809 - 109809

Published: Feb. 16, 2025

Language: Английский

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