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Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core.

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a "smart" drug delivery system to be specific for a tumour in vivo and to penetrat

The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy.

Cancer is a challenging problem for the global health community, and its increasing burden necessitates seeking novel and alternative therapies. Most cancers share six basic characteristics known as "cancer hallmarks", including uncontrolled proliferation, refractoriness to proliferation blockers, escaping apoptosis, unlimited proliferation, enhanced angiogenesis, and metastatic spread. Apoptosis, as one of the best-known programmed cell death processes, is generally promoted through two signaling pathways, including the intrinsic and extrinsic cascades. These pathways comprise several compone

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… Anticancer effect of wogonin in vivo was shown in athymic nude mice inoculated with two breast cancer cells (T47D and MDA-MB-231 cells). The results revealed a decreased xenografts burden by up to 88% without any toxicity after 4 weeks of treatment [ 90 ]. … Fisetin can activate both caspase-8 and caspase-9 in triple-negative breast cancer cell lines, including MDA-MB-468 and MDA-MB-231 cells [ 119 ]. …

Bone health in cancer: perspective on the use of osteoanabolic agents.

Cancer negatively impacts bone health through various mechanisms, including treatment-induced bone loss and malignant bone lesions, often leading to increased fracture risk and higher morbidity and mortality. Antiresorptive agents (bisphosphonates and denosumab) are the current standard of care to reduce the risk of skeletal-related events and prevent treatment-related fragility fractures in patients with cancer. While there is strong evidence to support their benefits in cancer, there is potential room for further reduction in the risk of pathologic and fragility fractures. This narrative rev

Osteocytes: New Kids on the Block for Cancer in Bone Therapy.

The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton. During the last decade, preclinical studies have identified new cellular mechanism

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… However, the ATP bi-product, adenosine, promoted the growth of MDA-MB-231 cells, suggesting distinct roles for ATP and adenosine released by osteocytes [ 31 ]. …

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

IntroductionPesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.MethodsAnalyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

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… Sui et al . found that emodin inhibited estrogen-induced proliferation of MCF-7 and MDA-MB-231 cells, promoted apoptosis and arrested the cell cycle in G0/G1 phase by downregulating the expression of cyclin D1 Bcl-2 and ERα proteins 118 . … Using the MDA-MB-231 cell model, it was found that the antitumor effects of emodin on BC metastasis were closely related to the downregulation of MMP-2, MMP-9, uPA, and uPAR and the decreased activity of P38 and ERK 1/2 133 . …

NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells.

Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to repro

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment.

Cancer is regarded as one of the most deadly and mirthless diseases and it develops due to the uncontrolled proliferation of cells. To date, varieties of traditional medications and chemotherapies have been utilized to fight tumors. However, their immense drawbacks, such as reduced bioavailability, insufficient supply, and significant adverse effects, make their use limited. Nanotechnology has evolved rapidly in recent years and offers a wide spectrum of applications in the healthcare sectors. Nanoscale materials offer strong potential for curing cancer as they pose low risk and fewer complica

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… For efficient drug delivery, folic acid-functionalized polyethylene glycol coated ZO nanosheet (FA-PEG-ZnO NS) was synthesized and evaluated on MDA-MB-231 cells. An anticancer drug, doxorubicin, was loaded on to FA-ZnO NS. …

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

Osteocytes and Bone Metastasis.

Bone is the most frequent site of breast cancer and prostate cancer metastasis, and one of the most common sites of metastasis for many solid tumors. Once cancer cells colonize in the bone, it imposes a major clinical challenge for the treatment of the disease, and fatality rates increase drastically. Bone, the largest organ in the body, provides a fertile microenvironment enriched with nutrients, growth factors and hormones, a generous reward for cancer cells. Dependent on cancer type, cancer cells can cause osteoblastic (bone forming) or osteolytic lesions to promote the net resorption and/o

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… A2b receptors are absent on ER-positive MCF-7 cells, whereas MDA-MB-231 cells express very high levels of A2b ( 90 ). …

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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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

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… MDA-MB-231 cells were originally isolated from the breast of a 40-year-old White female patient with breast cancer, and are commonly used in bone metastasis research. MDA-MB-231 and its bone metastatic subline have been used in intracardiac, in situ , intraosseous and caudal vein injection studies. …

Multimodal imaging of bone metastases: From preclinical to clinical applications.

Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

Bone, a Secondary Growth Site of Breast and Prostate Carcinomas: Role of Osteocytes.

Bone is the primarily preferred site for breast and prostate cancer to metastasize. Bone metastases are responsible for most deaths related to breast and prostate cancer. The bone's particular microenvironment makes it conducive for the growth of cancer cells. Studies on bone metastasis have focused on the interaction between cancer cells and the bone microenvironment. Osteocytes, the most common cell type of bone tissue, have received little attention in bone metastasis, although they are master signal sensors, integrators, and skeleton transducers. They play an important role in regulating b

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… In a xenograft model of bone metastasis, established using MDA-MB-231 cells implanted into the femur of nude mice, the researchers reported that the inhibition of sclerostin significantly improved overall survival and prevented osteolytic lesions [ 67 ]. …

Palbociclib as an Antitumor Drug: A License to Kill.

Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discus

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… In preclinical research, palbociclib in combination with cisplatin exhibited a synergistic effect in MDA-MB-231 cells in prolonged sequential strategy in which the CDK4/6 inhibitor sensitized the cells to cisplatin. … Importantly, the treatment of MDA-MB-231 cells with such a combination shows Rb dependence [ 61 ]. …

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies.

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibi

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidenc

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… Furthermore, tumors composed of TEO cells were half the size of tumors formed by the injection of MDA-MB-231 cells alone ( Figure 5 B). These results suggest that TEO cells contribute to suppressed breast cancer cell proliferation in-vivo. …

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of b

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… The combination of auranofin and vitamin C has been found to exert synergistic and H 2 O 2 -mediated cytotoxicity toward MDA-MB-231 cells and other breast cancer cell lines [ 65 ]. … The MDA-MB-231 cell line is commonly used to model late-stage breast cancer; it is also useful in terms of identifying genes and pathways responsible for metastasis in various cancers. …

Adiponectin signalling in bone homeostasis, with age and in disease.

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance. Within the bone, osteoblasts and osteoclasts express the adiponectin receptors, however, there are conflicting reports on the effects of adiponectin on bone formation and turnover. Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro: with increased osteoblast differentiation and activity, alongside lower levels of osteoclastogenesis. However, human studies often demonstrate an inverse relationship between adiponectin conc

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… Of note, adiponectin-induced signalling through the AMPK pathway in ER − MDA-MB-231 cells, whilst MAPK pathway was triggered in ER + MCF-7 cells. 61 However, the effects of adiponectin on the migratory capacity of ER- cells and their ability to metastasise to the bone remains unclear; with studies reporting …

The link between bone-derived factors osteocalcin, fibroblast growth factor 23, sclerostin, lipocalin 2 and tumor bone metastasis.

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23

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… Uncarboxylated osteocalcin promotes proliferation and metastasis of MDA-MB-231 cells through TGF-β/SMAD3 signaling pathway. BMC Mol Cell Biol (2022) 23:18. doi: 10.1186/s12860-022-00416-7 37. Ye R, Pi M, Cox JV, Nishimoto SK, Quarles LD. …