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1.
Nanomaterials (Basel) ; 14(15)2024 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-39120399

RÉSUMÉ

Curcumin is a nutraceutical known to have numerous medicinal effects including anticancer activity. However, due to its poor water solubility and bioavailability, the therapeutic impact of curcumin against cancer, including breast cancer, has been constrained. Encapsulating curcumin into chitosan nanoparticles (CHNPs) is an effective method to increase its bioavailability as well as antitumorigenic activity. In the current study, the effects of curcumin-encapsulated CHNPs (Cur-CHNPs) on cell migration, targeted homing and tumor growth were examined using in vitro and in vivo breast cancer models. Cur-CHNPs possessed a monodispersed nature with long-term colloidal stability, and demonstrated significant inhibition of cell viability in vitro, which was potentiated by 5-Fluorouracil (5-FU). Outcomes of the in vivo imaging studies confirmed effective tumor targeting and retention ability of Cur-CHNPs, thereby suppressing breast tumor growth in mice models. Overall, the results demonstrated that Cur-CHNPs could be an effective candidate drug formulation for management of breast cancer.

2.
Biomedicines ; 12(7)2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-39062100

RÉSUMÉ

The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

3.
Cancer Cell Int ; 22(1): 122, 2022 Mar 17.
Article de Anglais | MEDLINE | ID: mdl-35300689

RÉSUMÉ

BACKGROUND: Cancer stem cells (CSCs) play crucial role in tumor progression, drug resistance and relapse in various cancers. CSC niche is comprised of various stromal cell types including Tumor-associated macrophages (TAMs). Extrinsic ques derived from these cells help in maintenance of CSC phenotype. TAMs have versatile roles in tumor progression however their function in enrichment of CSC is poorly explored. METHODS: Mouse macrophages (RAW264.7) cells were activated by interaction with conditioned media (CM) of murine breast cancer cells (4T1) into TAMs and the effect of activated macrophage (TAM) derived factors was examined on enrichment of cancer stem cells (CSCs) and tumor growth using in vitro and in vivo models. RESULTS: In this study, we report that macrophages upon interaction with breast cancer cells activate tumor promoting function and exhibit differential expression of various proteins as shown by secretome analysis using proteomics studies. Based on secretome data, we found that Interleukin-6 (IL-6) is one of the up-regulated genes expressed in activated macrophages. Further, we confirm that TAMs produce high levels of IL-6 and breast cancer cell derived factors induce IL-6 production in activated macrophages via p38-MAPK pathway. Furthermore, we demonstrate that tumor activated macrophages induce enrichment of CSCs and expression of CSC specific transcription factors such as Sox-2, Oct-3/4 and Nanog in breast cancer cells. We further prove that TAM derived IL-6 plays a key role in TAM mediated CSC enrichment through activation of Signal transducer and activator of transcription 3 (STAT-3) signaling. TAM derived IL-6 influences breast cancer cell migration and angiogenesis. Moreover, our in vivo findings indicated that TAM derived IL-6 induces CSC population and resulting tumor growth in breast cancer. CONCLUSION: These finding provide evidence that TAM derived IL-6 plays a major role in CSC enrichment and tumor progression in breast cancer and IL-6 and its regulated signalling network may act as potential therapeutic target for management of breast cancer.

4.
Front Oncol ; 8: 72, 2018.
Article de Anglais | MEDLINE | ID: mdl-29616190

RÉSUMÉ

Advancements in the early detection of cancer coupled with improved surgery, radiotherapy, and adjuvant therapy led to substantial increase in patient survival. Nevertheless, cancer metastasis is the leading cause of death in several cancer patients. The majority of these deaths are associated with metastatic relapse kinetics after a variable period of clinical remission. Most of the cancer recurrences are thought to be associated with the reactivation of dormant disseminated tumor cells (DTCs). In this review, we have summarized the cellular and molecular mechanisms related to DTCs and the role of microenvironmental niche. These mechanisms regulate the dormant state and help in the reactivation, which leads to metastatic outgrowth. Identification of novel therapeutic targets to eliminate these dormant tumor cells will be highly useful in controlling the metastatic relapse-related death with several cancers.

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