In solid state ionizing radiation detectors, mainly two types of luminescent materials, scintillators and dosimeter materials, have been investigated for a long time. The former one transduces the ...energy of high energy ionizing radiation (keV–GeV) to thousands of UV-visible photons immediately and the latter storages energies under radiation exposure. After the excitation by visible photons (OSL) or thermal energies (TSL), dosimeter materials release the storage energies by UV-visible emission. In this work, Ce-doped CaF2, Eu-doped LiCaAlF6, Ce-doped LiCaAlF6, and Pr-doped LuAG were evaluated on their scintillation, OSL, and TSL properties. In Ce-doped CaF2, Eu-doped LiCaAlF6, and Pr-doped LuAG, scintillation and dosimeter properties showed a complementally relation while Ce-doped LiCaAlF6 exhibited different properties.
In recent years, research focused on the multifaceted landscape and functions of cancer-associated fibroblasts (CAFs) aimed to reveal their heterogeneity and identify commonalities across diverse ...tumors for more effective therapeutic targeting of pro-tumoral stromal microenvironment. However, a unified functional categorization of CAF subsets remains elusive, posing challenges for the development of targeted CAF therapies in clinical settings.The CAF phenotype arises from a complex interplay of signals within the tumor microenvironment, where transcription factors serve as central mediators of various cellular pathways. Recent advances in single-cell RNA sequencing technology have emphasized the role of transcription factors in the conversion of normal fibroblasts to distinct CAF subtypes across various cancer types.This review provides a comprehensive overview of the specific roles of transcription factor networks in shaping CAF heterogeneity, plasticity, and functionality. Beginning with their influence on fibroblast homeostasis and reprogramming during wound healing and fibrosis, it delves into the emerging insights into transcription factor regulatory networks. Understanding these mechanisms not only enables a more precise characterization of CAF subsets but also sheds light on the early regulatory processes governing CAF heterogeneity and functionality. Ultimately, this knowledge may unveil novel therapeutic targets for cancer treatment, addressing the existing challenges of stromal-targeted therapies.
•CAFs exhibit a phenotypic heterogeneity that define their functions in tumors.•Different CAF subsets are associated with an immunosuppressive microenvironment.•CAFs immunosuppressive functions act ...on both innate and adaptive immune response.•CAFs emerge as an attractive target for the development of anti-cancer therapies.
In tumors, Cancer-Associated Fibroblasts (CAFs) constitute the most prominent component of the tumor microenvironment (TME). CAFs are heterogeneous and composed of different CAF subsets exerting distinct functions in tumors. Specific CAF subpopulations actively influence various aspects of tumor growth, including cancer cell survival and proliferation, angiogenesis, extracellular matrix (ECM) remodeling, metastatic spread and chemoresistance. During the past decade, some CAF subsets have also been shown to modulate anti-tumor immune response. Indeed, they can increase the content in regulatory T lymphocytes and inhibit the activity of effector and cytotoxic immune cells. These functions are mainly controlled by their constitutive secretion of cytokines, chemokines, growth factors and ECM proteins, either directly in the surrounding extracellular space or through micro-vesicles. Some CAFs also express key regulators of immune checkpoints. The different roles played by CAFs, both as immunosuppressor or as physical support for tumor cell progression, set them as promising targets for anti-tumor therapies. In this review, we describe the main current knowledge on CAFs heterogeneity and immunosuppressive microenvironment, as well as their potential therapeutic implications.
Activated cancer-associated fibroblasts (CAFs) and fibroblasts that have undergone the epithelial-mesenchymal transition (EMT) in cancer stroma contribute to tumor progression and metastasis. ...However, no reports have investigated the CAF phenotype and its clinicopathological relevance in cutaneous malignant tumors, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Here, we investigated the CAF phenotype in cutaneous malignant tumors based on their histology and immunohistochemical expression of CAF-related markers, including adipocyte enhancer–binding protein 1 (AEBP1), podoplanin, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, fibroblast activating protein (FAP), CD10, S100A4, α-smooth muscle actin (α-SMA), and EMT-related markers (Zeb1, Slug, and Twist). In addition, we assessed the role of the CAF phenotype in cutaneous malignant cancers using hierarchical cluster analysis. Consequently, 3 subgroups were stratified based on the expression pattern of CAF- and EMT-related markers. Subgroup 1 was characterized by low expression of AEBP1, PDGFRα, PDGFRβ, FAP and Slug, whereas subgroup 2 was closely associated with high expression of PDGFRβ, S100A4 and Twist. In addition, high expression levels of podoplanin, PDGFRβ, CD10, S100A4, α-SMA, Zeb1, Slug and Twist were observed in subgroup 3. High expression of CD10 was commonly found in all 3 subgroups. These subgroups were correlated with histologic subtypes, that is, subgroup 1, MM; subgroup 2, BCC; and subgroup 3, SCC. We suggest that the expression pattern of CAF- and EMT-related proteins plays crucial roles in the progression of BCC, SCC, and MM.
•Three subgroups were defined by patterns of CAF- and EMT-related markers in cutaneous cancers.•These subgroups were correlated with histologic subtypes.•The CAF phenotype was closely associated with the pathogenesis of malignant cutaneous tumors.
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal cancer. The poor prognosis calls for a more detailed understanding of disease biology in order to pave the way for the development of ...effective therapies. Typically, the pancreatic tumor is composed of a minority of malignant cells within an excessive tumor microenvironment (TME) consisting of extracellular matrix (ECM), fibroblasts, immune cells, and endothelial cells. Research conducted in recent years has particularly focused on cancer-associated fibroblasts (CAFs) which represent the most prominent cellular component of the desmoplastic stroma. Here, we review the complex crosstalk between CAFs, tumor cells, and other components of the TME, and illustrate how these interactions drive disease progression. We also discuss the emerging field of CAF heterogeneity, their tumor-supportive versus tumor-suppressive capacity, and the consequences for designing stroma-targeted therapies in the future.
Tumors contain various stromal cells that support cancer progression. Some types of cancer, such as scirrhous gastric cancer, are characterized by large areas of fibrosis accompanied by ...cancer‐associated fibroblasts (CAFs). Asporin (ASPN) is a small leucine‐rich proteoglycan highly expressed in CAFs of various tumors. ASPN accelerates CAF migration and invasion, resulting in CAF‐led cancer cell invasion. In addition, ASPN further upregulated the expression of genes specific to a characteristic subgroup of fibroblasts in tumors. These cells were preferentially located at the tumor periphery and could be generated by a unique mechanism involving the CAF‐mediated education of normal fibroblasts (CEFs). In this review, we at first describe recent findings regarding the function of ASPN in the tumor microenvironment, as well as the mechanism involved in the generation of CEFs. CAFs are derived from heterogeneous origins besides resident normal fibroblasts. Among them, CAFs derived from mesothelial cells (mesothelial cell‐derived CAF MC‐CAFs) play pivotal roles in peritoneal carcinomatosis. We observed that MC‐CAFs on the surfaces of organs also participate in tumor formation by infiltrating into the parenchyma, promoting local invasion by gastric cancers. This review also highlights the potential functions of macrophages in the formation of MC‐CAFs in gastric cancers, by transfer the contents of cancer cell‐derived extracellular vesicles.
Metabolism is considered to be the core of all cellular activity. Thus, extensive studies of metabolic processes are ongoing in various fields of biology, including cancer research. Cancer cells are ...known to adapt their metabolism to sustain high proliferation rates and survive in unfavorable environments with low oxygen and nutrient concentrations. Hence, targeting cancer cell metabolism is a promising therapeutic strategy in cancer research. However, cancers consist not only of genetically altered tumor cells but are interwoven with endothelial cells, immune cells and fibroblasts, which together with the extracellular matrix (ECM) constitute the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are linked to poor prognosis in different cancer types, are one important component of the TME. CAFs play a significant role in reprogramming the metabolic landscape of tumor cells, but how, and in what manner, this interaction takes place remains rather unclear. This review aims to highlight the metabolic landscape of tumor cells and CAFs, including their recently identified subtypes, in different tumor types. In addition, we discuss various in vitro and in vivo metabolic techniques as well as different in silico computational tools that can be used to identify and characterize CAF-tumor cell interactions. Finally, we provide our view on how mapping the complex metabolic networks of stromal-tumor metabolism will help in finding novel metabolic targets for cancer treatment.
This research study presents the effect of CaF2 reinforcement on the microstructure, mechanical and self-lubricating (SL) tribological properties of Cu-Ni alloy/cBN metal matrix composite (MMC). The ...composite of Cu-Ni (CN) alloy/cBN reinforced with CaF2 nanoparticles (2–6 wt%) was developed by powder metallurgy, using pressure-less sintering without any additive. Microstructure studies proved uniform dispersion of cBN/ CaF2 particles in the Cu-Ni matrix. The maximum density and hardness were obtained at reinforcement of 2 wt% CaF2. The minimum coefficient of friction (0.15) and higher wear resistance were obtained for 4 wt% CaF2 reinforcement in CN alloy/cBN composite. Tribo-chemical reactions culminated in the formation of oxides of Cu, Ni, Fe and B at the interface, which significantly influenced the tribological properties and wear mechanisms. The worn surface analysis indicated that adhesive wear, oxidative wear and delamination are the predominated wear mechanism of CN alloy-cBN-CaF2 composite.
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•The friction and wear properties of Cu-Ni-cBN MMCs with CaF2 were investigated.•The CaF2 concentration had a significant effect on the tribological properties.•The formed tribo-layers on wear track is composed of CaF2, Cu2O, NiO, B2O3 and Fe2O3.•The relationship between the development of tribo-layers and the wear mechanism was studied.
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two ...myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.
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•Four CAF subsets identified in breast cancer accumulate differently in BC subtypes•CAF-S1 subset is associated with an immunosuppressive microenvironment•CAF-S1 cells attract and retain CD4+CD25+ T cells through OX40L, PD-L2, and JAM2•CAF-S1 cells increase CD25+FOXP3+ T lymphocytes, through B7H3, DPP4, and CD73
Costa et al. identify four subsets of carcinoma-associated fibroblasts (CAF) in breast cancer. CAF-S1 promotes an immunosuppressive microenvironment by recruiting CD4+CD25+ T cells, via secreting CXCL12, and promoting their differentiation to Tregs and survival, via expressing T cell interacting proteins.
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