Targeting tumor microenvironment for cholangiocarcinoma: Opportunities for precision medicine

Carloni, Riccardo; Rizzo, Alessandro; Ricci, Angela Dalia; Federico, Alessandro Di; Luca, Raffaele De; Güven, Deniz Can; Yalçın, Şuayib; Brandi, Giovanni

doi:10.1016/j.tranon.2022.101514

Cited by 14 publications

(14 citation statements)

References 93 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor microenvironment (TME) surrounding tumor cells comprises immune cells, fibroblasts, endothelial cells, and a wide range of soluble factors. The TME of cholangiocarcinoma is characterized by an abundant desmoplastic stroma and shows a high heterogeneity [ 19 , 20 ]. Pixel-wise entropy may capture tumor heterogeneity, which plays a central role in cancer progression and resistance to anticancer therapies [ 19 , 20 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…The TME of cholangiocarcinoma is characterized by an abundant desmoplastic stroma and shows a high heterogeneity [ 19 , 20 ]. Pixel-wise entropy may capture tumor heterogeneity, which plays a central role in cancer progression and resistance to anticancer therapies [ 19 , 20 , 21 ]. Furthermore, the fact that the clustering model was trained with mouse histopathology images and yet a similar trend was also obtained for humans with respect to pixel-wise entropy suggests that there is a morphological similarity between mouse and human histopathology images.…”

Section: Resultsmentioning

confidence: 99%

“…The TME of cholangiocarcinoma comprises abundant fibroblasts in the desmoplastic stroma, as well as immune cells, endothelial cells, and various other factors. It also manifests a high level of heterogeneity that plays a central role in cancer progression and resistance to anticancer therapies [ 19 , 20 ]. Our pixel-wise entropy analysis may capture this tumor heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…Our pixel-wise entropy analysis may capture this tumor heterogeneity. Such heterogeneity is due not only to the TME but also to the diversity of cancer cells at genetic and epigenetic levels [ 19 , 20 , 21 ], and it is expected to be amenable to spatiotemporal analysis through combined evaluation of pathological images and gene and molecular profiles [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Pixel-Level Clustering of Hematoxylin–Eosin-Stained Sections of Mouse and Human Biliary Tract Cancer

Inoue¹,

Aimono

Kasuga

et al. 2022

Biomedicines

View full text Add to dashboard Cite

We previously established mouse models of biliary tract cancer (BTC) based on the injection of cells with biliary epithelial stem cell properties derived from KRAS(G12V)-expressing organoids into syngeneic mice. The resulting mouse tumors appeared to recapitulate the pathological features of human BTC. Here we analyzed images of hematoxylin and eosin (H&E) staining for both the mouse tumor tissue and human cholangiocarcinoma tissue by pixel-level clustering with machine learning. A pixel-clustering model that was established via training with mouse images revealed homologies of tissue structure between the mouse and human tumors, suggesting similarities in tumor characteristics independent of animal species. Analysis of the human cholangiocarcinoma tissue samples with the model also revealed that the entropy distribution of cancer regions was higher than that of noncancer regions, with the entropy of pixels thus allowing discrimination between these two types of regions. Histograms of entropy tended to be broader for noncancer regions of late-stage human cholangiocarcinoma. These analyses indicate that our mouse BTC models are appropriate for investigation of BTC carcinogenesis and may support the development of new therapeutic strategies. In addition, our pixel-level clustering model is highly versatile and may contribute to the development of a new BTC diagnostic tool.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Pixel-Level Clustering of Hematoxylin–Eosin-Stained Sections of Mouse and Human Biliary Tract Cancer

Inoue¹,

Aimono

Kasuga

et al. 2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Targeting hypoxia in the tumor microenvironment is another strategy for the design of anticancer therapeutics and for preventing, in general, the onset and progression of cancer [227,228]. Similarly, reversing or reducing hypoxia in the tumor microenvironment is an effective strategy to improve the therapeutic performance of immunological and other drugs [227,228].…”

Section: Protein Interactions Of Chelators and Chelator-iron Complexe...mentioning

confidence: 99%

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

Kontoghiorghes¹

2022

IJMS

View full text Add to dashboard Cite

There is new and increasing evidence from in vitro, in vivo and clinical studies implicating the pivotal role of iron and associated metabolic pathways in the initiation, progression and development of cancer and in cancer metastasis. New metabolic and toxicity mechanisms and pathways, as well as genomic, transcription and other factors, have been linked to cancer and many are related to iron. Accordingly, a number of new targets for iron chelators have been identified and characterized in new anticancer strategies, in addition to the classical restriction of/reduction in iron supply, the inhibition of transferrin iron delivery, the inhibition of ribonucleotide reductase in DNA synthesis and high antioxidant potential. The new targets include the removal of excess iron from iron-laden macrophages, which affects anticancer activity; the modulation of ferroptosis; ferritin iron removal and the control of hyperferritinemia; the inhibition of hypoxia related to the role of hypoxia-inducible factor (HIF); modulation of the function of new molecular species such as STEAP4 metalloreductase and the metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); modulation of the metabolic pathways of oxidative stress damage affecting mitochondrial function, etc. Many of these new, but also previously known associated iron metabolic pathways appear to affect all stages of cancer, as well as metastasis and drug resistance. Iron-chelating drugs and especially deferiprone (L1), has been shown in many recent studies to fulfill the role of multi-target anticancer drug linked to the above and also other iron targets, and has been proposed for phase II trials in cancer patients. In contrast, lipophilic chelators and their iron complexes are proposed for the induction of ferroptosis in some refractory or recurring tumors in drug resistance and metastasis where effective treatments are absent. There is a need to readdress cancer therapy and include therapeutic strategies targeting multifactorial processes, including the application of multi-targeting drugs involving iron chelators and iron–chelator complexes. New therapeutic protocols including drug combinations with L1 and other chelating drugs could increase anticancer activity, decrease drug resistance and metastasis, improve treatments, reduce toxicity and increase overall survival in cancer patients.

show abstract

Tumor cell-derived exosomes regulate macrophage polarization: Emerging directions in the study of tumor genesis and development

Tan,

Tang,

Wang

et al. 2023

Heliyon

View full text Add to dashboard Cite

Targeting tumor microenvironment for cholangiocarcinoma: Opportunities for precision medicine

Cited by 14 publications

References 93 publications

Pixel-Level Clustering of Hematoxylin–Eosin-Stained Sections of Mouse and Human Biliary Tract Cancer

Pixel-Level Clustering of Hematoxylin–Eosin-Stained Sections of Mouse and Human Biliary Tract Cancer

New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

Tumor cell-derived exosomes regulate macrophage polarization: Emerging directions in the study of tumor genesis and development

Contact Info

Product

Resources

About