scholarly journals Changes in tumour vessel density upon treatment with anti-angiogenic agents: relationship with response and resistance to therapy

2013 ◽  
Vol 109 (5) ◽  
pp. 1230-1242 ◽  
Author(s):  
N S Vasudev ◽  
V Goh ◽  
J K Juttla ◽  
V L Thompson ◽  
J M G Larkin ◽  
...  
Keyword(s):  
Vessel Density ◽  
Resistance To Therapy ◽  
Tumour Vessel

scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

Angiogenesis ◽  
2021 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Vessel Density ◽  
In Vivo Studies ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAKWT/WT, PdgfrβCre + ;FAKY397F/Y397F and PdgfrβCre + ;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAKY861F/Y861F but not PdgfrβCre + ;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

scholarly journals Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

2020 ◽  
Author(s):  
Delphine M. Lees ◽  
Louise E. Reynolds ◽  
Ana Rita Pedrosa ◽  
Marina Roy-Luzarraga ◽  
Kairbaan M. Hodivala-Dilke
Keyword(s):  
Blood Vessel ◽  
Tumour Growth ◽  
Vascular Endothelial Cell ◽  
Growth Control ◽  
Vessel Density ◽  
Blood Vessel Density ◽  
Tumour Vessel ◽  
Vessel Regression ◽  
Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre+;FAKWT/WT, PdgfrβCre+;FAKY397F/Y397F and PdgfrβCre+;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre+;FAKY861F/Y861F but not PdgfrβCre+;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of a pericyte derived ‘pericrine’ signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

Blood Vessel Density Measured Using Dynamic Optical Coherence Tomography is a Tool for Wound Healers

2021 ◽  
pp. 153473462110173
Author(s):  
Rajgopal Mani ◽  
Jon Holmes ◽  
Kittipan Rerkasem ◽  
Nikolaos Papanas
Keyword(s):  
Blood Flow ◽  
Optical Coherence Tomography ◽  
Blood Vessel ◽  
Chronic Wounds ◽  
Vessel Density ◽  
Optical Coherence ◽  
Skin Microcirculation ◽  
Wound Edge ◽  
Venous Ulcers ◽  
Oct Imaging

Dynamic optical coherence tomography (D-OCT) is a relatively new technique that may be used to study the substructures in the retina, in the skin and its microcirculation. Furthermore, D-OCT is a validated method of imaging blood flow in skin microcirculation. The skin around venous and mixed arterio-venous ulcers was imaged and found to have tortuous vessels assumed to be angiogenic sprouts, and classified as dots, blobs, coils, clumps, lines, and curves. When these images were analyzed and measurements of vessel density were made, it was observed that the prevalence of coils and clumps in wound borders was significantly greater compared with those at wound centers. This reinforced the belief of inward growth of vessels from wound edge toward wound center which, in turn, reposed confidence in following the wound edge to study healing. D-OCT imaging permits the structure and the function of the microcirculation to be imaged, and vessel density measured. This offers a new vista of skin microcirculation and using it, to better understand angiogenesis in chronic wounds.

scholarly journals O7: APPARENT PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT THERAPY LEADS TO SELECTION OF TREATMENT RESISTANT CANCER STEM CELLS IN OESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
RC Walker ◽  
J Harrington ◽  
B Grace ◽  
M Lloyd ◽  
JP Byrne ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Rna Sequencing ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Oesophageal Adenocarcinoma ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Resistance To Therapy

Abstract Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

scholarly journals Radioembolization for Metastatic Colorectal Cancer

2021 ◽  
Author(s):  
David Guez ◽  
Patrick D. Sutphin ◽  
Suvranu Ganguli
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Salvage Treatment ◽  
Review Article ◽  
Prognostic Indicators ◽  
Common Site ◽  
First Line ◽  
Resistance To Therapy ◽  
Duration Of Response ◽  
Dominant Disease

AbstractThe liver is the most common site of metastatic disease in colorectal cancer, and, in the setting of liver-dominant disease, a chief contributor to mortality. Chemotherapy is the backbone of treatment for metastatic colorectal cancer; however, the duration of response is limited and resistance to therapy inevitably develops. Radioembolization represents a targeted treatment to the liver which has been studied in first-line, second-line, and in salvage treatment. Therapeutic rationale, outcomes, and prognostic indicators are presented in this systematic review article.

scholarly journals Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Meilin Chan ◽  
Licun Wu ◽  
Zhihong Yun ◽  
Trevor D. McKee ◽  
Michael Cabanero ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Malignant Pleural Mesothelioma ◽  
Neutralizing Antibodies ◽  
Pleural Mesothelioma ◽  
Spheroid Formation ◽  
Resistance To Therapy ◽  
Sarcomatoid Mesothelioma

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

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