A5061577675- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Ferroptosis and cancer prognosis
- TGF-β signaling in diseases
- Hepatocellular Carcinoma Treatment and Prognosis
- Hemophilia Treatment and Research
- Hippo pathway signaling and YAP/TAZ
- Radiomics and Machine Learning in Medical Imaging
- Renal cell carcinoma treatment
- Lipid metabolism and disorders
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Virus-based gene therapy research
- Ultrasound and Hyperthermia Applications
- Liver physiology and pathology
- Cancer Genomics and Diagnostics
- Hepatitis B Virus Studies
- Vitamin D Research Studies
- Radiation Therapy and Dosimetry
- Lipid metabolism and biosynthesis
- Cancer-related gene regulation
- Autophagy in Disease and Therapy
McGill University Health Centre
2020-2023
McGill University
2020-2023
Abstract Colorectal cancer liver metastasis (CRCLM) has two major histopathological growth patterns: angiogenic desmoplastic and non-angiogenic replacement. The replacement lesions obtain their blood supply through vessel co-option, wherein the cells hijack pre-existing vessels of surrounding tissue. Consequentially, anti-angiogenic therapies are less efficacious in CRCLM patients with lesions. However, mechanisms which drive co-option unknown. Here, we show that Runt Related Transcription...
Hemophilia A gene therapy targets hepatocytes to express B domain deleted (BDD) clotting factor VIII (FVIII) permit viral encapsidation. Since BDD is prone misfolding in the endoplasmic reticulum (ER) and ER protein followed by high-fat diet (HFD) can cause hepatocellular carcinoma (HCC), we studied how FVIII impacts HCC development using hepatocyte DNA delivery three proteins from same parental vector: (1) well-folded cytosolic dihydrofolate reductase (DHFR); (2) BDD-FVIII, which ER; (3)...
Vessel co-option is correlated with resistance against anti-angiogenic therapy in colorectal cancer liver metastases (CRCLM). co-opting lesions are characterized by highly motile cells that move toward and along the pre-existing vessels surrounding nonmalignant tissue co-opt them to gain access nutrients. To sinusoidal vessels, vessel must displace hepatocytes occupy their space. However, mechanisms underlying this displacement unknown. Herein, we examined involvement of apoptosis,...
Abstract Hepatocellular carcinoma (HCC) is the 3 rd most deadly malignancy. Activated hepatic stellate cells (aHSC) give rise to cancer-associated fibroblasts in HCC and are considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase-2 ( Scd2 ) aHSC globally suppresses nuclear CTNNB1 YAP1 tumors tumor microenvironment prevents liver tumorigenesis male mice. Tumor suppression associated with reduced leukotriene B4 receptor 2 (LTB4R2) its high...
Resistance to anti-angiogenic therapy is a major challenge in the treatment of colorectal cancer liver metastases (CRCLMs). Vessel co-option has been identified as key contributor resistance CRCLMs. Recently, we positive correlation between expression Angiopoietin1 (Ang1) and development vessel co-opting CRCLM lesions vivo. However, mechanisms underlying its stimulation are unclear. Herein, demonstrated Ang1 regulator actin-related protein 2/3 (ARP2/3) cells, vitro vivo, which known be...
Abstract Colorectal cancer liver metastatic (CRCLM) tumours present as two main histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement (RHGP). The DHGP obtain their blood supply by sprouting angiogenesis, whereas the RHGP utilize an alternative vascularisation known vessel co-option. In co-option, cells hijack mature sinusoidal vessels to supply. Vessel co-option has been reported acquired mechanism of resistance anti-angiogenic treatment in CRCLM. Here,...
Abstract Colorectal cancer liver metastases (CRCLM) have two major histopathological growth patterns (HGPs) including angiogenic desmoplastic HGP (DHGP) and non-angiogenic replacement (RHGP). The RHGP lesions obtain their blood supply through vessel co-option, where the cells hijack pre-existing vessels of surrounding tissue. Consequently, anti-angiogenic therapies are less efficacious in CRCLM patients with lesions. Recently, we identified a positive correlation between expression...
Abstract Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways that contribute to resistance against anti-angiogenic therapy. In vessel co-opted CRCLM lesions, cells are highly motile move toward and along pre-existing sinusoidal vessels hijack them gain access nutrient. The movement is accompanied by replacement hepatocytes. However, molecular mechanisms which this occurs unclear yet. To examine involvement apoptosis...
Abstract Colorectal cancer liver metastatic (CRCLM) tumours present as two main histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement (RHGP). The DHGP obtain their blood supply by sprouting angiogenesis, whereas the RHGP utilize an alternative vascularisation known vessel co-option. In co-option, cells hijack mature sinusoidal vessels to supply. Vessel co-option has been reported acquired mechanism of resistance anti-angiogenic treatment in CRCLM. Herein,...
Abstract Colorectal cancer liver metastasis (CRCLM) is one of the deadliest cancers. CRCLM tumours have two distinct histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement (RHGP). The DHGP are angiogenic, while their RHGP counterparts vessel co-opting. patients with a better response to anti-angiogenic agents chemotherapy, as well prognosis. To determine influence vitamin D supplementation in CRCLM, we analyzed HGPs 5-year OS (n=106). Interestingly, found...
252 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in North America with over 50% CRC patients developing liver metastases (LM) and 90% will die from metastatic disease. CRCLM are categorized into two main histological growth patterns (HGP) lesions: Desmoplastic (DHGP) Replacement (RHGP). We have previously published that HGPs display distinct vascularization, local invasion, response to treatment. Resected predominantly DHGP metastasis (~45%)...
Abstract Colorectal cancer liver metastasis (CRCLM) is one of the deadliest cancers. CRCLM tumours have two distinct histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement (RHGP). The DHGP are angiogenic, while their RHGP counterparts vessel co-opting. patients with showed poor response to anti-angiogenic agents, as well a worse prognosis. Herein, we conducted retrospective cohort study that comprised 106 examine effect vitamin D supplementation on HGPs...
Abstract Colorectal cancer liver metastasis (CRCLM) has two major morphological growth pattern subtypes including desmoplastic (DHGP) and replacement (RHGP). The DHGP tumors depend on angiogenesis for their growth. Conversely, RHGP are non-angiogenic obtain blood supply through vessel co-option, which the cells hijacking pre-existing vessels of surrounding tissue. Therefore, anti-angiogenic therapies have shown modest efficacy in CRCLM patients with lesions. In this study, we found...
Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death globally. Patients typically present at an advanced stage and less than 50% reach maximum 1-year survival rate, when given as first-line treatment, Sorafenib. This highlights need for early detection novel therapeutic targets crucial to increase overall (OS) patients with HCC. Given important role angiogenesis in HCC from its rich immune composition, anti-angiogenic checkpoint inhibitors (ICI), are...
Abstract Hemophilia A gene therapy targets hepatocytes to express B domain deleted-(BDD) clotting factor VIII (FVIII) permit viral encapsidation. Since BDD is prone misfolding in the endoplasmic reticulum (ER) and ER protein followed by high fat diet (HFD) can cause hepatocellular carcinoma (HCC), we studied how FVIII impacts HCC development using hepatocyte DNA delivery three proteins from same parental vector: 1) well-folded cytosolic dihydrofolate reductase (DHFR); 2) BDD-FVIII, which ER;...
Abstract Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways resistance against anti-angiogenic therapy. The cells are highly motile co-opted lesions, which move toward and along pre-existing sinusoidal vessels hijack them to gain access nutrient. movement is accompanied by displacement hepatocytes. However, molecular mechanisms underlying this unclear yet. To examine whether apoptosis involved hepatocytes we performed...