Search results for "Cancer"

Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

2018

Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although…

INFLAMMATORY BOWEL DISEASE, COLORECTAL CANCER AND TYPE 2 DIABETES MELLITUS: THE LINKS

2016

The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others. This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases. The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory med…

Hsp60 as a Novel Target in IBD Management: A Prospect

2019

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be …

Gut microbiota imbalance and colorectal cancer

2016

International audience; The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the g…

[How some commensal bacteria would exacerbate colorectal carcinogenesis?].

2016

International audience; The gut microbiota maintains a relationship with its host with strong mutual benefits. Changes in the composition of the intestinal microbiota have been detected in colorectal cancer patients to the extent that it is now considered as a real contributing factor in this pathology. In this review, we focus on three commensal bacterial species, namely Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli, which seem to emerge as pathogens and to contribute to colorectal carcinogenesis through their inflammatory and oncogenic properties.; Le microbiote intestinal entretient une relation mutualiste forte avec l’hôte. Depuis la mise en évidence de modificatio…

Colon cancer molecular subtype intratumoral heterogeneity and its prognostic impact: An extensive molecular analysis of the PETACC-8

2018

Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

2018

Dietary interventions may effectively control cancer development, with phytosterols (PS) being a class of cancer chemopreventive dietary phytochemicals. The present study, for the first time, evaluates the antiproliferative effects of a PS-ingredient used for the enrichment of several foods and its main PS, β-sitosterol, at physiological serum levels, in the most prevalent cancer cells in women (breast (MCF-7), colon (HCT116) and cervical (HeLa)). In all three cell lines, these compounds induced significant cell viability reduction without a clear time- and dose-dependent response. Moreover, all treatments produced apoptotic cell death with the induction of DNA fragmentation through the app…

A novel therapeutic approach to colorectal cancer in diabetes: role of metformin and rapamycin

2019

International audience; The link between colorectal cancer (CRC), diabetes mellitus (DM) and inflammation is well established, and polytherapy, including rapamycin, has been adopted. This study is a novel approach that aimed at assessing the effect of a combination therapy of metformin and rapamycin on the control or prevention of CRC in diabetic animals, in presence or absence of probiotics. Fifty NOD/SCIDs male mice developed xenograft by inoculating HCT116 cells. They were equally divided into diabetics (induced by Streptozotocin) and non-diabetics. Metformin was given in drinking water, whereas rapamycin was administered via intra-peritoneal injections. Probiotics were added to the doub…

Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib.

2017

Abstract Background The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects. Purpose There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens. Study design In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants. Results The combination of erlotinib with artesunate leads to synergistic inhibition of cell grow…

Abstract C097: Pyrrolo[2′,3′:3,4]cyclohepta[1,2-d][1,2]oxazoles: A new class of antimitotic agents

2019

Abstract Tubulin-binding molecules constitute an important class of antineoplastic agents, with broad activity in both solid and hematologic malignancies. Oxazoles represent the core structure of many drug candidates with multiple targets, providing an attractive scaffold in medicinal chemistry. Diaryl[1,2]oxazoles have emerged as potent analogues of the antitubulin compound combretastatin A-4 (CA-4). Naphtylcombretastin and its derivatives incorporating the isoxazole moiety displayed potent cytotoxic effects and inhibition of tubulin polymerization. In particular, 5-(naphthalen-2-yl)-4-(TMP)-1,2-oxazole and 4-(naphthalen-2-yl)-5-(TMP)-1,2-oxazole showed the same inhibitory potency as napht…