scholarly journals Modulating the Inflammatory Response to Wounds and Cancer Through Infection

2021 ◽  
Vol 9 ◽  
Author(s):  
Paco López-Cuevas ◽  
Stephen J. Cross ◽  
Paul Martin
Keyword(s):  
Inflammatory Response ◽  
Cancer Biology ◽  
Bacterial Infections ◽  
Early Cancer ◽  
Tumour Microenvironment ◽  
Confocal Imaging ◽  
Cellular Interactions ◽  
Neoplastic Cells ◽  
Automated Tracking ◽  
Early Inflammatory Response

The zebrafish (Danio rerio) has recently emerged as an excellent model to study cancer biology and the tumour microenvironment, including the early inflammatory response to both wounding and early cancer growth. Here, we use high-resolution confocal imaging of translucent zebrafish larvae, with novel automated tracking and cell:cell interaction software, to investigate how innate immune cells behave and interact with repairing wounds and early cancer (pre-neoplastic) cells expressing a mutant active human oncogene (HRASG12V). We show that bacterial infections, delivered either systemically or locally, induce a change in the number and behaviour of neutrophils and macrophages recruited to acute wounds and to pre-neoplastic cells, and that infection can modify cellular interactions in ways that lead to a significant delay in wound healing and a reduction in the number of pre-neoplastic cells. Besides offering insights as to how Coley’s toxins and other cancer bacteriotherapies may function to reduce cancer burden, our study also highlights novel software tools that can be easily adapted to investigate cellular behaviours and interactions in other zebrafish models.

The role of microRNA regulation in the early inflammatory response: miR-146a and NF-κB signaling in lung inflammation

Pneumologie ◽  
2013 ◽  
Vol 67 (S 01) ◽  
Author(s):  
X Lai ◽  
C Schulz ◽  
F Seifert ◽  
B Dolniak ◽  
O Wolkenhauer ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lung Inflammation ◽  
Microrna Regulation ◽  
Early Inflammatory Response

scholarly journals Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2067
Author(s):  
Rhynelle S. Dmello ◽  
Sarah Q. To ◽  
Ashwini L. Chand
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Cellular Interactions ◽  
Circulating Tumour Cells ◽  
Therapeutic Targeting ◽  
Colorectal Cancer Patients

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.

MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney

2007 ◽  
Vol 293 (5) ◽  
pp. F1556-F1563 ◽  
Author(s):  
Frank Y. Ma ◽  
Greg H. Tesch ◽  
Richard A. Flavell ◽  
Roger J. Davis ◽  
David J. Nikolic-Paterson
Keyword(s):  
Inflammatory Response ◽  
P38 Mapk ◽  
Renal Injury ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Direct Role ◽  
Mitogen Activated Protein ◽  
Early Inflammatory Response ◽  
Induced Apoptosis

Activation of the p38 mitogen-activated protein kinase (MAPK) pathway induces inflammation, apoptosis, and fibrosis. However, little is known of the contribution of the upstream kinases, MMK3 and MKK6, to activation of the p38 kinase in the kidney and consequent renal injury. This study investigated the contribution of MKK3 to p38 MAPK activation and renal injury in the obstructed kidney. Groups of eight wild-type (WT) or Mkk3−/− mice underwent unilateral ureteric obstruction (UUO) and were killed 3 or 7 days later. Western blotting showed a marked increase in phospho-p38 (p-p38) MAPK in UUO WT kidney. The same trend of increased p-p38 MAPK was seen in the UUO Mkk3−/− kidney, although the actual level of p-p38 MAPK was significantly reduced compared with WT, and this could not be entirely compensated for by the increase in MKK6 expression in the Mkk3−/− kidney. Apoptosis of tubular and interstitial cells in WT UUO mice was reduced by 50% in Mkk3−/− UUO mice. Furthermore, cultured Mkk3−/− tubular epithelial cells showed resistance to H2O2-induced apoptosis, suggesting a direct role for MKK3-p38 signaling in tubular apoptosis. Upregulation of MCP-1 mRNA levels and macrophage infiltration seen on day 3 in WT UUO mice was significantly reduced in Mkk3−/− mice, but this difference was not evident by day 7. The development of renal fibrosis in Mkk3−/− UUO mice was not different from that seen in WT UUO mice. In conclusion, these studies identify discrete roles for MKK3-p38 signaling in renal cell apoptosis and the early inflammatory response in the obstructed kidney.

Immunonutrition in elective colorectal surgery and early inflammatory response

2021 ◽  
Author(s):  
Jaqueline Velkoski ◽  
Franco Grimaldi ◽  
Laura Di Meo ◽  
Francesca Mion ◽  
Riccardo Pravisani ◽  
...  
Keyword(s):  
Colorectal Surgery ◽  
Inflammatory Response ◽  
Elective Colorectal Surgery ◽  
Early Inflammatory Response

scholarly journals Opiate Analgesia Treatment Reduced Early Inflammatory Response After Severe Chest Injuries

2016 ◽  
Vol 70 (6) ◽  
pp. 457
Author(s):  
Goran Krdzalic ◽  
Nermin Musanovic ◽  
Alisa Krdzalic ◽  
Indira Mehmedagic ◽  
Amar Kesetovic
Keyword(s):  
Inflammatory Response ◽  
Chest Injuries ◽  
Early Inflammatory Response

scholarly journals Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

2020 ◽  
Author(s):  
Abigail Elliot ◽  
Henna Myllymäki ◽  
Yi Feng
Keyword(s):  
Immune Cells ◽  
Cancer Biology ◽  
Inflammatory Responses ◽  
Live Imaging ◽  
Innate Immune ◽  
Leukocyte Recruitment ◽  
Innate Immune Cells ◽  
Neoplastic Cells ◽  
Tumour Development ◽  
Tumour Initiation

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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