Clinical immunology Gene expression disorders of innate antibacterial signaling pathway in pancreatic cancer patients: implications for leukocyte dysfunction and tumor progression

Słotwiński, Robert; Dąbrowska, Aleksandra; Lech, Gustaw; Słodkowski, Maciej; Słotwińska, Sylwia Małgorzata

doi:10.5114/ceji.2014.47736

Cited by 7 publications

(8 citation statements)

References 85 publications

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“…These patients were treated previously in other surgical wards and had organ damage after major abdominal surgeries, reoperations, including a fairly homogeneous group of patients with septic infections of the catheter for parenteral nutrition at home or a group of patients with severe acute pancreatitis. The current genetic tests were performed at the mRNA level and were preceded by the analysis of changes in the expression of the same genes during treatment (days 1, 3, 7) and in other groups of patients in order to reduce the impact of other factors on the tested parameters, as it happened many times during our previous studies on inflammatory response mediators [ 82 , 89 ].…”

Section: Discussionmentioning

confidence: 99%

“…The objective of this study was an attempt to determine whether the expression of genes involved in innate antibacterial response (TLR2, NOD1, TRAF6, HMGB1 and Hsp70) in peripheral blood leukocytes in critically ill patients, may undergo significant changes depending on the severity of the infection and the degree of malnutrition. The selection of genetic parameters studied was based on the results of our previous studies conducted in malnourished patients [ 81 , 82 ].…”

Section: Introductionmentioning

confidence: 99%

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Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition

Słotwiński¹,

Sarnecka²,

Dąbrowska³

et al. 2015

cejoi

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The aim of this study was an attempt to determine whether the expression of genes involved in innate antibacterial response (TL R2, NOD 1, TRAF6, HMGB 1 and Hsp70) in peripheral blood leukocytes in critically ill patients, may undergo significant changes depending on the severity of the infection and the degree of malnutrition. The study was performed in a group of 128 patients with infections treated in the intensive care and surgical ward. In 103/80.5% of patients, infections had a severe course (sepsis, severe sepsis, septic shock, mechanical ventilation of the lungs). Clinical monitoring included diagnosis of severe infection (according to the criteria of the ACC P/SCC M), assessment of severity of the patient condition and risk of death (APACHE II and SAPS II), nutritional assessment (NRS 2002 and SGA scales) and the observation of the early results of treatment. Gene expression at the mRNA level was analyzed by real-time PCR. The results of the present study indicate that in critically ill patients treated in the IC U there are significant disturbances in the expression of genes associated with innate antimicrobial immunity, which may have a significant impact on the clinical outcome. The expression of these genes varies depending on the severity of the patient condition, severity of infection and nutritional status. Expression disorders of genes belonging to innate antimicrobial immunity should be diagnosed as early as possible, monitored during the treatment and taken into account during early therapeutic treatment (including early nutrition to support the functions of immune cells).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition

Słotwiński¹,

Sarnecka²,

Dąbrowska³

et al. 2015

cejoi

Self Cite

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“…Stimulation of NOD1 and NOD2 was found to be protective in inflammation-induced CRC, [69][70][71]80 whereas there was no straightforward answer as to whether activation of NOD1 in the stomach promotes or prevents the development of GC. [72][73][74] Moreover, NOD1 was found to be upregulated in PC, 79 HNSCC, 77,78 OSCC, 76 and GC, 73,74 as opposed to certain studies that reported NOD1 downregulation in the cases of OSCC 75 and GC. 72 NOD2 was also found to be upregulated in GCs.…”

Section: The Role Of Nod Proteins In Cancer Developmentmentioning

confidence: 99%

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Nabergoj

Mlinarič-Raščan

Jakopin

2018

Medicinal Research Reviews

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In the last decade, cancer immunotherapy has emerged as an effective alternative to traditional therapies such as chemotherapy and radiation. In contrast to the latter, cancer immunotherapy has the potential to distinguish between cancer and healthy cells, and thus to avoid severe and intolerable side‐effects, since the cancer cells are effectively eliminated by stimulated immune cells. The cytosolic nucleotide‐binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are important components of the innate immune system and constitute interesting targets in terms of strengthening the immune response against cancer cells. Many NOD ligands have been synthesized, in particular NOD2 agonists that exhibit favorable immunostimulatory and anticancer activity. Among them, mifamurtide has already been approved in Europe by the European Medicine Agency for treating patients with osteosarcoma in combination with chemotherapy after complete surgical removal of the primary tumor. This review is focused on NOD receptors as promising targets in cancer immunotherapy as well as summarizing current knowledge of the various NOD ligands exhibiting antitumor and even antimetastatic activity in vitro and in vivo.

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“…In an orthotopic xenograft model of SCID mice, a combination of proteasome inhibitor (MG132) and ionizing radiation therapy resulted in a significant increase in the tumor growth delay and a decreased tumor tissue expression of TRAF6 [149]. Additionally, we have recently proposed that overexpression of TLR4, NOD1 and TRAF6 genes and lower MyD88 gene expression in peripheral blood leukocytes of patients with pancreatic cancer, could contribute to chronic inflammation and tumor progression by the up-regulation of the innate antibacterial response (e.g., to LPS) [150]. Although the evidence suggesting carcinogenic and therapeutic effects of stimulation or inhibition of TLRs is increasingly growing, it still remains unclear what kind of changes in gene expression of the TLR signaling pathways in leukocytes are associated with pancreatic cancer.…”

Section: Innate Antibacterial Signalingmentioning

confidence: 99%

Dysregulation of signaling pathways associated with innate antibacterial immunity in patients with pancreatic cancer

Słotwiński

Słotwińska

2016

cejoi

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Disorders of innate antibacterial response are of fundamental importance in the development of gastrointestinal cancers, including pancreatic cancer. Multi-regulatory properties of the Toll-like receptors (TLRs) (e.g., regulation of proliferation, the activity of NF-κB, gene transcription of apoptosis proteins, regulation of angiogenesis, HIF-1α protein expression) are used in experimental studies to better understand the pathogenesis of pancreatic cancer, for early diagnosis, and for more effective therapeutic intervention. There are known numerous examples of TLR agonists (e.g., TLR2/5 ligands, TLR6, TLR9) of antitumor effect. The direction of these studies is promising, but a small number of them does not allow for an accurate assessment of the impact of TLR expression disorders, proteins of these signaling pathways, or attempts to block or stimulate them, on the results of treatment of pancreatic cancer patients. It is known, however, that the expression disorders of proteins of innate antibacterial response signaling pathways occur not only in tumor tissue but also in peripheral blood leukocytes of pancreatic cancer patients (e.g., increased expression of TLR4, NOD1, TRAF6), which is one of the most important factors facilitating further tumor development. This review mainly focuses on the genetic aspects of signaling pathway disorders associated with innate antibacterial response in the pathogenesis and diagnosis of pancreatic cancer.

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Clinical immunology Gene expression disorders of innate antibacterial signaling pathway in pancreatic cancer patients: implications for leukocyte dysfunction and tumor progression

Cited by 7 publications

References 85 publications

Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition

Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Dysregulation of signaling pathways associated with innate antibacterial immunity in patients with pancreatic cancer

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