scholarly journals Bacteria–Cancer Interface: Awaiting the Perfect Storm

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1321
Author(s):  
Jonathan Pommer Hansen ◽  
Waled Mohammed Ali ◽  
Rajeeve Sivadasan ◽  
Karthika Rajeeve

Epidemiological evidence reveal a very close association of malignancies with chronic inflammation as a result of persistent bacterial infection. Recently, more studies have provided experimental evidence for an etiological role of bacterial factors disposing infected tissue towards carcinoma. When healthy cells accumulate genomic insults resulting in DNA damage, they may sustain proliferative signalling, resist apoptotic signals, evade growth suppressors, enable replicative immortality, and induce angiogenesis, thus boosting active invasion and metastasis. Moreover, these cells must be able to deregulate cellular energetics and have the ability to evade immune destruction. How bacterial infection leads to mutations and enriches a tumour-promoting inflammatory response or micro-environment is still not clear. In this review we showcase well-studied bacteria and their virulence factors that are tightly associated with carcinoma and the various mechanisms and pathways that could have carcinogenic properties.

2021 ◽  
Vol 9 (2) ◽  
pp. 01-06
Author(s):  
Kaushalendra Mani Tripathi

The hallmarks of cancer represent principals and mechanisms on which, different types of cancers function and proliferate, These principals which also include the revised edition include sustained proliferative signaling, Evading growth suppressors , avoiding immune destruction, enabling replicative immortality, tumor promoting inflammation, activating invasion and metastasis, Inducing angiogenesis, genome instability and mutation, resisting cell death, deregulating cellular energetics. This article reviews these hallmarks and suggests any additional hallmark that can be further investigated and integrated into the revised edition , Hanahan and Weinberg’s hallmark of cancer are great pillars of understanding for modern cancer study and are open to modification , making it easily approachable ,critiqued and adds the possibility of additions in the near future. The role of exosomes are discussed with the potential to categorize drug resistance as a separate hallmark to assist us in developing therapeutics that can counter or bypass these mechanisms that assist cancer cells to proliferate even further.


Author(s):  
Meng Li ◽  
Xiaoyang Huang ◽  
Qingcui Zhuo ◽  
Jinghui Zhang ◽  
Xiuli Ju

Neonatal sepsis (NS) occurs in neonates within 28 days, especially preterm infants. The dysregulation of miRNAs is widely detected in NS. The study investigated the expression changes and clinical significance of miR-129-5p in NS patients and further explored the regulatory role of miR-129-5p in the LPS-induced inflammatory response in monocytes. A total of 75 neonates with NS and 84 neonates without NS were recruited. qRT-PCR was used for the measurement of miR-129-5p expression. The receiver operating characteristic (ROC) curve was constructed for diagnostic value analysis. ELISA was used to detect the concentration of inflammatory cytokines. Monocytes were isolated from the blood of neonates to investigate the role of miR-129-5p in the LPS-induced inflammatory response in vitro. miR-129-5p was low expressed in the serum of NS cases compared with controls. Serum miR-129-5p had a diagnostic value for NS with a sensitivity of 82.7% and specificity of 79.8%. There was close association for serum miR-129-5p with TNF-α (r = -0.652, p < 0.001) and IL-8 (r = -0.700, p < 0.001) levels in NS patients. Overexpression of miR-129-5p reversed the increasing trend of TNF-α and IL-8 induced by LPS, whereas miR-129-5p downregulation aggravated the increase of TNF-α and IL-8 induced by LPS in monocytes. MiR-129-5p was downregulated in the serum of NS patients, and it might be a promising biomarker for disease diagnosis. Overexpression of miR-129-5p alleviated the inflammatory response of NS.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yi Zhou ◽  
Liang Hu ◽  
Wenqing Tang ◽  
Dongping Li ◽  
Lijie Ma ◽  
...  

Abstract Background Key hepatic molecules linking gut dysbiosis and hepatocarcinogenesis remain largely unknown. Gut-derived gut microbiota contains pathogen-associated molecular patterns (PAMPs) that may circulate into the liver and, consequently, be recognized by hepatic pattern recognition receptors (PRRs). NOD2, a general intracellular PRR, recognizes muramyl dipeptide (MDP), present in both gram (+) and gram (−) bacteria. Here, we investigated the role of NOD2 as a molecular sensor translating gut dysbiosis signaling into hepatocarcinogenesis. Methods NOD2 expression was measured in clinical hepatocellular carcinoma (HCC) samples using qPCR (80 pairs), western blotting (30 pairs) and immunostaining (141 pairs). The role of NOD2 in hepatocarcinogenesis was examined in the hepatocyte-specific Nod2-knockout (Nod2△hep), Rip2-knockout (Rip2△hep), Lamin A/C-knockout (Lamn△hep) and Rip2/Lamin A/C double-knockout (Rip2/Lamn△hep) mice models of diethylnitrosamine (DEN)/CCl4-induced HCC. Results NOD2 was upregulated and activated in HCC samples, and high NOD2 expression correlated with poor prognosis in HCC patients. Hepatic NOD2 deletion in vivo decreased DEN/CCl4-induced HCC by reducing the inflammatory response, DNA damage and genomic instability. NOD2 activation increased liver inflammation via RIP2-dependent activation of the MAPK, NF-κB and STAT3 pathways. Notably, a novel RIP2-independent mechanism was discovered, whereby NOD2 activation induces the nuclear autophagy pathway. We showed that NOD2 undergoes nuclear transport and directly binds to a component of nuclear laminae, lamin A/C, to promote its protein degradation, leading to impaired DNA damage repair and increased genomic instability. Conclusions We reveal a novel bridge, bacterial sensor NOD2, linking gut-derived microbial metabolites to hepatocarcinogenesis via induction of the inflammatory response and nuclear autophagy. Thus, we propose hepatic NOD2 as a promising therapeutic target against HCC.


Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 203
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Rui Medeiros

The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.


Pneumologie ◽  
2013 ◽  
Vol 67 (S 01) ◽  
Author(s):  
X Lai ◽  
C Schulz ◽  
F Seifert ◽  
B Dolniak ◽  
O Wolkenhauer ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document