Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Lang, Michaela; Baumgartner, Maximilian; Rożalska, Aleksandra; Frick, Adrian; Riva, Alessandra; Jarek, Michael; Berry, David; Gasché, Christoph

doi:10.1002/ijc.33028

Cited by 21 publications

(18 citation statements)

References 43 publications

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“…In humans, fecal samples from patients with a carcinoma are enriched in species belonging to the genus Bacteroides, Parabacteroides and Escherichia, besides others, compared to patients with adenomas and healthy controls. These bacterial taxa are also associated with inflammation and carcinogenesis in mouse model [34].…”

Section: Resultsmentioning

confidence: 99%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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Relevance. Treatment of solid tumors and biofilm-derived infections face a common problem: drugs often fail to reach and kill cancer cells and microbial pathogens because of local microenvironment heterogeneities. There are remarkable challenges for current and prospective anticancer and antibiofilm agents to target and maintain activity in the microenvironments where cancer cells and microbial pathogens survive and cause the onset of disease. Bacterial infections in cancer formation will increase in the coming years. Collection of approaches such as ROS modulation in cells, the tumor is promoted by microbe’s inflammation can be a strategy to target cancer and bacteria. Besides that, bacteria may take the advantage of oxygen tension and permissive carbon sources, therefore the tumor microenvironment (TM) becomes a potential refuge for bacteria. It is noteworthy that the relationship between cancer and bacteria is intertwined. Objective: To analyze similarities between biofilm and tumor milieu that is produced against stress conditions and heterogeneous microenvironment for a combination of approaches the bacteriotherapy with chemotherapy which can help in defeating the tumor heterogeneity accompanied with malignancy, drug-resistance, and metastasis. Method: An analytical review of the literature on keywords from the scientometric databases PubMed, Wiley. Results: Bacteria evade antimicrobial treatment is mainly due to persistence that has become dormant during the stationary phase and tolerance. Drug-tolerant persisters and cellular dormancy are crucial in the development of cancer, especially in understanding the development of metastases as a late relapse. Bioﬁlms are formed by groups of cells in diﬀerent states, growing or non-growing and metabolically active or inactive in variable fractions, depending on maturity and on chemical gradients (O2 and nutrients) of the bioﬁlms producing physiological heterogeneity. Heterogeneity in the microenvironment of cancer can be described as a non-cell autonomous driver of cancer cell diversity; in a highly diverse microenvironment, different cellular phenotypes may be selected for or against in different regions of the tumor. Hypoxia, oxidative stress, and inflammation have been identified as positive regulators of metastatic potential, drug resistance, and tumorigenic properties in cancer. It is proven that, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are noticeably sensitive to alterations in the intracellular oxidative environment. An alternative emerging paradigm is that many cancers may be promoted by commensal microbiota, either by translocation and adherence of microbes to cancer cells or by the distant release of inflammation-activating microbial metabolites. Microbial factors such as F. nucleatum, B. fragilis, and Enterobacteriaceae members may contribute to disease onset in patients with a hereditary form of colorectal cancer (CRC); familial adenomatous polyposis (FAP). These findings are linked with the creation of new biomarkers and therapy for identifying and treating biofilm-associated cancers. Currently, about 20% of neoplasms globally can be caused by infections, with approximately 1.2 million cases annually. Several antineoplastic drugs that exhibited activity against S. mutans, including tamoxifen, doxorubicin, and ponatinib, also possessed activity against other Gram-positive bacteria. Drug repurposing, also known as repositioning, has gained momentum, mostly due to its advantages over de novo drug discovery, including reduced risk to patients due to previously documented clinical trials, lower drug development costs, and faster benchtop-to-clinic transition. Although many bacteria are carcinogens and tumor promoters, some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive power to penetrate and colonize solid tumors, which has mainly led to neoplasm slower growth and tumor clearance. Different strains of Clostridia, Lactococcus, Bifidobacteria, Shigella, Vibrio, Listeria, Escherichia, and Salmonella have been evaluated against cancer in animal models. Conclusion. Cancer is a multifactorial disease and the use of bacteria for cancer therapy as an immunostimulatory agent or as a vector for carrying the therapeutic cargo is a promising treatment method. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer.

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Section: Resultsmentioning

confidence: 99%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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“…TMB refers to the total number of substitution, insertion, and deletion mutations per megabase in the exon coding region of the evaluated gene in the tumor cell genome [ 13 ]. Previous studies have shown that changes in the pathogenicity of cell functions due to changes in the genome are clinically called “driver mutations,” which can lead to tumors [ 14 ]. In this study, the level of TMB in advanced gastric cancer was 5–14, with an average of 8.58 ± 0.61.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

Zhang

et al. 2021

Journal of Oncology

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Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

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“…They registered an accumulation of follicular T-helper (TFH) cells in CRC patients and mice and the suppression of IEC apoptosis. This effect could be linked to the impairment of the immunosurveillance mechanisms by chemotherapy directed against CRC in mice [ 100 ]. Protective immune responses in the ileum were associated with the colonization of specific bacteria such as Bacteroides fragilis and Erysipelotrichaceae that stimulate the production of programmed cell death (PD-1) molecules +TFH by secretion of interleukin 1R1 and interleukin 12.…”

Section: Microbiotamentioning

confidence: 99%

“…Protective immune responses in the ileum were associated with the colonization of specific bacteria such as Bacteroides fragilis and Erysipelotrichaceae that stimulate the production of programmed cell death (PD-1) molecules +TFH by secretion of interleukin 1R1 and interleukin 12. Moreover, the demonstration of apoptosis in the ileum can be considered a prognostic factor for CRC patients [ 100 ].…”

Section: Microbiotamentioning

confidence: 99%

“…In particular, more relevant changes seem to occur at the stage of precancerous lesions of gastric carcinoma (PLGC), suggesting that it is a turning point during GC progression. Moreover, the depletion of some bacteria such as Akkermansia and an enrichment of pathogenic bacteria such as Escherichia Shigella can overlap with the tumor progression stage [ 100 ].…”

Section: Microbiotamentioning

confidence: 99%

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What Is Known about Theragnostic Strategies in Colorectal Cancer

et al. 2021

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Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.

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Crypt residing bacteria and proximal colonic carcinogenesis in a mouse model of Lynch syndrome

Cited by 21 publications

References 43 publications

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

What Is Known about Theragnostic Strategies in Colorectal Cancer

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