scholarly journals Fungal Gut Microbiota Dysbiosis and Its Role in Colorectal, Oral, and Pancreatic Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1326 ◽  
Author(s):  
Karolina Kaźmierczak-Siedlecka ◽  
Aleš Dvořák ◽  
Marcin Folwarski ◽  
Agnieszka Daca ◽  
Katarzyna Przewłócka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Gut Microbiota ◽  
Early Stage ◽  
Saccharomyces Boulardii ◽  
Cancer Development ◽  
Disease Stage ◽  
Fungal Microbiota ◽  
Colorectal Cancer Patients

The association between bacterial as well as viral gut microbiota imbalance and carcinogenesis has been intensively analysed in many studies; nevertheless, the role of fungal gut microbiota (mycobiota) in colorectal, oral, and pancreatic cancer development is relatively new and undiscovered field due to low abundance of intestinal fungi as well as lack of well-characterized reference genomes. Several specific fungi amounts are increased in colorectal cancer patients; moreover, it was observed that the disease stage is strongly related to the fungal microbiota profile; thus, it may be used as a potential diagnostic biomarker for adenomas. Candida albicans, which is the major microbe contributing to oral cancer development, may promote carcinogenesis via several mechanisms, mainly triggering inflammation. Early detection of pancreatic cancer provides the opportunity to improve survival rate, therefore, there is a need to conduct further studies regarding the role of fungal microbiota as a potential prognostic tool to diagnose this cancer at early stage. Additionally, growing attention towards the characterization of mycobiota may contribute to improve the efficiency of therapeutic methods used to alter the composition and activity of gut microbiota. The administration of Saccharomyces boulardii in oncology, mainly in immunocompromised and/or critically ill patients, is still controversial.

scholarly journals Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients

2021 ◽  
Author(s):  
Piero Sciavilla ◽  
Francesco Strati ◽  
Monica Di Paola ◽  
Monica Modesto ◽  
Francesco Vitali ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Gut Microbiota ◽  
Healthy Subjects ◽  
Fungal Isolates ◽  
Key Points ◽  
Health Promoting ◽  
Irritable Bowel

Abstract Studies so far conducted on irritable bowel syndrome (IBS) have been focused mainly on the role of gut bacterial dysbiosis in modulating the intestinal permeability, inflammation, and motility, with consequences on the quality of life. Limited evidences showed a potential involvement of gut fungal communities. Here, the gut bacterial and fungal microbiota of a cohort of IBS patients have been characterized and compared with that of healthy subjects (HS). The IBS microbial community structure differed significantly compared to HS. In particular, we observed an enrichment of bacterial taxa involved in gut inflammation, such as Enterobacteriaceae, Streptococcus, Fusobacteria, Gemella, and Rothia, as well as depletion of health-promoting bacterial genera, such as Roseburia and Faecalibacterium. Gut microbial profiles in IBS patients differed also in accordance with constipation. Sequence analysis of the gut mycobiota showed enrichment of Saccharomycetes in IBS. Culturomics analysis of fungal isolates from feces showed enrichment of Candida spp. displaying from IBS a clonal expansion and a distinct genotypic profiles and different phenotypical features when compared to HS of Candida albicans isolates. Alongside the well-characterized gut bacterial dysbiosis in IBS, this study shed light on a yet poorly explored fungal component of the intestinal ecosystem, the gut mycobiota. Our results showed a differential fungal community in IBS compared to HS, suggesting potential for new insights on the involvement of the gut mycobiota in IBS. Key points • Comparison of gut microbiota and mycobiota between IBS and healthy subjects • Investigation of cultivable fungi in IBS and healthy subjects • Candida albicans isolates result more virulent in IBS subjects compared to healthy subjects

scholarly journals Nanopore-Sequencing Characterization of the Gut Microbiota of Melolontha melolontha Larvae: Contribution to Protection against Entomopathogenic Nematodes?

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 396
Author(s):  
Ewa Sajnaga ◽  
Marcin Skowronek ◽  
Agnieszka Kalwasińska ◽  
Waldemar Kazimierczak ◽  
Karolina Ferenc ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Entomopathogenic Nematodes ◽  
Bacterial Species ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Nanopore Sequencing ◽  
Bacterial Phyla ◽  
Melolontha Melolontha

This study focused on the potential relationships between midgut microbiota of the common cockchafer Melolontha melolontha larvae and their resistance to entomopathogenic nematodes (EPN) infection. We investigated the bacterial community associated with control and unsusceptible EPN-exposed insects through nanopore sequencing of the 16S rRNA gene. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the most abundant bacterial phyla within the complex and variable midgut microbiota of the wild M. melolontha larvae. The core microbiota was found to include 82 genera, which accounted for 3.4% of the total number of identified genera. The EPN-resistant larvae differed significantly from the control ones in the abundance of many genera belonging to the Actinomycetales, Rhizobiales, and Clostridiales orders. Additionally, the analysis of the microbiome networks revealed different sets of keystone midgut bacterial genera between these two groups of insects, indicating differences in the mutual interactions between bacteria. Finally, we detected Xenorhabdus and Photorhabdus as gut residents and various bacterial species exhibiting antagonistic activity against these entomopathogens. This study paves the way to further research aimed at unravelling the role of the host gut microbiota on the output of EPN infection, which may contribute to enhancement of the efficiency of nematodes used in eco-friendly pest management.

scholarly journals Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiang Chen ◽  
Hongyu Li ◽  
Wenda Xu ◽  
Xiaozhong Guo
Keyword(s):  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Potential Role ◽  
Early Stage ◽  
Serum Levels ◽  
Diagnostic Efficacy ◽  
Diagnostic Biomarkers ◽  
The Poor

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.

scholarly journals The Role of Radiotherapy for Pancreatic Malignancies- A Population-based Analysis of the SEER-Medicare Database.

2020 ◽  
Author(s):  
yunxiu luo ◽  
Shengjun Xiao
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Adjuvant Radiotherapy ◽  
Adenosquamous Carcinoma ◽  
Early Stage ◽  
Pancreatic Head ◽  
Population Based ◽  
Anatomical Location ◽  
Duct Carcinoma

Abstract Background and objective. To investigate the role of adjuvant radiotherapy in patients after surgical resection for pancreatic cancer. Methods and patients. The patients with pancreatic cancer from 18 registered institutions in the Surveillance Epidemiology and End Results (SEER) database were retrospectively analyzed. The characteristics of patients who would benefit from adjuvant radiotherapy were screened, as well as whether neoadjuvant or adjuvant radiotherapy conferred to a better clinical outcome. Results. 30249 patients included in this study (21295 vs 8954 in surgery and adjuvant radiotherapy group) .The median survivals in the surgery (S) group and adjuvant radiotherapy (S+R) group were 24 and 21 months respectively, The 1, 3, and 5-year overall survival (OS) rates in the S group and S+R group were 68%, 40%, 31% ,and 75%, 30%, 20%, respectively (p<0.001).Stratified analysis showed patients with histological classified as adenocarcinoma(15 VS 21, P<0.0001), infiltrating duct carcinoma (17 VS 21,P<0.0001), adenosquamous carcinoma(10 VS 18,P<0.0001) could be benefit from adjuvant radiotherapy. Adjuvant radiotherapy was helpful to improve the OS for patients with pancreatic head (19 VS 21, P=0.0003) and duct carcinoma (18VS 28, P=0.0121). Subgroup stratified assay indicated specific patients with early stage (AJCC 7th I, II, T2, N0) pancreatic carcinoma had better OS after additional radiotherapy than surgery alone. Conclusion. Additional radiotherapy may contribute to improved prognosis for patients with pancreatic carcinoma of specific histological types (adenocarcinoma/carcinoma, infiltrating duct carcinoma, adenosquamous carcinoma, and squamous), anatomical location, and advanced stage. A specific subgroup of patients with an early stage (I/II, T2) pancreatic cancer should be considered for additional radiotherapy.

scholarly journals Roles of NOTCH1 as a Therapeutic Target and a Biomarker for Lung Cancer: Controversies and Perspectives

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lixia Guo ◽  
Ting Zhang ◽  
Ying Xiong ◽  
Yanan Yang
Keyword(s):  
Lung Cancer ◽  
Therapeutic Target ◽  
Early Stage ◽  
Small Population ◽  
Cancer Development ◽  
Potential Usefulness ◽  
Early Stage Lung Cancer ◽  
Human Carcinogenesis ◽  
Stage Lung Cancer

Lung cancer is one of the most common types of human malignancies and the leading cause of cancer-related death. Patients with surgically resectable early stage lung cancer are more likely curable, but currently only a small population of patients can be diagnosed at such a stage, partly due to our incomplete understanding of the biology of lung cancer and the lack of diagnostic and prognostic biomarkers. Recent studies have shown that NOTCH1 is a critical regulator of human carcinogenesis and has been implicated in multiple steps of cancer development and progression. Herein, we review recent findings about the role of NOTCH1 in lung cancer and discuss its potential usefulness as both a therapeutic target and a biomarker for lung cancer.

Hypoxia induced HIF1a-mediated O-GalNAc glycosylation of cytosolic O-GlcNAcylated proteins to regulate signaling pathways in pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15739-e15739
Author(s):  
Gerrit Wolters-Eisfeld ◽  
Baris Mercanoglu ◽  
Alina Strohmaier ◽  
Cenap Guengoer ◽  
Jakob R. Izbicki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Tumor Development ◽  
Hek293 Cells ◽  
Treatment Resistant ◽  
Tn Antigen ◽  
Cell Energy ◽  
Hif Pathway ◽  
The Impact

e15739 Background: Hypoxia induced reprogramming of cell energy metabolism and changes in glycosylation are hallmarks of cancer promoting the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development. We examined the impact of hypoxia on O-GalNAc glycosylation in human HEK293, PDAC cell lines and clinical specimens. Methods: We profiled the expression of 88 glycosylation related genes by qPCR in HEK293 cells subjected to hypoxia either induced by 1% O2 or 200 mm CoCl2 identifying key O-GalNAc glycosyltransferases downregulated. Functional assays and glycoprotein analysis displayed a pronounced rate of O-GalNAc modified cytosolic proteins derived from hypoxia treated cells and PDAC specimens. Glycosidase assays could validate specificity of detection method used. Aberrant glycotype could be induced by HIF pathway activator ML 228 and inhibited using Echinomycin. PTK and STK analysis of cell lysates displayed correlation between phosphorylation and O-glycosylation in hypoxic samples. Results: Mechanistically we could show, that hypoxia induced decreased levels of C1GALT1C1 results in reduced T-Synthase activity with subsequent expression of truncated O-glycans (Tn antigen). Differential O-GalNAc glycosylation is inducible using HIF pathway activator ML228 under normoxia and the effect is reversed using 5 µM Echinomycin under hypoxia underscoring the role of HIF1a regulated transcription. Interestingly, the pattern of Tn antigen modified proteins derived from hypoxic samples differs significantly from engineered COSMC deficient cells, displaying O-GalNAc moieties in addition to O-GlcNAc in cytosolic protein fractions. Conclusions: Our findings point to a novel crosstalk of O-GalNAc and O-GlcNAcylation under hypoxia extending the knowledge base of differential O-GalNAc glycosylation in pancreatic cancer.

Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery

2012 ◽  
Vol 21 (2) ◽  
pp. e49-e58 ◽  
Author(s):  
George H. Sakorafas ◽  
Gregory G. Tsiotos ◽  
Dimitrios Korkolis ◽  
Vasileios Smyrniotis
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Cancer Development ◽  
Management Options ◽  
Development Management

scholarly journals Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1946
Author(s):  
Yaroslav Teper ◽  
Guido Eibl
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cells ◽  
Current Knowledge ◽  
Review Article ◽  
Cancer Development ◽  
Detailed Knowledge ◽  
Inflammatory Macrophages ◽  
Pancreatic Neoplasia ◽  
The Impact

Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

Stage and histology influence the relationship between MDM2 promoter polymorphism and esophageal cancer and overall survival (OS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21047-21047
Author(s):  
H. J. Mackay ◽  
P. Bradbury ◽  
K. Asomaning ◽  
W. Zhou ◽  
M. Kulke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Early Stage ◽  
Disease Stage ◽  
Advanced Stage ◽  
Mdm2 Snp309 ◽  
Prognostic Role ◽  
Histologic Subtype ◽  
The Relationship

21047 Background: A single nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to affect OS of advanced stage gastric adenocarcinoma (AD) and early stage squamous (SQ) cell carcinoma of the lung. The aim of this study was to evaluate the role of this polymorphism in the prognosis of esophageal cancer, another aerodigestive cancer. Methods: 150 early stage (E) and 118 locally advanced stage (LA) esophageal cancers were genotyped for MDM2 SNP309 using Taqman. The primary endpoint was overall survival (OS). Results: E disease: n=23 stage I; n=127 stage II. LA disease: n=93, Stage III; n=25, Stage IVA. AD comprised 215 (81%), while SQ comprised 45 (17%) of cases; 8 (3%) had poorly differentiated tumors. Median follow-up = 32 months. Median OS were 36 and 21 months for E and LA disease, respectively. Both histology and disease stage affected the relationship between SNP309 and esophageal cancer OS (see Table ). The wildtype T/T genotype conferred a worse OS in E patients (log-rank, p=0.03), especially those with AD (log-rank, p=0.003). In Cox proportional hazards interaction analyses, after adjusting for age, gender, stage and PS, there were statistically significant interactions between MDM2 SNP309 and disease stage (interaction p=0.004) and between MDM2 SNP309 and histologic subtype (AD vs. SQ)(interaction p=0.02). Thus, the direction of SNP309 association from our AD and E esophageal cancer patients are opposite to those of our SQ and LA esophageal cancer patients. However, our SQ and LA results are similar to the SQ lung cancer and advanced stage gastric cancers previously reported. This suggests that biologic mechanisms underpinning the prognostic role of SNP309 are dependent on extent of disease and histologic subtype. Conclusion: Histology and disease stage interact with the prognostic role of MDM2 SNP309 polymorphism in esophageal cancer OS. [Table: see text] No significant financial relationships to disclose.

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