Disease ⇒ Cancer ⇒ Pancreatic Cancer {40000169}

Shared Reference Notes

• [1.1] 
  -pancreatic ductal adenocarcinoma (PDA) tumours in humans and mouse models of this #Cancer displayed an increase in #Fungi of about 3,000-fold compared to normal pancreatic tissue. - the fungal community that infiltrated PDA tumours was markedly enriched for #Malassezia spp. in both mice and humans. - Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, - repopulation with a #Malassezia species—but not species in the genera Candida, Saccharomyces or Aspergillus—accelerated oncogenesis. - ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, - Deletion of MBL or C3 in the extratumoral compartment—or knockdown of C3aR in tumour cells—were both protective against tumour growth.
• [1.2] [#Lactobacillus] [#Indole, #Tryptophan] [#Probiotic] 
• [1.3] [#kynurenine] 
• [1.4] 
  -Veillonella atypica, Fusobacterium nucleatum/hwasookii and Alloscardovia omnicolens were enriched in faeces of patients with PDAC, whereas Romboutsia timonensis, Faecalibacterium prausnitzii, Bacteroides coprocola and Bifidobacterium bifidum species clusters were depleted. In contrast, we did not detect any species with significantly differential abundance in the salivary microbiome when correcting for multiple tests, including previously reported associations, such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans,22 Neisseria elongata or Streptococcus mitis
• [1.5] 
  - Deletion of Col1 homotrimers increases overall survival of mice with pancreatic ductal adenocarcinoma (PDAC), associated with reprograming of the tumor microbiome with increased microaerophilic #Campylobacterales, which can be reversed with broad-spectrum antibiotics.
• [1.6] 
  - in a mouse model of PDA, #Malassezia from the colon infiltrated and accelerated PDA, a condition that was reversed with antifungal treatment.
• [1.7] [#Tryptophan] 
  - dietary Trp generated by the gut microbiota activate the aryl hydrocarbon receptor in myeloid cells, promoting an immune suppressive tumor microenvironment and facilitating pancreatic ductal adenocarcinoma growth.
• [1.8] [#Breast cancer, #Ovarian cancer] 
  - Fungi were detected in 35 #Cancer types and were often intracellular. - 0%–25% of the tumors per #Cancer type to be positive for either β-glucan or Aspergillus staining. - fungal staining was mainly evident within #Cancer cells in pancreatic, breast, and ovarian #Cancer, it mostly localized to macrophages in #Melanoma and lung cancers
• [1.9] 
  - gut microbe–derived metabolite trimethylamine N-oxide (#TMAO), enhanced antitumor immunity to Pancreatic ductal adenocarcinoma (PDAC) - Delivery of #TMAO intraperitoneally or via a dietary choline supplement to orthotopic PDAC-bearing mice reduced tumor growth, associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype, and activated effector T cell response in the tumor microenvironment. - #TMAO potentiated the type I interferon (IFN) pathway and conferred antitumor effects in a type I IFN–dependent manner. - bacteria producing an enzyme that generates #TMA was associated with positive immunotherapy outcomes in people with pancreatic cancer. - #Bacillus and #Paenibacillus species, were present at higher levels in people who survived for a long period of time after pancreatic cancer.
• [#Bacteroides fragilis toxin] - Enterotoxigenic #Bacteroides fragilis (ETBF) produces #Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and #Colorectal cancer (CRC).
• [1.11] 
  - there are significant blood concentration differences when #Ascorbic acid is given parenterally when compared to oral dosing. This pharmacologic difference appears to be critical for its role in oncology. - use of Intravenous pharmacologic #Ascorbic acid in a patient with poorly differentiated stage IV Pancreatic ductal adenocarcinoma as an exclusive chemotherapeutic regimen. - The patient survived nearly 4 years after diagnosis, with Intravenous pharmacologic #Ascorbic acid as his sole treatment, and he achieved objective regression of his disease.
• [1.12] 
  Pancreatic ductal adenocarcinoma (PDAC) > chemotherapy > microbiota-derived tryptophan metabolite #Indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. - Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. - In humans > a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. - Pancreatic ductal adenocarcinoma (PDAC) > #Bacteroides fragilis and #Bacteroides thetaiotaomicron produced 3-IAA in vitro were increased in Responder patients.
• [1.13] 
  - Stool from patients cured from PCa has more relative abundance of #Faecalibacterium prausnitzii and #Akkermansia muciniphila.
• [1.14] [#Enterobacteriaceae bacterium] 
  - the oral bacterium in the duodenum may be capable of entering the pancreas. For instance, the periodontal microbes (#Porphyromonas gingivalis and #Aggregatibacter actinomycetemcomitans) have been proven positively related to pancreatic cancer risk
• [1.15] [#Colorectal cancer, #Lung cancer] [#Veillonella atypica] 
  - #Veillonella genus is usually more abundant in treatment-naïve patients with lung, pancreatic (#Veillonella atypica) and colorectal #Cancer. - Furthermore, when comparing patients with advanced-stage #Cancer with and without weight loss, #Veillonella is more abundant in those who lost weight.
• [1.16] 
  - pancreatic ductal adenocarcinoma samples have been shown to be enriched for #Proteobacteria, #Bacteroides, and #Firmicutes compared to normal pancreatic tissue
• [1.17] [#Colorectal cancer, #Lung cancer] [#Veillonella atypica] 
  - #Veillonella genus is usually more abundant in treatment-naïve patients with lung, pancreatic (#Veillonella atypica) and colorectal #Cancer.
• [1.18] 
  - #Malassezia > new pathogenic roles in #Seborrheic dermatitis, #Psoriasis, #Crohn’s disease, and pancreatic ductal carcinoma.
• [1.19] 
  - In pancreatic cancers, in addition to #Fusobacterium nucleatum and #Porphyromonas gingivalis, strains of #Aggregatibacter actinomycetemcomitans, #Neisseria elongata, and #Streptococcus mitis have been described.
• [#Breast cancer] - #Fusobacterium nucleatum, previously reported to be enriched in colorectal tumors, was also a hit in our breast and pancreatic tumor cohorts
• - #Proteobacteria dominated the microbiome of pancreatic cancer, similarly to the normal duodenal microbiome makeup. - This may reflect a retrograde bacterial migration from the duodenum.
• [1.21] 
  - pancreatic Cancer > #Irisin effectively inhibited the growth, migration, and invasion of these cell lines by regulating the AMP-activated protein kinase (AMPK)-mTOR pathway and suppressing the epithelial-mesenchymal transition.
• [1.22] 
  - #TMAO is associated with increased risk of several #Cancer types including pancreatic #Cancer.
• - The microbial-related metabolite panel includes indoleacyrlic acid, an #Indole-derivative, and #TMAO. - #TMAO- and indoleacrylic-acid-producing #Bacteria include those in the phyla of #Bacillota, #Bacteroidota, #Actinomycetota, and Pseudomonadota. - #Bacillota species such as Cs and Er and Bacteriodota species including Bt and Pd have been shown to be increased in fecal samples of patients with PDAC compared with control subjects. - Relative abundances of fecal #Collinsella aeofaciens, a species of #Actinomycetota, is associated with poor prognosis in PDAC.
• - levels of #TMAO in cystic fluid were positively correlated with bacterial clusters corresponding to Enterobacteriacea, #Granulicatella, #Klebsiella, #Stenotrophomonas, #Streptococcus, #Haemophilus, and #Fusobacterium > associated with pancreatic cancer.
• - #TMAO is elevated in pancreatic cystic fluid of individuals presenting with high-risk intraductal papillary mucinous neoplasms or pancreatic cancer compared with those harboring non-cancerous cysts
• [1.23] [#Biliary tract cancer, #Colorectal cancer, #Esophageal cancer, #Gallbladder cancer] 
• [1.24] 
  - #Citrobacter freundii and #Shigella sonnei as part of the pancreatic cancer TME, while other studies suggested that these bacteria occur intracellularly
• [#Helicobacter pylori] - H. pylori, which was shown to be capable of invading host cells, enhances the risk of pancreatic cancer
• [1.25] [#Malassezia globosa] 
  - M. globosa can promote the development of pancreatic cancer by activating the MBL-C3 pathway
• [1.26] 
  - Lower levels of #Bifidobacterium will not be sufficient to inhibit tumor growth via the TNF-α-mediated pathway, and therefore, they can participate in pancreatic cancer progression.
• [1.27] [#Oral squamous cell carcinoma] 
  - pancreatic cancer > the #Mannose-binding #Lectin, which binds specifically to the #Glycans on the fungal wall, was activated mainly by the #Malassezia genus, showing potential for tumor formation. - the presence of #Malassezia sp. in OSCC is associated with a favorable prognosis
• [1.28] [#Porphyromonas gingivalis] 
  - P. gingivalis migrated from the oral cavity to the pancreas in mice and can be detected in human PanIN lesions. - Repetitive P. gingivalis administration to wild-type mice induced pancreatic acinar-to-ductal metaplasia (ADM), and altered the composition of the intrapancreatic microbiome. - In iKC mice, P. gingivalis accelerated PanIN to PDAC progression. In vitro, P. gingivalis infection induced acinar cell ADM markers SOX9 and CK19, and intracellular bacteria protected PDAC cells from #Reactive Oxygen Species-mediated cell death resulting from nutrient stress.
• [1.29] 
  -The long-term survivors showed a relative abundance of Pseudoxanthomonas, Saccharropolyspora and Streptomyces. The presence of all three taxa, as well as the species Bacillus Clausii, predicted better outcomes for patients.

References Notes