MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine

Cancer {40000133}

Record Keys


Definition:
Cancer
Class:[  ]

Details


Other Terms:[  ]
Initialisation date:
2020-09-06

Links


Meta Information


ICD:[  ]
Category:
Oncology
MedDra ID:[  ]
MedDra Level:[  ]

Notes


[  ]

Shared Notes


  • [1.1
    - Smectite clay promotes lactic acid bacteria (LABs) to form biofilms on its surface
    - Smectite with LABs inhibits tumor growth in mice
    - Smectite with LABs enhances anti-cancer chemo/immunotherapy in mice
    - Smectite with LABs activates dendritic cells via TLR2 signaling
  • [1.2
    - The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain.
    - Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells.
  • - Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T cell proliferation in a manner that can be rescued by BH4.
  • [1.3
    - Bifidobacterium is associated with antitumor effects, and oral administration of Bifidobacterium alone improved tumor control to the same degree as PD-L1 antibody therapy while combination treatment nearly abolished tumor growth in mice.
  • - Disruption of the microbiome leads to changes in intestinal barrier function, which could lead to bacterial translocation and result in chronic inflammation.
    - Chronic inflammation over the years results in altered immune responses and increases risk of tumor formation and progression.
  • [1.4
    - IL-15 signaling is required for NK cell proliferation, survival, and anti-tumor function in the tumor microenvironment .
  • [1.5
    - S. typhimurium, an intracellular pathogen, is chemoattracted to, and retained in, tumors due to the presence of metabolites produced by quiescent cancer cells within the TME (Tumor Micro envirounment).
    - Once in the tumor, S. typhimurium continues to proliferate and directly kills cancer cells by triggering of apoptosis, necrosis, and cell rupture.
    - S. typhimurium flagellin has been found to mount the antitumor response of CD8+ T and Natural Killer (NK) cells and to reduce the frequency of regulatory T cells (Tregs)
  • - Salmonella spp. also induce cancer cells to produce the gap junction protein, connexin 43, which enhances the transfer and cross-presentation of processed tumor antigenic peptides between cancer cells and dendritic cells (DCs), and reduce the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO)
  • - Listeria spp. target tumors through the intracellular infection of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which migrate to the immunosuppressive TME.
    - The transported Listeria is then transmitted from MDSCs to cancer cells via a unique cell–cell spread mechanism.
    - The shrinkage of tumors by Listeria spp. involves the combination of the direct killing of cancer cells by Listeria infection and cytotoxic T cell response toward Listeria antigens.
    - Listeria spp. convert a subpopulation of Listeria-infected MDSCs into an immune-stimulating phenotype that produces interleukin-12 (IL-12), a cytokine linked with heightened T cell and NK cell responses.
    - Listeria spp. directly kill cancer cells by activating NADP (+) oxidase and increasing intracellular calcium levels, which trigger the production of reactive oxygen species (ROS)
  • - Clostridium spp. destroy tumors by secreting exotoxins that damage the membrane structures of cancer cells and enter cells to disrupt essential cellular functions.
    - The introduction of Clostridium spp. recruits CD8+ T cells, granulocytes, and macrophages to the infection area and induces the release of TNF-related apoptosis-inducing ligand (TRAIL) from neutrophils.
  • - Certain probiotic bacteria reportedly demonstrated effects in suppressing and regressing cancer.
    - Their mechanisms include maintaining physicochemical conditions in the colon (e.g., pH and bile acid profile), balancing the quantity of beneficial gut microbiota members through the production of short-chain fatty acids, reducing the abundance of putrefactive bacteria producing enzymes such as azoreductase, β-glucosidase, β-glucuronidase, and nitroreductase, binding and degrading mutagenic compounds, as well as performing immunomodulatory activities.
    - Experimentations with wild-type probiotics have been performed against not only colorectal cancer, but also other cancers such as bladder, breast, cervical, and liver cancers.
    - Instead of oral administration, probiotics can also be delivered locally at tumor sites, which can reduce non-specific pharmacological effects on non-tumor tissues.
  • [1.6
    - High levels of plant dietary fibers in the gut resulted in proliferation of Faecalibacterium prausnitzii with anti-inflammatory and anti-tumor effects.
  • [1.7
    - Bacteria present in probiotics, particularly the common Lactobacillus and Bifidobacterium microbes, have been found to induce anti-cancer action by enhancing cancer cell apoptosis and protecting against oxidative stress.
    - Probiotics supplements also decrease the cancer-producing microorganism Fusobacterium.
  • - Bifidobacterium species decrease cancer cell proliferation via the inhibition of growth factor signaling as well as inducing mitochondrial-mediated apoptosis.
    - Bifidobacterium species reduce the adverse effects of chemo/immuno/radiation therapy by inhibiting proinflammatory cytokines.
  • [1.8
    - A recent analysis surveyed bacteria in primary tumors and adjacent normal tissue across seven cancer types from body sites both exposed to and protected from microbes [16].
    - Each tumor type displayed a unique microbial profile, with breast tumors harboring the richest and most diverse microbiome.
  • [1.9
    - Intratumoral bacteria can directly modulate antitumor immune responses.
  • - F. nucleatum and certain co-occurring bacteria were present not only in primary tumors but also in distant metastases. Preliminary evidence suggests that the bacterium is localized primarily within the metastatic cancer cells rather than in the stroma.
    - Antibiotic treatment of mice carrying xenografts of F. nucleatum–positive human colorectal cancer slowed tumor growth, consistent with a causal role for the bacterium in tumorigenesis.
  • [1.11
    - Bacteroides fragilis, Bifidobacterium longum, Barnesiella intestinihomins or Alistipes shahii to support anticancer immunity by activating dendritic cells (DCs), by stimulating the production of interleukin-12 (IL-12) by DCs, by enhancing recruitment of tumor-specific cytotoxic T lymphocytes (CTLs), by triggering the production of interferon-γ (IFNγ) by tumor-infiltrating γδ T cells or by elevating the production of TNFα by intratumoural myeloid cells.
  • [1.12
    - There is a growing body of epidemiological evidence that folate modulates anticarcinogenic properties through epigenetic changes, as folate deficiency reduces the potential for DNA methylation, and abnormal DNA methylation is associated with many types of cancer.
  • - Green tea contains polyphenols, which are natural compounds widely distributed in plant foods and with many biological activities including inhibition of DNA methylation.
  • [1.13
    - Calorie restriction (CR) without malnutrition remains the most robust intervention to date for cancer prevention in rodents and monkeys, and, in humans, it promotes anticarcinogenic adaptations such as decreased production of growth factors, inflammatory cytokines, and anabolic hormones as well as decreased oxidative stress and free-radical–induced DNA damage.
  • [1.14
    - In multiple murine tumour models, inulin—a widely consumed dietary fibre—formulated as a ‘colon-retentive’ orally administered gel can effectively modulate the gut microbiome in situ, induce systemic memory-T-cell responses and amplify the antitumour activity of the checkpoint inhibitor anti-programmed cell death protein-1 (α-PD-1).
    - Orally delivered inulin-gel treatments increased the relative abundances of key commensal microorganisms and their short-chain-fatty-acid metabolites, and led to enhanced recall responses for interferon-γ+CD8+ T cells as well as to the establishment of stem-like T-cell factor-1+PD-1+CD8+ T cells within the tumour microenvironment.
  • [1.15
    - High-salt diet (HSD) modulates effector and regulatory T cell functions and promotes tissue inflammation in autoimmune diseases.
    - HSD induces natural killer (NK) cell–mediated tumor immunity by inhibiting PD-1 expression while enhancing IFNγ and serum hippurate.
    - Salt enhanced tumor immunity when combined with a suboptimal dose of anti-PD1 antibody.
  • - HSD increased the abundance of Bifidobacterium and caused increased gut permeability leading to intratumor localization of Bifidobacterium, which enhanced NK cell functions and tumor regression.
    - Intratumoral injections of Bifidobacterium activated NK cells, which inhibited tumor growth.
  • [1.16
    - Bacteroides fragilis toxin (Bft), can indirectly damage the host DNA by eliciting high levels of reactive oxygen species (ROS)
  • - Cytolethal Distending Toxin (CDT) by Campylobacter jejuni and Colibactin by Escherichia Coli can directly damage DNA
  • - Antibiotic treatments have been shown to decrease the effectiveness of anti-PD-L1 antibody therapy

Common References