The role of bile acids in carcinogenesis

Cellular and Molecular Life Sciences, Год журнала: 2022, Номер 79(5)

Опубликована: Апрель 16, 2022

Abstract Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array metabolites. The bulk bile acid synthesis takes place primary acids; however, other tissues have also capacity to generate (e.g. ovaries). Hepatic then transported and released into intestines. In large intestine, fraction is converted secondary by gut bacteria. majority intestinal reuptake return liver. A small remains circulation exert receptor-mediated pure chemical effects acidic oesophageal cancer) on cancer cells. this review, we assess how changes biosynthesis, flux local concentration modulate behavior different cancers. Here, present in-depth involvement oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used supraphysiological concentration, sometimes concentrations 1000 times higher than highest reported tissue or serum likely eliciting unspecific effects, practice advocate against review. Furthermore, show that, although were classically considered as pro-carcinogenic agents cancer), dogma switch, lower correspond their reference possess anticancer activity subset Differences response cancers lie differential expression receptors between FXR vs. TGR5). UDCA, sold generic medication cholestasis biliary surge, its conjugates identified with almost purely features suggesting possibility for drug repurposing. Taken together, tumor inducers promoter molecules; nevertheless, certain cancers, like breast cancer, may act suppressors Janus-faced nature carcinogenesis.

Язык: Английский

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Inflammation and Immune Escape in Ovarian Cancer: Pathways and Therapeutic Opportunities

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 895 - 909

Опубликована: Янв. 1, 2025

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver OC progression, contributing immune evasion, tumor growth, metastasis. Inflammatory cytokines, including IL-6, TNF-α, IL-8, as well key signaling pathways such nuclear factor kappa B (NF-kB) signal transducer activator transcription 3 (STAT3), are upregulated in OC, promoting tumor-promoting environment. The microenvironment (TME) characterized by cells like tumor-associated macrophages (TAMs) regulatory T (Tregs), which suppress anti-tumor responses, facilitating evasion. Furthermore, utilize checkpoint pathways, PD-1/PD-L1, inhibit cytotoxic cell activity. Targeting these inflammatory evasion mechanisms offers promising therapeutic strategies. COX-2 inhibitors, Janus kinase/signal (JAK/STAT) pathway blockers, NF-kB inhibitors have shown potential preclinical studies, while targeting PD-1/PD-L1 CTLA-4 been explored with mixed results OC. Additionally, emerging research on microbiome inflammation-related biomarkers, microRNAs (miRNAs) exosomes, points new opportunities for early detection precision medicine. Future approaches treatment must focus personalized strategies that target TME, integrating anti-inflammatory therapies immunotherapy enhance patient outcomes. Continued into interplay between essential developing effective, long-lasting treatments.

Язык: Английский

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Current and Emerging Methods for Ovarian Cancer Screening and Diagnostics: A Comprehensive Review

Cancers, Год журнала: 2022, Номер 14(12), С. 2885 - 2885

Опубликована: Июнь 11, 2022

With a 5-year survival rate of less than 50%, ovarian high-grade serous carcinoma (HGSC) is one the most highly aggressive gynecological malignancies affecting women today. The high mortality HGSC largely attributable to delays in diagnosis, as patients remain undiagnosed until late stages -disease. There are currently no recommended screening tests for cancer and there thus remains an urgent need new diagnostic methods, particularly those that can detect disease at early when clinical intervention effective. While diagnostics share many same technical hurdles other types, low prevalence general population, coupled with notable lack sensitive specific biomarkers, have made development clinically useful strategy challenging. Here, we present detailed review overall landscape diagnostics, emphasis on emerging methods employ novel protein, genetic, epigenetic imaging-based biomarkers and/or advanced technologies noninvasive detection HGSC, risk due germline mutations such BRCA1/2. Lastly, discuss translational potential these approaches achieving implementable solution early-stage means ultimately improving patient outcomes both high-risk populations.

Язык: Английский

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The female reproductive tract microbiotas, inflammation, and gynecological conditions

Frontiers in Reproductive Health, Год журнала: 2022, Номер 4

Опубликована: Авг. 9, 2022

The intricate interactions between the host cells, bacteria, and immune components that reside in female reproductive tract (FRT) are essential maintaining homeostasis. Much of our current knowledge surrounding FRT microbiota relates to vaginal microbiota, where ‘health’ has long been associated with low bacterial diversity Lactobacillus dominance. This concept recently challenged as women can have a diverse microbial composition absence symptomatic disease. structures upper (the endocervix, uterus, Fallopian tubes, ovaries) distinct, lower biomass microbiotas than vagina; however, existence permanent at these sites is disputed. During homeostasis, balance exists bacteria system maintains quiescence. Alterations system, or local environment may result perturbances defined dysbiosis. inflammatory signature perturbed “dysbiotic” characterized by elevated concentrations pro-inflammatory cytokines cervical fluid. It appears homeostasis be disrupted two different mechanisms: first, shift toward increased trigger inflammation, second, immunity altered some manner, which disrupts response an environmental change. dysbiosis negative effects on health. review will examine increasing evidence for involvement inflammation gynecologic conditions such endometriosis, infertility, endometrial ovarian cancer; precise mechanisms involved remains speculative present. While only their infancy, use antibiotics probiotics therapeutically alter being studied discussed herein. Our understanding intimate relationship its early days, more research needed deepen mechanistic this assess how present harnessed assist diagnosis treatment conditions.

Язык: Английский

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The Role of The Tumor Microbiome in Tumor Development and Its Treatment

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 15, 2022

Commensal bacteria and other microorganisms that reside in the human body are closely associated with development treatment of cancers. Recently, tumor microbiome (TM) has been identified a variety cancers such as pancreatic, lung, breast TM different compositions tumors effects on tumors. plays an important role formation microenvironment, regulation local immunity, modification cell biology, directly affects efficacy drug for is expected to be biomarker tumors, engineered tumor-targeting anti-cancer microbial agents (GEN-001) have This paper reviews relevant studies recent years describes its distribution correlation clinical features, effect research directions treatment.

Язык: Английский

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Understanding the Complexities and Changes of the Astronaut Microbiome for Successful Long-Duration Space Missions

Life, Год журнала: 2022, Номер 12(4), С. 495 - 495

Опубликована: Март 28, 2022

During space missions, astronauts are faced with a variety of challenges that unique to spaceflight and have been known cause physiological changes in humans over period time. Several these occur at the microbiome level, complex ensemble microbial communities residing various anatomic sites human body, pivotal role regulating health behavior host. The is essential for day-to-day activities, alterations composition function linked diseases. For reasons, understanding impact conditions on important assess significant risks can emerge during long-term missions develop countermeasures. Here, we review caused by exploration discuss promoting or ameliorating conditions, as well space-related factors composition. topics explored pertain microgravity, radiation, immunity, bone health, cognitive function, gender differences pharmacomicrobiomics. Connections made between trifecta spaceflight, host microbiome, significance interactions successful missions.

Язык: Английский

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Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Янв. 13, 2023

Abstract Ovarian cancer (OC) is the second most common gynecological malignancy and fifth leading cause of death due to in women United States mainly late-stage diagnosis this cancer. It is, therefore, critical identify potential indicators aid early detection disease. We investigated microbiome associated with OC its role detection, progression as well prognosis identified a distinct general enrichment several microbial taxa, including Dialister , Corynebacterium Prevotella Peptoniphilus cohort all body sites excluding stool omentum which were not sampled from benign cohort. These taxa were, however, depleted advanced-stage high-grade patients compared early-stage low-grade suggestive decrease accumulation advanced disease could serve for OC. Similarly, we also observed these pathogenic adverse treatment outcomes those without events predicting patients’ responses treatment. findings provide important insights into use (1) screening (2) response Given limited number enrolled study, results would need be further confirmed larger study.

Язык: Английский

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Modulation of immunity by tryptophan microbial metabolites

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Июнь 21, 2023

Tryptophan (Trp) is an essential amino acid that can be metabolized via endogenous and exogenous pathways, including the Kynurenine Pathway, 5-Hydroxyindole Pathway (also Serotonin pathway), Microbial pathway. Of these, Trp metabolic pathways in gut have recently been extensively studied for their production of bioactive molecules. The microbiota plays important role host metabolism immunity, microbial metabolites influence development progression various diseases, inflammatory, cardiovascular neurological cancer, by mediating body’s immunity. This review briefly outlines crosstalk between microorganisms body, starting from three Trp. mechanisms which act on organism immunity are summarized, potential implications disease prevention treatment highlighted.

Язык: Английский

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The Interaction between Intratumoral Microbiome and Immunity Is Related to the Prognosis of Ovarian Cancer

Microbiology Spectrum, Год журнала: 2023, Номер 11(2)

Опубликована: Март 28, 2023

Microbiota can influence the occurrence, development, and therapeutic response of a wide variety cancer types by modulating immune responses to tumors. Recent studies have demonstrated existence intratumor bacteria inside ovarian (OV). However, whether microbes are associated with tumor microenvironment (TME) prognosis OV still remains unknown. The RNA-sequencing data clinical survival 373 patients in Cancer Genome Atlas (TCGA) were collected downloaded. According knowledge-based functional gene expression signatures (Fges), was classified into two subtypes, termed immune-enriched immune-deficient subtypes. subtype, which had higher infiltration enriched CD8+ T cells M1 type macrophages (M1) mutational burden, exhibited better prognosis. Based on Kraken2 pipeline, microbiome profiles explored found be significantly different between A prediction model consisting 32 microbial constructed using Cox proportional-hazard showed great prognostic value for patients. strongly hosts' factors. Especially, five species (Achromobacter deleyi Microcella alkaliphila, Devosia sp. strain LEGU1, Ancylobacter pratisalsi, Acinetobacter seifertii). Cell experiments that seifertii inhibit macrophage migration. Our study could subtypes intratumoral microbiota Furthermore, closely IMPORTANCE microorganisms. role development their interaction largely -deficient enrichment subtype Microbiome analysis an independent predictor interact expression. microbes, Together, findings our highlight important roles TME OV, paving way further investigation its underlying mechanisms.

Язык: Английский

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Role of gut microbiota derived short chain fatty acid metabolites in modulating female reproductive health

Human Nutrition & Metabolism, Год журнала: 2024, Номер 36, С. 200256 - 200256

Опубликована: Март 8, 2024

Short chain fatty acids (SCFA) have been linked to women's reproductive health, though a lesser extent, alteration in the production of SCFA and SCFA-producing bacteria has associated significantly with pregnancy-related complications, unfavourable pregnancy outcomes, menstrual anomalies, gynaecological cancer. The female system is delicate, intricate, hormone-dependent group tissues required for continuity life species' survival. Reproductive health impacts ovarian function implantation foetal development. Several environmental physiological factors contribute mammalian infertility concerns caused by change status. lifestyle demonstrated affect including age, body weight, smoking, alcohol consumption, work stress, exercise, diet, nutrition. Nutrition influences puberty, cycle, ovulation, conception, early This review provides an overview how intestinal derived SCFAs maintains summarizing current knowledge future perspectives. Microbial improve human metabolism interfering with, glucose homeostasis, appetite regulation lipid metabolism. Also host immunity barrier integrity via primary inhibition Histone deacetylases (HDAC) mechanism. Therefore, exhibit anti-inflammatory, anti-obesity, immunoregulatory, anti-diabetes, anti-cancer, hepatoprotective, cardiovascular protective neuroprotective properties. highlights recent findings on pathologies such as preeclampsia, gestational diabetes, polycystic ovary syndrome, bacterial vaginosis, endometriosis describe relationship between disease women.

Язык: Английский

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