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Communication between gut microbiota-derived metabolites and the tumor microenvironment.

The gut microbiota has been increasingly recognized as a critical player in maintaining human health and influencing disease development. The tumor microenvironment (TME) is pivotal in tumor development and progression, comprising immune cells, stromal elements, extracellular matrix components, and cytokines. Recent studies have highlighted the promising potential of gut microbiota-derived metabolites (e.g., short-chain fatty acids, bile acids, polyamines, and tryptophan derivatives) to reshape the TME in various ways, generating significant interest for the development of novel therapeutic st

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… Bile acids are primarily synthesized in the liver from cholesterol to modulate host physiology and immune functions, and further interact with the gut microbiota to undergo various biotransformation, generating secondary bile acids (e.g., deoxycholic acid [DCA], lithocholic acid [LCA]) ( 6 , 7 ). …

The Management of Hematopoietic Stem Cell Transplant in People with HIV.

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH

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… Cyclophosphamide undergoes biotransformation by various CYP450 enzymes, with CYP3A4 contributing variably (5–25% of total enzyme activity) [ 51 ]. …

Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.

Diabetes mellitus is an endocrine disorder characterized by prolonged hyperglycemia. It results from either insulin deficiency (type 1 diabetes mellitus, T1DM) or insulin resistance (type 2 diabetes mellitus, T2DM). This condition has emerged as a significant health concern in recent years. Hyperglycemia induces the overproduction of reactive oxygen species (ROS), which can modulate multiple pathways, including AGEs-RAGE, PKC stimulation, NF-κB and PI3K/AKT. These pathways contribute to diabetes-related complications such as inflammation, oxidative stress, insulin resistance, and reduced gluco

Advancing Brain Health Naturally: β-Caryophyllene and Xanthohumol as Neuroprotective Agents.

Neurodegenerative diseases (NDDs) represent a class of incurable and progressive disorders characterized by the gradual degeneration of the structure and function of the nervous system, particularly the brain and spinal cord. A range of innovative therapeutic approaches is currently under investigation, such as stem cell-based therapies, gene-editing platforms such as CRISPR, and immunotherapies directed at pathogenic proteins. Moreover, phytochemicals such as β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models. These natural agents exe

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… Apart from this, it is also characterized by relatively short half-life and extensive liver biotransformation via processes such as oxidation, reduction, glucuronidation etc. …

Molecular glue degrader for tumor treatment.

Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" prote

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… In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites. Anal Chem. (2002) 74:3726–35. doi: 10.1021/ac0203138 73. …

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to m

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… Among the advantages that motivated the development of albumin nanoparticles are (i) the presence of two sites for drug interaction and non-covalent binding in the protein structure; (ii) non-toxicity, non-immunogenicity, and in vivo biotransformation to harmless products (amino acids); (iii) possibility …

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.

Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose tr

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… The proper experimental design in clinical trials requires an adequately large cohort to compensate for interindividual differences in metabolism of chemicals, digestion, and other aspects of biotransformation of ascorbic acid from different sources [ 18 ]. …

The Link Between the Gut Microbiome and Bone Metastasis.

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors an

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… As concluded, gut microbiota composition might be responsible for decreased biotransformation of coumarin glycosides in breast cancer bone-metastatic mice. Therefore, coumarins might have reduced absorption in the bloodstream after oral administration of Wenshen Zhuanggu Formula [ 115 ]. …

Safety of solid oncology drugs in older patients: a narrative review.

The older population represents ∼50%-60% of the population of newly diagnosed patients with cancer. Due to physiological and pathological aging and the increased presence of comorbidities and frailty factors, this population is at higher risk of serious toxicity from anticancer drugs and, consequently, often under-treated. Despite the complexity of these treatments, a good knowledge of the pharmacology of anticancer drugs and potentially risky situations can limit the emergence of potentially lethal toxicities in this population. This review focuses on optimizing systemic oncology treatments f

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… aromatase inhibitors in cases of poor tolerance or contraindication (osteoporosis). 103 However, it is associated with a higher embolic risk and may increase the risk of endometrial cancer through its pro-estrogenic effect. 103 Selective estrogen receptor degrader (SERD) Fulvestrant is metabolized by biotransformation …

Chemoprevention in Skin Cancer: What Advice?

The incidence of melanoma and non-melanoma skin cancers (NMSCs) is increasing worldwide. While NMSCs are more common, melanoma remains the most challenging because of its higher aggressiveness. Although the use of sunscreens is key in high-risk populations, it provides limited protection, which highlights the need for alternative solutions. In this review, we discuss current evidence on chemopreventive therapies, as well as their efficacy and adverse events, including immunocompetent and immunosuppressed patients. Acitretin, nicotinamide, 5-fluorouracil, and photodynamic therapy have shown ove

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… Their main limitation is still their bioavailability and biotransformation. 4.3. …

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

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… Very relevant for drug–drug interactions, CBD also affects several biotransformation enzymes such as CYP3A4, UGT1A9, UGT2B7, CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 [ 11 ]. …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… HTB26, HTB132 | ↓ | ↑ | - | - | Cyclins, caspases, PI3K/Akt pathway, NFκB | [ 94 ] SKBR3, MDA- MB-231 | ↓ | ↑ | - | - | HER2 | [ 95 ] 4T1 | - | - | - | ↓ (lung mets) | TGFβ | [ 127 ] E0771 | ↓ | ↑ | - | ↓ (delayed tumor growth) | AMPK, cyclin D1 | [ 96 ] MDA-MB-231 | ↓ | ↑ | ↓ | ↓ | Mitochondria, NFκB, biotransformation …

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

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… Elaut G Török G Vinken M Major phase I biotransformation pathways of Trichostatin A in rat hepatocytes and in rat and human liver microsomes Drug Metab Dispos 2002 30 12 1320 1328 12433798 10.1124/dmd.30.12.1320 38. …

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge pr

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… Although EVOO serves as a natural delivery matrix, OC exhibits limited systemic bioavailability owing to poor aqueous solubility, extensive pre-systemic metabolism, and complex Phase I/II biotransformation, including glucuronidation and conjugation with dietary nucleophiles. …

Marine Bioactive Compounds from Functional Seafoods: Pharmacological Mechanisms and Health Applications.

Functional seafoods derived from marine organisms, including fish, shellfish and algae, are gaining increasing attention due to their high content of bioactive compounds, such as omega-3 fatty acids, peptides, polysaccharides and antioxidants, which provide health benefits beyond basic nutrition. These marine-derived compounds exhibit a wide range of biological activities and have been investigated for their potential roles in the prevention and management of chronic diseases, including cardiovascular, neurodegenerative, cancer and gastrointestinal disorders. Their effects are largely mediated

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… In addition, several classes of marine-derived compounds, including high-molecular-weight polysaccharides such as fucoidan or porphyran, may undergo limited intestinal absorption and substantial biotransformation by gut microbiota, potentially modifying their bioactivity profile in vivo, as discussed …

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are sti

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… Biotransformation of monoterpenoids and their antimicrobial activities Phytomedicine 2014 21 1597 1626 10.1016/j.phymed.2014.05.011 25442268 122. Koo H. Pearson S.K. Scott-Anne K. Abranches J. Cury J.A. Rosalen P.L. Park Y.K. Marquis R.E. Bowen W.H. …

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… cytidine deaminase CL: 167 L/h (SC) t 1/2 PO: ~0.5 h; SC or IV: 4 h E: PO: <2% unchanged (urine) IV: 85% (urine); <1% (feces) SC: 50% (urine) | Pyrimidine analog of cytidine that inhibits DNA/RNA methyltransferases Azacitidine is incorporated into RNA and DNA following cellular uptake and enzymatic biotransformation …

RESEARCH COMMUNICATIONS OF THE 34th ECVIM-CA CONGRESS.

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… | Fecal Bile Acid Dysmetabolism is Correlated with Relative Abundance of Peptacetobacter hiranonis and Oscillospirales in Cats with Chronic Kidney Disease ESCG‐O‐5 | 09.15‐09.30 | Winston | Multi‐omic Approach Identifies Expanded Bile Acid Pools, New Microbially Conjugated Bile Acids, and Bile Acid Biotransformation …

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

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… The metabolic interplay between nutrition and the gut microbiota results in the biotransformation of inactive dietary precursors into potent anticancer compounds, acting as mediators of a complex host–microbe signaling axis. …