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Targetable pathways for drug repurposing in gastric cancer.

Gastric cancer (GC) is both the fifth most common cancer worldwide and the fifth in mortality. Owing to a lack of symptoms in the early stages and unspecific clinical presentation in the later stages, GC is usually diagnosed at advanced stages. This means that only approximately 60% of patients are eligible for curative treatment, and overall, GC patients have a 5-year survival rate of only 28.3%, underscoring the importance of developing new treatment strategies. Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment beca

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… modulator | Postmenopausal osteoporosis | JAK2/STAT3 | Reduce tumor burden | Thilakasiri et al [ 76 ]; Wu et al [ 77 ] Fedratinib | JAK2 inhibitor | Myelofibrosis | JAK2/STAT3 | Inhibit cell proliferation | Wang et al [ 41 ]; Passamonti et al [ 78 ]; Miyazaki et al [ 79 ]; Mao et al [ 80 ] Disulfiram | Acetaldehyde … Disulfiram is a drug that is used to treat alcohol abuse through the inhibition of acetaldehyde dehydrogenase. Disulfiram has been shown to have anticancer effects and to reverse drug resistance, inhibit DNA methylation, and induce apoptosis. …

Exploring Human Brain Metabolism via Genome-Scale Metabolic Modeling with Highlights on Multiple Sclerosis.

Cerebral dysfunctions give rise to a wide range of neurological diseases due to the structural and functional complexity of the human brain stemming from the interactive cellular metabolism of its specific cells, including neurons and glial cells. In parallel with advances in isolation and measurement technologies, genome-scale metabolic models (GEMs) have become a powerful tool in the studies of systems biology to provide critical insights into the understanding of sophisticated eukaryotic systems. In this study, brain cell-specific GEMs were reconstructed for neurons, astrocytes, microglia,

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… Nine of them, including indoleacetate, d -glucarate, indole-3-acetaldehyde, 3-amino-propanal, and acetyl-CoA, are shared reporter metabolites in both oligodendrocyte and microglia MS. Arachidonate was identified as a reporter metabolite in our study. …

Association Between Changes in Alcohol Consumption and Cancer Risk.

ImportanceAlthough numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood.ObjectiveTo investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers.Design, setting, and participantsThis population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health sc

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… For example, 4-fold to 10-fold increases in cytochrome P450 2E1 (CYP2E1) have been found to be associated with alcohol consumption, 23 which result in the production of acetaldehyde, reactive oxygen species, and other carcinogenic substrates, such as nitrosamines, 24 whereas a rapid decline in CYP2E1 …

Decoding Cancer Risk: Understanding Gene-Environment Interactions in Cancer Development.

While lifestyle choices or behavioral patterns remain the most significant factors influencing cancer risk, environmental exposure to certain chemicals, both manufactured and natural, may also contribute to an individual's likelihood of developing cancer. This interplay of factors, coupled with an aging demographic and shifting lifestyle patterns, has led to an increasing prevalence of cancer in recent years. This study examines the environmental and behavioral factors that contribute to anomalies in the immune system and increase the risk of developing cancer. Significant environmental and oc

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… Alcohol has been shown by researchers to induce cancer via altering the action of alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 2E1. …

Secondary Primary Cancer after Primary Gastric Cancer: Literature Review and Big Data Analysis Using the Health Insurance Review and Assessment Service (HIRA) Database of Republic of Korea.

Advances in cancer screening and early detection, as well as improvements in surgical techniques and therapeutics, have contributed to decreasing gastric cancer mortality. The number of gastric cancer survivors continues to rise; however, long-term follow-up has revealed an increase in the risk of post-gastrectomy symptoms or other health problems, such as extra-gastric secondary primary cancer (SPC), in these survivors. Therefore, evidence-based screening for new primary cancer is needed in these populations; however, the incidence of SPC varies by country or continent and its characteristics

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… Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva. Int. J. Cancer. 2004;111:480–483. doi: 10.1002/ijc.20293. 43. Escobar P.A., Smith M.T., Vasishta A., Hubbard A.E., Zhang L. …

Sorcin: a novel potential target in therapies of cancers.

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic disease

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… to chemotherapy, cancer metastasis and recurrence, always accompanied with EMT activation. 43 – 45 EMT activation is a crucial event that can be always activated during cancer invasion and metastasis. 46 The depletion in MDA-MB-231 cells results in decrease of the populations of the CD44+/CD24- and acetaldehyde …

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

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… Specific mechanisms by which alcohol induces cirrhosis and cancers include, first, the metabolism of ethanol to acetaldehyde as part of the detoxification and excretion process ( Garaycoechea et al. 2018 ). … Acetaldehyde is a known carcinogen; individuals bearing inactive alleles of mitochondrial alcohol dehydrogenase (e.g., ALDH2*2) have higher levels of blood acetaldehyde and higher risk of esophageal cancer ( Yokoyama et al. 1996 ). …

Multiple myeloma cancer stem cells.

Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contribu

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… ALDH ALDH (aldehyde dehydrogenase) catalyzes the chemical transformation from acetaldehyde to acetic acid. Upregulation of ALDH expression has been detected in normal adult stem cells. ALDH is commonly deregulated in many tumors. …

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants

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… Among these 13 alkaloids, 6,10-dimethoxydihydrochelerythrine, 6S/R-acroleinyl-dihydrochelerythrine, 9-methoxy-10-hydroxy-norchelerythrine, 10-methoxy boconoline, 6-methoxydihydrosanguinarine, dihydrosanguinaline, and 6-acetaldehyde-dihydrochelerythrine exhibited a significant inhibitory potential with …

Role of Tryptophan Metabolism in Cancer.

Tryptophan (Trp) is an essential amino acid that serves as a precursor for the synthesis of several important bioactive compounds. Trp is involved in a variety of pathophysiological processes, including neuronal function, metabolism, inflammatory responses, oxidative stress, immune regulation, and intestinal homeostasis. The role of Trp metabolism in tumorigenesis and cancer progression is of particular significance. The influence of Trp and its metabolites on tumor growth and metastasis is mediated through various mechanisms, such as immune evasion, promotion of angiogenesis, and increased re

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… Indole pathway: A critical component of Trp decarboxylation, this pathway is catalyzed by gut microorganisms and converts Trp into tryptamine, which is subsequently metabolized into indoleacetic acid derivatives, including indoleacrylic acid, indole‐3‐acetic acid (IAA), and indole‐3‐acetaldehyde. …

Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatu … ems and it has been proposed that the genotoxic effects of ethanol are mediated via its metabolite, acetaldehyde. A brief summary is provided of the effects of chronic ingestion of alcohol including intoxication, liver damage, brain damage, and possible carcinogenicity. The CIR Expert Panel recognizes that certain ingredients in this group are reportedly used …

Advances in α-Lipoic Acid for Disease Prevention: Mechanisms and Therapeutic Insights.

α-Lipoic acid (ALA) is a naturally occurring compound with diverse biological functions, widely distributed in animal and plant tissues. It has attracted considerable attention due to its versatile therapeutic potential. However, despite these promising prospects, the clinical application of ALA remains limited by its low bioavailability and chemical instability and an incomplete understanding of its multifaceted mechanisms across various diseases. This review provides a comprehensive overview of the biochemical properties of ALA, including its direct free-radical-scavenging activity, regenera

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… IR, ischemia–reperfusion; LVSP, left ventricular systolic pressure; LVEDP, left ventricular end-diastolic pressure; LV, left ventricular; H/R, hypoxia/reoxygenation; HMGB1, high mobility group box 1; FUNDC1, FUN14 domain containing 1; ALDH2, acetaldehyde dehydrogenase 2. 3.3.2. …

Is Systemic Immunosuppression a Risk Factor for Oral Cancer? A Systematic Review and Meta-Analysis.

Even if the relationship between immunosuppression and increased incidence of systemic cancers is well known, there is less awareness about the risk of developing oral cancer in immunosuppressed patients. The aim of this review was to evaluate the association between immunosuppression and the development of oral cancer. Two authors independently and, in duplicate, conducted a systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) from their inception to 28 April 2023. The assessment of risk of bias and overall quality of e

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… Chronic candidosis and oral cancer in APECED-patients: Production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans Int. J. Cancer 2009 124 754 756 10.1002/ijc.23976 18975379 190. Shillitoe E.J. …

15th Report on Carcinogens.

BACKGROUND: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology … ystematic review methods and established criteria. The listed substances include the following. A: Acetaldehyde; 2-Acetylaminofluorene; Acrylamide; Acrylonitrile; Adriamycin; Aflatoxins; Alcoholic Beverage Consumption; 2-Aminoanthraquinone; o-Aminoazotoluene; 4-Aminobiphenyl; 1-Amino-2,4-dibromoanthraquinone; 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (see H …

NTP technical report on the toxicity and metabolism studies of chloral hydrate (CAS No. 302-17-0). Administered by gavage to F344/N rats and B6C3F1 mice.

Chloral hydrate is widely used as a sedative and a hypnotic in pediatric medicine. It is also a byproduct of water chlorination. Chloral hyd … ntermediates that resulted in endogenous lipid peroxidation, forming malondialdehyde, formaldehyde, acetaldehyde, acetone, and propionaldehyde. Similar concentrations of trichloroacetic acid and trichloroethanol, the primary metabolites of chloral hydrate, also generated free radicals and induced lipid peroxidation. Lipid peroxidation induced by trichloroaceti …

Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?

Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contri

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… , nausea and one subject complained heat and pressure in chest | ( 280 ) aged adults | 40 | 18 months | 180 mg/day | ↑improved SRT, ↑visual memory ↑attention, ↓neurodegeneration | safe | ( 281 ) healthy subjects | 14 | single dose | 30 mg | ↑plasma concentration of curcumin, ↑alcohol intoxication, ↓acetaldehyde … | no adverse side effects | ( 282 ) healthy subjects | 6 | | 150 mg, 210 mg | ↑absorption, ↑bioavailability curcumin, ↑alcohol intoxication, ↓acetaldehyde | safe, no serious adverse side effects | ( 283 ) healthy subjects | 9 | | 182.4 ± 1.0 mg | ↑absorption and bioavailability than BCM-95 and Meriva …

Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

In recent years, tumor immunotherapy has made significant breakthroughs in the treatment of malignant tumors. However, individual differences in efficacy have been observed in clinical practice. There is increasing evidence that gut microbial metabolites influence the efficacy of distal tumor immunotherapy via the gut-liver axis, the gut-brain axis and the gut-breast axis, a process that may involve modulating the expression of immune cells and cytokines in the tumor microenvironment (TME). In this review, we systematically explore the relationship between gut microbial metabolites and tumor i

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… . | ( 206 ) Jianpi Jiedu decoction | Tryptophan metabolites (indole-3-acetaldehyde, 3-methylindole, 5-hydroxyindoleacetic acid, kynur­enine, 5-methoxyindoleacetate, and L-tryptophan.) | Altering the composition of the intestinal flora, increasing the abundance of beneficial intestinal bacteria, decreasing …

Регулирование питания иммунной системы кишечного мозга происходит на протяжении всей жизни.

Иммунная ось кишечника объединяет микробные, иммунные и нейронные сигналы для регулирования нейроразвития, гомеостаза и подверженности болезням. Раннее питание, в частности молочные олигозакариды, формирует благотворный микробиотический состав, повышает гиппокампальную пластичность, способствует антивоспалительной микроглианской поляризации и поощряет иммунную терпимость. Микробиота - метаболиты гута, включая короткоцепные жирные кислоты, производные триптофана и вторичные желчные кислоты, регулируют микроглиатическое созревание, функцию астроцита, дифференциацию клеток Т, производство нейротр

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… EAE | Proinflammatory | Mice and human | [ 145 , 146 , 148 ] Bile acid metabolites | Promotes Treg differentiation while inhibiting Th17 by direct binding to RORγt and FOXP3 | Anti-inflammatory | Mice | [ 62 ] Serotonin | Promotes intestinal Treg differentiation by increasing intracellular indole-3-acetaldehyde …

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

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… In many reports, higher levels of unsaturated fatty acid are found in cancer stem cells, which inhibit the stearoyl-COA desaturase 1 (SCD1) and acetaldehyde dehydrogenase 1 A1 (ALDH1A1) that maintain stemness and growth of many tumors by inhibiting apoptosis [ 32 ]. …

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox

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… Disulfiram, also known as antabuse, was discovered almost a century ago as an agent that inhibits acetaldehyde dehydrogenase, resulting in an immediate hangover when alcohol is ingested. …