Learn more about Dr. Coy and the creation of his sugar solutions.
Dr Johannes Coy is a world-renowned scientist whose research focuses on the health benefits of sugar awareness. Dr Coy has made a number of important genetic discoveries which change our understanding of cancer and nutrition and make him the leading expert on sugars.
Book: Fit with Sugar, by Dr Johannes Coy
Dr Coy has written several books about cancer nutrition. His latest book, Fit with Sugar, is now available. In this book, you’ll discover the evolutionary role of sugar in the human body. Consuming too much conventional sugar isn’t good for our health, but with the right sugars, we can stop cell ageing, keep the brain fit, protect against diseases and switch on fat burning. Find out how you can maintain physical and mental performance using natural low- glycaemic sugars and sugar substitutes. The book includes many delicious recipes for cakes, snacks and desserts, so you can implement a sugar-conscious diet easily and intelligently, without giving up sweet treats.
Buy the book: Cancer-Fighting Diet: Diet and Nutrition Strategies to Help Weaken Cancer Cells and Improve Treatment, by Dr Johannes Coy.
Research & Resources
Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer
Fructose consumption has risen due to the use of high-fructose corn syrup, and it’s thought that fructose can fuel the growth of some cancers. This study shows that adding fructose to the diet increases tumor growth in animal models of melanoma, breast cancer, and cervical cancer, without causing weight gain or insulin resistance. While cancer cells can’t use fructose directly, liver cells process it into compounds called lysophosphatidylcholines (LPCs), which are then taken up by cancer cells to help build their cell membranes. Adding fructose increased LPC levels in the blood, promoting tumor growth. Blocking a key enzyme involved in processing fructose reduced LPC levels and slowed tumor growth.
Ecological impact of a rare sugar on grapevine phyllosphere microbial communities
Plants host a complex microbiota inside or outside their tissues, and phyllosphere microorganisms can be influenced by environmental, nutritional and agronomic factors. Rare sugars are defined as monosaccharides with limited availability in nature and they are metabolised by only few certain microbial taxa. Among rare sugars, tagatose (TAG) is a low-calories sweetener that stimulates and inhibits beneficial and pathogenic bacteria in the human gut microbiota, respectively. Based on this differential effect on human-associated microorganisms, we investigated the effect of TAG treatments on the grapevine phyllosphere microorganisms to evaluate whether it can engineer the microbiota and modify the ratio between beneficial and pathogenic plant-associated microorganisms. TAG treatments changed the structure of the leaf microbiota and they successfully reduced leaf infections of downy mildew (caused by Plasmopara viticola) and powdery mildew (caused by Erysiphe necator) under field conditions. TAG increased the relative abundance of indigenous beneficial microorganisms, such as some potential biocontrol agents, which could partially contribute to disease control. The taxonomic composition of fungal and bacterial leaf populations differed according to grapevine locations, therefore TAG effects on the microbial structure were influenced by the composition of the originally residing microbiota. TAG is a promising biopesticide that could shift the balance of pathogenic and beneficial plant-associated microorganisms, suggesting selective nutritional/anti-nutritional properties for some specific taxa. More specifically, TAG displayed possible plant prebiotic effects on the phyllosphere microbiota and this mechanism of action could represent a novel strategy that can be further developed for sustainable plant protection.
Cytoprotection by fructose and other ketohexoses during bile salt-induced apoptosis of hepatocytes
Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt-induced necrosis, the effect of fructose on bile salt-induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt-induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)-induced apoptosis in a concentration-dependent manner with a maximum inhibition of 72% +/- 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to <25% of basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8), which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually potentiated apoptosis 1.6-fold. Fructose cytoprotection also could not be explained by induction of bcl-2 transcription or metal chelation. Because we could not attribute fructose cytoprotection to metabolic effects, alterations in the expression of bcl-2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt-induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt-induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose-sensitive pathways appear to initiate both bile salt-induced cell apoptosis and necrosis, whereas dissimilar, pH-sensitive, effector mechanisms execute these two different cell death processes.
Fructose and tagatose protect against oxidative cell injury by iron chelation
To further investigate the mechanism by which fructose affords protection against oxidative cell injury, cultured rat hepatocytes were exposed to cocaine (300 microM) or nitrofurantoin (400 microM). Both drugs elicited massively increased lactate dehydrogenase release. The addition of the ketohexoses D-fructose (metabolized via glycolysis) or D-tagatose (poor glycolytic substrate) significantly attenuated cocaine- and nitrofurantoin-induced cell injury, although both fructose and tagatose caused a rapid depletion of ATP and compromised the cellular energy charge. Furthermore, fructose, tagatose, and sorbose all inhibited in a concentration-dependent manner (0-16 mM) luminolenhanced chemiluminescence (CL) in cell homogenates, indicating that these compounds inhibit the iron-dependent reactive oxygen species (ROS)-mediated peroxidation of luminol. Indeed, both Fe2+ and Fe3+ further increased cocaine-stimulated CL, which was markedly quenched following addition of the ketohexoses. The iron-independent formation of superoxide anion radicals (acetylated cytochrome c reduction) induced by the prooxidant drugs remained unaffected by fructose or tagatose. The iron-chelator deferoxamine similarly protected against prooxidant-induced cell injury. In contrast, the nonchelating aldohexoses D-glucose and D-galactose did not inhibit luminol CL nor did they protect against oxidative cell injury. These data indicate that ketohexoses can effectively protect against prooxidant-induced cell injury, independent of their glycolytic metabolism, by suppressing the iron-catalyzed formation of ROS.
Antioxidant and cytoprotective properties of D-tagatose in cultured murine hepatocytes
D-Tagatose is a zero-energy producing ketohexose that is a powerful cytoprotective agent against chemically induced cell injury. To further explore the underlying mechanisms of cytoprotection, we investigated the effects of D-tagatose on both the generation of superoxide anion radicals and the consequences of oxidative stress driven by prooxidant compounds in intact cells. Primary cultures of hepatocytes derived from male C57BL/6 mice were exposed to the redox cycling drug nitrofurantoin (NFT). Lethal cell injury induced by 300 microM NFT was completely prevented by high concentrations (20 mM) of D-tagatose, whereas equimolar concentrations of glucose, mannitol, or xylose were ineffective. The extent of NFT-induced intracellular superoxide anion radical formation was not altered by D-tagatose, indicating that the ketohexose did not inhibit the reductive bioactivation of NFT. However, the NFT-induced decline of the intracellular GSH content was largely prevented by D-tagatose. The sugar also afforded complete protection against NFT toxicity in hepatocytes that had been chemically depleted of GSH. Furthermore, the ketohexose fully protected from increases in both membrane lipid peroxidation and protein carbonyl formation. In addition, D-tagatose completely prevented oxidative cell injury inflicted by toxic iron overload with ferric nitrilotriacetate (100 microM). In contrast, D-tagatose did not protect against lethal cell injury induced by tert-butyl hydroperoxide, a prooxidant which acts by hydroxyl radical-independent mechanisms and which is partitioned in the lipid bilayer. These results indicate that D-tagatose, which is a weak iron chelator, can antagonize the iron-dependent toxic consequences of intracellular oxidative stress in hepatocytes. The antioxidant properties of D-tagatose may result from sequestering the redox-active iron, thereby protecting more critical targets from the damaging potential of hydroxyl radical.
BSN723T Prevents Atherosclerosis and Weight Gain in ApoE Knockout Mice Fed a Western Diet
This study tests the hypothesis that BSN723T can prevent the development of hyperlipidemia and atherosclerosis in ApoE-/- knockout mice fed a Western (high fat, high cholesterol, and high sucrose) diet. BSN723T is a combination drug therapy consisting of D-tagatose and dihydromyricetin (BSN723). D-tagatose has an antihyperglycemic effect in animal and human studies and shows promise as a treatment for type 2 diabetes and obesity. Many claims regarding BSN723’s pharmacological activities have been made including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory, and anti-atherosclerotic effects. To our knowledge this is the first study that combines D-tagatose and BSN723 for the treatment of hyperlipidemia and the prevention of atherosclerosis.ApoE-deficient mice were randomized into five groups with equivalent mean body weights. The mice were given the following diets for 8 weeks: Group 1 – Standard diet; Group 2 – Western diet; Group 3 – Western diet formulated with D-tagatose; Group 4 – Western diet formulated with BSN723; Group 5 – Western diet formulated with BSN723T. Mice were measured for weight gain, tissue and organ weights, total serum cholesterol and triglycerides and formation of atherosclerosis.The addition of D-tagatose, either alone or in combination with BSN723, prevented the increase in adipose tissue and weight gain brought on by the Western diet. Both D-tagatose and BSN723 alone reduced total cholesterol and the formation of atherosclerosis in the aorta compared to mice on the Western diet. Addition of BSN723 to D-tagatose (BSN723T) did not increase efficacy in prevention of increases in cholesterol or atherosclerosis compared to D-tagatose alone. Addition of either D-tagatose or BSN723 alone to a Western diet prevented weight gain, increases in total serum cholesterol and triglycerides, and the formation of atherosclerosis. However, there was no additive or synergistic effect on the measured parameters with the combination BSN723T treatment.
Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study
The present study was aimed to evaluate the safety, tolerability, and beneficial effects of a ketogenic diet (KD) on body composition and blood parameters and survival in patients with breast cancer. In this randomized, controlled trial, 60 patients with locally advanced or metastatic breast cancer and planned chemotherapy, were randomly assigned to a group receiving KDs (n ¼ 30) or to a control group with standard diet (n ¼ 30) for 3 months. Serum biochemical parameters and body composition were analyzed at baseline, every 3 weeks and end of each arm. Compliance and safety of KD were also checked weekly. Fasting blood sugar (FBS) was significantly decreased in intervention group compared to the baseline (84.5 ± 11.3 vs. 100.4 ± 11.8, P ¼ 0.001). A significant inter-group difference was also observed
for FBS level at end of intervention. There was an increasing trend in serum levels of ketone bodies in intervention group (0.007–0.92, P < 0.001). Compared to the control group, BMI, body weight, and fat% were significantly decreased in intervention group in last visit (P < 0.001). No severe adverse side effect was found regarding lipid profile and kidney or
liver marker. Overall survival was higher in KD group compared to the control group in neoadjuvant patients (P ¼ 0.04). Our results suggested that chemotherapy combined with KDs can improve the biochemical parameters, body composition, and overall survival with no substantial side effects in patients with breast cancer.
The Role of the Pentose Phosphate Pathway in Diabetes and Cancer
T2DM is a chronic metabolic disease featured by persistently abnormal hyperglycemia, which can cause serious chronic damage to kidneys, eyes, and nerves. Deregulated insulin secretion and progressive insulin resistance are two main characteristics of T2DM (6). Over the past few decades, studies on the pathogenesis of T2DM have revealed a close relationship between the PPP, obesity-related insulin resistance and T2DM. In this part, we will mainly focus on the role of the PPP in obesity-related insulin resistance, insulin secretion and chronic diabetic complications.
Mystery solved: Trehalose kickstarts autophagy by blocking glucose transport
Although vertebrates cannot synthesize the natural disaccharide trehalose, exogenous administration of trehalose to mammalian cells may be beneficial for protein misfolding disorders. In this issue, DeBosch et al. show that trehalose may also be useful in treating nonalcoholic fatty liver disease and identify inhibition of cellular glucose import through SLC2A (also known as GLUT) transporters as a mechanism by which trehalose stimulates autophagy through the adenosine monophosphate–activated protein kinase (AMPK).
Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis
The accumulation of lipids in hepatocytes that occurs in nonalcoholic fatty liver disease (NAFLD) can result in liver failure or liver cancer. Trehalose is a ubiquitous sugar that is present in the food consumed by animals. DeBosch et al. determined that trehalose blocked glucose uptake into cells by inhibiting glucose transporters in the plasma membrane, which induced a “starvation”-like response that activated autophagy even in the presence of adequate nutrients and glucose. Furthermore, providing trehalose to mice that are a model of NAFLD prevented lipid accumulation in the liver. As noted by Mardones et al. in the associated Focus, trehalose, which has been previously under investigation to treat neurodegenerative diseases characterized by toxic protein aggregates, may be a “silver bullet” for treating diseases resulting from inadequate cellular degradative metabolism.
Tumor Tissue Acidosis as a Factor Determining the Malignant Phenotype and Tumor Resistance to Chemotherapy
Currently, it has been shown that there are differences in the regulation of the functioning of normal and tumour cells. Based on this, the term “cell reprogramming” was introduced, meaning the formation of
a malignant phenotype.
Trehalose alleviates oxidative stress-mediated liver injury and Mallor-Denk body formation via activating autophagy in mice
Trehalose, a disaccharide, has been shown to induce autophagy and reduce cellular stress in various disease models. However, its effects in hepatocytes have not been fully investigated. In a study using mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), trehalose was found to induce autophagy, reduce endoplasmic reticulum stress, oxidative stress, Mallory-Denk body formation, and apoptosis in hepatocytes. Electron microscopy revealed the formation of autolysosomes in close proximity to the Mallory-Denk bodies. These findings suggest that trehalose has the potential to be a therapeutic agent for liver diseases associated with oxidative stress by activating autophagy.
A New Target for Hepatic Fibrosis Prevention and Treatment: The Warburg Effect
Hepatic fibrosis is a major public health problem that endangers human wellbeing. In recent years, a number of studies have revealed the important impact of metabolic reprogramming on the occurrence and development of hepatic fibrosis. Among them, the Warburg effect, as an intracellular glucose metabolism reprogramming, can promote the occurrence and development of hepatic fibrosis by promoting the activation of hepatic stellate cells (HSCs) and inducing the polarization of liver macrophages (KC). Understanding the Warburg effect and its important role in the progression of hepatic fibrosis will assist in developing new strategies for the prevention and treatment of hepatic fibrosis. This review focuses on the Warburg effect and the specific mechanism by which it affects the progression of hepatic fibrosis by regulating HSCs activation and KC polarization. In addition, we also summarize and discuss the related experimental drugs and their mechanisms that inhibit the Warburg effect by targeting key proteins of glycolysis in order to improve hepatic fibrosis in the hope of providing more effective strategies for the clinical treatment of hepatic fibrosis.
Biological function, regulatory mechanism, and clinical application of mannose in cancer.
This study focuses on the potential of mannose, a sugar found in the body, as a treatment for cancer. Unlike glucose, mannose is mainly involved in protein modification rather than energy metabolism. Recent research shows that mannose can directly inhibit cancer cell growth both in lab settings and in animals. Simple supplementation with mannose, either in cell cultures or drinking water, has shown promising results. It also appears to boost the effectiveness of existing cancer treatments like chemotherapy and radiotherapy. Additionally, mannose is being explored as a cancer biomarker and as a component in drug delivery systems to enhance treatment efficacy. The review summarizes the latest findings on mannose’s role in cancer progression, its mechanisms of action, and its applications in cancer diagnosis and therapy.
Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways
Recent research highlights that increased aerobic glycolysis, often seen in cancer cells, can actually drive cancer development rather than just being a result of it. In a 3D culture model of human breast cells, overexpressing GLUT3, a glucose transporter, triggered cancer-related signaling pathways, leading to abnormal cell growth and loss of tissue structure. On the other hand, reducing glucose intake in cancer cells helped them form organized structures and halted their growth. Interestingly, the differences between normal and cancerous cells in this model weren’t due to the usual pathways like HIF-1α or mTOR, but were linked to other mechanisms involving RAP1 and specific enzyme interactions. This suggests that targeting the ways in which increased glucose uptake drives cancer could offer new avenues for diagnosis and treatment.
Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment
This study explores the potential of using metabolite profiles as biomarkers to predict treatment outcomes in lung cancer patients. Researchers analyzed serum samples from 25 patients undergoing chemotherapy, with or without radiation, using nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). The results showed that metabolite profiles varied significantly before, during, and after treatment. Certain metabolites identified via GC-MS, such as hydroxylamine, tridecan-1-ol, and octadecan-1-ol, were linked to patient survival, while others like tagatose and threonine were associated with disease progression. 1H-NMR data were more reflective of the cancer stage and type. The findings suggest that metabolite profiling could serve as a valuable prognostic tool for assessing clinical outcomes in lung cancer patients, although further research with a larger patient group is needed.
Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer
This study explores the effects of a ketogenic diet on carbohydrate metabolism in patients with head and neck squamous cell carcinoma (HNSCC), where aerobic glycolysis is crucial for tumor energy supply. Researchers used quantitative microdialysis (μD) to measure metabolic parameters directly in both tumor and tumor-free tissues over several days. The study involved monitoring levels of urea, glucose, lactate, and pyruvate during a 24-hour period on a standard Western diet followed by up to four days on a ketogenic diet.
Results showed that after three days on the ketogenic diet, lactate levels significantly decreased in tumor tissue compared to tumor-free mucosa, while glucose and pyruvate levels increased. This suggests that the ketogenic diet impacts the tumor’s glucose metabolism, possibly indicating that HNSCC tumor cells may use lactate as a fuel source under these conditions. The findings highlight the potential for dietary interventions to influence tumor metabolism in cancer treatment.
AKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma
This study explored the role of the enzyme AKR1B1 in liver cancer linked to metabolic diseases. The researchers found that AKR1B1 levels were significantly higher in patients with metabolic-associated fatty liver disease (MASLD), metabolic-associated steatohepatitis (MASH), and liver cancer (HCC). In lab tests and mouse models, they discovered that AKR1B1 influences key metabolic processes, promoting the development of liver cancer in a high-sugar diet environment.
The study suggests that inhibiting AKR1B1 could prevent the early stages of liver cancer. The researchers propose AKR1B1 as a potential target for new cancer treatments and suggest measuring AKR1B1 levels in the blood as a diagnostic tool for liver diseases. The study highlights AKR1B1’s role in promoting a specific metabolic process (the Warburg effect) in liver cancer.
Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort.
This population-based study aimed to examine the association between sugary drinks, artificially sweetened beverages, and the risk of cancer. The study included over 101,000 participants and assessed their beverage consumption using dietary records. The results showed that consuming sugary drinks was significantly associated with an increased risk of overall cancer and breast cancer. However, artificially sweetened beverages did not show a significant association with cancer risk. Additionally, the consumption of 100% fruit juice was also found to be associated with an increased risk of overall cancer. These findings suggest that sugary drinks, including fruit juices, may be modifiable risk factors for cancer and warrant further investigation in future studies.
Blood Glucose and Risk of Incident and Fatal Cancer in the Metabolic Syndrome and Cancer Project (Me-Can): Analysis of Six Prospective Cohorts
This prospective study investigated the association between blood glucose levels and the risk of cancer in six European cohorts. The study included over 274,000 men and 275,000 women, with an average follow-up of 10.4 years. The results showed that higher blood glucose levels were associated with an increased risk of overall incident cancer and fatal cancer, independent of body mass index (BMI) and smoking status. The associations were stronger among women compared to men and for fatal cancer compared to incident cancer. Specific associations were found for various cancer sites, including the liver, gallbladder, respiratory tract, pancreas, urinary bladder, uterine corpus, cervix uteri, and stomach. These findings suggest that abnormal glucose metabolism, beyond BMI, may contribute to an elevated risk of cancer, highlighting the importance of glucose control for cancer prevention.
Serum glucose and risk of cancer: a meta-analysis
In this meta-analysis, the relationship between raised serum glucose levels and the risk of solid cancers was examined. PubMed and Embase databases were searched for relevant studies, and inclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, and well-described statistical methods
The underlying biological mechanisms are not fully understood, but the findings suggest that reducing serum glucose through lifestyle and dietary changes could potentially impact cancer mortality.
Elevated fasting serum glucose levels increase the risk of hepatocellular carcinoma: A prospective cohort study
This study investigated the relationship between fasting blood glucose (FBG) levels and the risk of hepatocellular carcinoma (HCC), a type of liver cancer. The study used competing risk regression models to account for death as an event that may occur before HCC. A cohort of 93,447 participants without prior HCC was followed, and their FBG concentrations were measured. The results showed that higher FBG levels were associated with an increased risk of HCC. Participants with FBG levels between 4.82 mmol/L and 5.49 mmol/L had a 47% increased risk, while those with FBG levels above 5.49 mmol/L had a 69% increased risk. These findings suggest that controlling FBG levels could potentially reduce the risk of HCC in the Chinese population.
Higher glucose and insulin levels are associated with risk of liver cancer and chronic liver disease mortality among men without a history of diabetes
This prospective study examined the associations between fasting glucose, insulin, and insulin resistance with liver cancer and chronic liver disease (CLD) mortality in Finnish male smokers. Participants were followed for up to 22 years, and various risk factors were considered. The results showed that elevated fasting glucose levels were positively associated with liver cancer risk. Undiagnosed, biochemically defined diabetes also increased the risk of liver cancer and CLD mortality. Similarly, higher serum insulin levels and insulin resistance were independently associated with increased risks of liver cancer and CLD mortality. These findings suggest that insulin and glucose dysregulation, even in the absence of diagnosed diabetes, may play a significant role in the development of liver cancer and CLD.
Insulin Resistance Is Associated with Early Gastric Cancer: A Prospective Multicenter Case Control Study
This study aimed to investigate the factors associated with early gastric cancer and evaluate the predictive value of the homeostasis model assessment of insulin resistance (HOMA-IR) index, fasting glucose, and lipid profile. The study included 63 patients with early gastric cancer and a matched control group. The results showed that higher levels of total cholesterol, fasting glucose, body mass index, and diastolic blood pressure were associated with an increased risk of early gastric cancer. Furthermore, hyperglycemia, lower high-density lipoprotein cholesterol levels, and a low HOMA-IR level were identified as potential risk factors for early gastric cancer.
Prostate Size Correlates with Fasting Blood Glucose in Non-Diabetic Benign Prostatic Hyperplasia Patients with Normal Testosterone Levels
This retrospective study aimed to evaluate the correlations between BMI, fasting glucose, insulin, testosterone level, insulin resistance, and prostate size in non-diabetic benign prostatic hyperplasia (BPH) patients with normal testosterone levels. The study included 212 patients who underwent transurethral resection of the prostate (TURP) due to medical treatment failure. The results showed that prostate size correlated positively with age, PSA levels, and fasting glucose levels, but not with BMI, testosterone, insulin level, or insulin resistance. Testosterone levels were inversely correlated with BMI, insulin level, and insulin resistance, but not with age, prostate size, PSA, or fasting glucose level. Multiple adjusted regression analysis revealed that prostate size was associated with elevated PSA and increased fasting glucose levels. In non-diabetic BPH patients with normal testosterone levels, fasting glucose level was identified as an independent risk factor for prostate hyperplasia.
Effects of a novel palatinose based enteral formula (MHN-01) carbohydrate-adjusted fluid diet in improving the metabolism of carbohydrates and lipids in patients with esophageal cancer complicated by diabetes mellitus
A study investigated the effects of a novel enteral formula (MHN-01) on perioperative management of patients with esophageal cancer and diabetes mellitus. MHN-01 showed promising results in suppressing post-prandial hyperglycemia, improving lipid metabolism, and reducing fat accumulation in animal experiments. In clinical cases, MHN-01 was successfully used in the perioperative management of patients with severe diabetes mellitus and esophageal cancer.
Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts
The role of trehalose as an innovative drug in the treatment of neurodegenerative diseases and other illnesses opening a new scenario of intervention in conditions difficult to be treated.
Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways
This study looked at the potential of trehalose, a natural sugar found in plants and microorganisms, to activate a pathway that regulates cellular balance and reduces oxidative stress. The study found that trehalose can activate this pathway in a way that induces autophagy (cellular cleaning) and increases the expression of antioxidant factors. This suggests that trehalose has the potential to be a useful treatment for chronic diseases that involve oxidative stress and problems with cellular balance.
Galactose inhibits migration and invasive growth of cancer cells
This study provides clear evidence that specific types of dietary sugar are implicated in either feeding, or starving, the spread of cancer: “In order to test whether TKT’s promotion of colorectal cancer metastasis is dependent on glycolysis, we used galactose which induced cells to survive on ATP provided by mitochondrial respiration instead of glucose.”
How Sugar Suppresses the Immune System Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment
Researchers investigated the correlation between hypoxia-related genes and the prognosis of colon adenocarcinoma (COAD) patients. They identified four hypoxia genes (TKTL1, SLC2A3, ALDOB, and ENO3) and developed a hypoxia risk model to predict overall survival. The model showed stability and could be used to assess the prognosis of COAD patients. Additionally, the hypoxia risk score was found to be associated with immunosuppression in the tumor microenvironment.
How Sugar Suppresses the Immune System A hypoxia-linked gene signature for prognosis prediction
The study aimed to develop a prognostic model using hypoxia-linked genes to predict the prognosis of hepatocellular carcinoma (HCC) patients and investigate the relationship between hypoxia and immune status in the tumor microenvironment (TME). Six hypoxia-linked genes (HMOX1, TKTL1, TPI1, ENO2, LDHA, and SLC2A1) were used to create the prediction model. The model showed satisfactory estimation power and could independently predict overall survival (OS) in HCC patients. Additionally, the model could distinguish between high- and low-risk groups based on immune status. The findings have implications for improving the diagnosis and treatment of HCC.
A hypoxia-linked gene signature for prognosis prediction and evaluating the immune microenvironment in patients with hepatocellular carcinoma
This study aimed to develop a prognostic model using six hypoxia-linked genes to predict the prognosis of hepatocellular carcinoma (HCC) patients and investigate the relationship between hypoxia and immune status in the tumor microenvironment. The model was created using transcriptome and clinical data from TCGA and validated using data from GEO. The model showed satisfactory estimation power and could independently predict overall survival in HCC patients. It also successfully distinguished between high- and low-risk groups in terms of immune status. The findings have implications for improving the diagnosis and treatment of HCC.
TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression
This study investigated the role of transketolase-like-1 (TKTL1) in metabolic reprogramming under hypoxic conditions in leukemia cells. Using THP-1 AML cells, the researchers found that knockdown of TKTL1 led to decreased activities of transketolase (TKT), glucose-6-phosphate dehydrogenase (G6PD), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This resulted in impaired hypoxia-induced overexpression of G6PD and GAPDH, affecting the redox capacity of NADPH- and NADH-related cells. TKTL1 knockdown also hindered the transcription of genes involved in glucose, pentose phosphate pathway (PPP), and amino acid metabolism, preventing cells from switching to enhanced glycolysis under hypoxia. These findings highlight the crucial role of TKTL1 in the metabolic adaptation to hypoxia in THP-1 AML cells, impacting glucose and amino acid metabolism through modulation of key enzymes and transporters.
Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides
In this study, researchers investigated the effects of a ketogenic diet enriched with omega-3 fatty acids and medium-chain triglycerides (MCT) on tumour growth in a mouse model of gastric adenocarcinoma. The ketogenic diet, characterized by low carbohydrate intake and high fat content, significantly delayed tumour growth compared to a standard diet. Tumours in the ketogenic diet group exhibited larger necrotic areas and fewer blood vessels in the viable tumour cell regions. These tumour cells in the border zone showed a glycolytic phenotype. The results suggest that the ketogenic diet can effectively impede tumour growth in this mouse model, although further research is needed to explore its impact on other tumour-related processes such as invasive growth and metastasis.
Transketolase Serves as a Biomarker for Poor Prognosis in Human Lung Adenocarcinoma
Half of the patients who undergo surgical resection for early-stage lung cancer experience relapse and succumb to the disease, despite the use of adjuvant chemotherapy, which only minimally reduces the risk of relapse. Identifying the factors driving relapse, determining who would benefit from adjuvant therapy, and finding new targets are crucial. The pentose phosphate pathway (PPP) has been implicated in cancer, but the role of transketolase (TKT), an enzyme involved in the PPP, in lung adenocarcinoma (LUAD) is not well understood. This study examined TKT expression in LUAD and found that it was elevated in cancer tissues compared to normal tissues. High TKT expression was associated with advanced tumor stage. Additionally, inhibiting TKT led to tumor cell apoptosis and cell cycle arrest. These findings highlight the significant role of TKT in LUAD progression and prognosis, suggesting its potential as a biomarker for predicting recurrence after lung cancer resection.
Inhibition of Transketolase Improves the Prognosis of Colorectal Cancer
This study explored the role of transketolase (TKT) in colorectal cancer (CRC). TKT was found to be up-regulated in CRC and associated with poor prognosis. Inhibiting TKT reduced tumor cell viability, proliferation, migration, and induced apoptosis. TKT may serve as a prognostic biomarker and therapeutic target for CRC.
Hypoxia-Related Gene-Based Signature Can Evaluate the Tumor Immune Microenvironment and Predict the Prognosis of Colon Adenocarcinoma Patients
This study focused on the prognosis of colon adenocarcinoma (COAD) patients in relation to hypoxia-related genes. A prognostic model using four hypoxia genes (TKTL1, SLC2A3, ALDOB, and ENO3) was constructed to predict overall survival. The hypoxia risk score from the model was also found to be associated with immunosuppression in the tumor microenvironment. This model provides a stable prediction of overall survival for COAD patients.
TKTL1 participated in malignant progression of cervical cancer cells via regulating AKT signal mediated PFKFB3 and thus regulating glycolysis
This study investigated the role of TKTL1 in cervical cancer (CC) cells and its involvement in glucose metabolism. The findings revealed that TKTL1 expression was increased in CC cells and its inhibition led to decreased cell proliferation, invasion, migration, and glycolysis. TKTL1 was shown to activate PFKFB3 through AKT signaling, contributing to the malignant progression of CC cells. Animal experiments also demonstrated that TKTL1 inhibition reduced tumor volume and improved histopathological status. Overall, TKTL1 plays a crucial role in CC by regulating glucose metabolism through AKT-mediated pathways.
Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation
This study focused on the role of transketolase (TKT) in colorectal cancer (CRC). The findings revealed that TKT expression was significantly increased in CRC and correlated with poor prognosis. TKT was found to promote CRC cell growth and metastasis. Further investigation showed that TKT interacted with GRP78 and enhanced glycolysis in CRC cells by increasing AKT phosphorylation, thereby facilitating metastasis. These findings suggest that TKT could serve as a prognostic indicator for CRC and provide insights for developing new treatment targets for the disease.
Hyperglycemia induces metabolic reprogramming into a glycolytic phenotype and promotes epithelial-mesenchymal transitions via YAP/TAZ-Hedgehog signaling axis in pancreatic cancer
This study investigated the impact of hyperglycemia on pancreatic ductal adenocarcinoma (PDAC). The findings revealed that hyperglycemia promotes epithelial-mesenchymal transition (EMT) and metabolic reprogramming in PDAC cells, leading to a glycolytic phenotype. Hyperglycemia also enhances chemoresistance and activates the Hedgehog pathway, contributing to tumor progression. Additionally, hyperglycemia stimulates YAP/TAZ expression in cancer-associated fibroblasts, leading to the production of tumor-promoting proteins in the tumor microenvironment. Inhibition of YAP/TAZ reverses these effects, suggesting YAP/TAZ as a potential therapeutic target in PDAC.
Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity | Cancer & Metabolism | Full Text (biomedcentral.com)
This study investigated the impact of ketogenic diets on melanoma progression and metabolism. The findings demonstrated that ketogenic diets effectively reduced tumor growth in mice with genetically and metabolically diverse melanoma xenografts. The diets also reduced metastasis in mice with a functional immune system. Targeted metabolomics analysis revealed that ketogenic diets induced changes in amino acid metabolism and reduced levels of alpha-amino adipic acid, a cancer biomarker, in circulation and tumors. Additionally, ketogenic diets affected sphingomyelin levels and hydroxylation in plasma and tumors. These findings suggest that ketogenic diets have antitumor effects on melanoma, regardless of genetic background or immune status, by altering multiple metabolic pathways and creating an unfavorable environment for tumor cell proliferation.
Scaling brain neurogenesis across evolution
The neocortex, responsible for cognitive abilities, has expanded and folded in mammals, partly due to basal radial glial cells (bRGs). A study by Pinson et al. reveals that a variant of transketolase-like protein 1 (TKTL1) in modern humans increases the number of bRGs and upper layer projection neurons. This genetic change may contribute to cognitive differences between modern humans and extinct archaic humans.
P1249: Inhibition of The Pentose-Phosphate-Pathway (Ppp) Mediates Macrophage Reprogramming From Supportive Bystander Function Towards Antibody-Dependent Lymphoma Cell Clearance And Lymphoma Suppression
This study investigated the metabolic pathways regulating macrophages in the tumor microenvironment (TME) of lymphoma and their impact on macrophage function in therapy. Inhibition of the pentose phosphate pathway (PPP) increased macrophage phagocytosis of lymphoma cells and induced morphological and functional changes. PPP inhibition also altered immune profiles and reduced support for CLL cells. Multiomics analyses revealed connections between PPP inhibition, metabolism, and immunity. In a mouse model, PPP inhibition improved macrophage maturation, prolonged survival, and enhanced pro-inflammatory polarization. The PPP was identified as a targetable modulator of macrophage function in lymphoma therapy.
Fructose and the Liver
In this study, it is revealed that fructose overconsumption is linked to metabolic syndrome and liver-related diseases. The detrimental effects include insulin resistance, inflammation, non-alcoholic fatty liver disease (NAFLD), and an increased risk of liver cancer. The study demonstrates that fructose activates proinflammatory, fibrogenic, and oncogenic pathways, particularly in the liver.
A dose- and time-dependent effect of oxythiamine on cell growth inhibition in non-small cell lung cancer
In this study, the researchers investigated the effect of Oxythiamine (OT), an antimetabolite of Thiamine-dependent enzymes (TDEs), on the growth of non-small-cell lung cancer (NSCLC) cells. They co-cultured A549 cells with varying doses of OT and examined cell proliferation and apoptosis. The results showed that OT treatment significantly inhibited the proliferation of A549 cells in a dose- and time-dependent manner. The inhibition of TDEs led to cell cycle arrest and induced apoptotic cell death. These findings suggest that OT could be a potential therapeutic target for NSCLC treatment.
The role of transketolase in human cancer progression and therapy
In this review, the researchers highlight the significance of Transketolase (TKT) and its family members, TKTL1 and TKTL2, in cancer regulation. TKT and TKTL1 have been implicated in various cancer-related processes, including cell proliferation, metastasis, invasion, chemoradiotherapy resistance, and patient prognosis. The detection of TKTL1 levels using EDIM technology has shown promise as a sensitive and specific method for early malignancy detection and evaluating the effectiveness of surgery. While targeted TKT therapy has demonstrated positive effects in suppressing cancer, it is important to consider potential detrimental effects on the organism. The review discusses the role of TKT in different tumors, underlying mechanisms, and its clinical applications, providing insights for future targeted therapy and cancer-related research.
Ingredients such as trehalose and hesperidin taken as supplements or foods reverse alterations in human T cells, reducing asbestos exposure-induced antitumor immunity
This study investigated the potential of trehalose (Treh) and glycosylated hesperidin (gHesp) to reverse the reduced antitumor immunity caused by asbestos exposure. Human immune cells exposed to asbestos were treated with Treh or gHesp, and gene expression levels related to immune response were assessed. The results suggest that Treh and gHesp may have the ability to restore antitumor immunity in T helper cells affected by asbestos exposure. Further research is needed to confirm these findings and evaluate their efficacy in asbestos-exposed populations.
Expression of Transketolase TKTL1 in Iraqi Breast Cancer Females
This scientific article discusses the expression of the TKTL1 gene in breast cancer patients and its relationship with clinical characteristics. The study involved 50 Iraqi breast cancer patients and 25 healthy controls. The findings revealed that breast cancer patients showed increased expression of the TKTL1 gene compared to the control group. The level of gene expression was higher on the right side compared to the left side. Significant differences in gene expression were observed based on tumor site, tumor grade, and cancer stage. The results suggest that TKTL1 gene expression may serve as a potential biomarker for early detection of breast cancer.
Trehalose alleviates oxidative stress-mediated liver injury and Mallor-Denk body formation via activating autophagy in mice
This study investigated the effects of trehalose on autophagy, ER stress, oxidative stress-mediated cytotoxicity, and Mallory-Denk body (MDB) formation in hepatocytes. The study used a mice model with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment and administered trehalose through intraperitoneal injection. The results showed that trehalose induced autophagy, reduced ER stress, oxidative stress, MDB formation, and apoptosis in hepatocytes. Electron microscopy revealed autolysosome formation close to the MDBs. These findings suggest that trehalose has the potential to be a therapeutic agent for oxidative stress-related liver diseases by activating autophagy.
Hyperglycemia and cancer in human lung carcinoma by means of Raman spectroscopy and imaging
This study used Raman spectroscopy and imaging to analyze human lung cancer cells and their response to glucose and deuterated glucose under normal and hyperglycemic conditions. The results showed that substituting glucose with deuterated glucose allowed the distinction between de novo lipid synthesis and lipid uptake from the diet. It was observed that glucose is primarily used for de novo lipid synthesis and that high glucose levels decrease mitochondrial oxidative phosphorylation, leading to a shift towards glycolysis (Warburg effect). This suggests that hyperglycemia may contribute to a more aggressive cancer phenotype by inhibiting oxidative phosphorylation and apoptosis.
Molecular Mechanisms for Ketone Body Metabolism, Signaling Functions, and Therapeutic Potential in Cancer
Ketone bodies (KBs) are alternative energy sources to glucose during nutrient deprivation. They play a role in cellular signaling, protect against inflammation and oxidative stress, and have therapeutic potential in various diseases, including cancer. Abnormal KB metabolism is involved in tumorigenesis, and targeting it through dietary interventions, like ketogenic diets, shows promise in cancer therapy. This review explores the molecular mechanisms of KB metabolism and their potential use in cancer treatment.
High Blood Sugar Levels Trigger Transition of Benign to Malignant Tumours in Pancreatic Cancer
High blood sugar levels (hyperglycemia) in pancreatic ductal adenocarcinoma (PDAC) cause metabolic changes that promote the transition of cancer cells and increase their resistance to chemotherapy. This is mediated by the overexpression of certain proteins (YAP and TAZ) and activation of the Hedgehog pathway. Hyperglycemia also affects the surrounding tissue, stimulating the production of proteins that support tumor growth. Blocking the activity of YAP and TAZ can reverse these effects and improve treatment outcomes.
Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination
Early stages of cancer involve a metabolic shift known as the “Warburg effect,” where cells rely on glycolysis instead of oxidative phosphorylation. In a zebrafish model, preneoplastic cells quickly activate glycolysis and impair oxidative phosphorylation. Blocking glycolysis inhibits cell growth, while enhancing glucose availability promotes proliferation and reduces cell death. Targeting impaired oxidative phosphorylation with metformin induces cell death specifically in preneoplastic cells. Additionally, mitochondrial fragmentation occurs early on and blocking it leads to increased cell death. These findings offer insights for targeted tumor prevention strategies.
High glucose promotes benign prostatic hyperplasia by downregulating PDK4 expression
This study investigated how high levels of glucose can affect prostate cells and potentially lead to benign prostatic hyperplasia (BPH), a condition that affects many aging men. The researchers focused on a specific gene called Pyruvate dehydrogenase kinase 4 (PDK4), which is involved in glucose metabolism and the development of various diseases. They treated normal and BPH prostate cells with high glucose levels and found that it caused these cells to grow more, change their characteristics, reduce cell death, and decrease PDK4 expression. Patients with diabetes-related BPH also had lower levels of PDK4. When they manipulated PDK4 levels in these cells, it had corresponding effects. They also used a medication called Rosiglitazone, which can increase PDK4 expression and suggested it might be a potential treatment for BPH. This study implies that high glucose levels could contribute to BPH development by reducing PDK4, making it a possible target for therapy.
Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study, Nutrition and Cancer
This study aimed to explore the safety and benefits of a ketogenic diet (KD) on patients with breast cancer undergoing chemotherapy. In a 3-month randomized trial with 60 participants, half followed a KD, and the other half maintained a standard diet. The KD group showed reduced fasting blood sugar, increased ketone levels, and significant improvements in BMI, body weight, and fat percentage compared to the control group. No severe adverse effects were observed in lipid profile or kidney/liver markers. Notably, overall survival was higher in the KD group, suggesting that combining chemotherapy with KD may enhance biochemical parameters and body composition while improving survival in breast cancer patients without major side effects.
Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma
This study examined glioblastoma (GBM), an aggressive brain tumor. Researchers investigated the Warburg effect, an abnormal energy metabolism in tumors, and its impact on GBM prognosis and the immune environment.
They developed a predictive model using GBM data, identifying age, treatment, and Warburg effect gene scores as key factors for prognosis. A predictive tool showed high accuracy.
The study revealed that high Warburg effect gene scores were associated with an immunosuppressive environment, limiting the effectiveness of immunotherapy. Drugs targeting these genes inhibited GBM cell growth in lab tests.
In summary, the Warburg effect affects GBM prognosis and the immune environment, and targeting related genes may offer new treatment options.
Ketogenic diet – a literature review
The ketogenic diet has gained attention for its potential benefits in various health conditions. It has been found to aid in weight reduction, improve lipid profile, and potentially reduce the need for antidiabetic drugs and insulin therapy in type 2 diabetes. Animal studies suggest positive effects in cancer treatment, although human studies are limited. Additionally, there are reports of the ketogenic diet delaying the onset of dementia symptoms. However, the long-term impact on cardiovascular risk is still unknown, emphasizing the need for careful consideration before adopting the diet.
Significant Systemic Insulin Resistance is Associated With Unique Glioblastoma Multiforme Phenotype
This study investigated the relationship between insulin resistance and a specific type of brain cancer called glioblastoma multiforme (GBM), which is characterized by the presence of gemistocytes (GCs). These GCs are typically associated with reactive astrocytes, a type of brain cell. The study aimed to find a connection between insulin resistance and the presence of GCs in newly diagnosed GBM patients.
The researchers looked at medical records of 220 patients with newly diagnosed GBM. Among these patients, 26.3% had a history of type 2 diabetes at the time of diagnosis. They found that in the group of GBM patients with GCs, poorly-controlled diabetes was more common compared to the group without GCs. Specifically, there was a higher prevalence of poorly-controlled diabetes in the GC-GBM group (18.75%) compared to the non-GC GBM group (9.5%). In the subset of diabetic patients, those with GC-GBM were more likely to exhibit characteristics of insulin resistance, such as being male, morbidly obese, and not using synthetic insulin before diagnosis.
In conclusion, this study suggests that systemic metabolic factors related to insulin resistance, including type 2 diabetes, morbid obesity, and male gender, are associated with a distinct histological subtype of GBM characterized by the presence of GCs. This association is particularly significant in poorly-controlled type 2 diabetes GBM patients who do not use synthetic insulin. The findings highlight the potential relevance of glucose metabolism in astrocytes and its connection to high-grade brain tumors. Further research is needed to explore how patients’ metabolic status, tumor characteristics, molecular changes, and use of anti-diabetic drugs impact survival in GBM patients.
Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
This study explores the link between pancreatic cancer, obesity, type 2 diabetes, and high levels of insulin in the blood (hyperinsulinemia). It is known that high insulin production is an independent risk factor for cancer, including pancreatic cancer. Previous research showed that reducing insulin production could suppress the development of pre-cancerous pancreatic lesions (PanIN) in mice with a specific genetic mutation (Kras). However, the precise mechanisms behind this connection and whether hyperinsulinemia directly affects PanIN precursor cells were unclear.
The study found that insulin receptors (Insr) in pancreatic acinar cells expressing the KrasG12D mutation were not essential for regulating glucose levels but were crucial for the formation of PanIN lesions in the presence of diet-induced hyperinsulinemia and obesity. The mechanism behind this involved an increase in the translation of digestive enzyme proteins, which led to local inflammation and the development of PanIN lesions in vivo. In laboratory experiments, insulin was shown to promote the transformation of acinar cells into ductal cells (acinar-to-ductal metaplasia) in a manner dependent on trypsin and insulin receptors.
In summary, this study sheds light on how obesity-driven hyperinsulinemia is connected to the development of pancreatic cancer. It shows that insulin receptors in pancreatic cells are not required for regulating blood sugar but play a crucial role in the formation of pre-cancerous pancreatic lesions under conditions of obesity and high insulin levels. The study provides insights into the mechanisms underlying the link between hyperinsulinemia and the development of pancreatic cancer.
Scaling brain neurogenesis across evolution
The neocortex, responsible for cognitive abilities, has evolved and expanded across mammals. Humans’ advanced cognitive abilities are attributed to neocortex size and structure. Basal radial glial cells (bRGs) play a role in neocortex expansion and folding. A study by Pinson et al. found that a variant of transketolase-like protein 1 (TKTL1) in modern humans increases the number of bRGs and upper layer projection neurons. This genetic change may contribute to cognitive differences between modern humans and extinct archaic humans.
Targeting Glucose Metabolism for HPV-Associated Cervical Cancer: A Sweet Poison
Targeting glucose metabolism (glycolysis and PPP) provides a new strategy for future clinical treatment of cervical cancer and offers a theoretical basis for the treatment of HPV-related diseases.
Targeting Metabolic Vulnerabilities in Pancreatic Cancer: The Synergistic Anti-Tumour Effects of a Ketogenic Diet and IDH1 Inhibition
A ketogenic diet exerts a strong anti-tumour effect in multiple pancreatic cancer mouse models, likely due to low glucose and increased fatty acid load. The metabolic shift towards an oxidative phosporylation (OXPHOS) phenotype makes pancreatic cancer cells particularly vulnerable to antioxidant and mitochondrial inhibitiors.
Proteomic Characterization of Gastric Cancer Response to Chemotherapy and Targeted Therapy Reveals New Therapeutic Strategies
Chemotherapy and targeted therapy are primary treatments for gastric cancer (GC), but drug resistance reduces their effectiveness. This study analyzed the proteome of 206 tumor tissues from GC patients undergoing chemotherapy or anti-HER2 therapy, identifying four subtypes (G-I–G-IV) with distinct clinical and molecular features.
Patients with high MSI-signature GC responded well to docetaxel combination therapy, showing an anticancer immune response. Those with high T cell receptor signaling responded better to anti-HER2 therapy, while activation of the extracellular matrix/PI3K-AKT pathway reduced the effectiveness of trastuzumab. The study found that CTSE enhances chemosensitivity to docetaxel, while TKTL1 reduces it.
Prognostic models were developed to predict therapeutic responses with high accuracy and validated in an independent cohort. This research offers valuable insights into the mechanisms and indicators of chemotherapy and targeted therapy in GC.
Human Papillomavirus Type 16 E6 Promotes Cervical Cancer Proliferation by Upregulating Transketolase Enzymatic Activity Through the Activation of Protein Kinase B
Over 99% of precancerous cervical lesions are linked to HPV, with types 16 and 18 present in over 70% of cervical cancer cases. The E6 gene of HPV16, which degrades p53, contributes to cancer but doesn’t fully explain HPV16’s oncogenic effects. This study explored additional targets of HPV16 E6.
We found significant changes in nonoxidative pentose phosphate pathway (PPP) metabolites in HPV16-positive cells. In HPV-negative cervical cancer cells (C33A), HPV16 E6 increased cell proliferation by activating the nonoxidative PPP and upregulating the enzyme transketolase (TKT) via AKT activation. TKT is highly expressed in cervical cancer and linked to poor prognosis.
Using the TKT inhibitor oxythiamine (OT) reduced tumor growth, with even better results when combined with cisplatin (DDP). Thus, HPV16 E6 promotes cervical cancer growth by enhancing TKT activity through AKT activation, and OT, especially with DDP, shows promise in inhibiting HPV16-positive cervical cancer.
Acidosis-medicated Increase in IFN-y-induced PD-L1 Expression on Cancer Cells as an Immune Escape Mechanism in Solid Tumors
Immune checkpoint inhibitors are effective cancer treatments but often limited by the tumor microenvironment (TME). This study shows that tumor acidity increases PD-L1 expression on cancer cells, helping them evade the immune system. Acidosis boosts IFN-γ activity, leading to higher PD-L1 levels.
Researchers found that neutralizing acidity with sodium bicarbonate reduced PD-L1 expression and tumor growth in responsive tumors. This effect was absent in nonresponsive tumors and IFN-γ-deficient mice.
These findings suggest tumor acidity and IFN-γ-induced PD-L1 are key to immune escape, offering potential biomarkers and new strategies to improve immunotherapy.
Metbolic Regulation of Homologous Recombinaton Repair by MRE11 Lactylation
Lactylation, where lactate attaches to proteins, affects their function. This study found that MRE11, a key DNA repair protein, is lactylated at K673 when DNA is damaged, aiding its ability to repair DNA through homologous recombination (HR). Blocking the enzymes CBP or LDH reduced this lactylation, impairing HR and making cancer cells more sensitive to chemotherapy. A peptide blocking MRE11 lactylation also increased cancer cells’ sensitivity to treatments like cisplatin. These findings suggest that targeting MRE11 lactylation could enhance cancer therapy effectiveness
Metabolic Management of Microenvironment Acidity in Glioblastoma
Glioblastoma (GBM) relies on fermentation metabolism for biomass and energy production, despite the tumor’s cellular and genetic diversity. This shift from respiration to fermentation is due to defects in mitochondrial structure and function in GBM tissue. Glucose and glutamine are the primary fuels for GBM growth. The waste products of GBM fermentation (lactic acid, glutamic acid, and succinic acid) acidify the tumor microenvironment, contributing to drug resistance, increased invasion, immunosuppression, and metastasis.
Current GBM treatments (surgery, radiation, chemotherapy, and steroids) further acidify the microenvironment, promoting tumor recurrence and complications. Restricting glucose and glutamine while increasing non-fermentable, anti-inflammatory ketone bodies can restore pH balance and provide a non-toxic strategy to kill cancer cells.
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