bims-medica Biomed News
on Metabolism and diet in cancer
Issue of 2024–12–29
fifteen papers selected by
Brett Chrest, Wake Forest University
  1. Optimized MALDI2-Mass Spectrometry Imaging for Stable Isotope Tracing of Tissue-Specific Metabolic Pathways in Mice.
  2. Restoring Mitochondrial Quantity and Quality to Reverse Warburg Effect and Drive Tumor Differentiation.
  3. Metabolic Adaptations To Acute Glucose Uptake Inhibition Converge Upon Mitochondrial Respiration For Leukemia Cell Survival.
  4. Limiting serine availability during tumor progression promotes muscle wasting in cancer cachexia.
  5. The Mitochondrial Lactate Oxidation Complex: endpoint for carbohydrate carbon disposal.
  6. Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet.
  7. Modifiable Risk Factors for Breast Cancer: Insights From Systematic Reviews.
  8. Systematic review of nutrition interventions in older patients with cancer: A synthesis of evidence and a future research priority.
  9. Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells.
  10. A Comprehensive Metabolomic and Microbial Analysis Following Dietary Amino Acid Reduction in Mice.
  11. Nutritional interventions in randomised clinical trials for people with incurable solid cancer: A systematic review.
  12. Not So Fast: Intermittent Fasting Fails to Improve Metabolic Flexibility in Mice With Obesity and Type 2 Diabetes.
  13. Association between glucose to lymphocyte ratio and prognosis in patients with solid tumors.
  14. A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models.
  15. Dietary polyunsaturated fatty acids and gastric cancer.
  1. Anal Chem. 2024 Dec 27.
    Optimized MALDI2-Mass Spectrometry Imaging for Stable Isotope Tracing of Tissue-Specific Metabolic Pathways in Mice.
    Yanyan Chen, Yuanyuan Song, Zhu Yang, Yi Ru, Peisi Xie, Jing Han, Xuyang Chai, Jianing Wang, Zongwei Cai.
      Spatial stable isotope tracing metabolic imaging is a cutting-edge technique designed to investigate tissue-specific metabolic functions and heterogeneity. Traditional matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) techniques often struggle with low coverage of low-molecular-weight (LMW) metabolites, which are often crucial for spatial metabolic studies. To address this, we developed a high-coverage spatial isotope tracing metabolic method that incorporates optimized matrix selection, sample preparation protocols, and enhanced post-ionization (MALDI2) techniques. We employed this approach to mouse kidney, brain, and breast tumors to visualize the spatial dynamics of metabolic flow. Our results revealed diverse regional distributions of nine labeled intermediates derived from 13C6-glucose across glycolysis, glycogen metabolism, and the tricarboxylic acid (TCA) cycle in kidney tissues. In brain sections, we successfully mapped six intermediates from the TCA cycle and glutamate-glutamine (Glu-Gln) cycle simultaneously in distinct neurological regions. Furthermore, in breast cancer tumor tissues, our approach facilitated the mapping of nine metabolic intermediates in multiple pathways, including glycolysis, the pentose phosphate pathway (PPP), and the TCA cycle, illustrating metabolic heterogeneity within the tumor microenvironment. This methodology enhances metabolite coverage, enabling more comprehensive imaging of isotope-labeled metabolites and opening new avenues for exploring the metabolic landscape in various biological contexts.
    DOI:  https://doi.org/10.1021/acs.analchem.4c04600
  2. Res Sq. 2024 Dec 13. pii: rs.3.rs-5494402. [Epub ahead of print]
    Restoring Mitochondrial Quantity and Quality to Reverse Warburg Effect and Drive Tumor Differentiation.
    Jiangbin Ye, Haowen Jiang, Sarah Tiche, Clifford He, Junyan Liu, Fuyun Bian, Mohamed Jedoui, Balint Forgo, Md Tauhidul Islam, Meng Zhao, Pamela Emengo, Bo He, Yang Li, Albert Li, Anh Truong, Jestine Ho, Cathyrin Simmermaker, Yanan Yang, Meng-Ning Zhou, Zhen Hu, Katrin Svensson, Daniel Cuthbertson, Florette Hazard, Lei Xing, Hiroyuki Shimada, Bill Chiu.
      Reduced mitochondrial quality and quantity in tumors is associated with dedifferentiation and increased malignancy. However, it remains unclear how to restore mitochondrial quantity and quality in tumors, and whether mitochondrial restoration can drive tumor differentiation. Our study shows that restoring mitochondrial function using retinoic acid (RA) to boost mitochondrial biogenesis and a mitochondrial uncoupler to enhance respiration synergistically drives neuroblastoma differentiation and inhibits proliferation. U-13C-glucose/glutamine isotope tracing revealed a metabolic shift from the pentose phosphate pathway to oxidative phosphorylation, accelerating the TCA cycle and switching substrate preference from glutamine to glucose. These effects were reversed by ETC inhibitors or in ρ0 cells lacking mtDNA, emphasizing the necessity of mitochondrial function for differentiation. Dietary RA and uncoupler treatment promoted tumor differentiation in an orthotopic neuroblastoma xenograft model, evidenced by neuropil production and Schwann cell recruitment. Single-cell RNA sequencing analysis of the orthotopic xenografts revealed that this strategy effectively eliminated the stem cell population, promoted differentiation, and increased mitochondrial gene signatures along the differentiation trajectory, which could potentially significantly improve patient outcomes. Collectively, our findings establish a mitochondria-centric therapeutic strategy for inducing tumor differentiation, suggesting that maintaining/driving differentiation in tumor requires not only ATP production but also continuous ATP consumption and sustained ETC activity.
    DOI:  https://doi.org/10.21203/rs.3.rs-5494402/v1
  3. bioRxiv. 2024 Nov 22. pii: 2024.11.20.624567. [Epub ahead of print]
    Metabolic Adaptations To Acute Glucose Uptake Inhibition Converge Upon Mitochondrial Respiration For Leukemia Cell Survival.
    Monika Komza, Jesminara Khatun, Jesse D Gelles, Andrew P Trotta, Ioana Abraham-Enachescu, Juan Henao, Ahmed Elsaadi, Andriana G Kotini, Cara Clementelli, JoAnn Arandela, Sebastian El Ghaity-Beckley, Agneesh Barua, Yiyang Chen, Bridget K Marcellino, Eirini P Papapetrou, Masha V Poyurovsky, Jerry Edward Chipuk.
      One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems. Our results reveal that while several metabolic adaptations occur in response to acute glucose uptake inhibition, the most critical is increased mitochondrial oxidative phosphorylation. KL-11743 treatment efficiently blocks the majority of glucose uptake and glycolysis, yet markedly increases mitochondrial respiration via enhanced Complex I function. Compared to partial glucose uptake inhibition, dependency on mitochondrial respiration is less apparent suggesting robust blockage of glucose uptake is essential to create a metabolic vulnerability. When wild-type and oncogenic RAS patient-derived induced pluripotent stem cell acute myeloid leukemia (AML) models were examined, KL-11743 mediated induction of mitochondrial respiration and dependency for survival associated with oncogenic RAS. Furthermore, we examined the therapeutic potential of these observations by treating a cohort of primary AML patient samples with KL-11743 and witnessed similar dependency on mitochondrial respiration for sustained cellular survival. Together, these data highlight conserved adaptations to acute glucose uptake inhibition in diverse leukemic models and AML patient samples, and position mitochondrial respiration as a key determinant of treatment success.
    DOI:  https://doi.org/10.1101/2024.11.20.624567
  4. Cell Death Discov. 2024 Dec 21. 10(1): 510
    Limiting serine availability during tumor progression promotes muscle wasting in cancer cachexia.
    Erica Pranzini, Livio Muccillo, Ilaria Nesi, Alice Santi, Caterina Mancini, Giulia Lori, Massimo Genovese, Tiziano Lottini, Giuseppina Comito, Anna Caselli, Annarosa Arcangeli, Lina Sabatino, Vittorio Colantuoni, Maria Letizia Taddei, Paolo Cirri, Paolo Paoli.
      Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of body weight occurring in about 80% of cancer patients, frequently representing the leading cause of death. Dietary intervention is emerging as a promising therapeutic strategy to counteract cancer-induced wasting. Serine is the second most-consumed amino acid (AA) by cancer cells and has emerged to be strictly necessary to preserve skeletal muscle structure and functionality. Here, we demonstrate that decreased serine availability during tumor progression promotes myotubes diameter reduction in vitro and induces muscle wasting in in vivo mice models. By investigating the metabolic crosstalk between colorectal cancer cells and muscle cells, we found that incubating myotubes with conditioned media from tumor cells relying on exogenous serine consumption triggers pronounced myotubes diameter reduction. Accordingly, culturing myotubes in a serine-free medium induces fibers width reduction and suppresses the activation of the AKT-mTORC1 pathway with consequent impairment in protein synthesis, increased protein degradation, and enhanced expression of the muscle atrophy-related genes Atrogin1 and MuRF1. In addition, serine-starved conditions affect myoblast differentiation and mitochondrial oxidative metabolism, finally inducing oxidative stress in myotubes. Consistently, serine dietary deprivation strongly strengthens cancer-associated weight loss and muscle atrophy in mice models. These findings uncover serine consumption by tumor cells as a previously undisclosed driver in cancer cachexia, opening new routes for possible therapeutic approaches.
    DOI:  https://doi.org/10.1038/s41420-024-02271-1
  5. Am J Physiol Endocrinol Metab. 2024 Dec 23.
    The Mitochondrial Lactate Oxidation Complex: endpoint for carbohydrate carbon disposal.
    Robert G Leija, Jose A Arevalo, Dianna Xing, José Pablo Vázquez-Medina, George A Brooks.
      The Lactate Shuttle concept has revolutionized our understanding and study of metabolism in physiology, biochemistry, metabolism, nutrition, and medicine. Seminal findings of the Mitochondrial Lactate Oxidation Complex (mLOC) elucidated the architectural structure of its components. Here, we report that the mitochondrial pyruvate carrier (mPC) is an additional member of the mLOC in mouse muscle and C2C12 myoblasts and myotubes. Immunoblots, mass spectrometry, and co-immunoprecipitation experiments of mitochondrial preparations revealed abundant amounts of mitochondrial lactate dehydrogenase (mLDH), monocarboxylate transporter (mMCT), basigin (CD147), cytochrome oxidase (COx), and pyruvate carriers 1 and 2 (mPC1 and 2). Additionally, using confocal laser scanning microscopy (CLSM) and in situ proximity ligation, we also demonstrated planar and 3D colocalization of pyruvate and lactate transporters with COx in fixed skeletal muscle sections, myotubes, and C2C12 myoblasts. This work serves as a landmark for configuring the final pathway of carbohydrate oxidation.
    Keywords:  Lactate; Lactate Shuttle; Mitochondral Reticulum; Pyruvate; Skeletal Muscle
    DOI:  https://doi.org/10.1152/ajpendo.00306.2024
  6. Cell Stem Cell. 2024 Dec 12. pii: S1934-5909(24)00413-2. [Epub ahead of print]
    Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet.
    Salma Merchant, Animesh Paul, Amanda Reyes, Daniel Cassidy, Ashley Leach, Dohun Kim, Sarah Muh, Gerik Grabowski, Gerta Hoxhaj, Zhiyu Zhao, Sean J Morrison.
      Fatty acid oxidation is of uncertain importance in most stem cells. We show by 14C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice. Young HSPCs had the plasticity to oxidize other substrates, including glutamine, and compensated for loss of fatty acid oxidation by decreasing pyruvate dehydrogenase phosphorylation, which should increase function. This metabolic plasticity declined as mice aged, when CPT1a or HADHA deficiency altered hematopoiesis and impaired hematopoietic stem cell (HSC) function upon serial transplantation. A high-fat diet increased fatty acid oxidation and reduced HSC function. This was rescued by CPT1a or HADHA deficiency, demonstrating that increased fatty acid oxidation can undermine HSC function. Long-chain fatty acid oxidation is thus dispensable in young HSCs but necessary during aging and deleterious with a high-fat diet.
    Keywords:  aging; fatty acid; hematopoiesis; high-fat diet; metabolic plasticity; metabolism; mitochondria; β-oxidation
    DOI:  https://doi.org/10.1016/j.stem.2024.11.014
  7. Public Health Nurs. 2024 Dec 22.
    Modifiable Risk Factors for Breast Cancer: Insights From Systematic Reviews.
    Xuehua Li, He Zhang, He Yang, Yingli Song, Fengpei Zhang, Aiping Wang.
       OBJECTIVE: To conduct a comprehensive review of reversible factors associated with breast cancer, with the aim of offering insights for the creation of early intervention strategies for breast cancer prevention.
    METHODS: The PubMed, EMBASE, and Scopus databases were systematically searched to collect systematic reviews and meta-analyses related to breast cancer risk. Searches were limited to literature published from the inception of each database up to May 1, 2024. Two investigators independently screened the literature, extracted data, and assessed the methodological quality and evidence synthesis of the studies included in our review.
    RESULTS: We included 31 systematic reviews in our analysis, and breast cancer risk factors were divided into four categories: diet and lifestyle habits, reproductive and familial factors, body weight and physical activity, and environmental and miscellaneous factors.
    CONCLUSION: Our findings suggest that a high-fat diet, low intake of dietary fiber, alcohol consumption, smoking, and obesity are linked to a higher risk of breast cancer. Conversely, physical activity and breastfeeding appear to lower breast cancer risk. However, the methodological and evidence quality of the reviewed studies was generally low, necessitating caution in the application of these findings. Additionally, there is a need for more research into lifestyle interventions to better develop and advocate for effective breast cancer prevention strategies.
    Keywords:  breast cancer; lifestyle; overview of systematic reviews; risk factors
    DOI:  https://doi.org/10.1111/phn.13504
  8. J Geriatr Oncol. 2024 Dec 26. pii: S1879-4068(24)00454-5. [Epub ahead of print] 102181
    Systematic review of nutrition interventions in older patients with cancer: A synthesis of evidence and a future research priority.
    Brenton J Baguley, Hannah Arnold, Ashlee Bence, Emma Bryant, Eliza Martino, Kiara Stojanoski, Samantha Ackerly, Erin Laing, Jessica Jong, Nicole Kiss, Jenelle Loeliger.
       INTRODUCTION: Older patients with cancer (65 years and older) are a growing population with unique nutrition-and treatment-related issues that accelerate aging. Nutrition interventions attenuate nutritional decline, muscle loss, and risk of malnutrition and sarcopenia in patients with cancer, however the evidence for older patients with cancer is limited. The aim of this systematic review was to evaluate the efficacy of nutrition interventions on nutritional status, body weight/composition and clinical outcomes in older patients with cancer and to identify future research priority areas.
    MATERIALS AND METHODS: Three databases were systematically searched from inception until January 2024. Eligible studies were randomised controlled trials (RCT) evaluating a nutrition intervention in older patients with cancer that reported nutrition-related and clinical outcomes. Studies including older patients were determined by the mean age ≥ 65 years with the error to the mean > 60 years. Between-group differences in nutritional and clinical outcomes were extracted.
    RESULTS: Eleven studies describing nine RCTs were included in this review. Three trials specifically included patients 65 years and older. Most interventions intended to reduce malnutrition risk across a mix of cancer types and treatments, and one trial was designed to reduce comorbidities after treatment. Changes in dietary intake (n = 4), nutrition status (n = 1), weight (n = 5), and muscle mass (n = 3) were inconsistently reported, but preliminary evidence showed dietary counselling with oral nutrition supplements (ONS) resulted in improved weight maintenance in patients with pancreatic cancer. There was limited evidence of a benefit from nutrition interventions on treatment tolerance or quality of life. The heterogeneous findings in methodological design, including dietary prescription and frequency of consultations and reporting of outcomes, inhibits evidence-based recommendations for older adults with cancer.
    DISCUSSION: Nutrition interventions designed specifically to address nutrition-related issues unique to older patients with cancer is a clear research priority. Research specifically targeting older patients post treatment, a period during which treatment-related side effects still occur, is limited. To support the growing population of older patients with cancer, future research must consistently report the dietary prescription, adherence to nutritional requirements, and clearly-defined nutrition-related parameters and clinical outcomes that are specific to older patients.
    Keywords:  Geriatric; Malnutrition; Nutrition; Older cancer patients; Sarcopenia
    DOI:  https://doi.org/10.1016/j.jgo.2024.102181
  9. Cancer Cell Int. 2024 Dec 26. 24(1): 432
    Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells.
    Barbara Guerra, Kristina Jurcic, Rachelle van der Poel, Samantha Lynn Cousineau, Thomas K Doktor, Laura M Buchwald, Scott E Roffey, Caroline A Lindegaard, Anna Z Ferrer, Mohammad A Siddiqui, Laszlo Gyenis, Brage S Andresen, David W Litchfield.
       BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a type of cancer characterized by a vast intracellular accumulation of lipids that are critical to sustain growth and viability of the cells in the tumour microenvironment. Stearoyl-CoA 9-desaturase 1 (SCD-1) is an essential enzyme for the synthesis of monounsaturated fatty acids and consistently overexpressed in all stages of ccRCC growth.
    METHODS: Human clear cell renal cell carcinoma lines were treated with small-molecule inhibitors of protein kinase CK2. Effects on the expression levels of SCD-1 were investigated by RNA-sequencing, RT-qPCR, Western blot, and in vivo studies in mice. Phase-contrast microscopy, fluorescence microscopy, flow cytometry, and MALDI-mass spectrometry analysis were carried out to study the effects on endogenous lipid accumulation, induction of endoplasmic reticulum stress, rescue effects induced by exogenous MUFAs, and the identity of lipid populations. Cell proliferation and survival were investigated in real time employing the Incucyte® live-cell analysis system. Statistical significance was determined by applying the two-tailed Student's t test when comparing two groups of data whereas the two-way ANOVA, multiple Tukey's test was employed for multiple comparisons.
    RESULTS: Here, we show that protein kinase CK2 is critical for preserving the expression of SCD-1 in ccRCC lines maintained in culture and heterotransplanted into nude mice. Consistent with this, pharmacological inhibition of CK2 leads to induction of endoplasmic reticulum stress linked to unfolded protein response activation and decreased proliferation of the cells. Both effects could be reversed by supplementing the growth medium with oleic acid indicating that these effects are specifically caused by reduced expression of SCD-1. Analysis of lipid composition by MALDI-mass spectrometry revealed that inhibition of CK2 results in a significant accumulation of the saturated palmitic- and stearic acids.
    CONCLUSIONS: Collectively, our results revealed a previously unidentified molecular mechanism regulating the synthesis of monounsaturated fatty acids corroborating the notion that novel therapeutic approaches that include CK2 targeting, may offer a greater synergistic anti-tumour effect for cancers that are highly dependent on fatty acid metabolism.
    Keywords:  CK2; Clear cell renal cell carcinoma; SCD-1; fatty acids; sunitinib
    DOI:  https://doi.org/10.1186/s12935-024-03611-y
  10. Metabolites. 2024 Dec 14. pii: 706. [Epub ahead of print]14(12):
    A Comprehensive Metabolomic and Microbial Analysis Following Dietary Amino Acid Reduction in Mice.
    Raghad Khalid Al-Ishaq, Carmen R Ferrara, Nisha Stephan, Jan Krumsiek, Karsten Suhre, David C Montrose.
      Introduction: Nutritional metabolomics provides a comprehensive overview of the biochemical processes that are induced by dietary intake through the measurement of metabolite profiles in biological samples. However, there is a lack of deep phenotypic analysis that shows how dietary interventions influence the metabolic state across multiple physiologic sites. Dietary amino acids have emerged as important nutrients for physiology and pathophysiology given their ability to impact cell metabolism. Methods: The aim of the current study is to evaluate the effect of modulating amino acids in diet on the metabolome and microbiome of mice. Here, we report a comprehensive metabolite profiling across serum, liver, and feces, in addition to gut microbial analyses, following a reduction in either total dietary protein or diet-derived non-essential amino acids in mice. Results: We observed both distinct and overlapping patterns in the metabolic profile changes across the three sample types, with the strongest signals observed in liver and serum. Although amino acids and related molecules were the most commonly and strongly altered group of metabolites, additional small molecule changes included those related to glycolysis and the tricarboxylic acid cycle. Microbial profiling of feces showed significant differences in the abundance of select species across groups of mice. Conclusions: Our results demonstrate how changes in dietary amino acids influence the metabolic profiles across organ systems and the utility of metabolomic profiling for assessing diet-induced alterations in metabolism.
    Keywords:  16S; amino acids; bacteria; diet; metabolomics; nutrition; protein
    DOI:  https://doi.org/10.3390/metabo14120706
  11. Clin Nutr. 2024 Dec 06. pii: S0261-5614(24)00449-7. [Epub ahead of print]44 201-219
    Nutritional interventions in randomised clinical trials for people with incurable solid cancer: A systematic review.
    Amy Mcluskie, Megan Bowers, Jo Bayly, Michael S Yule, Matthew Maddocks, Marie Fallon, Richard Je Skipworth, Barry J A Laird.
       BACKGROUND & AIMS: Malnutrition is highly prevalent in those with cancer and more so in those with incurable cancer. In incurable cancer, it is widely agreed that optimal nutritional care has the potential to positively impact patient and caregiver distress and oncological outcomes. The aim of this systematic review was to describe the diversity and frequency of nutritional interventions, whether given in isolation or as part of a multimodal intervention in those with incurable cancer, in randomised controlled trials. The secondary aims were to describe adherence and their efficacy.
    METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The following databases were searched electronically: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulated Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL) with the time frame from January 2000 to 7th September 2023. Eligible studies included adult patients (≥18 years) diagnosed with incurable solid cancer with a sample size ≥40. Studies were to be primary research and delivered for at least 14 days to allow for efficacy. They were to include a nutritional intervention encompassing at least one of the following: dietary counselling, oral nutritional supplements (ONS), enteral tube feeding and/or parenteral nutrition (PN), given in isolation or as part of a multi-modal intervention. Studies were excluded if the population contained patients who had completed curative treatment or are being treated with curative intent, haematological cancers, or if they examined the effects of micronutrients, proteins, amino acids or fatty acids given in isolation. The quality of the included studies was assessed using the Cochrane risk of bias tool for randomised trials (RoB2). A balloon plot was produced to present the results in addition to a table with a narrative summary of the primary outcomes.
    RESULTS: A total of 7968 studies were identified, of which 18 met the eligibility criteria. This included 2720 study participants. The included studies comprised: multimodal interventions (n = 7), dietary counselling (n = 2), nutritional supplementation with or without dietary counselling (n = 7) and PN (n = 2). Primary outcomes included quality of life (QoL), body composition and nutritional status. For QoL, this was reported in 15 studies, 4 studies showed a significant improvement. Body composition was evaluated in 15 studies, 5 of which showed a significant improvement in body weight and two in fat-free mass (FFM). Nutritional status was reported in 6 studies with one showing a significant difference in Patient-Generated Subjective Global Assessment (PG-SGA) score. The risk of bias was deemed 'low' in 6 studies, with 'some concerns' in 10 studies and a 'high risk' in 2 studies. There was heterogeneity between the studies.
    CONCLUSION: This systematic review has highlighted some positive findings in regard to QoL, body weight and nutritional intake. Optimum nutritional intervention was not identified. Future studies should evaluate the effectiveness of earlier nutritional interventions at the point of diagnosis, including regular reviews and the impact this has on nutritional outcomes, QoL and overall survival (OS).
    Keywords:  Advanced cancer; Body composition; Incurable cancer; Nutrition; Nutritional status; Quality of life
    DOI:  https://doi.org/10.1016/j.clnu.2024.12.008
  12. Physiology (Bethesda). 2024 Dec 24.
    Not So Fast: Intermittent Fasting Fails to Improve Metabolic Flexibility in Mice With Obesity and Type 2 Diabetes.
    Meghan O Conn, Daniel M Marko, Jonathan D Schertzer.
      
    Keywords:  Insulin; Intermittent Fasting; Metabolism; Obesity; Type 2 Diabetes
    DOI:  https://doi.org/10.1152/physiol.00060.2024
  13. Front Immunol. 2024 ;15 1454393
    Association between glucose to lymphocyte ratio and prognosis in patients with solid tumors.
    Rongqiang Liu, Yankun Shen, Jiahui Cui, Wangbin Ma, Jianguo Wang, Chen Chen, Weixing Wang.
       Background: Glucose-to-lymphocyte ratio (GLR) plays an important role in the prognosis of various tumors. The aim of this study was to comprehensively evaluate the prognostic value of GLR in solid tumors through the meta-analysis.
    Methods: A comprehensive search of eligible studies was performed by scrutinizing the Pubmed, Embase and Web of science databases until May 30, 2024. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate overall survival (OS), disease-free survival (DFS) and recurrence free survival (RFS).
    Results: A total of 22 studies from 14 articles involving 9472 patients were included in the study. The pooled analysis showed that cancer patients with high GLR was significantly associated with unfavorable OS (HR:1.48,95% CI:1.34-1.63) and DFS/RFS (HR:2.20,95% CI:1.66-2.92). Subgroup analysis further showed that high GLR had better predictive value in liver cancer (HR:2.66, 95%CI:1.80-3.93), breast cancer (HR:2.13, 95%CI:1.10-4.13) and pancreatic cancer (HR:1.92, 95%CI:1.30-2.84).
    Conclusions: GLR can be used as an effective prognostic marker in patients with solid tumors.
    Keywords:  glucose-to-lymphocyte ratio; meta-analysis; prognosis; survival; tumor
    DOI:  https://doi.org/10.3389/fimmu.2024.1454393
  14. Cancer Lett. 2024 Dec 19. pii: S0304-3835(24)00799-7. [Epub ahead of print]611 217404
    A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models.
    Maaike Van Trimpont, Amanda M Schalk, Kenneth Hofkens, Evelien Peeters, Sara T'Sas, Katrien Vandemeulebroecke, Ying Su, Ashley De Loera, Alyssa Garcia, Hui Chen, Tim Lammens, Pieter Van Vlierberghe, Steven Goossens, Arnon Lavie.
      L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity. EBD-200 showed comparable anti-cancer effects to PEGylated L-ASNase in ASNSlow ALL, melanoma and liver cancer models, with improved tolerability. Its potent anti-cancer efficacy and enhanced safety profile suggest that EBD-200 could benefit ALL patients and broaden treatment options for ASNSlow solid cancers.
    Keywords:  (Max 7); ASNS(low) solid tumors; Acute lymphoblastic leukemia; Asparagine synthetase; Liver cancer; Melanoma
    DOI:  https://doi.org/10.1016/j.canlet.2024.217404
  15. Eur J Cancer Prev. 2024 Dec 06.
    Dietary polyunsaturated fatty acids and gastric cancer.
    Ngoan Tran Le, Yen Thi-Hai Pham, Linh Thuy Le, Nguyen Ha Ta, Chung Thi-Kim Le, Xingyi Guo, Jennifer Cullen, Hung N Luu.
      Polyunsaturated fatty acids (PUFAs) are fatty acids, containing more than one double bond and have both anti-inflammatory properties and inhibit tumor progression effects as well as carcinogenic properties. There is inconclusive evidence regarding the effect of PUFA intake on gastric cancer in diverse populations. We, therefore, aimed to determine the association between PUFA intake and risk of gastric cancer in a hospital-based case-control study comprising 1182 incident cases of gastric cancer and 2965 controls in Vietnam. A semiquantitative validated food frequency questionnaire was used to derive PUFA intake. Unconditional logistic regression model was applied to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer in relation to PUFA intake. Overall, there was a dose-response inverse association between PUFA intake and gastric cancer risk (ORper-SD increment = 0.72, 95% CI: 0.65-0.79; Ptrend < 0.001). Compared with quintile 1 (the lowest quintile), the ORs and respective 95% CIs of gastric cancer for quintiles 2, 3, 4, and 5 of the PUFA intake were 0.65 (0.52-0.80), 0.51 (0.41-0.64), 0.47 (0.37-0.59), and 0.37 (0.28-0.48), respectively. A similar pattern was observed in both sexes and individuals aged <60 years and those aged 60 years or older. In summary, we found a risk reduction of gastric cancer in individuals with a higher intake of PUFA in the Vietnamese population, regardless of sex or age. Our findings have great implications for the prevention and control programs against gastric cancer in low-middle-income countries and similar limited-resource settings.
    DOI:  https://doi.org/10.1097/CEJ.0000000000000941
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