RESUMEN
Little is known about how metabolites couple tissue-specific stem cell function with physiology. Here we show that, in the mammalian small intestine, the expression of Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2), the gene encoding the rate-limiting enzyme in the production of ketone bodies, including beta-hydroxybutyrate (ßOHB), distinguishes self-renewing Lgr5+ stem cells (ISCs) from differentiated cell types. Hmgcs2 loss depletes ßOHB levels in Lgr5+ ISCs and skews their differentiation toward secretory cell fates, which can be rescued by exogenous ßOHB and class I histone deacetylase (HDAC) inhibitor treatment. Mechanistically, ßOHB acts by inhibiting HDACs to reinforce Notch signaling, instructing ISC self-renewal and lineage decisions. Notably, although a high-fat ketogenic diet elevates ISC function and post-injury regeneration through ßOHB-mediated Notch signaling, a glucose-supplemented diet has the opposite effects. These findings reveal how control of ßOHB-activated signaling in ISCs by diet helps to fine-tune stem cell adaptation in homeostasis and injury.
Asunto(s)
Dieta Alta en Grasa , Cuerpos Cetónicos/metabolismo , Células Madre/metabolismo , Ácido 3-Hidroxibutírico/sangre , Ácido 3-Hidroxibutírico/farmacología , Anciano de 80 o más Años , Animales , Diferenciación Celular/efectos de los fármacos , Autorrenovación de las Células , Femenino , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Hidroximetilglutaril-CoA Sintasa/deficiencia , Hidroximetilglutaril-CoA Sintasa/genética , Hidroximetilglutaril-CoA Sintasa/metabolismo , Intestinos/citología , Intestinos/patología , Masculino , Ratones , Ratones Noqueados , Receptores Acoplados a Proteínas G/metabolismo , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Células Madre/citología , Adulto JovenRESUMEN
This paper aims to elucidate the differentially coexpressed genes, their potential mechanisms, and possible drug targets in low-grade invasive serous ovarian carcinoma (LGSC) in terms of the biologic continuity of normal, borderline, and malignant LGSC. We performed a bioinformatics analysis, integrating datasets generated using the GPL570 platform from different studies from the GEO database to identify changes in this transition, gene expression, drug targets, and their relationships with tumor microenvironmental characteristics. In the transition from ovarian epithelial cells to the serous borderline, the FGFR3 gene in the "Estrogen Response Late" pathway, the ITGB2 gene in the "Cell Adhesion Molecule", the CD74 gene in the "Regulation of Cell Migration", and the IGF1 gene in the "Xenobiotic Metabolism" pathway were upregulated in the transition from borderline to LGSC. The ERBB4 gene in "Proteoglycan in Cancer", the AR gene in "Pathways in Cancer" and "Estrogen Response Early" pathways, were upregulated in the transition from ovarian epithelial cells to LGSC. In addition, SPP1 and ITGB2 genes were correlated with macrophage infiltration in the LGSC group. This research provides a valuable framework for the development of personalized therapeutic approaches in the context of LGSC, with the aim of improving patient outcomes and quality of life. Furthermore, the main goal of the current study is a preliminary study designed to generate in silico inferences, and it is also important to note that subsequent in vitro and in vivo studies will be necessary to confirm the results before considering these results as fully reliable.
RESUMEN
BACKGROUND: The objective of our study was to determine the role of retinoic acid receptor gamma (RARG) rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 single-nucleotide polymorphisms in identifying the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumors. METHODS: A total of 60 pediatric patients who had completed their treatment at least 2 years ago and 50 healthy children matched for age and sex were included in the study. All patients were evaluated for cardiotoxicity by echocardiography. The blood samples were analyzed for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms. Demographic characteristics, echocardiographic parameters, and genetic results of both groups were evaluated. RESULTS: In our study, the RARG rs2229774 AA genotype was associated with cardiotoxicity ( P =0.017). The SLC28A3 rs7853758 AA+GA genotype was detected more frequently in patients who did not develop cardiotoxicity ( P <0.023). Furthermore, the frequency of the SLC28A3 rs7853758 A allele was significantly lower in the cardiotoxicity group ( P <0.025). CONCLUSIONS: This is the first study in the Turkish population to investigate the correlation between the cardiotoxicity risk and 3 marker genes, which are recommended in the pharmacogenetic guideline for risk assessment in pediatric doxorubicin patients. The gene polymorphism that we investigated in this study was useful for the early prediction of cardiotoxicity risk.
Asunto(s)
Cardiotoxicidad , Neoplasias , Niño , Humanos , Antraciclinas , Cardiotoxicidad/genética , Doxorrubicina/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Polimorfismo de Nucleótido SimpleRESUMEN
It is a well-known fact that dietary fiber is recognized as one of the essential components of a healthy diet. The aim of this paper was to investigate the impact of dietary fiber on the incidence and mortality of various types of cancer, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. We identified meta-analyses that particularly focused on the association between dietary fiber consumption and the risk/mortality of cancer. A structured and comprehensive computer literature search was undertaken in the electronic databases PubMed/Medline, Web of Science (WoS), and Scopus. The search yielded a total of 25 papers and 28 reports. In the pooled analysis, higher dietary fiber consumption was associated with a 22% lower cancer risk (OR = 0.78, 95% CI: 0.74-0.83, p < 0.001) and a 17% lower mortality (RR = 0.83, 95% CI: 0.78-0.90, p < 0.001). In the secondary meta-meta-analysis, it was observed that there was an inverse association between dietary fiber intake and digestive tract cancers (OR = 0.68, 95% CI: 0.62-0.76) and breast cancer (OR = 0.92, 95% CI: 0.90-0.94). Taken together, this paper suggests that promoting a high-fiber diet may be an effective strategy for the prevention and management of cancer.
RESUMEN
Colorectal cancer (CRC) is the third most common cancer worldwide with a high mortality rate. Dietary fibers, both soluble and insoluble, are essential for reducing the risk of CRC. In this study, a meta-analysis was performed to examine the relationship between the soluble and insoluble dietary fiber consumption and CRC risk. The highest vs. lowest fiber concentrations were compared by using PRISMA guidelines. To determine publishing bias, the Egger test; assess study heterogeneity I2 statistics were used. Studies that reported adjusted relative risk estimates with 95% confidence intervals (Cl) for the associations of interest were included. The results reveal that the relationship between soluble and insoluble fiber intake and the risk of CRC is almost equal [The total fiber ES = 0.75 (95% CI = 0.66-0.86), soluble fiber ES = 0.78 (95% CI = 0.66-0.92), insoluble fiber ES = 0.77 (95% CI = 0.67-0.88)]. Funnel plot and Egger's linear regression tests demonstrated that there was no publication bias. Both soluble and insoluble fiber consumption appear to be protective against CRC, with a clinically significant reduction in CRC risk. It is critical to identify preventive steps to avoid the CRC development, especially by leading a healthier lifestyle that includes healthy diet.
Asunto(s)
Neoplasias Colorrectales , Fibras de la Dieta , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Humanos , Riesgo , Factores de RiesgoRESUMEN
The incidence of cancer has exhibited an increasing trend in recent years because of many reasons such as environmental and nutritional factors. There is a great need for the development of new and natural molecules with lower side effects in the therapy of cancer. It was aimed to evaluate the antiproliferative effect of semi-purified triterpene glycosides of Holothuria poli on different human cancer cell lines. The body walls of H. poli as the main sources of saponins were used and the saponin content of the extract was characterized by MALDI-TOF/MS. The antiproliferation activity of the characterized extract was tested on cancer cell lines. The extract showed antiproliferative effect on the studied cancer cell lines. The mass analysis results reveal that Holothurin A is one of the saponins within the extract. The measured IC50 values were found as 31.41 ± 2.20, 77.45 ± 0.23, and 34.79 ± 0.90 µg mL-1 for HT-29, UPCI-SCC-131, and T84 cell lines, respectively. H. poli secretes not only specific saponins but also a cocktail of them. Specific versus. cocktails of the saponins and by also applying organic modification must be studied in further research to understand their mechanisms in the antiproliferation studies since this paper reveals promising results.
Asunto(s)
Holothuria , Saponinas , Triterpenos , Animales , Línea Celular Tumoral , Holothuria/metabolismo , Humanos , Estructura Molecular , Extractos Vegetales/metabolismo , Saponinas/farmacología , Triterpenos/farmacologíaRESUMEN
Biological invasion is the successful spread and establishment of a species in a novel environment that adversely affects the biodiversity, ecology, and economy. Both invasive and non-invasive species of the Caulerpa genus secrete more than thirty different secondary metabolites. Caulerpin is one of the most common secondary metabolites in genus Caulerpa. In this study, caulerpin found in invasive Caulerpa cylindracea and non-invasive Caulerpa lentillifera extracts were analyzed, quantified, and compared using high-performance thin layer chromatography (HPTLC) for the first time. The anticancer activities of caulerpin against HCT-116 and HT-29 colorectal cancer (CRC) cell lines were also tested. Caulerpin levels were found higher in the invasive form (108.83 ± 5.07 µg mL-1 and 96.49 ± 4.54 µg mL-1). Furthermore, caulerpin isolated from invasive Caulerpa decreased cell viability in a concentration-dependent manner (IC50 values were found between 119 and 179 µM), inhibited invasion-migration, and induced apoptosis in CRC cells. In comparison, no cytotoxic effects on the normal cell lines (HDF and NIH-3T3) were observed. In conclusion, HPTLC is a quick and novel method to investigate the caulerpin levels found in Caulerpa extracts, and this paper proposes an alternative utilization method for invasive C. cylindracea due to significant caulerpin content compared to non-invasive C. lentillifera.
Asunto(s)
Alcaloides , Caulerpa , Neoplasias Colorrectales , Humanos , Indoles/farmacología , Caulerpa/química , Alcaloides/farmacología , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Background/aim: Natural products are popular insights for researchers to investigate promising anti-cancer agents since some of these substances have lesser adverse effects restricting the treatment than traditional chemotherapeutic agents. A well-known monoterpene Carvacrol, widely consumed in Mediterranean cuisine and lower risks of cancer, has efficient anticancer effects. However, the mechanism of action is yet to be discovered. Materials and methods: The investigation aims to illuminate a new perceptive in the role of this substance on colorectal cancer treatment, by the means of differences in a well-defined range of soluble factors. Carvacrol effect on both HT-29 and HCT-116 cell lines was evaluated on proliferation and the IC50 values were calculated by the RTCA xCELLigence device. Then MAGPIX assay was performed to obtain the changes in soluble factors of the cell lines. Results: The Multiplexing assay suggests some of these factors were altered in favor of surviving and proliferation in aggressive cell line HCT-116 whereas they were altered against these characters in HT-29, were correlated with the increased IC50 concentration of HCT- 116 in carvacrol treatment. Conclusion: The current study indicates that differences in the levels of these soluble factors could modulate the anticancer effect related to carvacrol.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Cimenos/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/química , Neoplasias Colorrectales/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Células HCT116 , Células HT29 , Humanos , Leptina/análisis , Prolactina/análisis , Factor de Crecimiento Transformador alfa/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisisRESUMEN
Background: The diagnostic and prognostic clinical value of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in pancreatic malignancies are unclear. Herein, we aimed to perform a meta-analysis to evaluate ctDNA and cfDNA as potential diagnostic and prognostic biomarkers. Methods: PRISMA reporting guidelines were followed closely for conducting the current meta-analysis. The PubMed/Medline, Scopus, and Web of Science (WoS) databases were scanned in detail to identify eligible papers for the study. A quality assessment was performed in accordance with the REMARK criteria. The risk ratios (RRs) of the diagnostic accuracy of ctDNA compared to that of carbohydrate antigen 19.9 (CA 19.9) in all disease stages and the hazard ratios (HRs) of the prognostic role of ctDNA in overall survival (OS) were calculated with 95% confidence intervals (CIs). Results: A total of 18 papers were evaluated to assess the diagnostic accuracy and prognostic value of biomarkers related to pancreatic malignancies. The pooled analysis indicated that CA19.9 provides greater diagnostic accuracy across all disease stages than ctDNA or cfDNA (RR = 0.64, 95% CI: 0.50-0.82, p < 0.001). Additionally, in a secondary analysis focusing on prognosis, patients who were ctDNA-positive were found to have significantly worse OS (HR = 2.00, 95% CI: 1.51-2.66, p < 0.001). Conclusion: The findings of this meta-analysis demonstrated that CA19-9 still has greater diagnostic accuracy across all disease stages than KRAS mutations in ctDNA or cfDNA. Nonetheless, the presence of detectable levels of ctDNA was associated with worse patient outcomes regarding OS. There is a growing need for further research on this topic. Systematic review registration: https://doi.org/10.37766/inplasy2023.12.0092, identifier INPLASY2023120092.
RESUMEN
Objectives: Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments. Methods: We determined the effects of current therapy options using a 3D static disease model on human colon carcinoma cell lines (HCT 116) and transforming growth factor-ß1 induced epithelial-to-mesenchymal transition (EMT) HCT 116 lines at 37⯰C and 42⯰C for 30, 60, and 120â¯min. We determined oxaliplatin's half maximal inhibitory concentrations in a 3D static culture by using viability assay. Clinical practices of HIPEC were applied in the developed model. Results: EMT-induced HCT 116 cells were less sensitive to oxaliplatin treatment compared to non-induced cells. We observed increased cytotoxicity when increasing the temperature from 37⯰C to 42⯰C and extending the treatment duration from 30 to 120â¯min. We found that 200â¯mg/m2 oxaliplatin administered for 120â¯min is the most effective HIPEC treatment option within the framework of clinic applications. Conclusions: The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening.
RESUMEN
Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified. Network clustering and pathway enrichments were applied to gene modules to prioritize potential targets, which were shortlisted by independent validation. Finally, drug-target interaction search led to three agents for primary and liver metastatic CRC phenotypes. Hesperadin and BAY-1217389 suppress colony formation over a 14-day period, with Hesperadin showing additional efficacy in reducing cell viability within 48 h. As both candidates target the G2/M phase proteins NEK2 or TTK, we confirmed their anti-proliferative properties by Ki-67 staining. Hesperadinin particular arrested the cell cycle at the G2/M phase. IL-29A treatment reduced migration and invasion capacities of TGF-ß induced metastatic cell lines. In addition, this anti-metastatic treatment attenuated TGF-ß dependent mesenchymal transition. Network analysis suggests IL-29A induces the JAK/STAT pathway in a preventive manner.
Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Indoles , Neoplasias Hepáticas , Neoplasias del Recto , Sulfonamidas , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transcriptoma , Quinasas Janus/metabolismo , Transducción de Señal , Factores de Transcripción STAT/metabolismo , Neoplasias del Colon/genética , Neoplasias del Recto/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Quinasas Relacionadas con NIMA/genéticaRESUMEN
During the COVID-19 pandemic, cancer patients were among the most vulnerable patient groups to the SARS-CoV-2 infection effects. This paper aimed to conduct an umbrella review and meta-meta-analysis to determine the severity of disease in cancer patients affected by COVID-19. The umbrella review and meta-meta-analysis were undertaken according to the PRISMA and MOOSE guidelines. The PubMed/Medline, Web of Science, and Scopus databases were searched for published papers from the start of the pandemic through July 18, 2022. The pooled effect sizes (ES) and odds ratios (ORs) were calculated using a random effect model in the 95% confidence interval (CI) for ICU (Intensive Care Unit) admissions and mortality in cancer patients infected with SARS-CoV-2. Egger's linear regression test, schematic illustrations of funnel plots, and Begg and Mazumdar's rank correlation tests were used to quantify the possibility of publication bias. The pooled ES was calculated based on 1,031,783 participants, and mortality was significantly increased in cancer patients affected by COVID-19 (OR = 2.02, %95 CI: 1.74-2.35, p < 0.001). The pooled ES for ICU admission was also significantly increased in cancer patients infected with SARS-CoV-2 (OR = 1.84, %95 CI: 1.44-2.34, p < 0.001). As a result, this synthesis of systematic reviews and meta-analyses by the meta-meta-analysis method revealed that disease severity is higher in cancer patients affected by COVID-19. Since cancer patients are a more sensitive and specific patient group, they should be evaluated more carefully, especially during the COVID-19 pandemic and other pandemics that may occur in the future.
Asunto(s)
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiología , Neoplasias/complicaciones , Neoplasias/epidemiología , Pandemias , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, particularly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence, using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was undertaken in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses (59 reports yielded from these studies) assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% confidence interval (CI): 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality; however, careful evaluation according to cancer types is critically important and recommended.
Asunto(s)
Neoplasias Pulmonares , Vitamina D , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitaminas , Calcifediol , Estudios EpidemiológicosRESUMEN
BACKGROUND: Epithelial-mesenchymal transition (EMT) plays an important role in the biological and biochemical processes of cells, and it is a critical process in the malignant transformation, and mobility of cancer. Additionally, EMT is one of the main mechanisms contributing to chemoresistance. Resistance to oxaliplatin (OXA) poses a momentous challenge in the chemotherapy of advanced colorectal cancer (CRC) patients, highlighting the need to reverse drug resistance and improve patient survival. In this study, we explored the response of cyanidin-3-O-glucoside (C3G), the most abundant anthocyanin in plants, on the mechanisms of drug resistance in cancer, with the purpose of overcoming acquired OXA resistance in CRC cell lines. METHODS: We generated an acquired OXA-resistant cell line, named HCT-116-ROx, by gradually exposing parental HCT-116 cells to increasing concentrations of OXA. To characterize the resistance, we performed cytotoxicity assays and shape factor analyses. The apoptotic rate of both resistant and parental cells was determined using Hoechst 33342/Propidium Iodide (PI) fluorescence staining. Migration capacity was evaluated using a wound-healing assay. The mesenchymal phenotype was assessed through qRT-PCR and immunofluorescence staining, employing E-cadherin, N-cadherin, and Vimentin markers. RESULTS: Resistance characterization announced decreased OXA sensitivity in resistant cells compared to parental cells. Moreover, the resistant cells exhibited a spindle cell morphology, indicative of the mesenchymal phenotype. Combined treatment of C3G and OXA resulted in an augmented apoptotic rate in the resistant cells. The migration capacity of resistant cells was higher than parental cells, while treatment with C3G decreased the migration rate of HCT-116-ROx cells. Analysis of EMT markers showed that HCT-116-ROx cells exhibited loss of the epithelial phenotype (E-cadherin) and gain of the mesenchymal phenotype (N-cadherin and Vimentin) compared to HCT-116 cells. However, treatment of resistant cells with C3G reversed the mesenchymal phenotype. CONCLUSION: The morphological observations of cells acquiring oxaliplatin resistance indicated the loss of the epithelial phenotype and the acquisition of the mesenchymal phenotype. These findings suggest that EMT may contribute to acquired OXA resistance in CRC. Furthermore, C3G decreased the mobility of resistant cells, and reversed the EMT process, indicating its potential to overcome acquired OXA resistance.
Asunto(s)
Fenómenos Bioquímicos , Neoplasias Colorrectales , Humanos , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Antocianinas/farmacología , Antocianinas/uso terapéutico , Vimentina/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Cadherinas/metabolismo , Fenotipo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Transición Epitelial-Mesenquimal , Resistencia a Antineoplásicos , Movimiento CelularRESUMEN
One of the most common extracranial solid tumors in childhood is neuroblastoma. In this study, it was aimed to perform a systematic review and meta-analysis to evaluate the risk of neuroblastoma in both high and low birth weights. The PRISMA and MOOSE guidelines were followed during the design, analysis, and reporting of this study. A comprehensive literature search was undertaken for the published papers in Embase, PubMed/Medline, Scopus, and the Web of Science (WoS) databases. The odds ratio (OR) of neuroblastoma in high and low birth weight groups, with 95% confidence intervals (CIs), were calculated using the random-effects and fixed-effects models. A total of 16 papers and 4,361,141 participants were included in this study. When the random-effects model and the fixed-effects model were used, high birth weight was associated with an increased risk of neuroblastoma (OR = 1.17; 95% CI: 1.06-1.29, P = 0.002; heterogeneity: Chi2 = 2.33, df = 15, I2 = 0%, P>0.05). Similarly, it was observed that individuals with low birth weights may also face an increased risk of developing neuroblastoma later in life (OR = 1.19; 95% CI: 1.03-1.37, P = 0.017; heterogeneity: Chi2 = 16.93, df = 15, I2 = 0%, P = 0.323). In conclusion, both high and low birth weight in individuals may be among the important risk factors for neuroblastoma development.
RESUMEN
Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin's cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients.
RESUMEN
BACKGROUND: Hepatocyte growth factor is a cytokine secreted by the stromal cells in the tumor microenvironment. There is little information about the clinical significance of serum hepatocyte growth factor level in patients diagnosed with pancreatobiliary cancer. The objective of the current study was to investigate the relationship between serum hepatocyte growth factor level with inflammation markers and the clinical features of patients with pancreatobiliary cancer. METHODS: A total of 62 patients with pancreatobiliary cancer were included in this study. Serum hepatocyte growth factor concentrations were evaluated utilizing the enzyme-linked immunosorbent assay method. RESULTS: The median serum hepatocyte growth factor level was 329.1 ng/mL (1.4-1051.1). The patients were categorized into 2 groups as those below the median hepatocyte growth factor level (low hepatocyte growth factor) and those above the median hepatocyte growth factor level (high hepatocyte growth factor). While 40.9% of the patients without metastasis were observed to be in the high hepatocyte growth factor group, 72.2% of the metastatic patients were observed to be in the high hepatocyte growth factor group (P = .025). The median levels of monocyte, monocyte-to-lymphocyte ratio, C-reactive protein, and C-reactive protein-to-albumin ratio were found to be significantly higher in the high hepatocyte growth factor group as compared to the low hepatocyte growth factor group (P < .050). CONCLUSION: The significant relationship between serum hepatocyte growth factor level and systemic inflammation markers in patients with pancreatobiliary cancer is shown for the first time in our study. This study, which showed a significant relationship between the presence of metastasis and serum hepatocyte growth factor level, suggests that serum hepatocyte growth factor level may be a prognostic biomarker in patients who are diagnosed with pancreatobiliary cancer.
Asunto(s)
Neoplasias Gastrointestinales , Factor de Crecimiento de Hepatocito , Humanos , Proteína C-Reactiva , Biomarcadores , Inflamación , Biomarcadores de Tumor/metabolismo , Pronóstico , Microambiente TumoralRESUMEN
BACKGROUND: Circulating tumor cells (CTCs) are cancer cells which separate from the primary tumor and enter systemic circulation. In this study, it was aimed to examine the relationship between CTCs isolated and identified from the peripheral blood of patients with pancreatobiliary cancer, with the clinicopathological characteristics of the patients and their overall survival. METHODS: A total of 21 patients were included the study. Density gradient centrifugation with the OncoQuick® assay was performed for isolation of CTCs from peripheral blood. In order to identify CTCs, enriched samples underwent flow cytometric analysis. RESULTS: The rate of patients with positive surgical margin in the high CTC group (CTC <15) was identified to be statistically significantly high compared to the group with low CTC (CTC ≤15) (83.3% vs. 16.7%; P = .041). Median neutrophil/lymphocyte ratio (NLR) was found to be higher in the high CTC group compared to the low CTC group, which was close to statistical significance (2.37 vs. 1.41; P = .055). CONCLUSIONS: Circulating tumor cells were identified to have a significant relationship with surgical margin positivity in our study for the first time, suggesting that the CTCs count in peripheral blood in preoperative patients may be a biomarker predicting positive surgical margin. Due to the very low number of studies assessing the relationship between CTCs and NLR, our study which identified relationship close to statistical significance between CTCs and NLR, significantly contributes to the literature on the topic of the possible role of lymphocytes in CTC clearance.
Asunto(s)
Neoplasias Gastrointestinales , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Pronóstico , Márgenes de Escisión , Biomarcadores de TumorRESUMEN
Introduction: Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC. Methods: One hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene. Results: Mutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy. Discussion: The results showed that "liquid biopsy" is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.
RESUMEN
Caulerpa spp. secrete more than thirty different bioactive chemicals which have already been used in cancer treatment research since they play a pivotal role in cancer metabolism. Colorectal cancer is one of the most common cancer types, thus using novel and effective chemicals for colorectal cancer treatment is crucial. In the cheminformatics pipeline of this study, ADME-Tox and drug-likeness tests were performed for filtering the secondary metabolites of Caulerpa spp. The ligands which were selected from the ADME test were used for in silico molecular docking studies against the enzymes of the oxidative branch of the pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphoglutarate dehydrogenase), which is of great importance for colorectal cancer, by using AutoDock Vina. Pharmacophore modeling was carried out to align the molecules. Molecular dynamic simulations were performed for each target to validate the molecular docking studies and binding free energies were calculated. According to the ADME test results, 13 different secondary metabolites were selected as potential ligands. Molecular docking studies revealed that vina scores of caulerpin and monomethyl caulerpinate for G6PDH were found as -10.6 kcal mol-1, -10.5 kcal mol-1, respectively. Also, the vina score of caulersin for 6PGD was found as -10.7 kcal mol-1. The highest and the lowest binding free energies were calculated for monomethyl caulerpinate and caulersin, respectively. This in silico study showed that caulerpin, monomethyl caulerpinate, and caulersin could be evaluated as promising marine phytochemicals against pentose phosphate pathway enzymes and further studies are recommended to investigate the detailed activity of these secondary metabolites on these targets.