Amplitude Modulated Radiofrequency Electromagnetic Field Treatment Combined With TAS-102 (Lonsurf) in Refractory Metastatic Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Refractory Metastatic Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 69709 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. We conducted a retrospective multicenter study to assess the effectiveness and safety of TAS-102 in consecutive patients with pretreated mCRC. In particular, we estimated the effectiveness and safety of TAS-102 in elderly patients (aged ≥70, ≥75 and ≥80 years) and in special subgroups, e.g., patients with concomitant heart disease. One hundred and sixty patients were enrolled. In particular, 71 patients (44%) were 70 years of age or older, 50 (31%) were 75 years of age or older, and 23 (14%) were 80 years of age or older. 19 patients (12%) had a concomitant chronic heart disease, three (2%) patients were HIV positive, and one (<1%) patient had a DPYD gene polymorphism. In 115 (72%) cases TAS-102 was administered as a third-line treatment. The median overall survival (OS) in the overall population was 8 months (95% confidence interval [CI], 6-9), while the median progression-free survival (PFS) was 3 months (95% CI, 3-4). No significant age-related reduction in effectiveness was observed in the subpopulations of elderly patients included. The toxicity profile was acceptable in both the whole and subgroups' population. Our study confirms the effectiveness and safety of TAS-102 in patients with pretreated mCRC, suggesting a similar risk-benefit profile in the elderly.
| S-EPMC10340604 | biostudies-literature
Project description:<p>With the rapid development of 5G networks, the influence of the radiofrequency field (RF) generated from 5G communication equipment on human health are gathering increasing attention. This study aimed at assessing the effects of long-term exposure to 4.9 GHz (one of the working frequency of 5G communication) RF field on fecal microbiome and metabolome profiles in 9-week-old male C57BL/6 mice. The animals were divided into sham group (n = 8) and radiofrequency group (RF group; n = 8), then whole body exposed or sham exposed to RF field for one hour per day during 3 weeks (21 days) at whole body Specific Absorption Rate (SAR) of 6.3 W/kg. After RF exposure, the mice fecal samples were collected to detect gut microorganisms and metabolites by 16S rRNA gene sequencing method and LC-MS method, respectively. The results showed that intestinal microbial compositions were altered in RF group, as evidenced by reduced microbial diversity and changed microbial community distribution. Metabolomics profiling identified 258 significantly differentially abundant metabolites in RF group, 57 of which can be classified to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Besides, functional correlation analysis showed that changes in gut microbiota genera were significantly correlated with changes in fecal metabolites. In summary, the results suggested that altered gut microbiota and metabolic profile are associated with 4.9 GHz radiofrequency exposure.</p>
2022-11-08 | MTBLS4186 | MetaboLights
Project description:We used RNA-sequencing to identify differentially expressed genes in the midgut of Aedes aegypti that contribute to the field derivied dengue susceptible (Cali-S) and dengue refractory (Cali-R) phenotypes
2020-05-01 | GSE90974 | GEO
Project description:This study assessed changes in gene expression in 7 mouse brain regions using Illumina Mouse WG-6 (v2) beadchips after exposure to 1.9 GHz pulse-modulated radiofrequency field exposure for 4h/day for 5 days. High dose RF field exposure was whole body average SAR and brain average SAR were 1.45 W/kg and 0.16 W/kg, respectively. Total RNA isolated from the amygdala, auditory cortex, caudate, cerebellum, hippocampus, hypothalamus and medial prefrontal cortex of 1.9 GHz pulse-modulated radiofrequency field exposed mice and compared to that in sham (handled) exposed animals. An unhandled control group was also included in the study design. A total of 20 RNA samples (5 independent biological tissues for each of 4 treatment groups) were collected for each brain region. When analysis of gene expression was conducted within individual brain regions when controlling the false discovery rate (FDR), no differentially expressed genes were identified relative to the sham control. However, it must be noted that most fold changes among groups were observed to be less than 1.5 fold and this study had limited ability to detect such small changes. While some genes were differentially expressed without correction for multiple-comparisons testing, no consistent pattern of response was observed among different RF-exposure levels or among different RF-modulations. The current study provides the most comprehensive analysis of potential gene expression changes in the rodent brain in response to RF field exposure conducted to date. Within the exposure conditions and limitations of this study, no convincing evidence of consistent changes in gene expression was found in response to 1.9 GHz pulse-modulated RF field exposure.
2016-04-22 | E-MTAB-4674 | biostudies-arrayexpress
Project description:This study assessed changes in gene expression in 7 mouse brain regions using Illumina Mouse WG-6 (v2) beadchips after exposure to 1.9 GHz continuous-wave radiofrequency field exposure for 4h/day for 5 days. High dose RF field exposure was whole body average SAR and brain average SAR were 1.36 W/kg and 0.19 W/kg, respectively. Total RNA isolated from the amygdala, caudate, cerebellum, hippocampus, hypothalamus and medial prefrontal cortex of 1.9 GHz continuous-wave radiofrequency field exposed mice and compared to that in sham (handled) exposed animals. An unhandled control group was also included in the study design. A total of 20 RNA samples (5 independent biological tissues for each of 4 treatment groups) were collected for each brain region. When analysis of gene expression was conducted within individual brain regions when controlling the false discovery rate (FDR), no differentially expressed genes were identified relative to the sham control. However, it must be noted that most fold changes among groups were observed to be less than 1.5 fold and this study had limited ability to detect such small changes. While some genes were differentially expressed without correction for multiple-comparisons testing, no consistent pattern of response was observed among different RF-exposure levels or among different RF-modulations. The current study provides the most comprehensive analysis of potential gene expression changes in the rodent brain in response to RF field exposure conducted to date. Within the exposure conditions and limitations of this study, no convincing evidence of consistent changes in gene expression was found in response to 1.9 GHz pulse-modulated RF field exposure.
2016-04-22 | E-MTAB-4675 | biostudies-arrayexpress
Project description:BackgroundsAs a new oral chemotherapy drug, TAS-102 is currently recommended as the third-line treatment for metastatic colorectal cancer (mCRC). Recently, studies have reported the efficacy of TAS-102 combined with bevacizumab in colon cancer patients after standard treatment fails. Here, we evaluated the efficacy and safety of TAS-102 combined with bevacizumab versus TAS-102 as a single agent by a systematic review and a meta-analysis.MethodsPubMed, Web of Science and Cochrane libraries were searched. Studies involving bevacizumab combined with TAS-102 in mCRC were included. Study characteristics (author, year of publication, country et al.), efficacy (disease control rate(DCR), progression-free survival(PFS), overall survival(OS)) and adverse effects were extract from studies. Forest plots were created based on Cox model analysis.ResultsAfter screening 550 studies, a total of 3 studies were included, which compared the safety and effectiveness of TAS-102 with or without bevacizumab. Analysis based on Cox regression showed that the combined treatment group had advantages in 6-month (OR= 2.93, 95% CI: 1.72 to 5.00, P<0.0001), 12-month(OR= 2.18, 95% CI: 1.24 to 3.81, P=0.006), and 18-month (OR=3.08, 95% CI: 1.34 to 7.12, P=0.008) OS. The combined treatment group demonstrated superiority in 6-month PFS rates (OR= 2.50, 95% CI: 1.18 to 5.31, P=0.02). The incidence of thrombocytopenia in the dual-drug treatment group was higher (OR= 1.96, 95% CI: 1.14 to 3.36 P=0.01). The proportion of serious adverse events were similar in tow groups (OR= 1.01, 95% CI: 0.76 to 1.34 P=0.93).ConclusionBevacizumab combined with TAS-102 could improve the prognosis of patients with mCRC who have failed standard treatment. In terms of side effects, the addition of bevacizumab did not increase serious adverse reactions, but the occurrence of thrombocytopenia was worth noting.
| S-EPMC8637322 | biostudies-literature
Project description:Background:Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods:We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results:In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P?=?0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P?=?0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P?=?0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P?=?0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion:Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
| S-EPMC5834058 | biostudies-literature
Project description:Transcriptomic data for 48 and 120 hpf zebrafish embryos developmentally exposed to 3.5 GHz of radiofrequency radiation.
2022-04-20 | GSE197627 | GEO
Project description:Radiofrequency heat ablation is an ideal radical cure for HCC treatment; however, insufficient radiofrequency ablation (IRFA) could lead to a high recurrence rate. N7-methylguanosine (m7G) on tRNAs is a heat-responding modification that is critical for yeast survival under high temperature, while its function and mechanism in HCC recurrence after IRFA are unknown. Here, we found that IRFA significantly up-regulates the level of m7G tRNA modification and its methyltransferase complex components METTL1 and WDR4 in multiple systems including HCC patient-derived xenograft (PDX) mouse, HCC tissues of patients, sublethal-heat-treated models of HCC cell lines and organoids. Functionally, gain- or loss-of function assays showed that METTL1 mediated m7G tRNA modification promotes HCC metastasis under sublethal heat exposure both in vitro and in vivo. Mechanistically, we found that METTL1 and m7G tRNA modification enhance the translation of SLUG and SNAIL in a codon frequency dependent manner under sublethal heat exposure. Overexpression of SLUG and SNAIL rescued the malignant potency of METTL1 knockdown HCC cells after sublethal heat stress. Our study uncovers the important physiological functions of m7G tRNA modification in heat stress responses and HCC recurrence after IRFA and suggests that targeting METTL1-m7G-SLUG and SNAIL axis could be a promising strategy to prevent HCC metastasis after radiofrequency heat ablation treatment.
2022-11-20 | GSE199966 | GEO
Project description:High-throughput RNA-seq analysis was performed using fresh residual CT26 tumors 3 days after incomplete radiofrequency abaltion (iRFA) as well as control tumors. We ound genes encoding damage-associated molecular patterns molecules (DAMPs), proinflammatory cytokines, chemokines, and genes associated with immunosuppression were overexpressed in the iRFA-treated tumor, indicating iRFA elicits inflammation and induces immunosuppression in residual tumors.
2019-10-02 | GSE138224 | GEO