scholarly journals Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis

2016 ◽  
Vol 17 (2) ◽  
pp. 209 ◽  
Author(s):  
Roland Croner ◽  
Müzeyyen Sevim ◽  
Metodi Metodiev ◽  
Peter Jo ◽  
Michael Ghadimi ◽  
...  
2020 ◽  
Vol 10 (3) ◽  
pp. 190-197
Author(s):  
A. B. Baichorov ◽  
A. O. Rasulov

The aim of the study was to compare functional results prior to and following neoadjuvant chemoradiation therapy.Materials and methods. An analysis of the functional results of a prospective clinical study was carried out. The study included 90 patients who underwent low anterior rectal resection for cancer of the lower or middle ampullar rectum with T1-4aN0-2M0 using various reconstruction methods.Results and discussion. Group A included 22 patients with J-shaped reservoirs; group B — 30 patients with side-to-end anastomoses; group C — 38 patients with end-to-end anastomoses. Out of the total study group (n = 90), 43 patients underwent neoadjuvant chemoradiotherapy vs. 47 patients without any preoperative treatment. No statistically significant difference was observed in the frequency of applied reconstructive techniques (р = 0.725) and the incidence of postoperative complications (p = 0.103) in the groups with and without neoadjuvant chemoradiotherapy. The baseline scores of the Wexner scale and the results of anorectal manometry in the comparison groups were comparable (p > 0.05). However, upon completion of neoadjuvant chemoradiotherapy and during the period from the moment of surgery up to 12 months after the closure of preventive intestinal stomas, the functional results were less satisfactory in the group of patients having received neoadjuvant chemoradiotherapy (n = 43) with regard to the comparison group (n =  47). Nevertheless, a statistically significant difference in the results was observed from the end of neoadjuvant chemoradiotherapy up to 3 months after closure of the stoma (p <0.05).Conclusions. Neoadjuvant chemoradiation therapy has a negative effect on the function of the anal sphincter, thus requiring concomitant therapy and physiotherapy both at the stages of neoadjuvant chemoradiotherapy and at long intervals after the main surgical stage. 


2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.


2021 ◽  
Vol 3 (3) ◽  
pp. 100-112
Author(s):  
Sarah Martinez Roth ◽  
Eveline E. Vietsch ◽  
Megan E. Barefoot ◽  
Marcel O. Schmidt ◽  
Matthew D. Park ◽  
...  

Thoracic high-dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.


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