Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Chen Ding
PROVIDER: PXD046566 | iProX | Mon Oct 30 00:00:00 GMT 2023
REPOSITORIES: iProX
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Project description:The molecular mechanisms of clinical response or resistance to therapy were evaluated in colorectal cancer patients in a prospective biomarker discovery project. Rectal adenocarcinomas, biopsied before (diagnostic biopsy) and after (surgical resection) pre-operative short-course radiotherapy [RT] or 5-flurouracil (5-FU)-based chemoradiotherapy [CRT], were profiled using Affymetrix HGU133 Plus 2.0 microarrays. Tumour tissues from untreated controls at diagnosis and surgical resection were used to identify treatment-independent gene expression changes. Candidate resistance biomarkers were identified in this pilot study for validation in a larger cohort.
2009-11-10 | E-MEXP-1901 | biostudies-arrayexpress
Project description:Dynamics of Breast Cancer under Different Rates of Chemoradiotherapy.
Mkango SB1, Shaban N1, Mureithi E1, Ngoma T2.
Author information
1
Department of Mathematics, University of Dar es Salaam, P.O. Box 35062, Dar es Salaam, Tanzania.
2
Department of Clinical Oncology, Muhimbili University of Health and Allied Sciences, P.O. Box 65000, Dar es Salaam, Tanzania.
Abstract
A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast cancer in Tanzania. We determine new treatment strategies, and finally, we show that when sufficient amount of chemotherapy and radiotherapy with a low decay rate is used, the drug will be significantly more effective in combating the disease while health cells remain above the threshold.
Copyright © 2019 Sara B. Mkango et al.
2020-01-20 | MODEL1912120005 | BioModels
Project description:Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. Specimens from 46 rectal cancer patients who approved to receive preoperative chemoradiotherapy were studied. We prospectively collected biopsy specimens during colonoscopic examination from rectal cancer before starting preoperative chemoradiotherapy. Specimens from tumors were snap-frozen in liquid nitrogen and stored at -80 C until use. Paralleled tumor specimens were formalin fixed and paraffin embedded for histologic examination and other specimens were used for RNA extraction. RNA was extracted from tumor tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. All patients received a total dose of 50.4 Gy of radiation, UFT(300-500mg/day) and LV (75mg/day) and underwent standardized curative resection, following an interval of 4 weeks after chemoradiotherapy.
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Project description:Neoadjuvant anlotinib combined with PD-1 blockade therapy can prolong the survival of patients, but the underlying mechanisms for the failure of patients to benefit from combination therapy remain to be explored. To explore the mechanism of drug resistance and predict patient response, we performed scRNA-seq from 6 NSCLC patients, including 3 post-treatment patients with major pathological response (MPR), and 3 Non-MPR patients to observe and analyze the dynamic changes of immune cells, stromal cells and cancer cells from the NSCLC patients who received neoadjuvant anlotinib combined with PD-1 blockade therapy and verified in an independent cohort.
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Project description:Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.
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Project description:Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.
2024-01-07 | GSE164427 | GEO
Project description:Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.
2024-01-07 | GSE164426 | GEO
Project description:Background: Immunotherapy has been employed in the neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma. To assess the feasibility of neoadjuvant radiotherapy combined with immunotherapy (NRIT), this study compares the efficacy and effectiveness of neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) and NRIT, while also exploring the underlying mechanisms of NRIT. Methods:This study retrospectively analyzed a cohort of 64 patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant therapy followed by esophagectomy between January 2019 and September 2023. Of these, 26 patients received neoadjuvant radiotherapy and immunotherapy (NRIT), while 38 patients were treated with neoadjuvant chemoradiotherapy (NICRT). The final analysis included pathological complete response (pCR), major pathological response (MPR), tumor regression grade (TRG), the rate of positive lymph node pCR, toxicity, surgical outcomes, postoperative complications, disease-free survival (DFS), and overall survival (OS). Additionally, paraffin-embedded tissue sections obtained before and after neoadjuvant NRIT were subjected to whole-exome sequencing, transcriptome sequencing, and immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) analysis. Results: There was no significant difference in the rates of MPR and PCR (28.95% vs 30.77%, P=0.873), TRG classification (P=0.338), surgical outcomes, or postoperative complications (P=0.148), as well as overall survival (OS) and disease-free survival (DFS) between the NICRT and NRIT groups. However, a notable difference was observed in grade 3 or higher adverse events during treatment, with the NICRT group experiencing a higher incidence (34.21% vs 7.69%, P = 0.017) and severe hematological toxicity (23.68% vs 0.00%, P = 0.008). In the NRIT group, patients with high CPS scores demonstrated improved pathological responses. Pre-treatment genomic analyses indicated no differences in tumor mutation burden (TMB), somatic mutations, and copy number variations between MPR and non-MPR patients post-surgery. Transcriptome analysis revealed a significant number of differentially expressed genes in patients before and after treatment, closely associated with key pathways related to immunity. Following treatment, MPR patients exhibited a marked upregulation of the type I interferon response and the MHC class I antigen presentation pathway. Additionally, the number of B cells and monocytes increased, while non-MPR patients showed a significant downregulation of dendritic cells (DCs) after treatment, alongside the activation of various immune cells, including CD8 naïve cells, NK cells, and B cells. Conclusion: There was no significant difference between the NRIT group and the NICRT group regarding pathological response, surgical outcomes, postoperative complications, and survival analysis; furthermore, NRIT demonstrated a better safety profile compared to NICRT during treatment. Additionally, the mechanism of action of NRIT has been elucidated through a comprehensive analysis of genomic, transcriptomic, immunohistochemical, and other methods in conjunction with clinical results, thereby establishing NRIT as a neoadjuvant treatment that is both effective and safe.
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