Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA853539 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19904954_1.fastq.gz | Fastqsanger.gz | |||
| SRR19904954_2.fastq.gz | Fastqsanger.gz | |||
| SRR19904955_1.fastq.gz | Fastqsanger.gz | |||
| SRR19904955_2.fastq.gz | Fastqsanger.gz | |||
| SRR19904956_1.fastq.gz | Fastqsanger.gz |
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Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
2022-05-01 | PXD027668 | Pride
Project description:Surgical ablation or radiation of tumor-draining lymph nodes can eliminate the primary tumor response to immunotherapy, indicating that local tumor response to immunotherapy is mediated by tumor-draining lymph nodes. Here, we show that immunoradiotherapy efficacy is dependent on immune cell migration from tumor to sentinel lymph nodes. Using a tamoxifen-inducible reporter paired with CITE-sequencing in a murine model of oral cancer, we characterized tumor immune cellular migration through lymphatic channels to sentinel lymph nodes at single-cell resolution. Within a structured approach of sequential immunomodulatory radiotherapy and checkpoint inhibition, we demonstrate that lymphatic-sparing, tumor-directed radiotherapy followed by PD-1 inhibition achieves complete and durable tumor responses. Mechanistically, this treatment approach enhances activated, migratory CCR7+ dendritic cell surveillance across the tumor-sentinel lymph node axis, revealing a shift from their canonical role in promoting tolerance to driving antitumor immunity. Overall, this work supports rationally sequencing immune-sensitizing, lymphatic-preserving, tumor-directed radiotherapy followed by immune checkpoint inhibition to optimize the tumor response. By characterizing the tumor-sentinel lymph node immunomigratome that drives durable antitumor response, we reveal a therapeutic opportunity to enhance the response to immunotherapy by optimizing activated dendritic cell migration to tumor-draining sentinel nodes.
2025-06-07 | GSE276434 | GEO
Project description:Surgical ablation or radiation of tumor-draining lymph nodes can eliminate the primary tumor response to immunotherapy, indicating that local tumor response to immunotherapy is mediated by tumor-draining lymph nodes. Here, we show that immunoradiotherapy efficacy is dependent on immune cell migration from tumor to sentinel lymph nodes. Using a tamoxifen-inducible reporter paired with CITE-sequencing in a murine model of oral cancer, we characterized tumor immune cellular migration through lymphatic channels to sentinel lymph nodes at single-cell resolution. Within a structured approach of sequential immunomodulatory radiotherapy and checkpoint inhibition, we demonstrate that lymphatic-sparing, tumor-directed radiotherapy followed by PD-1 inhibition achieves complete and durable tumor responses. Mechanistically, this treatment approach enhances activated, migratory CCR7+ dendritic cell surveillance across the tumor-sentinel lymph node axis, revealing a shift from their canonical role in promoting tolerance to driving antitumor immunity. Overall, this work supports rationally sequencing immune-sensitizing, lymphatic-preserving, tumor-directed radiotherapy followed by immune checkpoint inhibition to optimize the tumor response. By characterizing the tumor-sentinel lymph node immunomigratome that drives durable antitumor response, we reveal a therapeutic opportunity to enhance the response to immunotherapy by optimizing activated dendritic cell migration to tumor-draining sentinel nodes.
2025-06-07 | GSE276437 | GEO
Project description:RATIONALE: Diagnostic procedures, such as lymph node mapping during surgery and sentinel lymph node biopsy, may help doctors find micrometastases and predict cancer recurrence.
PURPOSE: This phase II trial is studying how well lymph node mapping during surgery together with sentinel lymph node analysis and blood testing work in detecting and predicting early micrometastases in patients with colorectal cancer.
| 2051412 | ecrin-mdr-crc
Project description:Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage ≥T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis.
2011-07-15 | GSE30688 | GEO
Project description:Gene expression signatures for B cells from tumor draining lymph node and normal lymph node
| PRJNA320737 | ENA
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Molecular Biomarkers Screened by Next-generation RNA Sequencing for non-sentinel lymph node status predicting in breast cancer patients with metastatic sentinel lymph node
| PRJNA272156 | ENA
Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC. Using AB1700 system, we determined the gene expression profiles of lymph nodes with metastasis of OSCC. Normal lymph node and salivary gland tissues were used as control samples.
2015-12-21 | E-GEOD-70604 | biostudies-arrayexpress
Project description:Several studies have demonstrated that melanoma-derived exosomes home in sentinel lymph nodes favoring metastasis. Here, we determined the proteomic signature in exosomes derived from lymph node metastatic models. We found a signature of genes over-expressed and proteins hyper-secreted in exosomes related to lymph node metastasis in the B16 mouse melanoma model. Out of these candidates, we found that Emilin1, a protein with an important function in lymph node physiology, was hyper-secreted in exosomes. Interestingly, we found that Emilin1 is degraded and secreted in exosomes as a mechanism favoring metastasis. Indeed, we found that Emilin1 has a tumor suppressor-like role regulating negatively cell viability and migration. Importantly, our in vivo studies demonstrate that Emilin1 overexpression reduced primary tumor growth and metastasis in mouse melanoma models. Analysis in human melanoma samples showed that cells expressing high levels of EMILIN1 are reduced in metastatic lesions. Overall, our analysis suggests a novel mechanism involved in the inactivation of Emilin1 in melanoma favouring melanoma progression and metastasis.
2021-07-16 | PXD018891 | Pride