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Local Consolidative Therapy in Colorectal Cancer

ABSTRACT: This is a Phase II randomized multisite trial to study the effect of a combination of local consolidative therapy with systemic therapy in subjects with oligometastatic colorectal cancer who have progressed on the first line of therapy.

DISEASE(S): Colorectal Neoplasms,Colorectal Cancer Metastatic

PROVIDER: 2391058 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer

Project description:This study aims to assess the clinical benefit of local ablative therapy (LAT) following initial standard first-line systemic treatment including the impact on survival, compared to continued standard first-line systemic treatment for oligometastatic colorectal cancer.

| 60310 | ecrin-mdr-crc

microRNA epxression patterns can discriminate between patients with oligometastatic and polymetastatic progression: tissues

Project description:Background Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy. Methods Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. Results Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression. Conclusions These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.

2010-11-25 | GSE25552 | GEO

Barley Systemic Immunity: Dataset Local and Systemic

Project description:Barley Systemic Immunity: Dataset Local and Systemic

| PRJEB7729 | ENA

Barley Systemic Immunity: Dataset Local and Systemic

Project description:Leaf-to-leaf, systemic immune signaling known as systemic acquired resistance (SAR) is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to SAR in Arabidopsis thaliana, systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid (SA). Instead, we documented a moderate local but not systemic induction of abscisic acid (ABA) after infection of leaves with Psj. In contrast to SA or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or ABA triggered systemic immunity to Xtc. RNA-seq analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest and quantitative RT-PCR associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors possibly facilitating transcriptional reprogramming to potentiate immunity.

2014-11-24 | E-MTAB-3063 | biostudies-arrayexpress

Proteomics on sera of mice following local high-dose heart irradiation

Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.

2021-09-10 | PXD024446 | Pride

Keratinocyte glucocorticoids enable local immune resilience to preserve skin homeostasis.

Project description:Endogenous glucocorticoids (GCs) are pivotal in controlling inflammation. Keratinocyte-derived GCs contribute to local skin homeostasis as deletion of the GC-producing enzyme 11β-hydroxylase (Cyp11b1) in keratinocytes exacerbated skin inflammation. Since local tamoxifen-induced knockout (KO) induction may contribute to skin irritation, we implemented intraperitoneal injections to induce a systemic skin GC depletion preventing experimental skin irritation in order to reveal the importance of skin GC in steady-state. Both, local and systemic skin GC deficiency models exhibited reduced skin GC levels and increased migration of skin antigen-presenting cells to draining lymph nodes. However, systemic skin GC ablation did not result in pronounced skin inflammation as seen in local model. Interestingly, systemic skin GC deficiency elevated systemic inflammatory markers and provoked adrenal GC synthesis. RNA sequencing of keratinocytes revealed distinct gene expression patterns between local and systemic KOs. Local skin GC ablation showed a stronger inflammatory and apoptotic response, while systemic skin GC deficiency triggered several compensatory regulatory pathways, mitigating extensive skin inflammation. These findings underscore the critical role of local GCs in skin immune resilience against minor skin irritations and highlight the interplay between skin and adrenal GC levels.

2024-08-01 | GSE271160 | GEO

Imaging Studies of Local Responses of Prostate Cancer to Radiation Therapy

Project description:Imaging Studies of Local Responses of Prostate Cancer to Radiation Therapy

| PRJNA540877 | ENA

Imaging Studies of Local Responses of Prostate Cancer to Radiation Therapy

Project description:Imaging Studies of Local Responses of Prostate Cancer to Radiation Therapy

| PRJNA540876 | ENA

Itaconate-producing neutrophils regulate local and systemic inflammation following trauma

Project description:Itaconate-producing neutrophils regulate local and systemic inflammation following trauma

2023-11-08 | GSE221134 | GEO

Expression profiles of peripheral blood monocytes in periodontal therapy

Project description:Periodontal infections have been associated with systemic inflammation and risk for atherosclerosis and vascular disease. We investigated the effects of comprehensive periodontal therapy on gene expression of peripheral blood monocytes. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis, and cell signaling. We concluded that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. Keywords: time course,disease state analysis

2007-12-31 | GSE6751 | GEO

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