Neoadjuvant immune checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/trunk undifferentiated pleomorphic sarcoma (NCT03307616)
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ABSTRACT:
PROVIDER: PRJNA835711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19117803_1.fastq.gz | Fastqsanger.gz | |||
| SRR19117803_2.fastq.gz | Fastqsanger.gz | |||
| SRR19117804_1.fastq.gz | Fastqsanger.gz | |||
| SRR19117804_2.fastq.gz | Fastqsanger.gz | |||
| SRR19117805_1.fastq.gz | Fastqsanger.gz |
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Project description:Recent evidence suggests that immune checkpoint blockade (ICB) has some activity in metastatic dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS). We conducted a randomized, non-comparative phase 2 trial (NCT03307616) of nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n=17) and extremity/truncal UPS (n=10), with UPS patients receiving concurrent radiation therapy. The primary endpoint of pathologic response as assessed by percent hyalinization was observed to be a median of 8.8% in DDLPS patients and 89% in UPS patients and similar in nivolumab and ipilimumab/nivolumab arms in both cohorts . Higher intratumoral densities of T-regulatory cells were associated with absence of pathologic response (hyalinization<30%). Tumor infiltration by B-cells was associated with higher densities of T-regulatory cells before treatment; this association was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB with concurrent radiation may have significant efficacy in UPS and is associated complex immune changes in the tumor microenvironment in DDLPS and UPS.
2024-01-01 | GSE202361 | GEO
Project description:An integrated profiling approach was performed to define molecular alterations associated to the aggressive behavior of retroperitoneal dedifferentiated liposarcoma. In particular, matched well and dedifferentiated components as well as normal adipose tissues, obtained from the same tumor sites, were comparatively investigated to higlight differences in gene expression.
2021-03-10 | GSE159659 | GEO
Project description:Genomic characterization of well differentiated/dedifferentiated retroperitoneal liposarcoma
| PRJNA670101 | ENA
Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS. Genomic DNA was extracted from a total of 49 samples, 31 Undifferentiated pleomorphic Sarcomas and 18 Leiomyosarcomas. The DNA was labeled using Bioprime array CGH labeling kit (Invitrogen). Promega pooled male DNA was used as reference. Labeled DNA was hybridized onto BAC arrays containing ~32 000 BAC clones printed in singlets. BAC arrays were produced at the SWEGENE DNA Microarray Facility at Lund University.
2010-10-08 | E-GEOD-13775 | biostudies-arrayexpress
Project description:Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival did not improve much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from combination of anlotinib and eribulin. In this study, we investigated combinational effect of anlotinib and eribulin on RLPS. Through transcriptome analysis, we uncovered and validated that synergistic effect mainly induced by endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo.
2024-08-01 | GSE261076 | GEO
Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.
2009-03-24 | GSE13775 | GEO
Project description:IntroductionDedifferentiated liposarcoma (DDLP) was initially defined as a tumor containing differentiated liposarcoma and distinct regions of nonlipogenic spindle cell or pleomorphic sarcoma. Retroperitoneal liposarcomas feature a characteristic appearance with a predominantly fatty component, and cystic liposarcomas are rare. We describe a case of retroperitoneal DDLP predominantly consisting of multilocular cysts.Case presentationA 77-year-old man previously visited a doctor because an echo scan unexpectedly revealed an abdominal tumor. Contrast computed tomography (CT) disclosed a large multilocular cystic tumor spanning from the left upper abdomen to the retroperitoneum, and poorly marginated soft tissue structures were present around the abdominal aorta, inferior vena cava, pancreas, mesentery, and left kidney. CT also revealed a right lung mass. The soft tissue structures in the retroperitoneal cystic tumor and right lung mass were strongly enhanced on 2-deoxy-2-[fluorine-18] fluoro-d-glucose positron emission tomography, suggesting a malignant retroperitoneal tumor and lung metastasis. CT-guided percutaneous biopsy targeting the left perirenal soft tissue structure was performed, and the tumor was diagnosed as DDLP. Lung metastasis was present, and the retroperitoneal tumor surrounded multiple organs. Therefore, the tumor was not suitable for surgical resection but it was indicated for chemotherapy based on multidisciplinary discussion.ConclusionWe experienced a case of retroperitoneal cystic DDLP diagnosed by percutaneous image-guided biopsy and treated appropriately based on the pathological diagnosis.
| S-EPMC10673338 | biostudies-literature
Project description:Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing and functional assays in paired WD and DD components from primary DDLPS tumors, we characterized the cellular heterogeneity of DDLPS tumor and micro-environment. We identified a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β high immunosuppressive tumor micro-environment.
2024-07-22 | GSE221493 | GEO
Project description:Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing and functional assays in paired WD and DD components from primary DDLPS tumors, we characterized the cellular heterogeneity of DDLPS tumor and micro-environment. We identified a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β high immunosuppressive tumor micro-environment.
2024-07-22 | GSE221492 | GEO
Project description:Background and objectivesRetroperitoneal liposarcoma (RPLS) are common soft tissue sarcomas of adulthood. The aim of this study is to show resectability of even giant liposarcomas and to identify factors associated with recurrence and survival in primary retroperitoneal liposarcomas.MethodsWe retrospectively reviewed the records of patients with retroperitoneal liposarcoma. Seventy-seven patients met inclusion criteria. Out of these 10 patients with primary giant, dedifferentiated retroperitoneal liposarcomas were operated with en bloc compartment resection with intention of radical resection. Treatment consisted of neoadjuvant radiochemotherapy and surgical resection or surgical resection.ResultsIn 6 patients, neoadjuvant radiochemotherapy was performed; 3 patients were treated with surgical resection alone and 1 patient received adjuvant chemotherapy. The median diameter of tumor size was 360 mm (300 to 440 mm). Operative outcome showed complete resection in all 10 patients. Local tumor free survival was in median 19 month. Tumor recurrence was seen in 3 of 4 patients (75%) without neoadjuvant radiochemotherapy, and in 2 of 6 patients (33%) after neoadjuvant radiochemotherapy in 2 years follow-up.ConclusionEven in case of giant retroperitoneal liposarcoma, complete resection is possible and remains the principal treatment. The rate of recurrence was improved in patients with neoadjuvant radiochemotherapy.
| S-EPMC7664077 | biostudies-literature