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Soft Tissue Sarcoma - Crossref

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Last Updated: 20 June 2022

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Abstract PR03: Immune-based classification of soft-tissue sarcoma is associated with clinical outcome and unveils tertiary lymphoid structures as surrogate biomarker for the clinic

"Abstract Soft tissue sarcoma are rare mesenchymal-originated tumors with more than 50 species of histologies have been identified. " Endothelial cell signature, an intermediate presence of neutrophils, and a rather poor infiltration by other immune cell species are characteristic of SIC B tumors. Interestingly, immune checkpoint genes exhibited significant expression differences between SICs. In the C2 class, we also discovered that the lymphoid structure-associated B cell chemoattractant chemokine CXCL13 is remarkably high. Although all histologies are distributed in each SIC group, LMS are more commonly found in the immune low SIC A1 and A2 groups, and we also extended our analysis to other histologies, such as synovial sarcoma or gastrointestinal stromal tumors. Our classification is linked to medical results, and SIC group C has the longest overall survival rate in comparison to a SIC group. SIC C tumors were significantly elevated in CD3, CD8 and CD20 densities. CD34+ endothelial cells in Tumor SIC B groups have a higher, albeit non-significant, expression. We enlarged the validation cohort to investigate the correlation between TLS and CD3+/CD20+/CD20+ tumor-infiltrating lymphocytes. "This validation result indicates that TLS is a good surrogate marker for the identification of SIC C groups and could be used in the future to measure immunotherapy in STS. ".

Source link: https://doi.org/10.1158/2326-6074.cricimteatiaacr18-pr03


Abstract A19: Systems biology approach predicts the diagnostic value of T effector: T regulatory cell ratio in clinical response to combined radiation/immunotherapy of high-risk soft tissue sarcoma

"The attraction comes from the fact that radiation-induced tumor cell death will result in the synthesis of tumor antigens capable of stimulating dendritic cells, enabling long-term adaptive T cell immunity against the tumor. " We developed a mathematical model analyzing the ages of T effector cells and T regulatory cells in every patient with high risk soft tissue sarcoma treated with intratumoral administration of autologous dendritic cells and local fractionated external beam radiation therapy in each patient that did or did not have a clinical response. Materials and Methods: The Phase II clinical trial included 15 Grade 2 high-risk soft tissue sarcoma patients who underwent radiation/dendritic cell therapy, of which there were five responders and ten non-responders. We built a mathematical model of tolerogenic and immunogenic tumor subpopulations in the patients and the accompanying clinical findings, including T effector and T regulatory cells. The comparison between responder and non-responder cohorts reveals that immune T effector cell proliferation and effectiveness are determinants of treatment response. Our first findings reveal that tumor growth dynamics are indistinguishable between high-risk soft tissue sarcoma patients responding to radio-immunotherapy and those who do not. T effector: T regulatory cell ratio in clinical response to combined radiation/immunotherapy of high-risk soft tissue sarcoma can be determined by a systems biology approach.

Source link: https://doi.org/10.1158/2326-6074.tumimm14-a19


Abstract A31: Tracking the evolution of soft tissue sarcoma and GIST using liquid biopsies

"Abstract Molecular analysis of circulating tumor DNA has a large potential for medical use in the United States, capturing mutations and heterogeneity by noninvasive sampling. The CircSarc studies aims to provide new insights into the clinical use of liquid biopsies in soft tissue sarcomas and gastrointestinal stromal tumors. We've recruited 35 high-grade soft-tissue sarcoma patients with localized disease in CircSarc STS. Using ultra-low-pass WGS or targeted NGS, genetic mutations in cfDNA are being identified. We find ctDNA in 30% of the first soft-tissue sarcoma samples with elevated or metastatic tumors at the time of surgery and/or progression. Plasma samples were obtained for a cohort of 30 metastatic GISTs and 50 GISTs at the time of diagnosis. Targeted NGS has identified synchronous mutations in ctDNA. The prevalence of somatic mutations in ctDNA are being linked to clinicopathologic features. In 36% of treatment-naefve GIST patients, including all patients with metastatic disease, the tumor burden was the most significant detection determinant, according to the disease determinant. While the investigation of metastatic GISTs is ongoing, repeated plasma samples in a new patient have shown that clonal change can be monitored over time. Our research has shown that mutation detection in plasma is especially useful for patients with elevated tumor burdens. Mutational analysis by using liquid biopsies can help capture the tumor's molecular heterogeneity and aid in treatment decisions during progression. "abstract] "Surviving the evolution of soft tissue sarcoma and GIST using liquid biopsies [abstract]. ".

Source link: https://doi.org/10.1158/1557-3265.liqbiop20-a31


Abstract PO-027: Associations of radiomics features with tumor necrosis following chemotherapy and/or radiation therapy in patients with extremity soft tissue sarcoma

"Abstract Introductory sentence: The aim of this investigation is to identify MRI radiomic signs of sarcomas pre and post radiation and/or chemotherapy therapies that correlate with the severity of necrosis demonstrated on tumor excision. " Patients with soft tissue upper and lower extremity sarcomas, as well as available pre- and post-treatment MRI tests were included in the study. For extraction of quantitative imaging data, we used MINT Lesion radiomics software from MINT Lesion radiomics. Patients were induced with tumor necrosis samples, and tumor necrosis data was collected following surgery. The percent necrosis was comparable to radiomic changes when using Pearson correlation results. Male u2013 and female - The clinical signs were similar: a male sarcoma, Leiomyosarcoma, Myxofibrosarcoma, and others; Grade 2-3; Radiation and/or chemotherapy of various doses and regimens. MRIs were obtained within 3 months before diagnosis was started and within 2 months after treatment was completed. The average necrosis on final pathology was 68% +/- 33% std. According to respective reports, the most closely related radiomic data includes first and second order measurements indicating the distribution of voxel intensities within the segmented image regions and statistical inter-relationships among neighboring voxels. Conclusions: We found delta-radiomics features in this pilot study, whether increased voxel volume, or increased vowel heterogeneity in second order radiomics, as well as increased vowel heterogeneity in sarcomas post radiation and/or chemotherapy. "abstract": The association of radiometrics contributes to tumor necrosis in patients with extremity soft tissue sarcoma patients after chemotherapy and/or radiation therapy.

Source link: https://doi.org/10.1158/1557-3265.adi21-po-027


Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma

"Abstract Purpose We tried to determine the effectiveness of [ 68 Ga]Ga-DOTA-FAPI-04 PET/CT for the treatment of recurrent soft tissue sarcoma, relative to [18 F]FDG PET/CT. Methods A total of 45 patients with 13 subtypes of STS underwent [18 F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT examination within a week for determining local relapse or distant metastasis. Positive lesions on PET/CT scans were confirmed by biopsy or 3-month follow-up. The McNemar test was used to determine the comparative values of [ 18 F]FDG and [ 68 Ga]Ga-DOTA-FAPI-04 in tumor lesions, and the McNemar test was used to determine the differences between both tracers. "Ga-DOTA-FAPI-04, a malignant solitary fibrous tumor sarcoma, and interdigitating dendritic cell sarcoma, all increased values of SUV max and TBR than [18 F]FDG PET/CT in liposarcoma, a nefarious tumor sarcoma sarcoma. ".

Source link: https://doi.org/10.1007/s00259-022-05700-4


A RASSF1A Polymorphism Restricts p53/p73 Activation and Associates with Poor Survival and Accelerated Age of Onset of Soft Tissue Sarcoma

"Abstract RASSF1A, a tumor suppressor gene that is frequently activated in human cancers," ataxia telangiectasia mutated on Ser131 on DNA damage, leading to the development of a p73-dependent apoptotic response. At residue 133 of RASSF1A, a single-nucleotide polymorphism found in the area of RASSF1A's main ATM activation site predicts the change of alanine to serine. In the serine isoform of RASSF1A, an alpha helix containing the ATM recognition site is disrupted, according to secondary protein structure prediction studies. We found a reduced ability of ATM to recruit and phosphorylate RASSF1A-p. 133Ser on DNA damage in this research. We discovered that male soft tissue sarcoma patients carrying the minor T allele coding RASSF1A-p. 133Ser had shorter longevity and early onset of disease in comparison to patients homozygous for the major G allele.

Source link: https://doi.org/10.1158/0008-5472.can-11-2906


IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression

"Abstract IFN regulatory factor 8 has been shown to reduce tumor formation at least partially by regulating apoptosis of tumor cells," IRF8's regulatory system is still not fully understood; however, the molecular mechanisms under IRF8 control of apoptosis are still not entirely understood. Flap mRNA stability is greatly improved when disrupting IRF8 function led to an elevated IRF8 protein level, according to a series of signaling events upstream of caspase-8. In addition, primary myeloid cells isolated from IRF8-null mice elevated FLIP protein levels, indicating that IRF8 could be a general repressor of FLIP. In 92% of human STS specimens, but 99% of human STS specimens showed FLIP expression, showing that the nuclear IRF8 protein level is inversely related to FLIP protein level in vivo. ".

Source link: https://doi.org/10.1158/0008-5472.can-08-2520


Soft Tissue Sarcoma Cells Are Highly Sensitive to AKT Blockade: A Role for p53-Independent Up-regulation of GADD45α

In soft tissue sarcoma, the AKT signaling pathway is stimulated. "Abstract" is a film that is on display in soft tissue sarcoma. Here, we investigated the in vitro and in vivo effects of AKT inhibition in STS cells. AKT pathway components were analyzed by Western blot analysis, which was used to determine the expression of AKT pathway components and the effects of AKT stimulation and inhibition on their phosphorylation. Cell culture assays were used to determine the effect of AKT blockade on STS cell growth, cell cycle, and apoptosis. Cell culture assays were used to determine the effects of AKT blockade on STS cell proliferation, cell cycle, and apoptosis. Gene expression changes in response to AKT inhibition were used by Oligoarrays to determine gene expression changes in response to AKT inhibition. AKT was triggered by multiple STS cell lines and cell lines on several STS cell lines, triggering AKT. In vitro, AKT inhibition reduced STS downstream target phosphorylation and growth; G2 cell cycle arrest and apoptosis were also observed; AKT inhibition reduced STS downstream target phosphorylation and growth in vitro. All STS cells treated in a non-mutation condition were treated without regard to p53 gene expression, resulting in GADD45u03b1 mRNA and protein expression in all STS cells treated without regard to p53 mutation status. Modulation of AKT kinase activity may be a novel molecularly based treatment for STS-targeted therapies. ".

Source link: https://doi.org/10.1158/0008-5472.can-07-6268


Vascular Endothelial Growth Factor Overexpression by Soft Tissue Sarcoma Cells: Implications for Tumor Growth, Metastasis, and Chemoresistance

"Several hundred combined immunodeficient mice bearing xenografts of transfected cell lines were used to determine the effect of VEGF overexpression and the effect of VEGF receptor 2 inhibition on STS growth, metastasis, and reaction to doxorubicin. " VEGF overexpression did not have an effect on the sarcoma cells per se; however, conditioned medium from VEGF transfectants promoted endothelial cell proliferation, migration, and chemoresistance. We conclude that VEGF is a key determinant of STS expansion and metastasis, as well as that STS chemoresistance, which in our example, is a process triggered by the interplay between STS cells and tumor-associated endothelial cells.

Source link: https://doi.org/10.1158/0008-5472.can-06-1217


Synergistic Antitumor Response of Interleukin 2 with Melphalan in Isolated Limb Perfusion in Soft Tissue Sarcoma–Bearing Rats

"IL-2 can cause vascular leakage and edema, and we investigated the antitumor activity of a combination therapy with IL-2 and melphalan in our well-established ILP in soft tissue sarcoma u2013bearing rats for this reason. While ILP with either IL-2 or melphalan alone has no anti-tumor effect, the combination of IL-2 and melphalan results in a strong synergistic tumor response, with no local or systemic toxicity, no regional or systemic toxicity. ED-1 cells were found in the localization of ED-1 cells, with an even distribution in the sham, IL-2, and melphalan therapies, however clustered ED-1 cells were discovered in the IL-2 plus melphalanu2013 treated tumors. The findings in our study show that the patented combination of IL-2 and melphalan in ILP has synergistic antitumor activity and could be a substitute for ILP with TNF and melphalan, as an alternative to ILP with TNF and melphalan. ".

Source link: https://doi.org/10.1158/0008-5472.can-04-2214

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions