Sarcoma

After observing additive impacts on phosphoprotein phosphorylation and anoikis-resistant growth with the dalotuzumab and SSO combination, we treated OS cells with dalotuzumab and the AAVrh74.U7 snRNA IR virus, which significantly slowed OS cell proliferation. While these viruses require further optimization, we highlight the potential for SSO therapy and viral vector delivery, as it may offer new treatment avenues for OS patients and be translated to other cancers.

By modulating key pathways and endocannabinoid system components, TUR demonstrates potential as a novel therapeutic agent for OA management. Future studies could explore its clinical applications and further validate its molecular mechanisms in vivo.

There is little published literature to guide care for low-grade NTRK3 mutation STS. This case highlights the importance of multidisciplinary care for STS.

Moreover, cell adhesion disappeared and cell morphology changed to a spindle shape, indicating sarcomatogenesis. In conclusion, this study reveals a mechanism for sarcoma development in OCS and provides novel therapeutic possibilities.

Imatinib increased tacrolimus blood concentrations after single and multiple administrations. Tacrolimus did not significantly affect the pharmacokinetics of imatinib after a single dose; however, tacrolimus might impact the absorption and metabolism of imatinib after multiple doses. The results showed that when imatinib and tacrolimus were co-administered, attention should be paid to the presence of drug-drug interactions.

Further investigation using mass spectrometry proteomics and transcriptomics uncovered KDELR1's involvement in modulating the Hippo-YAP pathway activity in CS cells. The KDELR1-Integrin-PLCγ-YAP1 axis emerges as a critical process mediating drug resistance and malignant behavior in CS, offering novel insights and potential therapeutic targets for CS treatment.

We thus propose a model where the CD99 High state develops a Cav-1 controlled signaling network to regulate cell survival that is distinct from the AKT-agnostic survival of CD99 Low cells. Overall, this work identifies a state transition of EwS cells and uncovers Caveolin-1 as a driver of survival signaling in a context-dependent manner.

We also show that WAY262611 induces osteoblastic differentiation of an OS patient-derived xenograft in vivo , as well as inhibiting metastasis. This work credentials DKK-1 as a therapeutic target in OS, allowing for manipulation of the Wnt signaling pathway and providing preclinical justification for the development of new biologics for prevention of osteosarcoma metastasis.

In this manuscript, we present the discovery process of ferroptosis, the mechanisms involved in ferroptosis, and the role of ferroptosis in a variety of orthopedic diseases. We expect that this manuscript can provide a new perspective on clinical diagnosis and treatment of related diseases.

15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8+ T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.

Simultaneously, the released Cu-elesclomol complexes induced proteotoxic stress responses and efficiently elicited cuproptosis, leading to increased release of proinflammatory factors and triggering anti-tumor immune activation. Our strategy holds promise for osteosarcoma treatment by inducing cuproptosis and achieving potent tumor suppression.

APC gene mutations were negative in this patient. Fibromatosis is a rare diagnosis which may have implications for the whole family and may present with congenital calf enlargement.

These molecular processes were disrupted by the PI3K-α specific inhibitor, alpelisib...Furthermore, we identified potential therapeutic vulnerabilities of PIK3CA mutations in response to PI3K-α inhibition mediated by MAPK signaling. In summary, we demonstrate that PIK3CA mutations perpetuate PI3K activation and reinforce immune enrichment to promote drug resistance in vascular cancers.

Interestingly, the expression of Ki67 and CTHRC1 exhibits a strong negative correlation, underscoring two distinct and mutually exclusive biological profiles in uLMS: (i) highly proliferative tumors, characterized by elevated Ki67 expression, and (ii) tumors driven by ECM remodeling, marked by high CTHRC1 levels. Taken together, this deep functional multi-omics approach contributes to the detection of new molecular features of uLMS and suggests that patients could benefit from precision oncology in clinical practice.

Likewise, new structural variations were identified in cyclin-dependent kinase 12 (CDK12). Whole genome profiling of metastatic GIST provides new insights to advance precision care of the disease, focusing on new therapeutic possibilities, especially for emerging targets such as CDK12.

In addition, Cur treatment decreases the EGFR/Src signaling pathway in the presence of active Src overexpression. Cur inhibits the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) by down-regulating EGFR/Src signaling axis, also resulting in coordinated weakening of its downstream regulatory genes, including Akt, STAT3, Bcl2, ERK1/2, among others signal axis (PI3K/Akt signaling pathway).

Together these data demonstrate that biphasic synovial sarcoma is immunologically different from monophasic synovial sarcoma and might be more susceptible to immunotherapies such as adoptive T-cell therapy. Finally, T-cell infiltration in primary synovial sarcoma was associated with prolonged overall survival of patients which suggests that intratumoral T cells may demonstrate anti-tumor activity.

Consistent with CIBERSORTx analysis, γ-H2AXlow LMS showed higher mast cell infiltration than γ-H2AXhigh LMS (p = 0.038). In conclusion, H2AX mRNA and γ-H2AX protein expression are associated with distinct biological behavior, differences in the immune cell environment, and might serve as useful prognostic biomarkers in LMS.

Both lack the defining 1p/19q co-deletion or copy-neutral heterozygosity of an oligodendroglioma and oligosarcoma. The findings in this case report both contribute to the apparent heterogeneity of the novel MC oligosarcoma and describe a second reported mesenchymal transformation of an IDH-mutant astrocytoma.

This study demonstrated the potential of radiomics features based on venous-phase CECT images to identify D842V mutation in GISTs. Our model may provide an alternative approach to guide TKI therapy for patients inaccessible to sequence variant testing, potentially improving treatment outcomes for GIST patients especially in resource-limited settings.

Finally, we discuss the potential impact of radiotherapy and specific drugs on miRNA expression and CD8 + T-cell activity within the TME. This review highlights the immense potential of targeting miRNAs to manipulate CD8 + T-cell activity for the development of novel and improved cancer immunotherapies.

Thus, the TYK2/STAT3/Bcl2 axis is a crucial mechanism through which SS18-SSX mediates apoptosis evasion in SS cells. In conclusion, our findings contribute to understanding how SS18-SSX-driven TYK2 expression mediates apoptosis evasion mechanisms and propose targeting TYK2 as a strategy to induce apoptosis in SS.

In human RD and RH30 lines, treatment with 0.01-1 μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50-100 μM cholesterol (CHO) supplementation. Treatment of RMS lines with higher doses of SREBP2 and MVP inhibitors (5-50 μM) promoted oxidative cell death and chemosensitization in combination with actinomycin D. Administration of lovastatin or fatostatin to RD and RH30 cells produced a rapid attenuation of Erk1/2 and Akt1 phosphorylation, detectable after 4 hours of treatment...Taken together, these data suggest that the axis formed by Akt1, SREBP2 and MVP is critical for RMS tumor growth, migration, and oxidative stress protection mainly through the maintenance of CHO levels that ensure proper intracellular signaling. Therefore, targeting CHO levels by SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol in RMS.

Molecular detection has shown that the mutation rate of BRAF in gastric LCH is up to 90.9%; more work is needed as the number of cases is small. Current data show a good prognosis for isolated gastric LCH in adults, but long-term follow-up for early detection of disease progression or systemic involvement is necessary.

Additionally, metastatic OS samples exhibited increased infiltration of resting immune cells, and single-cell RNA sequencing revealed communication between SNRNP70-expressing osteoblastic cells and macrophages via the ADGRE5/CD55 signaling pathway. Overall, our results showed that SNRNP70 knockdown inhibited OS progression, which was associated with the splicing of CD55, indicating SNRNP70 as a promising target for OS treatment.

Currently, there is no standard therapy for EIMS; however, existing studies advocate for the use of ALK tyrosine kinase inhibitors (TKIs) in its treatment. This case was reported to be in remission following treatment with crizotinib, thereby contributing to the understanding of the specific pathology of EIMS and facilitating accurate diagnosis and targeted therapy.

Retroperitoneal paraganglioma was initially misdiagnosed as angiosarcoma due to the overlapping imaging characteristics between the two tumors. This highlights the importance of raising suspicion on the possibility of retroperitoneal paraganglioma when imaging examination indicates angiosarcoma and to incorporate histopathological examination and immunohistochemistry in the diagnosis to avoid misdiagnosis.

Consequently, there is an important need for effective treatments for patients with NSCLC with STK11 or KEAP1 mutations. In this article, we describe new data on the prevalence of STK11 and KEAP1 mutations in a large clinical population, consider practicalities around the detection of these mutations using available biomarker testing methodologies, and describe experiences of managing some of these difficult-to-treat patients in our clinical practice.

Mechanistically, shikonin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced Nrf2 stability via inducing ubiquitin degradation, which suppressed the expression of Nrf2 downstream targets xCT and GPX4, and led to stimulating ferroptosis. Collectively, our findings indicated that shikonin induced OS cells ferroptosis through Nrf2/xCT/GPX4 regulatory axis, which might shed light on exploiting shikonin as a promising candidate for the future OS therapy.

Our results revealed that miR-615-3p modulated mTOR signaling, thus influencing the progression of OS. For OS treatment, molecular strategies that target the miR-615-3p/SESN2/mTOR pathway is promising.

Our case study revealed that the pathogenic BRCA2 c.5946del germline variant can be associated with an unusual tumour spectrum, which may lead to a delayed diagnosis of a hereditary tumour predisposition. Thus, upfront genetic testing using large multigene panels or whole-genome sequencing in encouraged, especially in cases with a prominent family history.

P=N/A, N=100, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

P2, N=100, Recruiting, Italian Sarcoma Group | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

P=N/A, N=300, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P=N/A, N=16, Not yet recruiting, Technical University of Munich

P2, N=16, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Aug 2025

P2, N=100, Recruiting, Fudan University | Not yet recruiting --> Recruiting

Advances in the understanding of the molecular pathogenesis of TGCT, has led to systemic therapies targeting the CSF1 receptor (CSF1R), including the first FDA approval in this space pexidartinib. These developments provide the foundation for further investigation into additional treatments, optimal sequencing and duration of therapies for patients with symptoms and reduced functionality secondary to TGCT.

ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.

Our assay panels generated selectivity profiles and quantitative binding interaction dissociation constants for small molecules and degraders against wild type, G12C, G12D, and G12V KRAS, which were congruent with published data. These assays can be leveraged for additional mutants of interest beyond those described in this study, using both overexpressed cell-free systems and cell-based systems with endogenous protein levels.

Toward this goal, we have developed a sotorasib-based molecular agent for PET imaging and tested its efficacy in targeting tumor lesions with KRAS G12C mutations. Here, we describe the synthesis, in vitro and in vivo evaluation of an [124I]I-Sotorasib analog in targeting G12C mutant tumor lesions using PET imaging.

Nitrogen bisphosphonates, such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases...Liquid chromatography-tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.