Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study.

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Frozen inactivated autograft replantation for bone and soft tissue sarcomas.

Background: The frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation. Methods: In this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale. Results: This study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3-35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union. Conclusion: Frozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

Identification and prognostic evaluation of differentially expressed long noncoding RNAs associated with immune infiltration in osteosarcoma.

Osteosarcoma is a malignant bone cancer that originates from the bone with the strongest invasiveness. Tumor formation strongly correlates with immune cell infiltration into the tumor immune microenvironment (TIME). Therefore, we aimed to identify TIME-related biomarkers as potential prognostic markers of osteosarcoma. The mRNA and long noncoding RNA (lncRNA) transcriptome data of 88 patients with osteosarcoma and the expression profile of GSE99671 were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Immune infiltration scores and types were evaluated using ESTIMATE and CIBERSORT. A linear model was established to identify the differentially expressed genes (DEGs) and lncRNAs (DElncRNAs). Functional enrichment analysis of DEGs was conducted by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis. DElncRNAs were analyzed using a weighted gene co-expression network. Least absolute shrinkage and selection operator regression was applied to screen for prognostic markers. Patient survival was predicted by the risk score and analyzed by receiver operating characteristic curve. Clinical features affecting patient survival were assessed. Immune infiltration positively correlated with osteosarcoma patient survival. Different immune cell infiltrates in patients with osteosarcma may serve as prognostic indicators and targets for immunotherapy. In total, 1125 DEGs, 80 DElncRNAs, and 11 pairs of co-expressed lncRNA-mRNAs were identified. DEGs in the three modules were associated with immune infiltration into the TIME. Four DElncRNAs, namely AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, showed good prognostic ability for osteosarcoma and were positively correlated with the immune score. Tumor metastasis and risk scores alone were good prognostic indicators, and a combination of the two variables can better predict the prognosis of osteosarcoma. We identified four lncRNAs, AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, as potential biomarkers for osteosarcoma prognosis.

Combining nanoparticle albumin-bound paclitaxel with camrelizumab in advanced soft tissue sarcoma: activity, safety, and future perspectives.

Background: It is still uncertain whether Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor have synergistic effects on metastatic soft tissue sarcomas (STSs). The purpose of this study was to evaluate the safety and activity of nab-paclitaxel plus camrelizumab (a PD-1 inhibitor) in patients with advanced STS who had previously failed chemotherapy. Methods: In this single-center, open-label, single-arm phase II clinical trial, patients with advanced (unresectable or metastatic) STS who had previously failed chemotherapy received up to six cycles of nab-paclitaxel plus camrelizumab, whereas camrelizumab treatment was continued for up to 1 year. The median progression-free survival (PFS), objective response rate (ORR) and safety were collected and evaluated. Results: This trial included 40 patients (28 men and 12 women). The overall ORR was 22.5%, and the median PFS was 1.65 months (95% confidence interval [CI], 1.3-2.0 months). Patients with epithelioid sarcoma demonstrated a longer PFS compared with those with other histological subtypes (2.3 months vs. 1.5 months, respectively); however, this difference was not significant. Patients who had received only one line of previous chemotherapy had a significantly longer PFS compared with those who had undergone two or more lines of previous chemotherapy (2.8 months vs. 1.3 months, respectively, p = 0.046). In terms of safety, the toxicity of this combination therapy is mild and no serious adverse events have occurred. Conclusion: Nab-paclitaxel plus camrelizumab exhibited modest activity and mild toxicity in treating epithelioid sarcoma, angiosarcoma, and fibrosarcoma. The overall effectiveness of this treatment regimen for advanced STS is relatively low. Further research on combining nab-paclitaxel with effective drugs, including chemotherapy and targeted agents, for these specific STS subtypes is needed.

Inactivation and replantation of the knee joint: an infeasible surgical method.

BACKGROUND: The inactivation and replantation of autologous tumor bones are important surgical methods for limb salvage in patients with malignancies. Currently, there are few reports on the inactivation and replantation of the knee joint. In this study, we aimed to evaluate the feasibility of our surgical approach. METHODS: This is a retrospective case series study. We retrospectively collected the clinical data of patients with sarcoma treated with knee joint inactivation and replantation and analyzed the efficacy of this surgical method. The bone healing and complications in these patients after inactivated autograft replantation were assessed. RESULTS: This study included 16 patients. Fifteen patients had osteosarcoma, and one had Ewing's sarcoma. The average length of the inactivated bone is 20.2 cm (range 13.5-25.3 cm). All the patients underwent internal plate fixation. The average follow-up duration was 30 months (range 8-60 months). Before the data deadline of this study, eight (50%) patients were still alive, and eight (50%) died of sarcoma metastasis. Eight (50%) patients achieved bone healing at the diaphysis site of the inactivated tumor bone, with an average bone healing time of 21.9 months (range, 12-36 months). Five (31%) patients died due to metastases and did not achieve bone healing. Two (12.5%) patients did not achieve bone healing because of infection, and one (6.3%) patient underwent amputation due to tumor recurrence. Ten (62.5%) patients experienced fractures around the joint ends of the inactivated replanted bone, and eight of these ten patients were combined with joint dislocation. CONCLUSION: The incidence of joint deformities after the knee-joint inactivation and replantation is extremely high and is not recommended for use.

Long bone shaft metastasis: a comparative study between cement filling and intercalary prosthesis.

BACKGROUND: Metastatic bone lesions in the extremities can cause severe pain and pathological fractures, significantly affecting patients' quality of life. Timely intervention and effective management of long bone metastases can positively influence patient outcomes, including survival rates and subsequent treatment options. OBJECTIVE: The objective of this study is to compare the efficacy and associated complications of two surgical reconstruction techniques and propose a more effective limb reconstruction approach for long bone metastases. METHODS: A retrospective study was conducted on 28 patients with complete clinical data who underwent a surgical procedure for long bone metastases of the extremities in our department between January 2017 and June 2022. The patients were divided into two groups based on their surgical methods. In group 1, the affected bones were curetted and filled with cement, then secured with plates or intramedullary nails. In group 2, the affected bone segments were completely removed and replaced with custom intercalary prostheses. Various factors, including general patient information, surgical details, surgical effectiveness, and common complications, were compared and analyzed. RESULTS: There were no significant differences in general patient information between the two groups, including age, gender, surgical site, and primary tumor type. The operative times were 115.37 min for group 1 and 108.90 min for group 2, respectively (p > 0.05). However, intraoperative blood loss differed significantly between the groups, with 769 ml in group 1 and 521 ml in group 2 (p < 0.05). The postoperative MSTS scores were 91% for group 1 and 92% for group 2 (p > 0.05). Postoperative complications included two cases of internal fixation failure and three cases of tumor recurrence in group 1, resulting in a 33% incidence rate, while group 2 experienced a 15% incidence rate with two cases of internal fixation failure. CONCLUSION: The results of this study suggest that both surgical techniques are effective for the treatment of long bone metastases of the extremities. However, the custom intercalary prostheses technique in group 2 showed a lower incidence of complications and less intraoperative blood loss. Therefore, it may be a more effective limb reconstruction approach for long bone metastases. Further studies with larger sample sizes are needed to confirm these findings.

Unveiling the prognostic implications of RPLP1 upregulation in osteosarcoma.

Osteosarcoma, a malignant bone tumor characterized by a high rate of metastasis and poor survival, presents a critical need for identifying novel biomarkers associated with metastasis. In this study, we conducted an extensive analysis utilizing transcriptional and clinical data sourced from databases such as GEO, TCGA, CCLE, R2, and Xena. And we discovered that Ribosomal protein LP1 (RPLP1) ranked among the top upregulated genes in relation to osteosarcoma metastasis. Notably, RPLP1 exhibited significant expression in both osteosarcoma cell lines and patient samples. Moreover, multiple osteosarcoma studies revealed a strong correlation between RPLP1 overexpression and worse metastasis-free survival as well as overall survival. Additionally, we observed a consistent association between dysregulation of RPLP1 and reduced overall survival across various tumor types. Knocking down of RPLP1 led to the down-regulation of MYL5 and functional enrichment toward cell cycle and cellular interaction. Based on these findings, we propose that RPLP1 has the potential to serve as a prognostic biomarker, indicating increased metastasis and worse survival outcomes in osteosarcoma. These insights contribute to a better understanding of the disease and may pave the way for future research and therapeutic approaches.

DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis.

Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In conclusion, our findings demonstrate that DLX2 may enhance the transcriptional regulation of CDH2 through interacting with HOXC8, which in turn promotes epithelial-mesenchymal transition and doxorubicin resistance in osteosarcoma. These findings hold great potential for clinical application and may guide the development of novel targeted therapies for osteosarcoma.

Ewing's sarcoma of proximal femur: case report of extreme osteotomy with 3D-printed prosthesis for the reconstruction.

Background: Resection and reconstruction of malignant bone tumors at the proximal femur in adolescent patients has remained a clinical challenge. Considering the growth and development requirements of adolescents, there is no unified standard for the reconstruction of bone defects at the proximal femur. Here, we report a case of 3D-printed titanium alloy customized prosthesis for the construction of proximal femoral bone defects in an adolescent patient with Ewing's sarcoma of the proximal femur. Case presentation: A 7-year-old female patient presented to a local hospital with left hip pain, and was diagnosed with Ewing's sarcoma on the proximal left femur. The patient received two courses of neoadjuvant chemotherapy before surgery according to the standard protocol. Considering growth and development problems associated with adolescents, we adopted a customized 3D-printed prosthesis of proximal femur for preservation of the femoral head and part of the femoral neck in the affected limb. Clinical outcomes, recorded after 12 months of follow-up, revealed excellent functional recovery and satisfactory functional scores of the affected limb, with no immediate complications. Conclusion: 3D-printed prosthesis is a feasible method for preserving femoral head and reconstruction of bone defects in adolescents' proximal femur.

Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy.

Background: Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs. Methods: Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021. Results: This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events. Conclusion: Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

Regulating Tumorigenicity and Cancer Metastasis through TRKA Signaling.

Tropomyosin receptor kinase (TRK) A, TRKA, is a specific binding receptor of nerve growth factor (NGF), which plays an essential role in the occurrence and progression of human cancers. TRKA overexpression has been proven to be a powerful carcinogenic driver and has been verified in many tumors. The TRKA receptor kinase domain is over-activated in an NGF-dependent manner, accompanied by activation of downstream signal pathways, such as RAS-MAPK, PI3K-AKT, JAK2-STAT3 pathway, PLC γ pathway, and Hippo pathway, which participate in tumor cell proliferation, invasion, epithelial-mesenchymal transition (EMT), perineural invasion (PNI), drug resistance, and cancer pain. In addition, chimeric oncogenes produced by the fusion of NTRK1 and other genes are also the direct cause of tumorigenesis and cancer development. The newly developed TRK inhibitors can improve symptoms and tumor regression in cancer patients with overexpression of TRKA or NTRK1 fusion gene. With the emergence of drug resistance, next generation of TRK inhibitors can still maintain strong clinical efficacy in the case of TRK kinase domain mutations, and these inhibitors are in clinical trials. This review summarizes the characteristics and research progress of TRKA, focusing on the regulatory role of the TRKA signal pathway in different tumors. In addition, we have summarized the clinical significance of TRKA and the TRK inhibitors. This review may provide a new reference for the study of the mechanism of TRKA in different tumors, and also provide a new perspective for the in-depth understanding of the role of TRKA as a biomarker and therapeutic target in human cancer.

Chemotherapeutic drugs for soft tissue sarcomas: a review.

Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes. anthracyclines are the most important systemic treatment for advanced STSs. Ifosfamide, trabectedin, gemcitabine, taxanes, dacarbazine, and eribulin exhibit certain activities in STSs. Vinca alkaloid agents (vindesine, vinblastine, vinorelbine, vincristine) have important therapeutic effects in specific STS subtypes, such as rhabdomyosarcoma and Ewing sarcoma family tumors, whereas their activity in other subtypes is weak. Other chemotherapeutic drugs (methotrexate, cisplatin, etoposide, pemetrexed) have weak efficacy in STSs and are rarely used. It is necessary to select specific second- or above-line chemotherapeutic drugs depending on the histological subtype. This review aims to provide a reference for the selection of chemotherapeutic drugs for multi-line therapy for patients with advanced STSs who have an increasingly long survival.

Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.

In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, proteins, and other secreted molecules. We conclude by discussing potential osteosarcoma-limiting agents and their clinical studies.

The promising roles of exosomal microRNAs in osteosarcoma: A new insight into the clinical therapy.

Osteosarcoma is the most common malignant bone sarcoma in children. Chemotherapy drugs resistance significantly hinders the overall survival of patients. Due to high biocompatibility and immunocompatibility, exosomes have been explored extensively. Multiple parent cells can actively secrete numerous exosomes, and the membrane structure of exosomes can protect miRNAs from degradation. Based on these characteristics, exosomal miRNAs play an important role in the occurrence, development, drug resistance. Therefore, in-depth exploration of exosome biogenesis and role of exosomal miRNAs will provide new strategies and targets for understanding the pathogenesis of osteosarcoma and overcoming chemotherapy drug resistance. Moreover, advancing evidences have showed that engineering modification could attribute stronger targeting to exosomes to deliver cargos to recipient cells more effectively. In this review, we focus on the mechanisms of exosomal miRNAs on the occurrence and development of osteosarcoma and the potential to function as tumor biomarkers for diagnosis and prognosis prediction. In addition, we also summarize recent advances in the clinical application values of engineering exosomes to provide novel ideas and directions for overcoming the chemotherapy resistance in osteosarcoma.

A nanomedicine based on stoichiometric coordination of camptothecin and organoplatinum (II) for synergistic antitumor therapy.

Precise combination therapy, involving multiple chemotherapeutics with pharmacologically synergistic antitumor effects, is a promising approach to address the challenge of monotherapy with insufficient activity towards their targets of interest. We employed Pt←pyridine coordination-driven assembly to construct a stoichiometric coordination complex of camptothecin and organoplatinum (II) (Pt-CPT). The Pt-CPT complex exhibited a remarkable synergistic effect toward several tumor cell lines, which is equal to the optimal synergistic effect of (PEt3)2Pt(OTf)2 (Pt) and CPT mixture at various ratios. An amphiphilic polymer with H2O2-responsiveness and glutathione (GSH)-depleting ability (PO) was used to encapsulate Pt-CPT complex to enable the nanomedicine (Pt-CPT@PO) with prolonged blood circulation and elevated tumor accumulation. The Pt-CPT@PO nanomedicine exhibited remarkable synergistic antitumor efficacy and antimetastatic effect on a mice orthotopic breast tumor model. This work demonstrated the potential of stoichiometric coordination-driven assembly of organic therapeutics with metal-based drugs in developing advanced nanomedicine with optimal synergistic antitumor activity. STATEMENT OF SIGNIFICANCE: In this study, for the first time, we employed Pt←pyridine coordination-driven assembly to construct a stoichiometric coordination complex of camptothecin and organoplatinum (II) (Pt-CPT), with an optimal synergistic effect at various ratios. Then it was encapsulated into an amphiphilic polymer with H2O2-responsiveness and glutathione (GSH)-depleting ability (PO) to enable the nanomedicine (Pt-CPT@PO) with prolonged blood circulation and elevated tumor accumulation. The Pt-CPT@PO nanomedicine exhibited remarkable synergistic antitumor efficacy and antimetastatic effect on a mice orthotopic breast tumor model.

The efficacies and biomarker investigations of antiangiogenic agents and PD-1 inhibitors for metastatic soft tissue sarcoma: A multicenter retrospective study.

Objective: To investigate the efficacy and safety of antiangiogenesis-immunotherapy in patients with advanced STS in China, and to explore the potential factors of prognosis. Patients and Methods: This retrospective study was conducted at three hospitals in China, and the patients with metastatic STS who were ineligible for or declined anthracycline-based chemotherapy received antiangiogenic agents (anlotinib or apatinib) plus programmed death-1 (PD-1) inhibitors (camrelizumab or sintilimab) between June 2019 and May 2022. The primary endpoint was progression-free survival rate at 6 months (6-month PFSR), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) and toxicity. Biomarkers that might affect the prognosis were explored. Results: Thirty-nine patients were included: five patients with alveolar soft tissue sarcoma (ASPS) and 34 with non-ASPS. With a median follow-up of 18.2 months, the 6-month PFSR was 51.3%, with the ORR of 20.5% and DCR of 76.9%. The median PFS and OS were 7.0 months and 17.2 months. The 6-month PFSR for patients with ASPS and non-ASPS was 80.0% and 47.1%, respectively. The most common adverse events were hypothyroidism (56.4%), followed by fatigue (46.2%), and hypertriglyceridemia (43.6%). No treatment-related deaths were observed. Patients with low baseline NLR (NLR < 4) had better 6-month PFSR than those with high NLR (NLR ≥ 4) (82.4% vs. 31.6%). Conclusion: Antiangiogenic agents plus PD-1 inhibitors showed acceptable toxicity and promising efficacy in patients with advanced STS, especially patients with ASPS, and a low NLR might serve as a reliable biomarker for 6-month PFSR, PFS, and OS. It provides a reference for randomized controlled trials.

NF1-Related MicroRNA Gene Polymorphisms and the Susceptibility to Soft Tissue Sarcomas: A Case-Control Study.

Soft tissue sarcomas (STS) are rare malignant tumors of mesenchymal origin, which are easy to metastasize and relapse and are a great threat to human health. In our previous study, the abnormal expression of neurofibromin 1 (NF1) is observed in tumor tissue of STS, and the NF1 gene is regulated by miRNAs. The study aimed to assess the association between NF1-related miRNA gene polymorphisms and the risk of STS. In this case-control study, the information and peripheral blood were collected from 169 patients with STS and 170 healthy controls. Six single-nucleotide polymorphisms of the NF1-related miRNAs were investigated and genotyped using a Sequenom MassARRAY® matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. The association between the polymorphisms and the risk of STS was estimated using unconditional logistic regression analysis. There was a significant statistical difference on genotype distribution of miR-199a2 rs12139213 between the case group and the control group (p = 0.026). Comparing with individuals with wild-type AA, individuals with the AT/TT genotype had a 1.753-fold (odds ratio [OR] = 1.753, 95% confidence interval [CI] = 1.090-2.819, p = 0.021) increased risk of STS and 1.907-fold (OR = 1.907, 95% CI = 1.173-3.102, p = 0.009) increased risk of STS adjusted for age and smoking status. Individuals with the AG/GG genotype for miR24-3p rs4743988 displayed a significantly reduced risk of STS compared with individuals with homozygous mutations AA (OR = 0.605, 95% CI = 0.376-0.973, p = 0.038). Individuals carrying the AT/TT genotype for miR-199a2 rs12139213 or the AA genotype for miR24-3p rs4743988 may be susceptible to STS, which could be potential biomarkers for the diagnosis of STS.

The pedicled sartorius flap and mesh (PSM) technique vs no reconstruction in repairing the defect after type III pelvic bone tumor resection: a retrospective study.

BACKGROUND: Type III pelvic bone tumor resections are often accompanied by postoperative complications. In order to reduce complications, we developed a novel pedicled sartorius flap and mesh (PSM) technique to reconstruct the pelvic ring defect. In this study, we evaluated the efficacy and risks of this PSM technique in type III pelvic bone tumor resections by comparing outcomes between patients that underwent PSM reconstruction and patients that did not receive any reconstruction. METHODS: We retrospectively reviewed a consecutive set of patients that underwent type III pelvic bone tumor surgeries in our center from January 2020 to January 2021 with either PSM reconstruction (designated as the PSM group) or without any reconstruction (designated as the control group). General information such as age, gender, tumor type, tumor size, and surgical-related information such as duration of surgery, blood loss, and the surgical margins was collected. Outcome data recorded included wound complications such as infection and dehiscence, local recurrence, and Musculoskeletal Tumor Society (MSTS) scores for postoperative functional evaluation. Statistical analysis between both groups was performed with GraphPad Prism v7. RESULTS: A total of 20 patients were included in this study (PSM group n = 12, control group n = 8). While no herniation was found in the PSM group, it occurred in 6 of 8 cases in the control group. The control group showed a significantly higher rate of bacterial infection (p = 0.03) and wound dehiscence (p = 0.02) but lower MSTS scores (p < 0.05) compared to the PSM group. CONCLUSIONS: The use of the PSM technique can significantly reduce postoperative complication rates and enhance postoperative function following type III pelvic bone tumor resection.

LncRNA STK4 antisense RNA 1 (STK4-AS1) promoted osteosarcoma by inhibiting p53 expression.

BACKGROUND: LncRNA STK4 antisense RNA 1 (STK4-AS1) has been identified as a potential biomarker associated with multiple cancers. We proposed that STK4-AS1 plays a role in the proliferation of osteosarcoma by regulating the cell cycle. METHODS: We compared the expression of STK4-AS1, p53, and p21 in osteosarcoma vs normal samples in clinical tissues and cell lines. We determined the effect of overexpression and knockdown of STK4-AS1 in p53 expressing osteosarcoma cells U2OS, p53 muted osteosarcoma cells MG63, and osteoblast cells hFOB on p53 and p21 expression and the cell viability. For U2OS and MG63, the cell cycle was analyzed and the expression of cyclin proteins was determined. We overexpressed p53 or p21 in STK4-AS1 overexpressed cells to explore the association of STK4-AS1 and p53 in U2OS. RESULTS: The STK4-AS1 expression was higher and p53 and p21 expression were lower in osteosarcoma tissue and cells than in their non-cancer counterparts. The expression of STK4-AS1 was negatively correlated with the expression of p53 or p21. Knockdown of STK4-AS1 in U2OS decreased the cell viability, increased cells in the G0/G1 phase, decreased cells in the S and G2/M phase, decreased expression of cyclin A and B, increased p53 and p21, and had no effect on cyclin D and cyclin E, while overexpression of STK4-AS1 did the opposes. Overexpression of p53 or p21 recovered some changes caused by STK4-AS1 overexpression in U2OS. MG63 expressed no p53 and the expression of p21, cyclin A, and cyclin B, cell viability, and cell cycle were not affected by altered STK4-AS1 levels. In hFOB cells, the expression of p53 and p21 was decreased and the cell viability was increased when STK4-AS1 was overexpressed, but they were not affected when STK4-AS1 was knocked down. CONCLUSION: LncRNA STK4-AS1 promoted the cell cycle of osteosarcoma cells by inhibiting p53 expression.