[Efficacy and safety of Anlotinib in the treatment of advanced sarcoma].

Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.

Application of personalized spacers made with 3D-printed mold in the two-stage procedure for periarticular infection.

BACKGROUND: Cement spacers treat periarticular infection after bone tumor resection in patients with bone defects. Complications such as poor joint function, poor soft tissue reconstruction, and poor postoperative daily living ability are present. We present a case of periarticular infection treated successfully after distal femoral osteosarcoma surgery with a personalized spacer made with a 3D-printed mold. CASE REPORT: A two-stage procedure was performed on an 18-year-old patient with high-grade conventional osteosarcoma of the left distal femur. After two biopsies, the boy developed a periarticular infection of the affected limb during neoadjuvant chemotherapy. We had a microbiologically confirmed methicillin-resistant Staphylococcus aureus (MRSA) infection. Because of the infection risk associated with primary joint replacement, a two-stage procedure was planned. In the first stage of surgery, we prepared a personalized spacer using a 3D-printed mold, antibiotic-loaded polymethylmethacrylate (PMMA), and an intramedullary needle. This spacer restored the function of the knee joint and the daily activities of the affected limb, and the infection was effectively eradicated. This spacer was firmly fixed two years after the surgery, and there were no surgical or spacer-related complications. The patient underwent a second stage of surgery to replace a permanent metal mega-prosthesis, and the knee joint functions returned to near normal. CONCLUSIONS: This case report describes limb-salvage surgery following distal femoral resection for periarticular infection. The personalized spacers prepared by a 3D-printed mold can be used in periarticular infection after long bone resection, mega-prosthetic infection, or limb-salvage surgery for temporary joints in small children.

[Role of CT and MRI image fusion and computer assisted simulation technique in guiding type â ¢ and â £ primary pelvic sarcoma surgeries].

Objective: To explore the possible clinical benefits of CT/MRI image fusion and computer-assisted simulation techniques in guiding type Ⅲ and Ⅳ primary pelvic bone tumor surgeries. Methods: The clinic data of primary bone sarcomas patients treated at Department of Bone and Soft Tissue,Zhenghzhou University Affiliated Cancer Hospital from January 2019 to December 2021 were retrospectively analyzed. Based on whether the CT and MRI image fusion technique was utilized for tumor evaluation and surgical planning,the patients were divided into image fusion group (n=21) or control group (n=27). There were 7 male and 14 female patients included in the image fusion group, with the age of (37.0±10.4) years(range: 18 to 67 years). In the control group, there were 10 males and 17 females with the age of (39.7±15.2) years (range: 16 to 65 years). Both groups included osteosarcoma,chondrosarcoma and undifferentiated polymorphic sarcoma as the pathological diagnosis. Clinical information such as gender,age,pathological diagnosis,location of disease,and metastasis at diagnosis were collected. Surgical related information such as duration of surgery,blood loss,surgical margin,and wound complications were also obtained. Periodical follow-ups every 3 months were performed for all patients to monitor the status of local recurrence,distant metastasis,and survival information. Independent t test and χ² test were used for data comparison between groups. Results: Significant reduced duration of surgery was observed in the image fusion group in comparison with control group both in type Ⅲ and Ⅳ surgeries ((144.0±31.6)min vs. (248.2±56) min,t=-8.084, P<0.01); (173.0±42.0)min vs. (306.1±62.0)min, t=-4.518, P<0.01). Blood loss was significantly reduced in the image fusion group compared with the control group ((484.8±226.3)ml vs. (836.1±359.8)ml,t=-4.130, P<0.01). In addition, significant lower ratio of R1 margin and recurrence rates of type Ⅲ and Ⅳ surgeries were found in the image fusion group comparing with the control group (4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040; 4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040).In the image fusion group, there were 3 cases of incision infection, 1 of which underwent secondary debridement.And in thecontrol group there were 7 cases of incision infection, 3 of which underwent secondary debridement. There was no significant difference in the incidence of complications between the two groups (14.2%(3/21)vs. 25.9%(7/27), χ²=0.645, P=0.422). Up to the last follow-up, 1 patient died in the image fusion group and 2 patients died in the control group, the difference was not statistically significant (χ²=1.885, P=0.220). Conclusion: Compared with the traditional operation,the image fusion technique can significantly reduce the duration of surgery,blood loss and lower the recurrence rate by achieving better surgical margins.

Suppression of tumor angiogenesis by targeting the protein neddylation pathway.

Inhibition of protein neddylation, particularly cullin neddylation, has emerged as a promising anticancer strategy, as evidenced by the antitumor activity in preclinical studies of the Nedd8-activating enzyme (NAE) inhibitor MLN4924. This small molecule can block the protein neddylation pathway and is now in clinical trials. We and others have previously shown that the antitumor activity of MLN4924 is mediated by its ability to induce apoptosis, autophagy and senescence in a cell context-dependent manner. However, whether MLN4924 has any effect on tumor angiogenesis remains unexplored. Here we report that MLN4924 inhibits angiogenesis in various in vitro and in vivo models, leading to the suppression of tumor growth and metastasis in highly malignant pancreatic cancer, indicating that blockage of angiogenesis is yet another mechanism contributing to its antitumor activity. At the molecular level, MLN4924 inhibits Cullin-RING E3 ligases (CRLs) by cullin deneddylation, causing accumulation of RhoA at an early stage to impair angiogenic activity of vascular endothelial cells and subsequently DNA damage response, cell cycle arrest and apoptosis due to accumulation of other tumor-suppressive substrates of CRLs. Furthermore, we showed that inactivation of CRLs, via small interfering RNA (siRNA) silencing of its essential subunit ROC1/RBX1, recapitulates the antiangiogenic effect of MLN4924. Taken together, our study demonstrates a previously unrecognized role of neddylation in the regulation of tumor angiogenesis using both pharmaceutical and genetic approaches, and provides proof of concept evidence for future development of neddylation inhibitors (such as MLN4924) as a novel class of antiangiogenic agents.