Low-density lipoprotein receptor-related protein 1 (LRP1, also known as CD91), a multifunctional endocytic and cell signaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, fibroblasts, neurons, astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. For example, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase (MMP)-2 and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor, the serine/threonine protein kinase signaling pathway, and the expression of Caspase-3. LRP1-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1 CpG islands. Furthermore, a novel fusion gene, LRP1-SNRNP25, promotes osteosarcoma cell invasion and migration. Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

Efficacy and safety of Apatinib in stage IV sarcomas: experience of a major sarcoma center in China

As the most aggressive type of skin cancer, melanoma seriously affects human health. Long noncoding (lncRNA) 19 has been demonstrated to be involved in the progression of a number of different types of human cancers. However, the involvement of lncRNA H19 in melanoma remains unknown. Therefore, the present study was performed to investigate the roles of H19 in the development and progression of melanoma. In the present study, 49 patients with melanoma were included. Expression of lncRNA H19 in tumor tissue, adjacent healthy tissue and various cell lines with different treatments was measured by reverse transcription‑quantitative polymerase chain reaction. The effects of H19 knockdown on melanoma cell proliferation, migration and invasion were detected by cell counting kit‑8, wound‑healing and transwell invasion assays, respectively. In addition, the effects of H19 knockdown on the expression of nuclear factor (NF)‑κB pathway‑associated proteins were investigated by western blotting. The results revealed that the expression level of H19 was significantly higher in tumor tissue than in the adjacent healthy tissue of 47 out of 49 patients. H19 knockdown significantly reduced the proliferation, migration and invasion ability of melanoma cells. H19 knockdown also inactivated the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway, which in turn inhibited the activation of the NF‑κB signaling pathway. Thus, downregulation of lncRNA H19 may inhibit the migration and invasion of melanoma cells by inactivating the NF‑κB signaling pathway via the inactivation of the PI3K/Akt signaling pathway. The present study provided references for future studies on the pathogenesis of melanoma and the clinical treatment of this disease.

Extraskeletal osteosarcoma (ESOS) is an extremely rare malignancy with poor prognosis, accounting for 2–4% of all osteogenic sarcomas. The purpose of this study was to examine the oncological outcomes of this disease related to surgical treatment and/or combined adjuvant therapies and to analyze the associated prognostic factors in ESOS. From January 1990 to June 2016, 22 patients with primary ESOS were analyzed in this retrospective study. Overall survival (OS) and progression-free survival (PFS) rates were calculated by Kaplan-Meier methods and compared with log-rank test. 22 patients were diagnosed with ESOS, 19 showed localized diseases and 3 presented with metastatic lesions. The median age at diagnosis was 55.5 years. Surgery resection was performed for all patients, 18 of whom received adjuvant chemotherapy. The median follow-up time was 48.5 months. There were 10 cases of recurrence and 9 patients developed new metastases. The 5-year OS rate for all patients was 58%. For localized cohort, the 5-year OS rate was 62%, and the 3-year PFS rate was 31% with a median PFS of 16 months. Univariate analysis of related prognosis factors showed that larger size of tumor (>5.5 cm) and higher histologic grade emerged as significant factors associated with worse OS. The addition of combination chemotherapy has no effect found on OS or PFS in this study. In summary, for patients who presented with ESOS, larger tumor size and higher histologic grade indicate a lower OS rate. The combination chemotherapy does not improve the OS or PFS.

Apatinib as targeted therapy for sarcoma Apatinib as Targeted Therapy for Sarcoma

Recombined humanized endostatin (Endostar) combined with chemotherapy for advanced bone and soft tissue sarcomas in stage IV Recombined humanized endostatin (Endostar) combined with chemotherapy for advanced bone and soft tissue sarcomas in stage IV