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Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

PurposeSurgical treatments are technically challenging for lumbar spinal tumor (LST) with extensive retroperitoneal involvements. Our study aimed to report the experience and outcomes concerning interdisciplinary surgical collaborations in managing such LSTs.Patients and MethodsNine patients underwent interdisciplinary surgical treatments which were performed by specialists, namely, spinal, vascular, and urinary surgeries. Data on clinical characteristics were collected, and the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association Score (JOAS) were used in the evaluation before and after surgery. The postoperative complications and the long-term outcomes were reported as well.ResultsThe interdisciplinary work included double J catheter indwelling (n = 9), nephrostomy (n = 5), replacement of the common iliac vein (n = 2), abdominal aorta repair (n = 3), and vital vessel repair (n = 8). The early-stage complications included complaints of moderate low back pain and slight implant shift (n = 1, 11.1%) and tardive ureterodialysis (n = 1, 11.1%). The 3- and 5-year disease-free survival rates were 76.2 ± 14.8 and 50.8 ± 23.0%, respectively, during the mean follow-up of 34.6 ± 17.9 months (range, 9.5–68.7). Besides this, more blood loss was associated with recurrent and metastatic tumor status (p = 0.043) and surgery time >5 h (p = 0.023). Remarkable pain relief and favorable quality of life were achieved based on the postoperative VAS (3.3 ± 0.9, p < 0.001) and JOAS (16.6 ± 0.5, p < 0.001).ConclusionsThe treatments of LSTs with wide-range retroperitoneal involvements require interdisciplinary surgical collaborations to lower the risks and improve the long-term outcomes. High-quality prospective cohort studies with large samples are warranted to establish general surgical protocols in managing LSTs with extensive retroperitoneal involvements.

BackgroundMalignant melanoma is the leading cause of skin cancer-related death. The role of PARVB in malignant melanoma remains unclear. Hypoxia is a hallmark of solid tumors including melanoma. But the regulation role of hypoxia in PARVB expression has not been reported.MethodsHuman malignant melanoma tissues, cell lines and their controls were collected. IHC staining, qRT-PCR and Western blot were performed to reveal the differential PARVB expression. The role of PARVB in tumor growth and metastasis of malignant melanoma was evaluated in vitro and in vivo. The regulation role and mechanism of hypoxia and HIFs in PARVB expression was validated by qRT-PCR, Western blot, ChIP-PCR and Luciferase reporter assays.ResultsPARVB was upregulated in malignant melanoma and correlated with patient survival. OverexpressionofPARVB promoted tumor growth and metastasis of malignant melanoma. Furthermore, hypoxia induced HIF-1α and HIF-2α expression activated PARVB transcription and expression through binding to the specific hypoxia-responsive element (HRE) in the promoter region of PARVB.ConclusionsIn malignant melanoma, Hypoxia induced HIF-1α and HIF-2α expression could directly activate PARVB expression, which further promoted tumor growth and metastasis, inducing poor prognosis. These results indicated that PARVB might be a potential therapeutic target for malignant melanoma.

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