• GFP
• Malignant melanoma (MM)
• Oncolytic virotherapy
• cIFNγ
• rNDV

• 2019-2022 Rakuno Gakuen University

Primary intracranial malignant melanoma (PIMM) is rare, and its prognosis is very poor. It is not clear what systematic treatment strategy can achieve long-term survival. This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature.

The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance. He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000. After the surgery, the patient received three cycles of chemotherapy but relapsed locally within 4 mo. Following the second surgery for total tumor resection, the patient received an injection of Newcastle disease virus-modified tumor vaccine, interferon, and β-elemene treatment. The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021. A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed. Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3^rd operation, and the patient recovered well without neurological dysfunction until the last follow-up in June 2022, which was 22 years following the initial treatment.

It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies. Long-term survival is not impossible in patients with these malignancies.

• Primary intracranial malignant melanoma
• Immunotherapy
• Newcastle disease virus-modified tumor vaccine
• β-elemene
• Long-term survival
• Case report

• hypoxia
• immunosuppression
• mechanotherapeutics
• tumor microenvironment
• tumor normalization

• Bone Neoplasms/therapy
• Humans
• Immunotherapy
• Osteosarcoma/therapy
• Sarcoma/drug therapy
• Soft Tissue Neoplasms
• Tumor Microenvironment

• Adenoviridae/genetics
• Genetic Therapy/methods
• Genetic Vectors/genetics
• Herpesviridae/genetics
• Humans
• Neoplasms/genetics
• Neoplasms/therapy
• Vaccine Development
• Viral Vaccines

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin.

Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma.

Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model.

Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

• Ki67
• histopathological assessment
• jaw fibrosarcoma
• patient-derived xenograft (PDX)
• plumbagin

Newcastle disease virus (NDV) is an oncolytic virus. As immunogenicity of tumor cells is enhanced by NDV infection, recombinant NDV-infected tumor vaccines (rNDV-TV) are effective methods for inducing specific immunity. However, several tumor cells resist NDV infection, and tumor specific immunity is not sufficiently induced by rNDV-TV. Therefore, we clarified the factor contributing to the suppression of NDV infection and attempted to improve rNDV-TV. Initially we investigated the correlation between the NDV infection rate and interferon-related gene expression in six murine tumor cell lines. A significant negative correlation was observed between the constitutive gene expression of Interferon-stimulated genes (ISGs) and NDV infectivity. The NDV infection rate was examined in each tumor cell treated with the Janus kinase (JAK) inhibitor ruxolitinib (Rux). Furthermore, we evaluated the Th1 response induction by Rux-treated rNDV-TV (rNDV-TV-Rux). In Rux-treated tumor cells, Oasl2 gene expression was significantly decreased and viral infectivity was increased. In immunized mice, the number of CD8⁺ cells, and those expressing the IFN-γ gene, were significantly increased as compared with Rux-untreated rNDV-TV. The infectivity of the virus was dependent on the degree of ISGs expression in tumor cells. To remedy for this problem, rNDV-TV-Rux was expected to have a Th1 immune response.

• ISG
• Newcastle disease virus
• ruxolitinib
• tumor
• vaccines

• DNA
• chemical modification
• chitosan
• chitosan derivatives
• vaccine

• Animals
• Biocompatible Materials/chemistry
• Chitosan/analogs & derivatives
• Chitosan/chemistry
• Drug Carriers/chemistry
• Drug Delivery Systems
• Humans
• Hydrophobic and Hydrophilic Interactions
• Ligands
• Molecular Structure
• Polyethylene Glycols/chemistry
• Vaccines/administration & dosage
• Vaccines/chemistry
• Vaccines/genetics
• Vaccines, DNA/administration & dosage
• Vaccines, DNA/chemistry
• Vaccines, DNA/genetics