Expression of Epstein-Barr virus antibodies EA-IgG, Rta-IgG, and VCA-IgA in nasopharyngeal carcinoma and their use in a combined diagnostic assay.

Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma, which can be monitored by the levels of Rta protein antibody IgG (Rta-IgG), early antigen antibody (EA-IgG), and viral capsid antibody (VCA-IgA). In the present study, we investigated the serum levels of Rta-IgG, EA-IgG, and VCA-IgA in nasopharyngeal cancer patients, and the diagnostic value of a combined assay that includes these antibodies in addition to the EBV-DNA. A total of 56 nasopharyngeal cancer patients were recruited as the study population, along with 48 benign rhinitis patients and 42 healthy individuals. Serum EA-IgG, Rta-IgG, and VCA-IgA levels were measured by enzyme-linked immunosorbent assay, and EBV-DNA was quantified with PCR. The diagnostic value of these indices was further evaluated by ROC curve analysis. The expression levels of EA-IgG, Rta-IgG, VCA-IgA, and EBV-DNA were elevated in the nasopharyngeal cancer patients, who had higher levels of these antibodies than those in the rhinitis patients, followed by the healthy individuals. These indices were also increased with advanced TNM stage. The overall diagnostic efficacy was ranked as follows: VCA-IgA, Rta-IgA, EA-IgA, and EBV-DNA. The combined diagnosis using these four indices increased the sensitivity to 98.21% and the negative predictive value to 98.61%, without any significant compromise on the test specificity. In conclusion, EA-IgG, Rta-IgG, VCA-IgA, and EBV-DNA expression levels were elevated in nasopharyngeal patients. The combined diagnostic value of these serum indices has important implications in nasopharyngeal carcinoma.

Evaluation of the expression and role of IGF pathway biomarkers in human sarcomas.

Recent studies have shown that insulin-like growth factor (IGF) signaling components have been involved in the pathogenesis and progression of different types of sarcomas. There has been some evidence to indicate the differential expression of IGF2 and insulin-like growth factor 1 receptor (IGF1R) in human sarcomas. The present study utilized immunohistochemistry (IHC) and in situ hybridization (ISH) to determine the expression of IGF2 and IGF1R in eighty-two cases of human sarcoma specimens and eight cases of non-tumor tissue (NTT). IGF2/IGF1R signaling was blocked by recombinant adenovirus-mediated IGF1R small hairpin RNA (shIGF1R), which was used to transfect into human osteosarcoma (OS) MG-63 cells. The expression of IGF2, IGF1R, matrix metallopeptidase-2 (MMP-2) and MMP-9 was detected by Real-time PCR. Cell migration was evaluated by wound healing assay. As a consequence, the expression of IGF1R and IGF2 was found in human OS with higher strong reactivity rate compared with the NTT (85.0 percent vs 50.0 percent, P=0.022; 95.0 percent vs 100.0 percent, P=0.042), elevating with the ascending order of tumor malignancy. Also, IGF1R had differential expression in different types of sarcomas (P=0.002), while IGF2 had no significant difference (P=0.105). Targeted blockade of IGF2/IGF1R signaling decreased the expression of IGF2, IGF1R, and MMP-2/-9, and diminished the migration capabilities of MG-63 cells. In conclusion, IGF1R is differentially-expressed in different types of human sarcomas, and targeted blockade of IGF1R pathway may inhibit human OS migration through down-regulation of MMP-2/-9 expression. IGF1R pathway may represent a significant therapeutic modality for the treatment of sarcomas.

Percutaneous Sacroplasty with or without Radiofrequency Ablation for Treatment of Painful Sacral Metastases.

BACKGROUND AND PURPOSE: Percutaneous sacroplasty is a variation of percutaneous vertebroplasty that has gained attention as a therapeutic option for patients with painful sacral insufficiency fractures due to osteoporosis or metastases. Additionally, percutaneous sacroplasty can also be used to treat painful sacral metastases without a pathologic fracture. The purpose of this retrospective study was to compare the efficacy and safety of fluoroscopy-guided percutaneous sacroplasty alone versus percutaneous sacroplasty plus radiofrequency ablation for the treatment of painful sacral metastases. MATERIALS AND METHODS: For this retrospective study, 126 patients (with a total of 162 painful sacral metastases) were enrolled from October 2012 to February 2021 and assigned to receive either percutaneous sacroplasty plus radiofrequency ablation (n = 51, group A) or percutaneous sacroplasty alone (n = 75, group B). Four different approaches were used for percutaneous sacroplasty: transiliac, interpedicular, anterior-oblique, and posterior. The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale were used to evaluate outcomes. RESULTS: The Visual Analog Scale, Oswestry Disability Index, and Karnofsky Performance Scale scores showed significant improvement in both groups after treatment (P < .05). The overall pain relief rate was significantly better in group A than in group B (90% versus 76%, P = .032). There were no significant differences in the incidence of polymethylmethacrylate leakage between the 2 groups or among the 4 different approaches (P > .05). CONCLUSIONS: Both percutaneous sacroplasty alone and the combination of percutaneous sacroplasty and radiofrequency ablation are safe and effective for treatment of painful sacral metastases. The combination of percutaneous sacroplasty and radiofrequency ablation appears to be more effective than percutaneous sacroplasty alone.

TopBP1 promotes malignant progression and correlates with poor prognosis in osteosarcoma.

OBJECTIVE: Topoisomerase IIß binding protein 1 (TopBP1) is involved in DNA damage and replication checkpoint and has been shown to be related to tumorigenesis in many cancer types. This study aimed to evaluate the biological role and clinicopathological significance of TopBP1 in OS. PATIENTS AND METHODS: TopBP1 expression in sarcoma patients was determined through the Oncomine database, and the prognostic role of TopBP1 expression was assessed in a retrospective cohort study. CCK-8 assay and colony formation assay were employed to evaluate the effect of TopBP1 on proliferation and chemoresistance in OS cells. Cell apoptosis and cell cycle assay were used to assess the effect of TopBP1 on apoptosis and cycle of OS cells. RESULTS: We observed that TopBP1 expression was elevated not only in OS, but also in other sarcoma types including myxofibrosarcoma, liposarcoma, and leiomyosarcoma. Knockdown of TopBP1 using small interfering (si) RNA blocked cell proliferation and colony formation ability, and caused cell apoptosis as well as G1-phase arrest in OS cells. Moreover, TopBP1 knockdown decreased the chemoresistance of OS cells to both doxorubicin and cisplatin. Lastly, the retrospective cohort study showed that high TopBP1 expression was not only associated with high local recurrence and low necrosis rate, but also correlated with poor overall survival and disease-free survival of OS patients. CONCLUSIONS: Our findings indicate that TopBP1 contributes to the cell survival and chemoresistance to doxorubicin and cisplatin of OS, suggesting TopBP1 may serve as a novel target for inhibition of progression and chemotherapeutic resistance in OS patients.

HGFK1 inhibits bone metastasis in breast cancer through the TAK1/p38 MAPK signaling pathway.

Breast cancer metastasis to bone represents a devastating complication of advanced breast cancer, frequently resulting in significant increases in morbidity and mortality. An understanding of the mechanisms that govern breast cancer metastasis at the molecular level should lead to more effective therapies. Recently, the kringle 1 domain of human hepatocyte growth factor (HGFK1) was identified as a candidate metastasis suppressor gene. Here, we investigated whether HGFK1 is a key regulator of breast cancer bone metastasis. Of the 193 human breast carcinoma tissue samples examined, HGFK1 expression was relative higher in 82 (42.4%) by western blot and in 84 (43.5%) by quantitative real-time PCR. The higher expression of HGFK1 was significantly associated with a better prognostic value (P<0.001) and inversely correlated with bone metastasis (P=0.003). The efficacy of adeno-associated virus carrying HGFK1 (AAV-HGFK1) in osteolytic bone metastasis was then evaluated using an in vivo bone metastasis model. AAV-HGFK1 significantly inhibited osteolytic bone metastasis and prolonged the survival of mice in this model (P<0.01). In vitro, HGFK1 expression resulted in significant anti-invasion effects, enhanced the phosphorylation of TAK1 (transforming growth factor-ß-activated kinase 1), p38 MAPK (mitogen-activated protein kinase) and MAPKAPK2 (MAPK-activated protein kinase 2) and decreased the expression of receptor activator of nuclear factor-κB (RANK), which was abrogated by the p38 MAPK inhibitor SB203580. This study shows for the first time that HGFK1 significantly inhibits the metastasis of breast cancer to bone by activating the TAK1/p38 MAPK signaling pathway and inhibiting RANK expression. Thus, AAV-HGFK1 treatment represents a potential therapy for bone metastasis in breast cancer.