Revision balloon kyphoplasty and vertebra-pediculoplasty using cannulated screws for osteoporotic vertebral fractures with cement dislodgement following conventional balloon kyphoplasty.

We report the usefulness of revision balloon kyphoplasty (re-BKP) and vertebra-pediculoplasty using cannulated screws (VPCS) for osteoporotic vertebral fractures (OVF) following cement dislodgement of conventional BKP. Between 2015 and 2020, three patients with OVF developed symptomatic cement dislodgement following BKP and underwent re-BKP. All three patients showed a loose cemented mass and spinal instability. Balloon inflation was performed in the gap between the loosened cemented mass and the remaining cortical bone rim, and this extended gap was filled with cement. To prevent re-dislodgement of the cement mass, a cannulated screw was inserted into the cemented mass through the pedicle. All patients achieved early pain relief, and improved vertebral stability of the fractured vertebra and all related symptoms, with no perioperative complications. Re-BKP and VPCS are innovative concepts and could be an effective minimally invasive treatment for OVF following cement dislodgement of conventional BKP treatment.

Aquaporin-1 and -5 are involved in the invasion and proliferation of soft tissue sarcomas.

BACKGROUND AND AIM: Recent studies of several carcinomas have reported that aquaporin possesses novel oncogenic properties. The aim of this study was to clarify the involvement of aquaporin-1 and -5 in the proliferation, invasion and metastasis of soft tissue sarcomas. MATERIALS AND METHODS: The expression of aquaporin-1 and -5 was immunohistochemically examined in 73 soft tissue sarcomas as well as in benign, locally aggressive soft tissue tumors, and in soft tissues of adult humans and human fetuses. The mRNA and protein expression of aquaporin-1 and -5 genes were quantified in 19 sarcoma tissues. RESULTS: Aquaporin-1 was expressed in the tumor cells of 37 (51%) and aquaporin-5 in 29 (40%) of 73 soft tissue sarcomas. Two expression patterns were identified: a differentiation-dependent pattern, similar to their expression in adult human soft tissue and in benign soft tissue tumors, and an aggressiveness-related pattern, that is similar to their expression in the mesenchymal cells of the developing fetal limb. The latter expression pattern proved to be an independent prognostic factor for patients with soft tissue sarcoma, in which aquaporin-1 was related to the invasiveness, and aquaporin-5 to the proliferation of soft tissue sarcoma cells. CONCLUSION: These results indicate pivotal roles for aquaporin-1 and -5 in the aggressive growth and metastatic potential of soft tissue sarcomas, suggesting that they are promising targets for the treatment of patients with intractable soft tissue sarcoma.

Identification of novel genes involved in the synergistic antitumor effect of caffeine in osteosarcoma cells using cDNA macroarray.

BACKGROUND: Caffeine enhances the cytocidal effects of DNA-damaging agents. This study investigated genes involved in the synergistic effect of caffeine on osteosarcoma cells using gene-profiling analysis. MATERIALS AND METHODS: Sensitivity to cisplatin and the synergistic effect of caffeine were evaluated in five osteosarcoma cell lines with different p53 gene status. Gene expression profiles were analyzed using cDNA macroarray and verified by real-time RT-PCR. RESULTS: The cell lines were grouped into three types with different cytotoxic patterns. Comparison of profiling data from these groups identified twelve novel genes associated with the synergistic effect of caffeine. Real-time RT-PCR analyses verified up-regulation of two apoptosis-enhancing genes and down-regulation of two interferon-inducible genes related to the synergy of caffeine. CONCLUSION: These findings provide new insights into the molecular mechanisms of the synergistic effect of caffeine related to p53 gene status in osteosarcoma, providing candidates for an assay of responsiveness to caffeine-potentiated chemotherapy for osteosarcoma.

Down-regulation of plakoglobin in soft tissue sarcoma is associated with a higher risk of pulmonary metastasis.

Soft tissue sarcomas (STS) behave with aggressiveness and metastatic potential, that can vary depending on their locations. There has been little information on the exact molecular mechanisms involved in their biological aggressiveness. To identify genes involved in the differences, the gene expression profiles were compared between STS-orthotopic and heterotopic implanted models, and their significance in human STS was verified. Human fibrosarcoma HT1080 cells were implanted either in the quadriceps femoris muscles or footpads of nude mice, and the gene expression profiles of the tumors were compared by cDNA arrays. The mRNA and protein levels of the identified genes were examined by both real time RT-PCR and immunohistochemistry not only in the tumors of the models, but also in clinical STS. The implanted HT1080 cells demonstrated different growth and metastatic potentials depending on their implant locations. cDNA array analyses showed decreased expression of the plakoglobin gene in the intramuscle-implanted group, which was statistically confirmed by real-time RT-PCR (p = 0.04). Plakoglobin was immunolocalized diffusely in the cytoplasm of tumor cells implanted in the footpads, but not those in the muscle. Real-time RT-PCR assays of clinical STS showed that the mean plakoglobin/glyceraldehyde 3-phosphate dehydrogenase (G3PDH) ratio in primary sarcoma tissues with pulmonary metastases (0.92) was significantly lower than in those without metastasis (6.58) (p < 0.0001), and that STS cases with high plakoglobin gene expression had an excellent prognosis. These results suggest that plakoglobin gene expression level might be useful as a new biomarker for metastasis and prognosis of human STS.

[Association of gene FN1 with pulmonary metastasis of human fibrosarcoma].

OBJECTIVE: To investigate the genes involved in pulmonary metastasis of human fibrosarcoma HT1080 cells in nude mice. METHODS: HT1080 cells were injected into the tail vein of BALB/ C nude mice. RNA samples were extracted from pulmonary metastatic tissues and normal control lung tissues, purified using Atlas Pure Total RNA labeling System (Clonetech Laboratories). cDNA probes labeled with 32P were prepared and hybridized to a cDNA membrane constructed with spots of 1176 human cancer related genes and radioactivities on the membrane were measeured by BAS 5000. The mRNA expression of gene FN1 was determined by real time RT-PCR using TaqMan methods. Furthermore, cells with FN1 expression were localized and obtained in situ in pulmonary metastatic foci by laser captured microdissection, and the FN1 expression was quantitated by real time RT-PCR. RESULTS: Of the total 1176 genes, 27 genes (2. 3%) revealed to be apparently up-regulated and 4 genes (0. 3% ) down-regulated. Real time RT-PCR analysis verified significant up-regulation of gene FN1. Laser captured microdissection/ real time RT-PCR analysis demonstrated up-regulated gene FN1 not in stroma cells but in tumor cell nests. CONCLUSION: Gene FN1 expression in fibrosarcoma HT1080 cells may be involved in pulmonary metastasis.

Expression Analysis for the Identification of Genes Involved in Acquired Resistance to Cisplatin in Osteosarcoma Cells.

BACKGROUND: Clinical observations indicate that tumour cells can acquire tolerance when an anticancer drug is administered repeatedly. In the present study, the gene expression in cisplatin-resistant cells was analysed to identify early changes in gene expression in the course of cisplatin exposure. MATERIALS AND METHODS: After establishing a cisplatin-resistant human osteosarcoma subline (OST/R) and two additional sublines by more brief repeated exposure, cDNA expression microarrays were used to study genes linked with prolonged exposure to cisplatin of human cancer cells. RESULTS: OST/R cells showed increased expression of 17 genes and reduced expression of 14. Genes associated with DNA repair, apoptosis, cell cycle progression, and proliferation were associated with the acquired resistance. Genes showing early changes were also identified. CONCLUSION: Identification of genes showing altered expression in the early stages of development of resistance to cisplatin may help to improve the therapeutic effectiveness of this drug.

Rapid determination method of caffeine and application to monitoring of caffeine-assisted chemotherapy.

Caffeine-assisted chemotherapy for bone and soft tissue tumours is very effective. However, high serum caffeine concentrations cause severe side effects, so monitoring of the serum level during therapy is important. For this purpose, a rapid determination method was established by high-performance liquid chromatography after solid-phase extraction. This method can measure caffeine and its three major metabolites in serum samples within 8 min. The mean serum caffeine concentrations of patients were 34.6+/-7.8, 54.5+/-11.9 and 73.0+/-12.8 microg/ml at 24, 48 and 72 h, respectively, after the start of a 1500 mg/m2/day continuous infusion for 72 h. The distribution volume of caffeine was 0.65+/-0.23 l/kg, and the total body clearance was 0.025+/-0.011 l/h/kg, which was one-third of the reported low dose clearance. The appropriate infusion rate was calculated to avoid severe side effects in the final phase of the infusion by using a one-compartment constant infusion model based on the serum levels measured at 24 and 48 h. Caffeine clearance did not correlate with the metabolite/caffeine ratio in serum at any time. It is concluded that individual monitoring with this method for the purpose of dose adjustment is useful for avoiding the side effects of caffeine-assisted chemotherapy.

Intentional marginal excision of osteosarcoma of the proximal fibula to preserve limb function.

Three cases of osteosarcoma (stage IIB) of the proximal fibula were successfully treated by marginal excision that preserved the common peroneal nerve and lateral stabilizers of the knee joint. Caffeine-assisted chemotherapy was administered to three boys, ages 15, 17, and 11 years, and resulted in a complete response. Two patients initially presented with peroneal nerve palsy that resolved completely with preoperative chemotherapy. The subsequent intentional marginal procedures resulted in preservation of the common peroneal nerves, lateral collateral ligaments, and biceps femoris tendons. In two cases the collateral ligament and biceps tendon were reattached to the tibia with a spike washer or suture anchors, and in the third case they were reattached by suture only to the ligamentous and capsular structure of the tibia. All three patients have normal ankle and knee joint function without evidence of recurrence 122, 120, and 61 months after surgery, respectively. Preservation of limb function without compromising the principles of tumor surgery is a desirable goal in any patient but particularly in young patients. For patients with osteosarcoma of the proximal fibula, this approach provides a better quality of life than conventional wide excision.

Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese Musculoskeletal Oncology Group study.

PURPOSE: The prognostic value of the time of identification of lung metastasis was investigated in 280 patients with metastatic lung osteosarcoma as a multi-institutional study of the Japanese Musculoskeletal Oncology Group. PATIENTS AND METHODS: The 280 patients with lung metastasis were divided into four groups: group 1, patients with lung metastasis identified at initial presentation; group 2, those with lung metastasis identified during preoperative chemotherapy; group 3, those with lung metastasis identified during postoperative chemotherapy, and group 4, those with lung metastasis identified after completion of treatment. Survivals of the four groups were compared. Additionally, the effects of number of metastatic nodules, metastasectomy, and the effect of chemotherapy on the primary tumor on survival of the four groups were analyzed. RESULTS: There were 46 patients in group 1, 30 in group 2, 94 in group 3, and 110 in group 4. The overall 2-year survival rates from the time of identification of lung metastasis were 33%, 31%, 24%, and 40% for groups 1, 2, 3, and 4, respectively, whereas the 5-year survival rates were 18%, 0%, 6%, and 31%, respectively. Patients in group 4 thus demonstrated significantly better prognosis than any of the other patients (P <.0001). CONCLUSION: Time of identification of lung metastasis is an important prognostic factor. In terms of clinical behavior, groups 2 and 3 are completely different than group 4. These data ensure the need to stratify stage III osteosarcomas into subgroups according to the time of diagnosis of lung metastases. To improve the survival of osteosarcoma patients, new treatment modalities should be introduced into the treatment armamentarium for lung metastasis from osteosarcoma, especially in groups 1, 2, and 3.