Search

Soft tissue sarcomas (STSs) are a rare cancer type. Almost half are unresponsive to multi‐pronged treatment and might therefore benefit from biologically targeted therapy. An emerging target is glycogen synthase kinase (GSK)3β, which is implicated in various diseases including cancer. Here, we investigated the expression, activity and putative pathological role of GSK3β in synovial sarcoma and fibrosarcoma, comprising the majority of STS that are encountered in orthopedics. Expression of the active form of GSK3β (tyrosine 216‐phosphorylated) was higher in synovial sarcoma (SYO‐1, HS‐SY‐II, SW982) and in fibrosarcoma (HT1080) tumor cell lines than in untransformed fibroblast (NHDF) cells that are assumed to be the normal mesenchymal counterpart cells. Inhibition of GSK3β activity by pharmacological agents (AR‐A014418, SB‐216763) or of its expression by RNA interference suppressed the proliferation of sarcoma cells and their invasion of collagen gel, as well as inducing their apoptosis. These effects were associated with G0/G1‐phase cell cycle arrest and decreased expression of cyclin D1, cyclin‐dependent kinase (CDK)4 and matrix metalloproteinase 2. Intraperitoneal injection of the GSK3β inhibitors attenuated the growth of SYO‐1 and HT1080 xenografts in athymic mice without obvious detrimental effects. It also mitigated cell proliferation and induced apoptosis in the tumors of mice. This study indicates that increased activity of GSK3β in synovial sarcoma and fibrosarcoma sustains tumor proliferation and invasion through the cyclin D1/CDK4‐mediated pathway and enhanced extracellular matrix degradation. Our results provide a biological basis for GSK3β as a new and promising therapeutic target for these STS types. [ABSTRACT FROM AUTHOR]

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5- HT3 receptor antagonists, neurokinin-1 receptor antagonists ( NK-1RAs), and dexamethasone for multiple high emetogenic risk ( HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting ( CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. [ABSTRACT FROM AUTHOR]

Background: A consensus has not been reached regarding the optimal pazopanib dosing schedule, which we determined in patients who received pazopanib at our Institution., Patients and Methods: Twenty-five patients who were prescribed pazopanib between 2012 and 2015 were included in this retrospective analysis., Results: The median progression-free survival (PFS) time was 7.7 months. This time (various doses) was similar to that achieved by high-dose pazopanib in the PALETTE study. The log-rank test revealed no significant differences in the PFS times between the low- and high-dose pazopanib groups, with the majority of patients receiving a dose of 400 mg, indicating that controlling the side-effects might be more critical than administering higher doses., Conclusion: Pazopanib should be started from a low dose with careful increase to avoid pazopanib-related side-effects, which is necessary to provide a balance between the life-prolonging effects of pazopanib and quality of life (QoL) of patients., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

We have established a "second-look operation" protocol that consists of whole biopsy of surgical scar tissue following radio-hyperthermo-chemotherapy (RHC) after unplanned excision of soft tissue sarcoma. Out of 30 patients who underwent RHC for soft tissue sarcoma at our Institution, 6 were enrolled into this study to undergo a second-look operation for unplanned excision. Radiotherapy was given to a total dose of 32 Gy. Hyperthermia was conducted once a week, for a total of five sessions. Chemotherapy was performed at weekly intervals. Surgery was performed to excise the scar tissue that was enhanced on preoperative MRI. In all six cases, no residual tumors were identified in resected scar tissue; thus, no additional wide excision was performed. The average follow-up period was 10.9 years. There were no local recurrences, and all patients were alive at their final follow-up. Long-term follow-up confirmed that RHC can replace additional wide excision for unplanned excision of soft tissue sarcoma., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Osteoid osteoma is one type of benign bone tumor that may respond to conservative treatment., Patients and Methods: A retrospective study of 11 patients with osteoid osteoma was performed. Initially, patients were treated with non-steroidal anti-inflammatories (NSAIDs), unless they continued to have intolerable pain, or if the patient requested surgical resection and radiofrequency ablation (RFA)., Results: Conservative therapy was successful for five patients. Three patients were treated with NSAIDs and the mean duration of pain was 22 months. The other two patients went into remission without medication by 9 and 24 months, respectively. Four patients underwent surgery after an average of 12 months. Two patients were treated with RFA after 47 and 11 months, respectively., Conclusion: Osteoid osteoma can be treated conservatively. Surgical resection and radiofrequency ablation should also be taken into consideration as an option when the results of conservative treatment are poor., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)