No abstract

Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.

Synovial sarcoma is an aggressive soft tissue sarcoma with only a modest response to conventional cytotoxic agents. In the present study, we evaluated the potential antitumor effects of a novel anti-angiogenesis agent, pazopanib, against synovial sarcoma cells. We found that pazopanib directly inhibited the growth of synovial sarcoma cells by inducing G1 arrest. Multiplex analyses revealed that the PI3K-AKT pathway was highly suppressed in pazopanib-sensitive synovial sarcoma cells. Furthermore, administration of pazopanib highly suppressed the tumor growth in a xenograft model. Taken Keywords: synovial sarcoma; pazopanib; PI3K-AKT pathway; molecular targeted therapy Synovial sarcoma accounts for approximately 5-10% of the soft tissue sarcoma in adults, and predominantly affects young adults in their third to fifth decade of life. 1 Typically, it is found as a slow-growing mass in the muscle of a limb or in the body wall. However, it is a clinically aggressive neoplasm, and patients suffering from this tumor have a relatively poor prognosis with a 5-year survival rate of 50-80%. 2,3 Past studies have accumulated a substantial amount of biological information on this neoplasm, including the characteristic chromosomal translocation, t(X;18)(p11.2;q11.2), which gives rise to a chimeric protein, SYT-SSX, 4 and extensive data on the gene expression profiling using cDNA microarrays. 5,6 Despite the progress in understanding the biology of synovial sarcoma, surgical removal still remains as the modality of choice, and other therapeutic approaches, including radiation and chemotherapy, have thus far not been shown to be highly curative. Therefore, there is much room for improvement of systemic therapy, especially given that the majority of patients who expire from synovial sarcoma die from metastatic disease.Pazopanib is a multi-kinase inhibitor which potently inhibits the activity of several receptor tyrosine kinases (RTKs), including vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1), VEGFR2, VEGFR3, platelet-derived growth factor (PDGF) receptor a (PDGFRa), PDGFRb, and c-Kit. 7 Since these RTKs are not only essential for tumor neoangiogenesis, but also for cell proliferation and survival in certain of tumors, treatment with pazopanib potentially has dimorphic effects in suppressing tumor growth in vivo. In accordance with these observations, pazopanib is currently being used in clinical practice to treat advanced renal cell carcinoma, which frequently produces high amounts of VEGF and PDGF from a loss of function of the von Hippel-Lindau tumor suppressor gene. 8 Although the clinical studies of pazopanib has mainly been focused on carcinoma patients, a recent phase II clinical study in which patients with intermediate to high-grade advanced soft tissue sarcoma were treated with pazopanib indicated the potential effectiveness of pazopanib against leiomyosarcoma and synovial sarcoma. 9 Based on this observation, a phase III clinical study is currently underway to further validate the antitumor eff...

To our knowledge, this is the first case of anaplastic transformation of DTC arising in a metastatic bone lesion described in the literature. In addition, the present case also exhibited severe leukocytosis accompanied by elevated serum G-CSF levels. Clinicians should be aware of the possibility of this occurring in their patients with DTC, as this development calls for a rapid change from observational follow-up to aggressive treatment.

BackgroundLi-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.Case presentationThe patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.ConclusionThis case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.