Heterogeneity of Soft Tissue Sarcomas and Its Implications in Targeted Therapy.

Soft tissue sarcomas are a set of malignancies of mesenchymal origin. Due to the rarity and similarity in clinical presentation, they are grouped together and treated similarly in clinic. The response rates for current chemotherapy are around 20% and the median overall survival for advanced soft tissue sarcoma are less than 2 years. Thus, the current strategy with identical treatment for all soft tissue sarcomas is far from satisfactory. In this study, we first reviewed the current clinical and genomic findings of soft tissue sarcoma, paying special attention to the heterogeneities among different tumors. Then we reviewed the state-of-art understanding of targeted therapy in soft tissue sarcoma. We observed tremendous heterogeneity both in clinical and genomic settings between different tumors. Individualized treatment plans demonstrated better response and disease control and should be advocated. In summary, heterogeneity of soft tissue sarcomas requires the development of individualized treatment plans such as targeted therapy.

Gene expression regulations by long noncoding RNAs and their roles in cancer.

Cancers are deadly diseases. The general mystery of carcinogenesis, primary and acquired drug resistance and distant organ metastasis are still puzzles to be solved. Long noncoding RNAs (lncRNAs) are receiving more and more attention in recent years since their roles in transcriptional regulation have been unveiled. Detailed functional annotations of lncRNAs have showed that their regulatory roles are largely determined by their binding partners. LncRNAs directly bind to DNA, RNA and proteins and regulate gene expression at transcriptional, post-transcriptional and post-translational levels. Here we review the current understanding of molecular functions of lncRNAs, will emphasize on their binding partners and summarize their biological roles in cancer.

Up-regulation of HDAC9 promotes cell proliferation through suppressing p53 transcription in osteosarcoma.

Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up-regulation or down-regulation of key genes involved in cell proliferation, cell-cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression.

Reverse posterior interosseous artery flap for reconstruction of the wrist and hand after sarcoma resection.

OBJECTIVE: To report our experience of posterior interosseous artery flap reconstruction of the wrist and hand after soft tissue sarcoma resection. METHODS: Thirteen patients who presented to our institution for treatment of soft tissue sarcomas of the wrist and hand from February 2007 to January 2009 were prospectively enrolled. After tumor resection, the soft tissue defects were covered with posterior interosseous artery flaps. Relevant patient characteristics, results of creation of flap and functional outcomes were reviewed. Relevant clinical characteristics were recorded prior to surgery. The size, pedicle length and thickness of flaps were measured intraoperatively and complications evaluated two weeks after surgery. Functional outcomes and aesthetic results were evaluated 6 to 24 months after surgery, using Enneking's Musculoskeletal Tumor Society (MSTS) 93 functional scoring system. RESULTS: The patients' ages ranged from 14 to 82 years (54.92 ± 19.09 years), including six aged >65 years. Flap sizes varied from 5 cm × 3 cm to 8 cm × 5 cm. Flap survival rate was 100%. One patient had partial necrosis of the Z-shaped incision, which healed with routine wound care. Mean Musculoskeletal Tumor Society functional score was 27.31 ± 3.68. Eleven patients were alive and disease-free at a mean follow-up of 36 months. One patient died of pulmonary metastases 18 months after surgery. One patient developed recurrence and underwent amputation 12 months after surgery. DISCUSSION: Reverse posterior interosseous flaps are reliable flaps for reconstruction of the wrist and hand after soft tissue sarcoma resection. They are suitable for elderly patients. The one-stage surgery and primary healing allow for timely postoperative adjuvant therapy following this type of reconstruction.