The landscape of gene mutations and clinical significance of tumor mutation burden in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

BACKGROUND: The aim of this study was to evaluate the landscape of gene mutations and the clinical significance of tumor mutation burden (TMB) in patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy. METHODS: A total of 68 patients with soft tissue sarcoma were included. Postoperative tumor tissue specimens from the patients were collected for DNA extraction. Targeted next-generation sequencing of cancer-relevant genes was performed for the detection of gene mutations and the analysis of TMB. Univariate analysis between TMB status and prognosis was carried out using the Kaplan-Meier survival analysis, and multivariate analysis was adjusted by the Cox regression model. RESULTS: No specific genetic mutations associated with soft tissue sarcoma were found. The mutation frequency of TP53, PIK3C2G, NCOR1, and KRAS of the 68 patients with soft tissue sarcoma were observed in 19 cases (27.94%), 15 cases (22.06%), 14 cases (20.59%), and 14 cases (20.59%), respectively. With regard to the analysis of TMB, the overall TMB of the 68 patients with soft tissue sarcoma was relatively low (median: 2.05 per Mb (range: 0∼15.5 per Mb)). Subsequently, TMB status was divided into TMB-Low and TMB-Middle according to the median TMB. Patients with TMB-Low and TMB-Middle were 37 cases (54.41%) and 31 cases (45.59%), respectively. Overall survival analysis indicated that the median overall survival of patients with TMB-Low and TMB-Middle was not reached, and 4.5 years, respectively (P=0.015). CONCLUSION: This study characterizes the genetic background of patients with STS soft tissue sarcoma. The TMB was of clinical significance for patients with soft tissue sarcoma who underwent surgical resection and received conventional adjuvant therapy.

miR-429 inhibits migration and invasion of breast cancer cells in vitro.

Accumulating evidence indicates that microRNAs (miRNAs) are involved in regulating cancer invasion and metastasis, and an increasing number of research demonstrates that miRNAs can promote or inhibit cell motility depending on genetic background of different cancers and the microenvironment. In the present study, we established an in vivo bone metastasis model of breast cancer by injecting MDA-MB-231 cells into the left ventricle of nude mice, and then screened the differentially expressed miRNAs between parental and bone-metastatic MDA-MB-231 cells using miRNA array. The results revealed that decreased expression of miR-429 was probably involved in negatively regulating bone metastasis of breast cancer cells. On the other hand, overexpression of miR-429 in MDA-MB-231 cells remarkably suppressed invasion in vitro. We identified ZEB1 and CRKL as potential targets of miR-429 by analyzing combined results from in silico search and global expression array of the same RNA samples. Immunoblot assay confirmed that miR-429 reduced their expression at protein level. Taken together, our results offer an opportunity for further understanding of the recondite mechanisms underlying the bone metastasis of breast cancer.

[Analysis of surgical treatment of soft tissue sarcomas of the adductor compartment].

OBJECTIVE: To review the outcomes and complications of 21 consecutive patients with soft tissue sarcomas of the adductor compartment treated in our hospital from July 2006 to March 2012. METHODS: Medical records of 21 patients who underwent resection of soft tissue sarcomas of the adductor compartment were reviewed. Eight of the patients had primary operation, other eight had secondary radical excision, and five were admitted for tumor recurrence after operation in local hospitals. Six cases used gracilis or sartorius muscle to fill the cavity after removal of adductor muscle group. Fifteen patients underwent adjuvant treatment including radiotherapy and/or chemotherapy. RESULTS: Seven patients (33.3%) developed wound complications. Five required further surgery and two received dressing changes. All the patients were followed up for 3 to 60 months. During the follow-up period, no tumor recurrence was found in all the patients, only one case had multiple bone and pulmonary metastases, and two cases died (one for pulmonary metastasis at 11 months after surgery, and the other died of heart disease at 36 months post operation). CONCLUSIONS: Good local control rate can be achieved in patients with soft tissue sarcomas of the adductor compartment by using adductor muscle group resection, but it carries a relatively high rate of wound complications requiring proper management.

[Complications and short-term outcomes of intraoperative electron radiotherapy (IOERT) in patients with periarticular soft-tissue sarcomas of the extremities].

OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty-one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen.

[Value of intraoperative electron radiation therapy in the treatment of malignant bone or soft tissue tumors around the joints].

OBJECTIVE: To evaluate the value of intraoperative radiation therapy with electrons (ELIOT) in treatment of malignant bone or soft tissue tumors around the joints. METHODS: From October 2008 to April 2012, nineteen patients with malignant bone or soft tissue tumors around the joints were treated with ELIOT. The tumors were located around the knee joint in 8 patients, around the hip joint in 6 patients, around the elbow joint in 4 patients and around the shoulder joint in one patient. All of the patients underwent limb salvage surgeries. R0 resections were performed in 18 patients, while R1 resection was performed in one patient. The doses of intraoperative radiation ranged from 10 Gy to 22 Gy. The median dose was 19 Gy. More than one ELIOT fields were used in 10 patients because of the large tumor size. RESULTS: Seven patients suffered wound complications. No grade ≥ 3 acute toxicities were observed. One patient developed radiation ulcer and arterial fistula 15 months after surgery and ELIOT, and resulted in amputation finally (grade 4 late toxicity). The mean Musculoskeletal Tumor Society (MSTS) 93 score was 26.26 ± 4.04 (87.5% ± 13.5%), with excellent to good extremity functions in 18 patients (94.7%). Four patients had local recurrences. The estimated locoregional control rates at 1, 2, and 3 years were 81.9%, 73.7%, and 73.7%, respectively. Seven patients died of the diseases. The estimated overall survivals of the entire group of patients at 1, 2, and 3 years were 76.3%, 61.2%, and 51.0%, respectively. CONCLUSIONS: ELIOT is a safe and well-tolerable technique and could be widely used for patients with malignant bone or soft tissue tumors around the joints with acceptable rates of acute and late toxicity. There is positive significance for controlling the tumor local recurrence, preserving the joint function and improving survival quality.

[Clinical treatment and prognosis for clear cell sarcoma: analysis of 19 cases].

OBJECTIVE: To explore the clinical features, prognosis, and optimal treatment strategy of clear cell sarcoma (CCS). METHODS: Nineteen patients, 12 males and 7 females, aged 30. 9, with histologically confirmed CCS, 3 with tumors > or =5 cm and 16 with tumors <5 cm, 5 tumors being located in the upper extremity, 2 in the hand, 6 in the lower extremity, 2 in the foot, 3 in the trunk, and 1 in the head, were hospitalized from March 1973 to March 2007. The primary tumors of all the cases were marginally excised before admission and 10 cases had local relapse at admission. Two presented local lymph node metastasis and 2 presented distant metastasis. Ten patients with tumor relapse underwent re-operation. Eight patients received chemotherapy, 8 radiotherapy and 1 combined chemotherapy and radiotherapy. The patients were followed up for 51.4 months (3-144 months). RESULTS: Tumor recurrence occurred in 1 of the 10 patients who received re-operation. 3 patients developed lymph node metastasis and 2 developed pulmonary metastasis. Of the 9 patients who did not undergo re-operation 7 developed lymph node metastasis, 6 developed pulmonary metastasis and 6 died. The overall 5-year survival rate was 75.2% and the 10-year survival rate was 37.5%. CONCLUSION: CCS is a rare and high grade soft tissue sarcoma with high incidence rates of local recurrence and metastasis, and poor prognosis. The role of chemotherapy and radiotherapy for CCS should be investigated further. The best choice after local recurrence is re-operation.

[Clinical analysis of 14 cases of epithelioid sarcoma].

BACKGROUND & OBJECTIVE: Epithelioid sarcoma is a rare soft tissue sarcoma with a high propensity for aggressiveness, regional nodal spread, and distant metastases. This study was to investigate the clinical features, diagnosis, treatment, and prognosis of epithelioid sarcoma. METHODS: The clinical data of 14 patients with epithelioid sarcoma, admitted to our hospital from 1990 to 2005, were analyzed. All of the 14 patients received initial operations at other hospitals. Eleven patients received extensive excision (9 patients) or amputation (2 patients), and 4 of them also received local lymph node dissection at our hospital; 3 patients received another local excision or extensive excision at other hospitals again. Nine patients received adjuvant radiotherapy and 3 of them also received adjuvant chemotherapy. RESULTS: All diagnoses of epithelioid sarcoma were confirmed by pathology. Of the 14 patients, 12 (85.7%) had local recurrence and 4 (28.6%) had local lymph node metastasis, 9 (64.3%) died within 3 years after initial operation. The overall 1-, 2-, 5-, 10-year survival rates were 71.43%, 55.56%, 27.78%, 13.89%, respectively. CONCLUSIONS: The prognosis of epithelioid sarcoma is poor because of a high propensity for local recurrence, node metastases, and distant metastases. Extensive excision or radical excision combined local lymph node dissection is effective for epithelioid sarcoma.

[Clinical features and prognosis of alveolar soft part sarcoma].

OBJECTIVE: To investigate the clinical feature, suitable treatment and prognosis of alveolar soft part sarcoma. METHODS: The clinical data of 58 such patients treated at our hospital from 1967 to 2006 were retrospectively analyzed. Fifty-three patients except 6 with distant metastasis underwent surgical resection including 33 extensive resection and 19 local resection. Furthermore, 19 patients received postoperative adjuvant radiotherapy or chemotherapy. RESULTS: Eleven of 50 patients who underwent complete resection developed local recurrence. Thirty-One (53.4%) was found to have lung metastasis. The overall 3-, 5-, 10-year survival rate was 89.5%, 74.1% and 57.7%, respectively. The median survival time of the patients was 125 months. The 3-, 5-, 10-year survival rate was 100.0%, 81.6% and 65.3% for female patients, but it was 79.6%, 67.2% and 49.7% for male patients, respectively. CONCLUSION: Alveolar soft part sarcoma usually grows slowly. Though local recurrence is rarely seen, distant metastasis is frequently observed. Lung is the most common organ of metastasis. However, survival can still be long even with lung metastasis. To achieve microscopically complete resection is quite critical to localized alveolar soft part sarcoma. No survival advantage was observed when adding adjuvant radiotherapy and/or chemotherapy. The phenomena of female patient or patient with X chromosome translocation showing better prognosis than the male or other patients needs further investigation.

[Repairing segmental radial bone defect with poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/sol-gel bioactive glass composite porous scaffold].

OBJECTIVE: To investigate the capability of the bone regeneration of poly (3-hydroxybutyrate-co-3-hydroxyvalerate/sol-gel bioactive glass (PHBV/SGBG) composite porous scaffold. METHODS: PHBV/ SGBG composite porous scaffold was implanted into the segmental radial bone defect of the New Zealand white rabbits, PHBV/hydroxylapatite (PHBV/HA) as experimental control. The degradability, biocompatibility, and bone regeneration capability of the implants were evaluated through radiological, histological, computerized graphic, and biomechanical analysis. RESULTS: The new bone formation occurred as early as 4 weeks after implantation of PHBV/SGBG composite porous scaffold. The defect was filled with new bone 8 weeks after the implantation, and was completely repaired 12 weeks after operation. The new bone had normal bone structure and the medullar cavity regenerated. The biomechanical study showed that the anti-compression force of radial specimen in PHBV/SGBG groups was significantly higher than in PHBV/ HA groups (P < 0.05), but no significant difference existed between PHBV/SGBG group and autograft bone group (P>0.05). The PHBV/SGBG composite porous scaffold degraded no sooner than 4 weeks after the implantation and most of scaffold was absorbed after 12 weeks. The proportion of the scaffold to new bone decreased from 60% by week 4 to 8% by week 12. CONCLUSIONS: PHBV/SGBG composite porous scaffold is a degradable bone substitute. It can achieve early bone generation and complete repair. It can be used as an ideal scaffold for tissue-engineering bone.

[Expression of integrin alpha5 and actin in the cells of intervertebral disc under cyclic hydrostatic pressure in vitro].

OBJECTIVE: To investigate the expression of integrin alpha5 and actin in the cells of intervertebral disc under cyclic hydrostatic pressure in vitro. METHODS: The porcine lumbar intervertebral disc cells were isolated and cultured in vitro, and the cells underwent cyclic hydrostatic loading. After that, the expression of integrin alpha5 and actin in intervertebral disc cells were studied by means of morphology observing, Western blot and immunohistochemistry staining. RESULTS: The morphology of intervertebral disc cells were changed into smaller and flatten shape, and the expression of integrin alpha5 and actin were decreased after loading. CONCLUSIONS: The expression of integrin alpha5 decreases under cyclic hydrostatic pressure, and the actin is affected at the same time when signals are transferred into the cells by integrin alpha5. That may be one of the important mechanisms of the mechanotransduction in the cells of intervertebral disc.