Osteofibrous dysplasia-like adamantinoma: A case report and literature review.

Abstract background: Osteofibrous dysplasia-like adamantinoma (OFD-like adamantinoma), classical adamantinoma and dedifferentiated adamantinoma were previously considered to be three subtypes of adamantinoma of long bones. In the 5th edition of the World Health Organization (WHO) classification of bone tumors in 2020, OFD-like adamantinoma was newly proposed and classified as an intermediate-locally aggressive tumor in other mesenchymal tumors of bone. OFD-like adamantinoma is rare, accounting for only 0.4% of all primary bone tumors. OFD-like adamantinoma is often misdiagnosed due to the insufficient understanding of it. Here we report a case of OFD-like adamantinoma treated in our hospital with a literature review. Case presentation: The patient, a 14-year-old male, had swelling in his right leg with intermittent pain for one year. Plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. Based on the radiological and histological examinations, a diagnosis of OFD-like adamantinoma was suspected. After admission, the patient underwent tumor resection of the right tibia, free transplantation of the left fibula and internal fixation. After resection of the tumor, the wound recovered well, the vital signs were stable, and activity was normal. The patient has been followed up for more than a year with no recurrence or distant metastasis. Conclusion: OFD-like adamantinoma is a rare primary bone tumor with nonspecific clinical features. Imaging examination can demonstrate the lesion and help diagnosis. The pathological discovery of epithelioid tissue is the key evidence for diagnosis.

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.

Decreased FOXF1 promotes hepatocellular carcinoma tumorigenesis, invasion, and stemness and is associated with poor clinical outcome.

Forkhead box F1 (FOXF1), a member of the forkhead transcription factor superfamily, plays critical roles in the progression of certain types of cancers. However, the expression and function of FOXF1 in human hepatocellular carcinoma (HCC) are still unclear. Quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry detected the relatively lower expression status of FOXF1 in HCC cases. Soft agar and transwell assays clearly demonstrated that FOXF1-knockdown cells showed significantly increased in vitro cell tumorigenesis and invasion, and FOXF1-overexpressing cells had significantly reduced growth and invasion potential. Our study also examined the role of FOXF1 in HCC cell stemness by sphere formation, aldehyde dehydrogenase (ALDH1) activity, and CD44/133-positive cell analysis. Enforced FOXF1 expression decreased HCC cell stemness, and the downregulation of FOXF1 promoted cancer cell stemness. The in vivo study showed that overexpressed FOXF1 inhibits nude mouse tumorigenicity with downregulation of CD44 and proliferating cell nuclear antigen. More importantly, loss of FOXF1 expression was linked to poor overall survival time by Kaplan-Meier analysis.

MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma.

To obtain microRNA (miRNA) profile and clarify their biological function in tumorigenic Sca-1(+) CD34(+) cells during carcinogenesis of lung adenocarcinoma. After intranasal infection with recombinant Adeno-Cre viruses (AdV-Cre), lung adenocarcinoma was identified pathologically in Lox-stop-lox Kras (LSL-Kras) G12D mice. Sca-1(+) CD34(+) cells were sorted by flow cytometry and tested for tumor-initiating ability, self-renewal and tumorigenicity. MiRNA profiles were obtained using microarray and further confirmed by real-time RT-PCR (qRT-PCR). MiRNA functions were predicted bioinformatically, and miR-294 function was verified to explore its role in tumor migration and invasion. Lung adenocarcinoma was induced in LSL-Kras G12D mice within 30 days. In vivo, the tumorigenicity of Sca-1(+) CD34(+) cells was 25 times stronger than Sca-1(-) CD34(-) cells. During tumorigenesis of lung adenocarcinoma, the expression of 145 miRNAs in Sca-1(+) CD34(+) cells increased and 72 miRNAs decreased (P < 0.01). Four successively up-regulated miRNAs (miR-15a*, miR-203, miR-294 and miR-295*) and three successively down-regulated ones (miR-19b, miR-483 and miR-615-5p) were identified. Among them, miR-294 could constitutively bind to 3'-UTR of matrix metalloproteinase 3 (MMP3), and down-regulate MMP3 protein expression. MiR-294 also significantly inhibited migration and invasion of Lewis lung cancer cells. MiRNAs are characteristically expressed in tumor-initiating Sca-1(+) CD34(+) cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma.

Synthesis, structure analysis, antitumor evaluation and 3D-QSAR studies of 3,6-disubstituted-dihydro-1,2,4,5-tetrazine derivatives.

3,6-Diaryl-dihydro-1,2,4,5-tetrazine derivatives were synthesized and their structures were confirmed by single-crystal X-ray diffraction. Monosubstituted dihydrotetrazines are the 1,4-dihydro structure, but disubstituted dihydrotetrazines are the 1,2-dihydro structure. The results of further research indicated there may be a rearrangement during the synthesis process of disubstituted dihydrotetrazines. Their antitumor activities were evaluated against A-549 and P388 cells in vitro. The results showed several compounds to be endowed with cytotoxicity in the low micromolar range. Two compounds were highly effective against A-549 cell and IC50 values were 0.575 and 2.08 µM, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 37 1,2,4,5-tetrazine derivatives with antitumor activity against A-549 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.744 and 0.757, respectively. Conventional r(2) values were 0.978 and 0.988, respectively, the predicted R(2) values were 0.916 and 0.898, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives.

[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.

[Damage control surgery for pancreatic injuries after blunt abdominal trauma].

OBJECTIVE: To summarize the management of pancreatic injuries after blunt abdominal trauma. METHODS: The clinical data of 42 patients with blunt pancreatic injury admitted from January 2001 to December 2010 was analyzed retrospectively. There were 38 male and 4 female patients, aging from 13 to 65 years with a mean of 31 years. The organ injury scaling of Committee of the American Association for the Surgery of Trauma (AAST grade): grade I in 3 patients, grade II in 12 patients, grade III in 9 patients, grade IV in 13 patients and grade V in 5 patients. The mean injury severity score was 27 ± 21. Patients above AAST grade II underwent peritoneal drainage and "three neostomy" (gastrostomy, jejunostomy and gallbladder) according to damage control theory. RESULTS: Thirty-eight patients got abdominal CT scanning with a positive rate of 79.9% (30/38). Forty patients underwent surgical procedures, and 2 patients with non-operative management. The surgical procedures include peritoneal drainage and "three neostomy" in 32 patients, pancreas suture or pancreatic tail resection in 6 patients, pancreatoduodenectomy or caudal pancreaticojejunostomy in 2 patients. Forty patients (95.2%) survived, 2 patients (4.8%) died and 16 patients (38.1%) had complications such as pancreatic fistula,pulmonary infection. CONCLUSIONS: Abdominal CT scanning will benefit the preoperative diagnosis of blunt pancreatic trauma. Although the survival rate of patients with blunt pancreatic trauma might be improved by using the damage control surgery, the management of damage control surgery also needs to be modified because of the high rate of complications.

[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.

MicroRNA expression profile of bronchioalveolar stem cells from mouse lung.

Increasing evidence has suggested that bronchioalveolar stem cell (BASC) is the progenitor cells of lung cancer stem cells. However, the mechanisms by which self-renewal of BSACs is controlled and how BASCs turn into cancer stem cells still remains to be unknown. In the present study, we successfully isolated bronchioalveolar stem cells (BASCs) from mouse lung using FACS. These BASCs were characterized by clonal growth, self-renewal and high capacity for differentiation, suggesting that these BASCs are indeed stem cells. We investigated the microRNA (miRNA) expression profile of these BASCs using miRNA array and quantitative RT-PCR. We discovered that BASCs possessed a unique miRNA profile, with altered expression of several microRNAs, such as miR-142-3p, miR-451, miR-106a, miR-142-5p, miR-15b, miR-20a, miR-106b, miR-25, miR-486, in BASCs compared to control cells. Our results suggest that microRNAs might play important roles in maintaining the self-renewal capacity of BASCs, and suggest the intriguing possibility that aberrant expression of microRNAs could involved in turning BASCs into lung cancer stem cells.

[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.

[Involvement of post-receptor signal transduction in alcohol addiction].

Alcohol abuse and addiction is not only a severe social problem, but also an important biological medical issue. Studies in neuropsychopharmacology and molecular neurobiology indicate that neurotransmitters and its receptors play important roles in alcohol abuse and addiction, and post-receptor signal transduction pathways, including cyclic adenosine 3', 5'-monophosphate (cAMP)-protein kinase A (PKA), phosphoinositide (PI), Ca2+ -calmodulin (CAM), phospholipase D (PLD) and tyrosine kinase Fyn signaling cascade. In this review, works on post-receptor signal transduction involved in alcohol addiction are systematically presented and summarized.

[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.

[Expression of calmodulin in the articular process of vertebrae of adolescent idiopathic scoliosis patients].

OBJECTIVE: To investigate the expression of calmodulin in the articular process of vertebrae of adolescent idiopathic scoliosis (AIS) patients and congenital scoliosis (CS) patients and its possible effects on the pathogenesis of AIS. METHODS: Nine AIS patients aged 13 - 17, and 10 patients of CS, aged 11 - 18, underwent orthopedic surgery. Specimens of the inferior articular process from the apical vertebrae and upper end vertebrae discarded during operation were collected from the AIS patients and specimens of the. Inferior articular process from the upper end vertebrae wee collected from the CS patients. Immunohistochemistry was used to detect the protein expression of calmodulin, and in situ hybridization was adopted to examine the mRNA expression of calmodulin. RESULTS: Calmodulin were expressed in the bone cells. There was no difference between the expression of calmodulin at the concave side and convex side, or between the apical vertebrae and end vertebrae. The expression of calmodulin of the AIS group was significant lower than that of the CS group (P < 0.05). The result of immunohistochemistry and that of in situ hybridization corresponded with each other. CONCLUSION: The expression of calmodulin in the articular process of vertebrae of AIS patients is low, suggesting that it plays a role in the development and progression of AIS.