Resection for malignant tumors in the elbow and individualized reconstruction under assistance of 3D printing technology: A case report.

RATIONALE: With a high failure rate and multiple postoperative complications, the resection for tumors in the elbow and reconstruction present a formidable challenge to orthopedic surgeons. The maturation of 3-dimension (3D) printing technology has facilitated the preoperative design, intraoperative navigation, and reconstruction of bone defects in patients with complex malignant tumors of the elbow joint. In order to improve prognosis, we explored a method of tumor resection and elbow reconstruction aided by 3D printing technology in this research. PATIENT CONCERNS: The patient underwent nephrectomy for clear cell carcinoma of the left kidney 3 years ago. Six months ago, the patient presented with limited movement and lateral tenderness in the right elbow joint. The tumor puncture biopsy demonstrated renal clear cell carcinoma metastasis. DIAGNOSES: Renal clear cell carcinoma with distal humerus bone metastasis. INTERVENTIONS: Thin-layer CT scan data of the patient was acquired, and a 3D reconstruction of both upper limb bones and joints was conducted, followed by a simulation of diseased tissue excision. According to the model, individualized osteotomy guidelines and elbow prostheses were designed and manufactured. Then, prior to the completion of the actual operation, a simulation of the preoperative phase was performed. OUTCOMES: The operation was completed without incident. At the 1-, 3-, and 6-month postoperative examinations, both the position and mobility of the prosthesis were found to be satisfactory, and no complications were observed. The hospital for special surgery score and mayo elbow performance score scores increased in comparison to the preoperative period. LESSONS: For patients with complex tumors in the elbow joint, 3D printing technology may assist in the precise excision of the tumor and provide an individualized elbow joint prosthesis that is more precise and effective than traditional surgery. It can accomplish a satisfactory treatment effect for patients when combined with early postoperative scientific rehabilitation training, so it is a method worth promoting.

REG3A overexpression suppresses gastric cancer cell invasion, proliferation and promotes apoptosis through PI3K/Akt signaling pathway.

Gastric cancer (GC) is the second most common cause of cancer-related deaths. In recent years some essential factors for resolution were identified, but the clinical trials still lack the effective methods to treat or monitor the disease progression. Regenerating islet-derived 3α (REG3A) is a member of REG protein family. Previous studies have investigated the altered expression of REG3A in various cancers. In this investigtion we aimed at the biological function and the underlying molecular mechanism of REG3A in GC. We found that REG3A was significantly downregulated in GC and closely related with patient prognoses. REG3A overexpression suppressed the invasion and proliferation promoting apoptosis of GC cells. While REG3A knockdown promoted the invasion, and proliferation suppressing apoptosis of GC cells. It was further found that REG3A performed its biological functions mainly through phosphatidylinositol 3 kinase (PI3K)/Akt-GSK3ß signaling pathway axis. REG3A may be a promising therapeutic strategy for GC.

LMO3 promotes gastric cancer cell invasion and proliferation through Akt-mTOR and Akt-GSK3ß signaling.

The present study assessed the biological functions of LIM domain only 3 (LMO3) in gastric cancer (GC) investigated and the underlying molecular mechanisms. It was revealed that the expression of LMO3 was significantly upregulated in GC tissues. A GC tissue microarray (n=164) indicated that LMO3 expression was closely associated with clinicopathological factors, as well as overall survival and disease-free survival of patients. After knockdown of LMO3 in MGC-803 and SGC-7901 cells, the invasion and proliferation were obviously suppressed. Furthermore, LMO3 knockdown suppressed the phosphorylation of Akt, mammalian target of rapamycin (mTOR) and glycogen synthase kinase (GSK)3ß signaling. An inhibitor of mTOR, dactolisib, abrogated recombinant LMO3 protein-induced GC cell invasion and proliferation, while an inhibitor of GSK3ß, CHIR-98014, only abrogated rLMO3 protein-induced proliferation. These results suggested that LMO3 promotes GC cell invasion and proliferation mainly through Akt/mTOR and Akt/GSK3ß signaling. LMO3 may serve as a potential therapeutic target for GC in the future.

DNA Methylation-Mediated Silencing of Regenerating Protein 1 Alpha (REG1A) Affects Gastric Cancer Prognosis.

BACKGROUND Gastric cancer (GC) is one of the most common cause of cancer-related deaths. The clinical trials still lack the effective methods to treat or monitor the disease progression. In this research, the biological function and the underlying molecular mechanism of regenerating protein 1 alpha (REG1A) in GC were investigated. MATERIAL AND METHODS Gene expression omnibus (GEO), KMplot datasets and GC tissue microarray (n=164) were used to analyze the expression of REG1A and related patient prognoses in GC. Transwell matrigel assay, flow cytometry analysis and CCK8 cell viability assay were performed to detect the biological functions of REG1A. Western blotting and real-time PCR were used to detect the REG1A expression and PI3K/Akt related signaling. RESULTS It was found that the expression of REG1A was significantly downregulated in GC and closely related with clinicopathological findings or patient prognoses. REG1A overexpression could suppress the invasion, cell viability and promote the apoptosis of GC cells. Moreover, we found that the epigenetic methylation suppressed the expression level of REG1A in GC, and REG1A overexpression could suppress the phosphorylation of Akt or GSK3ß signaling. CONCLUSIONS Taken together, REG1A regulates cell invasion, apoptosis and viability in GC through activating PI3K/Akt-GSK3ß signaling. REG1A may serve as a promising therapeutic strategy for GC.

The efficacy of high-dose versus moderate-dose chemotherapy in treating osteosarcoma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether the efficacy of high-dose chemotherapy in the treatment of primary well-differentiated osteosarcoma is superior to moderate-dose chemotherapy. METHODS: Cochrane systematic review method was used to retrieve literatures from MEDLINE, Embase, OVID, Cochrane Library database of clinical trials, Chinese Biomedical Literature Database CD-ROM, as well as manual searching from "China Oncology", "Chinese Journal of Clinical Oncology", "Cancer" etc. Meta-analysis was performed using the RevMan 5.0 software. RESULTS: A total of four studies, 937 cases of primary, non-metastatic, well-differentiated limb osteosarcoma patients were enrolled in the study. Meta-analysis results suggested that compared with moderate-dose group, 5-year disease-free survival, 5-year overall survival rate, the local recurrence rate, proportion of histologic response in good status, limb salvage rate showed no significant difference in high-dose chemotherapy group (All P > 0.05); good and poor response of preoperative chemotherapy tumor histologic of 5-year disease-free survival showed statistical difference (RR = 1.55; 95% CI: 1.19-2.00; P = 0.0009). CONCLUSION: High-dose chemotherapy for the treatment of primary osteosarcoma is not better than moderate-dose chemotherapy. It is expected that high quality of randomized controlled trials were performed to provide more reliable evidence in the future.

Neuroprotective effect of methylprednisolone combined with placenta-derived mesenchymal stem cell in rabbit model of spinal cord injury.

The aim of this study was to assess the ability of the combination treatment of methylprednisolone (MP) and placenta-derived mesenchymal stem cells (PDMSCs) in a rabbit model of spinal cord injury (SCI). Rabbits were randomly divided into four groups: group 1 (control), group 2 (MP), group 3 (PDMSCs) and group 4 (MP + PDMSCs). In all groups, the spinal cord injury model was created by the weight drop method. Levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined by kit. Histopathological examination was also performed. Neurological evaluation was carried out with the Tarlov scoring system. The results showed both MP and PDMSCs had neuroprotective effects, and combining the administration of MP with PDMSCs was shown a significant effect on the recovery of neurological function. Therefore, the combined use of MP and PDMSCs can be used as a potential therapeutic method for SCI.

Endosialin­expressing bone sarcoma stem­like cells are highly tumor­initiating and invasive.

It has been reported that the presence of a small group of cancer stem­like 'side population (SP)' cells is responsible for therapy failure and tumor recurrence. The present study demonstrated that primary human osteosarcoma samples contained a SP of about 3.9% which overexpressed ABC transporters, including ABCA1, ABCB1, ABCB2 and ABCG2, which are associated with drug resistance and may have contributed to multi­drug resistance of SP cells. Furthermore, these SP cells displayed increased expression of endosialin (CD248) and other stem cell surface proteins, including CD133, octamer­binding transcription factor 3/4A, Nanog and Nestin, which are ultimately responsible for high self­renewal and deregulated cell proliferation. In addition, it was shown that endosialin­overexpressing SP cells were able to regenerate the tumor population and had a high invasive potential. Therefore, the present study suggested that osteosarcoma SP cells were cancer stem cells, as they displayed stem­like properties; furthermore, endosialin may be a potential target to prevent osteosarcoma recurrence following chemotherapy.

Sensory and sympathetic innervation of cervical facet joint in rats.

OBJECTIVE: To explore the patterns of innervation of cervical facet joints and determine the pathways from facet joints to dorsal root ganglions (DRGs) in order to clarify the causes of diffuse neck pain, headache, and shoulder pain. METHODS: Forty-two male-Sprague-Dawley rats, weighing 250-300 g, were randomly divided into three groups: Group A (n=18), Group B (n=18), and Group C (n=6). Under anesthesia with intraperitoneal pentobarbital sodium (45 mg/kg body weight), a midline dorsal longitudinal incision was made over the cervical spine to expose the left cervical facet joint capsule of all the rats under a microscope. The rats in Group A underwent sympathectomy, but the rats in Group B and Group C did not undergo sympathectomy. Then 0.6 microlitre 5% bisbenzimide (Bb) were injected into the C1-2, C3-4 and C5-6 facet joints of 6 rats respectively in Group A and Group B. The holes were immediately sealed with mineral wax to prevent leakage of Bb and the fascia and skin were closed. But in Group C, 0.9% normal saline was injected into the corresponding joint capsules. Then under deep re-anesthesia with intraperitoneal pentobarbital sodium (45 mg/kg body weight), C1-C8 left DRGs in all rats and the sympathetic ganglions in Group B were obtained and the number of the labeled neurons was determined. RESULTS: Neurons labeled with Bb were present in C1-C8 DRGs in both Group A and Group B, and sympathetic ganglions in Group B. In the C1-2 and C3-4 subgroups, labeled neurons were present from C1 to C8 DRGs, while in C5-6 subgroups they were from C3 to C8. The number of Bb(+) neurons after sympathectomy was not significantly different in the injected level from that without sympathectomy. But in the other levels, the number of Bb(+) neurons after sympathectomy was significantly less than that without sympathectomy. CONCLUSIONS: The innervation of the cervical facet joints is derived from both sensory and sympathetic nervous system, and DRGs are associated with sympathetic ganglions through nerve fibers outside the central nerve system.