Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma.

Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (<30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma

A-770041 reverses paclitaxel and doxorubicin resistance in osteosarcoma cells

Background: Reversing multidrug resistance (MDR) has been an important goal for clinical and investigational oncologists. In the last few decades, significant effort has been made to search for inhibitors to reverse MDR by targeting ATP-binding cassette (ABC) transporters (Pgp, MRP) directly, but these efforts have achieved little clinical success. Protein kinases play important roles in many aspects of tumor cell growth and survival. Combinations of kinase inhibitors and chemotherapeutics have been observed to overcome cancer drug resistance in certain circumstances. Methods: We screened a kinase specific inhibitor compound library in human osteosarcoma MDR cell lines to identify inhibitors that were capable of reversing chemoresistance to doxorubicin and paclitaxel. Results: We identified 18 small molecules that significantly increase chemotherapy drug-induced cell death in human osteosarcoma MDR cell lines U-2OSMR and KHOSR2. We identified A-770041 as one of the most effective MDR reversing agents when combined with doxorubicin or paclitaxel. A-770041 is a potent Src family kinase (Lck and Src) inhibitor. Western blot analysis revealed A-770041 inhibits both Src and Lck activation and expression. Inhibition of Src expression in U-2OSMR and KHOSR2 cell lines using lentiviral shRNA also resulted in increased doxorubicin and paclitaxel drug sensitivity. A-770041 increases the intracellular drug accumulation as demonstrated by calcein AM assay. Conclusions: These results indicate that small molecule inhibitor A-770041 may function to reverse ABCB1/Pgp-mediated chemotherapy drug resistance. Combination of Src family kinase inhibitor with regular chemotherapy drug could be clinically effective in MDR osteosarcoma. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-681) contains supplementary material, which is available to authorized users

MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3

Steroid-induced osteonecrosis of femoral head (ONFH) is a serious complication of glucocorticoid (GC) use. We investigated the differential expression of miRs in the mesenchymal stem cells (MSCs) of patients with ONFH, and aimed to explain the relationship between GC use and the development of MSC dysfunction in ONFH. Cells were collected from bone marrow of patients with ONFH. Samples were assigned to either GCs Group or Control Group at 1:1 matched with control. We then used miRNA microarray analysis and real-time PCR to identify the differentially expressed miRs. We also induced normal MSCs with GCs to verify the differential expression above. Subsequently, we selected some of the miRs for further studies, including miRNA target and pathway prediction, and functional analysis. We discovered that miR-708 was upregulated in ONFH patients and GC-treated MSCs. SMAD3 was identified as a direct target gene of miR-708, and functional analysis demonstrated that miR-708 could markedly suppress osteogenic differentiation and adipogenesis differentiation of MSCs. Inhibition of miR-708 rescued the suppressive effect of GC on osteonecrosis. Therefore, we determined that GC use resulted in overexpression of miR-708 in MSCs, and thus, targeting miR-708 may serve as a novel therapeutic biomarker for the prevention and treatment of ONFH

Value of lectures on the standardization of image report writing in residency training of medical imaging

Objective To evaluate training course on the standardization of image report writing in medical imaging residency training in order to improve the uniformity of image report writing and report quality. Methods Residents who attended medical imaging training facility for study between September 2020 and September 2021 were divided into experimental and control groups according to whether or not they received lectures on imaging report standards. Tencent quiz software was used to evaluate the mastery of imaging report writing standards by two groups of residents. Results The results of resident self-assessment showed that the residents in the experimental group improved significantly in terms of reporting format specification, description of lesion-related secondary signs, report conclusion, report content, and total score of reporting standard after 6 months of training(PPConclusions The lecture on image report writing standard has a positive impact on the mastering of image report writing standard and the promotion of report quality by medical imaging training residents

Primary total knee arthroplasty using constrained condylar knee design for severe deformity and stiffness of knee secondary to post-traumatic arthritis

Abstract Background Key to a successful outcome of total knee arthroplasty (TKA) is to attain optimum alignment, adequate balance, and deformity correction. In primary TKA, this can be achieved efficiently by posterior stabilized (PS) design with or without the sub-periosteal release. However, certain circumstances such as post-traumatic arthritis are often associated with severe deformities with a significant bone defect, stiffness, and instability. Such deformities are extremely difficult to balance with soft tissue release only and require additionally constrained prostheses even in primary TKA. In such situation, constrained condylar knee (CCK) design is the ultimate choice. This study primarily aimed to report on clinical outcome, regain of function, and complication of patients who underwent primary CCK-TKA for severe deformity of the knee secondary to post-traumatic arthritis. The secondary aim was to find out the mid-term prostheses survival. Methods Between February 2007 and November 2013, 38 consecutive patients with post-traumatic arthritis of the knee received cemented primary CCK-TKA. Thirty-four patients (21 men and 13 women) who had a minimum of 3 years follow-up were included in this retrospective study. We used Knee Society Score (KSS), Hospital for Special Surgery (HSS) score, and roentgenographic evaluation form to assess the patients. Prostheses survival was assessed using Kaplan-Meier’s survival analysis. Results Patients were followed up for an average duration of 6.47 years. KSS knee score improved from 44 points (23–68) pre-operatively to 91 points (76–100) post-operatively [P < 0.001]. The average KSS functional score improved from 49 points (20–75) pre-operatively to 91 points (65–100) post-operatively [P < 0.001]. The average HSS score improved from 51 points (27–83) pre-operatively to 91 points (75–100) post-operatively [P < 0.001]. Similarly, the average ROM improved from 68.09° ± 35.99° (0°–120°) to 113.68° ± 8.90° (100°–130°) post-operatively [P < 0.001]. The average hip-knee-ankle (HKA) angle was 176.88° ± 14.48° (135°–199°) pre-operatively and 180.24° ± 1.77° (175°–184°) post-operatively. Radiolucencies were evident in 13 knees, mostly on the tibial side. Prostheses survival was 94.7% at a mean follow-up of 6.47 years. Conclusion Despite severe deformity, instability, and stiffness at a relatively young age, mid-term follow-up of primary CCK-TKA in post-traumatic arthritis provides satisfactory clinical and functional outcomes with 94.7% prostheses survival. However, it is not without complication

Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma.

Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (&lt;30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma

Glycybridins A–K, Bioactive Phenolic Compounds from <i>Glycyrrhiza glabra</i>

In an attempt to discover bioactive agents from the herbal medicine <i>Glycyrrhiza glabra</i> (widely known as licorice), 11 new phenolic compounds, glycybridins A–K (<b>1</b>–<b>11</b>), along with 47 known phenolics (<b>12</b>–<b>58</b>) were isolated. Their structures were elucidated on the basis of extensive NMR and MS analyses as well as experimental and computed ECD data. According to the clinical therapeutic effects of licorice, enzyme or cell-based bioactivity screenings of <b>1</b>–<b>58</b> were conducted. A number of compounds significantly activate Nrf2, inhibit tyrosinase or PTP1B, inhibit LPS-induced NO production and NF-κB transcription, and inhibit the proliferation of human cancer cells (HepG2, SW480, A549, MCF7). Glycybridin D (<b>4</b>) showed moderate cytotoxic activities against the four cancer cell lines, with IC₅₀ values ranging from 4.6 to 6.6 μM. Further studies indicated that <b>4</b> (10 mg/kg, ip) decreased tumor mass by 39.7% on an A549 human lung carcinoma xenograft mice model, but showed little toxicity

Representative expression of brachyury in chordoma tissues on TMA slide.

<p><b>a</b> 0 staining, no nuclear staining of tumor cells; <b>b</b> 1+ staining, <=30% nuclear staining of tumor cells, <b>c</b> 2+ staining 31% to 60% positive nuclear staining; and <b>d</b> 3+ staining, 61% to 100% nuclear staining.</p

Analyses of association between expression of brachyury and survival for chordoma.

<p>Kaplan-Meier survival analysis showed that the expression of brachyury was not associated with prognosis in patients with chordoma.</p