Establishment and Characterization of NCC-DDLPS4-C1: A Novel Patient-Derived Cell Line of Dedifferentiated Liposarcoma

Dedifferentiated liposarcoma (DDLPS) is a highly malignant sarcoma characterized by the co-amplification of MDM2 and CDK4. Although systemic chemotherapy is recommended for unresectable or metastatic cases, DDLPS is insensitive to conventional chemotherapy, leading to an unfavorable prognosis. Therefore, novel treatment methods are urgently required. Patient-derived cell lines are essential in preclinical studies. Recently, large-scale screening studies using a number of cell lines have been actively conducted for the development of new therapeutic drugs. However, the DDLPS cell line cannot be obtained from public cell banks owing to its rarity, hindering screening studies. As such, novel DDLPS cell lines need to be established. Accordingly, this study aimed to establish a novel DDLPS cell line from surgical specimens. The cell line was named NCC-DDLPS4-C1. NCC-DDLPS4-C1 cells retained copy number alterations corresponding to the original tumors. Further, the cells demonstrated constant growth, spheroid formation, and equivalent invasiveness to MG63 osteosarcoma cells. We also conducted drug screening and integrated the results with those of the previously reported DDLPS cell lines. Consequently, we identified the histone deacetylase inhibitor romidepsin as a novel candidate drug. In conclusion, the NCC-DDLPS4-C1 cell line is a useful tool for the basic study of DDLPS

Establishment and Characterization of NCC-MFS5-C1: A Novel Patient-Derived Cell Line of Myxofibrosarcoma

Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment

Radical Surgery of Only the Anterior Elements of the Spine at the Posterior Element Fusion Level due to Metastatic Thyroid Cancer

Spinal metastasis of differentiated thyroid cancer can have a favorable prognosis if radical surgery is performed. We encountered a case of spinal metastasis involving three anterior vertebral bodies at the posterior element fusion level and successfully achieved adequate stability by radical surgery involving only the anterior elements. A 67-year-old woman who had numbness and muscle weakness in the lower limbs caused by metastatic spinal tumor at the posterior element fusion level of L1–L3 vertebrae was treated with radical surgery of only the anterior element to gain stability. Similar situations may occur in cases involving other malignant tumor metastases or spinal primary tumors. If such a case occurs, this method could be useful in preventing metastasis to the posterior element

Automated acquisition of explainable knowledge from unannotated histopathology images.

Deep learning algorithms have been successfully used in medical image classification. In the next stage, the technology of acquiring explainable knowledge from medical images is highly desired. Here we show that deep learning algorithm enables automated acquisition of explainable features from diagnostic annotation-free histopathology images. We compare the prediction accuracy of prostate cancer recurrence using our algorithm-generated features with that of diagnosis by expert pathologists using established criteria on 13,188 whole-mount pathology images consisting of over 86 billion image patches. Our method not only reveals findings established by humans but also features that have not been recognized, showing higher accuracy than human in prognostic prediction. Combining both our algorithm-generated features and human-established criteria predicts the recurrence more accurately than using either method alone. We confirm robustness of our method using external validation datasets including 2276 pathology images. This study opens up fields of machine learning analysis for discovering uncharted knowledge

Combined effect of DBM, PRP, and bone marrow fluid on bone union in a rat posterolateral fusion model

Abstract Platelet-rich plasma (PRP) promotes bone union through osteoinduction. We investigated whether adding demineralized bone matrix (DBM), derived naturally from biomaterial and with various growth factors, for osteoconductivity and bone marrow fluid for osteogenesis results in different bone unions. Eight-week-old male Sprague–Dawley rats were divided into four groups of five based on transplantation material: sham control (C group); DBM alone (D group); DBM + PRP (DP group); and DBM + PRP + bone marrow fluid (DPB group). After posterolateral fusion at L3-5, postoperative weekly CT imaging determined average number of bone union in facet joints (4 joints × 5 animals = 20 joints) and bone formation. Pathological evaluation and bone strength were assessed using 3-point bending two weeks postoperatively. Facet joint bone union at four weeks postoperatively was 4/20 (20%, DP group) and 8/20 (40%, DPB group) joints. Six weeks postoperatively, it was 7/20 (35%, D group), 12/20 (60%, DP group), and 16/20 (80%, DPB group). Eight weeks postoperatively, it was 13/20 (65%, D group), 17/20 (85%, DP group), and 20/20 (100%, DPB group), suggesting that DPB > DP > D > C. Bone formation and bone strength showed a similar DPB > DP > D > C group trend. Adding PRP and bone marrow fluid to DBM promotes bone union and strength