Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1.

Recent studies have shown that transmembrane-type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM-A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM-A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM-A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM-A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM-A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM-A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM-A-targeted therapy ideally combined with LAT1-targeted therapy as a new therapeutic strategy against breast cancer.

The Accuracy of Cup Placement in Total Hip Arthroplasty (THA) Using an Augmented Reality-Based Navigation System.

Background AR HIP Navigation System® (AR-navi; Zimmer-Biomet, Warsaw, IN) is a portable navigation system employing augmented reality via a smartphone app, which was developed in Japan. We retrospectively analyzed the accuracy of cup placement in total hip arthroplasty (THA) using AR-navi, to investigate whether obesity is associated with an absolute value error in cup placement angle. Methods We retrospectively analyzed 45 hips in 43 patients who underwent THA using AR-navi (AR-navi group) and compared them with 45 hips in 45 patients who underwent THA using alignment rods (conventional group). Results The mean absolute error of cup placement (AR-navi group vs. conventional group) was found to be 2.60° (±2.11) in radiographic inclination (RI) for the AR-navi group and 4.61° (±3.28) for the conventional group, which indicates significant difference in the AR-navi group compared to that in the conventional group (p = 0.0036). The mean absolute error of radiographic anteversion (RA) was 3.57° (±3.36) for the AR-navi group and 3.87° (±2.97) for the conventional group (p = 0.4732). The mean absolute error of RI was 2.36° (±2.24) in the obese group and 3.16° (±2.03) in the nonobese group, and the mean absolute error of RA was 4.08° (±4.51) and 3.16° (±2.05) in the obese and nonobese groups, respectively. Conclusions Cup placement accuracy for THA using AR-navi was 2.60 ± 2.11° for RI and 3.87 ± 2.97° for RA. Compared to THA using the conventional method, the RI installation error was significantly improved with AR Navi. There was no significant difference in the mean absolute error of RI and RA among the obese and nonobese groups.

Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation.

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype with a bi-morphic histological appearance of a conventional chondrosarcoma component and it can abruptly transition to a high-grade non-cartilaginous sarcoma. To better understand the biological features of DDCSs and to help develop new therapies, a novel DDCS cell line, SMU-DDCS, was established. Tissue from an open biopsy of a tumor resected from a 75-year-old patient was subjected to primary culture. The cell line was established and authenticated by assessing DNA microsatellite short tandem repeats. The cells maintained in monolayer cultures exhibited constant growth, spheroid formation, and high invasive capacity. Out of the four mice inoculated with SMU-DDCS cells, tumors developed in three mice after 2 weeks. R132C mutation was found in the IDH1 but not the IDH2 genomic DNA sequence of SMU-DDCS cells. SMU-DDCS cells exhibited low chemosensitivity to doxorubicin, methotrexate, and cisplatin. This SMU-DDCS cell line harboring an IDH1 mutation will be a useful tool for investigating DDCS development and for evaluating novel therapeutic agents against it.

Treatment outcome of chest wall soft tissue sarcomas: Analysis of prognostic factors.

BACKGROUND: Primary soft tissue sarcomas (STSs) involving the chest wall are uncommon. The aim of this study was to identify factors that influence the prognosis of patients with primary chest wall STS. METHODS: The records of 38 patients (23 men and 15 women) who were treated at our institutions during 2002 to 2018 were reviewed. The following variables were evaluated as potential prognostic factors: sex, tumor size, chemotherapy, and completeness of surgical margins. Multivariate analysis was conducted to identify predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 38 included patients, 5 had low-grade tumors and 33 had high-grade tumors. Five patients required chest wall reconstruction including rib resection. Thirty patients (79%) underwent R0 resection. The 5-year OS and DFS rates were 45% and 27%, respectively. Local recurrence developed in 7 patients. Multivariate analysis identified tumor size (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.05-16.24; P = .04) and R1/2 resection (HR: 3.92; 95% CI: 1.12-13.66; P = .03) as predictors of OS. CONCLUSIONS: Prognostic factors for survival included tumor size and completeness of surgical margins. Complete tumor excision is desirable, particularly in cases of early detection.