Roles of ZEB1 and ZEB2 in E-cadherin expression and cell aggressiveness in head and neck cancer.

Zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in cancer cell differentiation and metastasis, and has been well studied in the field of cancer cell biology. ZEB2 has a highly similar conformation to ZEB1, but its role in head and neck squamous cell carcinoma (HNSCC) cells is not fully understood. Here, we separately overexpressed ZEB1 and ZEB2 in C57BL/6 mouse oral cancer (MOC) cells and investigated their cellular characteristics, including E-cadherin levels, motile properties, chemoresistance, and metastatic ability in immunocompetent mice. Both ZEB1 and ZEB2 overexpression reduced epithelial traits and converted cells to an aggressive phenotype. Surprisingly, ZEB1 overexpression increased the endogenous level of ZEB2 in MOC cells, and vice versa. The molecular mechanisms underlying these findings remain unclear. However, the in vitro anchorage-independent growth of MOC cells overexpressing ZEB2 was considerably greater than that of MOC cells overexpressing ZEB1. These findings suggest that ZEB2, like ZEB1, has the ability to induce the differentiation of cancer cells into those with highly aggressive traits.

Surface Markers and Chemokines/Cytokines of Tumor-Associated Macrophages in Osteosarcoma and Other Carcinoma Microenviornments-Contradictions and Comparisons.

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In recent years, the tumor microenvironment (TME) has gained attention as a therapeutic target for cancer. The immune component of OS TME consists mainly of tumor-associated macrophages (TAMs). They exhibit remarkable plasticity, and their phenotype is influenced by the TME. In general, surface markers such as CD68 and CD80 show anti-tumor effects, while CD163 and CD204 show tumor-promoting effects. Surface markers have potential value as diagnostic and prognostic biomarkers. The cytokines and chemokines produced by TAMs promote tumor growth and metastasis. However, the role of TAMs in OS remains unclear to date. In this review, we describe the role of TAMs in OS by focusing on TAM surface markers and the TAM-produced cytokines and chemokines in the TME, and by comparing their behaviors in other carcinomas. We found contrary results from different studies. These findings highlight the urgency for further research in this field to improve the stalled OS prognosis percentages.

Case report: Characteristics and nature of primary cardiac synovial sarcoma.

Primary malignant cardiac tumors rarely occur, and cardiac synovial sarcoma (SS) is especially rare among such tumors. Herein, we present the case of a 35-year-old female with primary cardiac SS treated with surgery, chemotherapy, and radiotherapy. She presented with chest symptoms and underwent imaging examinations. A cardiac tumor was suspected, and an open biopsy was performed. The pathological findings suggested cardiac SS. Next, we performed a resection, and the tumors persisted at a macroscopic level. Immunohistochemistry was negative for SS18-SSX and positive for the SSX C-terminus and cytokeratin CAM5.2, a reduction of SMARCB1/INI1 was observed, and fluorescence in situ hybridization showed positive SS18 split staining. Owing to the FNCLCC grade 3 tumor and R2 margins, adjuvant chemotherapy with ifosfamide, doxorubicin, and radiotherapy was initiated, and the patient was diagnosed with cardiac SS. The differences in patients with cardiac SS compared with general SS include male predominance, larger tumor size, and poorer prognosis. Pathological findings of immunohistochemistry and fluorescence in situ hybridization were found to be more reliable than imaging findings for a correct diagnosis. Additionally, because incomplete resection is frequently performed, adjuvant therapy, including chemotherapy and radiation therapy, may be performed. The findings indicate that multiple therapies, including surgery, chemotherapy, and radiotherapy, are essential treatment strategies for improving the prognosis of patients with cardiac SS.

Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway.

The prognosis of osteosarcoma (OS) has remained stagnant over the past two decades, requiring the exploration of new therapeutic targets. Cytokines, arising from tumor-associated macrophages (TAMs), a major component of the tumor microenvironment (TME), have garnered attention owing to their impact on tumor growth, invasion, metastasis, and resistance to chemotherapy. Nonetheless, the precise functional role of TAMs in OS progression requires further investigation. In this study, we investigated the interaction between OS and TAMs, as well as the contribution of TAM-produced cytokines to OS advancement. TAMs were observed to be more prevalent in lung metastases compared with that in primary tumors, suggesting their potential support for OS progression. To simulate the TME, OS and TAMs were co-cultured, and the cytokines resulting from this co-culture could stimulate OS proliferation, migration, and invasion. A detailed investigation of cytokines in the co-culture conditioned medium (CM) revealed a substantial increase in IL-8, establishing it as a pivotal cytokine in the process of enhancing OS proliferation, migration, and invasion through the focal adhesion kinase (FAK) pathway. In an in vivo model, co-culture CM promoted OS proliferation and lung metastasis, effects that were mitigated by anti-IL-8 antibodies. Collectively, IL-8, generated within the TME formed by OS and TAMs, accelerates OS proliferation and metastasis via the FAK pathway, thereby positioning IL-8 as a potential novel therapeutic target in OS.

Case Report: Angiomatoid fibrous histiocytoma in the hand: a rare clinical presentation and diagnostic challenge.

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of mesenchymal origin occurring in young adults. Based on its clinical course, it is said to have an intermediate potential. We present a case of a 59-year-old woman with AFH in the hand that was difficult to diagnose. A benign soft tissue tumor was suspected on magnetic resonance imaging, and its size and open biopsy suggested nodular fasciitis or inflammatory myofibroblastic tumor. A diagnosis of AFH was eventually made based on the analysis of the resected specimens. The characteristic findings of histopathology and immunohistochemistry in this case were relatively poor, so fluorescence in situ hybridization contributed to making the correct diagnosis. Considering its prognosis, careful follow-up was decided upon without additional surgery. Our case is a challenging one because of its atypical presentation and inconclusive imaging and histopathological findings.

Indolent Multinodular Synovial Sarcoma of Peripheral Nerves Mimicking Schwannoma: A Case Report and Literature Review.

BACKGROUND/AIM: Most cases of synovial sarcoma (SS) are aggressive and large-sized; only few show indolent behavior, having a small size. Nerves are rare sites of SS occurrence. An atypical case of SS can lead to its misdiagnosis as a benign tumor and delay its treatment. CASE REPORT: Here, we report a case of primary SS of indolent multinodular synovial sarcoma of peripheral nerves. Considering the clinical and imaging findings at the first visit, we suspected a benign tumor and continued careful follow-up. Three years later, marginal resection was performed and SS was suspected. We then performed an additional wide resection using a free flap. Histopathologically, the proximal tumor showed a diffuse proliferation of spindle cells without pleomorphism, whereas the distal tumor showed a similar histology with more hypercellularity. Additional wide-resection specimens showed remnant tumors derived from the peripheral nerve. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX in both tumors and fluorescence in situ hybridization showed positive staining for the SS18 split in both tumors. Finally, SS of the peripheral nerve was diagnosed. Owing to FNCLCC grade 2 tumor and tumor size, adjuvant chemotherapy was not performed. CONCLUSION: In cases of SS or other sarcomas with atypical clinical courses, with imaging findings mimicking benign tumors, we recommend marginal resection along with pathological examination for correct diagnosis.

Primary Synovial Sarcoma of the Bone: A Case Report and Literature Review.

BACKGROUND/AIM: Synovial sarcoma (SS), a spindle cell sarcoma, typically occurs in the soft tissues of the extremities and rarely develops in the bones as a primary tumor. To our knowledge, no case of SS in the metacarpal bone has been reported. CASE REPORT: We report a case of primary SS of the metacarpal bone. Considering the clinical and imaging findings, SS was difficult to diagnose; therefore, we performed an open biopsy. Next, we performed a wide resection following the management guidelines for SS of the soft tissue. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX, and fluorescence in situ hybridization showed positive staining for the SS18 split. Owing to FNCLCC grade 3 tumor and the R1 margin, adjuvant chemotherapy with ifosfamide and doxorubicin was initiated. Finally, SS of the bone was diagnosed. Furthermore, we reviewed a total of 37 published cases of primary bone SS, including our case. Age and sex were almost the same in all cases of bone SS, and the most frequent site was the long bone in the lower extremity. CONCLUSION: IHC for SS18::SSX and SSX antibodies are beneficial for diagnosing general SS and SS of the bone. Moreover, SS of the bone should be considered in the differential diagnosis of spindle cell sarcomas of the bone. Wide resection and chemotherapy are recommended as current treatment strategies, although further studies are required regarding treatment validity.

Advancing Tissue Factor-targeted Therapy for Osteosarcoma via Understanding its Role in the Tumor Microenvironment.

Coagulation activation is associated with cancer progression and morbidity. Recently, mechanisms through which coagulation proteases drive the tumor microenvironment (TME) have been elucidated. This review aims to develop a new strategy dependent on the coagulation system for treating osteosarcoma (OS). We focused on tissue factor (TF), the main initiator of the extrinsic coagulant pathway, as a target for OS treatment. It was found that cell surface-TF, TF-positive extracellular vesicles, and TF-positive circulating tumor cells could drive progression, metastasis, and TME in carcinomas, including OS. Thus, targeting tumor-associated coagulation by focusing on TF, the principle catalyst of the extrinsic pathway, TF is a promising target for OS.

Spindle Cell Lipoma with Ossification Mimicking Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma: A Case Report.

Although spindle cell lipoma (SCL) is a subtype of lipoma, the characteristics of SCL are observed in both lipomatous and non-lipomatous tumors. In this article, we present a case of SCL with ossification mimicking atypical lipomatous tumors/well-differentiated liposarcomas (ALTs/WDLs). Considering the findings of magnetic resonance imaging and needle biopsy, which exhibited ALTs/WDLs, marginal resection was performed. Histopathological findings demonstrated mature adipocytes and spindle cells without atypia and no malignant osteoid tissue in the ossified region. In addition, immunohistochemistry (IHC) showed positive staining for CD34, heterogeneous retinoblastoma protein deficiency, and negative staining for mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase. Fluorescence in-situ hybridization showed negative amplification of MDM2. The final diagnosis of the tumor was established using IHC as an extremely rare SCL with ossification.

Exogenous parathyroid hormone attenuates ovariectomy-induced skeletal muscle weakness in vivo.

Osteoporosis commonly affects the elderly and is associated with significant morbidity and mortality. Loss of bone mineral density induces muscle atrophy and increases fracture risk. However, muscle lipid content and droplet size are increased by aging and mobility impairments, inversely correlated with muscle function, and a cause of reduced motor function. Teriparatide, the synthetic form of human parathyroid hormone (PTH) 1-34, has been widely used to treat osteoporosis. Although PTH positively affects muscle differentiation in vitro, the precise function and mechanisms of muscle mass and power preservation are still poorly understood, especially in vivo. In this study, we investigated the effect of PTH on skeletal muscle atrophy and dysfunction using an ovariectomized murine model. Eight-week-old female C57BL/6J mice were ovariectomized or sham-operated. Within each surgical group, the mice were divided into PTH injection or control subgroups. Motor function was evaluated based on grip strength, treadmill running, and lactic acid concentration. PTH receptor was expressed in skeletal muscle cells and myoblasts. PTH inhibited ovariectomy-induced bone loss but not uterine atrophy or increased body weight; PTH not only abolished ovariectomy-induced reduction in grip strength and maximum running speed, but also significantly reduced the ovariectomy-induced increase in lactic acid concentration (compared with that observed in the vehicle control). PTH also abrogated the ovariectomy-induced reduction in the oxidative capacity of muscle fibers, their cross-sectional area, and intramyocellular lipid content, and induced cell proliferation, cell migration, and muscle differentiation, while reducing lipid secretion by C2C12 myoblasts via the Wnt/ß-catenin pathway. PTH significantly ameliorated muscle weakness and attenuated exercise-induced lactate levels in ovariectomized mice. Our in vitro study demonstrated that PTH/Wnt signaling regulated the proliferation, migration, and differentiation of myoblasts and also reduced lipid secretion in myoblasts. Thus, PTH could regulate several aspects of muscle function and physiology, and may represent a novel therapeutic strategy for patients with osteoporosis.

Improvement of locomotive syndrome after total hip arthroplasty: A two-year longitudinal cohort study.

OBJECTIVES: Patients requiring total hip arthroplasty (THA) may possibly have locomotive syndrome (LS). Therefore, we investigated changes of LS in patients undergoing THA and clarified key factors that affected LS stage. METHODS: A prospective cohort study was conducted with 88 patients undergoing THA (74 females, 14 males, mean age: 67.6 years). Data collected using LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale results were evaluated before THA, and 6 months, 1 year, and 2 years after THA. Key factors were determined using multivariate analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Before THA, all patients had fallen LS (stage1: 3.4% and stage2: 96.6%). Overall, 56.8% patients improved their LS stage, and 17.0% of patients overcame LS at 2 years after THA. The key factors that affected LS stage were preoperative two-step test and age. ROC analyses showed a preoperative two-step test score of 0.988 and an age of 67.5 years as a cut-off value for the change of LS stage. CONCLUSIONS: Patients experiencing LS due to hip disorders have the potential to recover after THA. Additional postoperative training may be beneficial for patients with low preoperative two-step test scores to improve their LS stage.