NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST.

Establishment of Rapid and Accurate Screening System for Molecular Target Therapy of Osteosarcoma.

Comprehensive analyses using clinical sequences subcategorized osteosarcoma (OS) into several groups according to the activated signaling pathways. Mutually exclusive co-occurrences of gene amplification ( and ) have been identified in approximately 40% of OS, representing candidate subsets for clinical evaluation of additional therapeutic options. Thus, it would be desirable to evaluate the specific gene amplification before starting therapy in patients with OS.

IRE1α-XBP1 but not PERK inhibition exerts anti-tumor activity in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor. However, the therapeutic results of the advanced cases at the first visit were still extremely poor. Therefore, more effective therapeutic options based on molecular profiling of OS are needed.

Identification of a Novel MAN1A1-ROS1 Fusion Gene Through mRNA-based Screening for Tyrosine Kinase Gene Aberrations in a Patient with Leiomyosarcoma.

Background: Soft tissue sarcomas are a heterogeneous group of rare malignant tumors. Advanced soft tissue sarcomas have a poor prognosis, and effective systemic therapies have not been established. Tyrosine kinases are increasingly being used as therapeutic targets for a variety of cancers and soft tissue sarcomas.

Nanostring-based screening for tyrosine kinase fusions in inflammatory myofibroblastic tumors.

Gene expression imbalances were measured for tyrosine kinase (TK) genes using Nanostring in 19 samples of inflammatory myofibroblastic tumor (IMT). All cases were immunohistochemically stained with anaplastic lymphoma kinase (ALK) and pan-tropomyosin-related-kinase (pan-Trk) antibodies. Five cases with imbalanced ALK expression, reported with Nanostring, were tested using fluorescence in situ hybridization (FISH); two cases with imbalanced neurotrophic tyrosine receptor kinase 3 (NTRK3) expression were tested using reverse transcription-polymerase chain reaction (RT-PCR).

Assessment of Predictive Biomarkers of the Response to Pazopanib Based on an Integrative Analysis of High-grade Soft-tissue Sarcomas: Analysis of a Tumor Sample from a Responder and Patients with Other Soft-tissue Sarcomas.

Background: Soft-tissue sarcomas are a rare group of malignant tumors that usually are treated with surgical excision and radiation therapy, but recently, pazopanib, an oral tyrosine kinase inhibitor, has been used in patients with metastases who do not respond to standard chemotherapy regimens. Based on patients with advanced soft-tissue sarcomas who had received prior chemotherapy, several clinical studies have reported the survival and sensitivity (approximately 5% to 10% sensitive) of patients with soft-tissue sarcomas treated with pazopanib. Recently, next-generation sequencing (NGS) technologies have been used to provide a wide genetic information and to develop personalized medicine in cancer treatment.

Preoperative denosumab treatment with curettage may be a risk factor for recurrence of giant cell tumor of bone.

Purpose: Giant cell tumor of bone (GCTB) is a local aggressive bone tumor, histologically classified as intermediate malignancy. Recently, the RANKL inhibitor, denosumab, was developed as a novel and effective treatment option for GCTB. Since the risk of preoperative use of denosumab with curettage had been previously reported, this study aimed to investigate the relationship between recurrences and clinicopathological features associated with adjuvant denosumab treatment in GCTB.

Detection of circulating sarcoma tumor cells using a microfluidic chip-type cell sorter.

Analyses of circulating tumor cells have been shown to be effective for the detection of cancer relapse and prognosis prediction. However, research regarding its utility in sarcoma remains scarce. In this study, the microfluidic chip-type cell sorter On-chip Sort was used to construct a system for detecting circulating sarcoma cells (CSCs).

Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.

Purpose: Giant cell tumors of bone (GCTBs) are locally aggressive osteolytic bone tumors. Denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTBs. Histologically, the post-denosumab-treated samples are characterized by two lesions: a residual stromal cell lesion with a few multinucleated giant cells (SL-lesion), and a fibro-osseous lesion (FO-lesion).

Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.

Synovial sarcoma (SS) is a malignant soft tissue lesion and most commonly arises in young adults. Chromosomal translocation t(X;18)(p11;q11) results in the formation of / by gene fusion of the SS18 gene on chromosome 18 to either , , or gene located on chromosome X, which is detected in more than 95% of SSs. Although multiple lines of evidence suggest that the fusion is the oncogene in this tumor, the protein expression profiles associated with / have yet to be elucidated.

is negatively regulated by Kit in gastrointestinal stromal tumors.

Our group has previously demonstrated that pfetin, encoded by the gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of in GIST, in addition to a possible association between alterations and protein expression, we examined 76 patients with GISTs for mutations by PCR-direct sequence, and compared these results with clinicopathologic data.

regulated by PAX3/FOXO1 fusion contributes to the acquisition of aggressive behavior in PAX3/FOXO1-positive alveolar rhabdomyosarcoma.

To better characterize the oncogenic role of the fusion protein in the acquisition of aggressive behavior in ARMS, we employed a proteomic approach using a PAX3-FOXO1 knockdown system in ARMS cell lines. This approach revealed a protein list consisting of 107 consistently upregulated and 114 consistently downregulated proteins that were expected to be regulated by PAX3-FOXO1 fusion protein. Furthermore, we identified 16 upregulated and 17 downregulated critical proteins based on a data-mining analysis.

IRE1α-XBP1 inhibitors exerted anti-tumor activities in Ewing's sarcoma.

Ewing's sarcoma (ES) is the second-most frequent pediatric bone tumor. Chromosomal translocation t(11;22)(q24:q12) results in the formation of EWS/FLI1 gene fusion, which is detected in approximately 90% of tumors of the Ewing family. Several transcriptome studies have provided lists of genes associated with EWS/FLI1 expression.

Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma.

Background: Alveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers.

Clinicopathological effects of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors.

Recently, several studies have reported that dysfunctions in protein phosphatase 2A (PP2A) caused by alterations in protein phosphatase 2 regulatory subunit A, alpha (PPP2R1A) are responsible for tumorigenesis and tumor progression in several types of cancers. The impact of PPP2R1A mutations remains unknown in gastrointestinal stromal tumors (GISTs), although mutations in KIT and PDGFRA, which result in constitutive activation of the receptor tyrosine kinase pathway, are important in GIST tumorigenesis. In this study, we performed mutation analysis of PPP2R1A to examine the frequency of PPP2R1A mutations and their clinicopathological correlation in 94 GIST cases.

Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab.

Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab.

Type 3 internal hemipelvectomy: a report of two cases.

Type 3 internal hemipelvectomy involves resection of the pubis. We report on 2 patients who underwent type 3 internal hemipelvectomy. One patient developed a bladder hernia, tumour recurrence, and a pathological fracture of the proximal femur.

Skeletal Metastasis of Unknown Primary Origin at the Initial Visit: A Retrospective Analysis of 286 Cases.

Background: Skeletal metastasis is a common metastatic event for several carcinomas, and the treatment for skeletal metastasis of unknown primary (SMUP) are a critical issue in cancer therapy. Making a diagnosis of the primary site is the most crucial step in the treatment of SMUP; however, the procedures are sometimes difficult and time-consuming, and the primary site often remains unknown. Therefore, to establish optimal diagnostic strategies and elucidate the overall survival rates of SMUP, we conducted this retrospective study.

Bilateral non-osteochondroma-related proximal tibiofibular synostosis.

We report the case of a 67-year-old male with bilateral proximal tibiofibular synostosis, presenting with unilateral symptoms. The patient complained of pain around the left fibular head, which was attributed to incomplete bone bridging between the proximal tibia and fibula; he underwent proximal fibular head resection, which alleviated the pain and improved knee mobility. Eleven months later, the patient continued to be pain-free and did not experience any adverse effects.

Desmoplastic fibroma of the rib with cystic change: a case report and literature review.

Desmoplastic fibroma (DF) is a rare, locally aggressive, solitary tumor microscopically composed of well-differentiated myofibroblasts with abundant dense collagen deposition. The most common sites are the long tubular bones and mandible. To our knowledge, only five cases of DF in the ribs have been reported.

Desmoplastic fibroma of the scapula with fluorodeoxyglucose uptake on positron emission tomography: a case report and literature review.

We present a case of desmoplastic fibroma (DF) arising from the right scapula that was incidentally identified by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging performed to evaluate the presence of metastasis due to a history of surgical treatment for endometrioid adenocarcinoma. A 65-year-old woman was admitted to our hospital for consultation about a bone lesion in the right scapula although she was asymptomatic. FDG-PET revealed moderate focal (18)F-FDG uptake in the right scapula with a maximal standardized uptake value of 3.

Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor.

Background: Prognostic biomarkers are required for risk stratification therapy in the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to identify prognostic biomarkers in GIST. We assessed the prognostic value of E twenty-six variant 1 (ETV1), a recently identified transcription factor unique to GIST.

p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1.

Giant cell tumor of bone (GCTB) is a benign tumor with a tendency for local recurrence. Secondary malignant GCTB is rare, occurring in less than 2 % of GCTB cases. Mechanisms of malignant transformation of GCTB remain unclear.

The prognostic value of pfetin: a validation study in gastrointestinal stromal tumors using a commercially available antibody.

Objective: Adjuvant treatment with imatinib mesylate is an effective treatment for gastrointestinal stromal tumor. However, 50% of patients with gastrointestinal stromal tumor can be cured by surgery alone; hence, risk stratification for therapy with imatinib mesylate is the next challenge. Previously, using a proteomic approach, we discovered a potential prognostic biomarker for gastrointestinal stromal tumor, pfetin, and immunohistochemically validated its clinical utility using our original monoclonal antibody.