Publications by authors named "Yoshinori Imura"

40 Publications

Impact of Surgical Resection and Reasons for Poor Prognosis of Pelvic Osteosarcoma Based on the Bone Tumor Registry in Japan.

Cancers (Basel) 2021 Jul 1;13(13). Epub 2021 Jul 1.

Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center, Tokyo 104-0045, Japan.

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13133320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268378PMC
July 2021

Tocilizumab Controls Paraneoplastic Inflammatory Syndrome but Does Not Suppress Tumor Growth of Angiomatoid Fibrous Histiocytoma.

Case Rep Oncol Med 2021 16;2021:5532258. Epub 2021 Jun 16.

Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that rarely metastasizes but lacks effective systemic therapy once it propagates. In some reports, high interleukin-6 (IL-6) production promotes tumor growth by autocrine stimulation and tocilizumab, an IL-6 receptor antagonist, can control AFH growth. Here, we present a case report on a patient with local recurrence and distant lymph node metastasis of AFH treated with tocilizumab. As a result, the inhibition of the IL-6 signaling pathway controlled paraneoplastic inflammatory syndrome (PIS); however, the local recurrent tumor progressed. This case implied that IL-6 is not necessarily the cause of tumor growth in AFH. Therefore, physicians should bear in mind that watchful observation is needed whether tocilizumab can control tumor progression despite the amelioration of PIS associated with the attenuated effect of IL-6 on AFH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5532258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225413PMC
June 2021

Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study.

Invest New Drugs 2021 Jun 12. Epub 2021 Jun 12.

Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Background osteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a novel tyrosine kinase inhibitor under investigation in a phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study. Patients and methods an analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule. Results a total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (>1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively. Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-021-01107-4DOI Listing
June 2021

Primary breast angiosarcoma with disseminated intravascular coagulation is successfully treated with self-subcutaneous unfractionated heparin calcium injection: A case report.

Mol Clin Oncol 2021 May 17;14(5):104. Epub 2021 Mar 17.

Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Angiosarcoma is a rare sarcoma with a poor prognosis and is prone to disseminated intravascular coagulation (DIC), where DIC often interferes with chemotherapy. Primary angiosarcoma of the breast (PASB) is a type of angiosarcoma that is located in mammary parenchyma and is not associated with radiation exposure. The current study reported a 47-year-old female with DIC associated with PASB. The DIC of the patient relapsed during mono-chemotherapy with paclitaxel (PTX) after first-line anticoagulant therapy using thrombomodulin-α. The second-line danaparoid sodium therapy, followed by self-subcutaneous injection of unfractionated heparin calcium (UFH), resulted in long-term stabilization of DIC. Under this second-line anticoagulant therapy, the patient continued chemotherapy and chemoradiotherapy for >13 months in the outpatient setting without impairment of quality of life. The present case suggested that self-subcutaneous injections of UFH may be a useful therapeutic option for long-term control of DIC associated with PASB. However, further prospective clinical trails are needed to verify the efficacy of self-subcutaneous injection of UFH in similar settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2021.2266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010513PMC
May 2021

Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report.

Mol Clin Oncol 2021 Feb 4;14(2):23. Epub 2020 Dec 4.

Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Malignant gastrointestinal neuroectodermal tumors (GNETs), also called clear-cell sarcoma-like tumors of the gastrointestinal tract, are rare and highly aggressive tumors originating in the gastrointestinal tract. These tumors are generally immunohistochemically positive for S-100 protein (S-100) and SRY-related HMG-box 10 (SOX10), and often contain EWSR1-ATF1 or EWSR1-CREB1. The histological features of GNETs overlap with those of clear-cell sarcoma of the tendons and aponeuroses. However, GNETs immunohistochemically lack melanocyte-specific markers and often demonstrate positivity for CD56, synaptophysin and neuron-specific enolase. The present case reports a woman with a history of desmoplastic malignant melanoma exhibiting a BRAF mutation, which later transformed into a GNET of the small intestine with both a BRAF mutation and two subtypes of EWSR1-ATF1 fusion genes. Tumor cells were revealed to be weakly immunoreactive or negative for S-100 and SOX10, lacked markers of melanocytic differentiation and were focally positive for CD56. Combination therapy with dabrafenib mesylate and trametinib dimethyl sulfoxide proved to be temporarily effective against this tumor. The present case is relatively unique as, to the best of our knowledge, there is no case of GNET with a history of melanoma. Furthermore, there is no report of GNET exhibiting both a BRAF mutation and an EWSR1-ATF1 fusion gene. Further accumulation of similar cases is necessary to elucidate the pathological significance of this GNET having a BRAF mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2020.2185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739819PMC
February 2021

Eribulin Provides a Remarkable Effect in Trabectedin-Resistant Myxoid Liposarcoma.

Case Rep Orthop 2020 12;2020:8873185. Epub 2020 Nov 12.

Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Adriamycin-based chemotherapy is commonly used for malignant soft tissue sarcoma including myxoid liposarcoma. However, in the case of unavailability or failure of the adriamycin-based regimen, trabectedin or eribulin can produce a good antitumor effect for myxoid liposarcoma. We relate the experience of a 64-year-old female with myxoid liposarcoma, who noticed a nodule on her left thigh and visited our institute. At initial presentation, the tumor was 18.7 cm in diameter, and the magnetic resonance imaging (MRI) showed a malignant lipomatous tumor with a myxoid component. We recommended that she undergo treatment; however, she refused. Three years later, the tumor had grown larger, so she finally decided to undergo treatment. A needle biopsy revealed a myxoid liposarcoma. The tumor massively involved the neurovascular structures; we thus determined that hip disarticulation was inevitable. Two years later, metastases in the right thigh, left lung, right ileum, and abdominal space were pointed out and chemotherapy was initiated. Adriamycin was unusable due to cardiac dysfunction, so trabectedin was administered; however, the tumors progressed. Eribulin was subsequently started and has been considerably effective for more than 2 years without severe adverse effects. In conclusion, we experienced a case showing the remarkable and long-lasting effect of eribulin against trabectedin-resistant myxoid liposarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8873185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683141PMC
November 2020

A case of Stewart-Treves syndrome occurring in the abdominal wall successfully treated with eribulin: A case report.

Mol Clin Oncol 2020 Nov 20;13(5):49. Epub 2020 Aug 20.

Musculoskeletal Oncology Service, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Angiosarcoma (AS) is a rare and aggressive tumor with high rates of local recurrence and distant metastasis. Stewart-Treves syndrome (STS) is defined as AS arising in the setting of chronic lymphedema, and is extremely uncommon in the lower abdominal wall. Eribulin mesylate (eribulin) is a non-taxane microtubule inhibitor that has been approved in Japan for treating soft tissue sarcoma. The current study reports the case of a 76 year-old woman with STS in the lower abdominal wall who exhibited an excellent response to eribulin. Having undergone surgery and postoperative radiation therapy (RT) for cervical cancer 12 years earlier, the patient presented with a mass in her left lower abdominal wall, where chronic lymphedema had developed. Contrast-enhanced computed tomography revealed multiple enhancing nodules in the left lower abdominal wall and edema of the subcutaneous tissues in the whole lower abdomen. A histologic analysis of the specimens revealed AS, and she was diagnosed as STS. A total of 3 cycles of combination chemotherapy with gemcitabine and docetaxel were administered, but the patient discontinued treatment owing to severe adverse events. RT was performed for the tumor, but multiple reddish nodules appeared in the whole lower abdominal wall 3 months later. At this point, eribulin administration was offered. After 4 cycles of treatment, there was a clear reduction in the size of the nodules. All lesions were stable, no new lesions had developed, and the side effects of treatment were minor over the course of 1 year. The results reveal that eribulin may serve as a potential therapeutic option for the treatment of STS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2020.2119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453393PMC
November 2020

Prognostic factors and skeletal-related events in patients with bone metastasis from gastric cancer.

Mol Clin Oncol 2020 Oct 22;13(4):31. Epub 2020 Jul 22.

Musculoskeletal Oncology Service, Osaka International Cancer Institute, Osaka 541-8567, Japan.

The number of studies on bone metastasis (BM) from gastric cancer (GC) is currently limited. Therefore, the aim of the present study was to investigate the characteristics, skeletal-related events (SREs) and prognosis of GC in patients with BMs. Data from 60 patients with BMs from GC were retrospectively retrieved and patient-, tumor- and BM-related characteristics were analyzed. Kaplan-Meier survival curves were analyzed using the univariate log-rank test. Multivariate analyses were conducted using the Cox proportional hazards model. The median patient age was 63.5 years (range, 26-83 years). Visceral or brain metastases were observed at BM diagnosis in 61.7% of the patients. Multiple BMs were detected in 83.3% and SREs occurred in 76.7% of the patients. The median overall survival (OS) after BM diagnosis and SRE occurrence was 9 months (range, 0-43 months) and 5 months (range, 0-36 months), respectively. On multivariate analysis, poor Eastern Cooperative Oncology Group performance status (P=0.030), the administration of chemotherapy prior to BM diagnosis (P<0.001) and no chemotherapy after BM diagnosis (P=0.002) were significant prognostic factors for unfavorable OS, whereas the non-use of bone-modifying agents (BMAs) was the only independent prognostic factor for poor SRE-free survival (SRS; P=0.022). Among patients without SREs at BM diagnosis, the median SRS duration was 7 months (range, 0-43 months). In conclusion, chemotherapy may confer a survival benefit in GC patients with BMs. In addition, the prognosis for GC patients with BMs presenting with SREs is poor, but treatment with BMAs may prevent or delay the development of SREs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2020.2101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403842PMC
October 2020

Clinical Outcomes of Osteoarticular Extracorporeal Irradiated Autograft for Malignant Bone Tumor.

Sarcoma 2020 30;2020:9672093. Epub 2020 Mar 30.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Methods: We retrospectively reviewed 33 patients who underwent osteoarticular ECIA after bone tumor resection from 1988 to 2014. We investigated complications, radiographic changes by the International Society of Limb Salvage graft evaluation criteria, and functional outcomes according to the Musculoskeletal Tumor Society scoring system.

Results: Fifteen patients were reoperated upon due to infection ( = 9), protruding fixation implant ( = 4), or fracture of the grafted bone ( = 2). The average radiographic evaluation score was 66.4%, and the median functional score was 23 (77%). The radiographic score for the proximal humerus or proximal tibia was lower than that for the other locations. The functional score was not different among the autograft sites but was related to the radiographic score.

Conclusion: Although osteoarticular ECIA is one of the reasonable surgical options for patients with tumors for which reliable prostheses are not available, we do not recommend osteoarticular ECIA as a routine procedure because of high complication rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9672093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149532PMC
March 2020

A long-term follow-up study of extracorporeal irradiated autografts in limb salvage surgery for malignant bone and soft tissue tumors: A minimum follow-up of 10 years after surgery.

J Surg Oncol 2020 Jun 4;121(8):1276-1282. Epub 2020 Apr 4.

Department of Orthopaedic Surgery, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan.

Background And Objectives: The aim of this study is to assess the survival, function, radiographic appearance, and modes of failure of extracorporeal irradiated (ECI) autografts in a long-term setting.

Methods: We retrospectively reviewed 87 patients who were treated for bone and soft tissue tumors using ECI autografts between 1988 and 2009.

Results: The 56 patients had a minimum follow-up of 10 years, and the median follow-up period was 16.5 years. The reimplantation procedures included 24 osteoarticular grafts, 16 intercalary grafts, 10 autograft-prosthetic composite grafts, and 6 hemicortical grafts. The 15-year graft and event-free survival rates were 76.8% and 47.9%, respectively. Infection and structural failure were the most common reasons for additional surgery. The time for additional surgery was significantly longer in patients with composite grafts (P < .01). The median Musculoskeletal Tumor Society score and the International Society of Limb Salvage score were 80% and 84%, respectively.

Conclusions: ECI autografts are a durable option for reconstruction after resection of musculoskeletal tumors and provide good function over more than 15 years. Most graft failures occurred within 5 years of the index surgery. However, composite grafts showed a tendency to fail more than 10 years after the surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.25918DOI Listing
June 2020

TAS-115 inhibits PDGFRα/AXL/FLT-3 signaling and suppresses lung metastasis of osteosarcoma.

FEBS Open Bio 2020 05 30;10(5):767-779. Epub 2020 Mar 30.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Osteosarcoma is the most common malignant bone tumor in adolescence and childhood. Metastatic osteosarcoma has a poor prognosis with an overall 5-year survival rate of approximately 20%. TAS-115 is a novel multiple receptor tyrosine kinase inhibitor that is currently undergoing clinical trials. Using the mouse highly lung-metastatic osteosarcoma cell line, LM8, we showed that TAS-115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of osteosarcoma at least partially through the inhibition of platelet-derived growth factor receptor alpha, AXL, and Fms-like tyrosine kinase 3 phosphorylation. We also show that these signaling pathways are activated in various human osteosarcoma cell lines and are involved in proliferation. Our results suggest that TAS-115 may have potential for development into a novel treatment for metastatic osteosarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.12827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193166PMC
May 2020

Clinical outcomes of chondroblastoma treated using synthetic bone substitute: risk factors for developing radiographic joint degeneration.

World J Surg Oncol 2020 Mar 2;18(1):47. Epub 2020 Mar 2.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB.

Methods: We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. Clinical data, radiographic images, treatments, and local recurrence were analyzed.

Results: We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8-35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13-239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004).

Conclusions: Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-020-01829-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053063PMC
March 2020

Author Correction: Establishment of a novel human CIC-DUX4 sarcoma cell line, Kitra-SRS, with autocrine IGF-1R activation and metastatic potential to the lungs.

Sci Rep 2020 Jan 15;10(1):684. Epub 2020 Jan 15.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-55752-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962364PMC
January 2020

Malignant peripheral nerve-sheath tumors in an adolescent patient with mosaic localized NF1: A case report.

Mol Clin Oncol 2020 Feb 17;12(2):155-159. Epub 2019 Dec 17.

Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.

Malignant peripheral nerve-sheath tumors (MPNSTs) are rare malignancies that are often observed in patients with neurofibromatosis type 1 (NF1). However, the occurrence of MPNST associated with mosaic localized NF1 is extremely rare. Previous reports have revealed that MPNST was associated with mosaic localized NF1 in only three patients who were >40 years of age. The present report details a 16-year-old man who presented with pain and a 3 cm mass on the medial side of the right knee. Magnetic resonance imaging revealed a circumscribed soft tissue tumor located in the subcutaneous tissue. His previous doctor believed that it was benign and conducted a marginal resection. However, postoperative histology results demonstrated spindle cell sarcoma, following which the patient was referred to The Osaka International Cancer Institute. Localized café-au-lait spots were identified in the affected leg, which inferred that the patient had NF1-related MPNST. A wide resection was performed to completely resect the residual tumor; however, a definitive histological diagnosis was challenging due to the small residual tumor. Hence, the genomic mutations of NF1 in the regional café-au-lait spots were analyzed. The result revealed an NF1 microdeletion and a consistently limited expression of NF1 in the tumor sample. Finally, the patient was diagnosed with MPNST with mosaic localized NF1. Local recurrence and distant metastasis were not observed 1.5 years after surgery. In conclusion, the present report presented MPNST in an adolescent patient with mosaic localized NF1. The occurrence of MPNSTs correlated with mosaic localized NF1 is extremely rare. However, it is of high-grade malignancy and therefore, its clinical features should be considered by orthopedists and pathologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2019.1969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951113PMC
February 2020

Clinical features and prognostic factors in patients with esophageal cancer with bone metastasis.

Oncol Lett 2020 Jan 22;19(1):717-724. Epub 2019 Nov 22.

Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, Osaka 541-8567, Japan.

There have been few reports on bone metastases (BMs) from esophageal cancer (EC). The aim of the present study was to investigate the clinicopathological features and prognostic factors in patients with EC with BMs. The present study retrospectively collected data from 58 patients with BMs from EC who were treated at our institution between 2007 and 2016. Patient, tumor and BM-associated characteristics were analyzed. Kaplan-Meier survival curves were constructed and analyzed using the univariate log-rank test. Multivariate analyses were conducted using the Cox proportional hazards model. The median patient age was 67 years (range, 39-84 years). Multiple BMs were detected in 38 patients (65.5%) and 52 patients (89.7%) exhibited osteolytic BMs. Skeletal-related events (SREs) occurred in 53 patients (91.4%). The one-year overall survival (OS) was 25.3%, and the median OS was 5 months (range, 0-54). Univariate analyses revealed that performance status, visceral or brain metastasis, serum carcinoembryonic antigen (CEA), C-reactive protein, albumin level, and receipt of chemotherapy following BM diagnosis were significantly associated with OS. Multivariate analyses of these factors demonstrated that higher serum CEA levels and no chemotherapy were significant risk factors for poor OS. Multiple osteolytic BMs are frequently observed in patients with EC with BMs, and SREs commonly occur. The prognoses of patients with EC with BMs are poor, but chemotherapy administration following the BM diagnosis should confer a survival benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2019.11142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924156PMC
January 2020

Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling.

Mol Cancer Ther 2020 03 3;19(3):742-754. Epub 2019 Dec 3.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Clear cell sarcoma (CCS) is a rare but chemotherapy-resistant and often fatal high-grade soft-tissue sarcoma (STS) characterized by melanocytic differentiation under control of microphthalmia-associated transcription factor (MITF). Eribulin mesilate (eribulin) is a mechanistically unique microtubule inhibitor commonly used for STS treatment, particularly liposarcoma and leiomyosarcoma. In this study, we examined the antitumor efficacy of eribulin on four human CCS cell lines and two mouse xenograft models. Eribulin inhibited CCS cell proliferation by inducing cell-cycle arrest and apoptosis, shrunk CCS xenograft tumors, and increased tumor vessel density. Eribulin induced MITF protein upregulation and stimulated tumor cell melanocytic differentiation through ERK1/2 inactivation (a MITF negative regulator) and Moreover, tumor reoxygenation, probably caused by eribulin-induced vascular remodeling, attenuated cell growth and inhibited ERK1/2 activity, thereby upregulating MITF expression and promoting melanocytic differentiation. Finally, downregulation of MITF protein levels modestly debilitated the antiproliferative effect of eribulin on CCS cells. Taken together, eribulin suppresses CCS through inhibition of cell proliferation and promotion of tumor differentiation by acting both directly on tumor cells and indirectly through tumor reoxygenation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-19-0358DOI Listing
March 2020

Establishment of a novel human CIC-DUX sarcoma cell line, Kitra-SRS, with autocrine IGF-1R activation and metastatic potential to the lungs.

Sci Rep 2019 11 1;9(1):15812. Epub 2019 Nov 1.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Approximately 60-70% of EWSR1-negative small blue round cell sarcomas harbour a rearrangement of CIC, most commonly CIC-DUX. CIC-DUX sarcoma (CDS) is an aggressive and often fatal high-grade sarcoma appearing predominantly in children and young adults. Although cell lines and their xenograft models are essential tools for basic research and development of antitumour drugs, few cell lines currently exist for CDS. We successfully established a novel human CDS cell line designated Kitra-SRS and developed orthotopic tumour xenografts in nude mice. The CIC-DUX fusion gene in Kitra-SRS cells was generated by t(12;19) complex chromosomal rearrangements with an insertion of a chromosome segment including a DUX pseudogene component. Kitra-SRS xenografts were histologically similar to the original tumour and exhibited metastatic potential to the lungs. Kitra-SRS cells displayed autocrine activation of the insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) pathway. Accordingly, treatment with the IGF-1R inhibitor, linsitinib, attenuated Kitra-SRS cell growth and IGF-1-induced activation of IGF-1R/AKT signalling both in vitro and in vivo. Furthermore, upon screening 1134 FDA-approved drugs, the responses of Kitra-SRS cells to anticancer drugs appeared to reflect those of the primary tumour. Our model will be a useful modality for investigating the molecular pathology and therapy of CDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-52143-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825133PMC
November 2019

Favorable outcomes of localized synovial sarcoma patients with a high utilization rate of neoadjuvant and/or adjuvant chemotherapy.

Mol Clin Oncol 2019 Aug 21;11(2):151-156. Epub 2019 May 21.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Synovial sarcoma (SS) is considered to be a chemosensitive, soft tissue sarcoma. Therefore, neoadjuvant and/or adjuvant chemotherapy (N/AC) is used for the treatment of high-risk SS patients. However, the role of N/AC remains controversial. The present study aimed to review the clinical outcomes of surgically treated localized SS and investigate the effects of N/AC with long-term observation. The clinical outcomes of 54 patients with surgically treated localized SS were retrospectively analyzed. The median patient age was 42 years (range, 8-81 years), and the median follow-up period was 94 months for survivors (range, 7-220 months). A total of 38 patients (70%) received chemotherapy. Of these, 32 (59%) patients received neoadjuvant chemotherapy, 33 (61%) received adjuvant chemotherapy, and 27 (50%) received neoadjuvant and adjuvant chemotherapy. Fourteen patients (26%) received adjuvant radiotherapy. Three patients (6%) had local recurrence and 13 patients (24%) developed distant metastasis. The overall survival (OS) rates at 5 and 10 years were 87 and 84%, respectively. N/AC did not improve survival. In conclusion, we found satisfactory long-term OS among patients with a high utilization rate of N/AC. Further study should be necessary to evaluate which population of SS would benefit from N/AC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2019.1863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587004PMC
August 2019

Prognostic implication of adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide in patients with extraskeletal osteosarcoma.

Int J Clin Oncol 2019 Oct 13;24(10):1311-1319. Epub 2019 Jun 13.

Department of Orthopaedic Surgery, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.

Background: Extraskeletal osteosarcoma (ESOS) is an extremely rare soft tissue sarcoma. Their prognosis remains poor. Our purposes were to identify the effective chemotherapeutic regimen for ESOS.

Methods: We retrospectively reviewed 16 patients with ESOS treated at the Osaka University Orthopaedic Oncology Group between 1992 and 2012. We extracted the clinical data on patients. Kaplan-Meier method and the log-rank test were used for survival analyses.

Results: Median age of the patients was 61.5 years (range 25-79 years). Wide local excision was performed for 11 patients and 9 patients were treated combined with chemotherapy. The 5-year disease-specific survival (DSS) rate was 53.9%. The 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy or not were 66.7% or 25%, respectively (p = 0.0215). Furthermore, the 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide and those treated with other regimens were 100% or 40%, respectively (p = 0.0327).

Conclusion: The present study demonstrated that adjuvant/neoadjuvant chemotherapy, especially consisting of doxorubicin and ifosfamide, was potentially efficacious for ESOS. Further prospective study using this multimodality treatment approach to patients with ESOS should be strongly warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-019-01475-1DOI Listing
October 2019

Survival analysis of elderly patients with osteosarcoma.

Int Orthop 2019 07 22;43(7):1741-1747. Epub 2019 Apr 22.

Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: Few studies have described the characteristics and prognostic factors of elderly patients with osteosarcoma. We retrospectively investigated clinico-pathological features and prognostic factors in osteosarcoma patients > 40 years old.

Methods: Patients with high-grade osteosarcoma > 40 years old who were treated at our institutions from 2000 to 2016 were recruited for this study. Information on patient, tumour, and treatment-related factors was collected and statistically analyzed. The median follow-up was 26.5 months (range, 5-139 months) for all patients.

Results: Fifty patients (30 males and 20 females) were included. The median age at diagnosis was 59.5 years (range, 41-81 years). The primary lesions were found in the limbs in 32 patients, trunk in 12, and craniofacial bones in six. Primary and secondary osteosarcoma occurred in 41 and 9 patients, respectively. Eight patients exhibited initial distant metastasis. Definitive surgery and chemotherapy were performed in 39 patients each. The rate of good responders after neoadjuvant chemotherapy was 38%. The five year overall survival (OS) rates for all patients and those without distant metastasis at diagnosis were 44.5% and 51.1%, respectively. Multivariate analysis showed that definitive surgery was the only significant prognostic factor in non-metastatic patients. The five year OS and disease-free survival (DFS) rates for non-metastatic patients who received definitive surgery were 64.3% and 60%, respectively. Among these patients, neoadjuvant and/or adjuvant chemotherapy significantly improved both OS and DFS.

Conclusions: Complete surgical resection and intensive chemotherapy should be performed for osteosarcoma patients > 40 years old despite distinct clinicopathological characteristics from those of younger patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00264-019-04332-yDOI Listing
July 2019

Clinical outcomes and significant factors in the survival rate after decompression surgery for patients who were non-ambulatory due to spinal metastases.

J Orthop Sci 2019 Mar 25;24(2):347-352. Epub 2018 Oct 25.

Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuuou, Osaka 541-8567, Japan.

Background: The development of effective chemotherapy regimens and molecular targeting agents are improving the overall survival rates in patients with cancer. However, patients who are non-ambulatory due to metastatic epidural spinal cord compression (MESCC) may be assessed as unable to tolerate chemotherapy secondary to poor performance status. This means that the ambulatory status of patients with cancer might be significant for survival time.

Methods: We investigated the functional outcomes and factors influencing overall survival in 31 patients who were non-ambulatory due to MESCC and underwent decompression surgery. The functional outcome was determined by the Frankel grading system.

Result: Twenty-one patients (68%) improved by at least 1 Frankel grade; 17 patients (55%) became ambulatory postoperatively. Most of postoperatively ambulatory patients could undergo postoperative chemotherapy (14/17, 82%). On the other hand, only a few postoperatively non-ambulatory patients could undergo postoperative chemotherapy (2/15, 13%). We observed a complication rate of 35.5% with specific complications including wound infection, pneumonia, and deep vein thrombosis/pulmonary embolus. The median survival duration was 7.0 months. Factors that significantly affected the overall survival in univariate analyses were revised Tokuhashi score (RTS) ≥ 4, postoperative chemotherapy, ambulatory status, and complications (RTS ≥ 4, P < 0.05; postoperative chemotherapy, P < 0.001; ambulatory status, P < 0.001; complications, P < 0.01).

Conclusions: Decompression surgery for patients who are non-ambulatory due to MESCC directly contributes to functional outcomes and may indirectly contribute to overall survival. If non-ambulatory patients who are assessed as unable to tolerate chemotherapy due to poor performance status regain the ability to walk by decompression surgery, they will have a chance to receive postoperative chemotherapy, thereby increasing their chances of prolonging survival. However, postoperative complications may shorten their survival; therefore, we should carefully consider the surgical indications. RTS is useful for judging the surgical indication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jos.2018.10.003DOI Listing
March 2019

Endoprosthetic Reconstruction for a Displaced Atypical Femoral Fracture in a Cancer Patient with Poor Prognosis.

Case Rep Orthop 2018 20;2018:7862516. Epub 2018 Sep 20.

Department of Orthopedic Surgery, Bellland General Hospital, 500-3 Higashiyama, Naka-ku, Sakai, 599-8247 Osaka, Japan.

Zoledronate or denosumab treatment is beneficial for cancer patients with bone metastasis. However, each agent may trigger atypical femoral fractures. Incomplete atypical femoral fractures can be successfully treated with prophylactic intramedullary nailing. On the other hand, intramedullary nailing for displaced atypical femoral fractures occasionally causes problems with regard to bone healing, resulting in long-term treatment. In cancer patients with poor prognosis who experience atypical femoral fractures, improvement in activities of daily living should be the priority. Thus, we performed endoprosthetic reconstruction for a displaced atypical femoral fracture in a breast cancer patient with poor prognosis to enable walking in the early stage after the operation. Two weeks after the operation, she could successfully walk. The postoperative Musculoskeletal Tumor Society score was 47%, and it had improved to almost the preoperative level before injury (50%). In conclusion, endoprosthetic reconstruction for displaced atypical femoral fractures may be a first-line treatment approach to acquire early postoperative walking ability for improving activities of daily living in cancer patients with poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/7862516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171208PMC
September 2018

Clinical Features and Prognosis of Patients With the Bone Metastasis of Pancreatic Cancer: A Single-Institutional Cohort Study.

Pancreas 2018 08;47(7):e43-e46

Department of Orthopedic Surgery Osaka University Graduate School of Medicine Musculoskeletal Oncology Service Osaka International Cancer Institute Osaka, Japan Department of Surgery Osaka International Cancer Institute Osaka, Japan Musculoskeletal Oncology Service Osaka International Cancer Institute Osaka, Japan Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute Osaka, Japan Musculoskeletal Oncology Service Osaka International Cancer Institute Osaka, Japan Department of Surgery Osaka International Cancer Institute Osaka, Japan Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute Osaka, Japan Department of Orthopedic Surgery Ashiya Municipal Hospital Hyogo, Japan Musculoskeletal Oncology Service Osaka International Cancer Institute Osaka, Japan Musculoskeletal Oncology Service Osaka International Cancer Institute Osaka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001098DOI Listing
August 2018

Calcific myonecrosis mimicking soft tissue sarcoma: A case report.

Oncol Lett 2018 May 22;15(5):7909-7913. Epub 2018 Mar 22.

Department of Orthopaedic Surgery, Belland General Hospital, Sakai, Osaka 599-8247, Japan.

Calcific myonecrosis is a rare soft tissue condition. The first case was reported in 1960, however, the precise pathophysiology of calcific myonecrosis remains unclear. The disease was thought to arise from compartment syndrome within a confined space resulting in necrosis and fibrosis, subsequent repeated intralesional hemorrhage, mass enlargement and calcification. Several previous reports have described calcific myonecrosis, which include the formation of calcific myonecrosis after a prolonged period of post trauma. Notably, calcific myonecrosis has typically been described in the lower legs and characteristic imaging findings have been indicated. Furthermore, surgical intervention carries a high risk of complications. In the present case report 2 cases of calcific myonecrosis that occurred after a prolonged period of time following a traumatic event that impacted the lower leg were reported. CT images revealed disruption of calcified fascia and disease expansion into the outside of the fascia. Previous reports have implied that there is late focal enlargement of calcific myonecrosis following earlier enlargement, which may be caused by herniation through muscle fascia. However, no previous publications have focused on images for evidence of late local enlargement. To the best of our knowledge, this is the first report focusing on fascial herniation of calcific myonecrosis using images. Analysis of this feature using images may aid clinicians to differentiate calcific myonecrosis from malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2018.8320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920900PMC
May 2018

Atypical femoral fracture associated with bone-modifying agent for bone metastasis of breast cancer: A report of two cases.

J Orthop Surg (Hong Kong) 2017 Sep-Dec;25(3):2309499017727916

Musculoskeletal Oncology Service, Osaka International Cancer Institute, Osaka, Japan.

Atypical femoral fractures (AFFs) are recently observed as a complication of long-term bone-modifying agent (BMA; bisphosphonate or denosumab) therapy for bone metastases. We describe the cases of two women diagnosed with breast cancer who developed incomplete AFF associated with BMAs prescribed for bone metastases. Radiographs of their femurs revealed thickening of the lateral subtrochanteric cortex, and tomosynthesis revealed a visible fracture line in the thickened cortex. They were initially treated with conservative management; however, the incomplete fracture resulted in a complete fracture. These cases highlight two major implications. First, symptomatic incomplete AFF associated with BMAs prescribed for bone metastases should be treated with surgical prophylaxis, given the fact that fracture healing is expected to require a longer duration and an incomplete fracture might potentially progress to a complete fracture during long-term conservative management. Second, tomosynthesis is useful in identifying radiolucent fracture lines that are reliable predictors of fracture propagation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2309499017727916DOI Listing
March 2018

Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis.

Int J Clin Oncol 2018 Feb 10;23(1):181-188. Epub 2017 Aug 10.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose: An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis.

Methods: We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables.

Results: The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival.

Conclusions: Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-017-1179-xDOI Listing
February 2018

Trabectedin is a promising antitumor agent potentially inducing melanocytic differentiation for clear cell sarcoma.

Cancer Med 2017 Sep 26;6(9):2121-2130. Epub 2017 Jul 26.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Clear cell sarcoma is an aggressive soft tissue sarcoma and highly resistant to conventional chemotherapy and radiation therapy. This devastating disease is defined by EWSR1-ATF1 fusion gene resulting from chromosomal translocation t(12;22)(q13;q12) and characterized by melanocytic differentiation. A marine-derived antineoplastic agent, trabectedin, inhibits the growth of myxoid liposarcoma and Ewing sarcoma by causing adipogenic differentiation and neural differentiation, respectively. In this study, we examined the antitumor effects and mechanism of action of trabectedin on human clear cell sarcoma cell lines. We showed that trabectedin decreased the cell proliferation of five clear cell sarcoma cell lines in a dose-dependent manner in vitro and reduced tumor growth of two mouse xenograft models. Flow cytometry and immunoblot analyses in vitro and immunohistochemical analysis in vivo revealed that trabectedin-induced G2/M cell cycle arrest and apoptosis. Furthermore, trabectedin increased the expression of melanocytic differentiation markers along with downregulation of ERK activity in vitro and the rate of melanin-positive cells in vivo. These results suggest that trabectedin has potent antitumor activity against clear cell sarcoma cells by inducing cell cycle arrest, apoptosis, and, in part, by promoting melanocytic differentiation through inactivation of ERK signaling. Our present study indicates that trabectedin is a promising differentiation-inducing agent for clear cell sarcoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.1130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603837PMC
September 2017

Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma.

BMC Cancer 2017 05 16;17(1):334. Epub 2017 May 16.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS.

Methods: We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib.

Results: We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respectively. TAS-115 treatment blocked the phosphorylation of PDGFRα as well as that of c-MET and their downstream effectors, leading to marked growth inhibition in both types of SS cell lines in in vitro and in vivo studies. Furthermore, PDGFRα phosphorylation, on at least four representative autophosphorylation sites, was impeded by TAS-115 equivalently to pazopanib.

Conclusions: These experimental results have demonstrated the significance of c-MET and PDGFRα signalling for growth and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose tumours are dependent upon either c-MET or PDGFRα signalling by functioning as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRα pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-017-3324-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434537PMC
May 2017

Functional and therapeutic relevance of hepatocyte growth factor/c-MET signaling in synovial sarcoma.

Cancer Sci 2016 Dec 19;107(12):1867-1876. Epub 2016 Dec 19.

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with a poor prognosis and, thus, novel therapeutic strategies for SS are urgently required. In the present study, we investigated the functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS. Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.13092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198956PMC
December 2016
-->