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Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly(lactic- co -glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.

Purpose: To investigate the effect of mebendazole on an in vivo solid tumor model of fibrosarcoma in hamsters. Methods: 24 Syrian golden hamsters of both sexes with the approximate body weight of 100g were randomly distributed in 2 experimental and 2 control groups, with 6 animals in each group. BHK-21/C13 cells (2 x 106) in 1 mL Glasgow Minimum Essential Medium (GMEM) were injected subcutaneously into the back of each animal in 3 groups. The experimental groups were treated with mebendazole (460 mg/kg) via a gastric tube on a daily basis, immediately after tumor inoculation. In addition, one experimental group received deoxycholic acid 20 mg/kg once a day. After 2 weeks, when the tumors were approximately 1 - 2 cm in the control group, all the animals were sacrificed, and their blood collected for laboratory analysis. The tumors were excised, their weight and diameters measured, and the volumes calculated. The tumor samples were histopathologically assessed and the main organs toxicologically analyzed. Images were taken and processed by an imaging software, and Ki-67-positive cells in the tumor samples were quantified. Results: Mebendazole diminished tumor mitosis from 18.5 ± 3.02 to 13.5 ± 3.45 (p < 0.05), vasculature and tissue penetration, and increased necroses in tumor slices. Tumor volume and weight were insignificantly attenuated. Toxicity was not observed. Conclusion: Mebendazole might be an effective non-toxic agent in sarcoma therapy. [ABSTRACT FROM AUTHOR]

A woman in her 20s presented with headache and back pain and was found to have a left renal mass with bony metastases. She underwent nephrectomy, and on histopathology was initially diagnosed with stage 4 clear cell sarcoma of the kidney. She underwent palliative radiation and chemotherapy; however, the disease progressed and she came to our centre. We started her on second-line chemotherapy and submitted her tissue blocks for review. Due to her age and lack of sclerotic stroma in the tissue, we had our doubts about the diagnosis and hence, tissue sample was submitted for next-generation sequencing (NGS). NGS detected an EWSR1::CREBL1 fusion, clinching the final diagnosis of sclerosing epithelioid fibrosarcoma of the kidney, a singular diagnosis rarely reported in the literature. Currently, the patient is post her third line of chemotherapy, is on maintenance, and is doing well and has resumed her daily activities., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Myxofibrosarcoma is a common sarcoma among older patients, with locally infiltrative behavior and a predilection for local postoperative recurrence. Some studies have reported the factors affecting prognosis, although only a few have mentioned the previous staging classification systems. This study investigated the clinical overview and prognosis of myxofibrosarcoma to determine the optimal treatment., Methods: This retrospective study analyzed the records of 349 patients with myxofibrosarcoma in the nationwide Bone and Soft Tissue Tumor Registry in Japan from 2006 to 2015. Clinical features, treatment options, and patient outcomes were investigated., Results: Ultimately, 349 patients were identified. The overall survival rates were 93.1% at 2 years and 84.3% at 5 years. A multivariate analysis was performed using the Cox proportional hazards model. The study identified four significant prognostic factors for survival: tumor size, depth, compartment status, and location. The prognostic score was calculated by summing the scores of all the factors. The overall survival rate was 69.3% at 5 years for the patients with prognostic scores of 6 or higher. Conversely, the patients with prognostic scores of 2 or lower had a survival rate of 95.6% at 5 years., Conclusions: Among myxofibrosarcomas, those larger than 5 cm, deep-seated, invaded into the external compartment, or in axial body parts were associated with a significantly worse prognosis. Adjuvant radiotherapy and chemotherapy did not contribute significantly to a better prognosis. Previous staging classification systems are impractical for prognosis prediction. Therefore, new classifications are needed. Further research on new treatment methods for patients with a poor prognosis will be crucial in the future., (© 2022. Society of Surgical Oncology.)

Fibrosarcoma is a relatively rapidly growing, poorly delineated spindle cell tumour. It has generally good prognosis and rarely metastasizes. Soft tissue sarcomas account for less than 1% of all malignancies in adults. High rates of sarcomas are, for example, seen in patients with tuberous sclerosis complex. This paper presents the case of a patient with knee joint destruction caused by a fibrosarcoma, on account of which an emergency medical team was summoned several times. We present data from three medical rescue team interventions to a patient with a tumour in the left lower leg. The data was obtained from the documentation generated during the interventions: dispatch order record (DOR) and medical emergency treatment report (METR). The patient had a history of the following chronic diseases (ICD-10): E11.8, I50.9, I10, and M15. Two interventions involved patient transportation to a hospital, whereas the third intervention was completed in the patient&apos;s home. The fibrosarcoma caused only slight pain. Frequent bleeding from an open cancerous wound was the main problem in this patient. Difficulty in wound healing could have been related to complications of diabetes mellitus and the patients advanced age.

Backgrounds: Myxofibrosarcomas (MFS) are malignant soft tissue sarcomas with an infiltrative growth pattern and propensity for local recurrence(LR).We aimed to assess our management of MFS and make recommendations about the role of a multidisciplinary team approach and margin widths., Methods: Fifty-seven patients were identified with MFS treated at a single sarcoma centre between 1998 and 2020. Patients were stratified based on whether they presented for a planned resection (59.6%) or after an unplanned resection (40.4%) performed at a non-specialized facility. All patients underwent radiotherapy before definitive surgery., Results: 73.7% underwent a combined onco-plastic approach. The 5 year LRFS rate was 78.2% (84.4%, planned, versus 70.1%, unplanned, P = 0.194) and found comparable oncological outcomes between the planned and unplanned groups for the 5 year metastasis free survival (74.5% versus 86.1%, P = 0.257), disease free survival (70.1% versus 72.4%, P = 0.677), and Overall Survival (64.5% versus 75.9%, P = 0.950). Margin width ≥ 2 cm was obtained in 84.2% of cases and improved local control (HR = 0.22; 95% CI 0.06-0.81; P = 0.023), metastasis (HR = 0.24; 95% CI 0.07-0.80; P = 0.019) and mortality rates (HR = 0.23; 95% CI 0.09, 0.61; P = 0.003) compared to <2 cm. Margin width > 3 cm did not further affect oncological outcomes., Conclusion: Our study shows that a multidisciplinary team approach allows the achievement of low local recurrence rate and good oncological outcomes of myxofibrosarcomas, regardless of presentation status. We recommend a minimum of 2 cm margin width., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

The effects of mild-temperature hyperthermia (MTH) and metformin, alone or in combination, on the efficacy of high-dose hypofractionated radiation against experimental tumors were investigated. FSaII fibrosarcoma grown subcutaneously in the hind legs of C3H mice was irradiated with a single 15 Gy dose using a 60Co irradiator. The radio frequency capacitive method was used to heat the tumors at 41.0°C for 30 min. Metformin was intraperitoneally (i.p.) administered daily to tumor-bearing mice at a dose of 150 mg/kg. The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and programmed cell death-ligand 1 (PD-L1) were determined by immunohistochemical staining of the excised tumor tissues. The apoptosis of tumor cells in vivo was quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cleaved caspase-3 staining of the excised tumor tissues. Irradiation of tumors markedly increased the expression of HIF-1α, VEGF, and PD-L1, and MTH and metformin used either alone or in combination significantly abrogated the radiation-induced upregulation of these proteins. MTH and metformin alone or combined increased the radiation-induced apoptosis in tumor cells and enhanced the radiation-induced suppression of tumor growth. The findings indicated that the increased tumor response to 15 Gy irradiation by MTH and metformin alone or in combination was due, in part, to the abrogation of the radiation-induced upregulation of HIF-1α and its downstream targets VEGF and PD-L1., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Chen, Yu, Xiao, Liu, Xia, Li, Wang, Xiang, Liu, Yang, Li and Xiao.)

Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 T cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ Treg differentiation and increasing inflammatory cytokines. Adoptive transfer of these T cells into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, and delayed tumor growth. Mechanistically, αKG leads to an energetic state that is reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation and expression of mitochondrial complex enzymes. Furthermore, carbons from ectopic αKG are directly utilized in the generation of fatty acids, associated with lipidome remodeling and increased triacylglyceride stores. Notably, inhibition of either mitochondrial complex II or DGAT2-mediated triacylglyceride synthesis restores Treg differentiation and decreases the αKG-induced inflammatory phenotype. Thus, we identify a crosstalk between αKG, mitochondrial metabolism and triacylglyceride synthesis that controls Treg fate., Competing Interests: Declaration of interests C.M., S.K., V.D., and N.T. are inventors on patents describing the use of ligands for detection of and modulation of metabolite transporters (N.T. gave up her rights), licensed to METAFORA-biosystems., (Copyright © 2021. Published by Elsevier Inc.)

The onset of malignant solid tumors in infants is insidious and difficult to diagnose on time. The purpose of our study is to provide a theoretical basis for clinical diagnosis by retrospective analysis of the data in the past 14 years. Here, we retrospectively collected the clinical data of infants aged 0-12 months with malignant solid tumors in Beijing Tongren Hospital Affiliated to Capital Medical University from May 2005 to May 2019. The epidemiology, clinical characteristics, treatments and prognosis were statistically analyzed. A total of 496 infants (294 males and 202 females) with malignant solid tumors were analyzed. The main period of onset was 1-11 months. The most common tumor was retinoblastoma (RB, 51.8%), followed by hepatoblastoma (HB, 26.6%), neuroblastoma (NB, 10.5%), rhabdomyosarcoma (RMS, 3.4%), malignant renal tumors (3.2%), infantile fibrosarcoma (IFS, 1.6%), malignant teratoma (1.2%), Ewing's sarcoma (ES, 0.8%), medulloblastoma (MB, 0.4%) and inflammatory myofibroblastic tumor (IMT, 0.4%). The median follow-up time was 32 months (range 2-162 months). The 1-year, 3-year, and 5-year overall survival of all patients were 97.3%, 89.2%, and 81.1%, respectively, and event-free survival was 94.7%, 84.8%, and 75.8%, respectively. In conclusion, as a special group, malignant solid tumors in infants are complex, heterogeneous, and relatively rare. The prognosis of RB, HB, NB, RMS, malignant renal tumors, IFS, malignant teratoma, ES, MB, and IMT, were excellent duo to timely diagnosis and rational treatment.

Objective: Disease spectrum in pediatric sarcoma differs substantially from adults. We report a cohort of very young children with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) detailing their molecular features, treatment, and outcome., Methods: We report features of consecutive children (age <2 years) with NRSTS (2000-2017). Archival pathological material was re-reviewed, with additional molecular techniques applied where indicated., Results: Twenty-nine patients (16 females, 55%) were identified (median age 6 months; range 0-23). Most common diagnoses included infantile fibrosarcoma (IFS, n = 14, 48%), malignant rhabdoid tumor (MRT, n = 4, 14%), and undifferentiated sarcoma (n = 4, 14%). Twenty-seven of 29 (93%) had tumor molecular characterization to confirm diagnosis. Clinical presentation included a swelling/mass (n = 23, 79%). Disease extent was localized (n = 20, 69%), locoregional (n = 6, 21%), or metastatic (n = 3, 10%). Seventeen of 29 (59%) who underwent surgery achieved complete resection (R0). Other treatments included conventional chemotherapy (n = 26, 90%), molecularly targeted therapies (n = 3, 10%), and radiation (n = 5, 17%). At last follow-up (median 3 years; range 0.3-16.4), 23 (79%) were alive, disease-free and six (21%) had died of disease. All patients with IFS were alive and all those with MRT died. A cancer predisposition syndrome (CPS) was confirmed in three of 10 (30%) genetically tested patients., Conclusion: We recommend tumor molecular characterization in all young patients including evaluation for CPS to optimize treatment options and prognostication., (© 2021 Wiley Periodicals LLC.)

Since its original description in 1995, the concept of sclerosing epithelioid fibrosarcoma (SEF) as a distinctive tumor has evolved in the literature. Subsequent studies suggested that the presence of low grade fibromyxoid sarcoma (LGFMS)-like zones, occasional FUS gene rearrangements, and immunoreactivity for MUC4 all pointed to a close inter-relationship with LGFMS; however, more recent studies showed that SEF is genetically distinct from LGFMS with predominantly EWSR1-CREB3L1 fusion and complex secondary genomic alterations. To better understand the relationship between these tumors, we studied 51 cases of SEF, the largest reported series to date, and directly compared them to a previously published series of LGFMS from the same institution. The male-to-female ratio was 1.4:1 with a median age of 45 years. Tumors occurred primarily in the lower extremity (12), intra-abdominal area/visceral organs (9) and chest wall/paraspinal region (9) with a median size of 8.2 cm. The median follow-up was 49 months in 45 patients: 12 developed local recurrences and 36 developed metastases, mainly to lung and bone. Molecular studies showed EWSR1 gene rearrangement in 13 cases, 3' deletion of EWSR1 in 6, monosomy for EWSR1 in 2; FUS gene rearrangements in 3; EWSR1-CREB3L1 fusion in 7; EWSR1-CREB3L2 fusion in 1; and YAP1-KMT2A fusion in 2. Overall survival of SEF was significantly less compared with LGFMS (P≤0.0001). These results indicate that SEF is a distinct sarcoma that behaves more aggressively than LGFMS with a shorter survival, higher metastatic rate, and greater propensity to involve deep soft tissue and bone., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Myxofibrosarcoma is a common soft-tissue sarcoma in elderly patients, characterized by an infiltrative growth pattern and a high risk for persistent local recurrence. A 35-years-old woman was diagnosed with myxofibrosarcoma on the right upper arm and the tumor is surgically resected. The tumor relapsed 7 months later. Then the patient received five cycles of low power cumulative high-intensity focused ultrasound (HIFU) treatments, which completely ablated the tumor without complications. Now the patient is disease free with a high quality of life more than 30 months. This case indicates HIFU ablation might be a novel, promising therapy for recurrent myxofibrosarcoma., (© 2021 Wiley Periodicals LLC.)

Benign and malign tumors can affect the temporomandibular joint (TMJ) as any other articulation. Nevertheless, TMJ tumors are rare and mostly benign. Their clinical expression is varied including symptomatology similar to TMJ dysfunctional disorders, otologic or neurologic pathologies. In some cases, they remain totally asymptomatic. Hence, diagnosis is difficult since the symptomatology can be misleading with TMJ dysfunctional disorders or otologic disorders wrongly diagnosed. There is thus frequently a long delay between symptoms onset and diagnosis. The great variety of TMJ lesions explains the wide range of possible treatment modalities, mostly based on surgery. We provide here a review of the lesions originating from the TMJ. Tumoral or cystic mandibular lesion affecting the TMJ through local extension will not be discussed. Osteoma, osteoid osteoma, osteoblastoma, chondroma, osteochondroma, chondroblastoma, tenosynovial giant cell tumors, giant cell lesions, non-ossifying fibroma, hemangioma, lipoma or Langerhans cell histiocytosis are all possible diagnosis among the benign tumors found in the TMJ. Pseudotumors include synovial chondromatosis and aneurysmal bone cyst. Finally, malign tumors of the TMJ include mainly sarcomas (osteosarcoma, chondrosarcoma, synovial sarcoma, Ewing sarcoma, and fibrosarcoma), but also multiple myeloma and secondary metastases. We will review the clinical, radiological and histological aspects of each of these lesions. The treatment and the recurrence risk will also be discussed., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The present study investigated possible therapeutic effects of radiofrequency or hypomagnetic fields on the growth rate of two types of implanted tumours. To this end, mice with implanted fibrosarcoma and pancreatic tumours were exposed continuously to a 2 µT, 10 MHz radiofrequency magnetic field (MF) perpendicular to a 45 µT static MF or to a hypomagnetic (~0.4-1 µT) field. The reasoning for a 10 MHz treatment was based on a current theoretical explanation for MF effects, which predicts a resonance phenomenon in this frequency range. Radiofrequency MFs reduced consistently the growth rate of two implanted tumour types (by ~30% in both cases). Also, hypomagnetic field hindered tumour growth in both tumour types, but the observation was not statistically significant with fibrosarcoma tumours. In conclusion, although experiments included a limited number of animals, the results indicate that MFs may offer a novel therapeutic strategy in the treatment of cancer.

Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma. In the majority of cases, there is overexpression of MUC4, and most cases show EWSR1-CREB3L1 gene fusions. A subset of SEF displays composite histologic features of SEF and low-grade fibromyxoid sarcoma (LGFMS). These "hybrid" tumors are more likely to harbor the FUS-CREB3L2 fusion, which is also seen in most LGFMS. We, here, characterize a series of 8 soft tissue neoplasms with morphologic features highly overlapping with LGFMS and SEF but lacking MUC4 expression and EWSR1/FUS-CREB3L gene fusions. Seven tumors showed fusions of the YAP1 and KMT2A genes, and 1 had a fusion of PRRX1 and KMT2D; all but 1 case displayed reciprocal gene fusions. At gene expression profiling, YAP1 and KMT2A/PRRX1 and KMT2D tumors were distinct from LGFMS/SEF. The patients were 4 female individuals and 4 male individuals aged 11 to 91 years. Tumors with known locations were in the lower extremity (5), trunk (2), and upper extremity (1); 3 originated in acral locations. Tumor size ranged from 2.5 to 13 cm. Proportions of SEF-like and LGFMS-like areas varied considerably among tumors. All tumors that showed infiltrative growth and mitotic figures per 10 HPFs ranged from 0 to 18. Tumor necrosis was present in 1 case. Follow-up was available for 5 patients (11 to 321 mo), 2 of whom developed local recurrences, and 1 died of metastatic disease. The clinical behavior of these soft tissue sarcomas remains to be further delineated in larger series with extended follow-up; however, our limited clinical data indicate that they are potentially aggressive.

Background: High-dose radiotherapy (RT) is known to be immunogenic, but is rarely capable of driving clinically relevant abscopal antitumor immunity as monotherapy. RT is known to increase antigen presentation, type I/II interferon responses, and immune cell trafficking to irradiated tumors. Bempegaldesleukin (NKTR-214) is a CD122-preferential interleukin 2 (IL-2) pathway agonist that has been shown to increase tumor-infiltrating lymphocytes, T cell clonality, and increase PD-1 expression. NKTR-214 has increased drug half-life, decreased toxicity, and increased CD8 + T cell and natural killer cell stimulation compared with IL-2., Methods: Animals bearing bilateral subcutaneous MCA-205 fibrosarcoma or CT26 colorectal tumors were treated with NKTR-214, RT, or combination therapy, and tumor growth of irradiated and abscopal lesions was assessed. Focal RT was delivered using a small animal radiation research platform. Peripheral and tumor-infiltrating immune phenotype and functional analyses were performed by flow cytometry. RNA expression profiling from both irradiated and abscopal lesions was performed using microarray., Results: We demonstrate synergy between RT of a single tumor and NKTR-214 systemic therapy resulting in dramatically increased cure rates of mice bearing bilateral tumors compared with RT or NKTR-214 therapy alone. Combination therapy resulted in increased magnitude and effector function of tumor-specific CD8 + T cell responses and increased trafficking of these T cells to both irradiated and distant, unirradiated, tumors., Conclusions: Given the increasing role of hypofractionated and stereotactic body RT as standard of care treatments in the management of locally advanced and metastatic cancer, these data have important implications for future clinical trial development. The combination of RT and NKTR-214 therapy potently stimulates systemic antitumor immunity and should be evaluated for the treatment of patients with locally advanced and metastatic solid tumors., Competing Interests: Competing interests: DCR is a former employee and current shareholder of Nektar therapeutics, a consultant to Venrock Ventures and Third Rock Ventures, a shareholder of Maze Therapeutics, and on the scientific advisory board of Akrevia Inc. UH is an employee and shareholder of Nektar therapeutics. WLR has received research funding from Galectin Therapeutics, Bristol-Myers Squibb, AstraZeneca, Merck, Nektar Therapeutics, Tesaro/GSK, Aeglea BioTherapeutics, Shimadzu, Inhibrx, Veana Therapeutics, and MiNA Therapeutics, is on the advisory board of Vesselon, and receives royalties from Galectin Therapeutics. JMW is a consultant to Jounce Therapeutics and Novocure., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

Background: 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line., Methods: Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy., Results: The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells., Conclusions: 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.

Peptide-based immunotherapy does not usually elicit strong immunological and clinical responses in patients with end-stage cancer, including sarcoma. Here we report a myxofibrosarcoma patient who showed a strong clinical response to peptide vaccinations and whose immune responses were reboosted by anti-PD1 therapy combined with peptide vaccinations. The 46-year-old man showed a strong response to the peptide vaccinations (papillomavirus binding factor peptide, survivin-2B peptide, incomplete Freund's adjuvant, and polyethylene glycol-conjugated interferon-alpha 2a) and subsequent wide necrosis and massive infiltration of CD8+ T cells in a recurrent tumor. The patient's immune responses weakened after surgical resection; however, they were reboosted following the administration of nivolumab combined with peptide vaccinations. Thus, anti-PD1 therapy combined with peptide vaccinations might be beneficial, as suggested by the observations in this sarcoma patient.

Background: Myxofibrosarcoma (MFS) is among the most highly complex sarcoma types. Molecular cytogenetic studies have identified a high level of genomic complexity., Summary: This review provides an update of the current research related to MFS, with particular emphasis on emerging mechanisms of tumorigenesis and their potential therapeutic impact. Many novel possible molecular markers have been identified, not only for prognostication in MFS, but also to serve as possible therapeutic targets, and thereby improve clinical outcomes. However, the molecular pathogenesis of MFS remains incompletely understood. Key Messages: Patients suffering from advanced MFS might benefit from expanded molecular evaluation in order to detect specific expression profiles and identify drug-able targets. Moreover, immunotherapy represents an intriguingly perspective due to the presence of "T-cell inflamed" tumor microenvironment., (© 2020 S. Karger AG, Basel.)

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype with a generally indolent pattern of clinical behaviour, but treatments for advanced disease are limited., Patients and Methods: A retrospective search of a prospectively maintained institutional database identified 102 patients treated from December 1994 to August 2018. We evaluated the outcome of patients and the efficacy and safety of non-surgical therapies in LGFMS., Results: Ninety-four out of 102 (92.2%) underwent primary resection, seven (6.9%) were treated with systemic therapy and one (1.0%) is currently being treated with pre-operative radiotherapy. The RECIST 1.1 response rate to first-line chemotherapy was 0%, and median progression-free survival was 1.84 months (95% confidence intervaI=0.10-3.6 months)., Conclusion: Conventional systemic therapy has limited efficacy in advanced LGFMS., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA-Sarcoma (SARC), we explored relapse-related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2-gene signature. The 2-gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse-free survival (RFS) (HR: 2.966, 95%CI: 1.995-4.410 P < .001), and disease-specific survival (DSS) (HR: 2.283, 95%CI: 1.358-3.835, P = .002), as a continuous variable. Gene-level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < -0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2-gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High-level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2-gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Dendritic cells (DCs) contribute essentially to the outset and course of immune responses. So in patients with malignancy, there have been considerable interests in use of these cells in different interventions., Objective: To evaluate the impact of Leishmania major's components on DC maturation and their use as a therapeutic agent against tumor cells., Methods: The cancer model was induced by injection of WEHI-164 cells (BALB/c derived fibrosarcoma cell line) subcutaneously in the right flank of animals. Bone-marrow derived DCs (BMDCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After 5 days, tumor lysate, Leishmania major's lysate, and Lipopolysaccharide (LPS) were added to the culture and incubated for 2 days. IL-12 production in DCs was measured by ELISA. For Immunotherapy, Mice received DCs subcutaneously around the tumor site. Two weeks after DCs injection, cytotoxicity assay and infiltration of CD8+ lymphocytes were evaluated., Results: Our results showed that immunotherapy with dendritic cells exposed to Leishmania extract led to producing a higher amount of IL-12, compare to the control group. A considerable increment in specific cytotoxic T cells activity, diminished tumor growth rate and improved survival of immunized animals were seen., Conclusion: This study indicates that the use of Leishmania major extract, as well as LPS, can enhance the efficiency of DC-based vaccines and provides a basis for the use of Leishmania major in DC-targeted clinical therapies.

Infantile fibrosarcoma is a very rare soft tissue tumor in infants and children most commonly located in extremities. It constitutes less then 1 percent of all childhood cancers. Prognosis and clinical course of it is relatively good compared to adult forms. Local recurrence is common but metastasis is infrequent. In this case report we present infantile fibrosarcoma with relapse and lung metastasis despite neoadjuvant chemotherapy, pelvic reconstruction surgery with wide surgical excision and adjuvant chemotherapy protocol. The patient was a 2-year-old girl at the time of diagnosis, and there was a huge mass in pelvic region. After neoadjuvant chemotherapy, type 1 pelvic resection and pelvic reconstruction with bone cement performed. The patient presented with relapse and lung metastasis 6 months after the surgery. This is the first report of pelvic infantile fibrosarcoma with pelvic resection surgery. This case suggests that these tumors may exhibit unpredictable clinical behavior., (Copyright © 2019 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

The clinical use of interleukin-12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor-homing peptide containing isoDGR, an αvβ3-integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head-to-tail cyclized-peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12-receptor recognition. Low-dose Iso1/Au/IL12, equivalent to 18-75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by innate immune cells, such as NK and iNKT cells, monocytes, and neutrophils. NK cell depletion completely inhibits its antitumor effects. Low-dose Iso1/Au/IL12 can also increase the therapeutic efficacy of adoptive T-cell therapy in mice with autochthonous prostate cancer. These findings indicate that coupling IL12 to isoDGR-tagged nanogold is a valid strategy for enhancing its therapeutic index and sustaining adoptive T-cell therapy., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although originally described to assist airway management of fetal congenital malformations with life-threatening airway obstruction, the indications for an ex utero intrapartum treatment (EXIT) have expanded to include surgical resection of lesions that are potentially incompatible with life in the absence of uteroplacental circulatory support. We describe the case of an infantile fibrosarcoma (IFS) that presented with fetal hydrops and was successfully managed with an emergency EXIT that necessitated the initiation of a massive fetal blood transfusion both with and without the support of uteroplacental circulation.

Background: Soft-tissue sarcomas are rare entities that are divided into approximately 50 histological subtypes. Myxofibrosarcoma (MFS) represents approximately 20% of all soft-tissue sarcomas, especially in elderly patients in their sixth to eighth decades of life. The treatment for soft-tissue sarcomas varies from primary surgical resection to neoadjuvant or adjuvant radiotherapy or cytotoxic chemotherapy. The aim of this study was to evaluate the prognostic factors affecting survival of patients with MFS, taking into account gender, tumour grade, state of the resection margin, local recurrence, use of radiotherapy, presence of metastases and blood levels of haemoglobin and C-reactive protein in a retrospective, single-centre analysis with a minimum follow-up period of 60 months (range=60-156 months)., Patients and Methods: The study included 34 patients (male/female=20/14). Tumour localization, tumour grade, tumour margins, local recurrence, the use of radiotherapy, the presence of metastasis, and the blood levels of haemoglobin and C-reactive protein preoperatively and during follow-up were evaluated., Results: MFS constituted the most common high-grade sarcoma (G2/G3, 79.4%) in our cohort and was generally located in a lower limb (73.6%). Negative margins (R0) were detected in 67.6% of patients after surgical resection, and local recurrence occurred in 23.5% of all patients after a mean disease-free period of 19.4 months. Both parameters exerted no significant influence on survival. Radiotherapy was performed in a neoadjuvant or an adjuvant setting in 50% of patients (eight neoadjuvant, nine adjuvant). Metastasis occurred after a mean of 20.4 months in 38.2% of the patients. Higher C-reactive protein levels showed a trend towards being associated with worse survival, but the association was not significant (p=0.084); haemoglobin level had no influence on the survival rate (p=0.426). Tumour grade and metastasis were significant prognostic factors of survival (log-rank test p=0.041 and p=0.00007). Ten patients (29.4%) died due to MFS during our follow-up period., Conclusion: The tumour grade and metastasis of MFS are independently associated with disease-specific survival, whereas negative surgical margins, local recurrence and blood levels of C-reactive protein and haemoglobin were not significant prognostic factors. The understanding of the molecular biological patterns that result in the metastasis of these tumours will help develop better treatment plans in the future., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To examine pediatric head and neck fibrosarcoma cases and review the demographics, management, and survival for these patients., Methods: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of a head and neck fibrosarcoma using ICD-O-3 head and neck primary sites and histology codes. Patients were included from birth-18 years of age. Additionally, a pediatric case of a head and neck infantile fibrosarcoma treated at the Nemours Children's hospital in Orlando, Florida is presented., Results: One hundred-thirteen pediatric head and neck fibrosarcomas were identified within the SEER database over the study period. The mean age at diagnosis was 9.8 years (SD: 6.2, range: 0.0-18.0). The mean age at diagnosis for infantile fibrosarcomas was 1.7 years (SD: 3.2, range: 0.0-12.0). Fifty-one (45.1%) patients were female. A majority (N = 67, 59.3%) of patients had dermatofibrosarcoma followed by 18 (15.9%) who had infantile fibrosarcomas. Nearly all patients (N = 107, 94.7%) received surgical intervention. 27.8% of patients with an infantile fibrosarcoma received chemotherapy as a part of their care compared to 1.5% of patients with a dermatofibrosaroma (p = .004). The 5-year disease-specific survival was 97%., Conclusions: Pediatric patients with head and neck fibrosarcomas are most likely to present in Caucasian males or females during late childhood or early adolescence. Infantile fibrosarcomas present in pediatric patients at a much earlier age. Surgical management is common for pediatric head and neck fibrosarcomas. Additionally, chemotherapy may be used for infantile fibrosarcomas of the head and neck. Survival rates for pediatric patients with a head and neck fibrosarcoma are excellent., (Copyright © 2018. Published by Elsevier B.V.)

Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is mediated by the cytosolic antibody receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is sufficient to restore transgene expression to near-naïve immune levels. TRIM21 is also responsible for blocking cytotoxic T cell induction by vaccine vectors, preventing a protective response against subsequent influenza infection and an engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an augmented immune response upon i.v. administration of the vector. Transcriptomic analysis of vector-transduced tissue reveals that TRIM21 is responsible for the specific up-regulation of hundreds of immune genes, the majority of which are components of the intrinsic or innate response. Together, these data define a major mechanism underlying the preimmune block to adenovirus gene therapy and demonstrate that TRIM21 efficiently blocks gene delivery in vivo while simultaneously inducing a rapid program of immune transcription., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Objectives: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR., Materials and Methods: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%), >5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR., Results: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049)., Conclusions: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c + MHCII lo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c + MHCII hi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue sarcoma which was initially observed in acral sites and characterised by spindle cells, pleomorphic bizarre cells and distinctive large Reed-Sternberg-like cells admixed with an intense inflammatory cell infiltrates. MIFS manifests as a slow growing often superficial lesion which can be mistaken as infectious or chronic inflammatory process or benign tumours such as nodular fasciitis, giant cell tumour of tendon sheath or synovial pseudocyst. We report a rare presentation of a MIFS in a 38-year-old man with extensive local spread from subcutaneous tissue to the ankle joint and bones as well as multiple synchronous metastases to lung, sixth rib and vertebra. Our case is peculiar for its aggressive clinical behaviour with short duration, fast growth and extensive metastases, a feature infrequent in MIFS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a child who developed a TFE3/Xp11.2 translocation renal cell carcinoma (RCC) when he was 3 years and 3 months old, after previous treatment for infantile fibrosarcoma (IFS). When he was 3 months old, a left axilla mass has been detected, which was tan and solid, was 1.5 cm in greatest dimension, and composed of sheets of spindle cells that was positive for vimentin and fibronectin. Fluorescence in situ hybridization showed positive result in ETV6 gene rearrangements. The final diagnosis was IFS. After surgery and chemotherapy, he remained disease-free until 3 years; later, he was detected to have a tumor in right kidney which measured 2.5 × 2 × 1.5 cm. The tumor comprised clear-cell features that were arranged in papillary and adenoid architecture. The tumor cells were positive for TFE3 and CK. The diagnosis was TFE3/Xp11.2 translocation RCC. Previous research has reported that the radio/chemotherapy for the first tumor might be involved in the pathogenesis of translocation RCC. In our report, this is the first time the IFS is included in the disease spectrum which can cause secondary translocation RCC.

The tumor microenvironment, essentially hypoxic, is sustained by the hypoxia inducing factor (HIF), released from the pro-tumorigenic tumor associated macrophages (TAMs), functionally identical to the M2 phenotype macrophages. Stability of HIF mainly depends on molecular oxygen and an iron-dependent enzyme prolyl hydroxylase, while its activity may be inhibited by high levels of reactive oxygen species and nitric oxide. The present work showcases a novel approach utilizing the anti-tumorigenic potential of a gold-manganese oxide nanocomposite material in the tumor microenvironment that affects tumor hypoxia, exploring the possibility of restoring the immunoregulatory nature of TAMs from their pro-tumorigenic state. Along with the biochemical markers, ELISA and FACS analyses have also confirmed the potential of these nanoparticles in reverting back the M2 phenotype of TAMs to their classically activated M1 phenotype., (Copyright © 2018. Published by Elsevier B.V.)

Background: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors., Procedure: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells. Real-time PCR was applied to evaluate tumor expression of chemokines/cytokines and tumor antigens., Results: Significant infiltration of both CD4 + and CD8 + T cells was found in seven of 10 IFS but rarely found in age- and sex-matched rhabdomyosarcoma tumors. The TILs from recurrent IFS tumors expressed high levels of costimulatory molecules such as CD28, 4-1BB, and OX40, but little or no coinhibitory molecules such as PD-1 and CTLA4, Tim3, Lag3, and CD39. Upon activation, large portions of TILs produced IFN-γ and TNF-α. Eighteen out of 40 T cell lines generated from surgically removed tumors could recognize autologous tumor cells. Moreover, we found that IFS tumors expressed high levels of T-cell chemokines such as CXCL10 and CXCL16, and also classic tumor antigens such as CTAG2, GAGE, and NY-ESO-1, whose expression could be further enhanced by treatment with epigenetic modulator decitabine., Conclusions: IFS tumors are highly immunogenic and expansion of TILs followed by adoptive cell transfer could be a potential immunotherapy for IFS patients undergoing tumor recurrence., (© 2017 Wiley Periodicals, Inc.)

An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.

Undifferentiated pleomorphic sarcomas, myxofibrosarcomas, and malignant peripheral nerve sheath tumors are characterized by complex genomic characteristics and aggressive clinical behavior. Recent advances in the understanding of the pathogenesis of these tumors may allow for the development of more-effective innovative therapeutic strategies, including immunotherapies. This review describes the current knowledge of the epidemiology, clinical presentation, treatment, and pathogenesis of these tumors and highlights ongoing and future research.

Rationale: Low-grade fibromyxoid sarcoma (LGFMS) is a pathological type of fibrosing fibrosarcoma that appears as a distinctive soft tissue masse with bland histological features. It is mostly located in the deep soft tissues of the extremities. Computed tomography (CT) plays an important role in diagnosing fibrosing fibrosarcoma in the abdomen. To date, several studies in the literature have reported on CT features of LGFMS., Patient Concerns and Diagnoses: We report another case of LGFMS, which presented with certain unique CT feature. The anterolateral region and the wall of the cystic nodules showed gradual enhancement and several nourishing vessels were seen after contrast administration. These imaging features were consistent with the histologic findings of LGFMS., Interventions and Outcomes: The patient underwent tumorectomy and implantation of radioactive implants. Two years after the operation, 1 metastasis mass occur in the right psoas major., Lessons: These CT features in LGFMS may be useful to assess the histological characteristics of LGFMS to facilitate preoperative diagnosis in the clinical setting and provide the supplemental imaging knowledge for future studies., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo., (© 2017 Wiley Periodicals, Inc.)

Background: Primary ovarian fibrosarcomas are rare and usually observed in perimenopausal and postmenopausal women. To our knowledge, to date, there are only 3 reports of ovarian fibrosarcoma in childhood and adolescence in the English-language literature. In this report, we aimed to present to our knowledge, the first pediatric case with advanced stage primary ovarian fibrosarcoma and to compare with previous cases., Case: A 14-year-old teenage girl was admitted because of a giant abdominal mass. Imaging techniques revealed a giant heterogeneous and vascular ovarian mass. Salpingo-oophorectomy along with staging procedures were performed. Pathologic examination confirmed grade III ovarian fibrosarcoma with severe nuclear atypia and high mitotic count. Because of pulmonary metastasis, she received 4 courses of adjuvant combination chemotherapy (Ewing protocol). The patient withstood the treatment well and is disease-free at 2 years of follow-up., Conclusion: Fibrosarcoma of the ovary is an uncommon neoplasm with poor prognosis. To our knowledge, the presented patient is the first pediatric case with advanced staged primary ovarian fibrosarcoma to be treated with surgery and adjuvant chemotherapy., (Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Myxoinflammatory fibroblastic sarcoma is a rare soft tissue tumor with most occurring in the distal extremities of adult patients. It has a high rate of local recurrence and a low rate of metastasis. Because it may appear benign on clinical examination, and because the microscopic features are generally underrecognized, it is often inadequately treated and misdiagnosed. In this review, based upon experience and that of the literature, the intent is to highlight salient clinicopathologic features, detail the broad microscopic spectrum including high-grade aggressive variants, review the molecular features, and discuss its relation to hemosiderotic fibrolipomatous tumor.

We report two infants with infantile fibrosarcoma (IFS) complicated by severe hypercalcemia. Assessment demonstrated suppressed parathyroid hormone and 1,25-dihydroxyvitamin D levels with elevated circulating levels of parathyroid hormone related protein, indicating the diagnosis of humoral hypercalcemia of malignancy (HHM). HHM is a paraneoplastic syndrome rarely associated with pediatric malignancies. Hypercalcemia manifested clinically with neurologic symptoms and soft tissue calcium deposition and required aggressive management with intravenous fluids, diuretics, and supplemental electrolytes. Following treatment with neoadjuvant chemotherapy, serum calcium levels precipitously declined requiring calcium repletion. These cases highlight the improvement of hypercalcemia secondary to HHM following chemotherapy., (© 2017 Wiley Periodicals, Inc.)

Fibrosarcoma is a locally aggressive malignant tumor with a high recurrence rate, so that wide excisional surgery is necessary for treatment. However, it is often difficult to resect with a sufficient margin of excision at the site of tumor infiltration. Recombinant tumor vaccine therapy is a useful method to induce specific immunity. In this study, we have shown its utility as a candidate for therapy by applying a recombinant Newcastle disease virus (rNDV) tumor vaccine (rNDV-TV). Although the therapeutic effect of similar viruses has been examined in several tumors, the vaccination efficacy against fibrosarcoma has not been demonstrated until now. In this study, we showed the induction of an antitumor response by rNDV-TV against murine fibrosarcoma and investigated the role of lymphocytes in tumor elimination. Intraperitoneal inoculation of murine fibrosarcoma (WEHI164) cells showed increased lethality in C.B.17scid/scid (scid) mice within 2 weeks of inoculation. The survival rate increased to 80% when the mice were transfused with CD3 + cells from BALB/c mice previously immunized with rNDV-TV. However, all mice died from tumor growth after inoculation with non-immunized CD3 + cells. Although the survival rate was around 50% in mice receiving only immunized CD4 + and CD8 + cells, the survival rate was not decreased in mice receiving CD3 + CD4 - CD8 - (natural killer T; NKT) cells together with immunized CD4 + and CD8 + cells. This study showed rNDV-TV induced an antitumor T cell response to WEHI164 cells, and major subsets of cells involved in tumor exclusion were CD4 + and CD8 + cells, together with NKT cells.

Purpose: A clinical feature of myxofibrosarcoma is local recurrence, but knowledge about distant metastasis is sparse. We evaluated the tendency of clinical and histological features of metastasis in myxofibrosarcoma patients., Methods: Fifty-eight patients with myxofibrosarcoma were treated in our hospitals, and a total of 16 consecutive patients with distant metastases were included in this retrospective study (9 males and 7 females, with a mean age of 77 years). Because there was no patient complicated by both lung and lymph node metastases, we compared the age, sex, tumor size and location, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, American Joint Committee on Cancer (AJCC) stage, and times of the first metastasis from the initial examination between the lung and lymph node groups. In addition, we examined factors affecting the prognosis., Results: The median follow-up period was 42.9 months (range 8-142). Eleven of 16 patients developed pulmonary metastases. The sites of extra pulmonary metastases were the lymph nodes in 5 patients, bone in 1, subcutaneous in 1, intramuscular in 1, and peritoneum in 1. The median time for patients to develop distant metastases was 17.4 months (range 0-59). The time until the onset of the first metastasis in the lung metastasis group was significantly shorter than in the lymph node group (p < 0.05). Also, the survival rate in the lymph node metastasis group was better than in the lung metastasis group (p < 0.05)., Conclusions: Not only lung metastasis but also lymph node metastasis occurs frequently in myxofibrosarcoma patients. Myxofibrosarcoma with lung metastasis is more aggressive than the type with lymph node metastasis.

We herein report the case of a patient presenting with myxofibrosarcoma (MFS) who underwent treatment with surgery, proton beam therapy (PBT), and pazopanib. A 64-year-old male was diagnosed with MFS, which ranged from the posterior neck to the shoulder. Surgery was performed as an initial treatment; however, the primary tumor recurred 83 months after the initial treatment. We, therefore, administered PBT. Although most of the recurrent tumor disappeared after PBT, multiple lung metastases were identified 3 months after the completion of PBT. We initiated antiangiogenic treatment with pazopanib. Although long-term survival was achieved with the treatments, the patient suffered from a skin ulcer and soft tissue necrosis and eventually died of general prostration caused by infection, and complicated by pneumonia. Although PBT and pazopanib were effective for treating the local recurrence and lung metastases of MFS, respectively, clinicians must be cognizant of the fact that the combination of high-dose irradiation and angiogenesis inhibitors, even in nonconcurrent cases, can result in a severe skin ulcer and soft tissue necrosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

A nine-year-old male neutered Golden Retriever presented with oral fibrosarcoma. Sa-Ahm Traditional Korean acupuncture was provided along with medicinal herb treatment. Based on Sa-Ahm's theory, the constitution of this case was hypoactive Large-Intestine (LI) meridian qi. The acupuncture treatment was focused on reinforcing LI meridian qi along with reinforcing Small-Intestine and Liver meridian qi. The necrosis of the tumor started from 8 months after treatments and was completely necrotized around 1 month after initiation of tumor necrosis. Karnofsky Performance Status score was 80 to 100 % throughout the treatment except during the active stage of tumor necrosis having KPS of 50%. In this study, oral fibrosarcoma was managed well by both Sa-Ahm acupuncture and medicinal herb treatment. The result suggested that Sa-Ahm acupuncture along with herbal treatment could be a potential medical option for canine oral FSA therapy., (Copyright © 2017. Published by Elsevier B.V.)

Introduction: Cytokine gene therapy is one of the cancer treatment strategies. Recently, granulocyte-monocyte colony-stimulating factor (GM-CSF), as an important cytokine in activating dendritic cells and boosting the anti-tumor immune responses, has been utilized as an immunotherapeutic agent in cancer gene therapy. The purpose of the present investigation was to study the GM-CSF gene therapy effects in regression of tumor masses in fibrosarcoma mouse model., Materials and Methods: To investigate the therapeutic efficacy of GM-CSF, WEHI-164 tumor cells were transfected with murine GM-CSF plasmid. For cytokine production by transfected cells, enzyme-linked immunosorbent assay test was used. Fibrosarcoma mouse model established with transfected cells which were injected subcutaneously into Balb/c mice. Tumor sizes were measured by caliper. Mice were sacrificed and the tumors were extracted. The expression of GM-CSF was studied by real-time polymerase chain reaction (PCR) and immunoblotting. The expression of Ki-67 (a tumor proliferative marker) in tumor masses was studied by immunohistochemical staining., Results: The group treated with GM-CSF indicated a decrease in tumor mass volume (P = 0.001). The results of western blotting and real-time PCR showed that GM-CSF expression increased in the group treated with GM-CSF (with a relative expression of 1.36). Immunohistochemical staining showed that Ki-67 expression has reduced in the group treated with GM-CSF., Conclusion: Monotherapy with GM-CSF has therapeutic effects on the regression of tumor masses in the fibrosarcoma mouse model.