scholarly journals Safety of an Oncolytic Myxoma Virus in Dogs with Soft Tissue Sarcoma

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 398 ◽  
Author(s):  
Amy MacNeill ◽  
Kristen Weishaar ◽  
Bernard Séguin ◽  
Barbara Powers
Keyword(s):  
Soft Tissue ◽  
Human Cancer ◽  
Treatment Options ◽  
Safety Information ◽  
Soft Tissue Sarcomas ◽  
Myxoma Virus ◽  
Oncolytic Viruses ◽  
Multiple Time ◽  
Viral Dna ◽  
Multiple Time Points

Many oncolytic viruses that are efficacious in murine cancer models are ineffective in humans. The outcomes of oncolytic virus treatment in dogs with spontaneous tumors may better predict human cancer response and improve treatment options for dogs with cancer. The objectives of this study were to evaluate the safety of treatment with myxoma virus lacking the serp2 gene (MYXVΔserp2) and determine its immunogenicity in dogs. To achieve these objectives, dogs with spontaneous soft tissue sarcomas were treated with MYXVΔserp2 intratumorally (n = 5) or post-operatively (n = 5). In dogs treated intratumorally, clinical scores were recorded and tumor biopsies and swabs (from the mouth and virus injection site) were analyzed for viral DNA at multiple time-points. In all dogs, blood, urine, and feces were frequently collected to evaluate organ function, virus distribution, and immune response. No detrimental effects of MYXVΔserp2 treatment were observed in any canine cancer patients. No clinically significant changes in complete blood profiles, serum chemistry analyses, or urinalyses were measured. Viral DNA was isolated from one tumor swab, but viral dissemination was not observed. Anti-MYXV antibodies were occasionally detected. These findings provide needed safety information to advance clinical trials using MYXVΔserp2 to treat patients with cancer.

scholarly journals Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a “Trojan Horse” in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 750
Author(s):  
Ivan Petrov ◽  
Ivaylo Gentschev ◽  
Anna Vyalkova ◽  
Mohamed I. Elashry ◽  
Michele C. Klymiuk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Soft Tissue ◽  
Vaccinia Virus ◽  
Soft Tissue Sarcomas ◽  
Trojan Horse ◽  
Myxoma Virus ◽  
Oncolytic Viruses ◽  
Host Immune System ◽  
Oncolytic Therapy

Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a “Trojan horse” for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.

scholarly journals Improving Immunotherapy Efficacy in Soft-Tissue Sarcomas: A Biomarker Driven and Histotype Tailored Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthieu Roulleaux Dugage ◽  
Elise F. Nassif ◽  
Antoine Italiano ◽  
Rastislav Bahleda
Keyword(s):  
Soft Tissue ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Soft Tissue Sarcomas ◽  
Oncolytic Viruses ◽  
Cellular Therapies ◽  
M1 Macrophage ◽  
Synovial Sarcomas

Anti-PD-(L)1 therapies yield a disappointing response rate of 15% across soft-tissue sarcomas, even if some subtypes benefit more than others. The proportions of TAMs and TILs in their tumor microenvironment are variable, and this heterogeneity correlates to histotype. Tumors with a richer CD8+ T cell, M1 macrophage, and CD20+ cells infiltrate have a better prognosis than those infiltrated by M0/M2 macrophages and a high immune checkpoint protein expression. PD-L1 and CD8+ infiltrate seem correlated to response to immune checkpoint inhibitors (ICI), but tertiary lymphoid structures have the best predictive value and have been validated prospectively. Trials for combination therapies are ongoing and focus on the association of ICI with chemotherapy, achieving encouraging results especially with pembrolizumab and doxorubicin at an early stage, or ICI with antiangiogenics. A synergy with oncolytic viruses is seen and intratumoral talimogene laherpavec yields an impressive 35% ORR when associated to pembrolizumab. Adoptive cellular therapies are also of great interest in tumors with a high expression of cancer-testis antigens (CTA), such as synovial sarcomas or myxoid round cell liposarcomas with an ORR ranging from 20 to 50%. It seems crucial to adapt the design of clinical trials to histology. Leiomyosarcomas are characterized by complex genomics but are poorly infiltrated by immune cells and do not benefit from ICI. They should be tested with PIK3CA/AKT inhibition, IDO blockade, or treatments aiming at increasing antigenicity (radiotherapy, PARP inhibitors). DDLPS are more infiltrated and have higher PD-L1 expression, but responses to ICI remain variable across clinical studies. Combinations with MDM2 antagonists or CDK4/6 inhibitors may improve responses for DDLPS. UPS harbor the highest copy number alterations (CNA) and mutation rates, with a rich immune infiltrate containing TLS. They have a promising 15-40% ORR to ICI. Trials for ICB should focus on immune-high UPS. Association of ICI with FGFR inhibitors warrants further exploration in the immune-low group of UPS. Finally translocation-related sarcomas are heterogeneous, and although synovial sarcomas a poorly infiltrated and have a poor response rate to ICI, ASPS largely benefit from ICB monotherapy or its association with antiangiogenics agents. Targeting specific neoantigens through vaccine or adoptive cellular therapies is probably the most promising approach in synovial sarcomas.

scholarly journals Reconstruction and Financial Remuneration Following Soft Tissue Sarcoma Surgery

2013 ◽  
Vol 95 (5) ◽  
pp. 160-162 ◽  
Author(s):  
S Hassan ◽  
J Gale ◽  
AGB Perks ◽  
A Raurell ◽  
RU Ashford
Keyword(s):  
Soft Tissue ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Clinical History ◽  
The Body ◽  
Complex Nature ◽  
Triple Assessment ◽  
Diagnostic Biopsy ◽  
Long Term Follow Up ◽  
The Uk

Soft tissue sarcomas are relatively uncommon, with approximately 3,200 new cases per year in the UK, accounting for 1% of all malignancies. They are a heterogeneous group of malignancies that occur anywhere in the body, and arise from the mesenchyme inclusive of muscle, endothelial cells, cartilage and supporting elements. Diagnosis is based on triple assessment with clinical history, imaging and diagnostic biopsy. Histological stage and grade is based on the Trojani classification. Owing to their complex nature, a specialist sarcoma multidisciplinary team (MDT) manages patients. Treatment options include one or more of surgery with wide or planned marginal excision, isolated limb perfusion, chemotherapy or radiotherapy. Long-term follow-up to rule out recurrence of disease is mandatory.

scholarly journals Study of soft tissue sarcomas over a period of 3 years

2017 ◽  
Vol 5 (6) ◽  
pp. 2678 ◽  
Author(s):  
Jenna Prabhakar ◽  
J. Sushma ◽  
B. V. S. Kartheek ◽  
A. Bhagya Lakshmi ◽  
Chapara Vaibhav
Keyword(s):  
Soft Tissue ◽  
Health Education ◽  
Soft Tissue Sarcoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Mesenchymal Cell ◽  
Histological Type ◽  
Treatment Modalities ◽  
Site Distribution

Background: Soft tissue malignancies constituted a heterogeneous group of rare solid tumors of mesenchymal cell origin with distinct clinical and pathological features. The aim of the study was to know the prevalence of soft tissue sarcoma, sex, age and site distribution, histopathology and various treatment options adopted with follow up.Methods: A total of 26 cases of soft tissue sarcoma were analyzed for a three-year period. Clinical presentation, age and sex distribution, histological type and treatment modalities adopted were recorded and analyzed.Results: Out of 26 cases 44% of cases were between 30-50 years and 44% of tumors were situated in lower extremity. The commonest histological type was liposarcomas and fibrosarcoma. Lymph node metastasis was seen in 4% of cases. Distant metastasis was present in 3 cases, 2 with lung metastasis and l with lung and liver metastasis. Surgery was the main modality of the treatment. 12% of the cases presented with recurrent tumor, the duration between surgery and recurrence was 6 months. Only 38% turned for follow up, 2 patients succumbed to death because of multiple pulmonary secondaries and chest infections.Conclusion: In the present study, all the cases of soft tissue sarcoma presented in late stage of the disease due to illiteracy and lack of health education. Recurrence was seen in 12% of cases. The overall survival rates and quality of life of the patients can be improved by frequent health camps at primary health centers for early detection of the disease, providing adequate health education, diagnostic and management facilities.

scholarly journals Neoadjuvant Treatment Options in Soft Tissue Sarcomas

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2061
Author(s):  
Mateusz Jacek Spałek ◽  
Katarzyna Kozak ◽  
Anna Małgorzata Czarnecka ◽  
Ewa Bartnik ◽  
Aneta Borkowska ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Neoadjuvant Therapy ◽  
Treatment Options ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Soft Tissue Sarcomas ◽  
Therapy Response ◽  
Response Assessment ◽  
Treatment Type ◽  
Therapy Response Assessment

Due to the heterogeneity of soft tissue sarcomas (STS), the choice of the proper perioperative treatment regimen is challenging. Neoadjuvant therapy has attracted increasing attention due to several advantages, particularly in patients with locally advanced disease. The number of available neoadjuvant modalities is growing continuously. We may consider radiotherapy, chemotherapy, targeted therapy, radiosensitizers, hyperthermia, and their combinations. This review discusses possible neoadjuvant treatment options in STS with an emphasis on available evidence, indications for each treatment type, and related risks. Finally, we summarize current recommendations of the STS neoadjuvant therapy response assessment.

scholarly journals Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies

2016 ◽  
Vol 05 (01) ◽  
pp. 15-19 ◽  
Author(s):  
Jyoti Bajpai ◽  
Deepa Susan
Keyword(s):  
Adjuvant Chemotherapy ◽  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Patient Outcomes ◽  
Treatment Options ◽  
Specific Treatment ◽  
Soft Tissue Sarcomas ◽  
Metastatic Potential ◽  
Diverse Group ◽  
Histologic Subtypes

AbstractSoft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations.

scholarly journals Chemotherapy in Pediatric-Type Soft-Tissue Sarcomas

2020 ◽  
Vol 26 ◽  
Author(s):  
K. M. Ingley ◽  
S. Cohen-Gogo ◽  
A. A. Gupta
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Alternative Treatment ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Targeted Agents ◽  
Soft Tissue Tumours ◽  
Cooperative Approach ◽  
Multi Agent

Soft-tissue sarcoma (STS) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (RMS) is most prevalent in children less than 10 years of age and peaks again during adolescence (16–19 years of age). Multi-agent chemotherapy constitutes the mainstay of treatment for RMS. In other non-rhabdomyosarcoma soft-tissue tumours, such as synovial sarcoma, evidence for routine use of chemo-therapy is less robust, and alternative treatment options, including targeted agents and immunotherapy, are being explored. In this review, we focus on chemotherapy for pediatric-type RMS and discuss the advances and challenges in systemic treatment for select non-rhabdomyosarcoma soft-tissue tumours in children and adolescents. We  support an increasingly cooperative approach for treating pediatric and adult STS.

Imaging of the Knee and Surrounding Structures Following Tumor Surgery

2018 ◽  
Vol 22 (04) ◽  
pp. 481-505
Author(s):  
Naomi Winn ◽  
Radhesh Lalam
Keyword(s):  
Soft Tissue ◽  
Treatment Options ◽  
Management Strategies ◽  
Soft Tissue Sarcomas ◽  
Soft Tissue Tumors ◽  
Artifact Reduction ◽  
Soft Tissue Lesion ◽  
Metallic Implants ◽  
Primary Bone ◽  
Tumor Management

AbstractLimb salvage is a key goal of tumor management around the knee, with surgical, medical, and radiologic treatment options. Primary bone and soft tissue sarcomas are optimally treated in specialist tertiary centers; however, metastatic disease is encountered in all aspects of radiologic practice, with overlap in the management strategies. Both specialist and generalist radiologists therefore need to be familiar with the expected normal appearances following these therapies and be able to recognize potential complications. This review article describes the techniques available for imaging the knee following treatment of bone and soft tissue tumors, with particular reference to artifact reduction. The therapeutic options for managing bone and soft tissue lesion are discussed, with emphasis on imaging appearances. Surgical, medical, and radiologic treatments are described. Complications and their imaging appearances are reviewed including local recurrence of tumor, infection, complications related to metallic implants, postradiation changes, and amputation. Normal imaging appearances and complications following radiologic treatment (namely radiofrequency ablation) of bone and soft tissue tumors are presented.

scholarly journals GSK3-beta as a candidate therapeutic target in soft tissue sarcomas

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
S. Verbeke ◽  
R. Perret ◽  
V. Chaire ◽  
E. Richard ◽  
V. Velasco ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Glycogen Synthase ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Prognostic Impact ◽  
Gene And Protein Expression ◽  
Apoptosis Protein ◽  
Rare Malignancy ◽  
Gsk 3Β

AbstractSoft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.

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