Immune Factors in Human Cancer: Malignant Melanomas, Skeletal and Soft Tissue Sarcomas

2015 ◽  
pp. 25-42 ◽  
Author(s):  
D. L. Morton ◽  
F. R. Eilber ◽  
R. A. Malmgren
Keyword(s):  
Soft Tissue ◽  
Human Cancer ◽  
Soft Tissue Sarcomas ◽  
Malignant Melanomas ◽  
Immune Factors

scholarly journals Quantitative Expression of TYR, CD34, and CALD1 Discriminates Between Canine Oral Malignant Melanomas and Soft Tissue Sarcomas

2021 ◽  
Vol 8 ◽  
Author(s):  
Mayra F. Tsoi ◽  
Tuddow Thaiwong ◽  
Rebecca C. Smedley ◽  
Erica Noland ◽  
Matti Kiupel
Keyword(s):  
Soft Tissue ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Rna Expression ◽  
Quantitative Expression ◽  
Malignant Melanomas ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Junctional Activity ◽  
Microscopic Diagnosis

Canine oral malignant melanomas (OMMs) exhibit a variety of morphologic phenotypes, including a spindloid variant. The microscopic diagnosis of spindloid OMMs is based on junctional activity and/or the presence of melanin pigment. In the absence of these features, spindloid OMMs are difficult to differentiate from soft tissue sarcomas (STS). An antibody cocktail (MDX) that includes Melan-A, PNL2, and tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) is the current gold standard for identifying amelanotic OMMs by immunohistochemistry (IHC). However, MDX is less sensitive for diagnosing spindloid amelanotic OMMs. This raises concern for biopsy specimens that lack overlying epithelium, making it potentially difficult to differentiate OMM from STS by IHC. The goal of this study was to identify additional markers to help differentiate between STS and OMMs that lack pigment and junctional activity. SOX-10 has recently been proposed as a sensitive marker for melanocytes in humans but has not been validated in dogs. Similarly, RNA expression for various genes has been analyzed in humans, but not in the context of diagnosing canine melanocytic neoplasms. For this retrospective study, formalin-fixed, paraffin-embedded tissues from 20 OMMs, 20 STS, and 20 oral spindle cell tumors (OSCTs) that lacked junctional activity and pigmentation were selected. IHC for MDX, SOX-10, and laminin, in parallel with RT-qPCR of TYR, SOX10, CALD1, CD34, DES, and LAMA1, was performed in all cases. TYR, CD34, and CALD1 were the most discriminatory genes in differentiating between OMM and STS, all having 100% specificity and 65, 95, and 60% sensitivity, respectively. While all 20 OMMs were immunohistochemically labeled for SOX-10, two STS were also labeled (100% sensitivity and 90% specificity). MDX IHC labeled all 20 OMMs and no STS. Surprisingly, none of the 20 OSCTs expressed TYR RNA above the cutoff, and 14/20 OSCTs expressed CALD1 or CD34 RNA above the cutoff, thereby confirming them as STS. Four OSCT were suspect STS, and no OSCTs were confirmed as OMMs based on IHC and RNA expression patterns. In conclusion, the RNA levels of TYR, CD34, and CALD1 should be evaluated in suspected amelanotic OMMs that are negative for MDX to accurately differentiate between OMM and STS.

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.

A phase I study of a novel MDM2-P53 antagonist APG-115 in Chinese patients with advanced soft tissue sarcomas.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3124-3124 ◽  
Author(s):  
Xing Zhang ◽  
Xizhi Wen ◽  
Chen Yang ◽  
Shan Zeng ◽  
Lichuang Men ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Human Cancer ◽  
Dose Range ◽  
Soft Tissue Sarcomas ◽  
Response Assessment ◽  
Median Number ◽  
Chinese Patients ◽  
Common Grade ◽  
Grade 3 ◽  
Mdm2 Amplification

3124 Background: APG-115 is a novel and orally active small-molecule MDM2 inhibitor. APG-115 alone or in combination with chemotherapeutic, targeted or IO agents have shown potent antitumor activities in multiple human xenograft tumor models and human cancer patient derived xenograft (PDX) models. Methods: The patients with advanced solid tumors were enrolled in this study in China (CTR20170975). The study objectives were to assess safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of APG-115. The patients received APG-115 (ranging 100–200 mg) orally QOD for first 21 days of a 28-day-cycle, until disease progression. Antitumor response assessment was performed every 8 weeks per RECIST v1.1. Archived tumor tissues were collected for analyses of MDM2 and TP53 before treatment. Results: As cut-off on Jan 4 2019, total 13 patients (9 soft tissue sarcomas (STSs), 2 adenoid cystic carcinomas (ACCs) and 2 osteosarcomas) were treated in 3 cohorts of APG-115 (100mg, 150mg, 200mg). The median number of prior systemic anticancer therapies was 2 (range 0-4). Two DLTs were observed in one patient at 200mg including thrombocytopenia and febrile neutropenia. The most common TEAEs (≥50% of pts) included: anemia, thrombocytopenia, vomiting, hypercholesterolaemia, and leukopenia. SAEs occurred in 7 patients (54%), four of which were treatment related. The most common Grade 3 or 4 TRAEs were anemia (38.5%), thrombocytopenia (38.5%), leukopenia (30.8%), and neutropenia (23.1%). One partial response was observed in a liposarcoma patient with MDM2-amplification and TP53-wild type at the 150mg cohort, 5 patients (3 STSs, 2 ACCs) had SD as the best overall response. PK analyses indicated an approximately dose proportional increase in Cmax and AUC0-t following a single or multiple oral administration across dose levels. Preliminary PD data showed that serum MIC-1 increase was exposure dependent within the dose range tested. Conclusions: Preliminary data suggested that APG-115 had promising anti-tumor activity in treatment of patients with MDM2-amplification and TP53-WT liposarcoma. Safety profile and PD effect were consistent with other MDM2 inhibitors. Dosing regimen optimization are ongoing. Clinical trial information: CTR20170975.

LOCAL RECURRENCES AFTER THE TREATMENT OF SOFT TISSUE MALIGNANT FIBROUS HISTIOCYTOMA (UNCLASSIFIEDPLEOMORPHIC SARCOMA) OF THE LIMBS

2019 ◽  
Vol 72 (8) ◽  
pp. 1523-1526
Author(s):  
Oleksandr O. Lytvynenko ◽  
Volodymyr F. Konovalenko ◽  
Anton Yu. Ryzhov
Keyword(s):  
Soft Tissue ◽  
Malignant Fibrous Histiocytoma ◽  
Fibrous Histiocytoma ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Primary Treatment ◽  
Radical Excision ◽  
Local Recurrences ◽  
Results Of Treatment

Introduction: The treatment of patients with malignant fibrous histiocytoma as well as other soft tissue sarcomas is not sufficiently effective up to date, and has largely changed and reflects the alterations, occurred in oncology as a whole. The number of amputation decreased over the last 10-15 years. Some researchers associate the improvement of treatment outcomes with the development of combined and complex methods. The aim of the study is an improvement of the results of treatment of patients with soft tissue malignant histiocytoma on the basis of determination of factors, influencing local recurrence development. Materials and methods: The basis of our study was a comprehensive analysis of examination and treatment results of 130 patients with MFH of the soft tissue of limbs, of them in 84 patients (64.6%) the recurrences developed. The group included 45 (53.6%) males and 39 (46.4%) females. The major part of patients – 82.1% (60 patients) were older than 40 years. Results and conclusions: The number of recurrences after the treatment in general surgical facilities is 86.9%, whereas in the patients after the treatment in the specialized oncological facilities this figure is twice lower (40%). The characteristic of the medical facility where the patient receives his/her primary treatment largely affects the development of local recurrences, patients’ quality of life and overall survival rates. The surgical method remains the leading modality in the treatment of MFH of ST. Wide and radical excision of tumors in the specialized oncological facilities allows achieving better survival outcomes of the patients.

Myxofibrosarcoma: clinical and prognostic value of MRI features

2020 ◽  
Vol 16 ◽  
Author(s):  
Paolo Spinnato ◽  
Andrea Sambri ◽  
Tomohiro Fujiwara ◽  
Luca Ceccarelli ◽  
Roberta Clinca ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Contrast Enhancement ◽  
Imaging Modality ◽  
Soft Tissue Sarcomas ◽  
The Elderly ◽  
High Rate ◽  
Imaging Features ◽  
High Grade ◽  
Mri Features

: Myxofibrosarcoma is one of the most common soft tissue sarcomas in the elderly. It is characterized by an extremely high rate of local recurrence, higher than other soft tissue tumors, and a relatively low risk of distant metastases.Magnetic resonance imaging (MRI) is the imaging modality of choice for the assessment of myxofibrosarcoma and plays a key role in the preoperative setting of these patients.MRI features associated with high risk of local recurrence are: high myxoid matrix content (water-like appearance of the lesions), high grade of contrast enhancement, presence of an infiltrative pattern (“tail sign”). On the other hand, MRI features associated with worse sarcoma specific survival are: large size of the lesion, deep location, high grade of contrast enhancement. Recognizing the above-mentioned imaging features of myxofibrosarcoma may be helpful to stratify the risk for local recurrence and disease-specific survival. Moreover, the surgical planning should be adjusted according to the MRI features

scholarly journals Multi-institutional experience treating metastatic soft tissue sarcomas using yttrium-90 microspheres

2015 ◽  
Vol 26 (2) ◽  
pp. S133 ◽  
Author(s):  
D.L. Transue ◽  
J. Hackworth ◽  
M.S. Johnson ◽  
A. Habib ◽  
R.J. Lewandowski ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Institutional Experience ◽  
Yttrium 90
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