scholarly journals Histone H3K4me3 and H3K9me3 are super over-methylated in soft tissue sarcoma compared to normal muscle in patient-derived xenograft (PDX) mouse models: an indicator of cancer methionine addiction

2021 ◽  
Author(s):  
Yusuke Aoki ◽  
Jun Yamamoto ◽  
Yasunori Tome ◽  
Kazuyuki Hamada ◽  
Sachiko Inubushi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cancer Cells ◽  
Mouse Models ◽  
Present Report ◽  
Histone H3 ◽  
Soft Tissue Sarcomas ◽  
Normal Muscle ◽  
Pleomorphic Sarcoma ◽  
Patient Derived Xenograft ◽  
Adenosyl Methionine

AbstractMethionine addiction is a fundamental and general hallmark of cancer discovered by us almost a half-century ago [Proc Natl Acad Sci U S A 73 (1976) 1523-1527]. Methionine addiction is defined as the requirement, specific for cancer cells of all types, for exogenous methionine despite the normal ability to synthesize methionine from homocysteine. The methionine addiction of cancer is termed the Hoffman-effect, analogous to the Warburg-effect of the high glucose requirement of cancer cells. Methionine addiction is due to excess transmethylation reactions resulting in high methionine flux in cancer cells, which causes them to selectively arrest under methionine restriction due to depletion of free methionine and S-adenosyl methionine. Recently we have shown methionine-addicted cancer cells over-methylate histone H3 lysine marks which are not over-methylated in normal cells or in low-malignancy methionine-independent revertants derived from methionine-addicted cancer cells. In the present report, we show that in patient-derived xenograft (PDX) mouse models of the most common soft tissue sarcomas: myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS) and liposarcoma, histone H3K4me3 and H3K9me3 are super over-methylated compared to normal muscle tissue. This new result is discussed along with our previous reports, regarding the potential of histone H3 over-methylation as a basis of malignancy.

scholarly journals Clinicopathological study of soft tissue sarcoma-retrospective study of tertiary cancer institute in eastern India

2020 ◽  
Vol 8 (11) ◽  
pp. 4075
Author(s):  
Kunhi Mohammed K. P. ◽  
Snehasis Pradhan ◽  
Supratim Bhattacharyya ◽  
Prafulla Kumar Das ◽  
Muhammed Navas N. K.
Keyword(s):  
Retrospective Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
The Body ◽  
Female Ratio ◽  
Pleomorphic Sarcoma ◽  
Frequent Variety ◽  
Male To Female

Background: Soft tissue sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise less than 1 percent of all adult malignancies. Although they occur anywhere in the body, they involve most commonly in extremities, trunk, retroperitoneum and head and neck. The aim of the study was to analyze clinical and histopathological features of various soft tissue sarcomas.Methods: This was a retrospective study, conducted in tertiary cancer centre in Odisha during the period 2015 to 2018. We collected clinical parameters like age, sex, site of swelling, any associated pain and biopsy reports and these variables were correlated with final histopathology reports.Results: A total of 107 patients were included in the study, with male to female ratio of 2:1(71 and 36) and average age of 43.45 years. All of them presented with a swelling. The lower extremities were the most common sites i.e. 44.62%. Pleomorphic sarcoma was the most frequent histologic variety comprising 43% and less frequent variety were angiosarcoma, and myxoid sarcoma.Conclusions: Soft tissue sarcoma are predominant in males and middle aged population are frequently affected. Most common affected site is lower extremity and pleomorphic sarcoma is the prominent histologic type.

scholarly journals LRRC15 Targeting in Soft-Tissue Sarcomas: Biological and Clinical Implications

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 757 ◽  
Author(s):  
Eytan Ben-Ami ◽  
Raul Perret ◽  
Ying Huang ◽  
Félicie Courgeon ◽  
Prafulla C. Gokhale ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Stromal Cells ◽  
Soft Tissue Sarcomas ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
In Vivo Experiments ◽  
Patient Derived Xenograft ◽  
Pdx Models ◽  
Antibody Drug

Background: LRRC15 is a member of the LRR (leucine-rich repeat) superfamily present on tumor-associated fibroblasts (CAFs) and stromal cells. The expression of LRRC15 is upregulated by the pro-inflammatory cytokine TGFβ. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) designed to target LRRC15, and which has shown significant anti-tumor activity in several tumor models. This is the first focused examination of LRRC15 expression and ABBV-085 activity in soft-tissue sarcomas (STS). Methods: We analyzed the LRRC15 expression profile by immunohistochemistry in 711 STS cases, covering a broad spectrum of STS histologies and sub-classifications. In vivo experiments were carried out by using LRRC15-positive and LRRC15-negative patient-derived xenograft (PDX) models of STS. Results: In contrast to patterns observed in epithelial tumors, LRRC15 was expressed not only by stromal cells but also by cancer cells in multiple subsets of STS with significant variations noted between histological subtypes. Overexpression of LRRC15 is positively correlated with grade and independently associated with adverse outcome. ABBV-085 has robust preclinical efficacy against LRRC15 positive STS patient-derived xenograft (PDX) models. Conclusion: We provide the first preclinical evidence that LRRC15 targeting with an antibody-drug conjugate is a promising strategy in LRRC15-positive STS. ABBV-085 is being evaluated in an ongoing clinical trial in STS and other malignancies.

scholarly journals Dedifferentiated Liposarcoma of the Esophagus: A Case Report and Selected Review of the Literature

Rare Tumors ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 201-202 ◽  
Author(s):  
Christopher L. Brett ◽  
Daniel H. Miller ◽  
Liuyan Jiang ◽  
Herbert C. Wolfsen ◽  
Steven Attia ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Case Report ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Radical Resection ◽  
Dedifferentiated Liposarcoma ◽  
Review Of The Literature ◽  
Pleomorphic Sarcoma ◽  
Disease Free

Soft tissue sarcomas of the esophagus represent an extremely rare cause of esophageal masses, and an even smaller proportion of these tumors represent dedifferentiated liposarcomas. We present a case of a 75-year-old gentleman presenting with dysphagia found to have a 5 cm pedunculated mass in the cervical esophagus, originating at the cricopharyngeus. This was found to have involvement limited to the superficial mucosa by endoscopic ultrasound, and the lesion was subsequently resected endoscopically. Pathology demonstrated an undifferentiated pleomorphic sarcoma later determined to represent dedifferentiated liposarcoma after fluorescence in situ hybridization analysis. The patient received no additional adjuvant therapy and remains disease free 20 months from the procedure. While treatment experience is limited, our case demonstrates that in selected patients, sustained local control can be obtained without radical resection.

scholarly journals Epirubicin is not Superior to Doxorubicin in the Treatment of Advanced Soft Tissue Sarcomas. The Experience of the EORTC Soft Tissue and Bone Sarcoma Group

Sarcoma ◽  
2000 ◽  
Vol 4 (1-2) ◽  
pp. 31-35 ◽  
Author(s):  
Ole S. Nielsen ◽  
Per Dombernowsky ◽  
Henning Mouridsen ◽  
Søren Daugaard ◽  
Martine Van Glabbeke ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Bolus Injection ◽  
Response Rate ◽  
Standard Dose ◽  
Present Report ◽  
Tumour Response ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Antineoplastic Effect ◽  
Duration Of Response

Purpose.Doxorubicin (dox) still appears to be one of the most active drugs in the treatment of soft tissue sarcomas. However, treatment duration is limited due to cumulative cardiotoxicity. A number of small studies from single institutions have suggested activity of other analogues. In two studies the EORTC STBSG tested whether epirubicin (epi) is an alternative to standard dose dox in the treatment of chemonaive patients with advanced soft tissue sarcoma. The present report gives the final results of these studies.Patients/Methods.In the first study 210 patients were randomized to receive either dox or epi both at a dose of 75 mg/m2given as bolus injection at 3-week intervals. In the second study 334 patients were randomized to dox 75 mg/m2, epi 150 mg/m2or epi 50 mg/m2days 1–3, all given as bolus injection at 3-week intervals.Results.In the first study no differences in median survival and duration of response were found. Of 167 evaluable patients the response rate was slightly in favour of dox (23% vs 18%) but at the expense of more toxicity.These data could suggest that increasing the epi dose may lead to a greater antineoplastic effect with acceptable toxicity. In the second study 15% of 314 evaluable patients had an objective tumour response. There were no differences between the three groups with regard to response rate, progression-free and overall survival, but both dose schedules of epi were more myelotoxic than dox.Conclusion.Regardless of schedule and dose, epi is not superior to dox in the treatment of patients with advanced soft tissue sarcomas. In addition, the results illustrate that the data from small studies of single institutions should always be confirmed by large multi-institutional studies before being taken for granted.

scholarly journals Undifferentiated Pleomorphic Sarcoma of Pancreas: A Case Report and Review of the Literature for the Last Updates

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Behnam Sanei ◽  
Amirhosein Kefayat ◽  
Melika Samadi ◽  
Parvin Goli ◽  
Mohammad Hossein Sanei ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Poor Prognosis ◽  
Digestive System ◽  
Fibrous Histiocytoma ◽  
Soft Tissue Sarcomas ◽  
Pancreatic Tumors ◽  
Review Of The Literature ◽  
Undifferentiated Pleomorphic Sarcoma ◽  
Pancreas Head ◽  
Pleomorphic Sarcoma

The most prevalent type of soft tissue sarcoma is undifferentiated pleomorphic sarcoma (UPS) or previously known as malignant fibrous histiocytoma. It accounts over 20% of all soft tissue sarcomas and occurs most frequently in the extremities, trunk, and retroperitoneum. However, it has been rarely observed in the digestive system. Pancreas sarcoma represents less than 1% of all pancreatic tumors, and primary UPS of the pancreas is even rarer. It exhibits high recurrence and poor prognosis. In this case, a 72-year-old woman with a UPS tumor which was located in the pancreas head and neck without adhesion to the retroperitoneum will be discussed.

scholarly journals Post-traumatic myositis ossificans: a benign lesion that simulates malignant bone and soft tissue tumours

2021 ◽  
Vol 6 (7) ◽  
pp. 572-583
Author(s):  
Olga Savvidou ◽  
Olympia Papakonstantinou ◽  
Eleftheria Lakiotaki ◽  
Dimitra Melissaridou ◽  
Pinelopi Korkolopoulou ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Myositis Ossificans ◽  
Traumatic Event ◽  
Benign Lesion ◽  
Soft Tissue Sarcomas ◽  
Sports Injury ◽  
Bone Lesions ◽  
Pleomorphic Sarcoma ◽  
Detailed Medical History ◽  
Post Traumatic

Myositis ossificans (MO) is a benign bone formation in an extra-skeletal location. The most common subtype of MO, the post-traumatic, usually develops in young males after a traumatic event or sports injury. MO may simulate malignant bone lesions such as extra-skeletal or surface osteosarcomas, or soft tissue sarcomas such as synovial sarcoma or undifferentiated pleomorphic sarcoma. In the early phase the diagnosis of MO is challenging because imaging and histopathological findings may be non-characteristic. Detailed medical history as well as clinical examination, follow-up imaging studies and histological assessment are crucial for a proper diagnosis. Early and accurate differential diagnosis between MO and malignant soft tissue and bone tumours is important to maximize. Cite this article: EFORT Open Rev 2021;6:572-583. DOI: 10.1302/2058-5241.6.210002

scholarly journals Prospective Evaluation of the Concordance of Commercial Circulating Tumor DNA Alterations with Tumor-Based Sequencing across Multiple Soft Tissue Sarcoma Subtypes

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1829 ◽  
Author(s):  
Bryce Demoret ◽  
Jeff Gregg ◽  
David A. Liebner ◽  
Gabriel Tinoco ◽  
Scott Lenobel ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Solid Tumor ◽  
Soft Tissue Sarcomas ◽  
Circulating Tumor Dna ◽  
Overlapping Genes ◽  
Copy Number Alterations ◽  
Pleomorphic Sarcoma ◽  
Comprehensive Genomic Profiling ◽  
Dna Alterations ◽  
Tumor Dna

Soft tissue sarcomas (STS) are diverse tumors with heterogenous alterations. Platforms to detect circulating tumor DNA (ctDNA) have rapidly increased in popularity as they may avoid invasive biopsy morbidity. However, ctDNA profiling concordance with standard solid tumor comprehensive genomic profiling (CGP) is poorly characterized. Here, we report the outcomes of a single-institution experience comparing mutational results from commercial ctDNA and solid tumor CGP in advanced STS subjects. We identified STS subjects who had undergone solid tumor based CGP in four distinct cohorts: Dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), and gastrointestinal stromal tumor (GIST). Subjects with radiographically measurable tumor were profiled using a commercial ctDNA CGP panel. Overlapping genes/exons on both biopsy panels were analyzed. Twenty-four subjects completed both ctDNA and solid tumor CGP. ctDNA was detected in 18/24 subjects. Subject level concordance rates in all overlapping genes were: LMS = 4/6; UPS = 2/6; DDLPS = 1/6; GIST = 0/6. Copy number alterations were notably poorly concordant. For subjects with short variant alterations and detectable tumor fractions, concordance with solid tumor CGP was 76% (13/17). LMS subjects had the highest median tumor fraction and concordance. No correlation was seen between tumor fraction or radiographic tumor volume largely driven by low estimated tumor fraction. A limitation of the study is that only targeted sequencing was performed. However, given the poor concordance in commonly altered genes, ctDNA panels in sarcoma cannot be broadly applied. Further, more extensive studies will need to be performed.

scholarly journals Giant Soft Tissue Sarcoma of Scalp with Skull and Cerebral Invasion

2021 ◽  
Vol 23 (4) ◽  
pp. 357-359
Author(s):  
Raghav Yelamanchi ◽  
Parikshith Manjunath ◽  
Nikhil Gupta ◽  
CK Durga
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Brain Parenchyma ◽  
Clinical Image ◽  
Tissue Mass ◽  
Surgical Department ◽  
Pleomorphic Sarcoma ◽  
Multimodality Approach

Scalp soft tissue sarcomas (STS) are very rare accounting for less than 0.1% of all malignancies. We report a rare clinical image of advanced stage soft tissue sarcoma of the scalp. A 65 year woman had presented to the surgical department with complaints of a rapidly growing swelling over the scalp for three months. On examination there was huge 20 x 20 cm swelling over the scalp in the left temporoparietal region with variegated consistency. Computed tomography of head revealed a large soft tissue mass with necrosis invading the bone and underlying brain parenchyma. Histopathological finding from core needle biopsy revealed pleomorphic sarcoma. STS are highly malignant tumors which should be diagnosed and treated using multimodality approach. Recurrences are common even after complete resection and prognosis is poor.

scholarly journals A unique case of classic pleomorphic sarcoma restricted to the toes

2021 ◽  
Vol 8 (8) ◽  
pp. 2488
Author(s):  
Abdul Rehman Siddiqui ◽  
Suha Mohammed Akbar
Keyword(s):  
Soft Tissue ◽  
Lower Extremity ◽  
Soft Tissue Sarcomas ◽  
Malignant Neoplasms ◽  
Nerve Sheath Tumor ◽  
High Grade ◽  
Spindle Cell Neoplasm ◽  
Pleomorphic Sarcoma ◽  
Wide Range ◽  
Specific Line

Over 50% of soft tissue sarcomas occurring in older adults are histologically pleomorphic and high grade. Most have traditionally been classified as malignant fibrous histiocytoma (MFH). MFH was originally defined as a malignant pleomorphic spindle cell neoplasm showing fibroblastic and histiocytic differentiation. More recently, pathologists have accepted that this morphology may be shared by a wide range of malignant neoplasms. Many sarcomas that were previously classified as pleomorphic MFH, on careful immunohistochemical and histopathologic analyses, revealed a specific line of differentiation and could be reclassified as myxofibrosarcoma (30%), myogenic sarcoma (30%), liposarcoma (4%), malignant peripheral nerve sheath tumor (2%), or soft tissue osteosarcoma (3%), whereas about 30% had no specific line of differentiation or were myofibroblastic. The term undifferentiated pleomorphic sarcoma (UPS) is now reserved for pleomorphic sarcomas that show no definable line of differentiation by current technology. The majority of extremity sarcomas occur in the lower extremity (74 vs. 26% in the upper limb). According to one of the studies conducted on 315 patients, non-metastatic soft tissue sarcoma of the lower extremity who were treated at one institution over a ten-year period. Sixty-six percent of the lesions were above the knee, and 60% were high grade. This case had a 3x3 cm ulcer at the 3rd toe in a 30-year-old male patient who subsequently underwent midfoot ampuatation.

Real-world data of a cohort of patients with soft tissue sarcoma in a single institution of Colombia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19259-e19259
Author(s):  
Luis Eduardo Pino ◽  
Ivan Camilo Triana ◽  
Aylen Vanessa Ospina Serrano ◽  
Javier Segovia ◽  
Diana Carolina Hennessey
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Real World ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Soft Tissue Sarcomas ◽  
Stage Iv ◽  
University Hospital ◽  
Single Institution ◽  
Pleomorphic Sarcoma

e19259 Background: Soft Tissue Sarcomas (STS) are a group of neoplasm with huge histological diversity and biological behaviors. They have a low prevalence and lack of data, especially in Colombia where there is no specific report of this disease. The objective of this study is to describe clinical characteristics and outcomes of patients with soft tissue sarcoma at Fundación Santafe, a university hospital located in Bogotá. Methods: This is an observational study of a cohort of soft tissue sarcoma patients treated at a single institution with a follow-up of 4 years (2015 - 2019). Clinical, molecular and epidemiological variables were registered, and overall survival was calculated for stage IV sarcomas. For the survival analysis a Kaplan Meier model was used. Results: Twenty-four patients were included. The histologies reported were: Pleomorphic sarcoma 25.0%, Ewing's sarcoma 20.8%, liposarcoma 16.7%, chondrosarcoma 8.3%, leiomiosarcoma 8.3%, synovial sarcoma 8.3%, soft part alveolar sarcoma 8.3%, and dermatofibrosarcoma protuberans 4.3%. OSm for the whole stage IV group was: 30.22m, according to subtypes OSm was: Ewing's sarcoma 37.13 OSm, liposarcoma 11 OSm, chondrosarcoma 12.3 OSm. Only 3 of the cases (2 Ewing's sarcoma and 1 alveolar sarcoma) had multigenic platform information. In these cases, main mutations in BCL2, SOX9, SATB2 and TFE3 were described. In two of the cases PDL1 expression was done with a negative result ( < 1%) (pleomorphic sarcoma and Ewing's sarcoma). Ifosfamide and anthracyclines was the most frequent chemotherapy regimen used, but in two of the cases checkpoint inhibitors were initiated. Conclusions: This real-world cohort of STS have a similar clinical and epidemiological distribution to historic cohorts, but our OSm for Ewing's sarcoma stage IV is longer than reported, even with a case of complete remission after consolidation with autologous bone marrow transplant. Other histologies had a worse prognosis with a less than 12 m OSm. Genomic data were scarce and useless for directed therapies or immunotherapy as usual in STS. [Table: see text]

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