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Cancers
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Bone and Soft Tissue Sarcoma
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Bone and Soft Tissue Sarcoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (10 December 2020) | Viewed by 22663

Special Issue Editor

Dr. Antonio Ruggiero

E-Mail Website
Guest Editor
Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy
Interests: clinical pharmacology; antineoplastic drugs; clinical trial; pediatric drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sarcomas are relatively rare both in children and adults. Sarcomas are a heterogeneous category of tumors and can arise in any body district. Bone and soft tissue sarcomas are the main types of sarcoma.

Over the last few decades, there have been remarkable advances in the multimodal treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins and radiotherapy, and the development of post-surgical bone and tissue reconstruction. Nevertheless, these cancers present challenges in new drug development partly because of their relative rarity and heterogeneity. However, based on recently obtained molecular data, several clinical trials are ongoing with new immunotherapeutic drugs and molecular targeted therapies.

In this Special Issue, experts in this field will review the current status of, and new approaches to, the interdisciplinary management of patients with bone and soft tissue sarcomas.


Prof. Dr. Antonio Ruggiero
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 186 KiB  
Editorial
Bone and Soft Tissue Sarcoma
by Antonio Ruggiero
Cancers 2020, 12(9), 2609; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092609 - 12 Sep 2020
Cited by 4 | Viewed by 1514
Abstract
Bone and soft-tissue sarcomas are relatively rare tumors both in children and adults [...] Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)

Research

Jump to: Editorial, Review

20 pages, 3785 KiB  
Article
Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile
by Jean Camille Mattei, Corinne Bouvier-Labit, Doriane Barets, Nicolas Macagno, Mathieu Chocry, Frédéric Chibon, Philippe Morando, Richard Alexandre Rochwerger, Florence Duffaud, Sylviane Olschwang, Sébastien Salas and Carine Jiguet-Jiglaire
Cancers 2020, 12(3), 583; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030583 - 03 Mar 2020
Cited by 9 | Viewed by 3040
Abstract
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of [...] Read more.
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60–70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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13 pages, 571 KiB  
Article
The Impact of Surgical Margins and Adjuvant Radiotherapy in Patients with Undifferentiated Pleomorphic Sarcomas of the Extremities: A Single-Institutional Analysis of 192 Patients
by Ole Goertz, Andreas Pieper, Leon von der Lohe, Ingo Stricker, Mehran Dadras, Björn Behr, Marcus Lehnhardt and Kamran Harati
Cancers 2020, 12(2), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12020362 - 05 Feb 2020
Cited by 15 | Viewed by 2622
Abstract
Background: Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. Methods: We retrospectively [...] Read more.
Background: Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. Methods: We retrospectively determined the relationship between local recurrence-free survival (LRFS), overall survival (OS), and potential prognostic factors in 192 patients with UPS of the extremities who were suitable for surgical treatment in curative intent. The median follow-up time was 5.1 years. Results: The rates of LRFS and OS after 2 years were 75.7% and 87.2% in patients with R0-resected primary tumors and 49.1% and 81.8% in patients with R1/R2-status (LRFS: p = 0.013; OS: p = 0.001). Adjuvant radiotherapy significantly improved LRFS (5-year: 67.6% vs. 48.4%; p < 0.001) and OS (5-year: 82.8 vs. 61.8; p = 0.016). Both, negative margins and adjuvant radiotherapy were found to be independent prognostic factors in multivariate analysis. Conclusions: The data from this study could underscore the beneficial prognostic impact of negative margins on LRFS and OS. However, the width of negative margins seemed to be not relevant. Notably, adjuvant radiotherapy was not only able to decrease the risk of local failure but also improved OS in a significant manner. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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17 pages, 3137 KiB  
Article
EP4 and Class III β-Tubulin Expression in Uterine Smooth Muscle Tumors: Implications for Prognosis and Treatment
by Jocelyn Reader, Amy K. Harper, Teklu Legesse, Paul N. Staats, Olga Goloubeva, Gautam G. Rao, Amy Fulton and Dana M. Roque
Cancers 2019, 11(10), 1590; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11101590 - 18 Oct 2019
Cited by 15 | Viewed by 3681
Abstract
The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III β-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E [...] Read more.
The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III β-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E2 receptor EP4 is linked to progression of a variety of human cancers and may represent a novel target for tumor inhibition in LMS. We evaluated the hypotheses that EP4 and class III β-tubulin have increased expression in LMS in comparison to normal myometrium or benign tumors and that expression of class III β-tubulin correlates with resistance to taxanes and poor clinical outcome. Gene expression was examined using TCGA data and correlated with clinicopathologic outcome which demonstrated that class III β-tubulin is more highly expressed in more aggressive sarcomas with EP4 being widely expressed in all subtypes of sarcoma. Immunohistochemistry for EP4 and class III β-tubulin was performed on patients with LMS, leiomyomatosis/STUMP, leiomyoma, and normal myometrium. Expression of EP4 and class III β-tubulin were characterized for cell lines SK-UT-1, SK-UT-1B, and PHM-41 and these cell lines were treated with docetaxel alone and in combination with EP4 inhibitors. In taxane-resistant cell lines that overexpress class III β-tubulin and EP4, treatment with EP4 inhibitor resulted in at least 2-fold sensitization to docetaxel. Expression of class III β-tubulin and EP4 in LMS may identify patients at risk of resistance to standard chemotherapies and candidates for augmentation of therapy through EP4 inhibition. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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Review

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25 pages, 652 KiB  
Review
Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy
by Silvia Triarico, Serena Rivetti, Michele Antonio Capozza, Alberto Romano, Palma Maurizi, Stefano Mastrangelo, Giorgio Attinà and Antonio Ruggiero
Cancers 2022, 14(13), 3103; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133103 - 24 Jun 2022
Cited by 8 | Viewed by 2240
Abstract
The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic [...] Read more.
The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus. Despite the lack of guidelines about the management of PAC, several studies have described the use and the potential fetal and neonatal adverse events of antineoplastic drugs during pregnancy. We provide a review of the available literature about the transplacental passage and fetal effects of chemotherapy and targeted agents, to guide the clinicians in the most appropriate choices for the management of PAC. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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20 pages, 2432 KiB  
Review
Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype
by Agnieszka Zając, Sylwia K. Król, Piotr Rutkowski and Anna M. Czarnecka
Cancers 2021, 13(6), 1317; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061317 - 15 Mar 2021
Cited by 7 | Viewed by 3529
Abstract
Chondrosarcoma (ChS) is a primary malignant bone tumor. Due to its heterogeneity in clinical outcomes and resistance to chemo- and radiotherapies, there is a need to develop new potential therapies and molecular targets of drugs. Many genes and pathways are involved in in [...] Read more.
Chondrosarcoma (ChS) is a primary malignant bone tumor. Due to its heterogeneity in clinical outcomes and resistance to chemo- and radiotherapies, there is a need to develop new potential therapies and molecular targets of drugs. Many genes and pathways are involved in in ChS progression. The most frequently mutated genes are isocitrate dehydrogenase ½ (IDH1/2), collagen type II alpha 1 chain (COL2A1), and TP53. Besides the point mutations in ChS, chromosomal aberrations, such as 12q13 (MDM2) amplification, the loss of 9p21 (CDKN21/p16/INK4A and INK4A-p14ARF), and several gene fusions, commonly occurring in sarcomas, have been found. ChS involves the hypermethylation of histone H3 and the decreased methylation of some transcription factors. In ChS progression, changes in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K–AKT–mTOR) and hedgehog pathways are known to play a role in tumor growth and chondrocyte proliferation. Due to recent discoveries regarding the potential of immunotherapy in many cancers, in this review we summarize the current state of knowledge concerning cellular markers of ChS and tumor-associated immune cells. This review compares the latest discoveries in ChS biology from gene alterations to specific cellular markers, including advanced molecular pathways and tumor microenvironment, which can help in discovering new potential checkpoints in inhibitory therapy. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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22 pages, 10675 KiB  
Review
Current Status of Management and Outcome for Patients with Ewing Sarcoma
by Asle Charles Hesla, Andri Papakonstantinou and Panagiotis Tsagkozis
Cancers 2021, 13(6), 1202; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061202 - 10 Mar 2021
Cited by 25 | Viewed by 5021
Abstract
Ewing sarcoma is the second most common bone sarcoma in children after osteosarcoma. It is a very aggressive malignancy for which systemic treatment has greatly improved outcome for patients with localized disease, who now see survival rates of over 70%. However, for the [...] Read more.
Ewing sarcoma is the second most common bone sarcoma in children after osteosarcoma. It is a very aggressive malignancy for which systemic treatment has greatly improved outcome for patients with localized disease, who now see survival rates of over 70%. However, for the quarter of patients presenting with metastatic disease, survival is still dismal with less than 30% of patients surviving past 5 years. Patients with disease relapse, local or distant, face an even poorer prognosis with an event-free 5-year survival rate of only 10%. Unfortunately, Ewing sarcoma patients have not yet seen the benefit of recent years’ technical achievements such as next-generation sequencing, which have enabled researchers to study biological systems at a level never seen before. In spite of large multinational studies, treatment of Ewing sarcoma relies entirely on chemotherapeutic agents that have been largely unchanged for decades. As many promising modern therapies, including monoclonal antibodies, small molecules, and immunotherapy, have been disappointing to date, there is no clear candidate as to which drug should be investigated in the next large-scale clinical trial. However, the mechanisms driving tumor development in Ewing sarcoma are slowly unfolding. New entities of Ewing-like tumors, with fusion transcripts that are related to the oncogenic EWSR1-FLI1 fusion seen in the majority of Ewing tumors, are being mapped. These tumors, although sharing much of the same morphologic features as classic Ewing sarcoma, behave differently and may require a different treatment. There are also controversies regarding local treatment of Ewing sarcoma. The radiosensitive nature of the disease and the tendency for Ewing sarcoma to arise in the axial skeleton make local treatment very challenging. Surgical treatment and radiotherapy have their pros and cons, which may give rise to different treatment strategies in different centers around the world. This review article discusses some of these controversies and reproduces the highlights from recent publications with regard to diagnostics, systemic treatment, and surgical treatment of Ewing sarcoma. Full article
(This article belongs to the Special Issue Bone and Soft Tissue Sarcoma)
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