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Osteosarcoma: Molecular Alterations, Heredity, and Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 7206

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Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy
Interests: neuroscience; pharmacology, toxicology and pharmaceutics; metabolic diseases
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Special Issue Information

Dear Colleagues, 

Osteosarcoma (OS) is the most common pediatric primary non-hematopoietic bone tumor. It arises mainly in the long bones of the extremities and the main feature is the detection of osteoid matrix produced by neoplastic cells. The etiology of osteosarcoma remains poorly understood.

This tumor has a complex karyotype, and it is a so-called “orphan cancer” with no known driver oncogenes. While the majority of OSs are sporadic, a small percentage occurs as a component of hereditary cancer syndromes. Li–Fraumeni syndrome, retinoblastoma, Rothmund–Thompson syndrome (type 2), Werner syndrome, and Bloom syndrome are some tumor syndromes predisposing to OS.

The therapeutic protocols include neoadjuvant conventional chemotherapy, surgical resection of the primary tumor, and post-operative chemotherapy. Patients’ survival is related to the development of metastasis and the response to chemotherapy.

It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile.

This Special Issue aims to enhance the ongoing efforts to define the sporadic and hereditary genetic and epigenetic changes that are associated with tumor formation and those associated with progression and metastasis.

Dr. Claudio Di Cristofano
Guest Editor

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Keywords

  • osteosarcoma
  • heredity
  • genetic
  • molecular
  • metabolism

Published Papers (3 papers)

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Research

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15 pages, 1851 KiB  
Article
Sorafenib and Doxorubicin Show Synergistic Effects in Human and Canine Osteosarcoma Cell Lines
by Ya-Ting Yang and Vilma Yuzbasiyan-Gurkan
Int. J. Mol. Sci. 2022, 23(16), 9345; https://doi.org/10.3390/ijms23169345 - 19 Aug 2022
Cited by 4 | Viewed by 2263
Abstract
Osteosarcoma (OSA) is the most common bone tumor in both humans and dogs and has a nearly ten-fold higher incidence in dogs than humans. Despite advances in the treatment of other cancers, the overall survival rates for OSA have stagnated for the past [...] Read more.
Osteosarcoma (OSA) is the most common bone tumor in both humans and dogs and has a nearly ten-fold higher incidence in dogs than humans. Despite advances in the treatment of other cancers, the overall survival rates for OSA have stagnated for the past four decades. Therefore, there is a great need to identify novel and effective treatments. We screened a series of tyrosine kinase inhibitors and selected sorafenib, a multi-kinase inhibitor, for further evaluation alone and in combination with cisplatin, carboplatin, and doxorubicin on canine and human OSA cell lines. Our data point to synergistic effects when sorafenib is combined with doxorubicin, but not when combined with cisplatin or carboplatin, in both human and canine OSA. Based on current findings, clinical trials using a combination of doxorubicin and sorafenib in proof-of-concept studies in dogs are warranted. These studies can be carried out relatively quickly in dogs where case load is high and, in turn, provide useful data for the initiation of clinical trials in humans. Full article
(This article belongs to the Special Issue Osteosarcoma: Molecular Alterations, Heredity, and Metabolism)
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24 pages, 3911 KiB  
Article
A Novel Cartesian Plot Analysis for Fixed Monolayers That Relates Cell Phenotype to Transfer of Contents between Fibroblasts and Cancer Cells by Cell-Projection Pumping
by Swarna Mahadevan, Kenelm Kwong, Mingjie Lu, Elizabeth Kelly, Belal Chami, Yevgeniy Romin, Sho Fujisawa, Katia Manova, Malcolm A. S. Moore and Hans Zoellner
Int. J. Mol. Sci. 2022, 23(14), 7949; https://doi.org/10.3390/ijms23147949 - 19 Jul 2022
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Abstract
We recently described cell-projection pumping as a mechanism transferring cytoplasm between cells. The uptake of fibroblast cytoplasm by co-cultured SAOS-2 osteosarcoma cells changes SAOS-2 morphology and increases cell migration and proliferation, as seen by single-cell tracking and in FACS separated SAOS-2 from co-cultures. [...] Read more.
We recently described cell-projection pumping as a mechanism transferring cytoplasm between cells. The uptake of fibroblast cytoplasm by co-cultured SAOS-2 osteosarcoma cells changes SAOS-2 morphology and increases cell migration and proliferation, as seen by single-cell tracking and in FACS separated SAOS-2 from co-cultures. Morphological changes in SAOS-2 seen by single cell tracking are consistent with previous observations in fixed monolayers of SAOS-2 co-cultures. Notably, earlier studies with fixed co-cultures were limited by the absence of a quantitative method for identifying sub-populations of co-cultured cells, or for quantitating transfer relative to control populations of SAOS-2 or fibroblasts cultured alone. We now overcome that limitation by a novel Cartesian plot analysis that identifies individual co-cultured cells as belonging to one of five distinct cell populations, and also gives numerical measure of similarity to control cell populations. We verified the utility of the method by first confirming the previously established relationship between SAOS-2 morphology and uptake of fibroblast contents, and also demonstrated similar effects in other cancer cell lines including from melanomas, and cancers of the ovary and colon. The method was extended to examine global DNA methylation, and while there was no clear effect on SAOS-2 DNA methylation, co-cultured fibroblasts had greatly reduced DNA methylation, similar to cancer associated fibroblasts. Full article
(This article belongs to the Special Issue Osteosarcoma: Molecular Alterations, Heredity, and Metabolism)
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Review

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19 pages, 1174 KiB  
Review
Regulation of Molecular Targets in Osteosarcoma Treatment
by Betul Celik, Kader Cicek, Andrés Felipe Leal and Shunji Tomatsu
Int. J. Mol. Sci. 2022, 23(20), 12583; https://doi.org/10.3390/ijms232012583 - 20 Oct 2022
Cited by 10 | Viewed by 2578
Abstract
The most prevalent malignant bone tumor, osteosarcoma, affects the growth plates of long bones in adolescents and young adults. Standard chemotherapeutic methods showed poor response rates in patients with recurrent and metastatic phases. Therefore, it is critical to develop novel and efficient targeted [...] Read more.
The most prevalent malignant bone tumor, osteosarcoma, affects the growth plates of long bones in adolescents and young adults. Standard chemotherapeutic methods showed poor response rates in patients with recurrent and metastatic phases. Therefore, it is critical to develop novel and efficient targeted therapies to address relapse cases. In this regard, RNA interference technologies are encouraging options in cancer treatment, in which small interfering RNAs regulate the gene expression following RNA interference pathways. The determination of target tissue is as important as the selection of tissue-specific promoters. Moreover, small interfering RNAs should be delivered effectively into the cytoplasm. Lentiviral vectors could encapsulate and deliver the desired gene into the cell and integrate it into the genome, providing long-term regulation of targeted genes. Silencing overexpressed genes promote the tumor cells to lose invasiveness, prevents their proliferation, and triggers their apoptosis. The uniqueness of cancer cells among patients requires novel therapeutic methods that treat patients based on their unique mutations. Several studies showed the effectiveness of different approaches such as microRNA, drug- or chemotherapy-related methods in treating the disease; however, identifying various targets was challenging to understanding disease progression. In this regard, the patient-specific abnormal gene might be targeted using genomics and molecular advancements such as RNA interference approaches. Here, we review potential therapeutic targets for the RNA interference approach, which is applicable as a therapeutic option for osteosarcoma patients, and we point out how the small interfering RNA method becomes a promising approach for the unmet challenge. Full article
(This article belongs to the Special Issue Osteosarcoma: Molecular Alterations, Heredity, and Metabolism)
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