The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

Bone sarcomas, mesenchymal origin tumors, represent a substantial group of varying neoplasms of a distinct entity. Bone sarcoma patients show a limited response or do not respond to chemotherapy. Notably, developing efficient chemotherapy approaches, dealing with chemoresistance, and preventing metastasis pose unmet challenges in sarcoma therapy. Insulin-like growth factors 1 and 2 (IGF-1 and -2) and their respective receptors are a multifactorial system that significantly contributes to bone sarcoma pathogenesis. Whereas failures have been registered in creating novel targeted therapeutics aiming at the IGF pathway, new agent development should continue, evaluating combinatorial strategies for enhancing antitumor responses and better classifying the patients that could best benefit from these therapies. A plausible approach for developing a combinatorial strategy is to focus on the tumor microenvironment (TME) and processes executed therein. Herewith, we will discuss how the interplay between IGF-signaling and the TME constituents affects sarcomas’ basal functions and their response to therapy. This review highlights key studies focusing on IGF signaling in bone sarcomas, specifically studies underscoring novel properties that make this system an attractive therapeutic target and identifies new relationships that may be exploited. Potential direct and adjunct therapeutical implications of the extracellular matrix (ECM) effectors will also be summarized.

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The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.634512 ◽

2021 ◽

Vol 9 ◽

Author(s):

Soudeh Ghafouri-Fard ◽

Atefe Abak ◽

Mahdi Mohaqiq ◽

Hamed Shoorei ◽

Mohammad Taheri

Keyword(s):

Growth Factor Signaling ◽

Regulate Cell Growth ◽

Non Coding Rnas ◽

Cerebral Ischemic ◽

Novel Therapeutic Strategies ◽

The Impact ◽

Ovarian Syndrome ◽

Insulin Like Growth Factors ◽

Igf Signaling

The insulin-like growth factors (IGFs) are polypeptides with similar sequences with insulin. These factors regulate cell growth, development, maturation, and aging via different processes including the interplay with MAPK, Akt, and PI3K. IGF signaling participates in the pathogenesis of neoplasia, insulin resistance, diabetes mellitus, polycystic ovarian syndrome, cerebral ischemic injury, fatty liver disease, and several other conditions. Recent investigations have demonstrated the interplay between non-coding RNAs and IGF signaling. This interplay has fundamental roles in the development of the mentioned disorders. We designed the current study to search the available data about the role of IGF-associated non-coding RNAs in the evolution of neoplasia and other conditions. As novel therapeutic strategies have been designed for modification of IGF signaling, identification of the impact of non-coding RNAs in this pathway is necessary for the prediction of response to these modalities.

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Bone sarcoma and trauma

Kazan medical journal ◽

10.17816/kazmj80474 ◽

2021 ◽

Vol 32 (2-3) ◽

pp. 195-197

Author(s):

D. Klebanov

Keyword(s):

Malignant Tumors ◽

Bone Sarcoma ◽

Scientific Thought ◽

Bone Sarcomas

Of 6-7 bone sarcomas, one is always associated with more or less significant trauma. Naturally, this circumstance did not escape the attention of observational doctors and the question of the role of trauma in the etiology of tumors from the day of studying the problem of malignant tumors to the present day has been the focus of medical scientific thought.

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Potential value of pretreatment neutrophil-to-lymphocyte ratio in patients with bone sarcomas

10.21203/rs.3.rs-16686/v1 ◽

2020 ◽

Author(s):

Hongzhi Hu ◽

Xin Huang ◽

Wenbo Yang ◽

Shangyu Wang ◽

Qianwen Zeng ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Meta Analysis ◽

Bone Sarcoma ◽

Neutrophil To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

High Diagnostic Accuracy ◽

Unfavourable Effect ◽

Bone Sarcomas

Abstract Background Increasing evidence indicates the important value of the neutrophil-to-lymphocyte ratio (NLR) in various cancers. In this meta-analysis, we will explore the potential role of pretreatment NLR in patients with bone sarcomas. Methods A systematic literature search of the PubMed, Embase and Web of Science databases for relevant articles was performed with the deadline of December 29, 2019. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated to evaluate the association between NLR and overall survival (OS) in patients with bone sarcomas. Results A total of 1131 patients in 6 studies were included in this meta-analysis. The pooled HR of 2.26 (95%CI: 1.83-2.69, p<0.001) indicated that an elevated NLR had an unfavourable eﬀect on OS. Subgroup analyses showed that elevated NLR was related to poor OS in patients with bone sarcomas, regardless of the type of cancer, ethnicity, sample size (≥200 or <200), the cut-off value for NLR (≥3 or <3), follow-up time (≥30 or <30) and paper quality (NOS scores ≥8 or <8). Additionally, the results of diagnosis analysis suggested that NLR had a relatively high diagnostic accuracy for bone sarcoma patients. Conclusion The results of this meta-analysis suggest that an elevated NLR is associated with poor survival of patients with bone sarcomas. Moreover, NLR had a relatively high diagnostic accuracy for bone sarcoma patients. All these findings suggest NLR might be a promising biomarker in the management of bone sarcomas.

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Extracellular matrix: the gatekeeper of tumor angiogenesis

Biochemical Society Transactions ◽

10.1042/bst20190653 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1543-1555 ◽

Cited By ~ 10

Author(s):

Maurizio Mongiat ◽

Simone Buraschi ◽

Eva Andreuzzi ◽

Thomas Neill ◽

Renato V. Iozzo

Keyword(s):

Extracellular Matrix ◽

Tumor Angiogenesis ◽

Signaling Cascades ◽

Cancer Growth ◽

Cell Behavior ◽

Metastatic Progression ◽

Surface Receptors ◽

The Matrix ◽

Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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Faculty Opinions recommendation of Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1092754.547672 ◽

2007 ◽

Author(s):

Brendan Lee

Keyword(s):

Extracellular Matrix ◽

Progenitor Cells

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Regulation of Anchorage-Independent Growth in Breast Cancer. Role of Signalling by Extracellular Matrix and Growth Factors.

10.21236/ada300473 ◽

1995 ◽

Author(s):

Ron Saulnier

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Growth Factors ◽

Anchorage Independent Growth

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PD-L1 Inhibitors for the Treatment of Prostate Cancer

Current Drug Targets ◽

10.2174/1389450121666200609142219 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1558-1565

Author(s):

Matteo Santoni ◽

Francesco Massari ◽

Liang Cheng ◽

Alessia Cimadamore ◽

Marina Scarpelli ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trials ◽

T Lymphocytes ◽

Chronic Inflammation ◽

Immune Cells ◽

Response To Therapy ◽

Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

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The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

Current Gene Therapy ◽

10.2174/1566523219666190716092203 ◽

2019 ◽

Vol 19 (4) ◽

pp. 255-263 ◽

Cited By ~ 13

Author(s):

Yuangang Wu ◽

Xiaoxi Lu ◽

Bin Shen ◽

Yi Zeng

Keyword(s):

Gene Expression ◽

Gene Therapy ◽

Extracellular Matrix ◽

Inflammatory Reaction ◽

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Protein Translation ◽

Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

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