methods-to-enable-spatial-transcriptomics-of-bone-tissues

Methods to Enable Spatial Transcriptomics of Bone Tissues

Understanding the relationship between the cells and their location within each tissue is critical to uncover the biological processes associated with ...

University of Pittsburgh

UPMC Hillman Cancer Center

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient's local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.

Fixation of pathological humeral fractures by the cemented plate technique.

Geller and colleagues report that adjuvant chemotherapy affected the adequacy of osteosarcoma local surgical control. Exogenous bone morphogenetic protein-2 (BMP-2) did not increase local recurrence, but the limited theoretical benefits of BMP-2 for a subset of patients with osteosarcoma may not justify the systemic and long-term risks.

"To B(MP-2) or Not To B(MP-2)" or "Much Ado About Nothing": Are Orthobiologics in Tumor Surgery Worth the Risks?

Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined.

Lung cells support osteosarcoma cell migration and survival.

The overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15-30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells . Here we evaluate its  efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS.

Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent  or-thotopic mouse model.

Surgical resection with negative margins is the foundation of extremity sarcoma management. Failure to achieve negative surgical margins can result in local recurrence (LR), a potentially devastating complication. Indocyanine green (ICG) is a US FDA-approved fluorophore previously used to guide carcinoma resections. We investigated the potential of ICG as an intraoperative guide during experimental sarcoma resection.

Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Osteosarcoma.

ASO Author Reflections: Tumor Painting with Indocyanine Green Dye: Why not Sarcoma, too?

Osteosarcoma (OSA) is the most common primary tumor of bone, mainly affecting children and adolescents. Here we discuss recent advances in surgical and systemic therapies, and highlight potentially new modalities in preclinical evaluation and prognostication.

Update on Osteosarcoma.

Osteosarcoma (OS) is the most frequent primary bone cancer, affecting mostly children and adolescents. Although much progress has been made throughout the years towards treating primary OS, the 5-year survival rate for metastatic OS has remained at only 20% for the last 30 years. Therefore, more efficient treatments are needed. Recent studies have shown that tumor metabolism displays a unique behavior, and plays important roles in tumor growth and metastasis, making it an attractive potential target for novel therapies. While normal cells typically fuel the oxidative phosphorylation (OXPHOS) pathway with the products of glycolysis, cancer cells acquire a plastic metabolism, uncoupling these two pathways. This allows them to obtain building blocks for proliferation from glycolytic intermediates and ATP from OXPHOS. One way to target the metabolism of cancer cells is through dietary interventions. However, while some diets have shown anticancer effects against certain tumor types in preclinical studies, as of yet none have been tested to treat OS. Here we review the features of tumor metabolism, in general and about OS, and propose avenues of research in dietary intervention, discussing strategies that could potentially be effective to target OS metabolism.

Article	Year
Fixation of pathological humeral fractures by the cemented plate technique. The Journal of bone and joint surgery. British volume\| PubMed ID: 21768635	2011
"To B(MP-2) or Not To B(MP-2)" or "Much Ado About Nothing": Are Orthobiologics in Tumor Surgery Worth the Risks? Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 25609065	2015
Lung cells support osteosarcoma cell migration and survival. BMC cancer\| PubMed ID: 28122543	2017
Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent or-thotopic mouse model. Oncotarget\| PubMed ID: 30046395	2018
Tumor Resection Guided by Intraoperative Indocyanine Green Dye Fluorescence Angiography Results in Negative Surgical Margins and Decreased Local Recurrence in an Orthotopic Mouse Model of Os... Annals of surgical oncology\| PubMed ID: 30588559	2019
ASO Author Reflections: Tumor Painting with Indocyanine Green Dye: Why not Sarcoma, too? Annals of surgical oncology\| PubMed ID: 31187368	2019
Update on Osteosarcoma. Current oncology reports\| PubMed ID: 33880674	2021
Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma. Journal of translational medicine\| PubMed ID: 34715874	2021

Kurt Richard Weiss

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