Molecular Targeted Therapy in the Treatment of Chordoma: A Systematic Review

Objectives: Chordoma is a rare bone malignancy that affects the spine and skull base. Treatment dilemma leads to a high rate of local relapse and distant metastases. Molecular targeted therapy (MTT) is an option for advanced chordoma, but its therapeutic efficacy and safety have not been investigated systematically. Therefore, a systematic review was conducted on studies reporting MTT regimens for chordoma.Methods: Clinical trials, case series and case reports on chordoma MTT were identified using MEDLINE, Cochrane library and EMBASE, and systematically reviewed. Data on clinical outcomes, such as median overall survival, progression-free survival, response rate and adverse events (AEs) were extracted and analyzed.Results: Thirty-three eligible studies were selected for the systematic review, which indicated that imatinib and erlotinib were the most frequently used molecular targeted inhibitors (MTIs) for chordoma. For PDGFR-positive and/or EGFR-positive chordoma, clinical benefits were achieved with acceptable AEs. Monotherapy is preferred as the first-line of treatment, and combined drug therapy as the second-line treatment. In addition, the brachyury vaccine has shown promising results.Conclusions: The selection of MTIs for patients with advanced or relapsed chordoma should be based on gene mutation screening and immunohistochemistry (IHC). Monotherapy of TKIs is recommended as the first-line management, and combination therapy (two TKIs or TKI plus mTOR inhibitor) may be the choice for drug-resistant chordoma. Brachyury vaccine is a promising therapeutic strategy and requires more clinical trials to evaluate its safety and efficacy

Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors

The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted protein nanomedicine for this purpose. Saporin, a toxin protein, was co-assembled with a boronated polymer for intracellular protein delivery, and the formed nanoparticles were further coated with an anionic polymer poly (aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo, and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity. The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells, exerting the anticancer activity of saporin by inactivation of ribosomes. As a result, the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose, and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo. This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors

Dissolution kinetics of malachite in ethylene diamine phosphate solutions

Ethylene diamine phosphate (EDP), as a synthetic organic reagent, was used for the first time to leach malachite, and a new method of using organic amine to leach copper oxide ore was developed. The effects of stirring speed, particle size, reagent concentration, and reaction temperature on EDP-dissolution malachite were investigated. Results showed that malachite rapidly dissolved in EDP solution. The malachite-dissolving rate also increased with increased reagent concentration, increased reaction temperature, and decreased particle size. Stirring speed exhibited nearly no effect on EDP-induced malachite dissolution. The leaching kinetics was found to follow the shrinking-core model, and dissolution was controlled by surface chemical reaction with an activation energy of 52.63kJ×mol−1. A semiempirical rate equation was obtained to describe the dissolution process expressed as 1-(1-XCu)1/3=0.0149(CEDP)0.7814 × (Pmalachite)−0.7982×exp(−6.3308/T) ×t

Image_5_Research hotspots and trends of chordoma: A bibliometric analysis.tiff

BackgroundChordoma is a type of mesenchymal malignancy with a high recurrence rate and poor prognosis. Due to its rarity, the tumorigenic mechanism and optimal therapeutic strategy are not well known.MethodsAll relevant articles of chordoma research from 1 January 2000 to 26 April 2022 were obtained from Web of Science Core Collection database. Blibliometrix was used to acquire basic publication data. Visualization and data table of collaboration network, dynamic analysis, trend topics, thematic map, and factorial analysis were acquired using Blibliometrix package. VOSviewer was used to generate a visualization map of co-citation analysis and co-occurrence.ResultsA total of 2,285 articles related to chordoma were identified. The most influential and productive country/region was the United States, and Capital Medical University has published the most articles. Among all high-impact authors, Adrienne M. Flanagan had the highest average citation rate. Neurosurgery was the important periodical for chordoma research with the highest total/average citation rate. We focused on four hotspots in recent chordoma research. The research on surgical treatment and radiotherapy was relatively mature. The molecular signaling pathway, targeted therapy and immunotherapy for chordoma are not yet mature, which will be the future trends of chordoma research.ConclusionThis study indicates that chordoma studies are increasing. Surgery and radiotherapy are well reported and always play fundamental roles in chordoma treatment. The molecular signaling pathway, targeted therapy, and immunotherapy of chordoma are the latest research hotspots.</p

Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration

Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis (PMO) and related diseases, such as bone degeneration, show multiple adverse effects nowadays. Targeting senescent cells (SnCs) and the consequent senescence-associated secretory phenotype (SASP) with a combination of dasatinib and quercetin (DQ) is a recently developed novel therapy for multiple age-related diseases. Herein, we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation, especially senescent mesenchymal stem cells (MSCs) characterized by exhaustion and dysfunction in middle aged rats. Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function. Local administration of DQ and bone morphogenetic protein 2 (BMP2) in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration. Our results repurposed DQ as an attractive therapy for treating PMO and related diseases

Image_4_Research hotspots and trends of chordoma: A bibliometric analysis.tiff

BackgroundChordoma is a type of mesenchymal malignancy with a high recurrence rate and poor prognosis. Due to its rarity, the tumorigenic mechanism and optimal therapeutic strategy are not well known.MethodsAll relevant articles of chordoma research from 1 January 2000 to 26 April 2022 were obtained from Web of Science Core Collection database. Blibliometrix was used to acquire basic publication data. Visualization and data table of collaboration network, dynamic analysis, trend topics, thematic map, and factorial analysis were acquired using Blibliometrix package. VOSviewer was used to generate a visualization map of co-citation analysis and co-occurrence.ResultsA total of 2,285 articles related to chordoma were identified. The most influential and productive country/region was the United States, and Capital Medical University has published the most articles. Among all high-impact authors, Adrienne M. Flanagan had the highest average citation rate. Neurosurgery was the important periodical for chordoma research with the highest total/average citation rate. We focused on four hotspots in recent chordoma research. The research on surgical treatment and radiotherapy was relatively mature. The molecular signaling pathway, targeted therapy and immunotherapy for chordoma are not yet mature, which will be the future trends of chordoma research.ConclusionThis study indicates that chordoma studies are increasing. Surgery and radiotherapy are well reported and always play fundamental roles in chordoma treatment. The molecular signaling pathway, targeted therapy, and immunotherapy of chordoma are the latest research hotspots.</p

Image_1_Research hotspots and trends of chordoma: A bibliometric analysis.tiff

BackgroundChordoma is a type of mesenchymal malignancy with a high recurrence rate and poor prognosis. Due to its rarity, the tumorigenic mechanism and optimal therapeutic strategy are not well known.MethodsAll relevant articles of chordoma research from 1 January 2000 to 26 April 2022 were obtained from Web of Science Core Collection database. Blibliometrix was used to acquire basic publication data. Visualization and data table of collaboration network, dynamic analysis, trend topics, thematic map, and factorial analysis were acquired using Blibliometrix package. VOSviewer was used to generate a visualization map of co-citation analysis and co-occurrence.ResultsA total of 2,285 articles related to chordoma were identified. The most influential and productive country/region was the United States, and Capital Medical University has published the most articles. Among all high-impact authors, Adrienne M. Flanagan had the highest average citation rate. Neurosurgery was the important periodical for chordoma research with the highest total/average citation rate. We focused on four hotspots in recent chordoma research. The research on surgical treatment and radiotherapy was relatively mature. The molecular signaling pathway, targeted therapy and immunotherapy for chordoma are not yet mature, which will be the future trends of chordoma research.ConclusionThis study indicates that chordoma studies are increasing. Surgery and radiotherapy are well reported and always play fundamental roles in chordoma treatment. The molecular signaling pathway, targeted therapy, and immunotherapy of chordoma are the latest research hotspots.</p

Image_3_Research hotspots and trends of chordoma: A bibliometric analysis.tiff

BackgroundChordoma is a type of mesenchymal malignancy with a high recurrence rate and poor prognosis. Due to its rarity, the tumorigenic mechanism and optimal therapeutic strategy are not well known.MethodsAll relevant articles of chordoma research from 1 January 2000 to 26 April 2022 were obtained from Web of Science Core Collection database. Blibliometrix was used to acquire basic publication data. Visualization and data table of collaboration network, dynamic analysis, trend topics, thematic map, and factorial analysis were acquired using Blibliometrix package. VOSviewer was used to generate a visualization map of co-citation analysis and co-occurrence.ResultsA total of 2,285 articles related to chordoma were identified. The most influential and productive country/region was the United States, and Capital Medical University has published the most articles. Among all high-impact authors, Adrienne M. Flanagan had the highest average citation rate. Neurosurgery was the important periodical for chordoma research with the highest total/average citation rate. We focused on four hotspots in recent chordoma research. The research on surgical treatment and radiotherapy was relatively mature. The molecular signaling pathway, targeted therapy and immunotherapy for chordoma are not yet mature, which will be the future trends of chordoma research.ConclusionThis study indicates that chordoma studies are increasing. Surgery and radiotherapy are well reported and always play fundamental roles in chordoma treatment. The molecular signaling pathway, targeted therapy, and immunotherapy of chordoma are the latest research hotspots.</p