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Start Over Descriptor "Bone neoplasm" Journal scientific reports
5 results on '"Bone neoplasm"'

1. Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma.

Author

Thongkumkoon, Patcharawadee, Sangphukieo, Apiwat, Tongjai, Siripong, Noisagul, Pitiporn, Sangkhathat, Surasak, Laochareonsuk, Wison, Kamolphiwong, Rawikant, Budprom, Piyaporn, Teeyakasem, Pimpisa, Yongpitakwattana, Petlada, Thepbundit, Viraporn, Sirikaew, Nutnicha, Klangjorhor, Jeerawan, Settakorn, Jongkolnee, Moonmuang, Sutpirat, Suksakit, Pathacha, Pasena, Arnat, Chaijaruwanich, Jeerayut, Yathongkhum, Wilawan, and Dissook, Sivamoke

Subjects
*PRIMARY cell culture, *WHOLE genome sequencing, *DRUG approval, *GENETIC profile, *CRYOPRESERVATION of cells, *CELL culture, *CRYOPROTECTIVE agents
Abstract

Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma

Author

Patcharawadee Thongkumkoon, Apiwat Sangphukieo, Siripong Tongjai, Pitiporn Noisagul, Surasak Sangkhathat, Wison Laochareonsuk, Rawikant Kamolphiwong, Piyaporn Budprom, Pimpisa Teeyakasem, Petlada Yongpitakwattana, Viraporn Thepbundit, Nutnicha Sirikaew, Jeerawan Klangjorhor, Jongkolnee Settakorn, Sutpirat Moonmuang, Pathacha Suksakit, Arnat Pasena, Jeerayut Chaijaruwanich, Wilawan Yathongkhum, Sivamoke Dissook, Dumnoensun Pruksakorn, and Parunya Chaiyawat

Subjects
Primary cell culture, Bone neoplasm, Whole-genome sequencing, Biological effects, Cryopreservation, Medicine, Science
Abstract

Abstract Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Published
2024
Full Text
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3. Role of HSP70 in response to (thermo)radiotherapy : analysis of gene expression in canine osteosarcoma cells by RNA-seq

Author

Nytko, Katarzyna J., Thumser-Henner, Pauline, Russo, Giancarlo, Weyland, Mathias S., Rohrer Bley, Carla, Nytko, Katarzyna J., Thumser-Henner, Pauline, Russo, Giancarlo, Weyland, Mathias S., and Rohrer Bley, Carla

Abstract

Pre-treatment of tumors with hyperthermia is often used to increase the efficacy of radiotherapy. One of the main proteins induced in response to hyperthermia is heat shock protein 70 (HSP70). The aim of our study was to investigate up- and down-regulated genes in response to (thermo)radiotherapy in HSP70 proficient and deficient canine osteosarcoma cell line (Abrams), and functional role of HSP70 in the mechanism of thermoradiosensitization. Cells were transfected with negative control siRNA or siRNA targeting HSP70 and treated with hyperthermia (HT), radiotherapy (RT), and thermoradiotherapy (HTRT). RNA sequencing was used to analyze gene expression. Hyperthermia and thermoradiotherapy, but not radiotherapy alone, induced differential gene expression. We identified genes differentially expressed only in HSP70 knockdown (thus HSP70-dependent) cells in response to hyperthermia and thermoradiotherapy. Interestingly, cell proliferation but not clonogenicity and apoptosis/necrosis was affected by the HSP70 knockdown in response to thermoradiotherapy. The results suggest that HSP70 regulates expression of specific genes in response to hyperthermia and thermoradiotherapy. Further investigations into the role of specific genes regulated in a HSP70-dependent manner in response to thermoradiotherapy could pave a way into new, combinatorial treatment options for (canine) osteosarcoma and other cancer types.

Published
2022

4. Clinical aspects of mCRPC management in patients treated with radium-223

Author

Valeria Dionisi, Stefano Fanti, Fabio Monari, Pietro Ghedini, Alessio G. Morganti, Elisa Lodi Rizzini, and Rizzini EL, Dionisi V, Ghedini P, Morganti AG, Fanti S, Monari F.

Subjects
0301 basic medicine, Oncology, Radium-223, Male, medicine.medical_specialty, Pain, lcsh:Medicine, Bone Neoplasms, Kaplan-Meier Estimate, Bone Neoplasm, Article, Metastasis, Cohort Studies, 03 medical and health sciences, Prostate cancer, Hemoglobins, 0302 clinical medicine, Text mining, Internal medicine, Clinical endpoint, medicine, Humans, In patient, Hemoglobin, lcsh:Science, Aged, Multidisciplinary, Radiotherapy, business.industry, lcsh:R, Anemia, Prostate-Specific Antigen, medicine.disease, Alkaline Phosphatase, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, Bone lesion, 030220 oncology & carcinogenesis, Toxicity, lcsh:Q, Cohort Studie, business, Human, medicine.drug, Radium
Abstract

Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alpha-emitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain. Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alpha-emitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain.

Published
2020

5. Role of HSP70 in response to (thermo)radiotherapy: analysis of gene expression in canine osteosarcoma cells by RNA-seq

Author

Mathias S. Weyland, Carla Rohrer Bley, Pauline Thumser-Henner, Giancarlo Russo, Katarzyna J. Nytko, University of Zurich, and Nytko, Katarzyna J

Subjects
Disease model, animal, 10253 Department of Small Animals, Vesicular Transport Proteins, lcsh:Medicine, Bone neoplasm, 615: Pharmakologie und Therapeutik, Membrane glycoprotein, Gene expression, Dog, Vesicular transport protein, Bone cancer, Cluster Analysis, RNA-Seq, 11434 Center for Clinical Studies, RNA, Small Interfering, lcsh:Science, Cancer, Regulation of gene expression, Gene knockdown, Osteosarcoma, Principal Component Analysis, Multidisciplinary, Membrane Glycoproteins, HSP70 heat-shock protein, Transfection, Photon, Gene Expression Regulation, Neoplastic, Matrix Metalloproteinase 1, Hyperthermia, 610 Medicine & health, Bone Neoplasms, Biology, Canine Osteosarcoma, Article, Dogs, medicine, Animals, HSP70 Heat-Shock Proteins, RNA, Messenger, Cell Proliferation, 1000 Multidisciplinary, Photons, 11077 Center for Applied Biotechnology and Molecular Medicine, Radiotherapy, Animal, 572: Biochemie, Cell growth, lcsh:R, Hyperthermia, Induced, medicine.disease, Disease Models, Animal, Cancer research, lcsh:Q
Abstract

Pre-treatment of tumors with hyperthermia is often used to increase the efficacy of radiotherapy. One of the main proteins induced in response to hyperthermia is heat shock protein 70 (HSP70). The aim of our study was to investigate up- and down-regulated genes in response to (thermo)radiotherapy in HSP70 proficient and deficient canine osteosarcoma cell line (Abrams), and functional role of HSP70 in the mechanism of thermoradiosensitization. Cells were transfected with negative control siRNA or siRNA targeting HSP70 and treated with hyperthermia (HT), radiotherapy (RT), and thermoradiotherapy (HTRT). RNA sequencing was used to analyze gene expression. Hyperthermia and thermoradiotherapy, but not radiotherapy alone, induced differential gene expression. We identified genes differentially expressed only in HSP70 knockdown (thus HSP70-dependent) cells in response to hyperthermia and thermoradiotherapy. Interestingly, cell proliferation but not clonogenicity and apoptosis/necrosis was affected by the HSP70 knockdown in response to thermoradiotherapy. The results suggest that HSP70 regulates expression of specific genes in response to hyperthermia and thermoradiotherapy. Further investigations into the role of specific genes regulated in a HSP70-dependent manner in response to thermoradiotherapy could pave a way into new, combinatorial treatment options for (canine) osteosarcoma and other cancer types., Scientific Reports, 10 (1), ISSN:2045-2322

Published
2020

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