Cancer Research and Treatment

Original Articles

Sarcoma

Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response: Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee; Cancer Res Treat. 2023;55(2):671-683. Published online September 27, 2022; DOI: https://doi.org/10.4143/crt.2022.251

Abstract PDF Supplementary Material PubReader ePub

Purpose
Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.
Materials and Methods
We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.
Results
Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.
Conclusion
Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Citations

Citations to this article as recorded by

Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Joohee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
Nature Communications.2024;[Epub] CrossRef
The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease
Jonathan Feicht, Ralf-Peter Jansen
RNA Biology.2024; 21(1): 312. CrossRef
Intracranial Relapse in Pediatric Sarcoma
Danielle E. Smith, Tyler Hamby, Kenneth Heym, Ashraf Mohamed, Kelly L. Vallance, Anish Ray
Journal of Pediatric Hematology/Oncology.2023; 45(7): e810. CrossRef

6,224 View
213 Download
3 Web of Science
3 Crossref

Characteristics and Treatment Patterns of Patients with Advanced Soft Tissue Sarcoma in Korea: Hyo Song Kim, Chung Mo Nam, Suk-Yong Jang, Sun Kyu Choi, Minkyung Han, Seonmin Kim, Maria Victoria Moneta, Sae Young Lee, Jae Min Cho, Diego Novick, Sun Young Rha; Cancer Res Treat. 2019;51(4):1380-1391. Published online February 18, 2019; DOI: https://doi.org/10.4143/crt.2018.476

Abstract PDF Supplementary Material PubReader ePub

Purpose
A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status.
Materials and Methods
The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases.
Results
A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis.
Conclusion
This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.

Citations

Citations to this article as recorded by

Relative Tumor Density of Soft-Tissue Sarcoma in Korean Population: An Institutional Review
Bo Bin Cha, Jung Yup Kim, Won-Serk Kim, Ga-Young Lee, Young-Jun Choi
Annals of Dermatology.2025; 37(2): 96. CrossRef
Demographic, clinical, pathologic and treatment pattern of soft tissue sarcoma at Tikur Anbessa specialized hospital, Ethiopia - retrospective cross-sectional study
Habtamu Dessie Mitiku, Melesew Abeje, Yonas Dandena
F1000Research.2025; 14: 313. CrossRef
Factors predictive of second‐line chemotherapy in soft tissue sarcoma: An analysis of the National Genomic Profiling Database
Takao Mochizuki, Masachika Ikegami, Toru Akiyama
Cancer Science.2024; 115(2): 575. CrossRef
Comparative Evaluation of Second-Line Chemotherapy Agents for Advanced Soft Tissue Sarcoma: Gemcitabine/Docetaxel, Pazopanib, and Alternatives
Tae Hun Kim, Ki Hyuk Sung, So Hak Chung
Journal of the Korean Orthopaedic Association.2024; 59(1): 22. CrossRef
Secondary hematological malignancies in patients with sarcoma: A single‑center retrospective study
Yoon Jang, Hong Jeong, Chang-Bae Kong, Won Song, Wan Cho, Dae Jeon, Heyjin Kim, Sung Yang, Im Na, Hyo-Rak Lee, Hye Kang
Oncology Letters.2024;[Epub] CrossRef
Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas
Qiuzhong Long, Zhengtian Li, Wenkang Yang, Ke Huang, Gang Du
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
First-Line Anlotinib Treatment for Soft-Tissue Sarcoma in Chemotherapy-Ineligible Patients: An Open-Label, Single-Arm, Phase 2 Clinical Trial
Tao Li, Ying Dong, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, Jia Chen, Wenhua Xiong, Nong Lin, Xin Huang, Meng Liu, Xiaobo Yan, Zhaoming Ye, Binghao Li
Clinical Cancer Research.2024; 30(19): 4310. CrossRef
Mortality patterns of soft-tissue sarcomas worldwide up to 2018, with predictions for 2025
Margherita Pizzato, Giulia Collatuzzo, Claudia Santucci, Matteo Malvezzi, Paolo Boffetta, Alessandro Comandone, Fabio Levi, Carlo La Vecchia, Paola Bertuccio, Eva Negri
European Journal of Cancer Prevention.2023; 32(1): 71. CrossRef
Chemotherapeutic drugs for soft tissue sarcomas: a review
Zhichao Tian, Weitao Yao
Frontiers in Pharmacology.2023;[Epub] CrossRef
Identification of m5C-related molecular subtypes and prediction models in the prognosis and tumor microenvironment infiltration of soft tissue sarcoma
Xianfeng Wang, Yicheng Mao, Hanlu Xu, Jiyang Chen, Xiao chen
Heliyon.2023; 9(9): e19680. CrossRef
Incidence, Treatment and Outcome of Patients with Retroperitoneal Soft‐Tissue Sarcoma in Switzerland 2005–2015: A Population‐Based Analysis
Johanna C. F. Willburger, Marco von Strauss, Caspar J. Peterson, Tracy R. Glass, Christoph Kettelhack
World Journal of Surgery.2022; 46(2): 461. CrossRef
A Necroptosis-Related lncRNA Signature Predicts Prognosis and Indicates the Immune Microenvironment in Soft Tissue Sarcomas
Binfeng Liu, Zhongyue Liu, Chengyao Feng, Chao Tu
Frontiers in Genetics.2022;[Epub] CrossRef
A novel inflammatory signature for evaluating immune microenvironment status in soft tissue sarcoma
Zhehong Li, Honghong Zheng, Lirui Liu, Zhen Fen, Haiying Cao, Jilong Yang, Junqiang Wei
Frontiers in Oncology.2022;[Epub] CrossRef
Issues of diagnostic search of soft tissue sarcoma
A. N. Sergeev, D. A. Maksimov, A. M. Morozov, M. A. Belyak, E. V. Penyaz', M. O. Popova
Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH).2022;[Epub] CrossRef
Issues of diagnostic search of soft tissue sarcoma
A. N. Sergeev, D. A. Maksimov, A. M. Morozov, M. A. Belyak, E. V. Penyaz', M. O. Popova
Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH).2022; 12(6): 15. CrossRef
Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma
Rui Shen, Bo Liu, Xuesen Li, Tengbo Yu, Kuishuai Xu, Jinfeng Ma
BMC Cancer.2021;[Epub] CrossRef
Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes
Wenjing Huang, Yuhe Duan, Xiuwei Yang, Cong Shang, Xin Chen, Huanyu Zhang, Fujiang Li
Frontiers in Oncology.2021;[Epub] CrossRef
Pulmonary metastasectomy in bone and soft tissue sarcoma with metastasis to the lung
Charles A Gusho, Christopher W Seder, Nicolas Lopez-Hisijos, Alan T Blank, Marta Batus
Interactive CardioVascular and Thoracic Surgery.2021; 33(6): 879. CrossRef
Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs
Li Zhang, Xianzhe Tang, Jia Wan, Xianghong Zhang, Tao Zheng, Zhengjun Lin, Tang Liu
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
Identification and Validation of Pyroptosis-Related lncRNA Signature and Its Correlation with Immune Landscape in Soft Tissue Sarcomas
Zhengjun Lin, Yiting Xu, Xianghong Zhang, Jia Wan, Tao Zheng, Hongxuan Chen, Shijie Chen, Tang Liu
International Journal of General Medicine.2021; Volume 14: 8263. CrossRef
Demographics, Changes in Treatment Patterns, and Outcomes of Bone and Soft Tissue Sarcomas in Korea—A Sarcoma-Specific, Institutional Registry-Based Analysis
Hyehyun Jeong, Hyeon-Su Im, Wanlim Kim, Jong-Seok Lee, Si Yeol Song, Joon Seon Song, Kyung-Ja Cho, Hye Won Chung, Min Hee Lee, Jeong Eun Kim, Jin-Hee Ahn
Cancer Management and Research.2021; Volume 13: 8795. CrossRef
Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma
Zhengjun Lin, Ke Pang, Hongli Li, Xianghong Zhang, Jia Wan, Tao Zheng, Tang Liu, Weijun Peng
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Real-World Outcomes of Pazopanib Treatment in Korean Patients with Advanced Soft Tissue Sarcoma: A Multicenter Retrospective Cohort Study
Chung Ryul Oh, Jung Yong Hong, Jee Hung Kim, Ji Sung Lee, Hyo Song Kim, Tae Won Kim, Jin-Hee Ahn, Jeong Eun Kim
Targeted Oncology.2020; 15(4): 485. CrossRef
Comprehensive profiling of immune-related genes in soft tissue sarcoma patients
Chuan Hu, Bo Chen, Zhangheng Huang, Chuan Liu, Lin Ye, Cailin Wang, Yuexin Tong, Jiaxin Yang, Chengliang Zhao
Journal of Translational Medicine.2020;[Epub] CrossRef

11,906 View
253 Download
22 Web of Science
24 Crossref

Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study: Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim; Cancer Res Treat. 2018;50(1):175-182. Published online March 30, 2017; DOI: https://doi.org/10.4143/crt.2016.535

Abstract PDF PubReader ePub

Purpose
This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence.
Materials and Methods
A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients.
Results
A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes.
Conclusion
GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

Citations

Citations to this article as recorded by

Real‐World Outcomes of Patients Treated With Gemcitabine Using Standardized Dose and Rate and Docetaxel for Advanced Soft Tissue Sarcoma in an Australian Sarcoma Center
Isabella Wilson, Madeleine Strach, Vivek Bhadri, Michelle Harrison, Whiter Tang, Peter Grimison
Asia-Pacific Journal of Clinical Oncology.2025; 21(3): 305. CrossRef
A review of cutaneous angiosarcoma: epidemiology, diagnosis, prognosis, and treatment options
Kohei Yamakawa, Dai Ogata, Kenjiro Namikawa, Eiji Nakano, Yukie Yamaguchi, Naoya Yamazaki
Japanese Journal of Clinical Oncology.2025;[Epub] CrossRef
Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma
Shuang Liang, Lanting Ji, Zhenyuan Yu, YaHsin Cheng, Ruifang Gao, Wenpeng Yan, Fang Zhang
Hereditas.2024;[Epub] CrossRef
Comparative Evaluation of Second-Line Chemotherapy Agents for Advanced Soft Tissue Sarcoma: Gemcitabine/Docetaxel, Pazopanib, and Alternatives
Tae Hun Kim, Ki Hyuk Sung, So Hak Chung
Journal of the Korean Orthopaedic Association.2024; 59(1): 22. CrossRef
Leiomyosarcoma of stomach extending to gastroesophageal junction and distal esophagus as a rare cause of dysphagia: a case report
Lilamani Rajthala, Sagar Gyawali, Sabin Banmala, Surendra Shah
Annals of Medicine & Surgery.2024; 86(5): 3133. CrossRef
Retrospective evaluation of the role of gemcitabine‐docetaxel in well‐differentiated and dedifferentiated liposarcoma
Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei‐Lien Wang, Jeffrey M. Cloutier, Elise F. Nassif, Emily Z. Keung, Christina L. Roland, Barry Feig, Dejka Araujo, Robert S. Benjamin, Anthony P. Conley, John A. Livingston, Joseph Ludwig, Shreyaskumar P
Cancer Medicine.2023; 12(4): 4282. CrossRef
Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is a Therapeutic Strategy for Sarcomas That Can Be Monitored in Real Time
Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N. Bui, Rossana Lazcano, Davis R. Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A. Pina, Cansu Karakas, Mi Li, Nicole M. Kettner, Neeta Somaiah, Peter J. Hougton, Osama Mawlawi, Alexander J. Lazar, Kel
Cancer Research.2023; 83(6): 939. CrossRef
A competing risk-based nomogram to predict cancer-specific survival in patients with retroperitoneal leiomyosarcoma
Qian Fang, Guojing Cai, Guizeng Chen, Xiang Xu, Haifeng Zeng, Yulong He, Shirong Cai, Hui Wu
Heliyon.2023; 9(6): e16867. CrossRef
Chemotherapeutic drugs for soft tissue sarcomas: a review
Zhichao Tian, Weitao Yao
Frontiers in Pharmacology.2023;[Epub] CrossRef
Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma
Szu-Yun Niu, Lou Sun, Shih-Tien Hsu, Sheau-Feng Hwang, Chih-Ku Liu, Yu-Hsiang Shih, Ting-Fang Lu, Yen-Fu Chen, Li-Ching Lai, Pei-Lun Chang, Chien-Hsing Lu
Frontiers in Oncology.2023;[Epub] CrossRef
Intensity modulated radiotherapy might be effective for locally advanced esophageal carcinosarcoma: A single center’s experience and review of literature
Siran Yang, Wenqing Wang, Nan Bi, Zongmei Zhou, Qinfu Feng, Zefen Xiao, Dongfu Chen, Jun Liang, Jima Lu, Jianyang Wang, Xin Wang, Jingbo Wang, Yong Yang, Ningning Lu, Hongxing Zhang, Luhua Wang
Medicine.2022; 101(42): e31215. CrossRef
Synovial sarcoma in children: A 15-YEAR experience at a tertiary pediatric center in Argentina
E. Rossetti, G. Gonzalez Diaz, J. Lopez Marti, S. Innocenti, W. Cacciavillano, G. Felizzia, M. Viso, M.L. Ramos, P. Zubizarreta, A. Rose
Pediatric Hematology Oncology Journal.2021; 6(4): 175. CrossRef
Gemcitabine Maintenance Therapy in Patients With Metastasized Soft Tissue Sarcomas
Dennis Christoph Harrer, Sebastian Buschauer, Ulrich Sterz, Karin Menhart, Christina Wendl, Daniel Heudobler, Matthias Grube, Tobias Pukrop, Wolfgang Herr, Martin Vogelhuber
Frontiers in Oncology.2021;[Epub] CrossRef
Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory mice
Waleed A. Q. Hailan, Faisal M. Abou-Tarboush, Khalid M. Al-Anazi, Areeba Ahmad, Ahmed Qasem, Mohammad Abul Farah
Drug and Chemical Toxicology.2020; 43(2): 158. CrossRef
Establishment of a Novel PDX Mouse Model and Evaluation of the Tumor Suppression Efficacy of Bortezomib Against Liposarcoma
Eun Byeol Jo, Doopyo Hong, Young Sang Lee, Hyunjoo Lee, Jae Berm Park, Sung Joo Kim
Translational Oncology.2019; 12(2): 269. CrossRef
Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology
Yu Jin Kim, Mingi Kim, Hyung Kyu Park, Dan Bi Yu, Kyungsoo Jung, Kyoung Song, Yoon-La Choi
Laboratory Investigation.2019; 99(9): 1309. CrossRef
The combination of gemcitabine and docetaxel arrests a doxorubicin-resistant dedifferentiated liposarcoma in a patient-derived orthotopic xenograft model
Kentaro Miyake, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Norihiko Sugisawa, Jun Ho Park, Sahar Razmjooei, Yuki Katsuya, Maryam Barangi, Yunfeng Li, Scott D. Nelson, Takashi Murakami, Yuki Homma, Yukihiko Hiroshima, Ryusei Matsuyama, Michael Bouve
Biomedicine & Pharmacotherapy.2019; 117: 109093. CrossRef
Adipogenesis induces growth inhibition of dedifferentiated liposarcoma
Yu Jin Kim, Dan Bi Yu, Mingi Kim, Yoon‐La Choi
Cancer Science.2019; 110(8): 2676. CrossRef
Leiomyosarcoma of the Stomach with Metastasis to the Liver: A Case Report With Review of the Literature
Varshil Mehta, Monali Rajawat, Sameer Rastogi, Ravi H Phulware, Roman Mezencev
Future Science OA.2018;[Epub] CrossRef
Systemic treatment in adult uterine sarcomas
I.M.E. Desar, P.B. Ottevanger, C. Benson, W.T.A. van der Graaf
Critical Reviews in Oncology/Hematology.2018; 122: 10. CrossRef
Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced esophageal carcinosarcoma: a case report and review of the literature
Tomoko Yoshimoto, Shinichiro Kobayashi, Kengo Kanetaka, Kazuma Kobayashi, Yasuhiro Nagata, Michi Morita, Yuriko Isagawa, Naoe Kinoshita, Mitsuhisa Takatsuki, Susumu Eguchi
Surgical Case Reports.2018;[Epub] CrossRef

14,088 View
372 Download
19 Web of Science
21 Crossref

Up-regulation of the DR5 Expression by Proteasome Inhibitor MG132 Augments TRAIL-Induced Apoptosis in Soft Tissue Sarcoma Cell Lines: Hee-Jeong Cheong, Kyu Sang Lee, In Sook Woo, Jong-Ho Won, Jae Ho Byun; Cancer Res Treat. 2011;43(2):124-130. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.124

Abstract PDF PubReader ePub

PURPOSE
Current chemotherapeutics for treating locally advanced or metastatic soft tissue sarcomas (STS) are limited. Accordingly, the present in vitro study was conducted to evaluate the effects of treatment of STS cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) applied as a single agent or in combination with a proteasome inhibitor, MG132.
MATERIALS AND METHODS
Sensitivity to TRAIL and activity of TRAIL-induced apoptotic pathways were analyzed in four STS cell lines: HTB-82 (rhabdomyosarcoma), HT-1080 (fibrosarcoma), HTB-93 (synovial sarcoma), and HTB-94 (chondrosarcoma). Reduction of the dye dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) was used to evaluate cytotoxic activity; western blots were used to evaluate TRAIL-induced apoptosis.
RESULTS
TRAIL induced apoptosis in HTB-93 cells, but had little effect in HTB-82, HT-1080, or HTB-94 cells. Expression of TRAIL receptor-1 and -2 did not correlate with sensitivity to TRAIL. Co-incubation of cells with TRAIL and a proteasome inhibitor, MG132, augmented the apoptotic effect of TRAIL in both TRAIL-sensitive and TRAIL-resistant cells. This effect was due to up-regulation of TRAIL receptors and members of the pro-apoptotic BCL-2 family by MG132.
CONCLUSION
These data show that combining TRAIL with MG132 enhances apoptosis and overcomes TRAIL resistance. This restoration of TRAIL sensitivity occurs through an increase in the expression of death receptor 5 and of pro-apoptotic BCL-2 family members such as BAX.

Citations

Citations to this article as recorded by

TRAIL-induced apoptosis and proteasomal activity – Mechanisms, signalling and interplay
Chiara Boccellato, Markus Rehm
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2024; 1871(4): 119688. CrossRef
Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies
Edoardo Agosti, Marco Zeppieri, Sara Antonietti, Tamara Ius, Marco Maria Fontanella, Pier Paolo Panciani
Journal of Personalized Medicine.2024; 14(3): 261. CrossRef
Proteasome inhibitors as anticancer agents
Giorgia Gazzaroli, Andrea Angeli, Arianna Giacomini, Roberto Ronca
Expert Opinion on Therapeutic Patents.2023; 33(11): 775. CrossRef
Combination therapy with c-met inhibitor and TRAIL enhances apoptosis in dedifferentiated liposarcoma patient-derived cells
Eun Byeol Jo, Young Sang Lee, Hyunjoo Lee, Jae Berm Park, Hyojun Park, Yoon-La Choi, Doopyo Hong, Sung Joo Kim
BMC Cancer.2019;[Epub] CrossRef
Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway
Mengxiong Wang, Mary E. Law, Bradley J. Davis, Elham Yaaghubi, Amanda F. Ghilardi, Renan B. Ferreira, Chi-Wu Chiang, Olga A. Guryanova, Daniel Kopinke, Coy D. Heldermon, Ronald K. Castellano, Brian K. Law
Cell Death Discovery.2019;[Epub] CrossRef
The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells
Jemal Adem, Mine Eray, Jonna Eeva, Ulla Nuutinen, Jukka Pelkonen
Leukemia Research.2018; 66: 57. CrossRef
Chondrosarcoma: An overview of clinical behavior, molecular mechanisms mediated drug resistance and potential therapeutic targets
Elahe Nazeri, Mohammad Gouran Savadkoohi, Keivan Majidzadeh-A, Rezvan Esmaeili
Critical Reviews in Oncology/Hematology.2018; 131: 102. CrossRef
TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data
Zakareya Gamie, Konstantinos Kapriniotis, Dimitra Papanikolaou, Emma Haagensen, Ricardo Da Conceicao Ribeiro, Kenneth Dalgarno, Anja Krippner-Heidenreich, Craig Gerrand, Eleftherios Tsiridis, Kenneth Samora Rankin
Cancer Letters.2017; 409: 66. CrossRef
Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear
Shyan‐Yuan Kao, Vitor Y.R. Soares, Arthur G. Kristiansen, Konstantina M. Stankovic
Aging Cell.2016; 15(2): 301. CrossRef
Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas
Akira Maekawa, Kenichi Kohashi, Masaaki Kuda, Kunio Iura, Takeaki Ishii, Makoto Endo, Tetsuya Nakatsura, Yukihide Iwamoto, Yoshinao Oda
BMC Cancer.2016;[Epub] CrossRef
The Importance of Being Dead: Cell Death Mechanisms Assessment in Anti-Sarcoma Therapy
Santiago Rello-Varona, David Herrero-MartÃn, Laura Lagares-Tena, Roser LÃ³pez-Alemany, NÃºria Mulet-Margalef, Juan Huertas-MartÃnez, Silvia Garcia-MonclÃºs, Xavier GarcÃa del Muro, Cristina MuÃ±oz-Pinedo, Oscar MartÃnez Tirado
Frontiers in Oncology.2015;[Epub] CrossRef
Development of a Novel Class of Mitochondrial Ubiquinol–Cytochrome c Reductase Binding Protein (UQCRB) Modulators as Promising Antiangiogenic Leads
Hye Jin Jung, Misun Cho, Yonghyo Kim, Gyoonhee Han, Ho Jeong Kwon
Journal of Medicinal Chemistry.2014; 57(19): 7990. CrossRef
Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells
Hye Jin Jung, Yonghyo Kim, Junghwa Chang, Sang Won Kang, Jeong Hun Kim, Ho Jeong Kwon
Journal of Molecular Medicine.2013; 91(9): 1117. CrossRef
Cell Death Pathways as Therapeutic Targets in Rhabdomyosarcoma
Simone Fulda
Sarcoma.2012; 2012: 1. CrossRef

11,797 View
72 Download
14 Crossref

Telomerase Activity and Expression of hTR and TERT in Human Soft Tissue Sarcomas: Jinyoung Yoo, Seok Jin Kang, Byung Kee Kim; Cancer Res Treat. 2002;34(1):46-51. Published online February 28, 2002; DOI: https://doi.org/10.4143/crt.2002.34.1.46

Abstract PDF

PURPOSE
Sarcomas have rarely been analyzed for telomerase, which is an RNA-dependent DNA polymerase to maintain telomeres and prevent telomere shortening. This study was undertaken to determine telomerase activity and the expression of the telomerase subunits human telomerase RNA (hTR) and telomerase reverse transcriptase (TERT) in soft tissue sarcomas.
MATERIALS AND METHODS
Twenty three sarcomas were analyzed for the telomerase activity by a radioactive PCR-based TRAP assay. All of the samples were further investigated for the expression of hTR by in situ hybridization and for TERT and p53 by immunohistochemistry.
RESULTS
Telomerase activity was detected in four (17%) samples. Expression of hTR was demonstrated in 11 (48%) cases, whereas TERT was expressed in 20 (87%).Of the four telomerase-positive tumors, three were positive for both hTR and TERT, and one was positive only for TERT. p53 overexpression was observed in nine (39%) tumors. The frequency of p53 expression increased as the tumor grade advanced (p= .064).
CONCLUSION
These data indicate that the reactivation of telomerase is an uncommon event in human soft tissue sarcomas. The high frequency of the expression of hTR and TERT in these tumors suggests that telomerase activity may be regulated at the transcriptional level and an additional event leading to telomerase activation exist.

Citations

Citations to this article as recorded by

Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer
Hui Yang, Hongyan Zhang, Yahua Zhong, Qiaoli Wang, Lei Yang, Hong Kang, Xiaojia Gao, Haijun Yu, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
Scientific Reports.2017;[Epub] CrossRef

4,359 View
28 Download
1 Crossref

E-Cadherin Expression and p53 Alterations in Soft Tissue Sarcomas: A Possible Role in Epithelial Differentiation: Jin Young Yoo, Seok Jin Kang, Woong Shick Ahn, Byung Kee Kim; Cancer Res Treat. 2001;33(4):343-349. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.343

Abstract PDF

PURPOSE
We investigated the expressions of E- Cadherin and p53 in soft tissue tumors to determine their significance in sarcoma development and/or progression and to assess their potential correlation with epithelial features.
MATERIALS AND METHODS
A total of 79 soft tissue sarcomas, including 10 tumors comprising epithelial components, were studied immunohistochemically in paraffin-embedded tissue sections. Further analysis was performed on 61 tumors by the application of a polymerase chain reaction technique and a direct sequence analysis procedure applied to exons 5 through 8 in the p53 gene.
RESULTS
E-Cadherin was expressed at the cell-cell boundaries in 8 (10%) tumors: 5 of grade 2 and 3 of grade 3. Of these, six (being 60% of the total of 10 tumors containing epithelial elements) contained and two did not contain histologic evidence of epithelial differentiation. Overexpression of p53 was detected in 26 (33%) samples, 7 of which demonstrated mutations in the p53 gene. No association was established between E-Cadherin immunoreactivities and p53 abnormalities. Tumor grade was found to be strongly correlated with p53 alterations (p=0.01) but not with E-Cadherin expression (p=0.09).
CONCLUSION
These data confirm a role for altered p53 in the pathogenesis of soft tissue sarcomas and suggest a possible role for E-Cadherin in the maintenance of epithelial architecture in these tumors regardless of p53 status.

Citations

Citations to this article as recorded by

Meloxicam Modulates Oxidative Stress Status, Inhibits Prostaglandin E2, and Abrogates Apoptosis in Carbon Tetrachloride–Induced Rat Hepatic Injury
Mohamed Edfawy, Memy H. Hassan, Ahmed Mansour, Abdel-Aziz Hamed, Hebat Allah A. Amin
International Journal of Toxicology.2012; 31(3): 276. CrossRef
Antioxidant and antiapoptotic effects of capsaicin against carbon tetrachloride-induced hepatotoxicity in rats
Memy H Hassan, Mohamed Edfawy, Ahmed Mansour, Abdel-Aziz Hamed
Toxicology and Industrial Health.2012; 28(5): 428. CrossRef
Expression of c-kit and p53 in Non-small Cell Lung Cancers
Jinyoung Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Sung Whan Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Hoon-Kyo Kim
Cancer Research and Treatment.2004; 36(3): 167. CrossRef
Expression of Caspase-3 and c-myc in Non-Small Cell Lung Cancer
Jin young Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Suji Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Seok Jin Kang, Hoon Kyo Kim
Cancer Research and Treatment.2004; 36(5): 303. CrossRef
The Expression of c-myc, bcl-2 and p53 Proteins in Adenocarcinomas of Lung
Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang
Cancer Research and Treatment.2004; 36(2): 146. CrossRef

3,863 View
18 Download
5 Crossref

Limb - Conserving Surgery and Interstitial Brachytherapy Plus External Radiation Therapy in Extremity Soft Tissue Sarcoma: Yong Chan Ahn, Do Hoon Lim, Jai Gon Seo, Moon Kyung Kim, Hong Gyun Wu, Dae Young Kim, Seung Jae Huh; J Korean Cancer Assoc. 1998;30(3):599-607.

Abstract PDF: PURPOSE
In order to avoid functional disability that may be caused by radical excision or amputation in extremity soft tissue sarcomas, authors employed limb-conserving surgery together with extemal radiation therapy plus interstitial brachytherapy.
MATERIALS AND METHODS
From June 1995 to Febrary 1997, 10 extremity soft tissue sarcoma patients were treated with limb-conserving surgery and external radiation therapy plus interstitial brachytherapy. In six patients, whose histologic diagnoses were made at the time of surgery, wide or marginal excision and interstitial brachytherapy was done 4 weeks before postoperative external radiation therapy. In four patients whose histologic confinnations were done before definitive treatment, preoperative external radiation therapy was given 4 weeks before surgery and interstitial brachytherapy. The types of surgery were wide excision in five patients, and marginal excision in five patients. Gross or microscopic residual was left at the surgical resection margins in four patients. The brachytherapy dose ranged from 17.5 Gy to 24 Gy and external beam radiation did from 40 Gy to 45 Gy.
RESULTS
With the median follow-up duration of 21.5 months(range: 13 to 29 months); one local recurrence, and three new distant metastases were observed. There were three patients with wound complications attributable to the current treatment regimen.
CONCLUSION
Satisfactory local tumor control may be achievable with limb-conserving surgery and external radiation therapy plus brachytherapy in patients with extremity soft tissue sarcomas, while more caution should be used to avoid wound problems.

2,430 View
12 Download

Chemotherapy of Advanced Soft Tissue Sarcoma with Etoposide, Ifosfamide, and Cisplatin (VIP): Won Seog Kim, Kyung Hae Jung, Hyun Ah Kim, Sung Hyun Yang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(1):128-135.

Abstract PDF: PURPOSE
Soft tissue sarcomas are uncommon primary malignancies. So studies on the effective chemotherapy for soft tissue sarcomas are limited. We started this study to evaluate the effectiveness of VIP (etoposide, ifosfamide, cisplatin) combination chemotherapy for advanced soft tissue sarcomas.
MATERIALS AND METHODS
Thirty patients with recurrent or metastatic soft tissue sarcoma were treated with VIP combination chemotherapy between December 1989 and June 1996. Each patient was given etoposide 75 mg/m2, ifosfamide 1000 mg/m2, cisplatin 20 mg/m2 intravenously for five consecutive days every three weeks. Mesna (sodium-2-mercaptoethansulfonate) was given to avoid the urologic toxicity.
RESULTS
Twenty-eight of 30 patients were evaluable for response, and among the 28 evaluable patients, there were 9 partial response (32%). Duration of response in 9 responders ranged from 4.1 to 16.2 months (median 8.8 months). Overall survival ranged from 1.7 to 41.5 months (median 11 months) and survival was better for patients with partial response (median survival 14.8 months vs. 9.7 months with stable disease vs. 5.1 months with progressive disease p=0.0006). Nausea and vomiting was noted in more than 90% of cycles, but was markedly severe in only 4%. Leukopenia was noted in 60% of cycles, including 11% of cycles with counts <2,000/mm3. There was no treatment related death, but we had to stop chemotherapy in 2 patients due to leukopenia (1 patient) and neurotoxicity (1 patient).
CONCLUSION
Combination of etoposide, ifosfamide, and cisplatin was fairly active for advanced soft tissue sarcoma, with myelosuppresion and peripheral neuropathy being the most serious toxicities.

3,702 View
39 Download

First
Prev
Page of 1
Next
Last

Search