Cancer Research and Treatment

Original Articles

Effect of Necrosis on the miRNA-mRNA Regulatory Network in CRT-MG Human Astroglioma Cells: So-Hee Ahn, Jung-Hyuck Ahn, Dong-Ryeol Ryu, Jisoo Lee, Min-Sun Cho, Youn-Hee Choi; Cancer Res Treat. 2018;50(2):382-397. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.551

Purpose
Glioblastoma multiforme (GBM) is the most common adult primary intracranial tumor. The remarkable features of GBM include central necrosis. MicroRNAs (miRNAs) have been considered as diagnostic/prognostic biomarkers for many cancers, including glioblastoma. However, the effect of necrosis on the miRNA expression profile and predicted miRNA-mRNA regulatory information remain unclear. The purpose of this study is to examine the effect of necrotic cells on the modulation of miRNA and mRNA expression profiles and miRNA-mRNA network in CRT-MG cells.
Materials and Methods
We used human astroglioma cells, CRT-MG, treated with necrotic CRT-MG cells to examine the effect of necrosis on the modulation of miRNA and mRNA by next-generation sequencing. For preparation of necrotic cells, CRT-MGcellswere frozen and thawed through cycle of liquid nitrogen–water bath. The putative miRNA-mRNA regulatory relationshipwas inferred through target information, using miRDB.
Results
The necrotic cells induced dysregulation of 106 miRNAs and 887 mRNAs. Among them, 11 miRNAs that had a negative correlation value of p < 0.05 by the hypergeometric test were screened, and their target mRNAs were analyzed by Gene Ontology enrichment analysis. Using the Kyoto Encyclopedia of Genes and Genomes database, we also found several necrotic cell treatment-activated pathways that were modulated by relevant gene targets of differentially expressed miRNAs.
Conclusion
Our result demonstrated that dysregulation of miRNA and mRNA expression profiles occurs when GBM cells are exposed to necrotic cells, suggesting that several miRNAs may have the potential to be used as biomarkers for predicting GBM progression and pathogenesis.

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Transcriptomic Signatures of Mitochondrial Dysfunction in Autism: Integrated mRNA and microRNA Profiling
Richard E. Frye, Zoe Hill, Shannon Rose, Sandra McCullough, Patricia A. Porter-Gill, Pritmohinder S. Gill
Genes.2025; 16(9): 1065. CrossRef
Crossroads of cell fate: miR-34-mediated regulation of apoptosis and autophagy in glioblastoma
Tareq Nayef AlRamadneh, Waleed K. Abdulsahib, Sajida Hussein Ismael, R. Roopashree, Priya Priyadarshini Nayak, S. Usha Nandhini, Vimal Arora, Ashish Singh Chauhan, Oybek Ruziyev
Discover Oncology.2025;[Epub] CrossRef
MiR-4492, a New Potential MicroRNA for Cancer Diagnosis and Treatment: A Mini Review
Aida Alizamir, Mohammad Amin Amini, Ashkan Karbasi, Mehdi Beyrami
Chonnam Medical Journal.2024; 60(1): 21. CrossRef
The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives
Edgar G. Ordóñez-Rubiano, Nicolás Rincón-Arias, Sebastian Espinosa, William J. Shelton, Andres F. Salazar, Alba Cómbita, Matías Baldoncini, Sabino Luzzi, César Payán-Gómez, Diego F. Gómez- Amarillo, Fernando Hakim, Javier G. Patiño-Gómez, Rafael Parra- Me
Current Research in Pharmacology and Drug Discovery.2024; 7: 100193. CrossRef
Evaluation of a Set of miRNAs in 26 Cases of Fatal Traumatic Brain Injuries
Serena Bonin, Stefano D’Errico, Caterina Medeot, Carlo Moreschi, Solange Sorçaburu Ciglieri, Michela Peruch, Monica Concato, Eros Azzalini, Carlo Previderè, Paolo Fattorini
International Journal of Molecular Sciences.2023; 24(13): 10836. CrossRef
MiR-4461 Inhibits Tumorigenesis of Renal Cell Carcinoma by Targeting PPP1R3C
Yuanyuan Zhao, Gang Ye, You Wang, Dan Luo
Cancer Biotherapy and Radiopharmaceuticals.2022; 37(6): 503. CrossRef
Potential role of microRNAs as biomarkers in human glioblastoma: a mini systematic review from 2015 to 2020
Manuela Rocha de Menezes, Maria Eduarda Azevêdo Acioli, Ana Carolina Lemos da Trindade, Suéllen Pedrosa da Silva, Raul Emídio de Lima, Vanessa Gabryelle da Silva Teixeira, Luydson Richardson Silva Vasconcelos
Molecular Biology Reports.2021; 48(5): 4647. CrossRef
The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression
Federica Caponnetto, Emiliano Dalla, Damiano Mangoni, Silvano Piazza, Slobodanka Radovic, Tamara Ius, Miran Skrap, Carla Di Loreto, Antonio Paolo Beltrami, Ivana Manini, Daniela Cesselli
Biomedicines.2020; 8(12): 564. CrossRef
Differential expression of miR‑4492 and IL‑10 is involved in chronic rhinosinusitis with nasal polyps
Linge Li, Juan Feng, Dinghao Zhang, Jun Yong, Yan Wang, Jianfeng Yao, Rongfu Huang
Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer
Xingsong Li, Xiaokang Yu, Yuting He, Yuhuan Meng, Jinsheng Liang, Lizhen Huang, Hongli Du, Xueping Wang, Wanli Liu
BioMed Research International.2018; 2018: 1. CrossRef

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Radiation-induced Necrosis Deteriorating Neurological Symptoms and Mimicking Progression of Brain Metastasis after Stereotactic-guided Radiotherapy: Young Zoon Kim, Dae Yong Kim, Heon Yoo, Hee Seok Yang, Sang Hoon Shin, Eun Kyung Hong, Kwan Ho Cho, Seung Hoon Lee; Cancer Res Treat. 2007;39(1):16-21. Published online March 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.1.16

Abstract PDF PubReader ePub

Purpose

Although radiation-induced necrosis (RIN) is not a tumor in itself, the lesion progressively enlarges with mass effects and diffuse peritumoral edema in a way that resembles neoplasm. To identify the RIN that mimics progression of brain metastasis, we performed surgical resections of symptomatic RIN lesions.

Meterials and Methods

From June 2003 to December 2005, 7 patients received stereotactic-guided radiotherapy (SRT) for metastatic brain tumor, and they later underwent craniotomy and tumor resection due to the progressive mass effects and the peritumoral edema that caused focal neurological deficit. On MR imaging, a ring-like enhanced single lesion with massive peritumoral edema could not be distinguished from progression of brain metastasis.

Results

Four patients had non-small cell lung cancer, 2 patients had colorectal cancer and 1 patient had renal cell carcinoma. The mean tumor volume was 8.7 ml (range: 3.0~20.7 ml). The prescribed dose of SRT was 30 Gy with 4 fractions for one patient, 18 Gy for two patients and 20 Gy for the other four patients. The four patients who received SRT with a dose of 20 Gy had RIN with or without microscopic residual tumor cells.

Conclusions

Early detection of recurrent disease after radiotherapy and identifying radiation-induced tissue damage are important for delivering adequate treatment. Therefore, specific diagnostic tools that can distinguish RIN from progression of metastatic brain tumor need to be developed.

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AI differentiates radionecrosis from true progression in brain metastasis upon stereotactic radiosurgery: Analysis of 124 histologically assessed lesions
Gaia Ressa, Riccardo Levi, Giovanni Savini, Luca Raspagliesi, Elena Clerici, Luisa Bellu, Luca A Cappellini, Marco Grimaldi, Saverio Pancetti, Beatrice Bono, Andrea Franzini, Marco Riva, Bethania Fernandez, Maximilian Niyazi, Federico Pessina, Giuseppe Mi
Neuro-Oncology.2025; 27(11): 3029. CrossRef
Local radiation enhances systemic CAR T-cell efficacy by augmenting antigen crosspresentation and T-cell infiltration
Nektarios Kostopoulos, Francesca Costabile, Elisavet Krimitza, Silvia Beghi, Denisa Goia, Renzo Perales-Linares, George Thyfronitis, Michael J. LaRiviere, Elise A. Chong, Stephen J. Schuster, Amit Maity, Constantinos Koumenis, John P. Plastaras, Andrea Fa
Blood Advances.2024; 8(24): 6308. CrossRef
Salvage craniotomy for treatment-refractory symptomatic cerebral radiation necrosis
Ashish H Shah, Anil K Mahavadi, Alexis Morell, Daniel G Eichberg, Evan Luther, Christopher A Sarkiss, Alexa Semonche, Michael E Ivan, Ricardo J Komotar
Neuro-Oncology Practice.2020; 7(1): 94. CrossRef
OAR sparing 3D radiotherapy planning supported by fMRI brain mapping investigations
Gábor Opposits, Csaba Aranyi, Csaba Glavák, Zsolt Cselik, Lajos Trón, Dávid Sipos, Janaki Hadjiev, Ervin Berényi, Imre Repa, Miklós Emri, Árpád Kovács
Medical Dosimetry.2020; 45(4): e1. CrossRef
The Role of Navigated Transcranial Magnetic Stimulation Motor Mapping in Adjuvant Radiotherapy Planning in Patients With Supratentorial Brain Metastases
Maximilian J. Schwendner, Nico Sollmann, Christian D. Diehl, Markus Oechsner, Bernhard Meyer, Sandro M. Krieg, Stephanie E. Combs
Frontiers in Oncology.2018;[Epub] CrossRef
Impact of the radiosurgery prescription dose on the local control of small (2 cm or smaller) brain metastases
Alireza M. Mohammadi, Jason L. Schroeder, Lilyana Angelov, Samuel T. Chao, Erin S. Murphy, Jennifer S. Yu, Gennady Neyman, Xuefei Jia, John H. Suh, Gene H. Barnett, Michael A. Vogelbaum
Journal of Neurosurgery.2017; 126(3): 735. CrossRef
Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects
Nathan McDannold, Yongzhi Zhang, Natalia Vykhodtseva
Journal of Neurosurgery.2016; 125(6): 1539. CrossRef
Analysis of risk and predictors of brain radiation necrosis after radiosurgery
Hongqing Zhuang, Yi Zheng, Junjie Wang, Joe Y. Chang, Xiaoguang Wang, Zhiyong Yuan, Ping Wang
Oncotarget.2016; 7(7): 7773. CrossRef
Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?
Ashish H. Shah, Brian Snelling, Amade Bregy, Payal R. Patel, Danoushka Tememe, Rita Bhatia, Evelyn Sklar, Ricardo J. Komotar
Journal of Neuro-Oncology.2013; 112(2): 141. CrossRef
Comparison of Swallowing Functions Between Brain Tumor and Stroke Patients
Dae Hwan Park, Min Ho Chun, Sook Joung Lee, Yoon Bum Song
Annals of Rehabilitation Medicine.2013; 37(5): 633. CrossRef

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TRAIL-Mediated Apoptosis in Human Liver Chang Cells: Channy Park, Sung Wook Hong, Sung Ho Jin, Nam Song Kim, Kyung Ho Cho, Jin Ho Cheon, Jae Yeon Ahn, Jung Ku Yang, Raekil Park; Cancer Res Treat. 2003;35(4):341-348. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.341

Abstract PDF

PURPOSE
Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL)/APO-2L is a member of the TNF family that can kill a wide variety of tumor cells, but not normal cells. This study was designed to investigate the down stream target proteins in TRAIL-mediated apoptosis of human liver, Chang cells.
MATERIALS AND METHODS
The expressions of DR4/DR5 in hepatoma cells, including Chang, HepG2 and Hep3B cells, were determined by RT-PCR. Cell viability was measured by MTT assay and apoptosis was assessed by DNA fragmentation assay. The catalytic activity of caspase- family proteases, including caspase-3 and -9, was tested by using fluorogenic biosubstrates. Expression of apoptotic mediators, including procaspase-3 and PARP proteins, was measured by Western blotting. The expression profile of proteins in Chang cells by using two-dimensional (2-D) gel electrophoresis and MALDI-TOF.
RESULTS
The results demonstrated that TRAIL (100 ng/ml) induced the apoptotic death of Chang cells, as characterized by the ladder-pattern fragmentation of genomic DNA. TRAIL increased the enzymatic activity of caspase- 3, corresponding to the time of appearance of cleaved PARP and caspase-9. In 2-D gel electrophoresis and MALDI- TOF analysis, the comparison of control versus apoptotic cells in the protein expressions revealed that signal intensity of 7 spots were decreased, whereas 6 spots were increased among 300 spots. These spots were resolved and identified as a protein information by MALDI-TOF.
CONCLUSION
We suggested that TRAIL induces the apoptotic death of Chang cells via proteome alterations inducing caspase cascade.

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Upregulation of NAD(P)H:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells
Eun K. Choi, Kaoru Terai, In-Mi Ji, Yeon H. Kook, Kyung H. Park, Eun T. Oh, Robert J. Griffin, Byung U. Lim, Jin-Seok Kim, Doo S. Lee, David A. Boothman, Melissa Loren, Chang W. Song, Heon Joo Park
Neoplasia.2007; 9(8): 634. CrossRef

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Avascular Necrosis of Bone Complicating Treatment of Malignant Lymphoma: Report of 6 cases: Hyung Chan Suh, Jee Sook Hahn, Bum Seok Kim, Seok Lee, So Young Chong, Yoo Hong Min, Yun Woong Ko; J Korean Cancer Assoc. 1997;29(2):344-351.

Abstract PDF: BACKGROUND
Several reports have documented the association of avascular necrosis (AVN) of bone and the treatment of malignant lymphoma with steroid-containing chemotherapy. It is important to recognize these conditions, as they can be mistaken for those of lymphomatous involvement.Cases: This report describes the experience at the Severance hospital over a 10-year period with 6 patients in whom AVN developed during or following treatment of malignant lymphoma. Four patients of non-Hodgkin's lymphoma and two of Hodgkin's disease were treated with steroid-containing chemotherapy. The predominant symptom is pain on motion or weight bearing. Symptoms leading to diagnosis of AVN developed between 5 and 27 months after starting prednisolone (mean 17.8 months), and the mean cumulative dose of prednisolone to the onset of AVN was 4,447 mg (range, 1,800~9,490 mg). All but one were involved in both hip joint. Diagnosis was based on the radiologic appearance, and in the majority radiographic changes consistent with AVN were present at the time of presentation of symptoms. Four patients received total hip replacement and two had conservative care.
CONCLUSION
Patients with malignant lymphoma who developed pain on joint during or after the use of steroid-containing chemothearpy should be carefully investigated with MRI and radionuclear bone scan for early diagnosis and proper management.

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Retroviral Vector - mediated Tumor Necrosis Factor - α Gene Transfer into Human Gastric Carcinoma Cell Lines: Jung Ae Rhee, Jung Ae Lee, Dae Seog Heo, Sung Koo Han, Noe Kyeong Kim; J Korean Cancer Assoc. 1994;26(5):677-688.

Abstract PDF: The tumor necrosis factor a (TNF-a) is a potent cytokine with antitumor activities including a direct cytotoxic effect on human cancer cells and the enhancement of a cytotoxic immune response against the tumor. However, its effectiveness in the human clinical trials is limited due to severe systemic toxicities. An alternative approach, that tumor cells are genetically engineered to secrete TNF-a locally to stimulate the immune system without systemic toxicities, is suggested as a form of gene therapy (tumor-cell-targeted lymphokine gene therapy). In this trial, cDNA encoding human TNF-a (TNF-NeoR) was introduced into five human gastric carcinoma cell lines using a retroviral vector to examine whether TNF-a gene could be transfected and expressed in gastric carcinoma cell lines in vitro. Successful transfer of TNF-a gene into five gastric csrcinoma cell lines was confirmed by polymerase chain reaction techniques. Supernatants (1: 2 dilution) from cultures of transduced gastric carcinoma cell lines demonstrated cytotoxicity to TNF-sensitive WEHI 164 cell lines in the range of 20-49%. TNF- transduced gastric carcinoma cell lines secreted TNF-a at the concetration of 479-8869 pg/10(6) cells-24 hours, whereas the parental cell lines did not secrete TNF-a. There were no differences in the growth rates between parental and TNF-transduced cell lines in vitro. The four TNF-transduced SNU cell lines showed the resistance to endogenous and exogenous TNF, except SNU-668 cell line. In conclusion, TNF-a gene was successfully transfected and expressed in gastric carcinoma cell lines in vitro. These data will be helpful in the development of tumor-cell-targeted lymphokine gene therapy for the treatment of advanced gastric carcinoma.

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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma: Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee; J Korean Cancer Assoc. 1999;31(1):134-143.

Abstract PDF: PURPOSE
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy.
MATERIALS AND METHODS
Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%.
RESULTS
Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care.
CONCLUSION
Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

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The Comparison of Blood TNF - α Level between Normal Person and Cancer Patients , and the Change of Blood TNF - α Level in Cancer Patients Receivint the Ablation Chemotherapy Regimens: Yong Koo Lee, Kyoung Nyeon Kim; J Korean Cancer Assoc. 1994;26(5):815-822.

Abstract PDF: Tumor Necrosis Factor(TNF) is a polypeptide hormone produced in vivo by activated macrophages and lymphocytes, and they called TNF-a and TNF4 respectively. TNF has diverse biological effects which may provide either benefical or detrimental to the host depending on the amount of TNF produced. Blood concentration of tumor necrosis factor- a(TNF-a)were measured by enzyme-linked immunosorbent assay(ELISA) methods in 28 patients receiving the ablative chemotherapy regimens. And serum TNF-a level of patients with solid tumors were examined(esophegeal 10, gastric 10, and lung 8)along with 27 healthy controis. The most striking finding was spontaneous production of TNF-a in a significant proportion of cancer patients(28.72+-23.74 pg/ml: p<0.005) against control person. We also found that chemotherapy increased TNF-a production with 48.4+-23.69 pg/mL This increase was significant(p<0.005) compared to the prechemotherapy. Activated macrophage have been shown to exhibit selective cytotoxicity for neoplastic cells and are thought to play a significant role in tumor regression. There is experimental evidence for its interaction with other biological agents and cytotoxic drugs. Several chemotherapy agents might increase macrophage-generated TNF-a through some mechanisms. For TNF-a the biological agents and importance is certain and methods designed to antagonize the release or effects of TNF may have clinical application.

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The Effect of the Degree of Tumor Necrosis on Survival in Patients with Hepatocellular carcinoma Treated with Curative Resection Following Preoperative Transcatheter Arterial Therapy: Chang Mok Lee, Dong Sup Yoon, Sung Won Kwon, Hoon Sang Chi, Byong Ro Kim; J Korean Cancer Assoc. 1998;30(6):1168-1174.

Abstract PDF: PURPOSE
To investigate the effect of patient and tumor factors on the degree of tumor necrosis and the effect of the degree of the tumor necrosis on the survival in patients treated with curative resection following transcatheter arterial therapy.
MATERIALS AND METHODS
90 patients diagnosed as having hepatocellular carcinoma and treated with curative resection following transcatheter arterial therapy at Yonsei Medical Center between January 1986 and December 1995. The subjects were classified into four groups: 100% necrosis group (Group I, n=29), over 95% necrosis group (Group II, n=28), 50-95% necrosis group (Group III, n=13) and below 50% necrosis group (Group IV, n=20). The factors which affect on the necrosis of the tumor were compared. The overall and disease-free survival rates according to the degree of tumor necrosis were illustrated.
RESULTS
There was no statistical difference in the degree of the tumor necrosis according to age, sex, HBsAg, g-FP, liver cirrhosis, tumor size and morphological classification. In the comparison between the preoperative transcatheter arterial therapies, however, transcatheter arterial chemo-oily embolization (TACOE), which used the injection of the mixture of 3 10 cc Lipiodol and 30-50 mg Adriamycin followed by Gelfoam em- bolization, showed the higher number of 100% necrosis and over 95% necrosis cases. The 1, 3 year overall survival rates were greater for Group I, although not statistically significant. The 1, 5 year disease-free survival rates were greater for Group I, although not statistically significant.
CONCLUSION
In the preoperative transcatheter arterial embolization, TACOE was most effective to get total necrosis of tumor. However overall survival and disease free survival were not affected by the amount of tumor necrosis.

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Effect of Combined Modality Treatment and Clinical Significance of P-Glycoprotein Overexpression in Patients with Osteosarcoma: Yong Seok Yun, Jae Kyung Roh, Hyun Cheol Chung, Jae Yong Cho, Kyoo Ho Shin, Soo Bong Han, Beom Seok Kim, Joon Oh Park, Soo Jung Gong, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jin Sik Min, Byung So; J Korean Cancer Assoc. 1996;28(6):1104-1117.

Abstract PDF: Osteosarcoma is a highly malignant bone tumor and usually encountered in the first three decades of life. The Prognosis of osteasarcoma treated with surgery alone had been poor, with 20% of the patients surviving 5 years. The addition of adjuvant chemotherapy after surgery has siginificantly improved the outcome of osteosarcoma. The new concept of pre-operative chemotherapy has permitted histological assessment of treatment effect and limb salvage procedures. As the role of chemotherapy has been raised, the resistance of tumors to multiple drugs, such as p-glycoprotein overexpression, has become a major problem in the treatment of osteosarcoma. We retrospectively reviewed the clinical records of 53 patients with stage IIB osteosarcoma who were treated at Yonsei Medical Center and Yonsei Cancer Center between March 1, 1986 and June 30, 1996. The purpose of this study was to assess the efficacy and toxicity of cisplatin(IA)-adriamycin(IV) combination pre-operative chemotherapy and the clinical significance of p-glycoprotein status and histologic response as prognostic factors. Among 53 patients, 33 were male and 20 were female with a median age of 21 years(range: 5~61). The tumor locations were as follows: distal femur 24(45.3%), proximal tibia 17(32.1%), humerus 7(13.2%), proximal femur 3(5.4%), fibular 1(1.9%), radius 1(1.9%). Histologic subclassifications were as follows: osteoblastic type 42(78.2%), telangiectatic type 4(7.5%), chondrablastic type 3(5.7%), fibroblastic type 2(3.8%) and undetermined 2(2.8%). The three year overall survival and disease-free survival rates were 66.1% and 61.9% respectively in all patients. Thirty-two patients were treated by pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy and 21 patients were taken only post-operative adjuvant chemotherapy. No significant difference was found between the two groups in probability of survival and recurrence rates. The histological response ta pre-operative chemotherapy was scored by degree of tumor necrosis. Twenty-two patients had a good response [grade IV, 13(40.6%);grade III, 8(25.0%)] and 11 patients had a poor response [grade II, 6(18.8%);grade I, 5(15.6%)]. The histological response was not significantly related to the probability of the survival rate. However, the recurrence rate was higher in the poor-response group(p=0.04). Overexpression of p-glycoprotein was found in tumors from 11 of l8 patients(61.1%) who were given only post-operative adjuvant chemotherapy. No relation was found between the p-glycoprotein expression and survival rate. The degree of tumor necrosis after pre-operative chemotherapy and initial serum alkaline-phosphatase level were considered as prognositic factors. Other clinicopathologic features including age, gender, anatomical site, histological subclassification,operation types,tumor size.p-glycoprotein expression were not associate with patient outcome. Treatment-related side effects were relatively tolerable and reversible by conservative treatment. Pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy in our study did not show improved survival than conventional post-operative chemotherapy with limited follow-up duration. The degree of histologic response after chemotherapy and the initial alkaline phosphatase level were found to be the major predictor for tumor recurrences, while p-glycoprotein overexpression did not alter the clinical outcome. Further studies are warranted to improve the efficacy of adjuvant chemotherapy and to evaluate the significance of multiple resistance gene overexpression in osteosarcoma.

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