Cancer Research and Treatment

Head and Neck cancer

Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Cancer Res Treat. 2025;57(4):968-980. Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195

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Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate, overall survival (OS), and progression-free survival (PFS).
Results
From October 2017 and August 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutation (H1047), patients with H1047 mutation exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutation showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of next-generation sequencing testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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Actualités 2025 par le comité de rédaction du Bulletin du Cancer : congrès ASCO, ESMO et au-delà
Stéphane Vignot, Audrey Bellesoeur, Delphine Borchiellini, Carole Bouleuc, Romain Cohen, Alexandre de Nonneville, Frédéric Delom, Serge Evrard, Nelly Firmin, Virginie Gandemer, Mohamed Khettab, Daniel Orbach, Manuel Rodrigues, Sébastien Thureau, Marie Wis
Bulletin du Cancer.2026; 113(1): 8. CrossRef
PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás, Marta Pojo
International Journal of Molecular Sciences.2025; 26(11): 5276. CrossRef

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Definitive Chemoradiotherapy Versus Surgery Followed by Adjuvant Radiotherapy in Resectable Stage III/IV Hypopharyngeal Cancer: Jun Won Kim, Mi Sun Kim, Se-Heon Kim, Joo Hang Kim, Chang Geol Lee, Gwi Eon Kim, Ki Chang Keum; Cancer Res Treat. 2016;48(1):45-53. Published online March 13, 2015; DOI: https://doi.org/10.4143/crt.2014.340

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Purpose
The purpose of this study is to compare the treatment outcomes for locally advanced resectable hypopharyngeal cancer between organ-preserving chemoradiotherapy (CRT) and surgery followed by radiotherapy (SRT).
Materials and Methods
We reviewed 91 patients with stage III/IV hypopharyngeal squamous cell carcinoma treated with radiotherapy (RT). In the CRT group (n=34), 18 patients were treated with concurrent CRT and 16 patients with induction chemotherapy plus concurrent CRT. In the SRT group (n=57), six patients were treated with total laryngopharyngectomy, 34 patients with total laryngectomy (TL) and partial pharyngectomy (PP), and 17 patients with PP, which were followed by adjuvant radiotherapy (n=41) or CRT (n=16). The median RT dose was 70 Gy for CRT and 59.4 Gy for SRT.
Results
Five-year local control (84.1% vs. 90.9%), and disease-free survival (DFS, 51.0% vs. 52.7%) and overall survival (OS, 58.6% vs. 56.6%) showed no significant difference between the CRT and SRT groups. The functional larynx-preservation rate was higher in the CRT group (88.2% vs. 29.8%). Treatment-related toxicity, requiring surgical intervention, occurred more frequently in the SRT group (37% vs. 12%). In the SRT group, TL resulted in a significantly higher DFS than larynx-sparing surgery (63.9% vs. 26.5%, p=0.027). Treatment outcome of the SRT group improved when only patients with TL were considered (n=40); however, 5-year OS (67.1% vs. 58.6%, p=0.830) and DFS (63.9% vs. 51.0%, p=0.490) did not improve significantly when compared to the CRT group.
Conclusion
Organ preserving CRT provided a treatment outcome that is comparable to SRT for locally advanced hypopharyngeal cancer, while offering an opportunity for functional larynx-preservation and reduced treatment-related toxicity.

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Prognostic Factors and Long-Term Outcome Prediction in Patients with Hypopharyngeal Carcinoma Treated with (Chemo)radiotherapy: Development of a Prognostic Model
Miloslav Pala, Pavla Novakova, Adam Tesar, Lucie Vesela, Antonin Vrana, Jarmila Sukova, Zdenka Pechacova, Petra Holeckova, Tereza Drbohlavova, Tomas Podlesak, Petra Tesarova
Biomedicines.2025; 13(2): 417. CrossRef
Efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as induction chemotherapy regimen for hypopharyngeal cancer
Cailing Jiang, Yulan Liu, Yunyan Mo, Lieyin Xu, Lin Zhu, Zhenya Li, Shengyuan Xu, Xi Qin, Guangteng Wu, Mafei Kang, Xiaosong He, Feng Xue
Frontiers in Oncology.2025;[Epub] CrossRef
Survival Outcomes of the Patients With Advanced Hypopharyngeal Squamous Cell Carcinoma Treated With Chemoradiotherapy and Total Pharyngolaryngectomy Based on Reports of Head and Neck Cancer Registry of Japan
Yuto Horichi, Hirotaka Shinomiya, Megumi Kitayama, Daisuke Kawakita, Takeshi Kodaira, Munenaga Nakamizo, Seiichi Yoshimoto, Ken‐ichi Nibu
Head & Neck.2025; 47(9): 2412. CrossRef
Comparative efficacy of surgery combined with chemoradiotherapy versus chemoradiotherapy alone in the treatment of locally advanced hypopharyngeal cancer
Feng Cai, Cui Cheng, Hongbo Xu, Xianwen Zhang, Gengming Wang, Shilong Song, Yajun Zhang, Lu Xu
Journal of Radiation Research and Applied Sciences.2025; 18(3): 101737. CrossRef
Patterns of recurrence in HNSCC patients treated definitively with upfront surgery, chemoradiation
Pei Yuan Fong, Thomas Kwok Seng Loh, Liang Shen, Donovan Kum Chuen Eu, Chwee Ming Lim
European Archives of Oto-Rhino-Laryngology.2024; 281(5): 2645. CrossRef
Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment
Yu-Hsuan Lin, Jenn-Ren Hsiao, Yuan-Hua Wu, Jeffrey S. Chang, Chun-Yen Ou, Wei-Ting Lee, Cheng-Chih Huang, Chan-Chi Chang, Yu-Hsuan Lai, Sen-Tien Tsai, Wei-Ting Hsueh, Chia-Jui Yen, Chen-Lin Lin, Yu-Shan Chen, Shih-Sheng Jiang, Yu-Chu Su, Shang-Yin Wu
Annals of Surgical Oncology.2023; 30(2): 1169. CrossRef
Survival analyses of different treatment modalities and clinical stage for hypopharyngeal carcinoma
Tian-Yun Lin, Tsung-Lun Lee, Yen-Bin Hsu, Shyh-Kuan Tai, Ling-Wei Wang, Muh-Hwa Yang, Pen-Yuan Chu
Frontiers in Oncology.2023;[Epub] CrossRef
Optimal treatment strategy and prognostic analysis for hypopharyngeal squamous-cell carcinoma patients with T3-T4 or node-positive: A population-based study
Linhui Zheng, Sha Fang, Linfeng Ye, Wenqi Cai, Wenbin Xiang, Yan Qi, Huachao Wu, Chunqian Yang, Runze Zhang, Yifeng Liu, Yue Liu, Chaoyan Wu, Haijun Yu
European Journal of Surgical Oncology.2023; 49(7): 1162. CrossRef
Study on the treatment outcomes of advanced laryngeal and hypopharyngeal cancer with induction chemotherapy
Hideoki Uryu, Shingo Tamura, Rina Kitagawa, Ayaka Koide, Kaori Hara, Ryutaro Uchi, Torahiko Nakashima
Toukeibu Gan.2023; 49(3): 249. CrossRef
Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment
Donghyeok Kim, Nalee Kim, Sungmin Koh, Man Ki Chung, Young-Ik Son, Dongryul Oh, Han-Sin Jeong, Yong Chan Ahn
Cancer Research and Treatment.2022; 54(1): 84. CrossRef
The impact of physician’s characteristics on decision-making in head and neck oncology: Results of a national survey
Emilien Chabrillac, Sébastien Lamy, Pascale Grosclaude, Fanny Cros, Benjamin Vairel, Jérôme Sarini, Sébastien Vergez, Antoine Nebout, Pierre Bories, Agnès Dupret-Bories
Oral Oncology.2022; 129: 105895. CrossRef
Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas
Yu-qin He, Xi-wei Zhang, Yi-ming Zhu, Xiao-guang Ni, Ze-hao Huang, Chang-ming An, Jun-lin Yi, Shao-yan Liu
Frontiers in Oncology.2021;[Epub] CrossRef
Tumor dimension‐dependent microscopic extensions of hypopharyngeal cancer: Therapeutic implications for larynx‐preserving hypopharyngectomy
Joongbo Shin, Jiyeon Lee, Nayoung Hwang, Sung Yong Choi, Woori Park, Nayeon Choi, Young‐Ik Son, Junhun Cho, Han‐Sin Jeong
Journal of Surgical Oncology.2021; 123(4): 872. CrossRef
Survival and complications with a surgical approach in advanced hypopharyngeal cancer
Maria Paz Galeano Machuca, Deborah L. Ng, Shyuang‐Der Terng, Wen‐Ching Wu, Chih‐Tao Cheng
Journal of Surgical Oncology.2021; 123(7): 1540. CrossRef
High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer
Jialing Wu, Kaiyun You, Changlong Chen, Huimin Zhong, Yanhui Jiang, Huaqian Mo, Juanjuan Song, Xingsheng Qiu, Yimin Liu
Frontiers in Oncology.2021;[Epub] CrossRef
Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy
Patricia García-Cabo, Fernando López, Mario Sánchez-Canteli, Laura Fernández-Vañes, César Álvarez-Marcos, José Luis Llorente, Maria Ángeles de la Rúa, Pilar Blay, Juan P. Rodrigo
Cancers.2021; 13(7): 1735. CrossRef
Physician practice variation in head and neck cancer therapy: Results of a national survey
Fanny Cros, Sébastien Lamy, Pascale Grosclaude, Antoine Nebout, Emilien Chabrillac, Sébastien Vergez, Pierre Bories, Agnès Dupret-Bories
Oral Oncology.2021; 117: 105293. CrossRef
Survival Benefits From Surgery for Stage IVa Head and Neck Squamous Cell Carcinoma: A Multi-Institutional Analysis of 1,033 Cases
Jun-Ook Park, Young Min Park, Woo-Jin Jeong, Yoo Seob Shin, Yong Tae Hong, Ik Joon Choi, Ji Won Kim, Seung Hoon Woo, Yeon Soo Kim, Jae Won Chang, Min-Sik Kim, Kwang-Yoon Jung, Soon-Hyun Ahn, Chul-Ho Kim, Ki Hwan Hong, Phil-Sang Chung, Young-Mo Kim, Se-Heo
Clinical and Experimental Otorhinolaryngology.2021; 14(2): 225. CrossRef
Prognostic significance of human papillomavirus status and treatment modality in hypopharyngeal cancer
Nina Burbure, Elizabeth Handorf, John A. Ridge, Jessica Bauman, Jeffrey C. Liu, Anshu Giri, Thomas J. Galloway
Head & Neck.2021; 43(10): 3042. CrossRef
Initial surgical versus non-surgical treatments for advanced hypopharyngeal cancer: A meta-analysis with trial sequential analysis
Jie Cui, Liping Wang, Jinsong Piao, Haiyan Huang, Weiquan Chen, Zhen Chen, Hong Yang, Xiaojun Tan, Jiansheng Li, Genglong Liu
International Journal of Surgery.2020; 82: 249. CrossRef
lncRNA HOXA11-AS Promotes Proliferation and Migration via Sponging miR-155 in Hypopharyngeal Squamous Cell Carcinoma
Jianing Xu, Qiyu Bo, Xiang Zhang, Dapeng Lei, Jue Wang, Xinliang Pan
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics.2020; 28(3): 311. CrossRef
Pacientes con carcinoma localmente avanzado de hipofaringe. Resultados a lo largo de un periodo de 30 años
Xavier León, Montserrat López, Jacinto García, Carlota Rovira, María Casasayas, Miquel Quer
Acta Otorrinolaringológica Española.2019; 70(6): 315. CrossRef
A Survival Analysis of Hypopharyngeal Cancer Patients: A Hospital-Cancer registry Based Study
Manigreeva Krishnatreya, Amal Chandra Kataki, Jagannath Dev Sharma, Nizara Baishya, Tashnin Rahman, Mouchumee Bhattcharyya, Ashok Kumar Das, Manoj Kalita
Indian Journal of Otolaryngology and Head & Neck Surgery.2019; 71(S1): 798. CrossRef
Long-term oncological and functional outcomes of induction chemotherapy followed by (chemo)radiotherapy vs definitive chemoradiotherapy vs surgery-based therapy in locally advanced stage III/IV hypopharyngeal cancer: Multicenter review of 266 cases
Eun-Jae Chung, Woo-Jin Jeong, Young Ho Jung, Seong Keun Kwon, Tack-Kyun Kwon, Soon-Hyun Ahn, Myung-Whun Sung, Bhumsuk Keam, Dae-Seog Heo, Jin Ho Kim, Hong-Gyun Wu, Keun-Wook Lee, Keun-Yong Eom, Young-Soo Rho
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Surgery is not the only determinant of an outcome in patients with hypopharyngeal carcinoma
Robert Smee, Janet R. Williams, Damian P. Kotevski
Head & Neck.2019; 41(5): 1165. CrossRef
Open-neck organ preservation surgery for hypopharyngeal cancer: indications, techniques, limits, and outcomes
Patrick J. Bradley, Liangfa Liu
Current Opinion in Otolaryngology & Head & Neck Surgery.2019; 27(2): 123. CrossRef
Oncologic and Functional Outcomes After Primary and Salvage Laryngopharyngoesophagectomy With Gastric Pull-Up Reconstruction for Locally Advanced Hypopharyngeal Squamous Cell Carcinoma
Jeroen Meulemans, Floor Couvreur, Eline Beckers, Philippe Nafteux, Hans Van Veer, Vincent Vander Poorten, Pierre Delaere, Willy Coosemans
Frontiers in Oncology.2019;[Epub] CrossRef
Patients With Locally Advanced Hypopharyngeal Carcinoma. Results Over a 30-year Period
Xavier León, Montserrat López, Jacinto García, Carlota Rovira, María Casasayas, Miquel Quer
Acta Otorrinolaringologica (English Edition).2019; 70(6): 315. CrossRef
Clinical value of ultrasonic imaging in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis
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Surgery vs. radiotherapy for locally advanced hypopharyngeal cancer in the contemporary era: A population‐based study
Yi‐Jun Kim, Rena Lee
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The impact of surgical margin status on the outcomes of locally advanced hypopharyngeal squamous cell carcinoma treated by primary surgery
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Acta Oto-Laryngologica.2018; 138(12): 1136. CrossRef
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Si‑Cong Zhang, Shui‑Hong Zhou, De‑Sheng Shang, Yang‑Yang Bao, Ling‑Xiang Ruan, Ting‑Ting Wu
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Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy
Shigemichi Iwae, Masato Fujii, Ryuichi Hayashi, Yasuhisa Hasegawa, Takashi Fujii, Kenji Okami, Akihiro Homma, Tetsuro Onitsuka, Takakuni Kato, Takenori Ogawa, Kyoichi Terao, Nobuya Monden, Naoki Otsuki, Hiroshi Nishino, Ichiro Ota, Yasushi Fujimoto, Kazut
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Survival benefit of surgical approach for advanced oropharyngeal and hypopharyngeal cancer: A retrospective analysis
Chih-Tao Cheng, Ching-Yuan Lin, Skye Hung-Chun Cheng, Yi-Ping Lin, Lay-Chin Lim, Nicolas Pennarun, Zhen-Ying Liu, Shyuang-Der Terng
Head & Neck.2017; 39(10): 2104. CrossRef
When is definitive radiotherapy the preferred treatment for head and neck squamous cell carcinoma?
William M. Mendenhall, Primož Strojan, Avraham Eisbruch, Robert Smee, Alessandra Rinaldo, Alfio Ferlito
European Archives of Oto-Rhino-Laryngology.2015; 272(10): 2583. CrossRef

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The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer: Yong Tai Kim, Chul Kim, Joo Hyuk Sohn, So Young Park, Soo Young Park, Nae Choon Yu, Young Sam Kim, Se Kyu Kim, Joon Chang, Kil Dong Kim, Kyung Young Chung, Joo Hang Kim; Cancer Res Treat. 2003;35(6):502-506. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.502

Abstract PDF

PURPOSE
The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty-five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events.
CONCLUSION
The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens.

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Serum Carcinoembryonic Antigen as an Index of the Therapeutic Effect of EGFR-TKIs in Patients with Advanced Non-Small Cell Lung Cancer
Jin Hee Park, Sung Bin Kim, Sung Jin Nam, Su Hyeon Jeong, Chul Ho Oak, Tae Won Jang, Maan Hong Jung
Journal of Lung Cancer.2010; 9(2): 97. CrossRef
A review of the benefit–risk profile of gefitinib in Asian patients with advanced non‐small‐cell lung cancer
Keunchil Park, Koichi Goto
Current Medical Research and Opinion.2006; 22(3): 561. CrossRef

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Increased Cytopathic Effect of Replicating Adenovirus Expressing Adenovirus Death Protein: Eunhee Kim, Joo Hang Kim, Taeyoung Koo, Joo Hyuk Sohn, Chae Ok Yun; Cancer Res Treat. 2003;35(5):425-432. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.425

Abstract PDF

PURPOSE
Replication-competent adenoviruses (Ads) are promising new modalities for the treatment of cancer. Selective replication of a viral agent in tumor may lead to improved efficacy over non-replicating Ads due to viral multiplication, lysis of the infected cancer cell and spread to surrounding cells. In our previous studies it was shown that the E1B 55 kD-deleted Ad (YKL-1) exhibits tumor specific replication and cell lysis, but with reduced cytolytic effects compared to the wild type adenovirus (Int J Cancer 2000;88: 454-463). Thus, improving the potency of oncolytic Ads remains an important goal for cancer gene therapy. To increase the oncolytic ability of YKL-1, an adenovirus death protein (ADP) gene was reintroduced under the control of a CMV or MLP promoter at the E3 region of the YKL-1, generating an YKL-cADP and YKL-mADP, respectively.
MATERIALS AND METHODS
The in vitro cytolytic effect of ADP expressing Ads was evaluated by MTT assay, and the induction of apoptosis by ADP expressing Ads was examined by TUNEL analysis. Finally, the antitumor effect of ADP expressing Ads was demonstrated in C33A xenograft tumor model. RESULTS: The YKL-cADP exerted a markedly enhanced cytolytic effect against H460 and SK-Hep1 cancer cell lines. The TUNEL assay indicated that the ADP-mediated cytotoxicity was largely driven by apoptosis. Finally, the YKL-cADP showed a superior antitumor effect than the YKL-1 or YKL-mADP in C33A xenografts. CONCLUSION: These lines of evidence demonstrate that the YKL-cADP induces efficient cell lysis, which is critical for the addition of therapeutic value to replicating Ads in cancer gene therapy.

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The Adenovirus Death Protein – a small membrane protein controls cell lysis and disease
Fanny Georgi, Urs F. Greber
FEBS Letters.2020; 594(12): 1861. CrossRef
A compendium of adenovirus genetic modifications for enhanced replication, oncolysis, and tumor immunosurveillance in cancer therapy
Aleksei A. Stepanenko, Vladimir P. Chekhonin
Gene.2018; 679: 11. CrossRef
Oncolytic viruses: adenoviruses
Julia Niemann, Florian Kühnel
Virus Genes.2017; 53(5): 700. CrossRef

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Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer: Yoon Jae Kim, Joo Hyuk Sohn, Chul Kim, Yong Tai Kim, Hai Jin Kim, Joong Bae Ahn, Se Kyu Kim, Joon Chang, Nae Choon Yoo, Joo Hang Kim, Jae Yong Cho; Cancer Res Treat. 2003;35(4):294-298. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.294

Abstract PDF: PURPOSE
With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies.
MATERIALS AND METHODS
Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks.
RESULTS
Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed.
CONCLUSION
The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.

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Clinical Features of Pulmonary Large Cell Neuroendocrine Carcinoma: Moo Suk Park, Kil Dong Kim, Jae Ho Chung, Dong Hwan Shin, Kyung Young Chung, Joo Hang Kim, Chang Yul Lee, Young Sam Kim, Hyung Joong Kim, Se Kyu Kim, Chul Min Ahn, Sung Kyu Kim, Joon Chang; Cancer Res Treat. 2003;35(3):245-253. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.245

Abstract PDF

PURPOSE
This study was performed to investigate the clinical features of large cell neuroendocrine carcinomas (LCNEC). MATERIALS AND METHODS: We retrospectively reviewed the histopathology and clinical information of 37 patients with LCNEC, diagnosed between June 1992 and May 2002 at the Severance Hospital, and performed immunohistochemical (IHC) staining. RESULTS: The prevalence of LCNEC among primary lung cancers was 0.3%, 37 out of 13, 012 cases over a 10 year period. The mean age was 61+/-12 years old, with 34 (92%) males and 3 (8%) females. 30 patients smoked, with an average of 42 packs per year. A cough was the most frequent symptom. The tumor was located at the periphery of the lung in 24 cases (65%). Among the 30 cases that underwent surgery, 4 were diagnosed pathological stage IA, 11 IB, 1 IIB, 13 IIIA and 1 IIIB. The 7 clinically non-operable cases were IIIB in 3, and IV in 4. The positive rates of CD56, thyroid transcription factor-1 (TTF-1), chromogranin A, synaptophysin and 34betaE12 for tumor cells were 88.9, 55.6, 42.1, 31.6 and 21.1%, respectively, from the IHC staining. The median survival time and 5 year-survival rate were 24 months and 27%, respectively. The group that underwent surgery had a better prognosis than those that did not.
CONCLUSION
The positive rates for the tumor markers varied, but those of the CD56 and TFT-1 were the highest. The possibility of LCNEC needs to be evaluated for the following situations: small cell carcinomas located at the periphery and not responding chemotherapy, small cell carcinomas diagnosed by percutaneous needle aspiration, poorly differentiated non-mall cell carcinomas, with uncertain histologic type, and unclassified neuroendocrine tumor, etc.

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Misleading wheeze in a case of atypical large cell neuroendocrine carcinoma of lung - A deadly variety
Jeevanandham Anandan, Zeenathalam Nadaf, Sneha Leo
IP Indian Journal of Immunology and Respiratory Medicine.2024; 8(4): 161. CrossRef
Pulmonary large cell neuroendocrine carcinoma (LCNEC): a population-based study addressing recent molecular-genetic advances and emerging therapeutic approaches
Jaffar Khan, Abdul Qahar Khan Yasinzai, Sabrina Matosz, Marjan Khan, Saleh Heneidi, Hector Mesa, Aman Chauhan, Jaydira Del Rivero, Nagla Abdel Karim, Asad Ullah
Clinical and Experimental Medicine.2023; 23(7): 3947. CrossRef
Hierarchical identification of a transcriptional panel for the histological diagnosis of lung neuroendocrine tumors
Juxuan Zhang, Jiaxing Deng, Xiao Feng, Yilong Tan, Xin Li, Yixin Liu, Mengyue Li, Haitao Qi, Lefan Tang, Qingwei Meng, Haidan Yan, Lishuang Qi
Frontiers in Genetics.2022;[Epub] CrossRef
Management of Large Cell Neuroendocrine Carcinoma
Virginia Corbett, Susanne Arnold, Lowell Anthony, Aman Chauhan
Frontiers in Oncology.2021;[Epub] CrossRef

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Development of a Conditional Replication Competent Adenovirus, Controlled by the Human Telomerase Promoter (hTERT): Eunhee Kim, Joo Hang Kim, Ha Youn Shin, Han Saem Lee, Joo Hyuk Sohn, Jai Myung Yang, Jungho Kim, Chae Ok Yun; Cancer Res Treat. 2003;35(3):191-206. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.191

Abstract PDF

PURPOSE
This study has been planned to generate a replication-competent adenovirus which replicates in a cancer cell-specific manner, thus minimizing the side effects and toxicity of cancer gene therapy. MATERIALS AND METHODS: we have generated an E1B 19 kD attenuated recombinant adenoviruses, Ad-TERT-delta19 and Ad-mTERT-delta19, which encode E1A gene driven by the wild type hTERT and modified m-hTERT promoter containing additional c-myc and Sp1 binding sites in the backbone of Ad-deltaE1B19. The in vitro efficacy and specificity of the hTERT and m-hTERT promoter have been evaluated by the comparison of viral replication and cytopathic effect in cancer cells and normal cell lines. To assess anti-tumor effect and safety of hTERT or m-hTERT promoter driven replication competent adenoviruses, tumor regression after subcutaneous injection in subcutaneous C33A xenografts and lacZ expression after systemic injection in organs were examined. RESULTS: The activation of hTERT or m-hTERT promoter was significantly up-regulated only in hTERT-positive cells, but not in hTERT-negative cells. Moreover, the activity of m-hTERT promoter was substantially increased in hTERT-positive cancer cells, but not in hTERT-negative cells. While Ad-TERT-delta19 replicated in and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT-delta19 enhanced viral replication and cytopathic effect in cancer cells only. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-mTERT-delta19. CONCLUSIONS: The use of m-hTERT promoter is not only useful in the regulation of therapeutic gene expression but also that replication-competent oncolytic adenovirus under the control of m-hTERT promoter may be a new promising tool for the treatment of human malignancies.

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Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy
Hiroshi Tazawa, Joe Hasei, Shuya Yano, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara
Cancers.2020; 12(2): 478. CrossRef
Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer
Hiroshi Tazawa, Shinji Kuroda, Joe Hasei, Shunsuke Kagawa, Toshiyoshi Fujiwara
International Journal of Molecular Sciences.2017; 18(7): 1479. CrossRef

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Therapeutics Approaches in the Treatment of Limited Small-Cell Lung Cancer: Joo Huyk Sohn, Joo Hang Kim; Cancer Res Treat. 2002;34(6):403-404. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.403

Abstract PDF: No abstract available.

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Phase II Study of Topotecan and Etoposide as Second-line Treatment in Chemotherapy-refractory Small-cell Lung Cancer: Chul Kim, Joo Hyuk Sohn, Joo Hang Kim, Se Kyu Kim, Young Sam Kim, Joon Chang, Jae Yong Cho; Cancer Res Treat. 2002;34(5):334-338. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.334

Abstract PDF

PURPOSE
Refractory small-cell lung cancer (SCLC) has a poor prognosis, and current salvage chemotherapy for refractory SCLC, such as CAV (cyclophosphamide, adriamycin, vincristine) or topotecan, has an unsatisfactory outcome, with a response rate and overall survival of less than 10% and 6 months, respectively. This phase II study evaluated the role of topotecan combined with etoposide in SCLC patients that have progressed, or relapsed, within 3 months following completion of the initial chemotherapy.
MATERIALS AND METHODS
Twenty-seven patients were entered into this study. Eligible patients had an ECOG performance status of less than, or equal to, 2, at least one bidimensionally measurable lesion and adequate end organ function. IV topotecan, 1.0 mg/m2/d for 5 consecutive days, and etoposide, 100 mg/m2/d through days 1 to 3, were administered every 3 weeks until disease progression or undue toxicity.
RESULTS
The major toxicity was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocy-topenia occurred in 14.2, 34.8, and 27.3% of cycles, respectively. There was no treatment-related death, and other non-hematologic toxicities were generally mild. Four patients achieved partial responses, with a response rate RR of 14.8%. The progression-free survival PFS ranged from 1 to 7 months, with a median of 2.0 months (95% confidence interval 1.22~2.78 months). Twenty-five patients died, with a median overall survival of 5.5 months (ranging from 1 to 21 months, 95% CI 4.32~6.68 months), and the 6-month survival rate was 32.1% (95% confidence interval 14.4~49.8%).
CONCLUSION
The combination of topotecan and etoposide chemotherapy showed a modest response rate, but failed to prolong survival of refractory SCLC patients compared to topotecan monotherapy.

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Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea
Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Lung Cancer: Targets and Therapy.2024; Volume 15: 149. CrossRef

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Evaluation of E1B-mutant Replicating Adenoviruses for Cancer Gene Therapy: Jae Sung Kim, Joo Hang Kim, Heui Ran Lee, Kyeong Cheon Jung, Chae Ok Yun; Cancer Res Treat. 2001;33(6):500-511. Published online December 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.6.500

Abstract PDF: PURPOSE
Gene-attenuated replication-competent adenoviruses are emerging as a promising new modality for the treatment of cancer. In an effort to continually improve upon cancer gene therapy, we have modified gene- attenuated replication-competent adenoviruses so as to cause them to replicate efficiently and lyse the infected cancer cells more effectively.
MATERIALS AND METHODS
We modified the E1 region of the adenovirus (Ad) systematically, generating Ad-deltaE1B19, Ad-deltaE1B55, Ad-deltaE1B19/55, and Ad-WT. The cytopathic effects (CPE) and viral replication of these four gene modified adenoviruses were compared, and the morphology and DNA fragmentation of the infected cells was evaluated.
RESULTS
Among the constructed adenoviruses, E1B 19kD-inactivated adenovirus (Ad-deltaE1B19) was the most potent, inducing the largest-sized plaques and markedCPE. Moreover, cells infected with Ad-deltaE1B19 showed complete cell lysis with disintegrated cellular structure whereas cells infected with Ad-WT maintained intact cellular and nuclear membrane with properly structured organelles. TUNEL assay was also used to monitor DNA integrity, and a more profound induction of apoptosis was observed in the Ad-deltaE1B19 infected cells in comparison to wild type adenovirus infected cells.
CONCLUSION
We demonstrate that the inactivation of the E1B19kD gene in a replicating adenovirus leads to increased CPE, rapid viral release, improved cell-to-cell viral spread and increased induction of apoptosis.

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Phase II clinical trial of recombinant human granulocyte colony-stimulating factor(fhG-CSF)(KRN8601) in advanced cancer patients with myelosuppression after chemotherapy: Jae Kyung Roh, Jin Hyuk Choi, Kyung Hee Lee, Hye Ran Lee, Nae Choon Yoo, Joo Hang Kim, Byung Soo Kim, Ho Young Lim; J Korean Cancer Assoc. 1993;25(5):725-735.

Abstract PDF: No abstract available.

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Prognostic Factors in Node - Negative Breast Cancer: Kyung Hee Lee, Hyun Cheol Chung, Jae Yong Cho, Sun Young Rha, Joong Bae Ahn, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Kyung Sik Lee, Kyl Beom Lee, Ho Yeong Lim, Jin Hy; J Korean Cancer Assoc. 1995;27(2):265-275.

Abstract PDF: Breast cancer is the third most common malignant neoplasm in Korean women. The effect of postoperative adjuvant systemic therapy in the treatment of primary breast cancer with pathologic involvement of the axillary lymph nodes has been well established. But, 20 30% of node-negative breast cancer patients will develop recurrent disease and risk death within 10 years after initial local therapy without adjuvant treatment. Therfore, it is reasonable to identify those node-negative breast cancer patients at significant risk for recurrence and who could be treated with adjuvant therapies. A clinical study was perofrmed in 184 cases of primary node-negative breast cancers from January 198l to December 1991 to study the natural course of the diaease and to find-out the prognostic factors. The following results were obtained; l) During 73 monthe(9-143) of follow-up duration, 5-year and 10-year relapse free survival rates were 88%, 77% respectively, and overall survival rates were 89%, 88%, respectively. 10 year recurrence rate was 19%. 2) Median disease-free and survival durations were 80 month, 17 months, respectively, in tumor size<2 cm group and 68.5 months, 62 months respectively in tumor size 2-5 cm group. 3) Median disease-free and overall survival durations were 73 months, 61 months, respectively, in premenopause patients and 74 months, 73 months in postmenopause patients. 4) No differences were found in disease-free and survival duration based on types of operation. 5) With adjuvant treatment, there was a decreasing tendency of systemic relapse. In conclusion, continuous relapse was found in node-negative breast cancer even after 5 years of operation. Even if decreasing tendency of systemic relapse was induced with adjuvant treatment, no clinically useful prognostic factors were found from surgical and pathologic factors until now. Further study of biological factors in node-negative breast cancer is warrented.

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Phase II trial of sequential VP-16, cisplatin combination chemotherapy and radiotherapy for locally advanced (stage III) non-small cell lung cancer: Hyun Cheol Chung, Jin Hyuk Choi, Yoon Seok Chung, Dong Jip Kim, Young Sik Lee, Joon Chang, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Sung Kyu Kim, Won Young Lee, Gwi Eon Kim; J Korean Cancer Assoc. 1991;23(1):131-139.

Abstract PDF: No abstract available.

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GEnetic Change in Transforming Growth Factor-B (TGF-B) Receptor Type I and Type II Genes with Resistance to TGF-B of Human Breast Cancer Cells: Hwa Young Lee, Sung Sil Jeon, Hyun Ja Kwon, Soo Jung Kong, Seon Young Rah, Joong Bae Ahn, Kwang Yong Sim, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Kyung Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Chul Chung; J Korean Cancer Assoc. 1998;30(4):683-691.

Abstract PDF: PURPOSE
Transforming growth factor-Bs (TGF-Bs) are prototypic multifunctional negative growth factors that inhibit the growth of many cell types. TGF-B type I and II receptors(RI, RII) are transmembrane receptors containing cytoplasmic serine/ threonine kinase domain and have been implicated in mediating TGF-B activity. Because a heteromeric complex of RI and RII is required for TGF-B signal transduction, cancer cells may reduce the expression of either RI or RII to escape from growth inhibition of TGF-B. We examined the correlation between the growth inhibitory activity of TGF-B1 and the genetic expression of RI &RII genes in human breast cancer cell lines.
MATERIALS AND METHODS
We examined the growth inhibitory activity of TGF-B1 in 5 breast cancer cell lines by incorporation of [3H] thymidine. To investigate the correlation between TGF-B1 insensitivity and genetic change of TGF-B receptor genes (RI, RII), Southem blot analysis, Northern blot analysis, and Western blot analysis were performed. We also examined whether microsatellite instability(RER) was associated with RII mutation.
RESULTS
We found that 3 breast cancer cell lines (MCF-7, YCC-B101, YCC-B151) were resistant to growth inhibitory effect of TGF-B1. MCF-7 cell line expressed no detectable RII mRNA and RII protein, but showed normal structure of RII gene and normal expression of RI gene. And we did not find any abnormal expression of mRNA, protein, and genetic structure of RI &RII in YCC-B101 and YCC-B151.
CONCLUSION
Our results suggest that aquired resistance to the growth inhibitory effect of TGF-B1> could be transcription regulation system of RII in MCF-7 cell line, and could be postreceptor signal transduction pathway in YCC-B101 and YCC-B151 cell lines.

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Phase II trial of 5-FU, etoposide, cisplatin (FEP) combination chemotherapy in unresectable non-small cell lung cancer: Jin Hyuk Choi, Hyun Cheol Chung, Dong Jip Kim, Je Yol Oh, Joon Chang, Eun Hee Koh, Joo Hang Kim, Jae Kyung Rho, Sung Kyu Kim, Won Young Lee, Gwi Eon Kim, John Kyu Loh Juhn; J Korean Cancer Assoc. 1991;23(1):120-130.

Abstract PDF: No abstract available.

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Expression and Significance of c-erbB-2 in Radically Resected Colorectal Cancer: Hyun Cheol Chung, Sun Young Rha, Joon Oh Park, Seung Hun Song, Jae Yong Cho, Jung Bae Aha, Hye Ran Lee, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sil Seong, Gwi Eon Kim, Jin Sik M; J Korean Cancer Assoc. 1995;27(3):389-403.

Abstract PDF: Overexpression of c-erbB-2 oncoprotein has been shown to correlate with poor prognosis and drug-resistance to the conventional chemotherapy with 5-fluorouracil in breast and gastric cancers. To evaluate the clinical significance of c-erbB-2 overexpreseion in colorectal cancer, immunohistochemical staining was performed with the paraffin-embedded tiasues of 141 colorectal cancer patients with curative surgery. The follow-up duration ranged from 7 to 61 months(median 30 months). Two-year disease- free and overall survival rate of the total patients were 77%, 91%, respectively. The c-erbB-2 positive rate was 24.8%, Even if patients with c-erbB-2 overexpression showed a tendency of poor prognosis than c-erbB-2 negative patients, T-factor and the TNM stage were independent prognostic factors in multivariate analysis. In subset analysis with c-erbB-2 negative patienta, there were no differences in recurrence rate and 2-year disease-free survival rate between pa- tients with chemotherapy and without chemotherapy(20.0% versus 26.1%)(80.0% versus 82.0%). However, in c-erbB-2 positive patients, those subgroup with chemotherapy showed tendencies toward advantages in relapse rate and 2-year disease-free survival rate than those of subgroup without chemotherapy(21.0% versus 50.0%; p=0.09)(76.0% versus 50.0%: p=0.06). Also, there was a tendency of increased time to relapse in patients with chemotherapy comparing to that of the patients without chemotherapy(7.5 months versus l7.0 months; p = 0.09). In stage III, patients with c-erbB-2 overexpression showed increased 2-year disease-free survival rate with chemotherapy as comparing to that of patients without chemotherapy(81.0% versus 29.0%; p= 0.003). Again, this survival benefit was not found in c-erbB-2 negative stage III patients regard- less of chemotherapy. In conclusion, c-erbB-2 overexyression might be a marker of relative drug resistance to 5-FU which will be converted with the high dose treatment of modulation with leucovorin. A prospective randomized trial is warrented to confirm this suggestion and for the clinical applica- tion of c-erbB-2 overexpression.

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The Efficacy and Safety of Docetaxel in Patients with Anthracychne pretreated Metastatic Breast Cancer: A Multicenter Phase II Study: Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hei Chul Jung, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Jin Hyuk Choi, Hyun Soo Kim, Hugh Chul Kim, Woo Kun Kim, Jae Kyung Roh; J Korean Cancer Assoc. 2000;32(2):235-243.

Abstract PDF: PURPOSE
Tbis phase II study was performed to evaluate the efficacy and safety of docetaxel in patients with anthracycline-pretreated metastatic breast cancer (MBC).
MATERIALS AND METHODS
From September 1996 to January 1998, 27 patients with metastatic breast cancer from 31 to 63 years of age with a performance status of 0 to 2 were registered in the phase II trial. All patients had metastatic breast cancer which had progressed or relapsed 2 during or after treatment with an anthracycline-based regimen. Docetaxel 75 mg/m2 was ad- ministered over 1 hour every 21 days until disease progression was documented or until toxic effects precluded further therapy. All patients received dexamethasone orally at the dose of 16 mg on days -1, 0, 1 of each cycle.
RESULTS
Objective responses were seen in 9 of 25 assessable patients (two complete and seven partial responses), with an overall objective response rale of 36%. The median duration of response was 36 weeks (range 19.0~40.5). The median time to progression and survival duration were 17.5 and 69 weeks, respectively, for assessable patients. One hundred fifty cycles (median, five) of docetaxel were administered. Among 27 patients assessable for toxicity, the following side effects were reported: nadir neutropenia grade 3 (4 patients) and grade 4 (22 patients); grade 2 stomatitis (6 patients); grade 2 alopecia (5 patients); grade 2 to 3 neurosensory toxicity (4 patients); no hypersensitivity reaction; mild fluid retention (4 patients).
CONCLUSION
Docetaxel is an active agent in patients with antracycline-pretreated metastatic breast cancer. Docetaxel was associated with severe but reversible neutropenia. Dexamethasone prevented hypersensitivity reactions and appeared to ameliorate fluid retention.

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Tumor - specific Virus Replication and Cytotoxicity of E1B 55 kD - deleted Adenovirus: Jaesung Kim, Boyoung Lee, Jinahn Kim, Joong Bae Ahn, Joon Oh Park, Nae Chun Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Heuiran Lee; J Korean Cancer Assoc. 2000;32(1):200-209.

Abstract PDF: PURPOSE
To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo.
MATERIALS AND METHODS
YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l.
RESULTS
PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1.
CONCLUSION
The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.

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A Phase 2 Clinical Trial of Recombinant Human Granulocyte Macrophage Colony Stimulatin: Sun Young Rha, Jae Kyung Roh, Kyung Hee Lee, Hyun Cheol Chung, Jong Inn Lee, Jin Hyuk Choi, Hye Ran Lee, Nae Chun Yoo, Joo Hang Kim, Dae Seog Heo, Jin Hyuk Choi, Ho Yeong Lim, Jee Sook Hahn, Byung So; J Korean Cancer Assoc. 1995;27(3):490-504.

Abstract PDF: Background
; Rh GM-CSF is known to stimulate the growth of granulocyte-macrophage pre- cursors and can prevent the neutropenia and infection after high dose chemotherapy. We planned to evaluate the efficacy and toxicities of rh GM-CSF and to determine the clinically recommended dose of yeast-derived rh GM-CSF(LBD-005), based on the biologicaily active doses from phase I clinical triaL Methods; Open non-randomized phase II study was carried out in 40 cancer patients with chemotherapy induced myelosuppression. After the control period(chemotherapy without rh GM-CSF), rh GM-CSF was started 24 hours after the second chemotherapy to 3 groups of patients with the doses of 150, 250, 350 ug/m(2)/d by once-daily subcutaneous admlnistration for 10 days. Resnlts; Of the 40 enrolled patients, two patients refused to be followed and. one patient couldn't finish the study due to the disease progression. So 37 patients were evaluable and the number of patients at the dose of 150, 250, 350 pg/m/d were 12, 12 and 13 petients, respectively. They were consisted of 12 with stomach cancers, 10 with breast cancers, 5 with osteosarcoma and 10 patients with other malignancies, and received chemotherapeutic agents like VP-16, cisplatinum, adriamycin. When we compared the hematologic parameters between the control and treatment periods, the mean nadir of WBC counts(/mm(3)) at the dose of 150ug/m(2)/d were 1480, 2085, each, l280, l997 at the dose of 250 ug/m/d, and 1091, 1788 at the dose of 350 ug/m(2)/d respectively. Also the recovery days of WBC counts from nadir to 4000/m(3) were improved from 8 days in control period to 4.7 days in treatment period at the dose of 150 ug/m(2)/d. There were the same results at the dose of 250 and 350 ug/m(2)/d, such as from 7.4 days to 4.4 days and from 8.5 days to 5.2 days, respectively. In view of neutrophils, we could find the same results(p<0.05). There are trends that the recovery from nadir at the dose of 250 ug/m(2)/d or more is rapid, rather than l50ug/m(2)/d. Two patients with 350ug/m(2)/d complained of severe (WHO toxicity grade III) skin reaction and chest tightness, but they tolerated well after reduction to 250 ug/m(2) /d dose. Conclasion; This study suggested the effects of yeast-derived rh GM-CSF with the dose of 1SO, 250, 350ug/m(2)/d, S.Q. for 10 days to prvent the chemotherapy induced neutropenia. And when we considered the efficacy and tolerability, 250 ug/m(2)/d is appropriate for phase III clinical triaL

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The role of combined induction chemotherapy and radical radiation therapy in the treatment of advanced nasopharyngeal cancer: Jin Hyuk Choi, Jae Kyung Roh, Ho Young Lim, Hyun Chul Jung, Nae Choon Yoo, Shin Ki Ahn, Eun Hee Koh, Joo Hang Kim, Chang Ok Seo, Kwi Un Kim, Joon Kyoo Roh, Byung Soo Kim; J Korean Cancer Assoc. 1993;25(3):403-416.

Abstract PDF: No abstract available.

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Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer: Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):464-474.

Abstract PDF: PURPOSE
Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer.
MATERIALS AND METHODS
The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years.
RESULTS
The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good.
CONCLUSION
Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.

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p53 gene mutation in hepatocellular carcinoma from Korean patients and in established hepatocellular carcinoma cell lines: Joo Hang Kim, Joo Bae Park, Mitsudomi Tetsuya, Jung Joo Choi, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Kyung Sik Lee, Byung Soo Kim; J Korean Cancer Assoc. 1993;25(3):359-367.

Abstract PDF: No abstract available.

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Efficacy of recombinant human granulocyte colony-stimulating factor(neutrogin) for chemotherapy induced neutropenia in patients with advanced lung carcinoma: Nae Choon Yoo, Joo Hang Kim, Yi Young Lee, Se Kyoo Kim, Sung Kyoo Kim, Won Young Lee, Bong Soo Cha, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1993;25(2):236-246.

Abstract PDF: No abstract available.

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Effects of verapamil, tamoxifen and cyclosporin A for the modulation of multidrug resistance in human lung cancer lines: Joo Hang Kim, Byung Soo Kim, Jung Joo Choi, Kyung Mi Kim, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Kyung Sik Lee, Byung Soo Kim; J Korean Cancer Assoc. 1993;25(2):225-235.

Abstract PDF: No abstract available.

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A Phase 3 Clinical Trial of Recombinant Human Granulocyte - Macrophage Colony Stimulating: Kyung Hee Lee, Sun Young Rha, Jae Kyung Roh, Jong In Lee, Hae Ran Lee, Jun Oh Park, Jae Woong Cho, Hyun Cheol Chung, Joo Hang Kim, Jee Sook Hahn, Yun Woong Ko, Byung Soo Kim, Ho Young Lim, Jin Hyuk Choi; J Korean Cancer Assoc. 1995;27(5):804-816.

Abstract PDF: Background
Recombinant human granulocyte-macrophage colony stimulating factor(rhGM- CSF, LBD-005) may reduce chemotherapy induced myelosuppression, and thus reduce the incidence of neutropenic fever and infection after the dose intensive chemotherapy. In previous phase I and II studies, clinical efficacies and side effects of rhGM-CSF were evaluated, and the dose of 250ug/m(2)/day for 10 consecutive days subcutaneous administration was recommended for the further clinical triaL Methods: In this phase III trial, we evaluated the efficacy and safety of rhGM-CSF in 35 advanced cancer pstients after combination chemotherapy. Every eligible patients received at least 2 cycles of chemotherapy with the same dose and schedule. At the first cycle, control period, scheduled chemotherapy was given without rhGM-CSF, and at the second cycle, treatment period, rhGM-CSF was administered for 10 consecutive days subcutaneously with the dose of 250u/m(2)/day after the same chemotherapy given previously. During observation and treatment period, clinical and pathoiogical effects were monitered. Resnlta: All enrolled 35 patients were evaluable, and 14 patients(40%) had stomach cancer. The hematologic parameters were compared between two periods; mean nadir of WBC(neutrophil) counts during the control period and treatment period were 1,154+-485/mm(3)(241/mm(3)+ 242) and 2,486+1,554/mm(3)(912+-1,186/mm(3)) respectively(P<0.0001). Also the recovery time of neutropenia was shortened(P<0.0001). Incidence of infection and the necessities of antibiotics administration were decreased(days of antibiotics adminiatration: 7 days during control period and 10 days during treatment period). Most petients showed mild, talerable toxicities like chest tightness and general malaise, except 2 patients with the reduced dose of 150 ug/m(2)/day due to grade II toxicities of chest tightness and abdominal pain. Conclnsion: Above results suggested that the administration of rhGM-CSF after chemotherapy can reduce the degree of neutropenia and the side effects of rhGM-CSF were acceptable.

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Semi - quantitative Comparison of Terminal Restriction Fragment Length and Telomerase in Breast Cancer for Biotherapy: Sun Young Rha, Kyu Hyun Park, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(2):231-241.

Abstract PDF: PURPOSE
We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment.
MATERIALS AND METHODS
We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting.
RESULTS
Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity.
CONCLUSION
In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.

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Efficacy of clodronate(ostac) on bone metastases in malignancy: Joo Hang Kim, Ho Young Lim, Nae Choon Yoo, Sun Young Rah, Jin Hyuk Choi, Eun Hee Koh, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1993;25(1):85-91.

Abstract PDF: No abstract available.

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Expression in Matrix - Metalloproteinases ( MMP-2 , MMP-9 ) in Gastric Cancer as new Targets for Biotherapy: Hyun Cheol Chung, Jae Yong cho, Sun Young Rha, Joon Oh Park, Joong Bae Ahn, Choong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeong Lim, Jin Hyu Choi; J Korean Cancer Assoc. 1995;27(6):897-907.

Abstract PDF: The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix-metalloproteinases (MMPs) and serine proteases. We measured the activities of MMP-9 and MMP-2 in the 120 normal and cancer tissue samples from the same patients using gelatin zymography. Inactive MMP-9(92 kD) was expressed in 73.3% of the normal and 87.5% of the cancer tissues, respectively (p=0.009), while active MMP-9(82 kD) was expressed in 24.2% and 53.3%, respectively (p=0.0001). Inactive MMP-2 (72kD) was expressed in 33.3% of the normal and 55.0% of the cancer tissues, respectively (p=0.001), while active MMP-2(62kD) was expressed in 4.2% and 31.7%, respectively (p=0.0001). In Tl state, only frequency of expression and enzymatic activity of the active MMP-2(62kD) were increased, while from T2 stage, the expression and the activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. The expression frequency of the MMP-9 was more common than of the MMP-2. The co-expression rate of the active forms (82 kD, 62 kD), activites of 82 kD and 62 kD, and the activation rates of the both MMPs were increased as the cancer invades and metastasizes to distant lymph node areas. In conclusion, MMP-2 activation was the main causes of the increased MMPs activity during the Tl phase of the gastric cancer, while production and activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. Therefore, we suggest that the different expression and activation of the MMPs in the gastric cancer progression can be a potential therapeutic target in gastric cancer biotherapy.

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Expression of Carcinoembryonic Antigen by Immunohistochemical Staining Method in Primary Male Breast Cancer: Hyun Cheol Chung, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Woo Ik Yang, Byung Soo Kim, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):440-451.

Abstract PDF: Carcinoembryonic antigen (CEA) immunohistochemistry was evaluated with 12 sections of male breast cancer diagnosed at Severance Hospital during the year of 1979-1990. Ten of twelve (83.3%) primary breast masses and four of five (80%) metastatic lymph nodes were CEA positive. There was concordance of CEA positivity and CEA positivity grade between primary mass and metastatic lymph nodes. The grade of CEA positivity did not appear to be related to size, tumor depth (T) and pathological stages. It was difficult to find a relationship between nuclear grade and CEA positive grade, because there was no nuclear grade 3 patient. Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region.

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