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Volume 37(3); June 2005
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Original Articles
High-Dose Chemotherapy of Cyclophosphamide, Thiotepa and Carboplatin (CTCb) followed by Autologous Stem-Cell Transplantation as a Consolidation for Breast Cancer Patients with 10 or more Positive Lymph Nodes: a 5-Year follow-Up Results
Hee-Jung Sohn, Sang-Hee Kim, Gyeong-Won Lee, Shin Kim, Jin-Hee Ahn, Sung-Bae Kim, Sang-We Kim, Woo Kun Kim, Cheolwon Suh
Cancer Res Treat. 2005;37(3):137-142.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.137
AbstractAbstract PDFPubReaderePub
Purpose

The benefit of consolidation high-dose chemotherapy (HDC) for high-risk primary breast cancer is controversial. We evaluated the efficacy and safety of consolidation HDC with cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) in resected breast cancer patients with 10 or more positive lymph nodes.

Materials and Methods

Between December 1994 and April 2000, 22 patients were enrolled. All patients received 2 to 6 cycles of adjuvant chemotherapy after surgery for breast cancer. The HDC regimen consisted of cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day and carboplatin 200 mg/m2/day intravenous for 4 consecutive days.

Results

With a median follow-up of 58 months, 11 patients recurred and died. The median disease-free survival (DFS) and median overall survival (OS) were 49 and 69 months, respectively. The 5-year DFS and OS rates were 50% and 58%, respectively. The 12 patients with 10 to 18 involved nodes had better 5-year DFS (67%) and OS (75%) than 10 patients with more than 18 involved nodes (30% and 38%, respectively). The most common grade 3 or 4 nonhematologic toxicity was diarrhea, which occurred in 5 patients (23%). No treatment-related death was observed.

Conclusion

Consolidation HDC with CTCb followed by ASCT for resected breast cancer with more than 10 positive nodes had an acceptable toxicity but does not show promising survival.

Citations

Citations to this article as recorded by  
  • Real-world Experience of Improvement in the Survival of Lymphoma and Myeloma Patients with Autologous Stem Cell Transplantation over a 25-year Period
    Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Jung Sun Park, Cheolwon Suh
    The Korean Journal of Medicine.2021; 96(6): 501.     CrossRef
  • Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45)
    X. Wang, J. Ren, J. Zhang, Y. Yan, N. Jiang, J. Yu, L. Di, G. Song, L. Che, J. Jia, X. Zhou, H. Yang, H. K. Lyerly
    Clinical and Translational Oncology.2016; 18(1): 82.     CrossRef
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The Surgeon's Expertise-Outcome Relationship in Gastric Cancer Surgery
Wansik Yu, Young Kook Yun, Ilwoo Whang, Gyu Seok Choi
Cancer Res Treat. 2005;37(3):143-147.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.143
AbstractAbstract PDFPubReaderePub
Purpose

The surgical caseload or duration of practice of a surgeon may influence the outcomes of gastric cancer surgery. This study aimed to clarify the surgical quality provided by specialized gastric cancer surgeons.

Materials and Methods

The postoperative courses of 1,877 patients who underwent surgery for gastric cancer were retrospectively reviewed. For classification of the surgeon's expertise, the number of yearly resections performed by, and consecutive years of practice of, the surgeons were used. The outcome measures used were the 30-day mortality and long-term survival.

Results

Surgical mortalities of patients who underwent surgery by a specialized surgeon and those by a general surgeon revealed no statistically significant difference. A significant difference in the five-year survival rates was found with surgeons with at least two consecutive years of practice compared to those with less than two years, when 50 or more cases had been conducted per year (63.9% and 59.7%; p=0.0380). In cases of four-years of consecutive practice, the five-year survival rate was significantly improved, even if only 10 cases were performed annually (64.9% and 58.3%; p=0.0023), although the best survival rate was found with surgeons that had performed 50 or more surgeries per year.

Conclusion

Improved survival rates, with acceptable surgical mortality, can be achieved for gastric cancer when the surgery is performed by a specialized surgeon. A specialized gastric cancer surgeon can be defined as one who has operated on more than 50 new cases per year, with 2 or more consecutive years of surgical practice.

Citations

Citations to this article as recorded by  
  • Lymphadenectomy for Gastric Cancer
    Jenny Hwang, Jacquelyn Carr
    Surgical Clinics of North America.2025; 105(1): 47.     CrossRef
  • Associations of Annual Hospital and Surgeon Volume with Patient Outcomes After Gastrectomy: A Systematic Review and Meta-analysis
    Jiafu Ji, Leiyu Shi, Xiangji Ying, Xinpu Lu, Fei Shan
    Annals of Surgical Oncology.2022; 29(13): 8276.     CrossRef
  • Keratinocyte cancer with incidental perineural invasion: A registry analysis of management and 5‐year outcomes
    Agnieszka Adams, Brian De’Ambrosis, Ben Panizza, Paul Belt, James Emmett, Tim Warren, David C. Whiteman
    Australasian Journal of Dermatology.2020; 61(3): 226.     CrossRef
  • Operation time as a simple indicator to predict the overcoming of the learning curve in gastric cancer surgery: a multicenter cohort study
    Tae-Han Kim, Keun Won Ryu, Jun Ho Lee, Gyu-Seok Cho, Woo Jin Hyung, Chan-Young Kim, Min-Chan Kim, Seung Wan Ryu, Dong Woo Shin, Hyuk-Joon Lee
    Gastric Cancer.2019; 22(5): 1069.     CrossRef
  • Are treatment outcomes in gastric cancer associated with either hospital volume or surgeon volume?
    Yosuke Mukai, Yukinori Kurokawa, Shuji Takiguchi, Masaki Mori, Yuichiro Doki
    Annals of Gastroenterological Surgery.2017; 1(3): 186.     CrossRef
  • Full robot-assisted gastrectomy: surgical technique and preliminary experience from a single center
    Yolanda Quijano, Emilio Vicente, Benedetto Ielpo, Hipolito Duran, Eduardo Diaz, Isabel Fabra, Luis Malave, Valentina Ferri, Antonio Ferronetti, Carlos Plaza, Vito D’Andrea, Riccardo Caruso
    Journal of Robotic Surgery.2016; 10(4): 297.     CrossRef
  • The positive impact of surgeon specialization on survival for gastric cancer patients after surgery with curative intent
    Yuexiang Liang, Liangliang Wu, Xiaona Wang, Xuewei Ding, Han Liang
    Gastric Cancer.2015; 18(4): 859.     CrossRef
  • Moderating Effect of Structural Complexity on the Relationship between Surgery Volume and in Hospital Mortality of Cancer Patients
    Kyungil Youn
    Health Policy and Management.2014; 24(4): 380.     CrossRef
  • Robot-Assisted Gastrectomy With Lymph Node Dissection for Gastric Cancer
    Jyewon Song, Sung Jin Oh, Wook Ho Kang, Woo Jin Hyung, Seung Ho Choi, Sung Hoon Noh
    Annals of Surgery.2009; 249(6): 927.     CrossRef
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Multidimensional Constructs of the EORTC Quality of Life Questionnaire (QLQ-C30) in Korean Cancer Patients with Heterogeneous Diagnoses
Eun-Hyun Lee, Mison Chun, Hee-Jung Wang, Ho Yeong Lim, Jin-Hyuk Choi
Cancer Res Treat. 2005;37(3):148-156.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.148
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study was to evaluate the multidimensional constructs of the EORTC Quality of Life Questionnaire (QLQ-C30) in patients with cancer, employing not only the commonly used multitrait scaling analysis and interscale correlations, but also the factorial and multidimensional scaling (MDS) analyses.

Materials and Methods

A total of 334 Korean cancer patients participated in this cross-sectional study. All patients completed the QLQ-C30.

Results

With the multitrait scaling analysis, the cognitive functioning scale did not meet item convergent and divergent validities. With the interscale correlations, the physical and role functioning scales were found to be highly correlated; this was also evident in the factorial analysis. The MDS showed that each item within the social, emotional, global health status/quality of life, and nausea/vomiting scales were clustered close together, but far from those of the other scales.

Conclusion

The authors conclude that the four way evaluation of the QLQ-C30 produced results that supported the original hypothesized constructs. However, the physical and role functioning scales were not distinctive, and that of the cognitive functioning was somewhat problematic in the Korean population with cancer.

Citations

Citations to this article as recorded by  
  • Validation of Gujarati Version of European Organization for Research and Treatment of Cancer Quality of Life Modules in Head and Neck Cancer Patients of Western India
    Sujal Parkar, Abhishek Sharma, Mihir Shah
    Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 2291.     CrossRef
  • Psychometric property of an instrument 1: content validity
    Eun-Hyun Lee
    Korean Journal of Women Health Nursing.2021; 27(1): 10.     CrossRef
  • Development of an Instrument to Assess the Nursing Professional Pride
    JaeHee Jeon, EunHee Lee, EunJoo Kim
    Journal of Korean Academy of Nursing.2020; 50(2): 228.     CrossRef
  • Reliability and Validity of the Arabic Version of the EORTC QLQ-C30 and QLQ-BR23 Questionnaires


    Ghufran Jassim, Ahmed AlAnsari
    Neuropsychiatric Disease and Treatment.2020; Volume 16: 3045.     CrossRef
  • Predictive Factors of Overall Well-Being Using the EORTC QLQ-C15-PAL Extracted from the EORTC QLQ-C30
    Kinsey Lam, Liang Zeng, Liying Zhang, Ling-Ming Tseng, Ming-Feng Hou, Alysa Fairchild, Vassilios Vassiliou, Reynaldo Jesus-Garcia, Mohamed A. Alm El-Din, Aswin Kumar, Fabien Forges PharmD, Wei-Chu Chie, Arjun Sahgal, Michael Poon, Edward Chow
    Journal of Palliative Medicine.2013; 16(4): 402.     CrossRef
  • Development and Validation of the Hospice Palliative Care Performance Scale
    So-Hi Kwon
    Journal of Korean Academy of Nursing.2011; 41(3): 374.     CrossRef
  • Translation and Validation of EORTC QLQ-C30 into Indonesian Version for Cancer Patients in Indonesia
    D. A. Perwitasari, J. Atthobari, I. Dwiprahasto, M. Hakimi, H. Gelderblom, H. Putter, J. W. R. Nortier, H.-J. Guchelaar, A. A. Kaptein
    Japanese Journal of Clinical Oncology.2011; 41(4): 519.     CrossRef
  • Psychometric Evaluation of a Need Scale for Cancer Patients Undergoing Follow-up Care
    Eun-Hyun Lee, Seongmi Moon, Soo-Yeon Cho, Young Taek Oh, Mison Chun, Sung Hwan Kim, Jae-Sung Kim, Hye Kyung Kim
    Journal of Korean Academy of Nursing.2010; 40(4): 551.     CrossRef
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Assessment of Tumor Regression by Consecutive Pelvic Magnetic Resonance Imaging and Dose Modification during High-Dose-Rate Brachytherapy for Carcinoma of the Uterine Cervix
Taek-Keun Nam, Byung-Sik Nah, Ho-Sun Choi, Woong-Ki Chung, Sung-Ja Ahn, Seok-Mo Kim, Ju-Young Song, Mi-Seon Yoon
Cancer Res Treat. 2005;37(3):157-164.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.157
AbstractAbstract PDFPubReaderePub
Purpose

To assess tumor regression, as determined by pelvic magnetic resonance imaging (MRI), and evaluate the efficacies and toxicities of the interim brachytherapy (BT) modification method, according to tumor regression during multi-fractionated high-dose-rate (HDR) BT for uterine cervical cancer.

Materials and Methods

Consecutive MRI studies were performed pre-radiotherapy (RT), pre-BT and during interfraction of BT (inter-BT) in 69 patients with cervical cancer. External beam radiotherapy (EBRT) was performed, using a 10 MV X-ray, in daily fraction of 1.8 Gy with 4-fields, 5 d/wk. Radiation was delivered up to 50.4 Gy, with midline shielding at around 30.6 Gy. Of all 69 patients, 50 received modified interim BT after checking the inter-BT MRI. The BT was delivered in two sessions; the first was composed of several 5 Gy fractions to point A, twice weekly, using three channel applicators. According to the three measured orthogonal diameters of the regressed tumor, based on inter-BT MR images, the initial BT plan was modified, with the second session consisting of a few fractions of less than 5 Gy to point A, using a cervical cylinder applicator.

Results

The numbers of patients in FIGO stages Ib, IIa, IIb and IIIb+IVa were 19 (27.5%), 18 (26.1%), 27 (39.2%) and 5 (7.2%), respectively. Our treatment characteristics were comparable to those from the literatures with respect to the biologically effective dose (BED) to point A, rectum and bladder as reference points. In the regression analysis a significant correlation was observed between tumor regression and the cumulative dose to point A on the follow-up MRI. Nearly 80% regression of the initial tumor volume occurred after 30.6 Gy of EBRT, and this increased to 90% after an additional 25 Gy in 5 fractions of BT, which corresponds to 73.6 Gy of cumulative BED10 to point A. The median total fraction number, and those at the first and second sessions of BT were 8 (5~10), 5 (3~7) and 3 (1~5), respectively. The median follow-up time was 53 months (range, 9~66 months). The 4-year disease-free survival rate of all patients was 86.8%. Six (8.7%) patients developed pelvic failures, but major late complications developed in only two (2.9%).

Conclusion

Our study shows that effective tumor control, equivalent survival and low rates of major complications can be achieved by modifying the fraction size during BT according to tumor regression, as determined by consecutive MR images. We recommend checking the follow-up MRI at a cumulative BED10 of around 65 Gy to point A, with the initial BT modified at a final booster BT session.

Citations

Citations to this article as recorded by  
  • Correlations of UICC tumor stage and tumor regression on T2-weighted MRI sequences during definitive radiotherapy of cervical cancer
    Florian Arend, Markus Oechsner, Clara B. Weidenbächer, Stephanie E. Combs, Kai J. Borm, Marciana N. Duma
    Tumori Journal.2021; 107(2): 139.     CrossRef
  • Target volume changes through high-dose-rate brachytherapy for cervical cancer when evaluated on high resolution (3.0 Tesla) magnetic resonance imaging
    Wenqing Sun, Sudershan K. Bhatia, Geraldine M. Jacobson, Ryan T. Flynn, Yusung Kim
    Practical Radiation Oncology.2012; 2(4): e101.     CrossRef
  • Metabolic Response of Lymph Nodes Immediately After RT Is Related With Survival Outcome of Patients With Pelvic Node-Positive Cervical Cancer Using Consecutive [18F]fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography
    Mee Sun Yoon, Sung-Ja Ahn, Byung-Sik Nah, Woong-Ki Chung, Ho-Chun Song, Su Woong Yoo, Ju-Young Song, Jae-Uk Jeong, Taek-Keun Nam
    International Journal of Radiation Oncology*Biology*Physics.2012; 84(4): e491.     CrossRef
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  • 3 Crossref
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Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors
Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung
Cancer Res Treat. 2005;37(3):165-170.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.165
AbstractAbstract PDFPubReaderePub
Purpose

Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features.

Materials and Methods

We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression.

Results

The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression.

Conclusion

This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.

Citations

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    Zhongqi Liu, Shi Cheng, Ganglan Fu, Fengtao Ji, Chengli Wang, Minghui Cao
    Life Sciences.2020; 251: 117604.     CrossRef
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    Joyce L. Moraes, Amanda B. Moraes, Veronica Aran, Marcelo R. Alves, Luciene Schluckbier, Mariana Duarte, Edson Toscano, Mauro Zamboni, Cinthya Sternberg, Emanuela de Moraes, José R. Lapa E Silva, Carlos Gil Ferreira
    Molecular and Clinical Oncology.2017; 6(4): 494.     CrossRef
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    Nurul Akmar Misron, Lai-Meng Looi, Nik Raihan Nik Mustapha
    Asian Pacific Journal of Cancer Prevention.2015; 16(4): 1553.     CrossRef
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    Justyna Urban, Łukasz Kuźbicki, Grzegorz Szatkowski, Agata Stanek-Widera, Dariusz Lange, Barbara W Chwirot
    BMC Cancer.2014;[Epub]     CrossRef
  • Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients
    Isabel Sicking, Karlien Rommens, Marco J Battista, Daniel Böhm, Susanne Gebhard, Antje Lebrecht, Cristina Cotarelo, Gerald Hoffmann, Jan G Hengstler, Marcus Schmidt
    BMC Cancer.2014;[Epub]     CrossRef
  • 10,068 View
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  • 5 Crossref
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Co-Expression of Cox-2, C-Met and β-catenin in Cells Forming Invasive front of Gallbladder Cancer
Woo Sung Moon, Ho Sung Park, Ho Lee, Rama Pai, Andrzej S. Tarnawski, Kyung Ryoul Kim, Kyu Yun Jang
Cancer Res Treat. 2005;37(3):171-176.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.171
AbstractAbstract PDFPubReaderePub
Purpose

Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E2 (PGE2), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and β-catenin; thus, enhancing colon cancer cell growth and invasiveness in vitro. To determine whether these findings are applicable to clinical conditions, we examined the expression and cellular localization/co-localization of Cox-2, c-Met, β-catenin, EGFR and c-erbB2 in gallbladder cancer.

Materials and Methods

Thirty-five specimens of invasive gallbladder cancer, 8 in situ carcinoma and 7 adenoma specimens were immunostained with specific antibodies against Cox-2, c-Met, β-catenin, EGFR and c-erbB2. The cellular distribution, localization and colocalization were examined, and the signal intensities quantified in: a) the central area of gallbladder cancer and b) cancer cells forming the invasive front.

Results

Cox-2, c-Met, β-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. β-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and β-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co-expressions of Cox-2, c-Met, β-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front.

Conclusion

The overexpressions, and often co-localizations, of Cox-2, c-Met and β-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion.

Citations

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    Biochemical Pharmacology.2020; 172: 113745.     CrossRef
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    Eric I Marks
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    Amani Kazem, Khaled El Sayed, Yasser El Kerm
    Alexandria Journal of Medicine.2014; 50(3): 211.     CrossRef
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    S.G. Barreto, A. Dutt, A. Chaudhary
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    Takamitsu Sasaki, Kuniyasu Hiroki, Yuichi Yamashita
    BioMed Research International.2013; 2013: 1.     CrossRef
  • Significance of epithelial growth factor in the epithelial–mesenchymal transition of human gallbladder cancer cells
    Takamitsu Sasaki, Hiroki Kuniyasu, Yi Luo, Daisuke Kato, Satoshi Shinya, Kiyomu Fujii, Hitoshi Ohmori, Yuichi Yamashita
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    A. Martínez, M.L. Spencer, J. Borlando, M. Flores, I.G. Rojas
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Intensity of Tumor Budding as an Index for the Malignant Potential in Invasive Rectal Carcinoma
Sang-Sik Ha, Hong-Jo Choi, Ki-Jae Park, Jung-Min Kim, Sung-Heun Kim, Young-Hoon Roh, Hyuk-Chan Kwon, Mee-Sook Roh
Cancer Res Treat. 2005;37(3):177-182.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.177
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential.

Materials and Methods

Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately-differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12~108).

Results

Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5±5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2±5.0 vs. 10.2±4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0±3.4 vs. 11.9±5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease-free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively).

Conclusion

Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.

Citations

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Synergistic Effect of Ionizing Radiation and β-lapachone against RKO Human Colon Adenocarcinoma Cells
Eun Jung Kim, In-Mi Ji, Ki-Jung Ahn, Eun Kyung Choi, Heon-Jin Park, Byung Uk Lim, Chang W. Song, Heon Joo Park
Cancer Res Treat. 2005;37(3):183-190.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.183
AbstractAbstract PDFPubReaderePub
Purpose

To reveal the interaction between β-Lapachone (β-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined β-lap treatment and radiotherapy for cancer treatment.

Materials and Methods

The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice.

Results

β-lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in β-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that β-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation-induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with β-lap. The combination of β-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors.

Conclusion

β-lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. β-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against caner cells.

Citations

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Enhancement of Radiation Effects by Flavopiridol in Uterine Cervix Cancer Cells
Suzy Kim, Hong-Gyun Wu, Jin Hee Shin, Hye Jin Park, In Ah Kim, Il Han Kim
Cancer Res Treat. 2005;37(3):191-195.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.191
AbstractAbstract PDFPubReaderePub
Purpose

To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line.

Materials and Methods

Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone.

Results

The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation.

Conclusion

Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.

Citations

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    Uttam Singh Baghel, Priyanka Kriplani, Neelam M. Patel, Manpreet Kaur, Kapil Sharma, Monika Meghani, Abhay Sharma, Deeksha Singh, Bhawani Singh, William N. Setzer, Javad Sharifi-Rad, Daniela Calina
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    Hyun-Gyo Lee, Jong-Woo Baek, So-Jin Shin, Sang-Hoon Kwon, Soon-Do Cha, Won-Jin Park, Rosa Chung, Eun-Som Choi, Gun-Ho Lee, Chi-Heum Cho
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    Suzy Kim
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Correlative Effect between in vivo Hollow Fiber Assay and Xenografts Assay in Drug Screening
Keyong Ho Lee, Ki Hyeong Rhee
Cancer Res Treat. 2005;37(3):196-200.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.196
AbstractAbstract PDFPubReaderePub
Purpose

This study was carried out to assess the usage of an in vivo hollow fiber assay to screen drugs with highly predictive accuracy.

Materials and Methods

The assay systems used were the hollow fiber and xenografts assays. The hollow fiber assay was carried out with the following steps; preparation of fibers, preparation of cells, loading and implanting fibers, treatment with drugs, removal of fibers and assaying for the cell viability by the MTT assay. For the xenografts assay, cell suspensions were subcutaneously transplanted into the mice. Therapy was started when the tumor volume reached 100~200 mm3. The tumor volumes were calculated using the formula V=[length+(width)2]/2, and used for evaluating the efficacy of the drugs. The drug treatment doses used were adriamycin 2.1 mg/kg, mitomycin-C 0.25 mg/kg, 5-fluorouracil 24.5 mg/kg and paclitaxel 2.5 mg/kg, and administrated intravenously five times daily.

Results

The correlation between the xenografts and hollow fiber assays was evaluated in 20 tumor cell lines and 4 anti-cancer agents. In the 20 tumor cell lines, the overall predictive accuracy of the hollow fiber assay for sensitivity was 83%, with a predictive accuracy for resistance of 92%.

Conclusion

The hollow fiber assay was assessed as effective in drug efficacy evaluation, and found to be compatible with that of the xenografts assay.

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