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Volume 35(3); June 2003
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Editorial
Cancer Gene Therapy: Limitations and Progress
Dae Seog Heo
Cancer Res Treat. 2003;35(3):175-176.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.175
AbstractAbstract PDF
No abstract available.

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  • Advances of Nanomaterials in Cancer Photocatalysis Therapy
    Songhua Ma, Linxuan Jiang, Wenjie Yang, Fan Liu, Devin Wang, Feng Wang, Jun Huang
    Materials Today Sustainability.2025; 29: 101023.     CrossRef
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Review Article
Treatment of Small Cell Lung Cancer
Atsushi Horiike, Nagahiro Saijo
Cancer Res Treat. 2003;35(3):177-180.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.177
AbstractAbstract PDF
Among patients with lung cancer, approximately 15% have small cell lung cancer (SCLC), SCLC is usually staged as either limited and extensive. Extensive-stage SCLC is treated primarily with chemotherapy. A recent Japanese randomized trial compared cisplatin and irinotecan (IP) with cisplatin and etoposide (EP). Patients in the IP arm did significantly better than patients in the EP arm. In the IP arm, the response rate was 84%, and the median overall survival period was 12.8 months. Limited- stage SCLC is usually treated with concurrent chemotherapy and accelerated radiation therapy, and approximately 20% of patients are cured. Future research should focus on optimizing chemotherapy regimens and radiation therapy schedules. The role of molecular targeted drugs in the treatment of SCLC must also be evaluated.
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Original Articles
Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo
Su Mi Bae, Yong Wook Kim, Joo Hee Yoon, Jin Young Yoo, Young Seok Seo, Sang Lyun Nam, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Yong Wan Kim, Woong Shick Ahn
Cancer Res Treat. 2003;35(3):181-190.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.181
AbstractAbstract PDF
PURPOSE
Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns.
CONCLUSION
The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.

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  • Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated Tumor
    Eun-Kyung Park, Young-Wook Kim, Joon-Mo Lee, Sung-Eun NamKoong, Do-Gang Kim, Heung-Jae Chun, Byoung-Don Han, Su-Mi Bae, Hyun-Sun Jin, Jeong-Im Sin, Woong-Shick Ahn
    Cancer Research and Treatment.2005; 37(1): 63.     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
AbstractAbstract 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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Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer: Role as Therapeutic Target
Kyung Hee Lee, Myung Soo Hyun, Jae Ryong Kim
Cancer Res Treat. 2003;35(3):207-212.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.207
AbstractAbstract PDF
PURPOSE
Increased expression of the hepatocytes growth factor (HGF) receptor (c-Met) and urokinase type plasminogen activator (uPA) correlate with the development and metastasis of cancers. However, the mechanisms by which HGF/c-Met signaling mediate cancer progression and metastasis are unclear. Therefore, we investigated the roles of HGF/c-Met in tumor progression and metastasis in pancreatic cancer cell lines, L3.6PL and IMIN-PC2. MATERIALS AND METHODS: To see the functional c-Met protein, we were performed immunoprecipitation for functional c-Met protein. And also performed western bolot analysis and gel zymography for the functional uPA protein. To see the inhibition effects of uPAR monoclonal antibody on invasiveness of two pancreatic cancer cell lines, we were carried out standard two chamber invasion assay. RESULTS: At first, we observed the HGF-mediated c-Met phosphorylation and cell growth. c-Met phosphorylation was increased in the HGF-treated cells in a dose dependent manner. HGF resulted in increments of cell growth and ERK phosphorylation. HGF treatment increased the uPA expression and the uPA activity. A monoclonal antibody 3936, specific to uPAR receptor, inhibited HGF- mediated tumor cell invasion in a dose dependent manner.
CONCLUSION
These results suggest that functional c- Met and HGF/c-Met signaling up-regulate the activity of uPA and result in increments of invasion-metastasis in the pancreatic cancer cells.

Citations

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  • PP2A complex disruptor SET prompts widespread hypertranscription of growth-essential genes in the pancreatic cancer cells
    He Xu, Di Wu, Mingming Xiao, Yubin Lei, Yalan Lei, Xianjun Yu, Si Shi
    Science Advances.2024;[Epub]     CrossRef
  • Reactive oxygen species regulate the generation of urokinase plasminogen activator in human hepatoma cells via MAPK pathways after treatment with hepatocyte growth factor
    Kyung Hee Lee, Jae-Ryong Kim
    Experimental and Molecular Medicine.2009; 41(3): 180.     CrossRef
  • Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells
    Kyung Hee Lee, Sang Woon Kim, Jae-Ryong Kim
    Journal of Experimental & Clinical Cancer Research.2009;[Epub]     CrossRef
  • Cellular Mechanisms of Hepatocyte Growth Factor-Mediated Urokinase Plasminogen Activator Secretion by MAPK Signaling in Hepatocellular Carcinoma
    Kyung Hee Lee, Eun Young Choi, Myung Soo Hyun, Jong Ryul Eun, Byung Ik Jang, Tae Nyeun Kim, Heon Ju Lee, Dong Shik Lee, Sung Su Yun, Hong Jīn Kim, Jung Hye Kim, Jae-Ryong Kim
    Tumori Journal.2008; 94(4): 523.     CrossRef
  • Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells
    K.H. Lee, E.Y. Choi, M.S. Hyun, B.I. Jang, T.N. Kim, S.W. Kim, S.K. Song, J.H. Kim, J.-R. Kim
    European Surgical Research.2007; 39(4): 208.     CrossRef
  • Hepatocyte Growth Factor/c-Met Signaling in Regulating Urokinase Plasminogen Activator in Human Stomach Cancer: A Potential Therapeutic Target for Human Stomach Cancer
    Kyung Hee Lee, Eun Young Choi, Myung Soo Hyun, Byung Ik Jang, Tae Nyeun Kim, Sang Woon Kim, Sun Kyo Song, Jung Hye Kim, Jae-Ryong Kim
    The Korean Journal of Internal Medicine.2006; 21(1): 20.     CrossRef
  • Expression of E-Cadherin and uPA and their Association with the Prognosis of Pancreatic Cancer
    Sang Joon Shin, Kyeong Ok Kim, Min Kyoung Kim, Kyung Hee Lee, Myung Soo Hyun, Keuk Jun Kim, Joon Hyuk Choi, Hong Seok Song
    Japanese Journal of Clinical Oncology.2005; 35(6): 342.     CrossRef
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Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study
Jung Hye Choi, Myung Ju Ahn, Seock Ah Im, Bong Seog Kim, Ho Suk Oh, Heung Woo Lee, Yeung Chul Mun, Chu Myung Seong, Soon Nam Lee, Young Yeul Lee, Il Young Choi, In Soon Kim
Cancer Res Treat. 2003;35(3):213-217.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.213
AbstractAbstract PDF
PURPOSE
Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS: Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement.
RESULTS
Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION: This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients.
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Prognostic Effect of Vascular Endothelial Growth Factor and Angiogenesis in Gastric Carcinoma
Myoung Im Kim, Si Young Kim, Jae Jin Lee, Hwi Joong Yoon, Yoon Wha Kim, Kyung Sam Cho
Cancer Res Treat. 2003;35(3):218-223.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.218
AbstractAbstract PDF
PURPOSE
Many studies have shown that angiogenesis has an important role in the growth, progression, and metastasis of solid tumors. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, we investigated the prognostic significance of the expression of VEGF in patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Specimens from 54 gastric adenocarcinoma patients were stained using a polyclonal antibody against VEGF. Correlations of the expression of VEGF, microvessel density, and various other clinicopathological factors were analysed. RESULTS: Seventeen (31.5%) and 37 cases (68.5%) were VEGF-negative and positive, respectively. There was significant correlation between the expression of VEGF and pathological differentiation. There were no significant correlations between the expression of VEGF, stage and recurrence of a gastric carcinoma. The microvessel density was significantly higher in the VEGF-positive than the VEGF-negative tumors. Survivals of the VEGF-negative patients were significantly prolonged compared to those of the VEGF-positive patients. CONCLUSION: The results of this study show that the expression of VEGF may be a useful prognostic factor for patients with a gastric adenocarcinoma.

Citations

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  • RETRACTED ARTICLE: KRAS activation in gastric cancer stem-like cells promotes tumor angiogenesis and metastasis
    Changhwan Yoon, Jun Lu, Yukyung Jun, Yun-Suhk Suh, Bang-Jin Kim, Jacob E. Till, Jong Hyun Kim, Sara H. Keshavjee, Sandra Ryeom, Sam S. Yoon
    BMC Cancer.2023;[Epub]     CrossRef
  • Vascular Endothelial Growth Factor Gene Polymorphisms Associated with Prognosis for Patients with Colorectal Cancer
    Jong Gwang Kim, Yee Soo Chae, Sang Kyun Sohn, Yoon Young Cho, Joon Ho Moon, Jae Yong Park, Seoung Woo Jeon, In Taek Lee, Gyu Seog Choi, Soo-Han Jun
    Clinical Cancer Research.2008; 14(1): 62.     CrossRef
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Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer
Jin Hyung Kang, Yoo Lim Kim, Hea Kyoung Cho, Eun Sook Lee, Soo Jin Cha, Young Sun Hong, Kyung Shik Lee, Hyo Jeong Kuh
Cancer Res Treat. 2003;35(3):224-231.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.224
AbstractAbstract PDF
PURPOSE
Tegafur, an oral prodrug of 5-fluorouracil (5-FU), has been used in the treatment of gastric cancers. UFT (tegafur + uracil) has been developed to enhance the efficacy of tegafur. This study was conducted to assess the pharmacokinetics (PK) of tegafur in gastric cancer patients given the ECU-E regimen (epirubicin, cisplatin, UFT-E, an enteric-coated formula of UFT). A preliminary evaluation of antitumor efficacy and toxicity of ECU-E regimen was also performed. MATERIALS AND METHODS: Of the 32 gastric cancer patients registered for the ECU-E regimen, 8 participated in the PK study. The plasma concentration of tegafur was determined using HPLC. RESULTS: Seven out of the 8 patients were evaluable for response after 2 cycles, and showed 3 partial responses, 1 stable disease and 3 progressive diseases. No major toxicities were observed. Plasma profiles of the tegafur after the first dose showed significant differences in the amount and rate of absorption, i.e., rapid absorption group vs. slow absorption group. The level of C(max) in the rapid absorption group was 1.8 fold higher, and the AUC(0-5h) 4 fold greater, than those in the slow absorption group, nonetheless, the steady state concentrations showed no significant difference. These data indicate that the different absorption rates may not affect the overall exposure to tegafur. The patients with low Cp(ss, peak) showed poor efficacy compared to those with high Cp(ss, peak), suggesting that the concentration of tegafur may be one of the pharmacodynamic determinants in patients administered with ECU-E. CONCLUSION: This study evaluated the pharmacokinetics of tegafur in gastric patients given the ECU-E regimen, and provides preliminary data on the relationship between the plasma tegafur level and the efficacy, which warrants further evaluation.
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FDG-PET in Mediastinal Nodal Staging of Non-small Cell Lung Cancer: Correlation of False Results with Histopathologic Finding
Hee Jong Baek, Jin Haeng Chung, Jong Ho Park, Jae Ill Zo, Gi Jeong Cheon, Chang Woon Choi, Sang Moo Lim, Soo Yong Choi, Jong Myeon Hong, Jang Soo Hong
Cancer Res Treat. 2003;35(3):232-238.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.232
AbstractAbstract PDF
PURPOSE
Mediastinal staging of non-small cell lung cancer can be markedly improved by FDG-PET scan, but the problem of false staging of mediastinal nodes by PET scan in non-small cell lung cancer has not yet been overcome. The aim of this study was to identify the mechanism underlying the false staging of mediastinal nodes by FDG-PET in the case of non-small cell lung cancer. MATERIALS AND METHODS: To evaluate the factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was performed in 62 patients with NSCLC. GLUT-1 expression was studied by immunohistochemistry of the mediastinal nodes (n=111, true positive 31, true negative 41, false positive 27, false negative 12) using the anti-GLUT-1 antibody. The size, percentage of tumor (tumor ratio), labeling index (rate of stained tumor), staining intensity of the tumor, level of follicular hyperplasia, and staining intensity of the follicle center in the mediastinal node were also studied. RESULTS: There was no significant difference in size among the 4 nodal groups (TP, TN, FP, FN), nor in the tumor ratio of the metastatic nodes between the TP and FN groups. The labeling index and staining intensity of the TP group were higher than those of the FN group (Mann-Whitney test, p=.001, p=.007) in the case of the metastatic nodes. The level of follicular hyperplasia of the FP group was higher than that of the TN group in the case of the non-metastatic nodes (p=.000). CONCLUSION: These results suggest that in mediastinal staging of non-small cell lung cancer by FDG-PET, the FN node is associated with low uptake of FDG due to low expression of GLUT-1, and that the FP node is associated with a high level of follicular hyperplasia as a result of there being a reactive change to an inflammatory and/or immune reaction. This is the first report on the mechanism underlying the false results that are sometimes obtained, and which constitute a major problem in the clinical application of FDG-PET to the mediastinal staging of non-small cell lung cancer.

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  • Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer
    Hongsik Kim, Song-Yi Choi, Tae-Young Heo, Kyeong-Rok Kim, Jisun Lee, Min Young Yoo, Taek-Gu Lee, Joung-Ho Han
    World Journal of Clinical Cases.2024; 12(5): 931.     CrossRef
  • Associations between GLUT expression and SUV values derived from FDG-PET in different tumors—A systematic review and meta analysis
    Hans-Jonas Meyer, Andreas Wienke, Alexey Surov, Pankaj K Singh
    PLOS ONE.2019; 14(6): e0217781.     CrossRef
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A Phase II Study of Paclitaxel and Cisplatin Combination Chemotherapy in Advanced Non-small-cell Lung Cancer
Jung Ae Lee, Keun Seok Lee, Jin Seok Ahn, Jae Ho Byun, Hun Ho Song, Dae Young Zang, Young Iee Park, Young Suk Park, Eun Kyung Mo, Dong Kyu Kim, Myung Goo Lee, In Gyu Hyun, Ki Suck Jung, Soo Mee Bang, Gye Young Park, Jeong Woong Park, Eun Kyung Cho, Seong Hwan Jeong, Dong Bok Shin, Jae Hoon Lee
Cancer Res Treat. 2003;35(3):239-244.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.239
AbstractAbstract PDF
PURPOSE
Paclitaxel and cisplatin, active drugs in the treatment of non-small-cell lung cancer (NSCLC), have been found to be synergistic and less myelotoxic in combination when the paclitaxel is given 24 hr prior to the cisplatin. Their antitumor activity and toxicity in patients with advanced NSCLC has been evaluated herein. MATERIALS AND METHODS: Seventy-four chemonaive patients, with advanced NSCLC, were enrolled. Paclitaxel, 175 mg/m2, was administered on day 1, followed 24 hr later by cisplatin, 75 mg/m2, on day 2. RESULTS: The overall response rate, median time to progression and median survival time were 51%, 7.1 months (95% confidence interval (CI), 5.5~8.7 months) and 13.7 months (95% CI, 11.3~16.1 months), respectively. There were significant differences in the overall survival rates in relation to stage and the ECOG performance status(PS). The toxicity was mainly nonhematological. Grade > or =3 neuropathy occurred in 2 (3%) patients, myalgia in 3 (4%), and bone pain in 3 (4%). The hematological toxicity was mild, and no grade 3 or 4 neutropenia was observed.
CONCLUSION
The combination of paclitaxel and cisplatin is an effective and tolerable treatment regimen for advanced NSCLC during first line chemotherapy. The main toxicity was nonhematological, such as peripheral neuropathy, myalgia and bone pain, whereas the hematological toxicity itself was mild.

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  • The Efficacy and Safety of Padexol® (Paclitaxel) and Cisplatin for Treating Advanced Non-small Cell Lung Cancer
    Hoon-Kyo Kim, Jun Suk Kim, Hun Mo Ryoo, Dong Gun Shin, Byoung Young Shim, Kyong Hwa Park, Sung Hwa Bae, Chi Hong Kim
    Cancer Research and Treatment.2006; 38(2): 66.     CrossRef
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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
AbstractAbstract 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.

Citations

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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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Detection of p16(INK4A) in the Mixed Cell Populations of Normal Peripheral Blood Mononuclear Cells and Cervical Cancer Cell Lines
Ji Young Kwon, Yoon Sung Jo, Ye Hoon Choi, Jong Gyu Chang, Ki Sung Ryu, Jong Gu Rha, Ku Taek Han
Cancer Res Treat. 2003;35(3):254-260.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.254
AbstractAbstract PDF
PURPOSE
Human papilloma viruses (HPVs) play a central role in the pathogenesis of neoplastic lesions of the uterine cervix. The viral oncoprotein HPV E6 degrades the p53 protein, and the HPV E7 protein inactivates pRB and increases the expression of the CDK inhibitor, p16(INK4A). We investigated the usefulness of p16(INK4A) as a biologic marker for the cervical dysplastic and neoplastic cells.
MATERIALS AND METHODS
We examined the expression of p16(INK4A) and cytokeratin in a mixed population of normal peripheral blood mononuclear cells (PBMC) and the cervical cancer cell lines (HeLa, SiHa, and CasKi) using flow cytometry. RESULTS: The DNA indices of the HeLa, SiHa and CasKi cell lines were 1.89, 1.53 and 1.75, respectively, indicating that these cells are aneuploid cells. Furthermore, the positive rate of p16(INK4A) expression was 86.7% for the HeLa mixed population, 85.6% for the SiHa mixed population, and 92.2% for the CasKi mixed population. According to the FL3A vs FL3W histogram, electrical gating of the HeLa, SiHa and CasKi mixed populations showed the expression levels of both cytokeratin and p16(INK4A) to be identical, at 86.6%, 84.8% and 85.0%, respectively. These findings revealed that almost all cells selected through electrical gating were cervical cancer cells originating from the epithelium and which expressed cytokeratin and p16(INK4A). On the other hand, when each mixed population was electrically gated for normal PBMC, we found that the PBMCs expressed neither cytokeratin nor p16(INK4A).
CONCLUSION
Using flow cytometry, we observed the enhanced expression of p16(INK4A) in cervical cancer cell lines. These RESULTS suggest the usefulness of p16(INK4A) for the selective detection of cervical dysplastic and cancer cells in the liquid-based samples, which are taken from the cervices and contaminated with blood and stromal cells.

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  • 2-Methoxyestradiol: A Hormonal Metabolite Modulates Stimulated T-Cells Function and proliferation
    J.G.Y. Luc, R. Paulin, J.Y. Zhao, D.H. Freed, E.D. Michelakis, J. Nagendran
    Transplantation Proceedings.2015; 47(6): 2057.     CrossRef
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Docetaxel and Cisplatin Combination Chemotherapy in Patients with Squamous Cell Carcinomas of the Head and Neck
Jung Hyun Lee, Kyung Woo Lee, Young Jin Choi, Jae Hoon Choi, Ho Jin Shin, Joo Seop Chung, Goon Jae Cho, Byung Ju Lee, Soo Geun Wang
Cancer Res Treat. 2003;35(3):261-266.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.261
AbstractAbstract PDF
PURPOSE
The objective of this phase II study was to assess the clinical antitumor activity and toxicities of docetaxel and cisplatin chemotherapy, in patients with locally advanced and metastatic, recurrent squamous cell carcinomas of the head and neck (SCCHN). MATERIALS AND METHODS: All eligible patients with locally advanced and metastatic, recurrent SCCHN had received two courses of chemotherapy followed by repeated head and neck examinations and computed tomography. Patients who had received prior chemotherapy with taxanes were ineligible. If the patients achieved a response (either CR or PR), they received one more course of chemotherapy prior to undergoing definitive local treatment. The combination chemotherapy consisted of docetaxel, 70 mg/m2, and cisplatin, 75 mg/m2, on day 1, with the cycles repeated every 3~4 weeks. RESULTS: All 32 patients were assessable for response and toxicity analyses. The most common grade 3/4 adverse event was neutropenia, which occurred in 11% of cases. No febrile neutropenia was noticed. The other grade 3/4 adverse events included: anemia (2%) and stomatitis (3%). The response rate in patients with locally advanced cancer was 19/21 (90%). Fifteen patients (71%) achieved a CR and 4 (19%) a PR. Out of the 4 patients presenting with a distant metastatic disease, 1 each achieved CR and PR, with 2 stable disease (SD). Out of the 7 patients with a recurrence at a distant site, 1 each achieved PR and SD, and 5 (71%) had a progression of the disease (PD). The overall response rate was 22/32 (69%).
CONCLUSION
Docetaxel plus cisplatin is an effective regimen with an acceptable toxicity profile. This regimen may offer high antitumor activity on short outpatient administration, with a low incidence of severe toxicity.

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  • The Analysis of Induction Chemotherapy Using Docetaxel and Platinum in Treatment of Hypopharyngeal Carcinoma
    Jongseung Kim, Kyengsuk Lee, Byungeon Hwang, Sangho Lim, Sunho Ryu, Ilwoo Ha, Eun Jung Lee, Kihwan Hong, Yunsu Yang
    Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2010; 53(11): 706.     CrossRef
  • The Efficacy of an Induction Chemotherapy Combination with Docetaxel, Cisplatin, and 5-FU Followed by Concurrent Chemoradiotherapy in Advanced Head and Neck Cancer
    Jae-Sook Ahn, Sang-Hee Cho, Ok-Ki Kim, Joon-Kyoo Lee, Deok-Hwan Yang, Yeo-Kyeoung Kim, Je-Jung Lee, Sang-Chul Lim, Hyeoung-Joon Kim, Woong-Ki Chung, Ik-Joo Chung
    Cancer Research and Treatment.2007; 39(3): 93.     CrossRef
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Paclitaxel and Cisplatin Combination Chemotherapy in Pretreated Breast Cancer
Joo Hyuk Sohn, Yong Tai Kim, Sun Young Rha, Nae Choon Yoo, Jae Kyung Roh, Byung Soo Kim, Chang Ok Suh, Gwi Eon Kim, Woo Ick Jang, Hyun Cheol Chung
Cancer Res Treat. 2003;35(3):267-273.   Published online June 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.3.267
AbstractAbstract PDF
PURPOSE
A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy.

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    Shiva Mehran, Afshin Taravati, Esfandiar Baljani, Yousef Rasmi, Zafar Gholinejad
    Breast Disease.2021; 40(3): 117.     CrossRef
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    Molecular Cancer Therapeutics.2021; 20(6): 1210.     CrossRef
  • A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics
    Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Kévin Hardonnière, Daniel Stanciu, Stefano Fais, Jesús Devesa
    International Journal of Molecular Sciences.2020; 21(3): 1110.     CrossRef
  • Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era
    Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Stefano Fais, Jesús Devesa
    International Journal of Molecular Sciences.2020; 21(20): 7475.     CrossRef
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