Nuclear Factor-κB Activation Correlates with Better Prognosis and Akt Activation in Human Gastric Cancer Byung Lan Lee, Hye Seung Lee, Jieun Jung, Sung Jin Cho, Hee-Yong Chung, Woo Ho Kim, Young-Woo Jin, Chong Soon Kim, Seon Young Nam Clinical Cancer Research.2005; 11(7): 2518. CrossRef
PURPOSE Alternative splicing of CD44 and aberrant levels of soluble CD44 (sCD44) protein in the serum of cancer patients has been correlated to tumor progression and metastasis. The purpose of this study was to evaluate the concentrations, and the prognostic potential of sCD44s, sCD44v5 and sCD44v6, in patients with gastric cancer. MATERIALS AND METHODS: The serum levels of sCD44s, sCD44v5 and sCD44v6 were determined quantitatively using an enzyme-linked immunosorbent assay.
Serum samples were obtained from 116 patients with gastric cancer, both before and after surgery, and from 30 healthy controls. RESULTS: The serum sCD44v6 levels were significantly higher in patients with gastric cancer than in the healthy controls, whereas those of sCD44s and sCD44v5 were no different. The surgical resection of the tumor resulted in a significant reduction in all the sCD44 proteins, whereas if a surgical resection was not performed the concentrations of the sCD44v5 and sCD44v6 were not reduced prior to surgery. The serum sCD44v6 levels correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. CONCLUSION: The preoperative serum level of sCD44v6 in patients with gastric cancer was significantly higher than that in the healthy controls, and correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. These results suggest that an elevation of the serum sCD44v6 level might be used as a new predictor of tumor invasiveness, and poor prognosis, in patients with gastric cancer.
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BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients Myong Cheol Lim, Sokbom Kang, Sang-Soo Seo, Sun-Young Kong, Bo-Yon Lee, Seon-Kyung Lee, Sang-Yoon Park Journal of Cancer Research and Clinical Oncology.2009; 135(11): 1593. CrossRef
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PURPOSE One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF).
HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis. MATERIALS AND METHODS: The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay. RESULTS: Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p<0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (> or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p<0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p<0.05) CONCLUSION: The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer.
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MET in gastric cancer with liver metastasis: The relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis Han S. Kim, Hong J. Chon, Hyunki Kim, Su‐Jin Shin, Volker Wacheck, Aaron M. Gruver, Jong S. Kim, Sun Y. Rha, Hyun C. Chung Journal of Surgical Oncology.2018; 117(8): 1679. CrossRef
Hepatocyte growth factor induced up-regulations of VEGF through Egr-1 in hepatocellular carcinoma cells Kyung Hee Lee, Jae-Ryong Kim Clinical & Experimental Metastasis.2009; 26(7): 685. 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
PURPOSE The significance of abnormal E-cadherin/ catenin complex expression and the correlation of each of its components in cancer remain unclear. This study aimed to characterize the clinical significance of the abnormal membrane expression of the E-cadherin/ catenin complex and the localization patterns of the beta- catenin and p120CTN in early gastric cancer. MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, alpha-, beta- and gamma-catenin and p120CTN were performed on 47 early gastric cancer specimens. The patterns of membrange expression of the E-cadherin/catenin complex, and the localization patterns of the beta-catenin and p120CTN, were semi quantitatively graded as loss, reduced, preserved or negative and positive. RESULTS: An abnormal immunoreactivity of at least one of E-cadherin/catenin complex proteins was noted in 46 (97.8%) of the 47 early gastric cancer cases.
There were no significant correlations of the membrane E-cadherin/catenin expression with, either, sex, age, location, size, macroscopic type, depth of invasion or lymphovascular invasion. Abnormal expressions of membrane E-cadherin, beta-catenin and gamma-catenin were more frequent in the diffuse-type than in the intestinal type. No linear correlation was shown for the beta-catenin between the membrane and cytoplasmic expressions. Nuclear staining of the beta-catenin was observed in 5 (10.6%) cases, but nuclear staining of the p120CTN, a promotor of Kaiso transcriptional factor, was not seen. CONCLUSION: These results suggest that alterations of the E-cadherin/catenin complex may be involved in the early stages of gastric cancer. Although beta-catenin functions as a transcriptional factor, the inactivation of membrane E-cadherin does not appear to result in significant increases in the level of cytoplasmic beta-catenin. Kaiso transcriptional factor may not be involved in the early carcinogenesis of gastric cancer.
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PURPOSE Heptaplatin, a new platinum analog, has favorable toxicity profiles and antitumor activity, comparable to those of cisplatin, in the treatment of gastric cancer. This study was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of heptaplatin administered by an intraperitoneal route in patients with resected advanced gastric cancer. MATERIALS AND METHODS: Seventeen patients with resected advanced gastric cancer were entered onto the study. After completion of a curative resection and an astomosis, heptaplatin was administered intraperiton eally in one liter of 5% dextrose solution. The starting heptaplatin dose was 400 mg/m2 of the body surface area, and was escalated in 200 mg/m2 increments, to cohorts of three patients. A pharmacokinetic analysis was carried out to determine the total and ultrafiltratable platinum concentrations in the plasma, peritoneal fluid, and urine. RESULTS: Patients were unable to tolerate a 1, 000 mg/m2 dose level, and at 800 mg/m2, reVersible Grade III toxic ities, including elevated creatinine, proteinuria, hypon- atremia, abdominal pain, and intraabdominal bleeding were noted. No significant toxicity was noted up to a 600 mg/m2 dose level. The ratio of the peak peritoneal to peak plasma drug concentrations were 19.4, 16.6 and 22.8 at doses of 400 mg/m2, 600 mg/m2 and 800 mg/m2, respectively. The pharmacological advantage, expressed as the peritoneal to plasma AUC ratio ranged from 4.3 to 7.0. CONCLUSION: Heptaplatin can be delivered by an intra peritoneal route, with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.
The MTD of intraperitoneal heptaplatin was 800 mg/m2. The major DLTs were nephrotoxicity and intraabdominal bleeding.
The recommended starting dose for a subsequent study would be 600 mg/m2.
PURPOSE A combination of paclitaxel and cisplatin is an effective and safe regimen for advanced non-small cell lung cancer (NSCLC). We conducted a multi-center, phase II trial to evaluate the efficacy and safety of Genexol(R) (paclitaxel) and cisplatin in patients with NSCLC. MATERIALS AND METHODS: Chemotherapy-na ve patients having histologically confirmed NSCLC were enrolled. Genexol(R) was administered at 175 mg/m2 as a 3-hour intravenous infusion and cisplatin at 75 mg/m2 as an intravenous infusion on day 1 every 3 weeks. RESULTS: Twenty-five of 27 patients that were entered from 5 hospitals between Jan 2001 and Aug 2001 received chemotherapy. On an intent-to-treat basis, 9 patients (36%) achieved a partial response, 7 patients (28%) a stable disease, and 5 patients (20%) The overall response rate was 36% (95% CI, 17 to 55%). progressed. The median duration of the response was 7.8 months (95% CI, 6.6 to 9.0 months). The median time to progression was 7.4 months (95% CI, 5.3 to 9.5 months), and median overall survival was 13.3 months (95% CI, 10.8 to 15.9 months) for the intent-to-treat population. The major oxicity was hematological, with grade 3 and 4 neutropenia in 10% (10/106) of the total cycles. The non-hematologic oxicity was mild, and grade 3 emesis was observed in 2 patients (8%). One patient experienced a moderate degree hypersensitivity reaction. CONCLUSION: The results suggest that a combination of Genexol(R) and cisplatin is an effective and well-tolerated regimen for patients with NSCLC.
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PURPOSE The aims were to evaluate the main risk factors (RFs) of breast cancer and to estimate the individual disease-probability from combinations of RFs in Korean female. MATERIALS AND METHODS: We conducted case-control study of 1, 687 incident cases of invasive carcinoma and 1, 238 controls during 1996~2000. A breast cancer disease-probability model was established by a general modeling process using a multivariate logistic regression model, which included the main Korean RFs and synergistic interaction-terms. RESULTS: The main Korean RFs selected were age, family history of second relatives, BMI, age at first full term pregnancy, breast-feeding, and a special test on the breasts. Two synergisms were observed between age and breast-feeding, and between special test and age at first fullterm pregnancy. The disease-probability and model are shown in Table 4, and Appendix 1. CONCLUSION: The availability of previous Western models was limited for Korean female due to the differences inhazard-rates and the characteristics of breast cancer between Asian and Western females. Due to limited basic data, i.e. incidence, hazard-rate and cancer-cohorts, the developing-probability of breast cancer for Korean females was not calculated.
Therefore, the disease-probability was calculated instead.
This approach might be more beneficial for Koreans, and help in the decision- making for regular screening or hospital visit-interval, counseling in breast-cancer clinics, prescribing high-risk population, and in educating for primary prevention, although it over-estimates the relative probability compared to the developing-probability and the 65% predictive validity.
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PURPOSE One of the most controversial aspects of surgery for esophageal cancer is the appropriate extent of lymphadenectomy to achieve the best outcome. The purpose of this study was to clarify the effects of an extended lymphadenectomy (complete 2-field lymphadenectomy; complete 2-FL or 3-field lymphadenectomy; 3-FL) in esophageal cancer surgery. MATERIALS AND METHODS: In order to prevent a local recurrence and improve the long-term survival following surgery, an extended lymphadenectomy has systematically been performed at four hospitals of the Catholic University College of Medicine since 1995. And since that time, until the end of 2001, a total of 98 patients have undergone the procedure. Their clinical results were compared with those of 54 esophageal cancer patients who received an incomplete 2-field lymphadenectomy (incomplete 2-FL), between 1990 and 1994, at the same hospitals. RESULTS: After an extended lymphadenectomy a recurrence was noted in 41 cases (44.6%), a local recurrence occurred in 23 cases (25.0%) and a metastatic recurrence in 18 (19.6%), with the 5-year survival rate improved to 39.5%, than the 29% of the incomplete 2-FL. There was no difference in the morbidity of the fatal complications and the mortality between the two groups. CONCLUSION: The long survival rate was improved with an extended lymphadenectomy, but the morbidity and mortality rate had not increased.
PURPOSE Retinoic acid (RA) has been known to inhibit the proliferation, and to induce apoptosis, of various cancer cell lines. We investigated the correlation between the protein levels of the RAR and RXR receptor families, IGFBP-3 and AFP, and the RA sensitivity in hepatoma cell lines. MATERIALS AND METHODS The cell growth inhibition was examined by assaying various 1 to 10muM RA treated hepatoma cell lines. Western blot analysis for the RAR and RXR families, AFP and IGFBP-3 were performed after treatment with 10muM RA. RESULTS: The 1 to 10muM RA treatment induced growth inhibition in the SNU368, SNU354, SNU398 and HepG2 cells. The cell growth of SNU449 and Hep3B were not suppressed by 1muM, but were slightly suppressed by 10muM RA. An increased expression of IGFBP-3 in HepG2, SNU354, SNU398 and SNU368 cells, and a decreased expression of alpha-fetoprotein (AFP), was observed from the western blot analysis in all hepatoma cells tested, whereas no confirmed tendency of RAR expressions was seen. CONCLUSION: Our result showed that the growth inhibition of RA differed according to the sensitivity of the type of cells to RA. We supposed that RA-induced cell growth inhibition may be related to the expressions of IGFBP-3 and AFP, but no exact correlation exists between the growth inhibition and receptor expression status in hepatoma cell lines.
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PURPOSE This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.
PURPOSE The dosimetric advantages of multiple non-coplanar stationary fields for stereotactic radiotherapy or adiosurgery (SRT/S) are well known. However, this technique is not widely used due to the logistical problems associated with producing and testing customized collimators. We report our experience of SRT/S using multiple non-coplanar stationary fields (conformal SRT/ S). MATERIALS AND METHODS: Between August 1997 and February 2002, we performed frameless SRT/S in 63 patients. We chose conformal SRT/S when the tumor was of a very irregular shape or larger than 4 cm. We obtained three pieces of information: 1) the couch translations required to bring the target point to the isocenter, 2) the distance between the stereotaxic markers in the CT study, and the distance between the markers determined from orthogonal beam films, taken in the anterior- posterior and lateral directions, and 3) the rotational movement of the head position between the CT study and actual treatment position. We evaluated two kinds of data: 1) the precision of the isocenter setup, and 2) the reproducibility of the head position in the a) translational and b) rotational components. RESULTS: Twenty-six of the 63 patients receiving stereotactic treatment received conformal SRT/S. The precision of the isocenter setup for the conformal SRT/S was x=-0.03+/-0.26 mm, y=0.19+/-0.25 mm and z=-0.20+/-0.27 mm. The reproducibilities of the head position with the conformal SRT/S were 0.5 mm and less than 1degrees C, for the translational and rotational components, in any plane. CONCLUSION: We were able to apply conformal stereotactic irradiation, which has a dosimetric advantage, to irregularly shaped intracranial tumors, with precision and reproducibility of head position for the isocenter setup nearly equivalent to that of frame-based SRS or multiple-arc SRT/S.
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PURPOSE 7-Bromomethylbenz[alpha]anthracene is a known mutagen and carcinogen. The mutagenic potency of its two major DNA adducts, i.e., N2-(benz[alpha]anthracen-7-ylmethyl)-2'-deoxyguanosine (b[alpha]a2G) and N6-(benz[alpha]anthracen-7-ylmethyl)-2'-deoxyadenosine (b[alpha]a6A), as well as the simpler benzylated analogs, N2-benzyl-2'-deoxyguanosine (bn2G) and N6-benzyl-2'-deoxyadenosine (bn6A), were determined in E.
coli. MATERIALS AND METHODS: Double-stranded and gapped plasmid vectors were used to determine the mutagenicity of b[alpha]a2G, b[alpha]a6A, bn2G and bn6A in E. coli. The four, suitably protected, bulky exocyclic amino-substituted adducts were incorporated into 16-base oligodeoxyribonucleotides, in place of normal guanine or adenine residues, which form part of the ATG initiation codon for the lacZ' alpha-complementation gene. The site-specifically modified oligodeoxyribonucleotides were then incorporated into double-stranded plasmids, which contained uracil residues in the complementary strand in the vicinity of the initiation codon. The uracil residues lead to the creation of a gap in the complementary strand due to the actions of E. coli uracil-DNA glycosylase and AP endonuclease. Following the transfection of these plasmid vectors into E. coli strain GP102, a lacZ alpha complementing version of the parent strain AB1157, their propensity to induce mutation was investigated. RESULTS: The percentages of mutant colonies produced by the four modified nucleosides, in both the double-stranded and gapped plasmid vectors, were not significantly different from those produced by the unmodified plasmids. The mutagenicities of the b[alpha]a2G and b[alpha]a6A were extremely low, and a totally unexpected result, whereas, those of the bn2G and bn6A were undetectable. CONCLUSION: In this E. coli site-specific mutagenesis system, these bulky aralkylated adducts exhibited no significant mutagenicities, either with or without SOS induction.
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