• Radiation Oncology Journal
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• v.20 no.4
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• pp.328-333
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• 2002

Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Journal of Life Science
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• v.33 no.2
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• pp.149-157
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• 2023

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that affects not only the survival and growth of cancer cells but also the activity of immune cells. Although it has been generally accepted that cancer cell-derived TGF-β could promote the survival and growth of early cancer cells and have immunosuppressive roles, it has been known that TGF-β has differential effects according to the type or stage of cancer cells. Therefore, it is hard to clearly define its role in cancer progression and immune responses. This study investigated the effects of TGF-β signaling on the expression of five NKG2D ligands and the NK cell-mediated anticancer immune response in the primary colon cancer cell line KM12C and its two metastatic cell lines, KM12SM and KM12L4A. At the surface protein level, exogenous TGF-β decreased the expression of MICA, MICB, ULBP1, and ULBP2, and galunisertib increased the expression of MICA, MIAB, ULBP1, ULBP2, and ULBP3 in KM12C. However, KM12SM and KM12L4A showed no significant changes in the expression of NKG2DLs after treatment with TGF-β or galunisertib. TGF-β signaling inhibition via galunisertib improved the NK cell-mediated anticancer immune response against KM12C but did not show a significant response to KM12SM and KM12L4A. Therefore, the suppression of TGF-β signaling could improve the NK cell-mediated anticancer immune response against KM12C. However, an increase in NKG2DLs expression and an enhanced NK cell-mediated cancer immune response is hard to expect due to the alteration of TGF-β signaling in KM12SM and KM12L4A.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.245-253
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• 2000

The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: $3{\sim}13$). High level amplification was present in 4 cases at 9p23, $12p21.1{\sim}q13.1$, 3q and $8q24{\sim}24.3$. Fourteen cases(78.9%, mean: 3.00, range: $1{\sim}8$) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: $1{\sim}9$) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at $3q24{\sim}26.7$, $3q27{\sim}29$, $1q22{\sim}31$, $5p12{\sim}13.3$, $8q23{\sim}24$, and 11q13.1-13.3. The minimal common regions of losses were detected at $9q11{\sim}21.3$, 17p31, $13q22{\sim}34$, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q($1q22{\sim}31$) and 11q($11q13.1{\sim}13.3$) were mainly detected in higher stage group. The loss at $13q22{\sim}34$ was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at $3q24{\sim}26.3$, $1q22{\sim}31$, and $5p12{\sim}13.3$ and losses at $9q11{\sim}21.3$, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at $3q24{\sim}26.3$, $3q27{\sim}29$, $5p12{\sim}13.3$ and 5p are associated with the early progression of oral cancer. Gains at $1q22{\sim}31$ and $11q13.1{\sim}13.3$ and loss at 13q22-34 could be involved in the late progression of oral cancers.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Journal of Gastric Cancer
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• v.8 no.2
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• pp.70-78
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• 2008

Purpose: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). Materials and Methods: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. Results: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). Conclusion: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.29-33
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• 2005

Purpose: To determine the prognostic values of the hematologic parameters checked preoperatively in gastric cancer patients, we evaluated and compared the relationship between hematologic parameters and clinicopathologic factors of gastric cancer patient. Materials and Methods: The medical records of 357 consecutive patients who had undergone surgery for gastric cancer at the Department of Surgery, Hanyang University Hospital, between Dec. 2,000 and Dec. 2003 were reviewed. To exclude any adverse effect of invasive procedures to hematologic parameters, the samples taken immediately at outpatient department was used. The normal range of serum albumin was defined above 3.5 g/dl, serum hemoglobin above 12 g/dl, and serum platelet count under $400\times10^{3}{\mu}l$. Patients were defined as group 1 when any of these parameters was abnormal, and defined as group 2 when all parameters were normal. The relationships between hematologic parameters and survival rate were investigated. Results: The mean values of platelet count increased, but level of serum albumin and serum hemoglobin decreased significantly according to the advancement of the disease stage (P=0.000). The differences of depth of tumor invasion and lymph node metastasis between the group 1 and the group2 was statistically significant (P=0.001). Three-year survival difference between group 1 and group 2 was significant (P=0.037). Conclusion: The hematologic parameters checked preoperatively in patients of gastric cancer are simple and cheap, meanwhile reflect the general condition of the patients. Any presence of anemia, hypoalbuminemia, or thrombocytosis can predict the progression of the disease and poor survival rates.

• Journal of Gastric Cancer
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• v.7 no.1
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• pp.1-8
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• 2007

Purpose: There has been increased the number of early gastric cancer and laparoscopy-assisted gastrectomy (LAG), due to early detection through mass screening program. We started the LAG in April 2004 and performed 119 cases of gastric cancer in 2005, so we report a surgical outcome compared with that of open gastrectomy (OG). Materials and Methods: 119 patients underwent LAG in 2005, and for open group, 126 patiens of early gastric cancer were selected sequentially from January 2005 to March 2005. We compared clinicopathologic characteristics, postoperative courses and complications between two groups. Results: There was no significant difference between age, a length of hospital stay, distal resection margin and a number of retrived lymph nodes. The operation time was longer in LAG group (239.2 vs 123.3 mins, P<0.001) and a diet progression was faster in LAG group (first flatus: 3.05 vs 3.70 days, SOW: 2.86 vs 3.22 days, liquid diet: 3.87 vs 4.19 days, soft diet: 4.84 vs 5.26 days, P<0.001). But there was no difference statistically in postoperative discharge date (7.73 vs 8.25 days, P=0.229). The additional requirement of analgesic injection was less frequent in LAG group (2.97 vs 4.92 times, P<0.001). The harvested lymph nodes were similar in both groups (23.9 vs 23.1, P=0.563). A complication rate was lower in LAG group (4.9% vs 9.5%), but there was no statistical significance (P=0.179). There was no mortality in both groups and no conversion to open gastrectomy in the LAG group. Conclusion: LAG can be performed safely and accepted in view of curative procedure in treatment of early gastric cancer. But we need the follow up of long-term period to evaluate the survival rate and recurrence, and a prospective randomized controlled study should be done to establish that LAG will be a standard operation for early gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8063-8067
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• 2014

Background: Cervical cancer is a major public health problem in Bangladesh. Persistence of high risk human papillomavirus (HRHPV) influences the progression of the disease, with an important role in followup for cervical intraepithelial neoplasia (CIN). Objective: To establish application of high risk HPV DNA test in the follow-up of women after treatment of CIN. Materials and Methods: This cross-sectional and hospital based study was carried out among 145 CIN treated women during the previous six months to three years at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka, between January 2011 and June 2012. Pap smear and HPV samples were collected and colposcopy was performed to find out the persistence of the disease. Cervical samples obtained were tested for HPV DNA using the Hybrid Capture II (HC-II) test. A cervical biopsy was collected whenever necessary. The results were compared to assess the efficacy of different methods during follow up such as Pap smear, HPV test and colposcopy. Results: Mean age of the recruited women (n=145) was 33.6 (${\pm}7.6$), mean age of marriage was 16.8 (${\pm}2.9$) and mean age of 1st delivery was 18.8 (${\pm}3.5$) years. More than half had high grade CIN before treatment and 115 (79.3%) women were managed by LEEP and 20.7% were managed by cold coagulation. Among the 145 treated women, 139 were negative for HPV DNA and six of them (4.1%) were HPV positive. Sensitivity of Pap smear (40.0) and HPV DNA test (40.0) was poor, but specificity was quite satisfactory (>93.0) for all the tests. Conclusions: The high risk HPV DNA test can be an effective method of identifying residual disease. It can be added to colposcopy and this should be applied to all treated women attending for their first or second post-treatment follow-up visit at 6 months to one year, irrespective of the grade of treated CIN.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.