• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4271-4274
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• 2014

The epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and plays an important role in drug resistance and metastasis in diverse solid tumors. We previously reported that 48 h treatment of anti-cancer drug doxorubicin could induce EMT in human gastric cancer BGC-823 cells. However, the long term effects of this transient drug treatment were unknown. In this study we found that after 48 h treatment with $0.1{\mu}g/ml$ doxorubicin, most cells died during next week, while a minor population of cells survived and formed colonies. We propagated the surviving cells in drug free medium and found that these long term cultured drug survival cells (abbreviated as ltDSCs) retained a mesenchymal-like cell morphology, and expressed high levels of EMT-related molecules such as vimentin, twist and ${\beta}$-catenin. The expression of chromatin reprogramming factors, Oct4 and c-myc, were also higher in ltDSCs than parental cells. We further demonstrated that the protein level of p300 was upregulated in ltDSCs, and inhibition of p300 by siRNA suppressed the expression of vimentin. Moreover, the ltDSCs had higher colony forming ability and were more drug resistant when compared to parental cells. Our results suggested that an epigenetic mechanism is involved in the EMT of ltDSCs.

• Journal of Gastric Cancer
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• v.3 no.1
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• pp.33-37
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• 2003

Purpose: Alpha-fetoprotein (AFP) is widely accepted as a useful tumor marker for diagnosis of hepatocellular carcinomas. On rare occasions, however, an abnormal elevation of serum AFP also has been reported in an adenocarcinoma of the gastrointestinal tract. We evaluated the influence of preoperative abnormal elevation of serum AFP (AFP positivity) on the prognosis of resectable gastric cancers. Materials and Methods: 812 gastric cancer patients, who were investigated for serum AFP before their operations and who underwent gastric resections with D2 or more extended lymph node dissection, were enrolled in the study. The survival rates were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. Results: Fifty patients ($6.2\%$) were AFP positive (10.1. 4322.6 ng/ml). The survival rate of the AFP positive group was significantly lower than that of the AFP negative group ( $46.6\%\;vs.\;67.0\%$; P=0.0002). The depth of tumor invasion, the degree of regional lymph node metastasis, distant metastases, the TNM stage, the gross type, differentiation, the extent of gastric resection, and the curability of the surgery also significantly influenced survival. Multivariate analysis revealed that the depth of tumor invasion, the degree of regional lymph node metastasis, the curability of the surgery, and AFP positivity were independent prognostic indicators. Conclusion: Preoperative serum AFP can be used as an independent prognostic factor of resectable gastric cancer.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.186-191
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• 2004

Primary small-cell carcinomas of the stomach are rare and aggressive malignancies with poor survival rates. Preoperative diagnosis is difficult and a standard treatment is not yet established. We have recently experienced two cases of a primary small-cell carcinoma of the stomach. The first case was a 65-year-old man with epigastric soreness. Endoscopic biopsy showed an adenocarcinoma. He underwent a radical subtotal gastrectomy with D2 lymph-node dissection. Pathology revealed a collision tumor of a smallcell carcinoma and an adenocarcinoma with submucosal invasion and with metastasis in 20 out of 48 lymph nodes (T1N3M0). The second case was a 64-year-old man with epigastric soreness. Endoscopic biopsy revealed a small-cell carcinoma. There was no evidence of a primary tumor in the lung. A radical subtotal gastrectomy with D2 lymph-node dissection was performed. Pathology showed a pure smallcell carcinoma with proper muscle invasion and with metastasis in 1 out of 36 lymph nodes (T2aN1M0).

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.272-278
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• 2004

Recently, Pepe et al. (2003) employed the receiver operating characteristic (ROC) approach to rank candidate genes from a microarray experiment that can be used for the biomarker development with the ultimate purpose of the population screening of a cancer, In the cancer microarray experiment based on n patients the researcher often wants to compare the tumor tissue with the normal tissue within the same individual using a common reference RNA. This design is referred to as a reference design or an indirect design. Ideally, this experiment produces n pairs of microarray data, where each pair consists of two sets of microarray data resulting from reference versus normal tissue and reference versus tumor tissue hybridizations. However, for certain individuals either normal tissue or tumor tissue is not large enough for the experimenter to extract enough RNA for conducting the microarray experiment, hence there are missing values either in the normal or tumor tissue data. Practically, we have $n_1$ pairs of complete observations, $n_2$ 'normal only' and $n_3$ 'tumor only' data for the microarray experiment with n patients, where n=$n_1$+$n_2$+$n_3$. We refer to this data set as a mixed data set, as it contains a mix of fully observed and partially observed pair data. This mixed data set was actually observed in the microarray experiment based on human tissues, where human tissues were obtained during the surgical operations of cancer patients. Pepe et al. (2003) provide the rationale of using ROC approach based on two independent samples for ranking candidate gene instead of using t or Mann -Whitney statistics. We first modify ROC approach of ranking genes to a paired data set and further extend it to a mixed data set by taking a weighted average of two ROC values obtained by the paired data set and two independent data sets.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4151-4155
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• 2013

Background: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. Patients and Methods: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). Results: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (${\chi}$=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST ($r^2$=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions ($r^2$=0.935 and $r^2$=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. Conclusions: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.65-73
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• 2003

The researches for tumor and the developments for new anti-tumor medicine are being continuously developed in the oriental as well as the west. The principles therapy of anti-tumor activity was based on knowledge of the method of support the healthy energy and strengthen the body resistance, promote blood circulation to remove blood stasis, clear away heat and toxic materials, dissipate phlegm and disperse the accumulation of evils. But the major clinical features of tumor was to be considered in developing a treatment plan include (1) distinguish between clinical and pathologic staging - acute and chronic, (2) classification of pathologic pattern, and (3) distinction of body situation : for examples asthenia - sthenia etc. It was most important to distinguish between supporting the healthy and eliminating the evil factors and to treat differently at the root and the branch cause of a neoplasm. In clinical study and experimental study, the effects of oriental medicine could be summarized as three that were decreasing toxicity of chemo-therapy, directly suppressing and killing cancerous cell and increasing chemo-effect through preventing metastasis. Improving organic immunity with oriental medicine could be summarized as five that were promoting phagocytosis of macrophage, inducing interferon, promoting formation of immnoglobulin, increasing number of T-cell and promoting transformation of lymphocyte. It is suggested that effective use of immune activating herbs inhibited metastasis and decreased recurrence and then we were able to expect increasing survival rate and improving clinical symptoms and quality of life(QOL) of tumor patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.639-643
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• 2013

Aim: Connexin 43 (Cx43) and E-cadherin are important biomarkers related with cancer. Their expression at protein and mRNA levels was here investigated in 50 primary lung carcinoma tissues and 20 samples of adjacent normal tissue of Chinese patients with non-small cell lung cancer (NSCLC). Methods: Protein and mRNA expression were evaluated by ABC immunohistochemistry and RT-PCR. Results: (1) The positive expression rates of Cx43 and E-cadherin protein were higher in the adjacent normal tissues than those in the primary lung carcinoma tissues; (2) the positive expression rates of Cx43 and E-cadherin protein decreased with NSCLC progression; (3) the expression of E-cadherin protein was not related with the pathological type of NSCLC; and (4) the relative quantity of the Cx43 or E-cadherin mRNA expression was correlated with the the histological type, clinical stage, cancer cell differentiation and the lymph node metastasis. Conclusion: The data suggested that the Cx43 and E-cadherin are reduced with NSCLC progression, and might be important biomarkers for judging the metastasis and prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4973-4976
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• 2013

Background: To identify correlation and incidence of bone metastases in prostate cancer patient with low Gleason scores (GS) and prostate specific antigen (PSA) levels. Materials and Methods: This descriptive restrospective study covered patients with prostate cancer in Cipto Mangunkusumo Hospital in 2006-2011. Of a total of 478, those who had PSA values, histological examination, and bone scan were included, resulting in 358 eligible cases. PSA values were measured using the sandwich electrochemiluminescent immunoassay. Histological examination was graded according to Gleason's grading system and divided into 3 categories: well differentiated ($GS{\leq}6$), moderately differentiated (GS 7) and poorly differentiated (GS 8-10). Bone scans were performed using a radiopharmaceutical agent ($T_c$ 99m methylenen diphosphonate) with images captured by gamma camera. Results: The mean age was $67.5{\pm}7.8$, mean GS was $7.7{\pm}1.3$ and median PSA was 56.9 (range: 0.48-17000 ng/mL). There were 11 patients (3.0%) with positive bone scan with PSA<20 ng/mL and GS<8. Furthermore, there were 2 patients (0.6%) with $GS{\leq}6$ and PSA<10 ng/mL showing bone metastasis. Conclusions: In our study, there were still small percentage of patients with bone metastasis even when low values of PSA (PSA<10 ng/mL) and GS ($GS{\leq}6$) were applied.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.91-96
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• 2004

Primary lung cancer frequently metastasizes to distant organs. But breast is a very rare site of metastasis. So, accurate diagnosis is essential to rule out primary breast cancer. A 62-year old woman who had complained of cough was diagnosed as small cell lung carcinoma of the right lower lobe. She had a 2.5cm sized lobular mass in left upper mid portion of breast. Sonoguided breast biopsy revealed small cell carcinoma consistent with metastatis from primary lung cancer. She also had bone metastses to the scapula and the vertebrae. We report the case of metastatic breast cancer from small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.56-60
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• 2012

A patient who has multiple lung masses with a history of malignancy in organs other than the lung is more likely to be diagnosed with metastatic rather than primary lung cancer. Rarely, metastatic cancer can coexist with primary. We experienced a case of concurrent diagnosis of primary small cell lung cancer and pulmonary metastasis of uterine malignant mixed M$\ddot{u}$llerian tumor (MMMT). The patient was a 52-year-old female with femur fracture and multiple lung masses with a history of an operation for uterine MMMT. The small cell lung cancer was diagnosed by bronchoscopic biopsy. The central lung mass decreased after chemotherapy for small cell lung cancer but multiple peripheral masses increased. A percutaneous biopsy for one of peripheral masses revealed metastatic uterine MMMT. We suggest that we have to consider the possible presence of concomitant malignancies of different origins in one organ especially with patients who had a history of malignancy in another organ.