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Kang, Sokbom,Kim, Jae Weon,Kang, Gyeong Hoon,Lee, Sun,Park, Noh Hyun,Song, Yong Sang,Park, Sang Yoon,Kang, Soon Beom,Lee, Hyo Pyo Alan R. Liss, Inc 2006 International journal of cancer Vol.118 No.9
<P>The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. © 2005 Wiley-Liss, Inc.</P>
Kang, Sokbom,Kim, Tae-Joong,Nam, Byung-Ho,Seo, Sang-Soo,Kim, Byoung-Gie,Bae, Duk-Soo,Park, Sang-Yoon Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of surgical oncology Vol.101 No.1
<B>Background</B><P>This meta-analysis was designed to determine the ability of pretreatment CA-125 level to predict optimal cytoreduction in advanced ovarian cancer (OC).</P><B>Methods</B><P>Through literature search, 14 studies were identified. In addition, we retrospectively reviewed the data of 154 patients with OC. Using the bi-variate model, diagnostic performance of CA-125 was assessed at the various cut-off levels. An overall odds ratio was obtained using random effects model.</P><B>Results</B><P>A total of 2,192 patients were included in the analysis. The pooled optimal cytoreduction rate and the mean of median CA-125 levels were 53.7% and 580 U/ml, respectively. At the cut-off of 500 U/ml, overall sensitivity and specificity were 68.9% (95% confidence interval [CI] 62.0–75.1%) and 63.2% (95% CI 53.7–71.7%), respectively. Positive and negative likelihood ratios were 1.87 (95% CI 1.40–2.50) and 0.49 (95% CI 0.37–0.66). The CA-125 >500 U/ml showed strong association with a risk of suboptimal cytoreduction with an odds ratio of 3.69 (95% CI 2.02–6.73).</P><B>Conclusions</B><P>The current analysis indicates that CA-125 is a strong risk factor of suboptimal cytoreduction and it may be applied in preoperative counseling and treatment planning. However, it also shows that CA-125 lacks the ability to predict optimal cytoreduction accurately. J. Surg. Oncol. 2010;101:13–17. © 2009 Wiley-Liss, Inc.</P>
Kang, Sokbom,Nam, Byung-Ho,Park, Jeong-Yeol,Seo, Sang-Soo,Ryu, Sang-Young,Kim, Jae Weon,Kim, Seung-Cheol,Park, Sang-Yoon,Nam, Joo-Hyun Grune Stratton ; American Society of Clinical Onco 2012 Journal of clinical oncology Vol.30 No.19
<P>Our study aimed to develop a model to predict distant recurrence in locally advanced cervical cancer, which can be used to select high-risk patients in enriched clinical trials.</P>
Kang, Sokbom,Dong, Seung Myung,Kim, Boh-Ram,Park, Mi Sun,Trink, Barry,Byun, Hyun-Jung,Rho, Seung Bae Springer US 2012 Apoptosis Vol.17 No.9
<P>Recently, thioridazine (10-[2-(1-methyl-2-piperidyl) ethyl]-2-methylthiophenothiazine), a well-known anti-psychotic agent was found to have anti-cancer activity in cancer cells. However, the molecular mechanism of the agent in cellular signal pathways has not been well defined. Thioridazine significantly increased early- and late-stage apoptotic fraction in cervical and endometrial cancer cells, suggesting that suppression of cell growth by thioridazine was due to the induction of apoptosis. Cell cycle analysis indicated thioridazine induced the down-regulation of cyclin D1, cyclin A and CDK4, and the induction of p21 and p27, a cyclin-dependent kinase inhibitor. Additionally, we compared the influence of thioridazine with cisplatin used as a control, and similar patterns between the two drugs were observed in cervical and endometrial cancer cell lines. Furthermore, as expected, thioridazine successfully inhibited phosphorylation of Akt, phosphorylation of 4E-BP1 and phosphorylation of p70S6K, which is one of the best characterized targets of the mTOR complex cascade. These results suggest that thioridazine effectively suppresses tumor growth activity by targeting the PI3K/Akt/mTOR/p70S6K signaling pathway.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s10495-012-0717-2) contains supplementary material, which is available to authorized users.</P>
Alteration in Lipid and Protein Profiles of Ovarian Cancer: Similarity to Breast Cancer
Kang, Sokbom,Lee, Aera,Park, Young Seung,Lee, Seok Cheol,Park, Sang Yoon,Han, Sang Yun,Kim, Kwang Pyo,Kim, Young Hwan,Yoo, Chong Woo,Kim, Hark Kyun BMJ 2011 International journal of gynecological cancer Vol.21 No.9
<B>Abstract</B><P>This study was undertaken to evaluate protein and lipid profiles of ovarian cancer tissue samples. Twenty-three frozen ovarian cancer samples and 6 adjacent normal samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization mass spectrometry. Sinapinic acid and 2, 5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify protein and lipid profiles respectively, and mass spectra were acquired using a matrix-assisted laser desorption/ionization-time of flight instrument. Protein and lipid profiles classify 11 cancer and 3 adjacent normal samples in 100 random test sets with 92.9% median accuracy. Phosphatidylcholines {32:3} [M + Na]<SUP>+</SUP> (<I>m</I>/<I>z</I> = 750.66), {34:1} [M + K]<SUP>+</SUP> (<I>m</I>/<I>z</I> = 798.60), and {36:2} [M + K]<SUP>+</SUP> (<I>m</I>/<I>z</I> = 824.56) were found to be increased in ovarian cancer. Interestingly, breast cancer-associated changes in lipid and protein profiles were also found in ovarian cancer. Thus, protein and lipid profiles accurately distinguish ovarian cancer from adjacent normal tissue samples. Common cancer-associated alterations in lipid and protein profiles were identified between ovarian and breast cancers.</P>
Kang, Sokbom,Kim, Tae-Joong,Seo, Sang-Soo,Kim, Byoung-Gie,Bae, Duk-Soo,Park, Sang-Yoon S. Karger AG 2011 Gynecologic and obstetric investigation Vol.72 No.1
<P>Abstract</P><P><I>Background:</I> We aimed to determine whether the inclusion of additional cycles of carboplatin-paclitaxel is beneficial to patients with high posttreatment serum CA-125 levels. <I>Methods:</I> Among patients who achieved remission after six cycles of carboplatin-paclitaxel chemotherapy, those with CA-125 of 10–35 U/ml at the time of remission were divided into two groups (group A: six cycles of standard chemotherapy vs. group B: two or more additional cycles) and were analyzed. <I>Results:</I> Among the 436 patients with advanced epithelial ovarian cancer, 154 patients (46.8%) had CA-125 of 10–35 U/ml at the time of remission. Fifty-six patients (36.4%) received two or more cycles after the first six cycles of chemotherapy (group B). The addition of two or more cycles of chemotherapy did not improve the progression-free survival (p = 0.660). There was no statistical difference in the rates of CA-125 falling to <10 U/ml between the two groups (p = 0.256). Moreover, the degree of CA-125 decrease after six cycles of chemotherapy was similar regardless of the additional cycles (p = 0.656). <I>Conclusion:</I> The addition of two or more cycles of standard chemotherapy based on posttreatment CA-125 levels was not beneficial.</P><P>Copyright © 2011 S. Karger AG, Basel</P>
Interleukin-1 Beta -511 Polymorphism and Risk of Cervical Cancer
Kang, Sokbom,Kim, Jae Weon,Park, Noh Hyun,Song, Yong Sang,Park, Sang Yoon,Kang, Soon Beom,Lee, Hyo Pyo The Korean Academy of Medical Sciences 2007 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.22 No.1
<P>Cervical cancer is almost invariably associated with infection by human papillomavirus. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The <I>IL1B</I> gene, encoding IL-1β cytokine, contains several single nucleotide polymorphisms. One of them which is in the positions -511 (C-T) related with promoter region has been associated with increased IL-1β production and with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We assessed the association between the <I>IL1B</I> -511 polymorphism and cervical cancer risk in a hospital-based case-control study among 546 Korean women (182 cases; 364 age-matched controls). The allele frequencies of the case subjects (C, 0.42; T, 0.58) were not significantly different from those of control subjects (C, 0.43; T, 0.57). Control subjects were in Hardy-Weinberg equilibrium. The carriers with -511 C/T or T/T genotypes were at higher risk of cervical cancer with odds ratio of 2.42 (95% CI 1.31-4.46, <I>p</I><0.005). However, there was no difference of cervical cancer risk between C/T heterologous genotypes and T/T homologous genotypes. In conclusion, in Korean population, <I>IL1B</I> -511 C/C genotypes were significantly associated with a decreased risk of cervical cancer.</P>
Kang, Sokbom,Kang, Woo Dae,Chung, Hyun Hoon,Jeong, Dae Hoon,Seo, Sang-Soo,Lee, Jong-Min,Lee, Jae-Kwan,Kim, Jae Weon,Kim, Seok-Mo,Park, Sang-Yoon,Kim, Ki Tae Grune Stratton ; American Society of Clinical Onco 2012 Journal of clinical oncology Vol.30 No.12
<P>The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery.</P>
Kang, Sokbom,Kim, Tae-Joong,Seo, Sang-Soo,Kim, Byoung-Gie,Bae, Duk-Soo,Park, Sang-Yoon Korean Society of Gynecologic Oncology and Colposc 2011 Journal of Gynecologic Oncology Vol.22 No.4
<P><B>Objective</B></P><P>We aimed to determine the ideal cut-off of nadir serum CA-125 level for prediction of progression free survival.</P><P><B>Methods</B></P><P>Among 267 patients who achieved complete remission after chemotherapy, the correlation between nadir CA-125 and progression free survival were compared among the subgroups classified according to the distribution of CA-125. The diagnostic odds ratio and area under the receiver operator characteristics curve were compared at various cut-off points.</P><P><B>Results</B></P><P>The nadir CA-125 levels did not have prognostic value under 12 U/mL (to 75 percentile). In contrast, they were significantly correlated with progression free survival only when the CA-125 level was greater than 12, which was 75 percentile (p=0.034). In predicting progression free survival <6 and 12 months, the cut-off value of 18 (90 percentile) showed superior diagnostic performance over 10 or 12 U/mL. Compared with patients who showed nadir levels between 0 and 12 U/mL (0 to 75 percentile), those with nadir >18 U/mL showed a hazard ratio of 2.85 (95% confidence interval, 1.70 to 4.76; p<0.001); patients with nadir levels between 18 and 12 U/mL showed a the hazard ratio of 1.68 (95% confidence interval, 1.11 to 2.56; p=0.015) compared with those whose nadir levels were under 12 U/mL.</P><P><B>Conclusion</B></P><P>The predictive power of the traditional cut-off of 10 U/mL to classify a risk group or to identify high risk patients was unsatisfactory. The optimal diagnostic performance was observed at the cut-off of 18 U/mL and this can be proposed to dichotomize cut-off values to predict outcomes among individual patients.</P>