• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7635-7638
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• 2013

Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.143-148
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• 2004

Purpose: To determine the clinical value of the Siewert classification for gastic-cancer patients in Korea, we evaluated and compared the clinicopathologic factors of type II and type III cancer. Materials and Methods: The medical records of 89 consecutive patients who had undergone surgery for an adenocarcinoma of the gastroesophageal junction (GEJ) at the Department of Surgery, Hanyang University Hospital, between Jun. 1992 and Dec. 2003 were reviewed retrospectively. Results: There were one patient with type I, 12 pateints with type II and 77 patients with type III. During the same period, 1,341 patients underwent surgery for a gastric carcinoma, so proportion of GEJ cancer being $6.6\%$. The median followup duration was 31 months (range: $2\∼135$ months), and the follow-up rate was $100\%$. Between type II and type III cancers, there were no significant differences in the clinicopathologic variables including age, sex, gross appearance, histologic type, depth of invasion, and pathologic stage. The longest diameter of the tumor was larger in type III ($6.1\pm2.1$ cm) than in type II ($3.9\pm1.1$ cm)(P=0.001). A total gastrectomy with Roux-en-Y esophagojejunostomy was done most frequently, while jejunal interposition was done in 3 cases of type II and 2 cases of type III. More than a D2 lymphadenectomy was done all cases. The numbers of dissected lymph nodes and metastatic lymph nodes in type II were 43.8 and 5.8 respectively, while they were 49.8 and 8.1 in type III, but the difference between the two groups were not statistically significant. The mean length of the proximal resection margin was $15\pm5$ mm in type II and $21\pm13$ mm in type III, but this difference was not statistically significanct. The time to recurrence after operation was 19.3 months in type II and 16.9 months in type III. The five-year survival rates of type II and III were $68.8\%\;and\;52.7\%$ respectively, but difference was not significant. Conclusion: There were no significant differences in the clinicopathologic variables, including survival rate, between type II and type III cancers in Korean patients According to these findings, it appears to be reasonable to classify type III cancer as a cardia cancer in a broad sense.

• Journal of Gastric Cancer
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• v.4 no.1
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• pp.1-6
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• 2004

Purpose: Despite numorous reports on the relationship between the level of carcinoembryonic antigen (CEA) in gall bladder bile and liver metastasis in colorectal cancer, no similar studies have been carried out for gastric carcinomas. We, therefore, undertook the present study to establish the relationship between the gall bladder bile CEA and liver metastasis as well as the post-operative survival rate in gastric carcinoma patients with curative resections. Materials and Methods: In 373 gastric cancer patients (252 males, 121 females, age $21\∼76$ years) operated on at Kosin University Hospital between 1989 1996, the CEA concentration in the gall bladder bile was determined during the operation and the value was related to the rates of post-operative survival and liver metastasis during follow-up period. Results: The overall rate of patient survival decreased gradually with increase in TNM stage. The 13-year postoperative survival rates for stages Ia, Ib, II, IIIa, and IIIb were $95.7\%,\;92.5\%,\;79.9\%,\;50.9\%,\;and\;43.3\$, respectively, and the 10-year survival rate for stage IV was $22.6\%$. The patients with a high ($\geq$10 ng/ml) biliary CEA showed a significantly lower rate of survival than those with a low (<10 ng/ml) biliary CEA. The 13-year cumulative survival rate was $55.4\%$ for the high CEA group and $76.5\%$ for the low CEA group (P<0.01). Also, the patients with a high biliary CEA showed a significantly higher rate ($11.5\%$) of liver metastasis than those with a low biliary CEA ($1.9\%$) (P<0.000). In patients with TNM stages (I and II), the CEA level did not affect the post-operative survival rates ($95.4\%\;and87.7\%$ in the high and low CEA groups, P>0.10), but in those with high TNM stages (III and IV), the survival rate was significantly lower in the high CEA group ($25.9\%$) than in the low CEA group ($57.8\%$) (P<0.05). Conclusion: These result suggest that the gall bladder bile CEA level obtained in an advanced-staged gastric cancer operation may be used in predicting the post-operational survival rate and in sorting out patients with a high risk for cancer recurrence, especially in the liver area.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3595-3600
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• 2016

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.311-317
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• 2004

Purpose: The purpose of this study was to determine the utility of tumor marker CA 15-3 in the following: the diagnosis of breast cancer relapse after curative mastectomy, and the differentiation or the value of tumor marker by site of metastases. Materials and Methods: Two hundred two patients (median age 48 years) with breast cancer included in the follow-up after curative mastectomy. The tumor marker CA 15-3 was determined by IRMA (CIS BIO INTERNATIONAL, France). Test values > 30 U/ml were considered elevated (positive). Results: Among 202 patients, recurrent diseases were found in 16 patients. CA 15-3 was elevated in 5 of 16 patients with recurrences. There was no false-positive patient who had elevated CA 15-3. Sensitivity and specificity of CA 15-3 for detection of breast cancer recurrence were 31%, and 100%. CA 15-3 was elevated in all of the 4 patients with liver metastases. CA 15-3 was elevated in none of the patients who relapsed with metastasis to bone-only or contralateral breast-only. Conclusion: The tumor marker CA 15-3 in the detection of breast cancer relapse after curative mastectomy is specific, but not sensitive. However, it is useful to rule out liver metastases of breast cancer, which indicates bad prognosis.

• Journal of Gastric Cancer
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• v.14 no.1
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• pp.15-22
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• 2014

Purpose: To evaluate the prevalence of esophageal reflux-induced symptoms after gastrectomy owing to gastric cancer and assess the relationship between esophageal reflux-induced symptoms and quality of life. Materials and Methods: From January 2012 to May 2012, 332 patients were enrolled in this cross-sectional study. The patients had a history of curative resection for gastric cancer at least 6 months previously without recurrence, other malignancy, or ongoing chemotherapy. Esophageal reflux-induced symptoms were evaluated with the GerdQ questionnaire. The quality of life was evaluated with the European Organization for Research and Treatment QLQ-C30 and STO22 questionnaires. Results: Of the 332 patients, 275 had undergone subtotal gastrectomy and 57 had undergone total gastrectomy. The number of GerdQ(+) patients was 58 (21.1%) after subtotal gastrectomy, and 7 (12.3%) after total gastrectomy (P=0.127). GerdQ(+) patients showed significantly worse scores compared to those for GerdQ(-) patients in nearly all functional and symptom QLQ-C30 scales, with the difference in the mean score of global health status/quality of life and diarrhea symptoms being higher than in the minimal important difference. Additionally, in the QLQ STO22, GerdQ(+) patients had significantly worse scores in every symptom scale. The GerdQ score was negatively correlated with the global quality of life score (r=-0.170, P=0.002). Conclusions: Esophageal reflux-induced symptoms may develop at a similar rate or more frequently after subtotal gastrectomy compared to that after total gastrectomy, and decrease quality of life in gastric cancer patients. To improve quality of life after gastrectomy, new strategies are required to prevent or reduce esophageal reflux.

• Journal of Gastric Cancer
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• v.10 no.3
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• pp.111-117
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• 2010

Purpose: The aim of this study was to determine the prognostic factors and the significance of metastatectomy for Krukenberg's tumors of gastric origin.Materials and Methods: Among the patient who underwent gastric surgery from 1992 through 2005, 90 female patients with Krukenberg's tumors of gastric origin were identified. We retrospectively reviewed the clinicopathologic characteristics, prognostic factors, and treatments for primary gastric cancer. We also investigated the prognostic risk factors for the onset of metachronous Krukenberg's tumors and the survival time of patients who underwent an operation for metachronous Krukenberg's tumors. Results: The presence of a synchronous Krukenberg's tumor (mean survival time=17.6 months, P<0.01), peritoneal seeding (14.5 months, P<0.01), and non-curative resection (15.1 months, P<0.01), were statistically significant prognostic factors for survival time in female patients with gastric cancer. The stage of primary gastric cancer (P=0.049) and lymph node metastasis (P=0.011) were statistically significant risk factors for recurrence time of a metachronous Krukenberg's tumor. In the metachronous Krukenberg's tumor group (n=53), the mean survival time of the metastatectomy group (n=46, 43.2 months, P=0.012) was longer than that in the chemotherapy or conservative treatment groups (n=7 and 24 months, respectively). Metastatectomy, presense or abscence of residual tumor and extent of residual tumor were significant prognostic factors for survival time in female patients with metachronous Krukenberg's tumor of gastric origin. Conclusions: A close observation and evaluation with ultrasound or computed tomography is necessary in female patients with advanced gastric cancer to detect a metachronous Krukenberg's tumor as soon as possible. The surgeon must operate more aggressively in patients with metachronous Krukenberg's tumors.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• 한국노년학
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• v.40 no.1
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• pp.111-130
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• 2020

This qualitative study aims to understand family members' caregiving experience for middle-aged and elderly breast cancer survivors at early stages. A total of four families of breast cancer survivors were given focus group interviews(FGI), and an additional family was interviewed individually. The thematic analyses of the FGI and individual in-depth interview discussions revealed the following four themes: first, day-to-day feelings like walking on thin ice (entangled emotions with each treatment stage, regret of watching a survivor's pain, fear of recurrence and death, concerns of changes in family relationships, and various feelings experienced as a daughter), second, caregiving has become a mainstay in my life (unfamiliar and unskilled care, losing my life), third, beginning to recover and different experiences between a survivor and a family caregiver (not understanding a survivor's pain from the abyss, forgetting that the survivor is still a cancer patient and that treating him or her casually), and fourth, moving forward (hope that things will be better, taking care of myself to prevent exhaustion). Based on the results of this study, we proposed social welfare services and policy measures to reflect the psychosocial needs of family caregivers of breast cancer survivors and support family caregivers during the care process.