• Journal of Gastric Cancer
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• 제14권2호
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• pp.111-116
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• 2014

Purpose: The standard surgical procedure recommended to treat gastric cancer in advanced cases is dissection of D2 lymph nodes (LNs). However, the optimum number of LNs that should be retrieved in advanced gastric cancer (AGC) remains debatable. Therefore, this study aimed to investigate the optimum number of retrieved LNs and determine the clinical implications of retrieved LN numbers on the treatment of AGC. Materials and Methods: Of 575 AGC patients reviewed, 369 who underwent open curative gastrectomy with D2 or more extensive LN dissection at our institution were analyzed according to their clinicopathologic characteristics and number of LNs retrieved. Results: Multivariate regression analysis revealed that tumor size (P=0.006), depth of invasion (P=0.000), LN metastasis (P=0.000), and stage (P=0.000) were independent variables with predictive value. The 5-year survival rates were differed significantly according to the numbers of LNs retrieved ([1] 15~25 vs. >25 and [2] 15~39 vs. ${\geq}40$) in patients with differentiated carcinoma. Conclusions: Tumor size, depth of invasion, LN metastasis, and stage were independent predictive factors for survival. The number of retrieved LNs was significantly associated with a long-term survival benefit in patients with differentiated carcinoma. Therefore, our data suggest that the retrieval of a minimum of 15 LNs may not be sufficient to warrant a recommendation for further curative surgery and that extensive LN dissection should be considered in advanced carcinoma of the differentiated type.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8599-8604
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• 2016

Ovarian cancer is the main cause of mortality in gynecological malignancy and extensive studies have been conducted to study the underlying molecular mechanisms. The BRCA2 gene is known to be an important tumor suppressor in ovarian cancer, thereby BRCA2 alterations may lead to cancer progression. However, the BRCA2 gene is rarely mutated, and loss of function is suspected to be mediated by epigenetic regulation. In this study we investigated the methylation status and gene expression of BRCA2 in ovarian cancer patients. Ovarian cancer pateints (n=69) were recruited and monitored for 54 months in this prospective cohort study. Clinical specimens were used to study the in situ expression of aberrant BRCA2 proteins and the methylation status of BRCA2. These parameters were then compared with clinical parameters and overall survival rate. We found that BRCA2 methylation was found in the majority of cases (98.7%). However, the methylation status was not associated with protein level expression of BRCA2 (49.3%). Therefore in addition to DNA methylation, other epigenetic mechanisms may regulate BRCA2 expresison. Our findings may become evidence of BRCA2 inactivation mechanism through DNA methylation in the Indonesian population. More importantly, from multivariate analysis, BRCA2 expression was correlated with better overall survival (HR 0.32; p=0.05). High percentage of BRCA2 methylation and correlation of BRCA2 expression with overall survival in epithelial ovarian cancer cases may lead to development of treatment modalities specifically to target methylation of BRCA genes.

• Journal of Gastric Cancer
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• 제10권4호
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• pp.196-205
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• 2010

Purpose: We did a retrospective study to understand the prognostic effects of preoperative blood transfusions in stomach cancer surgery. Materials and Methods: Data for 1,360 patients who underwent gastrectomy for stomach cancer between 2001 and 2009 were retrospectively reviewed. We analyzed factors that affect preoperative transfusion and clinicopathologic features. We also analyzed 5-year and overall survival rates of the transfusion and non transfusion subgroups. Results: Sixty patients (4.4%) required blood transfusion within the preoperative period. The transfused group included patients who took aspirin or clopidogrel (P<0.001), with more advanced T stages (P<0.001), with more advanced nodal metastasis (P=0.00), and with more advanced stages (P=0.00) than the non transfusion group. On multivariate analysis, preoperative transfusion was a statistically significant negative influence on 5-year survival and overall survival rates (58.2% vs 79.9% (P=0.00), 58.2% vs 76.8% (P=0.00)). Applying Cox-regression analyses, blood transfusion did appear to have an effect on prognosis and on 5-year and overall survival rates. Conclusions: We found a direct negative relation between preoperative transfusion and long term prognosis in patients receiving gastric cancer surgery.

• Journal of Gastric Cancer
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• 제10권2호
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• pp.55-62
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• 2010

Purpose: We evaluated the clinicopathological charicterics and prognostic impacts of lymphatic vessel invasion in gastric cancer without lymph node involvement. Materials and Methods: Among 1,795 patients who underwent gastric surgery with gastric cancer at the department of surgery, Hanyang university college of medicine from June 1992 to March 2009, we retrospectively evaluated 890 patients with lymph node negative gastric cancer. Results: The lymphatic vessel invasion correlated significantly with tumor stage, age, tumor size, perineural invasion and operation method. The survival rates were only significantly different between the patients with and without lymphatic vessel invasion in patients with stage Ia (P=0.036). Univariate and multivariate analysis demonstrated that blood vessel invasion and preoperative serum CEA level were significant factor influencing the survival rate in lymph node negative gastric cancer patients with lymphatic invasion. Conclusions: In patients with lymph node negative gastric cancer, the survival rate is significantly lower in those with lymphatic vessel invasion than in those without. Especially, in patients with stage Ia gastric cancer, the survival rates is significantly different between those with and those without lymphatic vessel invasion. Blood vessel invasion and preoperative serum CEA level is an adverse prognostic indicator in patients with stage Ia gastric cancer with lymphatic invasion. Thus we should consider further adjuvant therapies in case of need and need to show more concern to identify gastric cancer patients early at risk for recurrence.

• Journal of the Korean Data and Information Science Society
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• 제17권3호
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• pp.999-1007
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• 2006

The semiparametric gamma frailty models have been often used for multivariate survival analysis because they give an explicit marginal likelihood. The commonly used estimation procedure is the profile likelihood method based on marginal likelihood, which provides the same parameter estimates as the EM algorithm. In this paper we show in finite samples the standard profile-likelihood method can lead to an underestimation of parameters, particularly for the frailty parameter. To overcome this problem, we propose an adjusted profile-likelihood method. For the illustration a numerical example and a small-sample simulation study are presented.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4079-4083
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• 2014

Background: Previous studies have showed that argonaute 2 is a potential factor related to genesis of several cancers, however, there have been no reports concerning gliomas. Methods: Paraffin specimens of 129 brain glioma cases were collected from a hospital affiliated to Binzhou Medical University from January 2008 to July 2013. We examined both argonaute 2 mRNA and protein expression by real-time quantitative PCR (qRT-PCR), Western blot analysis, and immunohistochemistry (IHC). The survival curves of the patients were determined using the Kaplan-Meier method and Cox regression, and the log-rank test was used for statistical evaluations. Results: Both argonaute 2 mRNA and protein were upregulated in high-grade when compared to low-grade tumor tissues. Multivariate analysis revealed that argonaute 2 protein expression was independently associated with the overall survival (HR=4.587, 95% CI: 3.001-6.993; P=0.002), and that argonaute 2 protein expression and WHO grading were independent prognostic factors for progression-free survival (HR=4.792, 95% CI: 3.993-5.672; P<0.001, and HR=2.109, 95% CI: 1.278-8.229; P=0.039, respectively). Kaplan-Meier analysis with the log-rank test indicated that high argonaute 2 protein expression had a significant impact on overall survival (P=0.0169) and progression-free survival (P=0.0324). Conclusions: The present study showed that argonaute 2 expression is up-regulated in gliomas. Argonaute 2 might also serve as a novel prognostic marker.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• 대한골관절종양학회지
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• 제3권1호
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• pp.1-8
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• 1997

Osteosarcoma is the most common primary bony malignancy and its survivorship has been progressed markedly through refined chemotherapy and surgery. But still there are many non-responders and analysis of prognostic factors may be helpful for them. Two hundred and sixty-six patients were enlisted between Mar, 1985 and Sep. 1994. Among them our inclusion criteria were: 1)primary, nonmetastatic classical osteosarcoma 2)extremity in location 3)no prior treatment at other institute and completed neoadjuvant chemotherapy and surgery according to our protocol. One hundred and eleven cases were eligible. Analyzed factors were:age, sex, location, tumor size, and pathologic response. Statistical methods were log-rank test for univariate and Cox's test for multivariate analysis. Male to female ratio was 69:42 with an average age of 17.2 years. Locations of tumor were distal femur 59, proximal tibia 29, and proximal humerus 8. Tumor size were measured by its maximal diameter and 48 cases were above 10cm and 47 cases were below 10cm. For pathologic response, 57 cases showed more than 90% and 54 cases were less than that. Limb salvage procedure was 101 cases and amputation was 10 cases and their local recurrence rate were 3.6%. Average follow-up period was 24(9-78.2) months and their final status was CDF 86, AWD 8, NED 5, and DOD 12 cases. In univariate study: type of operation(p=0.005), tumor size(p=0.005), and pathologic response(p=0.02) were significant variables. Pathologic response(p=0.03) and type of operation(p=0.01) were meaningful prognostic factors on multivariate analysis. But the latter result was interpreted as a bias, so pathologic response remained as a sole meaningful prognostic factor. More aggressive chemotherapy will be needed to improve the survival.

• Radiation Oncology Journal
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• 제37권3호
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• pp.185-192
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• 2019

Purpose: The effectiveness of thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer (ES-SCLC) patients is increasingly reported, but there is no definite consensus on its application. The aim of this study was to identify factors associated with better outcomes of TRT among patients with ES-SCLC, focusing on whether a higher TRT dose could improve treatment outcome. Materials and Methods: The medical records of 85 patients with ES-SCLC who received TRT between January 2008 and June 2017 were retrospectively reviewed. Eligibility criteria were a biological effective dose with α/β = 10 (BED) higher than 30 Gy₁₀ and completion of planned radiotherapy. Results: During a median follow-up of 5.3 months, 68 patients (80.0%) experienced disease progression. In univariate analysis, a BED >50 Gy₁₀ was a significant prognostic factor for overall survival (OS; 40.8% vs. 12.5%, p = 0.006), progression-free survival (PFS; 15.9% vs. 9.6%, p = 0.004), and intrathoracic PFS (IT-PFS; 39.3% vs. 20.5%, p = 0.004) at 1 year. In multivariate analysis, a BED >50 Gy₁₀ remained a significant prognostic factor for OS (hazard ratio [HR] = 0.502; 95% confidence interval [CI], 0.287-0.876; p = 0.015), PFS (HR = 0.453; 95% CI, 0.265-0.773; p = 0.004), and IT-PFS (HR = 0.331; 95% CI, 0.171-0.641; p = 0.001). Response to the last chemotherapy was also associated with better OS in both univariate and multivariate analysis. Conclusion: A TRT dose of BED >50 Gy₁₀ may be beneficial for patients with ES-SCLC. Further studies are needed to select patients who will most benefit from high-dose TRT.

• Oncology Letters
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• 제18권6호
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• pp.5731-5738
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• 2019

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Novel biomarkers of ccRCC may provide crucial information on tumor features and prognosis. The present study aimed to determine whether the expression of γ-aminobutyric acid (GABA) A receptor subunit θ (GABRQ) could serve as a novel prognostic marker of ccRCC. GABA is the main inhibitory neurotransmitter in the brain that activates the receptor GABAA, which is comprised of three subunit isoforms: GABRA3, GABRB3 and GABRQ. A recent study reported that GABRQ is involved in the initiation and progression of hepatocellular carcinoma; however, the role of GABRQ in ccRCC remains unknown. In the present study, clinical and transcriptomic data were obtained from cohorts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential GABRQ expression levels among early (TI and II), late (TIII and IV), nonmetastatic (M0) and metastatic (M1, primary tumor) stages of ccRCC samples were then identified. Furthermore, the use of GABRQ as a prognostic gene was analyzed using Uno's C-index based on the time-dependent area under the curve (AUC), the AUC of the receiver operating characteristic curve at 5 years, the Kaplan-Meier survival curve and multivariate analysis. The survival curve analysis revealed that low GABRQ mRNA expression was significantly associated with a poor prognosis of ccRCC (P<0.001 and P=0.0012 for TCGA and ICGC data, respectively). In addition, analyses of the C-index and AUC values further supported this discriminatory power. Furthermore, the prognostic value of GABRQ mRNA expression was confirmed by multivariate Cox regression analysis. Taken together, these results suggested that GABRQ mRNA expression may be considered as a novel prognostic biomarker of ccRCC.