Side population (SP) cells have stem cell-like properties with a capacity for self-renewal and are resistant to chemotherapy and radiotherapy. Therefore the presence of SP cells in human breast cancer probably has prognostic value. Objective: To investigate the characteristics of SP cells and identify the relationship between the SP cells levels and clinico-pathological parameters of the breast tumor and disease-free survival (DFS) in breast cancer patients. Materials and Methods: A total of 122 eligible breast cancer patients were consecutively recruited from January 1, 2006 to December 31, 2007 at Yunnan Tumor Hospital. All eligible subjects received conventional treatment and were followed up for seven years. Predictors of recurrence and/or metastasis and DFS were analyzed using Cox regression analysis. Human breast cancer cells were also obtained from fresh human breast cancer tissue and cultured by the nucleic acid dye Hoechst33342 with Verapami. Flow cytometry (FCM) was employed to isolate the cells of SP and non-SP types. Results: In this study, SP cells were identified using flow cytometric analysis with Hoechst 33342 dye efflux. Adjusted for age, tumor size, lymph nodal status, histological grade, the Cox model showed a higher risk of recurrence and/or metastasis positively associated with the SP cell level (1.75, 1.02-2.98), as well as with axillary lymph node metastasis (2.99, 1.76-5.09), pathology invasiveness type (1.7, 1.14-2.55), and tumor volume doubling time (TVDT) (1.54, 1.01-2.36). Conclusions: The SP cell level is independently associated with tumor progression and clinical outcome after controlling for other pathological factors. The axillary lymph node status, TVDT and the status of non-invasive or invasive tumor independently predict the prognosis of breast cancer.
Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of $CD4^+$, $CD19^+$, $CD44^+$, $CD25^+$, NK cells, and an increased $CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating $CD19^+$ lymphocytes compared to those with low $CD19^+$ lymphocytes (P=0.037), with $CD19^+$ showing an important cutoff of $7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival.
Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathological factors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patients who underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198 expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factor and its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher in patients with poor prognosis than those with good prognosis (P<0.05). Kaplan-Meier analysis results showed that the miR-198 expression level had a significant correlation with survival time (P=0.030) and that patients with a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed that patient prognosis (P=0.014), tumor length (P=0.040) and expression (P=0.012), and survival time had a significant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker for selection of cases requiring especial attention.
Kim, Kyung Hwan;Chang, Jee Suk;Keum, Ki Chang;Ahn, Joong Bae;Lee, Chang Geol;Koom, Woong Sub
Radiation Oncology Journal
/
v.31
no.1
/
pp.25-33
/
2013
Purpose: We reviewed the treatment outcomes and prognostic factors for patients with anal canal carcinoma who were treated with curative intent chemoradiotherapy (CRT) at Severance Hospital from 2005 to 2011. Materials and Methods: Data for 38 eligible patients treated during this period were reviewed. All patients were treated with curative intent using radiotherapy (RT) with (n = 35) or without concomitant chemotherapy (n = 3). Among 35 patients who received CRT, most of the chemotherapeutic regimens were either 5-fluorouracil (5-FU) plus mitomycin C (23 patients) or 5-FU plus cisplatin (10 patients). Recurrence-free survival (RFS), colostomy-free survival (CFS), overall survival (OS), and locoregional control (LRC) rates were calculated using the Kaplan-Meier method and survival between subgroups were compared using the log-rank test. Cox's proportional hazard model was used for multivariate analysis. Results: Over a median follow-up period of 44 months (range, 11 to 96 months), 3-year RFS, CFS, OS, and LRC were 80%, 79%, 85%, and 92%, respectively. In multivariate analysis, tumor size >4 cm was an independent predicting factor for poorer RFS (hazard ratio [HR], 6.35; 95% confidence interval [CI], 1.42 to 28.5; p = 0.006) and CFS (HR, 6.25; 95% CI, 1.39-28.0; p = 0.017), while the presence of external iliac lymph node metastasis was an independent prognosticator for poorer OS (HR, 9.32; 95% CI, 1.24 to 70.3; p = 0.030). No treatment-related colostomies or deaths occurred during or after treatment. Conclusion: Curative intent CRT resulted in excellent outcomes that were comparable to outcomes in previous randomized trials. No severe treatment-related toxicities were observed.
Proceedings of the Korean Society of Agricultural Engineers Conference
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1999.10c
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pp.155-161
/
1999
The land reclamation area of Saemangeum(Kunsan) is located between 126$^{\circ}$10' E~126$^{\circ}$50' E and 35$^{\circ}$35' N~356$^{\circ}$05'N at the western coast of the Korean peninsula. The are many small islands including extensive areas of semi-diurnally flooded and dewatered tidal flats. The reclamation area of Saemangeum has a range of 5.6m spring tide and the maximum tidal current speed is about 1.41m s-1 in ordinary spring tide. Most of the sediments deposited on the tidal flats are transported from the Geum river, the Manjyung river and The Dongjin river. The soil in this area consists of silty sand with the depth of 10m to 30m . The wind in winter is strong from the direction of northwest. In the past twenty years, land reclamation projects for agricutural purpose or industrial cocmplex have been mostly implemented along the western coast of Korea. Saemangeum coastal area is being constructed the33km sea dike and 40, 100ha reclamation area. The purpose of this study is to find the residual circulations in four seasons after the dike construction by a robust diagnostic and prognostic numerical model. Heat flux at the sea surface in January ,May , August , October was asopted on the basis on the daily inflow of solar radiation at the earth surface, assuming an average atomospheric transmission and no clouds , as a function of latitude and time of year(George L.P.J.E William, 1990). The discharge from the Geum , the Mankyung and the Dongjin rivers was adopted on the basis of experience formula of river flow in January , May ,August, October (The M. of C.Korea, 1993) . Water temperature and salinity along the open boundaries are obtained from the results of field observation s.
Introduction: The extent of lymphadenectomy in the surgical treatment of gastric cancer is a topic of controversy among surgeons. This study was conducted to analyze the American National Cancer Database (NCDB) and conclude the optimal extent of lymphadenectomy for gastric adenocarcinoma. Methods: The NCDB for gastric cancer was utilized. Patients who received at least a partial gastrectomy were included. Patients with metastatic disease, unknown TNM stages, R1/R2 resection, or treated with a palliative intent were excluded. Joinpoint regression was used to identify the extent of lymphadenectomy that reflects the optimal survival. Cox regression analysis and Bayesian information criterion were used to identify significant survival predictors. Kaplan-Meier was applied to study overall survival and stage migration. Results: 40,281 patients of 168,377 met the inclusion criteria. Joinpoint analysis showed that dissection of 29 nodes provides the optimal median survival for the overall population. Regression analysis reported the cutoff ${\geq}29$ to have a better fit in the prognostic model than that of ${\geq}15$. Dissection of ${\geq}29$ nodes in the higher stages provides a comparable overall survival to the immediately lower stage. Nonetheless, the retrieval of ${\geq}15$ nodes proved to be adequate for staging without a significant stage migration compared to ${\geq}29$ nodes. Conclusion: The extent of lymphadenectomy in gastric adenocarcinoma is a marker of improved resection which reflects in a longer overall survival. Our analysis concludes that the dissection of ${\geq}15$ nodes is adequate for staging. However, the dissection of 29 nodes might be needed to provide a significantly improved survival.
Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.
Purpose: To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). Materials and methods: Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. Results: We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). Conclusions: Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.
Seelam, Sudhakara Reddy;Lee, Ji Youn;Kim, Young Joo;Lee, Yun-Sang;Jeong, Jae Min
Journal of Radiopharmaceuticals and Molecular Probes
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v.1
no.2
/
pp.137-144
/
2015
Hypoxia is an important adverse prognostic factor for tumor progression and is a major cause of failure of radiation therapy. In case of short-term hypoxia, the metabolism can recover to normal, but if hypoxia persists, it causes irreversible cell damage and finally leads to death. So a hypoxia marker would be very useful in oncology. In particular, 2-nitroimidazole can be reduced to form a reactive chemical species, which can bind irreversibly to cell components in the absence of sufficient oxygen, thus, the development of radiolabeled nitroimidazole derivatives for the imaging of hypoxia remains an active field of research to improve cancer therapy result. 2-nitroimidazole based hypoxia marker, [$^{18}F$]FMISO holds promise for the evaluation of tumor hypoxia by Positron emission tomography (PET), at both global and local levels. In the present study, [$^{18}F$]FMISO was synthesized using an automatic synthesis module with high radiochemical purity (>99%) in 60 min. Immunohistochemical analysis using pimonidazole confirmed the presence of hypoxia in xenografted CT-26 tumor tissue. A biodistribution study in CT-26 xenografted mice showed that the increased tumor-to-muscle ratio and tumor-to-blood ratios from 10 to 120 min post-injection. In the PET study, [$^{18}F$]FMISO also showed increased tumor-to-muscle ratios from 10 to 120 min post-injection. In conclusion, this study demonstrates the feasibility and utility of [$^{18}F$]FMISO for imaging hypoxiain mouse colon cancer model using small animal PET.
In acute uncomplicated falciparum malaria, there is a continuum from mild to severe malaria. However, no mathematical system is available to predict uncomplicated falciparum malaria patients turning to severe malaria. This study aimed to devise a simple and reliable model of Malaria Severity Prognostic Score (MSPS). The study was performed in adult patients with acute uncomplicated falciparum malaria admitted to the Bangkok Hospital for Tropical Diseases between 2000 and 2005. Total 38 initial clinical parameters were identified to predict the usual recovery or deterioration to severe malaria. The stepwise multiple discriminant analysis was performed to get a linear discriminant equation. The results showed that 4.3% of study patients turned to severe malaria. The MSPS = 4.38 (schizontemia) + 1.62 (gametocytemia) + 1.17 (dehydration) + 0.14 (overweight by body mass index; BMI) + 0.05 (initial pulse rate) + 0.04 (duration of fever before admission)-0.50 (past history of malaria in last 1 year). 0.48 (initial serum albumin)-5.66. Based on the validation study in other malaria patients, the sensitivity and specificity were 88.8% and 88.4%, respectively. We conclude that the MSPS is a simple screening tool for predicting uncomplicated falciparum malaria patients turning to severe malaria. However, the MSPS may need revalidation indifferent geographical areas before utilized at specific places.
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