• The Korean Journal of Applied Statistics
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• v.37 no.2
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• pp.225-237
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• 2024

In the analysis of competing risks data, some of covariates may not be fully observed for some subjects. In such cases, excluding subjects with missing covariate values from the analysis may result in biased estimates and loss of efficiency. In this paper, we studied multiple imputation and the augmented inverse probability weighting method for regression parameter estimation in the cause-specific proportional hazards model with missing covariates. The performance of estimators obtained from multiple imputation and the augmented inverse probability weighting method is evaluated by simulation studies, which show that those methods perform well. Multiple imputation and the augmented inverse probability weighting method were applied to investigate significant risk factors for the risk of death from breast cancer and from other causes for breast cancer data with missing values for tumor size obtained from the Prostate, Lung, Colorectal, and Ovarian Cancer Screen Trial Study. Under the cause-specific proportional hazards model, the methods show that race, marital status, stage, grade, and tumor size are significant risk factors for breast cancer mortality, and stage has the greatest effect on increasing the risk of breast cancer death. Age at diagnosis and tumor size have significant effects on increasing the risk of other-cause death.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.241-247
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• 2008

Paclitaxel is a taxane diterpene amide, which was first extracted from the stem bark of the western yew, Taxus brevifolia. This natural product has proven to be useful in the treatment of a variety of human neoplastic disorders, including ovarian cancer, breast and lung cancer. Paclitaxel is a highly hydrophobic drug that is poorly soluble in water. It is mainly given by intravenous administration. Therefore, The pharmaceutical formulation of paclitaxel ($Taxol^{(R)}$; Bristol-Myers Squibb) contains 50% $Cremophor^{(R)}$ EL and 50% dehydrated ethanol. However the ethanol/Cremophor EL vehicle required to solubilize paclitaxel in $Taxol^{(R)}$ has a pharmacological and pharmaceutical problems. To overcome these problems, new formulations for paclitaxel that do not require solubilization by $Cremophor^{(R)}$ EL are currently being developed. Therefore this study utilized a supercritical fluid antisolvent (SAS) process for cremophor-free formulation. To select hydrophilic polymers that require solubilization for paclitaxel, we evaluated polymers and the ratio of paclitaxel/polymers. HP-${\beta}$-CD was used as a hydrophilic polymer in the preparation of the paclitaxel solid dispersion. Although solubility of paclitaxel by polymers was increased, physical stability of solution after paclitaxel/polymer powder soluble in saline was unstable. To overcome this problem, we investigated the use of surfactants. At 1/20/40 of paclitaxel/hydrophilic polymer/ surfactant weight ratio, about 10 mg/mL of paclitaxel can be solubilized in this system. Compared with the solubility of paclitaxel in water ($1\;{\mu}g/mL$), the paclitaxel solid dispersion prepared by SAS process increased the solubility of paclitaxel by near 10,000 folds. The physicochemical properties was also evaluated. The particle size distribution, melting point and amophorization and shape of the powder particles were fully characterized by particle size distribution analyzer, DSC, SEM and XRD. In summary, through the SAS process, uniform nano-scale paclitaxel solid dispersion powders were obtained with excellent results compared with $Taxol^{(R)}$ for the physicochemical properties, solubility and pharmacokinetic behavior.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5445-5450
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• 2012

Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8447-8450
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• 2014

Background: To evaluate factors for predicting the granulosa cell tumor of the ovary (GCTO) pre-operatively. Materials and Methods: This retrospective designed study was conducted on 34 women with GCTO as the study group and 76 women with benign ovarian cysts as the control group. Data were recorded from the hospital database and included age, body mass index (BMI), parity, serum estradiol ($E_2$) levels, diameter of the mass, ultrasonographic features, serum CA125 level, risk of malignancy index (RMI), duration of menopause, postoperative histopathology result, and the neutrophil/lymphocyte ratio (NLR). Results: The demographic parameters showed no statistically significant difference between the groups. Preoperative diameter of the mass, CA125, duration of menopause, and neutrophil/lymphocyte ratio were significantly different between the groups. ROC curve analysis demonstrated that diameter of the mass, serum estradiol and Ca125 levels, RMI and NLR may be discriminative factors in predicting GCTO preoperatively. Conclusions: In conclusion, we think that a careful preoperative workshop including diameter of the mass, serum estradiol ($E_2$) and Ca125 levels, RMI and NLR may predict GCTO and may prevent incomplete approaches.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.37-45
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• 2012

목적 : 최근 NF-${\kappa}B$와 STAT3의 활성억제와 관련된 항암제 연구가 주목받고 있으며, 본 연구는 사독(蛇毒)이 세포자멸사 관련 단백질의 발현 조절을 통하여 세포자멸사를 유도하고, NF-${\kappa}B$와 STAT3의 활성억제를 유도하여 난소암 PA-1 세포의 성장을 억제하는지를 확인하고, 해당 기전을 살펴보고자 하였다. 방법 : 사독을 처리한 후 난소암 PA-1 세포의 세포자멸사의 관찰에는 DAPI, TUNEL staining assay를 시행하였고, 세포자멸사 조절단백질 및 NF-${\kappa}B$, STAT3의 활성 변동 관찰에는 western blot analysis를 시행하였다. 결과 : 1. 사독을 처리한 후 난소암 PA-1 세포에서 세포자멸사가 유도되어 암세포성장이 억제되었다. 2. 사독을 처리한 후 세포자멸사 관련 단백질 중 세포자멸사 촉진 단백질인 cleaved caspase-3, Bax의 발현은 증가되었고, 세포자멸사 억제 단백질인 Bcl-2의 발현은 감소되었다. 3. 사독을 처리한 후 난소암 PA-1 세포의 NF-${\kappa}B$와 STAT3 발현은 감소되었고, 각각의 길항제인 salicylic acid와 stattic 처리 후 NF-${\kappa}B$와 STAT3 발현은 더욱 감소되었다. 결론 : 사독은 난소암 세포의 세포자멸사 유발과, NF-${\kappa}B$와 STAT3의 활성억제를 통해 치료 효율이 높고, 내성이 적은 난소암 치료제의 개발에 도움이 될 것으로 기대된다.

• Bulletin of the Korean Chemical Society
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• v.23 no.8
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• pp.1139-1143
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• 2002

Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.4
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• pp.237-244
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• 2020

Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500-600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.

• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.201-205
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• 2009

Triglyceride solid lipid with medium chain fatty acid, tricaprin (TC), was used as a core matrix of lipid nanoparticles (LN) to solubilize water-insoluble paclitaxel and enhance the stability of nanoparticles by immobilization of incorporated drug in the solid core during storage at low temperature. In the present study, TC-LN containing paclitaxel was prepared by hot melt homogenization method using TC as a core lipid and phospholipids as stabilizers. The particle size of TC-LN containing paclitaxel was less than 200 nm and its zeta potential was around -40 mV. Calorimetric analysis showed TC core could be solidified by freezing and thawing in the manufacturing process in which the hot dispersion should be prepared at elevated temperature and subsequently cooled to obtain solid lipid nanoparticles. The melting transition of TC core was observed at $27.5^{\circ}C$, which was lower than melting point of TC bulk. The particle size of TC-LN remained unchanged when kept at $4^{\circ}C$. Paclitaxel containing TC-LN showed comparable anticancer activity to the Cremophore ELbased paclitaxel formulation against human ovarian (OVCAR-3) and breast (MCF-7) cancer cell lines. Thus, lipid nanoparticles with medium chain solid lipid may have a potential as alternative delivery system for parenteral administration of paclitaxel.

• Genomics & Informatics
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• v.14 no.4
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• pp.187-195
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• 2016

In genetic association studies with high-dimensional genomic data, multiple group testing procedures are often required in order to identify disease/trait-related genes or genetic regions, where multiple genetic sites or variants are located within the same gene or genetic region. However, statistical testing procedures based on an individual test suffer from multiple testing issues such as the control of family-wise error rate and dependent tests. Moreover, detecting only a few of genes associated with a phenotype outcome among tens of thousands of genes is of main interest in genetic association studies. In this reason regularization procedures, where a phenotype outcome regresses on all genomic markers and then regression coefficients are estimated based on a penalized likelihood, have been considered as a good alternative approach to analysis of high-dimensional genomic data. But, selection performance of regularization procedures has been rarely compared with that of statistical group testing procedures. In this article, we performed extensive simulation studies where commonly used group testing procedures such as principal component analysis, Hotelling's $T^2$ test, and permutation test are compared with group lasso (least absolute selection and shrinkage operator) in terms of true positive selection. Also, we applied all methods considered in simulation studies to identify genes associated with ovarian cancer from over 20,000 genetic sites generated from Illumina Infinium HumanMethylation27K Beadchip. We found a big discrepancy of selected genes between multiple group testing procedures and group lasso.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.4
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• pp.151-157
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• 2014

Objective: To evaluate the association between the severity of endometriosis and the preoperative neutrophil-to-lymphocyte ratio (NLR) and serum level of cancer antigen 125 (CA 125). Methods: Data were obtained from the medical records of 419 patients who underwent laparoscopic conservative surgery for ovarian endometrioma between April 2005 and March 2013. Each patient's preoperative complete blood count was recorded and the endometriosis score was assessed. Results: The endometriosis score was not associated with either the NLR or the serum level of CA 125. The endometriosis score was negatively related to preoperative hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The only positive association was between NLR and the patients' age. NLR and preoperative serum anti-M$\ddot{u}$llerian hormone level were found to be negatively related. Conclusion: The severity of endometriosis was not associated with the serum level of CA 125 or the NLR. The presence of a negative correlation between the severity of endometriosis and red blood cell dynamics needs further investigation.