• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4331-4338
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• 2014

$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.249-253
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• 2013

Background: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor. Materials and Methods: In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group. Results: The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. Conclusions: The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9395-9404
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• 2014

Background: Primary vaginal yolk sac tumor is a rare malignancy in the pediatric population, and a diagnostic challenge and appropriate initial treatment remains unsolved. The aim of this study was to investigate the clinicopathologic features, treatment and prognosis of this tumor. Materials and Methods: Eight cases of primary vaginal yolk sac tumor were reported with a literature review. Results: There were 4 pure yolk sac tumor cases and four mixed germ cell tumors containing yolk sac tumor element, including two cases with embryonal carcinoma and two cases with embryonal carcinoma and dysgerminoma. Partial vaginectomy was performed in four cases and all patients received chemotherapy. 85 cases in literatures were reviewed and 9 cases were misdiagnosed. Follow-up data was available in 77 cases and 5-year overall survival rate was 87.6%. 5-year survival rate of biopsy with chemotherapy, conservative surgery with chemotherapy and radical surgery with chemotherapy was 91.1%, 100% and 28.6%, respectively (p<0.001). Compared to cases without relapse or metastasis after initial treatment, patients with relapse or metastasis had a shorter overall survival (35.6% vs 96.6%, p<0.001). Conclusions: Mixed germ cell tumor containing yolk sac tumor element was not uncommon and partial vaginectomy may be a good choice for primary vaginal mixed yolk sac tumor type to eradicate local tumor cells and provide complete information for pathological diagnosis and postoperative adjuvant therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7575-7581
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• 2014

MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.827-831
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• 2012

To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of $62{\pm}11$ years. Median duration of follow-up was $47{\pm}31$ months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ${\geq}70$ years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.

• Journal of KIISE:Databases
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• v.41 no.4
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• pp.249-255
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• 2014

Copy number variations(CNVs) are a recently recognized class of human structural variations and are associated with a variety of human diseases, including cancer. To find important cancer genes, researchers identify novel CNVs in patients with a particular cancer and analyze large amounts of genomic and clinical data. We present a tool called CNVDAT which is able to detect CNVs from NGS data and systematically analyze the genomic and clinical data associated with variations. CNVDAT consists of two modules, CNV Detection Engine and Sequence Analyser. CNV Detection Engine extracts CNVs by using the multi-resolution system of scale-space filtering, enabling the detection of the types and the exact locations of CNVs of all sizes even when the coverage level of read data is low. Sequence Analyser is a user-friendly program to view and compare variation regions between tumor and matched normal samples. It also provides a complete analysis function of refGene and OMIM data and makes it possible to discover CNV-gene-phenotype relationships. CNVDAT source code is freely available from http://dblab.hallym.ac.kr/CNVDAT/.

• Journal of Hospice and Palliative Care
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• v.14 no.2
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• pp.101-109
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• 2011

Purpose: The Assessing Care Of Vulnerable Elders project has developed indicators for the quality of the end-of-life (EOL) care. However, family members of cancer patients may have a different view on the quality indicators (QIs) established by health care experts. We evaluated the QIs from the family members' perspective. Methods: The information used in this study was gathered by surveying family members of cancer patients who were admitted to the inpatient hospice ward in Korea. A cross-sectional anonymous questionnaire was distributed to 120 potential respondents from July to October 2009. We included 69 responses in this study (effective response rate, 57.5%). Statistical analysis was performed by using SPSS for Win ver. 14.0, with independent t-test and Pearson's chi-square test. Results: Among QIs for good hospice care, families agreed the most on "Medical examination by the palliative care team or specialist" (88.4%) and "Dying in the family's presence" (88.4%). They agreed the least on "Discussing cardiopulmonary resuscitation with patients" (15.9%). Among QIs for bad hospice care, "Occurrence of fall or pressure ulcer are undesirable" showed the highest agreement rate (94.2%). The lowest agreement rate was 11.6% on "Dying in the hospital is undesirable." In addition, women, patients who were aware of their prognoses, and people with a high socioeconomic status tended to agree more on the QIs. Conclusion: Patients' families did not agree on some of the QIs recommended by previous studies. Family members' characteristics were related to their opinions on QIs.

• Journal of Life Science
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• v.27 no.10
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• pp.1225-1231
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• 2017

Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.128-132
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• 2011

Purpose: Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs). However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy. Methods: We examined 35 patients (27 men and 8 women) diagnosed with IC-GCTs between August 2004 and April 2008 and received risk-adapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR) or high-risk (HR) groups and a retrospective analysis was performed using information from the medical records. Results: Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS) was 95.7%. The EFS rate was 100% in the LR group and 90% in the HR group, respectively. Conclusion: Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatin-based treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.

• Tuberculosis and Respiratory Diseases
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• v.71 no.1
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• pp.15-23
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• 2011

Background: Gefitinib and erlotinib are useful, molecular targeted agents in patients with non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. We compared the efficacy and toxicity of two drugs in patients with squamous cell lung cancer, most of whom are male smokers. Methods: We retrospectively reviewed the clinical information on patients with NSCLC who were treated with gefitinib or erlotinib treatment at Chonnam National University Hwasun Hospital between July 2002 and November 2009. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were compared between the two drugs. Results: A total of 182 (100 gefitinib vs. 82 erlotinib) of 584 patients treated by targeted agents had squamous histology. Of the 182 patients, 167 (91.7%) were male and 159 (87.4%) were smokers. The ORR and disease control rate (DCR) were 4.9% and 40.6%, and there was no significant difference between gefitinib and erlotinib (ORR, 5.0% vs 4.8%; p=0.970; DCR, 40.0% vs 41.4%; p=0.439). The median OS in the gefitinib group was 12.1 months, and that in the erlotinib was 12.7 months (hazard ratio [HR], 1.282; 95% confidence interval [CI], 0.771~2.134; p=0.339). The median PFS for the gefitinib group was 1.40 months, compared with 1.37 months for the erlotinib group (HR, 1.092; 95% CI, 0.809~1.474; p=0.564). Skin rash ${\geq}$grade 3 was more common in erlotinib (12.2%) than gefitinib (1.0%, p=0.003) groups. Conclusion: This retrospective study showed that the two drugs appear to have similar antitumor efficacy and toxicity except for skin rash.