• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8503-8512
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• 2016

The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline, WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the mechanisms of the action of WP631 and DOX suggest that this bisanthracycline can be an effective alternative in ovarian cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9107-9112
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• 2014

Purpose: To investigate and study the relationship between the PLCE1 rs2274223 gene polymorphism and susceptibility to esophageal cancer by meta-analysis. Materials and Methods: The literature was searched in Wanfang, CNKI, PubMed, CBM, Web of Science, MEDLINE, EMBASE, Springer, Elsevier and Cochrane databases from the date of January $1^{st}$ 2004 to April $1^{st}$ 2014 to collect case-control studies on the PLCE1 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer and control groups, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as effect indexes. Disqualified studies were excluded. Odds ratios of PLCE1 rs2274223 genotype distributions in the group of patients with esophageal cancer and the group of healthy control were calculated. The metaanalysis software, RevMan5.0, was applied for heterogeneity test, pooled OR and 95% confidence intervals. Sensitivity analysis and publication bias were also explored. Results: A total of twelve case-control studies were included, covering a total of 9, 912 esophageal cancer cases and 13, 023 controls were included. The pooled odds ratio of PLCE1 rs2274223 genotype GA vs AA was 1.29 (95%CI=1.17~1.43), p<0.01, GG vs AA was 1.65 (95%CI=1.32~2.05), p<0.01, GG/GA vs AA was 1.30 (95%CI=1.16~1.46), p<0.01 and GG vs GA/AA was 1.48 (95%CI=1.22~1.80), p<0.01. The PLCE1 rs2274223 polymorphism was thus associated with risk of esophageal cancer in all genetic models. In the stratified analysis by ethnicity, and source of controls, no significantly increased risk was observed for white persons. There was no obvious publication bias detected. Conclusions: This meta-analysis showed there was a significantly association between PLCE1 rs2274223 polymorphism and esophageal cancer in yellow race populations. Due to some minor limitations, our findings should be confirmed in further studies.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.255-261
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• 2010

Cefprozil is a broad-spectrum oral beta-lactam cephalosporin consisting of cis- and trans-isomeric mixture whose ratio is approximately 90:10. Cefprozil is used to treat certain infections caused by bacteria such as bronchitis and ear, skin, and throat infections. The purpose of the present study was to evaluate the bioequivalence of two cefprozil tablets, $Cefzil^{(R)}$ tablet 250 mg (BMS Pharmaceutical Korea., Ltd.) and Procezil tablet 250 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of cefprozil from the two cefprozil formulations were tested using KP VIII Apparatus I method with water dissolution media. Thirty five healthy male subjects, $24.00{\pm}1.53$ years in age and $69.77{\pm}9.99$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After four tablets containing 1000 mg as cefprozil were orally administered, blood samples were taken at predetermined time intervals and the concentrations of cefprozil in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in water tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ on the basis of total-cefprozil were calculated, and computer program (K-BE Test 2002) was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Cefzil^{(R)}$ tablets, were -0.81%, -3.00% and -6.83% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.9515~log 1.0454 and log 0.9613~log 1.0465 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to $Cefzil^{(R)}$ tablet.

• Journal of Preventive Medicine and Public Health
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• v.49 no.6
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• pp.349-366
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• 2016

Objectives: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). Methods: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). Results: Thirty-two studies had parity categories of 1, 2, and ${\geq}3$. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p<0.01; Q = 59.46; $I^2=47.9%$). Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and >13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p = 0.17; Q = 18.79, $I^2=25.5%$). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. Conclusions: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6077-6081
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• 2012

Background: This study was performed to analyze the prognostic implications of pretreatment or preoperative thrombocytosis in women with gynecologic malignancies. Material and Methods: We surveyed 2 medical databases, PubMed and EMBASE, to identified all relevant studies. A total of 14 (n=3,490) that evaluated the link between thrombocytosis and 5-year survival were included. REVMAN version 5.1 was used for our analysis and publication bias was evaluated using the Begg's funnel plot and tested by STATA 11.0. Risk ratios (RRs) with 95% confidence intervals (CIs) generated by the random effect model were used to assess the strength of any association. Results: 709(20.3%) of the 3,490 patients exhibited thrombocytosis (platelet counts > $400{\times}10^9/L$) at primary diagnosis, and their mortality was 1.62-fold higher compared with the others (RR=1.62, 95%CI=[1.28-2.05], p<0.0001). Thrombocytosis failed to have a stronger effect on the survival of advanced patients of stages III to IV in our study (n=478, RR=1.29, 95% CI=[1.13-1.48], p=0.0003), nor in women with cervical cancer in stage IB (n=1371, RR=1.73, 95% CI=[1.71-2.58], p=0.007). In addition, when adjusted for different carcinoma, it was associated with worse prognosis for all except the ones with vulvar cancer (n=201, RR=0.43, 95% CI=[0.14-1.29], p=0.13). Conclusions: This meta-analysis indicated that thrombocytosis might be associated with a worse prognosis for patients with gynecologic malignancies but without specificity or sensitivity for the ones in advanced stage. When adjusted for different gynecologic malignancies, it showed a significant effect on survival of all except vulvar cancers.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.10
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• pp.1299-1307
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• 2010

This study was conducted to evaluate the effect of dietary antioxidant and energy density on performance and antioxidative status in transition cows. Forty cows were randomly allocated to 4 dietary treatments in a $2{\times}2$ factorial design. High or low energy density diets (1.43 or 1.28 Mcal $NE_L$/kg DM, respectively) were formulated with or without antioxidant (AOX, a dry granular blend of ethoxyquin and tertiary-butylhydroquinone; 0 or 5 g/cow per d). These diets were fed to cows for 21 days pre-partum. During the post-partum period, all cows were fed the same lactation diets, and AOX treatment followed as for the pre-partum period. Feeding a high energy diet depressed the DMI, milk yield, and 4% fat-corrected milk (FCM) of cows. However, AOX inclusion in the diet improved the milk and 4% FCM yields. There was an interaction of energy density by AOX on milk protein, milk fat and total solids contents. Feeding a high energy diet pre-partum increased plasma glucose and ${\beta}$-hydroxybutyrate, whereas dietary AOX decreased plasma ${\beta}$-hydroxybutyrate value during the transition period. There were also interactions between time and treatment for plasma glutathione peroxidase activity and malondialdehyde content during the study. Cows fed high energy diets pre-partum had higher plasma glutathione peroxidase activity 3 days prior to parturition, compared with those on low energy diets. Inclusion of AOX in diets decreased plasma glutathione peroxidase activity in cows 3 and 10 days pre-partum. Addition of AOX significantly decreased malondialdehyde values at calving. Energy density induced marginal changes in fatty acid composition in the erythrocyte membrane 3 days post-partum, while AOX only significantly increased cis-9, trans-11 conjugated linoleic acid composition. The increase in fluidity of the erythrocyte membrane was only observed in the high energy treatment. It is suggested that a diet containing high energy density pre-partum may negatively affect the anti-oxidative status, DMI and subsequent performance. Addition of AOX may improve the anti-oxidative status and reduce plasma ${\beta}$-hydroxybutyrate, eventually resulting in improved lactation performance; the response to AOX addition was more pronounced on the high energy diet.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.3
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• pp.311-319
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• 2012

This study examined the effects of supplementation of fish oil and canola oil in the diet on milk yield, milk components and fatty acid composition of Holstein dairy cows in early lactation. Eight multiparous early lactation Holstein cows ($42{\pm}12$ DIM, $40{\pm}6kg$ daily milk yield) were fed a total mixed ration supplemented with either 0% oil (Control), 2% fish oil (FO), 1% canola oil +1% fish oil (FOCO), or 2% canola oil (CO) according to a double $4{\times}4$ Latin square design. Each period lasted 3 wk; experimental analyses were restricted to the last week of each period. Supplemental oils were added to a basal diet which was formulated according to NRC (2001) and consisted of 20% alfalfa, 20% corn silage and 60% concentrate. Milk yield was similar between diets (p>0.05), but dry matter intake (DMI) was lower (p<0.05) in cows fed FO diet compared to other diets. Milk fat percentage and daily yield decreased (p<0.01) with the supplementation of fish and canola oil. The daily yield and percentage of milk protein, lactose and solids-not-fat (SNF) were not affected by diets (p>0.05). The proportion (g/100 g fatty acids) of short chain fatty acids (SCFA) decreased and polyunsaturated fatty acids (PUFA) increased (p<0.05) in milk of all cows fed diets supplemented with oil. The proportions of 6:0, 8:0, 10:0 12:0 and 14:0 fatty acids in milk fat decreased (p<0.01) for all diets supplemented with oil, but the proportions of 14:1, 16:0 and 16:1 fatty acids were not affected by diets (p>0.05). The proportion of trans(t)-18:1 increased (p<0.01) in milk fat of cows fed FO and FOCO diets, but CO diet had the highest proportion of cis(c)-11 18:1 (p<0.01). The concentration of t-10, c-12 18:2, c-9 t-11 18:2, 18:3, eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) increased (p<0.05) in FO and FOCO diets in comparison with the other two diets. These data indicate that including fish oil in combination with canola oil significantly modifies the fatty acid composition of milk.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3165-3172
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• 2012

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3525-3531
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• 2014

Objective: Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a new technique for identifying different malignant tumors using different uptake values between tumor cells and normal tissues. Here we assessed the diagnostic accuracy of 18F-FDG-PET in patients with testicular cancer by pooling data of existing trials in a meta-analysis. Methods: PubMed/MEDLINE, Embase and Cochrane Central Trials databases were searched and studies published in English relating to the diagnostic value of FDG-PET for testicular cancer were collected. The summary receiver operating characteristic (SROC) curve was used to examine the FDG-PET accuracy. Results: A total of 16 studies which included 957 examinations in 807 patients (median age, 31.1 years) were analyzed. A meta-analysis was performed to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratio (NLR). SROC were derived to demonstrate the diagnostic accuracy of FDG-PET for testicular cancer. The pooled sensitivity and specificity were 0.75 (95% confidence interval (CI), 0.70-0.80) and 0.87 (95% CI, 0.84-0.89), respectively. The pooled DOR was 35.6 (95% CI, 12.9-98.3). The area under the curve (AUC) was 0.88. The pooled PLR and pooled NLR were 7.80 (95% CI, 3.73-16.3) and 0.31 (95% CI, 0.23-0.43), respectively. Conclusion: In patients with testicular cancer, 18F-FDG-PET demonstrated a high SROC area, and could be a potentially useful tool if combined with other imaging methods such as MRI and CT. Nevertheless, the literature focusing on the use of 18F-FDG-PET in this setting still remains limited.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5965-5972
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• 2013

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.