• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.165-171
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• 2007

Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5797-5804
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• 2013

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1785-1787
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• 2016

Granular cell tumor (GCT) of the oral cavity is a benign lesion. Half of oral GCTs demonstrate pseudocarcinomatous hyperplasia (PCH) of the mucosa which can mimic invasive islands of oral squamous cell carcinoma (SCC). Such similarity can be confusing when diagnosing or evaluating the two conditions, potentially leading to misdiagnosis or misclassification. Indeed, several misdiagnosed cases of oral GCT have been reported in the literature as OSCC or malignant oral GCT that resulted in unnecessary aggressive treatment for the affected patients. The aim of this study was to investigate if the cytokeratin pattern of the PCH can help in differentiating GCT from oral SCC. To distinguish between these two entities, we examined 12 patient specimens of oral GCT-PCH and oral SCC histologically and via immunohistochemistry (IHC) for CK13, CK17 and P75. The results suggest that the cytokeratin profile of PCH is similar to that of oral SCC. Therefore, consideration of IHC findings for epithelial markers alone may lead to erroneous diagnosis; thus, the presence of the granular tumor underneath the PCH and its immunopositivity for P75 or other neural definition markers can be essential to identify the underlying tumor and exclude oral SCC. Finally we recommend more studies on the molecular biology of PCH to understand how it can mimic oral SCC histologically without harboring its malignant phenotype clinically, which could have significant translational potential for understanding invasive oral SCC.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.129-137
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• 2018

Objective: The objective of this research was to evaluate the physico-chemical, microbiological and sensorial qualities of restructured steaks processed from beef trimmings (grade I and II) and frozen beef (fresh beef as control and frozen beef). Methods: Beef trimmings from commercial butcher were collected, designated into 4 treatments differing in beef trimmings grade and freezing, processed into restructured steaks with 1% microbial transglutaminase and then analyzed for product quality. Results: The results showed that all meat from different groups could be tightly bound together via cross-linking of myosin heavy chain and actin as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Microbial counts of psychrotrophic and mesophilic bacteria were not affected by treatments (p>0.05), and no detectable of thermophilic bacteria were found. Regarding effect of beef trimmings grade, steaks made from beef trimmings grade II (16.03% fat) showed some superior sensorial qualities including higher tenderness score (p<0.05) and tendency for higher scores of juiciness and overall acceptability (p<0.07) than those made from beef trimmings grade I (2.15% fat). Moreover, a hardness value from texture profile analysis was lower in steaks processed from beef trimmings grade II than those made from grade I (p<0.05). Although some inferior qualities in terms of cooking loss and discoloration after cooking were higher in steaks made from beef trimmings grade II than those made from beef trimmings grade I (p<0.05), these differences did not affect the sensory evaluation. Frozen beef improved the soft texture and resulted in effective meat binding as considered by higher cohesiveness and springiness of the raw restructured product as compared to fresh beef (p<0.05). Conclusion: The results indicated the most suitable raw beef for producing restructured steaks without detrimental effect on product quality was beef trimmings grade II containing up to 17% fat which positively affected the sensory quality and that frozen beef trimmings increased tenderness and meat binding of restructured beef steaks.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10847-10853
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• 2015

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

• Asia-Pacific Journal of Business
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• v.6 no.2
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• pp.19-33
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• 2015

Studies focusing on the constantly changing buying behavior and product preferences of a booming teen market are rare and this is particularly true in the Philippines. To address this gap in the literature, this study focused on the supermarket brands of cologne preferred by teens in the Philippines such as Lewis & Pearl (L&P), Johnson's Baby Cologne, Juicy, Bench, Ellips, Fiona, Bambini and Baby Flo which are manufactured by various competing companies. Essentially, this study presented and described the profile and buying behavior of cologne users and non-cologne users and determined whether preferential differences existed between these brands. The respondents consisted of 473 teens all over the Philippines stratified in terms of general location via the three major groups of islands in the Philippines: Luzon, Visayas and Mindanao. Respondents came from selected schools in Quezon City in Metro Manila, Sariaya in Quezon Province, Cebu City, and Digos City to represent the Greater Metro Manila Area, Luzon, Visayas and Mindanao, respectively. Findings showed that almost all of the respondents used cologne at varying degrees. In general, teens use several scents and brands of cologne and continually shift from one scent/brand to another scent/brand. This made it difficult for any company to capture loyal consumers. The most popular brands used by teenagers were Bench (61.7%), Lewis and Pearl (59%), Juicy (42%), Afficionado (32%), Fiona (19.3%), Penshoppe (18%), Bambini (12.6%), Ellips (11.3%) and Zen Zest (7.5%). Fragrance or scent is the top priority of teenagers in choosing a cologne brand, followed by brand name, affordability, bottle design and endorser. The spray bottle type of colognes is preferred even if cologne spray bottles are priced higher than the splash cologne bottle type. Managerial implications of these findings for market players, marketing scholars and prospective investors are presented.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.659-664
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• 2017

Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration. Moreover, after administration of the lisdexamfetamine, dopamine levels in the striatal synaptosomes were significantly increased. Although some modifications should be made to the analytical methods, performing high performance liquid chromatography studies on synaptosomes can aid in predicting dependence liability when studying new psychoactive substances in the future. Collectively, lisdexamfetamine has potential for dependence possible via dopaminergic pathway.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.545-552
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• 2005

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. it provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

• Science of Emotion and Sensibility
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• v.3 no.2
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• pp.29-40
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• 2000

Autonomic and EEG responses were analyzed in 32 college students exposed to visual stimulation with Korean Affective Picture System (KAPS) and 36 students exposed to the International Affective Picture System (IAPS). Cardiac, electrodermal, and electrocortical measures were recorded during 30 sec of viewing affective pictures. The slides intended to elicit basic emotions (fear, anger, surprise, disgust, and sadness) were presented to subjects via Kodak slide-projector. The aim of the study was to differentiate autonomic and EEG responses associated with the same negative valence emotions elicited by KAPS and IAPS stimulation and to identify the influence of cultural relevance on physiological reactivity. The analysis of obtained results revealed significant differences in physiological responsiveness to emotionally negative valence slides from KAPS and IAPS. The typical response profile for all emotions elicited by the KAPS included HR acceleration (except surprise), and increase of electrodermal activity, slow and fast alpha blocking and fast beta power increase in EEG, which was not associated with significant asymmetry (except fast alpha in sadness). Stimulation with the IAPS evoked HR deceleration, specific electrodermal responses with relatively high tonic electrodermal activation, alpha-blocking and fast beta increase, and was accompanied also by theta power increase and marked frontal asymmetry (e.g., fast beta, theta asymmetries in sadness, fast alpha in fear). Physiological responses to fear and anger-eliciting slides from the IAPS were significantly less profound and were accompanied by autonomic and EEG changes more typical for attention rather than negative affect. Higher cardiovascular and electrodermal reactivity to fear emotion observed in the KAPS, e.g., as compared to data with the IAPS as stimuli, can be explained by cultural relevance and higher effectiveness of the KAPS in producing certain emotions such as fear in Koreans.