• Journal of Korean Neurosurgical Society
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• v.55 no.1
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• pp.5-11
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• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.701-705
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• 2013

Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the response to platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newly diagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147, rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction (PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatment response when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TT genotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, and the hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, we found a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotype when compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our study found that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-based chemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.238-244
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• 2015

Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-${\gamma}$ (IFN-${\gamma}$)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-${\gamma}$ (10 ng/mL) in a dose dependent manner. Dieckol (5 and $10{\mu}M$) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.7-13
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• 2001

Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.326-334
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• 1996

Effects of methanol extract of Astragali Radix (AR) on the immune responses were studied using ICR mice. Mice were divided into 4 groups (10mice/group), and methanol extracts of AR at doses of 0.05, 0.25 and 1.25g/kg were orally administered to ICR mice once a day for 2 weeks. Mice were immunized and challenged with sheep red blood cells (SRBC). The results of this study were summarized as follows; (1) Methanol extract of AR at 0.05, 0.25 and 1.25g/kg didn't affect the weight ratios of thymus to body, as compared with those in controls, but significantly increased spleen weight ratio. (2)Methanol extract of AR at 0.05 and 0.25g/kg significantly increased hemagglutination titer and splenic plaque forming cells corresponding to humoral immunity, as compared with those in controls, but their enhancements were somewhat lowered at a high dose (1.25g/kg). (3) Methanol extract of AR at 0.05 and 0.25g/kg siginificantly increased delayed-type hypersensitivity reaction resulted from cell-mediated immunity, as compared with those in controls, but not so significant increases were observed at a high dose (1.25g/kg). (4) Methanol extract of AR at 0.05 and 0.25g/kg significantly increased phagocytic activity and the number of circulating leukocyte compared with those in controls, but their enhancements were lowered at a high dose (1.25g/kg). These results suggest that methanol extract of Astragali Radix increased humoral and cell-mediated immune responses, phagocytic activity and the number of circulating leukocyte, dependent upon dose, but inhibited their enhancement effects were decreased at a high dose (1.25g/kg).

• YAKHAK HOEJI
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• v.52 no.6
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• pp.507-513
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• 2008

The purpose of this study is to analyze the factors affecting financial performance of community pharmacies after the implementation of the new drug policy in Korea: separation of drug prescription and dispensing (SPD). The online survey questionnaires were sent to the active pharmacists of the total 20,633 community pharmacies in Korea and 1,147 pharmacists responded to the survey (the response rate was 5.5%). The questionnaire asked simple financial data in order to compare their financial performances before and after the policy. With the SPSS package (version 12.0), two levels of data analysis were used: 1) descriptive statistics to see the financial status of the pharmacies; and 2) multiple regression analysis to find the factors. {or A multiple regression method was used for the data analysis.} The finding illustrated that the average net benefit of the pharmacies was 4,870 thousand won in August 2006, and the major factors affecting the net benefit were the location of pharmacy (geographical proximity to medical institutions), number of prescriptions, drug management services for patients, chain pharmacy membership. The findings of this study suggest that service improvement for patients, revitalization of non-prescription drug sales, professional management will contribute to promote community based pharmacy business.

• Korean Management Science Review
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• v.29 no.3
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• pp.81-89
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• 2012

Since introduced by Vining and Myers in 1990, the concept of dual response approach based on response surface methodology has widely been investigated and adopted for the purpose of robust design. Separately estimating mean and variance responses, dual response approach may take advantages of optimization modeling for finding optimum settings of input factors. Explicitly assuming functional relationship between responses and input factors, however, it may not work well enough especially when the behavior of responses are poorly represented. A sufficient number of experimentations are required to improve the precision of estimations. This study proposes an alternative to dual response approach in which additional experiments are not required. An artificial neural network has been applied to model relationships between responses and input factors. Mean and variance responses correspond to output nodes while input factors are used for input nodes. Training, validating, and testing a neural network with empirical process data, an artificial data based on the neural network may be generated and used to estimate response functions without performing real experimentations. A drug formulation example from pharmaceutical industry has been investigated to demonstrate the procedures and applicability of the proposed approach.

• Journal of Plant Biology
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• v.39 no.4
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• pp.287-293
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• 1996

The effect of taxol and ethyl-N-phenylcarbamate (EPC) on the growth and gravitropism of maize roots and coleoptiles was studied. Taxol is known to promote the assembly of microtubules (MTs) and stabilizes MTs by preventing depolymerization. EPC, on the contrary, is an anti-microtubule drug that promotes disassembly of MTs. Taxol, at 1 $\mu$M, inhibited gravitropic response of maize roots to about 40%, but did not inhibit growth; at 10 $\mu$M, it inhibited the gravitropic response of coleoptile segments of maize by approximately 50%, but did not inhibit growth, while 0.5 mM EPC inhibited both the gravitropic response and growth of maize roots by approximately 50%. Taxol, which inhibited the gravitropic response of maize roots and coleoptile segments, had no effect on either the polar or the bilateral transport of auxin. These results indicated that MT polymerization could not occur normally with taxol or EPC, so that if there was any abnormal rearrangement of MT, the gravitropic response was inhibited, which resulted from the inhibition of neither growth nor auxin transport. This results suggested that gravitropic response was related to the MT arrangement, and that both straight growth and the differential growth in gravitropic response could be regulated by different mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3971-3977
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• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.195-203
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• 2005

Cytochrome P45O 17$\alpha$-hydroxylase (CYPI 7) and cytorhrome P45O aromata.ie (CYPI 9) are key steroidogenic enzymes in androgen and estrogen synthesis. ThiL study evaluated the effects of nonylphenol (NP) on CYP17 and CYP19 expression in the ovary of Sprague-Dawley rats. All female rats were administered orally with the vehicle (control, corn oil), diethylstilbestrol (DES, 5.0 $\mu$g/kg) and NP (50, 100, or 200 mg/kg/day), which was startinB when they were weaned at 21 days of age for 20 days. Twenty four hours after final dose, the animals were anelthetized with ether. Significant decreases in the uterus (wet weight) were observed with 5.0 $\mu$g/kg/day DES (78$\%$, of control) and 200 mg/kg/day NP (62$\%$ of control), respectively Additionally, ovarian weight was significantly decreased with 5.0 $\mu$g/kg/day DES (63$\%$ of control) and 200 mg/kg/day NP (72$\%$ of control). The serum estradiol levels were sligHtly lower in DES and high dose NP treatment groups, but the 74 levels were not affected by DES and NP. The expression of the ovarian CYP19 gene increased with low doses (50 and 100 mg/kg/day) of NP. while DES and high dose oi NP (200 mg/kg/day) did not affect on the CYP19 mRNA levels. In contrast to the CYP19 gene, the CYP17 gene expreLsion level was significantly down-regulated by the DES and 200 mg/ks/day NP. This result suggestE that NP inhibits ovarian estrogen synthelis by supprelsing CYP17 mRNA efprelsion, And different mechanisml might exist for the expression of Lteroidogenic CYP17 and CYP19 genes in the ovary of Sprague-Dawley rats in response to NP.