• Journal of Gastric Cancer
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• 제21권4호
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• pp.418-425
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• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• Journal of Veterinary Science
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• 제21권2호
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• pp.27.1-27.10
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• 2020

The efficacies of a supraglottic airway device (SGAD) and an endotracheal tube (ETT) in cats under general anesthesia with volume-controlled ventilation (VCV) were compared. Thirty healthy cats were randomly allocated for airway control using either an SGAD or an ETT. Five tidal volumes (6, 8, 10, 12, and 14 mL/kg) were randomly tested, and respiratory rates were adjusted to achieve a minute ventilation of 100 mL/kg/min. The dose of propofol necessary to insert the SGAD or ETT, the static respiratory pressure, leakage during VCV, and end tidal CO₂ (ETCO₂) were recorded. Dosages of propofol and static respiratory measurements for the SGAD and ETT groups were compared using a t-test. The distribution of leakages and hypercapnia (ETCO₂ > 45 mmHg) were compared using Fisher's exact test. A significance level of p < 0.05 was established. No significant difference in dose of propofol was observed between the SGAD and ETT groups (7.1 ± 1.0, 7.3 ± 1.7 mg/kg; p = 0.55). Static resistance pressure of the SGAD (22.0 ± 8.1 cmH₂O/L/sec) was significantly lower than that of the ETT (36.6 ± 12.9 cmH₂O/L/sec; p < 0.01). Of the 75 trials, leakage was more frequent when using an SGAD (8 events) than when using an ETT (1 event; p = 0.03). Hypercapnia occurred more frequently with SGAD (18 events) than with ETT (3 events; p < 0.01). Although intubation with an ETT is the gold standard in small animal anesthesia, the use of an SGAD can reduce airway resistance and the work of breathing. Nonetheless, SGAD had more dead space and the tidal volume for VCV needs adjustment.

• Restorative Dentistry and Endodontics
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• 제48권4호
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• pp.33.1-33.12
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• 2023

Objectives: This study aimed to evaluate the bleaching efficacy and hydrogen peroxide permeability in the pulp chamber by the at-home bleaching gel in protocols applied on different dental surfaces. Materials and Methods: Forty premolars were randomly into 4 groups: control group no bleaching, only application on the buccal surface (OB), only application on the lingual surface (OL) and application in buccal and lingual surfaces, simultaneously (BL). At-home bleaching gel (White Class 7.5%) was used for the procedure. The bleaching efficacy was evaluated with a digital spectrophotometer (color change in CIELAB [ΔE_ab] and CIEDE 2000 [ΔE₀₀] systems and Whitening Index for Dentistry [ΔWI_D]). The hydrogen peroxide permeability in the pulp chamber (㎍/mL) was assessed using UV-Vis spectrophotometry and data were analyzed for a 1-way analysis of variance and Tukey's test (α = 0.05). Results: All groups submitted to bleaching procedure showed bleaching efficacy when measured with ΔE_ab and ΔE₀₀ (p > 0.05). Therefore, when analyzed by ΔWI_D, a higher bleaching efficacy were observed for the application on the groups OB and BL (p = 0.00003). Similar hydrogen peroxide permeability was found in the pulp chambers of the teeth undergoing different protocols (p > 0.05). Conclusions: The application of bleaching gel exclusively on the OB is sufficient to achieve bleaching efficacy, when compared to BL. Although the OL protocol demonstrated lower bleaching efficacy based on the ΔWI_D values, it may still be of interest and relevant in certain clinical scenarios based on individual needs, requiring clinical trials to better understand its specificities.

• IMMUNE NETWORK
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• 제22권1호
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• pp.3.1-3.21
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• 2022

Cancer is one of the leading causes of death worldwide and the number of cancer patients is expected to continuously increase in the future. Traditional cancer therapies focus on inhibiting cancer growth while largely ignoring the contribution of the immune system in eliminating cancer cells. Recently, better understanding of immunological mechanisms pertaining to cancer progress has led to development of several immunotherapies, which revolutionized cancer treatment. Nonetheless, only a small proportion of cancer patients respond to immunotherapy and maintain a durable response. Among multiple factors contributing to the variability of immunotherapy response rates, commensal microbiota inhabiting patients have been identified as one of the most critical factors determining the success of immunotherapy. The functional diversity of microbiota differentially affects the host immune system and controls the efficacy of immunotherapy in individual cancer patients. Moreover, clinical studies have demonstrated that changing the gut microbiota composition by fecal microbiota transplantation in patients who failed a previous immunotherapy converts them to responders of the same therapy. Consequently, both academic and industrial researchers are putting extensive efforts to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy. In this review, we will summarize the immunological roles of commensal microbiota in cancer treatment and give specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy. We will also list ongoing clinical trials testing the anticancer effect of commensal bacteria.

• Archives of Pharmacal Research
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• 제24권5호
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• pp.455-465
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• 2001

The highly potent cytotoxic DNA-DNA cross-linker consists of two cyclopropa[c]pyrrolo[3,4-3]indol-4(5H)-ones insoles [(+)-CPI-I] joined by a bisamido pyrrole (abbreviated to "Pyrrole"). The Pyrrole is a synthetic analog of Bizelesin, which is currently in phase II clinical trials due to its excellent in vivo antitumor activity. The Pyrrole has 10 times more potent cytotoxicity than Bizelesin and mostly form DNA-DNA interstrand cross-links through the N3 of adenines spaced 7 bp apart. The Pyrrole requires a centrally positioned GC base pair for high cross-linking reactivity (i.e., $5^1$-T$AT_2$A*-$3^1$), while Bizelesin prefers purely AT-rich sequences (i.e., $5^1$-T$AT_4$A*-$3^1$, where /(equation omitted) represents the cross-strand adenine alkylation and A* represents an adenine alkylation) (Park et al., 1996). In this study, the high-field $^1$H-NMR and rMD studies are conducted on the 1 1-mer DNA duplex adduct of the Pyrrole where the 5′(equation omitted)TAGTTA*-3′sequence is cross-linked by the drug. A severe structural perturbation is observed in the intervening sequences of cross-linking site, while a normal B-DNA structure is maintained in the region next to the drug-modified adenines. Based upon these observations, we propose that the interplay between the bisamido pyrrole unit of the drug and central C/C base pair (hydrogen-bonding interactions) is involved in the process of cross-linking reaction, and sequence specificity is the outcome of those interactions. This study suggests a mechanism for the sequence specific cross-linking reaction of the Pyrrole, and provides a further insight to develop new DNA sequence selective and distortive cross-linking agents.

• 생명과학회지
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• 제30권5호
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• pp.476-482
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• 2020

벼 농사에서 마릅으로 불리는 올방개는 문제의 잡초 종류 중 하나로서 제초 작용의 대상이다. 하지만, 올방개는 임상적으로 황달, 해열 및 통경을 위한 전통 의학에 쓰여왔다. 올방개는 오랫동안 임상적으로 사용되어왔음에도 불구하고, 분자생물학 기반의 생물학적 효과는 아직 밝혀지지 않았다. 때문에, 본 연구진은 LPS로 유도된 대식세포 내에서 올방개 추출물 처리에 의한 NO 생산량을 스크리닝 함으로써 항염증 효과를 조사했다. 가장 효과적인 항염증 fraction을 찾기 위해, 본 연구진은 HP20 column chromatography를 이용하여 5 종류의 EtOH sub-fraction을 동정하였다; 20%, 40%, 60%, 80%, 및 100% EtOH. 동정한 sub-fraction 중에서, 60%와 80% 성분에서 가장 유의성 있는 NO 생산의 저해를 나타냈으며, 세포독성 효과도 나타내지 않는 결과를 나타냈다. 추가적으로 80% sub-fraction은 유의성 있는 iNOS 저해와 전염증성 매개체의 mRNA; IL-6, TNF-α, 그리고 IL-1β를 저해하였으며, 이 결과는 MAPKs 세포신호전달과 관련 있는 JNK 및 ERK 단백질의 인산화 저해가 원인임을 밝혔다. 본 연구진의 결과는 올방개 추출물 80% sub-fraction EtOH가 항염증 활성을 가장 효과적으로 저해하는 성분 임을 밝혔으며, 이는 MAPKs 세포신호전달의 과 발현에 의한 염증성 질병의 치료제 후보 성분 일 수 있음을 시사한다.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.584-589
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• 2001

Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

• 척추신경추나의학회지
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• 제10권2호
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• pp.13-25
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• 2015

Objectives : To find out the standardized chuna manual technique for non-acute low back pain. Methods : The survey questions were developed by the consensus from the professor who major in Rehabillitation Medicine of Korean Medicine(RMKM). August 15th to september 1st 2015, the questionnaire was given to 23 RMKM doctors by e-mail. 20(90.9%) the questionnaire were retrieved out. Standardized technique of chuna were selected through experts consesus based on questionaire results. Results : Two essential techniques and two selective techniques were selected as standardized Chuna manual technique for lumbar region. Six essential technique and one selective technique were selected as standardized Chuna manual technique for iliac region. Conclusions : This is the first consensus of experts opinion for Chuna manual technique for operating randomized controlled trials(RCT). These reports are helpful for Korean Medicine doctor who operate Chuna manual technique and expected to make clinical evidence of Chuna manual medicine

• 한국임상약학회지
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• 제20권3호
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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.

• 한국임상약학회지
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• 제20권3호
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• pp.235-241
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• 2010

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active ${\beta}_2$-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, $Bambec^{(R)}$ tablet 10 mg (Yuhan Co., Ltd.) and Bambucol tablet 10 mg (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). In vitro release of bambuterol from two bambuterol hydrochloride formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male Korean volunteers, $23.86{\pm}1.65$ years in age and $68.98{\pm}9.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 10 mg as bambuterol hydrochloride were orally administered, blood samples were taken at predetermined time intervals, and the concentrations of bambuterol in serum were determined using column switching HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test with 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, $Bambec^{(R)}$, were -8.10%, -3.82% and 12.65% 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 (i.e., log 0.8093~log 1.0302 and log 0.8564~log 1.1280 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to $Bambec^{(R)}$ tablet 10 mg.