Purpose: The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature with meta-analysis to estimate the predictive value of TS expression from published studies. Methods: We indentified 24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcome were hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) for overall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects meta-analysis. Results: Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and nine studies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Meta-analysis of estimates showed high TS expression was significantly associated with poor OS in the advanced setting (HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroup analysis demonstrated TS expression to haves even greater value in predicting OS, EFS and ORR in advanced GC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS: 1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95). Conclusion: High levels of TS expression were asssociated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, high TS expression was also associated with a worse EFS. Additional studies with consistent methodology are needed to define the precise predictive value of TS.
Background: Although the nutritional may exert effect on the breast cancer risk, it is not clear whether the role diet is the same in sedentary and physically active women. The aim of this study was to evaluate the association between fruit, vegetable and carbohydrate intake and the risk of breast cancer among Polish women considering their physical activity level. Materials and Methods: A case-control study was conducted that included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis, aged 28-78 years. The study was based on a self-administered questionnaire to ascertain physical activity, dietary intake, sociodemographic characteristics, reproductive factors, family history of breast cancer, current weight and high, and other lifestyle factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in unconditional logistic regression analyses including a broad range of potential confounders. Results: With comparison of the highest vs lowest quartile of intake, strong significant associations were observed for total vegetables (OR=0.37, 95%CI=0.20-0.69 P for trend <0.01 and OR=0.53, 95%CI=0.29-0.96, P for trend <0.02), and total fruits (OR=0.47, 95%CI=0.25-0.87, P for trend <0.05 and OR=0.47, 95%CI=0.24-0.90, P for trend <0.02) among women characterized by the lowest and the highest quartile of physical activity. No associations were observed for total carbohydrate intake. Additional analysis showed a positive association for sweets and desert intake among women in the lowest quartile of physical activity (OR=3.49, 95%CI=1.67-7.30, P for trend <0.009) for extreme quartiles of intake comparing to the referent group. Conclusions: The results suggest that a higher consumption of vegetable and fruit may be associated with a decreased risk of breast cancer, especially among women who were low or most physically active throughout their lifetimes. These findings do not support an association between diet high in carbohydrate and breast cancer. However, a higher intake of sweets and deserts may by associated with an increased risk of breast cancer among women who were less physically active.
The effect of dose enhancement was evaluated using Snyder head phantom, dependence on size of gold nanoparticle and material concentration in megavoltage X, ${\gamma}$-ray. Monte Carlo simulation using MCNPX was used for 4, 6, 10, 15 MV and Co-60 ${\gamma}$-ray. Described the tumor in Snyder head phantom, gold nanoparticle of 25, 75, 125nm diameter was inserted inside tumor. Concentration of dose enhancement material was used for 5, 15, 25 mg/g and dose enhancement factor was calculated on the basis of the no dose enhancement material. The lower incident energy and the higher concentration of material were that high dose enhancement factor is indicated. The size of gold nanoparticle had relatively high dependence on lower incident energy and higher concentration of material. It will increase dose inside the tumor, and be additional effect of use of gold nanoparticles in radiation therapy.
Kim, Jong-Min;Jeon, Hyung-Joon;Kim, Hyun-Ji;Cho, Chong-Kwan;Yoo, Hwa-Seung
Journal of Pharmacopuncture
/
v.17
no.4
/
pp.66-69
/
2014
Objectives: Treating complex regional pain syndrome (CRPS) is difficult because it still does not have a recommended therapy. A 29-year-old man was diagnosed with CRPS after surgery on his $4^{th}$ and $5^{th}$ left toes 7 years ago. Though he had undergone diverse pain treatment, the symptoms persisted, so he visited Dunsan Korean Medicine Hospital of Daejeon University. This case report presents results on the effect of bee venom pharmacopuncture in treating patient with CRPS. Methods: Bee venom pharmacopuncture (BVP), 0.15 to 0.4 mL dosage, was administered at GB43. The treatment was applied each week for a total 14 times. The symptoms were evaluated using a numeric rating scale (NRS) and the dosage of pain medicine. Results: On the first visit, he was taking an anticonvulsant, a trycyclic antidepressant, and an analgesic. On the NRS the worst pain in the toes received a score of 8. He also complained of severe pain and hypersensitivity when the $4^{th}$ and the $5^{th}$ toes were touched just slightly. Other complaint included dyspepsia, rash, and depression. After treatment, on the NRS, the score for toe pain was 0, and he no longer needed to take pain medication. During the 4-months follow-up period, he has remained without pain; neither have additional symptoms appeared nor adverse events occurred. Conclusion: BVP may have potential benefits for treating patients with CRPS.
We examined the effects of food on pharmacokinetic and pharmacodynamic properties of fenofibrate released from sustained-release(SR) capsule as therapy for hypolipidemia. Twenty-four healthy volunteers were used in $3{\times}3$ crossover pharmacokinetic and pharmacodynamic study; Additional six volunteers were used as a control group (i.e., no fenofibrate administration). A single dose of fenofibrate (SR capsule, 250 mg) was administered on three occasions: after overnight fasting, after consumption of a standard breakfast, and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high performance liquid chromatography, and pharmacokinetic parameters were calculated using ADAPT II program. Plsama triglyceride concentrations were measured by blood chemistry analyzer (CH-100). The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than did the standard breakfast and fasted conditions. Plasma concentrations of triglyceride at 24 hours decreased significantly after the administration of fenofibrate compared with the concentration at 0 hours(P<0.05). In healthy volunteers, the bioavailability of fenofibrate was greater when administered via sustained-release capsules immediately after the consumption of food than after fasting condition.
Background: It is recommended to use aerosolized (AS) colistin in patients undergoing mechanical ventilation therapy as an adjunctive in the latest guidelines, in spite of high nephrotoxicity and limited studies. In this study, systematic reviews and meta-analyzes were conducted to evaluate the safety and efficacy of AS colistin in patients with ventilator-associated pneumonia Methods: Two authors independently searched related literature published from Pubmed and EMBASE until July 2016 and included a study comparing adjunctive AS colistin with intravenous (IV) colistin monotherapy. The primary outcome was the clinical response rate, the secondary outcome was the overall mortality, and nephrotoxicity. The publication bias was evaluated using the Egger's test. Results: Of the total 279 articles, nine were finally included in the final analysis. There was a significant difference between the adjunctive AS colistin group and the IV colistin monotherapy group for the treatment-response rate (odds ratio (OR), 1.56; 95% CI, 1.14-2.14; p = 0.005; $I^2=36%$), although there was no significant difference in overall mortality (OR, 0.77; 95% CI, 0.57-1.04; p = 0.09; $I^2=20%$). However, there was no significant difference between the two groups in nephrotoxicity (OR, 1.13; 95% CI, 0.74-1.74; p = 0.57; $I^2=4%$). Conclusion: The addition of aerosolized colistin to IV colistin monotherapy showed better results in terms of efficacy than IV colistin monotherapy and did not show any significant difference in terms of total mortality and nephrotoxicity. Additional large-scale studies of this need to be verified.
Introduction: Recently identified human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Bioinformatics study of hABH2 and hABH3 had led to the discovery of a novel DNA repair mechanism. Very little is known about structure and function of hABH4, one of the members of this superfamily. Therefore, in present study we are intended to predict its structure and function through various bioinformatics tools. Materials and Methods: Modeling was done with modeler 9v7 to predict the 3D structure of the hABH4 protein. This model was validated with the program Procheck using Ramachandran plot statistics and was submitted to PMDB with ID PM0076284. The 3d2GO server was used to predict the functions. Residues at protein ligand and protein RNA binding sites were predicted with 3dLigandSite and KYG programs respectively. Results and Discussion: 3-D model of hABH4, ALKBH4.B99990003.pdb was predicted and evaluated. Validation result showed that 96.4 % residues lies in favored and additional allowed region of Ramachandran plot. Ligand binding residues prediction showed four Ligand clusters, having 24 ligands in cluster 1. Importantly, conserved pattern of Glu196-X-Pro198- Xn-His254 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. Conclusion and Prospects: The predicted and validated model of human homologue hABH4 resulted from this study may unveil the mechanism of DNA damage repair in human and accelerate the research on designing of appropriate inhibitors aiding in chemotherapy and cancer related diseases.
Objectives: Alzheimer's Dementia is somewhat common in clinical stages, and there are many reports and papers regarding this subject. We explain the present state of Alzheimer's Dementia in JON (The Journal of Oriental Neuropsychiatry) for the benefits of clinical practice. Methods: We searched for articles in JON from 1990 to 2014 and selected ones that were related to Alzheimer's Dementia; then, we analyzed the data and placed it in four categories, like experimental study, case study, Clinical Data-Analysis study, and clinical trial. Results: 1) We found 47 articles relating to Alzheimer's Dementia in JON from 1997 to 2014: 41 experimental studies, 1 case study, 1 Clinical Data-Analysis study, and 4 Clinical trials. 2) There were Chung-kyung Acupuncture Method, Auricular acupuncture, and Cha-rak Acupuncture Method to treat Alzheimer's Dementia. 3) There were many additional treatments, like aroma therapy. 4) In the experimental study, they reported on several herbs, including herbal prescriptions that affected the suppression of related mRNAs and genes. 5) There were 4 clinical trials regarding herbal prescription that was effective for treating Alzheimer's Dementia. Conclusions: In JON, regarding Alzheimer's Dementia, the majority dealt with experimental studies. Therefore, we also have to expand our sight into other fields of study. We need more clinical trials and case studies for the treatment of Alzheimer's Dementia in Oriental Neuropsychiatry.
Purpose: To determine the efficacy and safety of oral propranolol as a first-line treatment for superficially located infantile hemangioma (IH) and propose an assessment tool to measure treatment response. Methods: Patients with superficial IH under 1 year of age were prospectively recruited between May 2012 and December 2013 at the Department of Pediatrics of Chungbuk National University Hospital. Propranolol was administered to 12 infants (median age, 3.8 months) while monitoring cardiovascular and adverse metabolic effects. If a patient showed no adverse events, the dosage was gradually increased up to 3 mg/kg/day and maintained for 1 year. We used our own scoring system to assess treatment response using parameters like change in color, and longest diameter, and thickness of the IH. Results: Eleven out of 12 patients completed the protocol with consistent improvement of hemangiomas during therapy. Patients on propranolol showed a more than 50% involution in the first 3 months, with additional steady involution until 1 year. Patients with the highest scores at 1 month maintained their score and showed better responses until treatment termination. The patient with the lowest score at 1 month did not show any further regression and stopped propranolol treatment 4 months after initiation. In two children with recurrences after successful therapeutic regression, propranolol was effective after being reintroduced. Propranolol treatment was not interrupted in any patient due to adverse events. Conclusion: Oral propranolol at 3 mg/kg/day showed a consistent, rapid, and therapeutic effect on superficial IHs without significant adverse events.
Cationic liposomes have been actively used as gene delivery vehicle because of their minimal toxicity, but their relatively low efficiency of gene delivery is the major disadvantage of these vectors. Recently, cysteine residue incorporation to HIV-1 Tat peptide increased liposomemediated transfection compared with unmodified Tat peptide. Therefore, we designed a novel modified Tat peptide having a homodimeric (Tat-CTHD, Tat-NTHD) and closed structure (cyclic Tat) simply by using the disulfide bond between cysteines to develop a more efficient and safe nonviral gene delivery system. The mixing of Tat-CTHD and Tat-NTHD with DNA before mixing with lipofectamine increased the transfection efficiency compared with unmodified Tat peptide and lipofectamine only in MCF-7 breast cancer cells and rat vascular smooth muscle cells. However, cyclic Tat did not show any improvement in the transfection efficiency. In the gel retardation assay, Tat-CTHD and Tat-NTHD showed more strong binding with DNA than unmodified Tat and cyclic Tat peptide. This enhancement was only shown when Tat-CTHD and Tat-NTHD were mixed with DNA before mixing with lipofectamine. The effects of Tat- CTHD and Tat-NTHD were also valid in the experiment using DOTAP and DMRIE instead of lipofectamine. We could not find any significant cytotoxicity in the working concentration and more usage of these peptides. In conclusion, we have designed a novel transfection-enhancing peptide by easy homodimerization of Tat peptide, and the simple mix of these novel peptides with DNA increased the gene transfer of cationic lipids more efficiently with no additional cytotoxicity.
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