• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.159-164
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• 2013

Purpose: Indoxyl sulfate and p-cresyl sulfate are important protein-bound uremic retention solutes whose levels can be partially reduced by renal replacement therapy. These solutes originate from intestinal bacterial protein fermentation and are associated with cardiovascular outcomes and chronic kidney disease progression. The aims of this study were to investigate the levels of indoxyl sulfate and p-cresyl sulfate as well as the effect of probiotics on reducing the levels of uremic toxins in pediatric patients on dialysis. Methods: We enrolled 20 pediatric patients undergoing chronic dialysis; 16 patients completed the study. The patients underwent a 12-week regimen of VSL#3, a high-concentration probiotic preparation, and the serum levels of indoxyl sulfate and p-cresyl sulfate were measured before treatment and at 4, 8, and 12 weeks after the regimen by using fluorescence liquid chromatography. To assess the normal range of indoxyl sulfate and p-cresyl sulfate we enrolled the 16 children with normal glomerular filtration rate who had visited an outpatient clinic for asymptomatic microscopic hematuria that had been detected by a school screening in August 2011. Results: The baseline serum levels of indoxyl sulfate and p-cresyl sulfate in the patients on chronic dialysis were significantly higher than those in the children with microscopic hematuria. The baseline serum levels of p-cresyl sulfate in the peritoneal dialysis group were significantly higher than those in the hemodialysis group. There were no significant changes in the levels of these uremic solutes after 12-week VSL#3 treatment in the patients on chronic dialysis. Conclusion: The levels of the uremic toxins p-cresyl sulfate and indoxyl sulfate are highly elevated in pediatric patients on dialysis, but there was no significant effect by probiotics on the reduction of uremic toxins in pediatric dialysis patients. Therefore, studies for other medical intervention to reduce uremic toxins are also necessary in pediatric patients on dialysis.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.165-172
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• 2012

Purpose: To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Materials and Methods: Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. Results: With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. Conclusion: In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.775-781
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• 2015

Background: RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. In this study, we investigated the influence of RB1 single nucleotide polymorphisms (SNPs) on the efficacy of platinum-taxane regimens in advanced NSCLC patients. Materials and Methods: 234 cases of patients with advanced NSCLC who were treated with first-line platinum-taxane agents were enrolled in this study. Genomic DNA was extracted from patients' peripheral blood samples using a QIAamp DNA Maxi Kit, and genotyped by iSelect HD Bead-Chip. Results: Regression analyses were conducted through the univariate and multivariate Cox proportional hazards model in the 234 patients. The results showed that of the eight RB1 tagSNPs, only rs4151510 was a positive predictive factor for the advanced NSCLC patients treated with platinum taxanes regimen. The patients with G/G genotype of RB rs4151510 had longer overall survival (OS) than the non-G/G genotype (p=0.018). The histology was also correlated with OS in the whole advanced NSCLC patients. Three tagSNPs of RB1, rs4151510, rs4151465, rs9568036 were significantly associated with OS in the advanced NSCLC patients with squamous cell histology using Kaplan-Meier overall survival analysis stratified by histology. Conclusions: RB1 genomic variants were correlated with the efficacy of platinum-taxanes regimen. RB rs4151510 is an independent factor of the prognosis of NSCLC patients receiving platinum-taxane chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1357-1362
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• 2016

Metastatic gestational trophoblastic neoplasia (GTN) is an uncommon cancer. The principal treatment consists of chemotherapy with or without surgery or radiotherapy. We here retrospectively reviewed the outcomes of metastatic GTN treated at our institute between January, 1999 and December, 2013. Sixty-three patients met the criteria. The median age was 30.0 years and almost 90% were referral cases. Nearly 40% of the studied patients presented with vaginal bleeding while 22.2% were asymptomatic. The most common antecedent pregnancy was hydatidiform mole (57.1%) followed by term pregnancy (20.6%). The median interval time from antecedent pregnancy to the development of GTN was three months and the median pretreatment B-hCG was 58,274 mIU/ml. Stage III (74.6%) was the most common staging followed by stage IV (20.6%) and stage II (4.8%). The most frequent surgery was hysterectomy (31.7%). Thoracotomy and craniotomy were performed in three and two patients, respectively. The most common first line chemotherapy regimen was methotrexate and folinic acid (36.5%) followed by EMA (etoposide, methotrexate, actinomycin D) (34.9%), EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (17.5%) with the remission rate of 66.7%. Nearly one-third of the patients were given a subsequent chemotherapy regimen after failure with the first line therapy and showed a final response rate of 73.0%. However, in stage IV, the response to first line treatment was only 38.5%. In conclusion, the outcomes of metastatic GTN were poor especially with the higher stages.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6621-6626
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• 2015

Purpose: To evaluate effects of metformin on clinical outcome of non-diabetic patients with stage IV NSCLC. Materials and Methods: A prospective, randomized, open-label, controlled pilot study was conducted on patients with stage IV NSCLC with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2, excluding patients with diabetes and lactic acidosis. Thirty chemo-$na\ddot{i}ve$, non-diabetic patients with stage IV NSCLC were enrolled. Fifteen patients received intravenous gemcitabine/cisplatin regimen alone (arm B) while fifteen patients received the same regimen plus daily oral metformin 500mg (arm A). The effect of metformin on chemotherapy-response rates, survival, and adverse events in these patients was evaluated. Results: Objective response rate (ORR) and median overall survival (OS) in arms A and B were 46.7% versus 13.3% respectively, p=0.109 and 12 months versus 6.5 months, respectively, p=0.119. Median progression free survival (PFS) in arms A and B was 5.5 months versus 5 months, p=0.062. No significant increase in toxicity was observed in arm A versus arm B. Percentage of patients who experienced nausea was significantly lower in arm A versus arm B, at 26.7% versus 66.7% respectively, p=0.028. Conclusions: Metformin administration reduced occurrence of chemotherapy induced-nausea. Non-statistically significant improvements in the ORR or OS were observed. Metformin had no effect on PFS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7603-7606
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• 2015

Background: The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrate-Rasoul Hospital in Tehran. Materials and Methods: A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was $130mg/m^2$, every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms. Results: Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ${\geq}25$. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without. Conclusions: Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1581-1584
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• 2014

Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$, day 1) and cisplatin ($75mg/m^2$, day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6681-6686
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• 2013

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

• Journal of the East Asian Society of Dietary Life
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• v.15 no.3
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• pp.346-356
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• 2005

This study was conducted to investigate how to apply the theories of oriental medicine appropriately, which direction should be taken, and how it should be developed The results are as follows. First, to develop medicinal cuisine, it is necessary to grasp the theoretical system, considering Ohaeng and Omi, the five viscera and the six entrails, organs and body, by raising the level of understanding comprehensively about the relationship between the characteristics of each groups of Sasang Constitutions and the theories of Eumyangohaeng, and the relationship between the theory of Kimi. and food, and then to explain developed medicinal cuisine and apply those theories to inventing new ones. Secondly, to develop medicinal cuisine for health enhancement, it is also required not only to consider constitutions but also to suggest the need of knowledge for moderation in terms of regimen along with the theory of Kimi. Thirdly, to develop medicinal cuisine according to the perspective of Kimi. Theory, what should be taken into account is not only the understanding of the characteristics of food materials, but also the properties of them that the theory of Kimi, Eumyangohaeng, and Sasang Constitutions share so that it is possible to invent medicinal cuisine which is good for anybody to protect disease specific to a certain group of constitutions with, and serves as the dietary regimen customed to each constitution group. Lastly, the scientific effect of the medicinal cuisine which is developed according to the theory of Kimi., Eumyangohaeng, and Sasang Constitutions should be verified by scientific researches and clinical experiments. And it is believed to be essential for the government to make efforts to set a standard and laws to validate the medicinal effects and the process of assessment so that the systematic development can be encouraged, and to prepare guidance to food development for national health improvement.

• Toxicological Research
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• v.16 no.3
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• pp.187-193
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• 2000

The antidotal, anticonvulsant and neuroprotective effects of physostigmine and procyclidine. the combinational prophylactics for organophosphate poisoning, were evaluated in rats. In comparison with a low protective effect (1.6 fold) of atropine (15 mg/kg) and 2-pralidoxime (30 mg/kg), the traditional antidotes regimen, a marked protection ratio of 7.3 fold was achieved by combinational pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg), which was superior to that (3.5 fold) with pyri-dostigmine (0.1 mg/kg) and atropine (15 mg/kg). Rats exposed to a high dose (10 mg/kg. 2 X $LD_{50}$) of diisopropylfluorophosphate showed severe epileptiform seizures on electroencephalography, resulting in necrotic and apoptotic brain injuries in discrete brain regions under histopathological and TUNEL immuno-histochemical examinations in 24 hr. Such seizures and excitotoxic brain injuries were fully prevented by pretreatment with physostigmine (0.05 mg/kg) and procyclidine (10 mg/kg). in contrast to a negligible effect of pyridostigmine (0.1 mg/kg) and atropine (15 mg/kg). Taken together, it is proposed that the prophylactics composed of physostigmine and procyclidine could be a promising regimen for the prevention of lethality, seizures and brain injuries induced by organophosphate poisoning.