• Toxicological Research
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• v.21 no.1
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• pp.77-85
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• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.133-149
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• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• Korean Journal of Oriental Medicine
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• v.16 no.2
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• pp.143-157
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• 2010

Objectives : The objective of this study was to access the effect of Artemisiae capillaris herba Extracts on the organogenetic reproductive toxicity of New Zealand White rabbits when administered by oral gavage. Methods : Gestational New Zealand White rabbits were dosed from 6 days of gestation to 18 days of gestation. It was conducted in accordance with the recommendations of the KFDA Guideline for Detection of Toxicity to Reproduction for Medicinal Products. In addition, serum AST, ALT, LDH and ALP levels were detected with their necropsy and histopathological observation Results: No significant changes of body weights, gains and food consumption were demonstrated in all dosed groups compared to those of vehicle control group except for 2,000mg/kg-dosing group, which showed significantly increase of body weight compared to that of vehicle control group. Normal gross findings were demonstrated in all tested groups. No significant changes of number of corpora lutea, implantation, implantation rate, number of fetal death, loss rate of post-implantation, number of live youngs at C-section, survival rate of post-implantation, number of male live youngs at C-section, number of female live youngs, sex ratio of live young, external anomalies of live youngs and body weight of live youngs were demonstrated in all dosed groups compared to those of vehicle control group. Although some visceral variations such as thymic reminant in the neck, dilation of renal pelvis, dilated ureter and malpositioned left common carotid artery, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. Some malformations and variation were demonstrated with retardations. However, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. In addition, similar ossification numbers were detected in sternebrae, metacarpals, metatarsals, phalanges, cervical vertebrae, and sacral and caudal vertebrae. No Artemisiae capillaris herba Extracts treatment-related changes of serum AST, ALT, LDH and ALP levels were demonstrated in all dosed levels in this study. Conclusions : We could conclude that oral administration of Artemisiae capillaris herba Extracts hasn't an influence on the organogenetic reproductive toxicity.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.139-153
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• 2010

Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide ($NO_x$), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.

• Journal of fish pathology
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• v.19 no.3
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• pp.277-284
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• 2006

Application of wood vinegar in fish farms has been used for the disinfection of pathogenic microorganisms and the treatment of infectious diseases. This study was performed to know the acute toxicity of wood vinegar to carp Cyprinus carpio, flounder Paralichyhus olivaceus, rock fish Sebastes schlegeli and black sea bream Pagrus major. The 24 hr, 48 hr and 96 hr LC50 respectively were: carp 1243, 1143 and 1016 ppm; flounder 1397, 1253 and 1226 ppm; rock fish 1058, 993 and 967 ppm; and black sea bream 650, 616 and 596 ppm. Death and survival of fish exposed to lethal concentrations of wood vinegar were apparently related to massive necrosis, fusion and epithelial lifting of gill lamellar epithelium, suggesting the osmotic imbalance and lack of oxygen uptake.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7421-7426
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• 2013

Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4863-4865
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• 2016

Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma.

• The Korean Journal of Pain
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• v.29 no.1
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• pp.3-11
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• 2016

A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration.

• Journal of Korean Neurosurgical Society
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• v.48 no.3
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• pp.199-206
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• 2010

Objective : Paraclinoid segment internal carotid artery (ICA) aneurysms have historically been a technical challenge for neurovascular surgeons. The development of microsurgical approach, advances in surgical techniques, and endovascular procedures have improved the outcome for paraclinoid aneurysms. However, many authors have reported high complication rates from microsurgical treatments. Therefore, the present study reviews the microsurgical complications of the extradural anterior clinoidectomy for treating paraclinoid aneurysms and investigates the prevention and management of observed complications. Methods : Between January 2004 and April 2008, 22 patients with 24 paraclinoid aneurysms underwent microsurgical direct clipping by a cerebrovascular team at a regional neurosurgical center. Microsurgery was performed via an ipsilateral pterional approach with extradural anterior clinoidectomy. We retrospectively reviewed patients' medical charts, office records, radiographic studies, and operative records. Results : In our series, the clinical outcomes after an ipsilateral pterional approach with extradural anterior clinoidectomy for paraclinoid aneurysms were excellent or good (Glasgows Outcome Scale : GOS 5 or 4) in 87.5% of cases. The microsurgical complications related directly to the extradural anterior clinoidectomy included transient cranial nerve palsy (6), cerebrospinal fluid leak (1), worsened change in vision (1), unplanned ICA occlusion (1), and epidural hematoma (1). Only one of the complications resulted in permanent morbidity (4.2%), and none resulted in death. Conclusion : Although surgical complications are still reported to occur more frequently for the treatment of paraclinoid aneurysms, the permanent morbidity and mortality resulting from a extradural anterior clinoidectomy in our series were lower than previously reported. Precise anatomical knowledge combined with several microsurgical tactics can help to achieve good outcomes with minimal complications.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2967-2970
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• 2015

Many patients with few cerebral metastases receive radiosurgery alone. The goal of this study was to create a tool to estimate the survival of such patients. To identify characteristics associated with survival, nine variables including radiosurgery dose, age, gender, Eastern cooperative oncology group performance score (ECOG-PS), primary tumor type, number/size of cerebral metastases, location of cerebral metastases, extra-cerebral metastases and time between cancer diagnosis and radiosurgery were analyzed in 214 patients. On multivariate analysis, age (p=0.03), ECOG-PS (p=0.02) and extra-cerebral metastases (p<0.01) had significant impacts on survival. Scoring points for each patient were obtained from 12-month survival rates (in %) related to the significant variables divided by 10. Addition of the scoring points of the three variables resulted in a patient's total predictive score. Two groups were designed, A (10-14 points) and B (16-17 points). Twelve-month survival rates were 33% and 77%, respectively (p<0.001). Median survival times were 8 and 20 months, respectively. Because most patients of group A died from extra-cerebral disease and/or new cerebral lesions, early systemic treatment and additional WBI should be considered. As cause of death in group B was mostly new cerebral metastases, additional WBI appears even more important for this group.