• Journal of Life Science
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• v.17 no.10
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• pp.1447-1451
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• 2007

Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

• Sleep Medicine and Psychophysiology
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• v.3 no.2
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• pp.32-42
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• 1996

Objectives : Upper airway resistance syndrome(UARS) is a sleep-related breathing disorder characterized by abnormal negative intrathoracic pressure during sleep. Abnormally increased negative intrathoracic pressure results in microarousal and sleep fragmentation which underlay UARS-associated complaints of daytime fatigue and sleepiness. Although daytime dysfunction in patients with UARS is comparable to that of sleep apnea syndrome, UARS has been relatively unnoticed in clinical setting. That is why UARS is apt to be excluded in diagnosing of sleep-related breathing disorders since its respiratory disturbance index and arterial oxygen saturation are within normal limits. The current study presents a summary of clinical and polysomnographic characteristics found in patients with UARS. The present study aims (1) to explore characteristics of patients diagnosed with UARS, (2) to characterize the polysomnographic findings of UARS patients, and (3) to enhance the understanding of UARS through those clinical and laboratory characteristics. Methods : This was a retrospective study of 20 UARS patients (male 15, female 5) and 30 obstructive sleep apnea (OSA) patients (male 21, female 9) at the Stanford Sleep Disorders Clinic. We diagnosed patients as having UARS when they met critenia, RDI < 5 characteristic findings of an elevated esophageal pressure($<-10\;cmH_2O$), frequent arousals secondary to an elevated esophageal pressure, and symptoms of daytime fatigue and sleepiness. We used polysomnographic value, which is standardized by Williams et al(1974), as normal control. Statiotical test were done with student t-tests. Results : (1) Mean age of UARS was $41.0\;{\pm}\;14.8$ years and OSA was $50.9\;{\pm}\;12.0$ years. UARS subject was significantly younger than OSA subject (p<0.05). (2) The total score of Epworth Sleepiness Scale (ESS) was UARS $9.7\;{\pm}\;6.3$ and OSAS $11.2\;{\pm}\;6.3$. There was no significant difference between two groups. (3) The mean body mass index was UARS $28.1\;{\pm}\;5.7\;kg/m^2$ and OSAS $32.9\;{\pm}\;7.0\;kg/m^2$. UARS had significantly lower meen body man index than OSAS subjects (p<0.05). (4) The polysomnographic parameters of UARS were not significantly different from those of OSA except RDI(p<0.001), $SaO_2$ (p<0.001) and slow wave sleep latency (p<0.05). (5) Compared with normal control, Total sleep time in UARS subjects was significantly shorter (p<0.001), sleep efficiency index was significantly lower (p<0.001), total awakening percentage was significantly higher (p<0.001), and sleep stage 1 (p<0.001) were significantly higher. (6) OSA patients showed poor sleep quality and distinct abnormal sleep architectures compared with normal control. Conclusions : Conclusions from the above results are as follows : (1) UARS patients were younger and had lower body mass index when umpared with OSA patients. (2) The quality of sleep and sleep architectures of the UARS and OSA patients are significantly different from those of normal control. (3) ESS scores and awakening frequencies of UARS are similar with those of OSA, suggesting that daytime dysfunction of UARS patients may be comparable to those of OSA patients. (4) The RDI and the $SaO_2$ which are important indicators in diagnosing sleep-related breathing disorders, of UARS subjects are close to normal value. (5) According to the the above results, we unclude that despite the absence of $SaO_2$ drops and the absence of an elevated number of apnea and hypopnea, subjects developed clinical complaints which were associated with laborious breathing, elevated Pes nadir, and frequently snoring. (6) Accordingly, we suggest including LIARS in the differential diagnosis list when sleep related breathing disorder is suspected clinically and overnight polysomnographic findings except snoring and frequent microarousal are within normal limits.