ERRATUM: Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms / Journal of the Korean Cancer Association, 대한암학회지

For the data represented in Fig. 4B, we have generated a new figure from one of these repeat experiments.

Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Caveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2-expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear. MATERIALS AND METHODS: We investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models. RESULTS: The levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV-1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1-low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1-transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model. CONCLUSION: We clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.

The Blocking of c-Met Signaling Induces Apoptosis through the Increase of p53 Protein in Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer. MATERIALS AND METHODS: The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry. RESULTS: SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein. CONCLUSION: Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer.

Impact of Interhospital Transfer in Mortality of Critically Ill Patients

PURPOSE: Interhospital transfer of critically ill patients is often necessary for optimal patient care. However it is known that transport of critically ill patients has been associated with high rate of potentially detrimental complications. This study was designed to determine whether mortality of critically ill patients with interhospital transfers is different from critically ill patients with direct admissions. METHODS: The retrospective cohort study was conducted at an academic medical center with 3906 critically ill patients from 2003 to 2004, of whom 1652 were direct admissions and 2254 were interhospital transfers. Death within 48 hours in interhospital transfers and direct admissions were compared using univariate and multivariate regression analyses that adjusted for severity of illness. Severity of illness was measured using Simplified Acute Physiology Score (SAPS) II and Charles comorbidity score. To measure hospital performance standardized mortality ratio (SMR) was calculated by dividing observed mortality by SAPS II-predicted mortality. RESULTS: Death within 48 hours were not significantly higher for interhospital transfer patients than for directly admitted patients (7.5% vs 8.1%, p<0.05). But directly admitted patients had significantly higher SMR than transferred patients (0.94 vs 0.81, p=0.001). Finally, transferred patients with hepatic failure had significantly higher mortality rates (odds ratio=4.636) as compared with directly admitted patients, confirming the "transfer effect"for this patients' subgroup. CONCLUSION: Admission source is not an important determinant of outcome.

Clinical Study of Hospital Mortality in Patients Visiting the Emergency Room at Nighttime in a City of Korea

PURPOSE: Attention has been focused recently on the impact of sleep deprivation, in-house staff, and overwork on patient outcome. The objective of this study was to determine whether any associations existed between the timing of a patient visit to an emergency setting and hospital mortality. METHOD: We analyzed retrospectively a series of consecutive visits to the emergency room of our hospital in 2003. Patients were divided according to the times of their visits to emergency room daytime (from 8:00 am to 6:00 pm) and nighttime (all others). We further divided nighttime visits into early nighttime (from 6:00 pm to 1:00 am) and late nighttime (from 1:00 am to 8:00 am) visits. The odds of death within 48 hours after visit for patients in the nighttime group were analyzed by using a multivariate logistic regression. The independent variable was visit to the emergency room during nighttime. RESULT: The patients visiting at night had a lower mortality (0.9% vs 1.6%, p=0.000), with an odd ratio for death within 48 hours, adjusted for severity of illness, of 1.265 (95% CI, 0.955-1.674). Severity of illness was the main contributor to the increased mortality rates of patients in the nighttime group. There was no significant difference in mortality rates between the early and the late nighttime subgroups. CONCLUSION: Nighttime visits to the emergency room are not associated with a higher mortality than daytime visits.

Apoptosis in Respiratory Epithelial Cells: Triggering by Paraquat and Modulation by L-ascorbic acid

PURPOSE: Apoptosis is a programmed cell death that is a selective process of physiological cell deletion. This study was undertaken to evaluate a paraquat-triggered apoptosis and the ability of ascorbic acid to modulate the process in the A549 cell line, a well-characterized cellular model of human lung alveolar cells. METHODS: A 549 cells were incubated with different concentrations of paraquat for up to 24 hour, followed by 24, 48, and 72 hours of recovery in paraquat-free medium. To test the abilities of antioxidants as modulators of paraquatinduced apoptosis, we pre-treated the cells for 4 hours with 250 micrometer L-ascorbic acid (vitamin C) before exposure to paraquat, and we incubated cells with paraquat in the presence of 250 micrometer L-ascorbic acid. Apoptosis was assayed by staining the cells with FITC-annexin V, and the cells were analyzed by using flow cytometry. RESULTS: Paraquat was inducer of apoptosis. A549 cells incubated with paraquat for up to 24 hour showed no apoptotic features, but the following incubation in a paraquat-free medium resulted in a time-dependent appearance of apoptosis. The ascorbic acid proved effective in reducing paraquat-induced apoptosis. CONCLUSION: We propose an experimental model for investigating the steps and mechanism of paraquat-induced apoptosis in alveolar cells

Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death

Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H2O2), but also to endow cancer cells with resistance to both H2O2 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.

Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death

Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H2O2), but also to endow cancer cells with resistance to both H2O2 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.

Detection of Glycoproteins (B and D) and Ttymidine Kinase Genes of Herpes simplex virus Type 2 Strain G

BamHI restriction patters and genomic library of Herpes simplex virus type 2 (HSV-2) stram G were constructed, and locations of the glycoproteins gB and gD, and it genes on the fragments were detected by Southern blot analysis. HISV-2 genomic DNAs were cleaved into twenty-seven fragments by BamHI enzyme in the range of 0.72 to 15.08 (total 150.44 kb), which were cloned into the BamHI site of pBluescript SK(+) to construct genome library of the HSV-2. The library was named by the order of the fragment size from smallest one to largest one. HSV-2 glycoprotein gD gene was located in PHLA2-21 and PHLA2-22 recombinant plasmids, gB gene in PHLA2-24 plasmic, and it gene in PHLA2-11 clone by Southern blot analysis.

Detection of Glycoproteins (B and D) and Ttymidine Kinase Genes of Herpes simplex virus Type 2 Strain G

BamHI restriction patters and genomic library of Herpes simplex virus type 2 (HSV-2) stram G were constructed, and locations of the glycoproteins gB and gD, and it genes on the fragments were detected by Southern blot analysis. HISV-2 genomic DNAs were cleaved into twenty-seven fragments by BamHI enzyme in the range of 0.72 to 15.08 (total 150.44 kb), which were cloned into the BamHI site of pBluescript SK(+) to construct genome library of the HSV-2. The library was named by the order of the fragment size from smallest one to largest one. HSV-2 glycoprotein gD gene was located in PHLA2-21 and PHLA2-22 recombinant plasmids, gB gene in PHLA2-24 plasmic, and it gene in PHLA2-11 clone by Southern blot analysis.

Clinical Observation on Hydronephrosis / 대한비뇨기과학회지

A clinical observation was made on 97 cases of hydronephrosis who were admitted to the Urologic Department of the Maryknoll Hospital during the period from July 1, 1976 to December 31, 1981 (5 and 1/2 years). The results are as follows: 1. The rate of hydronephrosis accounted for 8.7% of the total patients (1,109 patients) admitted to the Urologic Department and 20.6% of the patients with urinary tract obstruction (471 patients). 2. The patients in this series were distributed over all ages, from a 12-month-old baby up to a 76-year-old patient. The most common age group Was the 5th decade (29.9%) and the male to female ratio was 1.5 to 1. 3. In underlying diseases, the most common cause of hydronephrosis was ureteral stone (40.2%), and 16.5%was idiopathic. 4. In lateralization of hydronephrosis, the left side was more affected than the right side by about 1.2 times and 19.6% was bilateral. In site and level of obstruction, upper tract was 76.3%, mid and lower tract was 7.2%, intraurinary tract lesion was 97.9% and extraurinary tract lesion was 2.1%. 5. The most commonly obstructed organ was the ureter (59.8%). 6. The most common symptom on admission was flank pain (46.8%). 7. In laboratory findings, increased B.U.N. and creatinine was 11.3%. Pyuria was 58.8% in urinalysis and the most common organism in urine culture was E. Coli (50.0%). 8. The most common complication of hydronephrosis was non-functioning kidney (42.2%). 9. In treatment, surgical treatment was 75.3% and conservative treatment, 24.7%. Of the surgical treatment, the most common operation was nephrectomy (30.9%), while the rate of conserving kidney was 69.1% and about 2.2 times higher than nephrectomy cases.