Kyung-Woon Kim

A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a common and serious regimen-related toxicity after hematopoietic stem cell transplantation (HSCT). There is no safe and proven therapy for established VOD, and focus has been on its prevention. Previous studies have shown that a continuous infusion of unfractionated heparin or ursodiol may reduce the incidence of VOD. In order to compare the efficacy of heparin plus ursodiol with that of heparin alone, we conducted a prospective, randomized study involving 165 consecutive patients who underwent HSCT for a variety of disorders. Eighty-two patients were assigned to receive heparin plus ursodiol, and 83 were assigned to receive heparin alone. Thirteen and 16 patients were diagnosed as having VOD in the heparin plus ursodiol group and the heparin alone group, respectively (15.9% vs 19.3%; P = 0.348). Eighty-nine percent of the heparin plus ursodiol group and 89.2% of the heparin alone group were surviving at day 100 post-HSCT (P = 0.298). The only independent variable associated with an increased risk of VOD was an allogeneic type of HSCT (P = 0.018). In conclusion, this study shows that there is no difference in efficacy between heparin plus ursodiol and heparin alone for the prevention of hepatic VOD.Bone Marrow Transplantation (2002) 29, 137–143. doi:10.1038/sj.bmt.1703342

High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases.

To determine the role of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in extranodal NK/T-cell lymphoma patients, we conducted a retrospective analysis. In our previous study, we searched for patients who had received HDC/ASCT and identified 16 eligible patients and compared the treatment outcome with historical control group (n=246). Nine patients received HDC/ASCT in the first (CR1) or second complete remission (CR2), while seven patients received HDC/ASCT as salvage. Twelve of 16 patients achieved or maintained CR after HDC/ASCT. Among the 12 patients, five patients relapsed. Estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates were 71.3±12.4% and 25.8±14.3%, respectively. There was a tendency of better survival in patients who received HDC/ASCT as compared to those who did not (P=0.091). In subset analysis, patients who underwent HDC/ASCT at CR (P=0.049) and patients with stage III or IV (P=0.001) had a favorable outcome. Patients with NKIPI 3,4 or EUNKTL, who underwent HDC/ASCT had more prolonged survival without statistical significance (P=0.055 and 0.056). In conclusion, HDC/ASCT may be considered as a treatment option for patients with extranodal NK/T-cell lymphoma, especially those in CR, with advanced disease (stage III/IV or EUNKTL) and high NKIPI scores.

Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer

Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial. In total, 40 mg m−2 epirubicin (reduced to 30 mg m−2 due to high incidence of febrile neutropaenia; 75%) intravenously (i.v.) over 30 min, followed by 60 mg m−2 docetaxel i.v. over 1 h, then 75 mg m−2 cisplatin i.v. over 1 h was administered every 3 weeks. Between January 2002 and February 2003, 30 patients (epirubicin 40 mg m−2, eight; 30 mg m−2, 22) were enrolled. The median age was 52 years (range, 33–68). The patients received a median of four cycles (range, 1–8). One patient (3%) achieved a complete response, 13 (43%) showed partial responses, 13 (43%) had stable diseases and three (10%) progressed. The overall response rate was 47% (95% CI, 28–66%), and the median duration of response was 5.0 months (95% CI, 3.0–7.0). The median time to progression was 4.1 months (95% CI, 2.4–5.9), and the median overall survival was 11.0 months (95% CI, 9.5–12.4). Grade 4 neutropaenia were observed in 41%, and febrile neutropaenia in 32%, out of the patients receiving 30 mg m−2 of epirubicin. Grade 3 nonhaematological toxicities included nausea, vomiting, anorexia and peripheral neuropathy. In conclusion, EDP is active in gastric cancer, with a manageable and predictable toxicity profile.

High-density inductively coupled plasma chemical vapor deposition of silicon nitride for solar cell application

Abstract The silicon nitride films were deposited by means of high-density inductively coupled plasma chemical vapor deposition in a planar coil reactor. The process gases used were pure nitrogen and a mixture of silane and helium. Passivated by silicon nitride, solar cells show efficiency above 13%. Strong H-atom release from the growing SiN film and Si–N bond healing are responsible for the improved electrical and passivation properties of SiN film. This paper presents the optimal refractive index of SiN for single layer antireflection coating as well as double layer antireflection coating in solar cell applications.

AKR1B10 is Associated with Smoking and Smoking-Related Non-Small-Cell Lung Cancer

This prospective study explored the relationship between expression of AKR1B10 mRNA and various clinical parameters in non-small-cell lung cancer (NSCLC) in terms of its validation as a marker for NSCLC. Tumour tissue samples were collected from 229 patients with NSCLC. Tissue samples from adjacent non-malignant lung tissue (> 5 cm from the tumour) of 89 of these patients and samples from 20 patients with benign lung disease were used as controls. Quantitative reverse transcription–polymerase chain reaction showed significantly higher levels of AKR1B10 mRNA expression in NSCLC tumour tissue than in adjacent non-malignant lung tissue and benign lung tissue. Statistically significant factors for AKR1B10 mRNA over-expression were found to be male gender, smoking, squamous cell carcinoma and moderate or poor cell differentiation. It is concluded that AKR1B10 seems to have potential as a prognostic marker for NSCLC and warrants further investigation.

Suppressive effects of bee venom on the immune responses in collagen-induced arthritis in rats

The effect of bee venom (BVA) on the development of type II collagen (CII)-induced arthritis (CIA) in rats has been studied. Male rats were immunized with an emulsion of 200 microg of CII and complete Freunds adjuvant (CFA). The rats were then given intraperitoneally (i.p.) injection of a suspension of BVA or saline during the experiment. The effect of BVA on cellular responses to CII was examined. In the control rats, the onset of arthritis was observed at the 24th day after the CII-immunization, and the severity of CIA was developed gradually. As compared with rats treated with saline, BVA i.p. injected at doses of more than 20 microl/100g mouse once a day for 14 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-1beta, -2, -6, tumor necrosis factor-alpha and interferon-gamma when the cells were obtained from rats 24 days after immunization and cultured in vitro with CII. When rats were injected i.p. with sheep red blood cells, hemagglutination titers in BVA-treated and control rats did not differ significantly when low doses of BVA was given to rats. However, i.p. injection of BVA at doses of more than 10 microl/100g/day suppressed antibody production. Pretreatment of rats with BVA could inhibit the development of collagen arthritis even when 10-20 microl/100g/day of the BVA were used for pretreatment. Interestingly, higher doses than 10 microlBVA/100g mouse were much effective for arthritis incidence. Treatment of rats with BVA prevented the development of collagen arthritis in a dose-dependent manner. Doses of BVA (15 and 20 microl/100g) resulted in decreased incidence of arthritis. In conclusion, therapeutic i.p injection with BVA improved the clinical course of the disease and the immune response to CII.

Effect of dual frequency on the plasma characteristics in an internal linear inductively coupled plasma source

An internal-type linear inductive antenna, referred to as a “double comb-type antenna,” was used as a large area plasma source with a substrate size of 880×660mm2 (fourth generation glass size). The effects of the dual frequency (2 and 13.56MHz) radio frequency (rf) power to the antenna as well as the power ratio on the plasma characteristics were investigated. High-density plasma on the order of 1.7×1011cm−3 could be obtained with a dual frequency power of 5kW (13.56MHz) and 1kW (2MHz) at a pressure of 15mTorr Ar. This plasma density was lower than that obtained for the double comb-type antenna using a single frequency alone (5kW, 13.56MHz). However, the use of the dual frequency with a rf power ratio of approximately 1(2MHz):5(13.56MHz) showed better plasma uniformity than that obtained using the single frequency. Plasma uniformity of 6.1% could be obtained over the substrate area. Simulations using FL2L code confirmed the improvement in the plasma uniformity using the dual frequency to the double comb-...

Thymidine synthase, thymidine phosphorylase, and excision repair cross-complementation group 1 expression as predictive markers of capecitabine plus cisplatin chemotherapy as first-line treatment for patients with advanced oesophageal squamous cell carcinoma

Background:Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer.Method:A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1.Results:The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1–54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0–7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39–10.0, P=0.009).Conclusion:These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.

Membrane type sialidase inhibits the megakaryocytic differentiation of human leukemia K562 cells

The membrane type sialidase (Neu3) has been suggested to participate in cell growth, migration and differentiation. To determine whether a Neu3 is able to modulate megakaryocytic differentiation of K562 cells, we studied the functional significance of human Neu3 induced by phorbol 12-myristate 13-acetate (PMA). Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) indicated that the induction of hST3Gal V, which synthesizes ganglioside GM3 and reduction of Neu3 by PMA, are linked for the expression of differentiation marker protein, CD41b surface antigen. To elucidate the mechanism underlying the down-regulation of the CD41b surface antigen expression when Neu3 gene is expressed in PMA-treated cells, we characterized the Neu3-mediated signaling pathway. Neu3 overexpression inhibited the PMA-induced ERK1/2 and p38 MAPK phosphorylation in the K562 cells. Down-regulation of expression of CD41b surface antigen was dependent on expression of Neu3 gene. However, a Neu3 inhibitor Neu5Ac2en induced morphological changes, showing megakaryocytic differentiation of K562 cells, with expression of CD41b surface antigen, while a specific glucosylceramide synthase inhibitor PDMP inhibited megakaryocytic differentiation of K562 cells. The molecular mechanisms involved in Neu3-involved inhibition of CD41b surface antigen expression in K562 cells have been suggested: the Neu3 degrades membrane sialic acids and the resulting signaling pathway of the PKC/ERKs/p38 MAPK is down-regulated, causing a decrease in CD41b surface antigen expression and inhibition of megakaryocytic differentiation of K562 cells.

Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by down-regulation of the expression of Bcl-2 protein.

Scutellaria barbata D. Don (Lamiaceae; SB) inhibited the growth of leiomyomal cells (LM). A time‐dependent antiproliferative effect was noted when 10−5 m buserelin, gonadotrophin‐releasing hormone (GnRH) agonist or 20–40 µg/mL SB was added. The inhibition of cell growth decreased with the addition of the PKC activator (12‐O‐tetradecanoylphorbor‐13‐acetate; TPA) much as it did with the addition of SB, and the decreases in the viable cells caused by the addition of SB were reversed completely by pretreatment with a protein kinase C (PKC) inhibitor (calphostin C). The findings suggest that SB inhibits cell proliferation in cultured human uterine leiomyoma cells accompanied by PKC activation. Next, the study investigated the effect of SB on fetal development for toxicity. Pregnant Sprague‐Dawley rats, from gestation day 6–15, were administered 20 g/L or 50 g/L SB in the drinking water and then killed on day 20. No maternal toxicity was observed, however, embryonic loss in the treatment groups was double that of the controls (p < 0.05). No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to SB were found to be significantly heavier than the controls, an effect that was greater in female fetuses and was not correlated with increased placental size. The results suggest that the SB had no toxicity and that in utero exposure to SB resulted in increased early embryo loss with increased growth in surviving fetuses. On the other hand, Western blot analyses revealed that Bcl‐2 protein of a 26 kDa was abundant in leiomyomal cells, but not in normal myometrial cells. The addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl‐2 protein expression in the cultured leiomyoma cells. However, the addition of SB (20 µg/mL) resulted in a significant reduction in Bcl‐2 protein expression in the cells. The results indicated that human uterine leiomyomal cells express Bcl‐2 protein and progesterone enhances its expression, however, SB reduces the expression of Bcl‐2 protein in human uterine leiomyoma cells. Copyright