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The Effect of Tyrosine Kinase Inhibitors on the L-type Calcium Current in Rat Basilar Smooth Muscle Cells

  • Bai, Guang-Yi;Yang, Tae-Ki;Gwak, Yong-Geun;Kim, Chul-Jin
    • Journal of Korean Neurosurgical Society
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    • v.39 no.3
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    • pp.215-220
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    • 2006
  • Objective : Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type $Ca^{2+}$ channels playa role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type $Ca^{2+}$ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type $Ca^{2+}$ channels currents in freshly isolated smooth muscle cells from rat basilar artery. Methods : The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Results : Patch clamp studies revealed a whole-cell current which resembles the L-type $Ca^{2+}$ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein[n=5], tyrphostin A-23[n=3]. A-25[n=6] $30{\mu}M$ reduced the amplitude of the L -type $Ca^{2+}$ channel current in whole cell mode. In contrast, diadzein $30{\mu}M$ [n=3]. inactive analogue of genistein, did not decrease the amplitude of the L-type $Ca^{2+}$ channels current. Conclusion : These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [$Ca^{2+}$]i, by inhibition of L-type $Ca^{2+}$ channel.

A Study on the Performance of Priority Mechanisms in ATM Multiplexer (ATM 멀티플렉서에서의 우선순위 메카니즘에 관한 연구)

  • 윤성호;박광채;이재호
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.18 no.6
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    • pp.779-792
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    • 1993
  • In a switching node or an ATM multiplexer of the ATM network, a good bandwidth utilization can be achieved by the priority control using the 1-bit(Cell Loss priority) in ATM cell header. In this paper, the mixed mechanism is proposed to make up for shortcomings of existing space priority control mechanisms and to decrease the loss probability of high priority cell and its performance is analyzed about the cell loss probability. To estimate the performance of proposed mixed mechanism, its cell loss probability is compared with those of non-priority mechanism, push-out mechanism and partial buffer sharing mechanism. The cell loss probability is analyzed using a M/D/1/N modeling and a 2-state MMPP/D/1/N modeling and also comparison between two modelings is made. To verify this result of numerical analysis, the computer simulation is performed for each mechanism using the simulation language, SIMSRIPT II.5.

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Effect of Depletion and Oxidation of Cellular GSH on Cytotoxicity of Mitomycin Small Cell Lung Cancer Cells

  • Lee, Chung-Soo
    • Biomolecules & Therapeutics
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    • v.12 no.2
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    • pp.92-100
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    • 2004
  • Effect of the depletion or oxidation of GSH on mitomycin c (MMC)-induced mitochondrial damage and cell death was assessed in small cell lung cancer (SCLC) cells. MMC induced cell death and the decrease in the GSH contents in SCLC cells, which were inhibited by z-LEHD.fmk (a cell permeable inhibitor of caspase-9), z-DQMD.fmk (a cell permeable inhibitor of caspase-3) and thiol compound, N-acetylcysteine. MMC caused nuclear damage, release of cytochrome c and activation of caspase-3, which were reduced by N-acetylcysteine. The depletion of GSH due to L-butionine-sulfoximine enhanced the MMC-induced cell death and formation of reactive oxygen species in SCLC cells, whereas the oxidation of GSH due to diamide or $NH_2Cl$ did not affect cytotoxicity of MMC. The results show that MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to activation of caspase-9 and -3. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by the depletion of GSH. In contrast, the oxidation of GSH may not affect cytotoxicity of MMC.

Neuroprotective effects of some herbal medicine plant extract against ischemia·reperfusion-induced cell death in SK-N-SH neuronal cells (허혈·재관류 유도성 신경세포사멸에 대하여 신경보호효과를 가지는 약용식물 추출물의 검색)

  • Oh, Tae-Woo;Lee, Mi Young;Lee, Hye Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.45-53
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    • 2013
  • Objectives : The purpose of the study is to determine the neuroprotective effects of the water and 80% EtOH extract of some herbal medicine plant on ischemia reperfusion-induced cell death in SK-N-SH human brain neuronal cells. Methods : SK-N-SH cells were treated with 3mM sodium azide and 10 mM 2-deoxy-D-glucose for 45 min, ptior to the addition of different concentrations of herbal medicine plant extract (0, 10, 25, 50, 100, 250, 500, 1000 ${\mu}g/ml$) for 2 hr and then reperfused with growth medium, incubated for 24 h. Cell viability was determined by WST-1 assay, and ATP/ADP levels were measured by ADP/ATP ratio assay kit. Results : Herbal medicine plant extract significantly inhibited decreasing the cell viability in ischemia-induced SK-N-SH cells. Also increased the ratio of ADP/ATP in ischemia-induced neuronal cells. Conclusions : Our results suggest that herbal medicine plant extract has a neuroprotective property via increasing the energy levels in neuronal cells, suggesting that extract may has a therapeutic potential in the treatment of ischemic brain injury. The exact component and mechanism remains for the future study.

N-Acetylphytosphingosine Enhances the Radiosensitivity of Lung Cancer Cell Line NCI-H460

  • Han, Youngsoo;Kim, Kisung;Shim, Ji-Young;Park, Changsoe;Song, Jie-Young;Yun, Yeon-Sook
    • Molecules and Cells
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    • v.25 no.2
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    • pp.224-230
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    • 2008
  • Ceramides are well-known second messengers that induce apoptosis in various kinds of cancer cells, and their effects are closely related to radiation sensitivity. Phytoceramides, the yeast counterparts of the mammalian ceramides, are also reported to induce apoptosis. We investigated the effect of a novel ceramide derivative, N-acetylphytosphingosine (NAPS), on the radiosensitivity of NCI-H460 human lung carcinoma cells and its differential cytotoxicity in tumor and normal cells. The combination of NAPS with radiation significantly increased clonogenic cell death and caspase-dependent apoptosis. The combined treatment greatly increased Bax expression and Bid cleavage, but not Bcl-2 expression. However, there was no effect on radiosensitivity and apoptosis in BEAS2B cells, which derive from normal human bronchial epithelium. Cell proliferation and DNA synthesis were significantly inhibited by NAPS in both NCI-H460 and BEAS2B cells, but only the BEAS2B cells recovered by 48h after removal of the NAPS. Furthermore, the NCI-H460 cells underwent more DNA fragmentation than the BEAS2B cells in response to NAPS. Our results indicate that NAPS may be a potential radiosensitizing agent with differential effects on tumor vs. normal cells.

Long Term Survival of Patients with Unsuspected N2 Disease in Non-Small Cell Lung Cancer

  • Lee, Deok Heon;Kim, Jae Bum;Keum, Dong Yoon;Hwang, Ilseon;Park, Chang Kwon
    • Journal of Chest Surgery
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    • v.46 no.1
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    • pp.49-55
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    • 2013
  • Background: The aim of this study was to determine the survival rate of patients with non-small cell lung cancer (NSCLC) who were preoperatively diagnosed with a negative N2 lymph node, but postoperatively confirmed as a positive N2 node based on a pathological evaluation. Materials and Methods: The hospital records of 248 patients from 1994 to 2009 with resected primary NSCLC who were preoperatively diagnosed with negative N2 lymph node, were retrospectively reviewed. Of these, after surgery, there were 148 (59.7%) patients with pathological N0, 54 (21.8%) with pathological N1 and 46 (18.5%) with pathological N2. Results: The median follow-up period was 24 months (range, 1 to 132 months). The 5-year disease free survival rates were 60% in pN0, 44% in pN1, and 29% in pN2. The 5-year overall survival rates were 63.1% in pN0, 51.9% in pN1, and 33.5% in pN2. There were no statistically significant differences between pN1 and pN2 (p=0.326 and p=0.106, respectively). Thirty-three (71.7%) of the 46 pN2 patients had single-zone metastasis, and 13 patients (28.3%) had multiple-zone metastases over the two nodal zone metastasis. There were no statistical differences in the 5-year disease free survival rate and the 5-year overall survival rates between the two groups. Conclusion: The 5-year disease free survival and the overall survival rate of the patients with unsuspected N2 disease were statistically similar with that of the patients with pathological N1 disease. There was no statistically significant difference between the patients with a single-zone metastasis and a multiple zone metastasis.

Overall and disease-specific survival outcomes following primary surgery for oral squamous cell carcinoma: analysis of consecutive 67 patients

  • Sim, Yookyeong Carolyn;Hwang, Jong-Hyun;Ahn, Kang-Min
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.45 no.2
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    • pp.83-90
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    • 2019
  • Objectives: This study evaluated the predictive factors for survival of patients with oral squamous cell carcinoma (OSCC) and investigated the overall and disease-specific survival (DSS) outcomes. Materials and Methods: A total of 67 consecutive patients who underwent surgery for OSCC from January 2006 to November 2014 were included in this study. Patients were classified according to age, sex, pTNM stages, primary sites, smoking and alcohol drinking habits, depth of invasion, perineural and lymphovascular invasion, cell differentiation and postoperative radiotherapy. Kaplan-Meier methods were used to estimate the survival categorized by patient groups. Cox regression methods were used to investigate the main independent predictors of survival. Results: Nineteen patients died of OSCC during follow-up periods. Another five patients died of other diseases including lung adenocarcinoma (n=1), cerebral infarction (n=1), general weakness (n=2), and pneumonia (n=1). The tongue (n=16) was the most common site for primary origin, followed by buccal mucosa (n=15), mandibular gingiva (n=15), maxillary gingiva (n=9), floor of mouth (n=9), retromolar trigone (n=2), and palate (n=1). Eleven patients had pTNM stage I disease, followed by stage II (n=22) and stage IV (n=34). No patients had pTNM stage III disease in this study. The overall survival of all patients was 64.2% and the DSS was 71.6%. DSS of patients with stage I and II disease was 100%. Stepwise Cox regression showed the two predictors for DSS were pTNM stage (P<0.0001, odds ratio=19.633) and presence of metastatic lymph nodes (P=0.0004, odds ratio=0.1039). Conclusion: OSCC has been associated with poor prognosis; however, there were improved survival outcomes compared with past studies. Advanced-stage disease and presence of metastatic lymph nodes were associated with poorer survival compared with early-stage OSCC and absence of neck node metastasis. Stage I and II OSCC were associated with excellent survival results in this study.

Synthesis of a series of cis-diamminaedichloro-platinum (II) Complexes Linked to Uracil and Uridine as Candidate An-titumor Agents.

  • Kim, Jack-C.;Kim, Mi-Hyang;Kim, Seon-Hee;Choi, Soon-Kyu
    • Archives of Pharmacal Research
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    • v.18 no.6
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    • pp.449-453
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    • 1995
  • The search for patinum (II)-based compounds with improved therapeutic properties was prompted to design and synthesize a new family of water-soluble, third generation cis-diamminedichlorplatinum (II) complexes linked to uracil and uridine. Six heretofore undescribed uracil and uridine-platinum (II) complexes are ; [N-(2-aminoethyl)uracil-5-carboxamide]dichloroplatinum (II)(3a), [N-2(2-aminoethyl)uracil-6-carboxmide]dichloroplatinum (II) (3b),[5-(2-aminorthyl)carbamoyl-2',3',5',-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl)-carbamoyl]-2',3',5',-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl)carbamoylu-ridine]dihloroplatinum (II) (7a), [6-(2-aminoethyl)carbamoyluridine]dichloroplatinum (II) (7b). These analogues were prepared from the key starting materials, 5-carboxyuracil (1a) and 6-carboxyuracil (1b) which were reacted with ethylenediamine to afford the respective N-(2-aminoethyl)uracil-5-carboxmide (2a) land N-(2-aminoethyl)uracil-6-carboxamide (2b). The cisplatin complexes 3a and 3b were obtained through the reaction of the respective 2a and 2b ficiently introduced on the .betha.-D-ribose ring via a Vorbruggen-type nucleoside coupling procedure with hexamethyldisilazane, trimethylchlorosilane and stannicchloride under anhydrous acetonitfile to yield the sterospecific .betha.-anomeric 5-carboxy-2',3',5'-tri-O-acetyluridine (4a) and 6-carboxy-2',3',5'-tri-O-acetyluridine (4b), respective 5-(2-aminoethyl)carbamoyl-2',3',5'-tri-O-acetyluridine (5a) and 6-(2-aminoethyl)carbamoyl-2',3',5'-tri-O-acetyluridine (5b). The diamino-uridines 5a and 5b were reacted with potassium tetrachloroplatinate (II) to give the novel nucleoside complexes, 6a and 6b respectively which were deacetylated into the free nucleosides, 7a and 7b by the treatment with CH/sub 3/ONa. The antitumor activities were evaluated against three cell lines (K-562, FM-3A and P-388).

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The characteristics and treatment results of squamous cell carcinomas of oral tongue (구강설에 발생한 편평상피세포암의 특성과 치료효과)

  • Kim, Ki-Ho;Choi, Eun-Joo;Kim, Hyung-Jun;Nam, Woong;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.1
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    • pp.15-20
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    • 2011
  • Introduction: The characteristics of oral tongue squamous cell carcinomas (SCC) and the treatment results were reviewed to determine the appropriate treatment strategies. Materials and Methods: The medical records of 140 patients diagnosed and treated for oral tongue SCC at Yonsei University Health System from January 1995 to December 2004 were reviewed. For statistic analysis, the survival rate was determined using the Kaplan-Meier method with SPSS version 12.0, and the difference in survival rates was evaluated using a log-rank test. Results: The mean age of the patients with oral tongue SCC patients was 55 (19-85 years old). According to the T, N and pathologic stage, the patients were distributed from a higher to a lower incidence of cases, as follows: T2 (46.4%), T1 (37.9%), T4 (8.5%), and T3 (7.1%); N0 (65%), N1 (20.7%), N2 (13.6%), and N3 (0.7%); and stage I (31.4%), stage II(25.7%), stage IV (22.2%), and stage III (20.7%). Local and regional recurrence and distant metastasis was present in 13.6%, 5% and 4.2% of patients, respectively. The five-year survival rate was 72.2%, and the prognostic factors for oral tongue SCC included neck metastasis, pathologic stage of the disease, cell differentiation, treatment modality, neck dissection as part of the treatment plan, and neck node recurrence. Discussion: It is suggested that ipsilateral neck dissection or bilateral neck dissection should be selected as a treatment of tongue SCC patients with advanced stage.

The Effect of Abraxane on Cell Kinetic Parameters of HeLa Cells

  • Gurses, Nurcan;Topcul, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4229-4233
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    • 2013
  • Abraxane (nab-paclitaxel) is a member of the group of nano chemotherapeutics. It is approved for metastatic breast cancer and non small cell lung cancer. Trials for several cancer types including gynecological cancers, head and neck, and prostatic cancer are being studied. In this study, the antiproliferative and apoptotic effect of abraxane was evaluated on HeLa cell line originated from human cervix carcinoma. Three different doses ($D_1$=10 nM, $D_2$=50 nM, $D_3$=100 nM) were administered to HeLa cells for 24, 48 and 72 h. The 50 nM dose of abraxane decreased DNA synthesis from 4.62-0.08%, mitosis from 3.36-1.89% and increased apoptosis from 10.6-30% at 72 h. Additionally, tripolar metaphase plates were seen in mitosis preparations. In this study, abraxane effected cell kinetic parameters significantly. This results are consistent with other studies in the literature.