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Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice

  • Thi, Van Anh Do;Jeon, Hyung Min;Park, Sang Min;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.42 no.12
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    • pp.869-883
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    • 2019
  • Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4+ T, CD8+ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

Analysis of the Biological Function of ELDF15 Using an Antisense Recombinant Expression Vector

  • Liu, Yan;Wang, Long;Wang, Zi-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9131-9136
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    • 2014
  • ELDF15, homologous with AT2 receptor-interaction protein 1 (ATIP1), may play an important role in cell differentiation, proliferation, and carcinogenesis. We aimed to understand the biological function of ELDF15 via construction and transfection of a recombinant expression vector containing antisense ELDF15. Recombinant expression vectors were successfully constructed and transfected into K562 cells. A stable transfectant, known as pXJ41-asELDF15, stably produced antisense ELDF15. Compared with K562 and K562-zeo cells, K562-pXJ41-asELDF15 cells showed inhibition of cell proliferation. RT-PCR analysis showed that the expression and protein level of ELDF15 decreased significantly in K562 cells transfected with pXJ41-asELDF15. Expression of hemoglobin increased in K562 cells transfected with pXJ41-asELDF15 by benzidine staining. increases NBT reduction activity in K562 cells transfected with pXJ41-asELDF15.Colony forming efficiency in two-layer soft agar was clearly inhibited as assessed by electron microscopy. These results suggest that ELDF15 plays a potential role in cell differentiation, proliferation and carcinogenesis.

A Study over Catalytic Behavior Octane Enhancer, TAME Synthesis with Ion Exchange Resin Catalysts (이온교환수지 촉매를 이용한 옥탄가 향상제인 TAME 합성반응의 연구)

  • Park, Jin-Hwa
    • Applied Chemistry for Engineering
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    • v.7 no.5
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    • pp.832-842
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    • 1996
  • TAME synthesis was studied in a fixed bed reactor with 3 different types of exchanged resins i.e, Amberlyst-15, Amberlyst-15(wet) and Amberlyst XN-1010. Amberlyst-15 has highest activity, presumably due to the higher reaction participation of the inner active sites of gel shape microparticular resin structure. The optimum reaction conditions for TAME synthesis were found as follows ; reaction temperature of $135^{\circ}C$, molar ratio(MeOH/I.A.A) of 1.0~4.0 and W/F of 2.0~4.0 gr.-cat. hr/gr.-mole. The cross-linking bond of styrene divinyl benzene was observed at $2{\theta}=20$ in XRD pattern. The DSC analysis showed that the thermal stability was in order of Amberlyst-15>Amberlyst-15(wet)>Amberlyst XN-1010. The apparent activation energies of TAME synthesis reaction with Amberlyst-15, Amberlyst-15(wet) and Amberlyst XN-1010 were 12.36, 12.46 and 14.72 kcal/mole, respectively.

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Upregulation of STK15 in Esophageal Squamous Cell Carcinomas in a Mongolian Population

  • Chen, Guang-Lie;Hou, Gai-Ling;Sun, Fei;Jiang, Hong-Li;Xue, Jin-Feng;Li, Xiu-Shen;Xu, En-Hui;Gao, Wei-Shi;Cao, Jian-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6021-6024
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    • 2014
  • Background: The STK15 gene located on chromosome 20q13.2 encodes a centrosome-associated kinase critical for regulated chromosome segregation and cytokinesis. Recent studies have demonstrated STK15 to be significantly associated with many tumors, with aberrant expression obseved in many human malignancies. The purpose of this study was to investigate expression of STK15 in esophageal squamous cell carcinomas (ESCCs) in a Mongolian population. Methods: Two non-synonymous single nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls. We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas and corresponding adjacent tissues by real time PCR. Results: rs2273535 showed a significant association with ESCC in our Mongolian population (rs227353, P allele = 0.0447, OR (95%CI) = 1.259 (1.005~1.578)). Real time PCR analysis of ESCC tissues showed that expression of STK15 mRNA in cancer tissues was higher than in normal tissues (p = 0.013). Conclusions: Our study showed that functional SNPs in the STK15 gene are associated with ESCC in a Mongolian population and up-regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues. STK15 may thus have an important role in the prognosis of ESCC and be a potential therapeutic target.

Spectrophotometric Study of the Interaction between Tetraethylammonium Halides and Aza-15-crown-5 with I2 and ICl in Acetonitrile Solution

  • Semnani, Abolfazl;Pouretedal, Hamid Reza;Hossein Keshavarz, Mohammad
    • Bulletin of the Korean Chemical Society
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    • v.27 no.6
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    • pp.886-892
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    • 2006
  • The interaction between tetraethylammonium chloride (TEACl) with ICl and tetraethylammonium iodide (TEAI) and aza-15-crown-5 (A15C5) with $I_2$ and ICl have been examined spectrophotometrically in acetonitrile solution. The results of TEACl-ICl indicate the formation of $ICl_2$ - through equilibrium reaction. In the case of TEAI-$I_2$ and A15C5-$I_2$, the equilibrium formation of $I_3$ - is confirmed. The interaction of TEAI-ICl begins with the simultaneous production of $I_2$ and IC$I_2$ - (at TEAI/ICl < 0.5) as well as continues with the simultaneous consumption of $I_2$ and formation of I$I_3$ - (at TEAI/ICl > 0.5). Similar behavior is also observed for A15C5-ICl system. However, the changes are seen at A15C5/ICl mole ratios less and more than 0.66. Several equations have been suggested for the formation of detected species. The formation constants of various reactions were evaluated from the computer fitting of the absorbance-mole ratio data. IR spectra of A15C5 and 1:1 A15C5:ICl or A15C5:$I_2$ complexes are compared and the effect of complexation on absorption bands is discussed.

Extending Network Domain for IEEE1394

  • Lee, Seong-Hee;Park, Seong-Hee;Choi, Sang-Sung
    • Proceedings of the Korea Society of Information Technology Applications Conference
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    • 2005.11a
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    • pp.177-178
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    • 2005
  • Wireless 1394 over IEEE802.15.3 must allow a data reserved for delivery over a wired 1394 network to be delivered over an IEEE802.15.3 wireless network through bridging IEEE 1394 to IEEE802.15.3. Isochronous transfers on the 1394 bus guarantee timely delivery of data. Specifically, isochronous transfers are scheduled by the bus so that they occur once every $125\;{\mu}s$ and require clock time synchronization to complete the real-time data transfer. IEEE1394.1 and Protocol Adaptation Layer for IEEE1394 over IEEE802.15.3 specify clock time synchronization for a wired 1394 bus network to a wired 1394 bus network and wireless 1394 nodes, which are IEEE802.15.3 nodes handling 1394 applications, over IEEE802.15.3. Thus, the clock time synchronizations are just defined within a homogeneous network environment like IEEE1394 or IEEE802.15.3 until now. This paper proposes new clock time synchronization method for wireless 1394 heterogeneous networks between 1394 and 802.15.3. If new method is adopted for various wireless 1394 products, consumer electronics devices such as DTV and Set-top Box or PC devices on a 1394 bus network can transmit real time data to the AV devices on the other 1394 bus in a different place via IEEE 802.15.3.

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Channel Searching Method of IEEE 802.15.4 Nodes for Avoiding WiFi Traffic Interference (WiFi 트래픽 간섭을 피하기 위한 IEEE 802.15.4 노드의 채널탐색방법)

  • Song, Myong Lyol
    • Journal of Internet Computing and Services
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    • v.15 no.2
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    • pp.19-31
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    • 2014
  • In this paper, a parallel backoff delay procedure on multiple IEEE 802.15.4 channels and a channel searching method considering the frequency spectrum of WiFi traffic are studied for IEEE 802.15.4 nodes to avoid the interference from WiFi traffic. In order to search the channels being occupied by WiFi traffic, we analyzed the methods measuring the powers of adjacent channels simultaneously, checking the duration of measured power levels greater than a threshold, and finding the same periodicity of sampled RSSI data as the beacon frame by signal processing. In an wireless channel overlapped with IEEE 802.11 network, the operation of CSMA-CA algorithm for IEEE 802.15.4 nodes is explained. A method to execute a parallel backoff procedure on multiples IEEE 802.15.4 channels by an IEEE 802.15.4 device is proposed with the description of its algorithm. When we analyze the data measured by the experimental system implemented with the proposed method, it is observed that medium access delay times increase at the same time in the associated IEEE 802.15.4 channels that are adjacent each other during the generation of WiFi traffic. A channel evaluation function to decide the interference from other traffic on an IEEE 802.15.4 channel is defined. A channel searching method considering the channel evaluations on the adjacent channels together is proposed in order to search the IEEE 802.15.4 channels interfered by WiFi, and the experimental results show that it correctly finds the channels interfered by WiFi traffic.

Interferon Stimulated Gene - ISG15 is a Potential Diagnostic Biomarker in Oral Squamous Cell Carcinomas

  • Laljee, Rupesh Puthenparambil;Muddaiah, Sunil;Salagundi, Basavaraj;Cariappa, Ponappa Muckatira;Indra, Adarsh Surendran;Sanjay, Venkataram;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1147-1150
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    • 2013
  • Background: Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Materials and Methods: Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Results: Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. Conclusions: To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers.

De novo interstitial deletion of 15q22q23 with global developmental delay and hypotonia: the first Korean case

  • Kim, Ha-Su;Han, Jin-Yeong;Kim, Myo-Jing
    • Clinical and Experimental Pediatrics
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    • v.58 no.8
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    • pp.313-316
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    • 2015
  • Interstitial deletions involving the chromosome band 15q22q24 are very rare and only nine cases have been previously reported. Here, we report on a 12-day-old patient with a de novo 15q22q23 interstitial deletion. He was born by elective cesarean section with a birth weight of 3,120 g at 41.3-week gestation. He presented with hypotonia, sensory and neural hearing loss, dysmorphism with frontal bossing, flat nasal bridge, microretrognathia with normal palate and uvula, thin upper lip in an inverted V-shape, a midline sacral dimple, severe calcanovalgus at admission, and severe global developmental delay at 18 months of age. Fluorescence in situ hybridization findings confirmed that the deleted regions contained at least 15q22. The chromosome analysis revealed a karyotype of 46,XY,del(15) (q22q23). Parental chromosome analysis was performed and results were normal. After reviewing the limited literature on interstitial 15q deletions, we believe that the presented case is the first description of mapping of an interstitial deletion involving the chromosome 15q22q23 segment in Korea. This report adds to the knowledge of the clinical phenotype associated with the 15q22q23 deletion.

The novel gene LRP15 is regulated by DNA methylation and confers increased efficiency of DNA repair of ultraviolet-induced DNA damage

  • Xu, Zhou-Min;Gao, Wei-Ran;Mei, Qi;Chen, Jian;Lu, Jing
    • BMB Reports
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    • v.41 no.3
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    • pp.230-235
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    • 2008
  • LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.