• Title/Summary/Keyword: killing

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Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

The Lymphocyte Dependent Bactericidal Assay of Human Monocyte and Alveolar Macrophage for Mycobacteria (마이코박테리아에 대한 인체 말초혈액 단핵구와 폐포대식세포의 림프구 의존적 살해능에 관한 연구)

  • Cheon, Seon-Hee;Lee, You-Hyun;Lee, Jong-Soo;Bae, Ki-Sun;Shin, Sue-Yeon
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.1
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    • pp.5-16
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    • 2002
  • Background : Though mononuclear phagocytes serve as the final effectors in killing intracellular Mycobacterium tuberculosis, the bacilli readily survive in the intracellular environment of resting cells. The mechanisms through which cellular activation results in the intracellular killing is unclear. In this study, we sought to explore an in vitro model of a low-level infection of human mononuclear phagocytes with MAC and $H_{37}Ra$ and determine the extent of the lymphocyte dependent cytotoxicity of human monocytes and alveolar macrophages. Materials and Methods : The peripheral monocytes were prepared using the Ficoll gradient method from PPD positive healthy people and tuberculosis patients. The alveolar macrophages were prepared from PPD positive healthy people via a bronchoalveolar lavage. The human mononuclear phagocytes were infected at a low infection rate (bacilli:phagocyte 1:10) with MAC(Mycobacterium avium) and Mycobacterium tuberculosis $H_{37}Ra$. Non-adherent cells(lymphocyte) were added at a 10:1 ratio. After 1,4, and 7 days culture in $37^{\circ}C$, 5% CO2 incubator, the cells were harvested and inoculated in a 7H10/OADC agar plate for the CFU assay. The bacilli were calculated with the CFU/$1{\times}10^6$ of the cells and the cytotoxicity was expressed as the log killing ratio. Results : The intracellular killing of MAC and $H_{37}Ra$ within the monocyte was greater in patients with tuberculosis compared to the PPD positive controls (p<0.05). Intracellular killing of MAC and $H_{37}Ra$ within the alveolar macrophage appeared to be greater than that within the monocytes of the PPD positive controls. There was significant lymphocyte dependent inhibition of intracellular growth of the mycobacteria within the monocytes in both the controls and tuberculosis patients and within the macrophages in the controls(p<0.05). There was no specific difference in the virulence between the MAC and the $H_{37}Ra$. Conclusion : This study is an in vitro model of a low-level infection with MAC and $H_{37}Ra$ of human mononuclear phagocytes. The intracellular cytotoxicity of the mycobacteria within the phagocytic cells was significantly lymphocyte dependent. During the 7 days culture after the intracellular phagocytosis, the actual confinement of the mycobacteria was observed within the monocytes of tuberculosis patients and the alveolar macrophages of the controls as in the case of adding lymphocytes.

Effect of Anesthesia Killing and non-Bleeding on Physicochemical Properties of Plaice, Paralichthys olivaceus Muscle at early Period after Death. (마취사 및 무방혈이 넙치육의 사후조기의 물리${\cdot}$화학적변화에 미치는 영향)

  • CHO Young-Je;CHO Min-Sung;KIM Sang-Moo;CHOI Young-Joon
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.30 no.4
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    • pp.589-594
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    • 1997
  • This study was performed to clarify the effect of anesthesia killing and non-bleeding on the physicochemical and rheological properties of plaice, Paralichthys olivaceus muscle at early period after death. Live plaice was killed by the two different methods: spiking at the brain instantly with bleeding and dipping In seawater containing anesthetic (2,000 ppm ethyl-aminobenzoate) for 10 min without bleeding. These samples were stored at $0^{\circ}C$ and used in checking rigor-mortis, ATP breakdown, the content of ATP and its related compounds, breaking strength, and lactate accumulation through storage. The rigor-mortis, ATP breakdown, and lactate accumulation was faster in samples killed by spiking than in samples killed by anesthesia. ATP in samples killed by anesthetic showed little breakdown until 22.5 hrs, but it was decomposed completely after 30 hrs storage. Breaking strength of samples killed by spiking at the brain instantly with bleeding decreased steadily and showed the maximum value over 10 hrs $(2207.3{\pm}60.2g)$. However, in case of the dipping fresh flesh without bleeding in seawater containing anesthetic, the value and time reached around the maximum breaking strength were $2147.8{\pm}29.0g$ and 13 hrs respectively, but it maintained constantly until 20 hrs passed. From these results, it could be suggested that anesthesia killing and non-bleeding is more effective in maintaining firmness of fresh plaice muscle than spiking killing with bleeding at the early period after death.

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A Review on Experimental Research about Anticancer Drug Combined Treatment with Herbal Medicine for Killing or Inhibiting Proliferation of Cancer cells in Korea. (항암제와 한약재의 병용투여 시 암세포 증식억제 효과에 대한 국내 실험연구 문헌고찰)

  • Lee, Ji Eun;Choi, Jin Yong;Han, Chang Woo;Choi, Jun Yong;Park, Seong Ha;Kim, So Yeon
    • Herbal Formula Science
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    • v.25 no.3
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    • pp.391-412
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    • 2017
  • Objective : In this study, we searched the experimental research about combined treatment of anticancer drug and herbal medicine for killing or inhibiting proliferation of Cancer cells searched in OASIS and KISS. This study aimed to analyze the experimental research paper about anticancer drug combined treatment with herbal medicine. Methods : We collected the research paper including killing or inhibiting proliferation of Cancer cells in OASIS and KISS using keyword anticancer drug with herbal medicine, tumor suppressor with herbal medicine, inhibition of Cancer with herbal medicine and combined treatment with herbal medicine. Assorting by cancer cells, we analyzed experimental results cancer cell viability, anticancer drug dosage, tumor weight and survival rate. Also, we checked the effects of herbal medicine on cancer and additive effect reducing side effect of anticancer drug. Results : Total 45 studies were selected. 38 studies reported combined treatment of anticancer drug and herbal medicine was more effective than only anticancer drug. The death of cancer cells was synergistically induced by the cotreatment of anticancer drug and herb extracts. The studies suggest that the cotreatment of anticancer drug and herb extracts could reduce side effect of anticancer drug. In addition, some studies reported cotreatment mechanism like apoptotic death signal processes. In combined treatment of anticancer drug and herb extracts, The expression of Fas/Fas L, Bax, Bcl2, Caspase-3 etc.. was markedly increased in cancer cells. Conclusions : Our results suggest that anticancer drug combined treatment with herbal medicine could be efficient for killing or inhibiting proliferation of cancer cells. However, this paper had some limitation as follows: First, collected studies have been published only for korean journal. Second, results of research and effects of combined treatment are not collected objectively. To solve these problems, more objective and balanced studies should be performed.

Transformation of Ancient Greek Tragedy Revealed in The Killing of a Sacred Deer (<킬링 디어>에 드러난 고대 그리스 비극의 변용)

  • Kwon, Eunsun
    • The Journal of the Convergence on Culture Technology
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    • v.8 no.3
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    • pp.393-398
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    • 2022
  • Yorgos Lanthimos' The Killing of a Sacred Deer (2017) uses Iphigeneia in Aulis written by Euripides, one of the three great Greek tragedies writers, as the archetypal narrative. Thus, Lanthimos introduces a mythical world stained with 'blood violence by a divine being' within the cinematic diegesis of a modern American metropolis. And the mythical motifs of curses and scapegoats are varied. This thesis tried to read the scapegoat mechanism, the oldest mechanism of escape from the crisis of collective sacrifice, and the imitative and mutual characteristics of desire and violence through René Girard through the mythical world built in the modern time and space of the film. Martin places a cursed oracle on Steven when his desire to place him in his father's place is thwarted. The 'good' reciprocity between two people is rapidly transformed into a 'bad' reciprocity. The Killing of Sacred Deer is an excellent portrayal of how the scapegoat mechanism works through Steven's family. The selection of the scapegoat by lot gives the sacrificial lamb a sacred character thanks to its divine nature, and the scapegoat becomes a sacred being, and the family order is re-established.

Symptoms of the subject in a movie based on Lacan's work on psychosis - Focusing On Lars von Trier's film (라캉의 정신병 연구에 근거한 영화 속 주체의 증상 - 라스 폰 트리에의 <살인마 잭의 집>을 중심으로)

  • HAN JINGZHI
    • Trans-
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    • v.16
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    • pp.69-105
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    • 2024
  • The House that Jack Built (2018), a film about how the protagonist Jack is reborn as a "mad artist" with psychotic symptoms during a 12-year killing spree, provides an interesting opportunity to analyze the film in terms of psychoanalysis and religion. Jack, an engineer who suffers from OCD, finds pleasure in the accidental murder of a character and considers killing people as an art form, overcoming his OCD in the process. The question we are interested in is whether the symptoms of OCD are truly overcome by the act of repeated killing. The idea is that Jack's OCD is not overcome by killing, but rather that the symptoms disappear as he moves from neurosis to a stabilized psychotic state. According to the theory of the famous French psychoanalyst Lacan, the hallucinations or delusions that human subjects experience when they lose their realistic stability are a phenomenon that occurs when they are confronted with The Real, which penetrates through the cracks of the symbolic system. Phenomena such as Jack's illusory reality and delusions in the movie are pathological symptoms of the absence of a paternal figure in his life, causing the Name-of-the-Father to fail to take hold. This paper deciphers the psychotic structure of Jack, the protagonist of Lars von Trier's House of Jack, through Lacanian psychoanalysis.

Endangered Tiger (절종위기의 호랑이)

  • Moon Hong-Sik
    • Journal of the korean veterinary medical association
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    • v.14 no.2
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    • pp.117-119
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    • 1978
  • Tigers are the large cats with prominent, black or brawn, stripes. They are common in jungles of India and Java, but range as far as the snowy, forested mountains of Siberia. Legal and illegal killing(over-hunting, poaching for skin, and also its bones, f

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Effects of Zinc Containing Solution on Oral Microorganisms (Zinc 수용액이 구강 미생물에 미치는 영향)

  • 이상구;김은숙;이승우
    • Journal of Oral Medicine and Pain
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    • v.23 no.4
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    • pp.343-352
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    • 1998
  • This experiment was performed to investigate effects of zinc containing solution on the major normal flora Staphylococccus aureus, Streptococus mutans and Candida albicans and to observe the variation according to anionic change and concentration difference. Zinc chloride, zinc iodide and zinc acetate solution were added to werially diluted broth culture so that each final concentration might be 0.25%, 0.5%. 1%. After that, 100ul of each aliquot was spreaded on each selective media plate( Mannitol Salts Agar plate for Staphylococcus aureus, Mitis Salivarius Agar plate for Streptococcus mutans and Sabouraud Destrose Agar plate for Candida albicans). The % killing was calculated bu CFU count after incubation under the appropriate condition. 1. zinc iodide, zinc chloride, and zinc acetate solutions showed inhibitory effects on Staphylococcus aureus, Streptococcus mutans and Candida albicans. 2. The inhibitory effects on Staphylococcus aureus were ranked in order of ainc iodide, zinc chloride and zinc actate. 3. The inhibitory effects on Streptococcus mutans were ranked in orfer of zinc iodide, zinc chloride and zinc acetate. 4. the inhibitory effects on Candida albicans showed no difference among zinc iodide, zinc chloride and zinc acetate. 5. The inhibitory effects of zinc chloride and zinc acetate on Staphylococcus aureus and Streptococcus mutnas showed increasing pattern as the concentration increase. But the inhibitory effects of zinc iodide on Staphylococcus aureus and Streptococcus mutans showed no apparent difference according to concentrations and it was the case with the inhibitory effects of zinc iodide, zinc chloride and zinc acetate on Candida albicans.

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