• Title/Summary/Keyword: T cell survival

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Cell Surface Interaction with Expression of Fas Ligand Mediates Prolactin-Induced Apoptosis In Rat Luteal Cell Culture (Rat 황체세포 배양에 있어서 Prolactin에 의한 황체퇴행 및 Fas Ligand의 발현)

  • 장규태;박미령;선동수;윤창현
    • Journal of Embryo Transfer
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    • v.13 no.2
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    • pp.179-190
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    • 1998
  • Prolactin (PRL) surge in cycling rats at proestrous afternoon has previously been reported as an inducer of apoptotic cell death of luteal cells. This death-inducing action of PRL seeins unusual, because PRL can he categorized as a cell-survival factor, if other known physiological functions of PRL are taken into account. In this study, the apoptotic action of PRL was assessed in cultured cells prepared from rat luteal tissue and underlying molecular /cellular mechanism of PRL-induced luteolysis was analyzed. The latest crop of corpora lutea (CLs) were enucleated from rat ovaries at 18:00 h on the proestrous day before the next ovulation. Donor rats were pretreated with CB154, a dopamine agonist, in order to he exempted from the endogenous PRL surge. The harvested GLs were dispersed and cultured with or without PRL (2$\mu$g /ml) for 24 or 48 h. An addition of PRL to the culture medium changed the parameters indicative of cell death via apoptosis: a decrease in cell viability (MTT) and an increase in chromatin condensation. Most of the DNA breakdown in nuclei induced by PRL occurred in steroidogenic cells which were identified by 3$\beta$-HSD activity staining, and the number of 3$\beta$-HSD-positivecells were significantly decreased. Interestingly, most of the cells with an apoptotic nucleus adhered to one or more intact and seemingly non-steroidogenic cells. Because the expression of Fas has heen shown to be abundant in murine ovary, and Fas is known to have an exact physiological role in occurrence of apoptotic cell death, the membrane form-Fas ligand (rnFasL) was quantified in the cell lysate. An addition of PRL increased expression of mFasL. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, in place of PRL, enhanced the apoptotic parameters. Cumulatively, the apoptotic PRL action was addressed to cells unknown than steroidogenic lute~ cells. The most prohable candidate for the direct target cells is Tcells in the luteal tissue that can express mFasL in response to PRL.

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A CLINICOSTATISTICAL ANALYSIS OF ORAL CANCER PATIENTS FOR RECENT 8 YEARS (최근 8년간 구강암 환자에 대한 임상통계학적 연구)

  • Kim, Myoung-Yun;Kim, Chin-Soo;Lee, Sang-Han;Kim, Jin-Wook;Jang, Hyun-Jung
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.660-668
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    • 2007
  • We investigated 248 patients who were diagnosed as malignant tumor in the department of Oral and maxillofacial Surgery of Kyungpook National University from 1999 to 2006, and following results were obtained. 1. Among 248 patients who have malignant tumor, 164 were men and 84 were women, which made the ratio of male to female 1.95:1. 2. The average age of oral cancer patients was 58.3. 3. As of the primary origin site, lower alveolus and gingiva were the greatest with 70 cases(28.2%), followed by tongue(l6.9%), upper alveolus and gingiva(14.9%), palate(13.7%), mouth floor(9.7%), buccal mucosa(4.8%), retromolar trigone(4.4%), Mx. & Mn. bone(3.2%) and lip(2.8%). 4. As of histologic distribution, squamous cell carcinoma was the greatest with 170 cases(68.6%), followed by sarcoma with 17 cases(6.9%), adenoid cystic carcinoma with 17 cases(6.9%), malignant lymphoma with 15 cases(6.0%), mucoepidermoid carcinoma with 13 cases(5.2%), metastatic carcinoma with 6 cases(2.4%) and malignant melanoma with 4 cases(1.6%). 5. Period between recognition of the symptom and the first visit to hospital was less than 3 months for 58.9% of the patients, and more than 3 months for 41% of the patients. 6. Investigation of whether the patients drink or smoke revealed that the number of non-smoking and non-drinking patients was 63 among 170 patients(37.0%) that were able to investigate. The number of patients who smoke only was 29(17.1%) and both drinking and smoking patients were 78(45.9%). 7. In clinical stage order, Stage IV(61.7%) was found th be the largest, followed by stage I(17.2%), stage II(13%) and stage III(7.8%). 8. The 5-year survival rate of the entire oral cancer patients appeared to be 57.7%. The survival rate was higher in younger group and women had higher survival rate but there was no statistical significance to this. In the aspect of stage, the survival rate was Stage I, Stage II, Stage IV and Stage III in decreasing order. The order according to T classification was the same. In N classification, patients with N0 had the highest survival rate and the survival rate decreased in the order of N1 and N2. Survival rate was especially low in patients with N2.

MicroRNA-126 Regulates the Expression of Stem Cell Transcription Factors (Sox2 and Lin28) in Various Ovarian Tumors (MicroRNA-126은 난소 종양세포의 줄기세포 전사인자 (Sox2와 Lin28) 발현을 조절한다)

  • Park, Ho;Jekal, Seung Joo
    • Korean Journal of Clinical Laboratory Science
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    • v.47 no.4
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    • pp.298-305
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    • 2015
  • Stem cell-like tumor cells are reported to be the main reason for tumor recurrence and metastasis. As one of the new approaches to overcome cancer, studies are emerging to inhibit the expressions of stem cell transcriptional factors (Oct4, Sox2, Klf-4, and Lin28) in cancer cells. MicroRNAs are master genetic regulators that can control development and differentiation of stem cells. In this study using various ovarian tumors (Skov3, Ovcar3, Tov112D, Tov21G, PA-1 and Hsc832(c)T), we examined the expressions of stem cell-related transcription factors, and the biological changes in cell survival and growth by miR-126 that targets stem cell transcriptional factors. We observed that treatment of miR-126 induced the morphological changes and cell suspension in most cells. In addition, miR-126 induced gradual regression of cell division except Skov3 cells, especially significant time-dependent reduction in Tov112D, Tov21G and PA-1. When we examined the expression of stem cell transcriptional factors, Sox2 was shown to be down-regulated after miR-126. Our results demonstrate that miR-126 treatment can provide the reversible environment to regulate cell division and to induce cell death of ovarian tumors, suggesting the molecular biological clues for clinical usage.

Inhibitory Effect of Lactic Acid Bacteria-fermented Chrysanthemum indicum L. on Adipocyte Differentiation through Hedgehog Signaling (감국의 유산균 발효물이 hedgehog 신호를 통한 지방구세포 분화 억제효과)

  • Choi, Jae Young;Lim, Jong Seok;Sim, Bo Ram;Yang, Yung Hun
    • Journal of Life Science
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    • v.30 no.6
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    • pp.532-541
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    • 2020
  • In this study, we describe the inhibition of adipocyte differentiation by the lactic acid bacteria (LAB) fermentation product of Chrysanthemum indicum L. (CI) extract to control obesity. Preparation of LAB-fermented products was performed to overcome the cytotoxicity of CI extract. During fermentation and 3T3-L1 cell line experiment, cytotoxicity was not induced in the CI fermentation products over 1 day in culture. Fermented materials from highly proliferative cultures were selected for treatment of 3T3-L1 cells and for comparison with unfermented control groups. Cell survival and undifferentiated cell populations were decreased differentiation population in all experimental groups compared with controls, as measured using fluorescence-activated cell sorting analysis. Akt pathway activity increased upon treatment with these fermented extracts in 3T3-L1 cells. Gli2 depleted at the protein level in association with adipocyte differentiation. LAB KCTC 3115- and 3109-fermented extract treatment caused controlled Gli2 protein accumulation. Moreover, KCTC 3115 and 3109 were found to reduce C/EBPα and FAS was depleted, whereas pACC was increased at the protein level upon treatment with the fermentation products of each of the four LAB used in this study. With Lactococcus lactis subsp. lactis KCTC 3115 fermentation, the regulation of adipose differentiation and hedgehog signaling were also suppressed, thereby inhibiting the differentiation of progenitor cells. The basis for the activation of hedgehog signaling may provide insights into the treatment of obesity and the inhibition of adipocyte differentiation.

The research on antioxidative effect of Sasa quelpaertensis extractum and assessment of cytotoxicity (제주조릿대 잎 추출물의 항산화효능 및 세포독성 평가에 관한 연구)

  • Lee, Song Hee;Lee, Moo Sung
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.3
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    • pp.687-693
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    • 2017
  • This research analyzed cell survival rate according to antioxidative effect and cytotoxicity using Sasa quelpaertensis and Ethanol extracts. Sasa quelpaertensis used extracts of $95^{\circ}C$ boiled-water extract and 70% ethanol liquid each. For total polyphenol content, tannin content, and flavonoid content, polyphenol content of $95^{\circ}C$ boiled-water extract was 26.6 mg/g while that of 70% ethanol extract liquid was 22.3 mg/g, which means polyphenol content was higher in $95^{\circ}C$ boiled-water extract. Tannin content was 72.1 mg/g in $95^{\circ}C$ boiled-water extract which was higher than 61.2 mg/g in 70% ethanol extract liquid. Total flavonoid content was higher in 70% ethanol extract liquid (25.4 mg/g) than in $95^{\circ}C$ boiled-water extract (17.8 mg/g). Further, the researcher measured DPPH radical elimination and ABTS radical elimination. As a result, as the concentration of each extract increased, DPPH radical elimination and ABTS radical elimination increased. In the DPPH radical elimination, L-ascorbic acid was eliminated at 500 ppm and showed no change even though the concentration increased, whereas it increased in BHT and Sasa quelpaertensis leaf extracts according to concentration. ABTS radical elimination indicated the similar phenomenon, whereas BHT showed maximum elimination at 500 ppm and decreased gradually as the concentration increased. On the other hand, it gradually increased in Sasa quelpaertensis leaf extract and showed 90% elimination at 10,000 pm, and it increased in $95^{\circ}C$ boiled-water extract. Using human skin fibroblasts (3T3) to check the cell survival rate of Sasa quelpaertensis leaves showed that cell survival rate decreased between 85.6 and 66.6% in $95^{\circ}C$ boiled-water extract. The cell survival rate was between 95.4 and 92.1% when using 70% ethanol extracts. Sasa quelpaertensis has efficacy as a natural antioxidant as well as a material hyangjang.

Poor Prognostic Factors in Surgically Resected Stage I Non-small Cell Lung Cancer: Histopathologic and Immunohistochemical Analysis

  • Cho, Suk-Ki;Park, Tae-In;Lee, Eung-Bae;Son, Shin-Ah
    • Journal of Chest Surgery
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    • v.45 no.2
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    • pp.101-109
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    • 2012
  • Background: A better understanding of the histopathology and molecular biology of lung cancer might improve our capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I non-small cell lung cancer. Materials and Methods: One hundred ten patients at the Kyungpook National University Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. Results: Univariate analysis showed that the T stage, differentiation, visceral pleural invasion, and survivin expression were significantly associated with recurrence. Multivariate analysis demonstrated that differentiation and survivin overexpression emerged as independent prognostic factors of recurrence. Conclusion: In resected stage I non-small cell lung cancer, poor differentiation and survivin overexpression have been identified as independent predictors of poor disease-free survival.

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

  • Alexandra A. Wolfarth;Swati Dhar;Jack B. Goon;Ugonna I. Ezeanya;Sara Ferrando-Martínez;Byung Ha Lee
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.5.1-5.22
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    • 2022
  • The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

CNS Relapsed T-cell Lymphoma in a Young Cat (어린 고양이에서 발생한 중추신경계로 재발한 T세포 림프종)

  • Seo, Kyoung-Won;Oh, Ye-In;Han, Sei-Myoung;Go, Du-Min;Lee, Jeong-Ha;Youn, Hwa-Young
    • Journal of Veterinary Clinics
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    • v.31 no.3
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    • pp.226-232
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    • 2014
  • An 8-month-old domestic shorthair cat presented with decreased activity and anorexia. Diagnostic imaging revealed cranial mediastinal mass and enlarged mesenteric lymph nodes. Fine needle aspirates showed a marked increase in malignant lymphocytes. Multicentric lymphoma (stage V-b) was diagnosed. The cat treated with COP protocol chemotherapy, and complete remission was induced. CNS relapse developed 314 days after the initiation of chemotherapy. Treatment with rescue protocol greatly reduced the clinical signs for a short period. The cat was in partial remission for 33 days and overall survival time was 383 days. Multicentric T-cell lymphoma with brain involvement was confirmed after necropsy by histopathology and immunohistochemistry.

Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis

  • Wu, Lu;Liu, Yan-Yang;Li, Zhi-Xi;Zhao, Qian;Wang, Xia;Yu, Yang;Wang, Yu-Yi;Wang, Yi-Qin;Luo, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.489-494
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    • 2014
  • Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.

Antitumor and Immunomodulatory Effects of Dangguihwalhyultang on Murine Melanoma-induced Lung Metastasis (당귀활혈탕(當歸活血湯)의 폐전이억제(肺轉移抑制) 및 면역조절작용(免疫調節作用)에 의한 항암효과(抗癌效果))

  • Ko, Eun-Tae;Ha, Jee-Yong;Lee, Seon-Goo;You, Byeong-Gil
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.6 no.1
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    • pp.29-45
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    • 2000
  • In order to investigate the antitumor effect by Dangguihwalhyultang after B-l6 cells were transplanted in C57BL/6 mice, and the immune responses in mice induced by methotrexate, the extract of Dangguihwalhyultang was orally administered to the ICR mice. Experimental studies were performed for measurance of metastasis, cell cytotoxicity in vitro, life extention, weight of cancer, natural killer cell activity. productivity of interleukin-2. The results were summarized as follows: 1. Mean survival time in Dangguihwalhyultang-treated group was prolonged, as compared with control group(14.63%) significantly(P<0.05). 2. Inhibition of metastasis in Dangguihwalhyultang-treated group was higher than control group with significance on 14th day(P<0.05). 3. On the weight of solid tumor. Dangguihwalhyultang-treated group was less than control group with significance(P<0.05). 4. On the MTT assay. Dangguihwalhyultang concentration inhibited cell viability was $368.8{\mu}g/well$. 5. Natural killer cell activity in Dangguihwalhyultang-treated group was significantly increased on 100:1, 50:1 E/T(effect cell/target cell) ratio(P<0.05). 6. Production of interleukin-2 in Dangguihwalhyultang-treated group was significantly increased(P<0.05).

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