• Title, Summary, Keyword: tumor cells

Search Result 4,737, Processing Time 0.047 seconds

Impact of IL-2 and IL-2R SNPs on Proliferation and Tumor-killing Activity of Lymphokine-Activated Killer Cells from Healthy Chinese Blood Donors

  • Li, Yan;Meng, Fan-Dong;Tian, Xin;Sui, Cheng-Guang;Liu, Yun-Peng;Jiang, You-Hong
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.18
    • /
    • pp.7965-7970
    • /
    • 2014
  • One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

Influence of Bujeonghangamtang Extract against Chemically Induced Tumor and Xenografted Mice Tumor and Its Immunological Response (부정항암탕(扶正抗癌湯)이 항종양(抗腫瘍) 면역반응(免疫反應)에 미치는 영향(影響))

  • Im, Mi-Ryang;Jeon, Byeong-Hun;Won, Jin-Hui;Mun, Gu;Mun, Seok-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
    • /
    • v.3 no.1
    • /
    • pp.67-84
    • /
    • 1997
  • Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene. (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeonghangamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells activities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

  • PDF

Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma

  • Kim, Han-Seok;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • v.36 no.3
    • /
    • pp.85-93
    • /
    • 2014
  • Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

IL-12 Production and Subsequent Natural Killer Cell Activation by Necrotic Tumor Cell-loaded Dendritic Cells in Therapeutic Vaccinations

  • Kim, Aeyung;Kim, Kwang Dong;Choi, Seung-Chul;Jeong, Moon-Jin;Lee, Hee Gu;Choe, Yong-Kyung;Paik, Sang-Gi;Lim, Jong-Seok
    • IMMUNE NETWORK
    • /
    • v.3 no.3
    • /
    • pp.188-200
    • /
    • 2003
  • Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.

Antitumor Responses of Adoptively-Transferred Tumor-Specific T-Cell Cultures in a Murine Lymphoma Model

  • Kim, Hee-Sue;Lee, Hee-Gu;Lim, Jong-Seok;Lee, Ki-Young;Kim, Jae-Wha;Chung, Kyeong-Soo;Choe, Yong-Kyung;Choe, In-Seong;Chung, Tai-Wha;Kim, Kil-Hyoun
    • BMB Reports
    • /
    • v.28 no.6
    • /
    • pp.556-561
    • /
    • 1995
  • The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

  • PDF

Inhibition of Tumor Invasion and Metastasis by Calcium Spirulan(Ca-SP), a Novel Sulfated Polysaccharide Derived from a Blue-Green Alga Spirulina Platensis

  • Saiki, Ikuo;Murata, Jun;Fujii, Hideki;Kato, Toshimitsu
    • Nutritional Sciences
    • /
    • v.7 no.3
    • /
    • pp.144-150
    • /
    • 2004
  • We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

Cryptotanshinone Induces Inhibition of Breast Tumor Growth by Cytotoxic CD4+ T Cells through the JAK2/STAT4/ Perforin Pathway

  • Zhou, Jun;Xu, Xiao-Zhen;Hu, Yao-Ren;Hu, Ai-Rong;Zhu, Cheng-Liang;Gao, Guo-Sheng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.6
    • /
    • pp.2439-2445
    • /
    • 2014
  • Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

Growth Suppression Effect of Traditional Fermented Soybean Paste(Doenjang) on the Various Tumor Cells (순창 재래식 된장의 암세포 성장억제 효과)

  • 최신양;최미정;이정진;김현정;홍석산;정건섭;이봉기
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.28 no.2
    • /
    • pp.458-463
    • /
    • 1999
  • Methanol extract and its fraction of traditional fermented soybean paste(doenjang) from Soonchang area were studied for growth suppression on the various tumor cells and suppression components, by using HPLC and GC were analysed. Hexane fraction of methanol extract was indicated 79%, 76%, 67%, 66%, 78% of growth suppression on L1210, P338D1, HepG2, WiDr and SNU 1 tumor cells, respectively. Ethylacetate fraction of methanol extract also showed 81%, 75%, 75%, 76% and 82% of growth suppression on the same tumor cells, respectively. Peak 8 obtained from HPLC of ethylacetate fraction indicated 81%, 77%, 77%, 75% and 79% of growth suppression on the same tumor cells and identified as a genistein, by comparing with standard one by HPLC analysis. Hexane fraction of methanol extract contained oleic acid, linoleic acid and palmitic acid.

  • PDF

Imprint Cytology of a Desmoplastic Small Round Cell Tumor -A Case Report- (결합조직형성소원형세포종양의 압착도말 세포학적 소견 -1예 보고-)

  • Kim, Yong-Jin;Kim, Jae-Hwang;Choi, Joon-Hyuk
    • The Korean Journal of Cytopathology
    • /
    • v.18 no.1
    • /
    • pp.81-86
    • /
    • 2007
  • Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm. It mainly involves the abdominal or pelvic peritoneum of male adolescents. We report here the imprint cytologic features of a case of DSRCT occurring in the intraabdominal cavity of a 21-year-old man. A microscopic examination showed moderate cellularity. The tumor cells were singly arranged and arranged in clusters. The cells had round to oval nuclei with finely granular chromatin, inconspicuous nucleoli and scanty cytoplasm. Some tumor cells showed nuclear molding, and some cells had an epitheloid appearance with a large amount of lightly eosinophilic cytoplasm. A rosette-like pattern was present. Spindle-shaped, fibroblastic stromal cells were occasionally found. The tumor cells were immunoreactive for the markers cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), desmin, vimentin and neuron specific enolase (NSE).

Ultrastructures of Canine Transmissible Venereal Turner Cells at Stages of Maturation and Regression (개 전이성 생식후 종양 세포의 성숙기 및 퇴축기에 따른 미세구조)

  • Park, Nam-Yong;Rhee, Young-Hwan
    • Applied Microscopy
    • /
    • v.17 no.1
    • /
    • pp.169-176
    • /
    • 1987
  • Naturally occurring canine transmissible venereal tumors of genital organs in mature and regressive stages from 6 dogs were examined by transmission electron microscope. The tumor cells at the stage of maturation were comprised of large round and ovoid cells with prominent nuclei and nucleoli, a few spindle-shaped cells, and irregularly shaped cells. The mature round cells were characterized by the presence of a central ovoid to irregularly round nucleus with a large eccentric nucleolus, vesicular endoplasmic reticulum, round to oval swollen mitochondria with few cristae, Golgi's apparatus, and plasma membranes with numerous microvilli. As the tumor degenerated, the tumor cells were increased in the number of spindle-shaped, fibroblast-like and irregularly shaped cells, collagen bundles, and mainly lymphocytes, in contrast to those of the stage of maturation. Regressing tumor cells were characterized by the swelling and vacuolation of mitochondria and endoplasmic reticulum, membrane-bound granules, lamellar complex, tubular structures, and dense bundles of collagen. It was suggested that transformation might occur in the course of tumor growth causing morphological change from the round to the fibroblast-like cells, and that there was the evidence of cell-mediated tumor cell lysis by lymphocyte infiltration.

  • PDF