• Title, Summary, Keyword: B-cell lymphoma T-cell lymphoma

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Effects of Bikiwhan on the Anti-tumor Immune Responses in the Mouse (비기환이 항종양(抗腫瘍) 면역반응(免疫反應)에 미치는 영향(影響))

  • Moon, Byung-Ha;Moon, Goo;Mun, Seok-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.1 no.1
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    • pp.167-190
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    • 1995
  • Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

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Red pepper seed water extract inhibits preadipocyte differentiation and induces mature adipocyte apoptosis in 3T3-L1 cells

  • Kim, Hwa-Jin;You, Mi-Kyoung;Lee, Young-Hyun;Kim, Hyun-Jung;Adhikari, Deepak;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.12 no.6
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    • pp.494-502
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    • 2018
  • BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at $4^{\circ}C$ (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR-{\gamma}$), CCAAT/enhancer-binding proteins ${\alpha}$ (C/EBP ${\alpha}$), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 ($0-75{\mu}g/mL$) or its fractions ($0-50{\mu}g/mL$) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of $PPAR-{\gamma}$, C/EBP ${\alpha}$, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity.

Attenuation of Reperfusion Injury with Angiotension $AT_1$ Receptor Blockade in Rat Myocardial Ischemic Model (백서 심근 허혈 모델에서 angiotension $AT_1$수용체 차단제의 재관류 손상 감소 효과)

  • Choi, Jun-Young;Choi, Dong-Ju;Ahn, Hyuk
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.34 no.3
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    • pp.203-211
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    • 2001
  • 배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

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Characteristics of Cancer Stem Cells and Immune Checkpoint Inhibition (암줄기세포의 특성 및 면역관문억제)

  • Choi, Sang-Hun;Kim, Hyunggee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.499-508
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    • 2019
  • Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

Deoxynivalenol- and zearalenone-contaminated feeds alter gene expression profiles in the livers of piglets

  • Reddy, Kondreddy Eswar;Jeong, Jin young;Lee, Yookyung;Lee, Hyun-Jeong;Kim, Min Seok;Kim, Dong-Wook;Jung, Hyun Jung;Choe, Changyong;Oh, Young Kyoon;Lee, Sung Dae
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.4
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    • pp.595-606
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    • 2018
  • Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

  • Li, Qiong;Yin, Jun;Wang, Xu;Wang, Li-Ming;Shi, Yi-Jun;Zheng, Liang;Tang, Wei-Feng;Ding, Guo-Wen;Liu, Chao;Liu, Rui-Ping;Gu, Hai-Yong;Sun, Jia-Ming;Chen, Suo-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4301-4306
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    • 2013
  • Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.