Journal of the Mass Spectrometry Society of Japan
Online ISSN : 1880-4225
Print ISSN : 1340-8097
ISSN-L : 1340-8097
54 巻, 3 号
選択された号の論文の7件中1~7を表示しています
総説
  • —癌免疫療法の具現化に向けて—
    佐藤 昇志
    2006 年 54 巻 3 号 p. 75-80
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    We have studied human tumor antigens applicable for a wide variety of tumors, and determined immunogenic peptide epitopes from these tumor antigen molecules presented particularly by HLA-A24. Our study indicated that peptides (survivin 2B) derived from survivin, an inhibitor of apoptosis proteins (IAP), are immunogenic in more than 50% of cancer patients with a wide variety of tumors. These vaccine candidates are now under clinical trials, and with careful immunological monitoring, we would be able to know finally if these vaccines can work clinically. To establish a potent clinical protocol, the immunological tumor escape mechanism should be more drastically examined in human materials. We have recently succeeded in establishing anti-HLA-A, B, and C alleles-specific monoclonal antibody EMR8-5 which can be used in routine paraffin-embedded sections. Unexpectedly enough, our data indicated that high percentage of human cancers lost HLA-class I molecules in primary cancer tissues. Particularly, more than 80% of breast and prostate cancers lost HLA-class I. Metastatic breast cancers indicated almost complete loss of HLA-class I. I will discuss possibilities for resolution of this old but yet new important problem. Meanwhile, recent evidences have been accumulating for an important role of the heat shock proteins (HSPs) as so called danger signals in initiating innate immunity as well as acquired immunity. The precise immunological basis for this phenomenon remains to be elucidated. T-cell immunity could be achieved after vaccination with tumor cells with MHC mismatching, which could not present antigen to T cells directly. This phenomenon is known as cross priming, and it may be mediated by Hsp-peptide complexes which are released from tumor cells. We show that exogenous Hsp90-peptide complexes can gain access to MHC class I presentation pathway and cause cross priming by bone marrow derived dendritic cells. Interestingly, this presentation is TAP-independent and follows endocytic pathways. We also show Hsp90-peptide complexes as a potential tumor vaccine by using HLA-A24 transgenic mouse model.
解説
  • —ガスクロマトグラフィー—
    小村 啓, 家田 曜世, 落合 伸夫, 中原 一晃, 馬野 克己
    2006 年 54 巻 3 号 p. 81-90
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Gas chromatography (GC) is one of the most efficient analytical methods for volatile mixtures. GC can offer suitable combinations to meet analytical needs by choosing proper injection systems, columns, and detectors from the items available. In addition to traditional single-dimensional GC, two-dimensional GC systems are also commercially available. By connecting quadrupole mass spectrometer or time-of-flight mass spectrometer to a recently developed GC system, comprehensive two-dimensional gas chromatograph (GC×GC), identification of four photoreaction products of citral was achieved. Applications using traditional two-dimensional GC are also described.
  • 堀江 正一, 竹上 晴美
    2006 年 54 巻 3 号 p. 91-96
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    In recent years, there has been a steadily growing demand in Japan for variety of livestock products as the eating habits of the Japanese become more Westernized. This has brought about great changes in the methods of raising livestock in Japan and elsewhere, notably with larger numbers of animals being raised together within limited space. In spite of the increased demand for meat and fowl, the Japanese, who populate an island archipelago, still prize seafood as a main source protein. The internationally implemented limitations on fishing, necessary for conservation, have created a need for farm-raised seafood to supplement catches. This relatively new industry is becoming more prosperous year by year. Various veterinary drugs, such as antibiotics and synthetic antibacterials, are widely used in the rearing of food-producing animals to prevent and treat infectious diseases and to promote their growth. Although these drugs have been a boon to the aquiculture industry, there are some problems in using them in the same way that the use of certain pesticides in agriculture has been paradoxically both benefical and detrimental to human and animal welfare. Residues of antibiotics and synthetic antibacterials are found in the edible tissues and resistant bacterial strain have appeared. According to the Japanese Food Sanitation Law, no food should contain antibiotics and, in addition, meat, poultry eggs, fish, and shellfish should not contain synthetic antibacterials. In order to monitor the drug residues levels in livestock products, simple and reliable method are required. For the analysis of residual veterinary drugs in food, many assay techniques have been developed such as HPLC and LC/MS. Legal regulation and LC/MS analysis of these chemicals are outlined in this paper.
  • 上口 権二郎, 鳥越 俊彦, 山本 雅明, 佐藤 昇志
    2006 年 54 巻 3 号 p. 97-102
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Several mechanisms have been described by which malignant cells escape from the immune system and/or chemotherapy. Recently we isolated TUCAN-54 gene that is over-expressed in a wide variety of epithelial cancers but not in normal counterparts. TUCAN-54 inhibited both death receptor-mediated and mitochondria/cytochrome C-mediated apoptosis. Moreover, down-regulation of TUCAN-54 in colon cancer cells by siRNA treatment could increase the sensitivity of the cells to an anti-cancer drug. Finally, we revealed that Fas-associated death domain protein (FADD) was physically associated with TUCAN-54, but not with TUCAN-48. Thus, TUCAN-54 might be a novel tumor-specific anti-apoptotic molecule, which might aggravate malignant potential of cancer cells, such as immunoresistance and chemoresistance.
  • —安定同位体と質量分析を用いた方法—
    三浦 真
    2006 年 54 巻 3 号 p. 103-108
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    Amino acids are constituents of protein that is the major functional and structural component of all the cells of the body, and are required for health and reproduction. In the nutritional classification, the amino acids are categorized into two groups, essential (indispensable) and non-essential (dispensable). The essential amino acids (L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine) have carbon skeletons that cannot be synthesized from simpler molecules in animals, and therefore must be provided in the diet. The earlier methodologies for determining amino acid requirements, which was based on nitrogen balance, were criticized because of their experimental design, but now essential amino acid requirements for adult humans are estimated by isotopic tracer methods and linear regression analysis. This article reviews recent advances in studies on amino acid requirements estimated by using the 13C-labeled amino acid oxidation method, isotope ratio mass spectrometry (IRMS) for the measurement of 13CO2-12CO2 ratio in expired breath CO2 and gas chromatography-mass spectrometry (GC/MS) for the measurement of isotopic enrichment of the precursor in 13CO2 production.
技術報告
  • 東山 喜三彦, 土屋 耕一, 原村 昌幸, 田中 明人
    2006 年 54 巻 3 号 p. 109-116
    発行日: 2006年
    公開日: 2006/06/01
    ジャーナル フリー
    There are now thousands of known bioactive compounds in vivo. However, we thought that most of their target proteins, immediately bound to the compounds and perturbation of their activities by other methods also exhibited similar bio-activity in vivo, are still unclear. Therefore we now focus on our effort for identification of specific binding proteins to known bioactive compounds such as drugs using affinity resins bearing them because we believed that some of them could be new drug targets. Sensitive analysis of specific binding proteins in SDS-PAGE gel and reliability of LC-MS/MS system were vital for performing our project. We here show 1) development of a cutting-apparatus for preparation of pieces of acrylamide-gel including specific binding protein, 2) optimization of pre-treatment system for effective reduction of carry-over samples in a stacking-column in LC-MS/MS system, and 3) optimization of experimental condition of in-gel digestion without calcium ion, from our efforts to optimize our system for sensitive identification of proteins using a LC-MS/MS system.
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