• Title/Summary/Keyword: biological response modifier (BRM)

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Isolation of Bacteria Producing a B-Cell-Specific Biological Response Modifier Found in Korean Fermented Soybean Paste

  • CHUNG KUN SUB;KIM JOO YOUNG;HONG SUNG WOOK;LEE BONG KI
    • Journal of Microbiology and Biotechnology
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    • v.16 no.1
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    • pp.126-135
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    • 2006
  • In a previous study, a biological response modifier (BRM) specifically enhancing the function of B-cells was isolated from Korean fermented soybean paste (Kfsp), but not from non-fermented soybeans. In this study, we attempted to isolate the bacteria producing the BRM from Kfsp (KfspBRM) by ELISA using anti-KfspBRM and by B-cell proliferation. Five bacteria whose culture supernatants showed the BRM activities were isolated, and one of them was identified as Bacillus licheniformis E1. The bacterial BRM (bBRM) originated from a slime layer of B. licheniformis El had a molecular weight of 1,594 kDa, and contained $33\%\;(w/w)$ of reduced sugar and $4.6\%\;(w/w)$ of protein content. The bBRM appeared to be a glycoprotein that is physically, structurally, and functionally similar to the KfspBRM, suggesting that the isolates including B. licheniformis El may produce the KfspBRM in the fermentation process of soybean paste. The mass production of the BRM by the bacterium may help to study B-cells in immunology, and the enrichment of the BRM in Kfsp may help patients in future who are medically in need of potentiation of B-cell proliferation and antibody production.

The Bacterial Biological Response Modifier Enriched Chungkookjang Fermentation (면역증강물질 강화 청국장 발효)

  • Hong, Sung-Wook;Kim, Joo-Young;Lee, Bong-Ki;Chung, Kun-Sub
    • Korean Journal of Food Science and Technology
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    • v.38 no.4
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    • pp.548-553
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    • 2006
  • The aim of this study was to produce Chungkookjang-a food produced through fermentation with Bacillus licheniformis E1-that contains an increased concentration of a bacterial biological response modifier (B-BRM). Unfortunately, sensory studies have indicated that B. licheniformis E1-fermented Chungkookjang is unacceptable for commercial use. We isolated another bacterial strain from this food product: B. subtilis S2. The optimum time and temperature for Chungkookjang fermentation with B. licheniformis E1 and B. subtilis S2 were 48 hr and $40^{\circ}C$, respectively. Sensory studies showed that Chungkookjang fermented by both B. licheniformis E1 and B. subtilis S2 was more acceptable than B. licheniformis E1 only. The amino nitrogen and crude protein content of the product were 359 mg% and 45.6% respectively. Additionally, it was confirmed that the proliferation of mouse splenic lymphocytes increased significantly, when the cells were treated with the BRM from Chungkookjang fermented using the mixture of bacterial strains in vitro. These results suggest that the enriched Chungkookjang may help patients who are medically in need of potentiation of lymphocytes proliferation.

Screening of Antineoplastic Immunomodulator from Herbal Medicines (천연물로부터 항암면역증강물질 탐색연구)

  • Song, Jie-Young;Yang, Hyun-Ok;Pyo, Suhk-Neung;Park, Sin-Young;Kim, Ki-Hwan;Son, Eun-Hwa;Kang, Nam-Sung;Yun, Yeon-Sook
    • YAKHAK HOEJI
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    • v.42 no.2
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    • pp.132-139
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    • 1998
  • Currently, cancer is the primary cause of death and 50% of cancer patients are incurable by surgery, radiotherapy and chemotherapy. Therefore, immunotherpy is interested as the fourth remedy. Biological response modifier (BRM), such as organometallic compounds, glycoproteins, polysaccharides and other natural products. Is the one which can enhance the immune response against cancer cell. To develop new BRM from natural sources, we investigated 63 species Korean traditional medicines by observing the mitogenic activity to splenocytes, generation of activated killer cells and activation of macrophages. Finally, we selected 9 species including Angelicae gigantis Radix, Mori Cortex Radicis, Arisaematis Tuber, Salviae Radix, Cnidii Rhizoma, Ligusti Fructus, Pasoraliae Semen, Loranthi Ramulus, Ginseng Radix. Bioassay-guided fractionation and purification is undergoing.

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Efficacy of Oral Administration of Lentinula eododes Mycelia Extract for Breast Cancer Patients Undergoing Postoperative Hormone Therapy

  • Suzuki, Nobutaka;Takimoto, Yuko;Suzuki, Riho;Arai, Takanari;Uebaba, Kazuo;Nakai, Masuo;Strong, Jeffry Michael;Tokuda, Harukuni
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3469-3472
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    • 2013
  • Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

Augmentation of antitumor activity of antitumor drugs in combination with Lactobacillus casei HY2782 (항암제와 Lactobacillus casei HY2782의 병용투여에 의한 항암효과의 증강)

  • Yoon, Sang-Kun;Bae, Hyoung-Suk;Kim, Gyung-Tae;Baek, Young-Jin
    • Microbiology and Biotechnology Letters
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    • v.24 no.1
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    • pp.37-43
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    • 1996
  • Augmentation of antitumor activity of antitumor drugs in combination with Lactobacillus casei HY2782 (LC2782) was studied against Sarcoma-180 (S-180) and Lewis lung carcinoma (3LL). Antitumor drugs used in this study were 5-fluorouracil (5-fu) and cyclophosphamide (CP). The prolongation effect of LC2872 on the life span of mouse intraperitoneally implanted with S-180 was stronger than that of OK-432 and BCG, while the inhibitory effect of OK-432 and BCG on the growth of 3LL solid tumor was a little stronger than that of LC2782. Average survival rates of mice administrated LC2782, OK-432 and BCG were 192%, 141%, and 112%, respectively, when that of the control was 100%, Intralesional administration of 5-Fu, CP, 5-Fu+LC2782 and CP+LC2782 resulted in 93%, 69%, 99% and 73% inhibition rates against 3LL solid tumor proliferation. The combination therapy of 5-Fu or CP with LC2782 significantly prolonged the life span of S-180-inoculated ICR mice. Average survival rates of mice administrated 5-Fu and CP alone were 115% and 99%. Furthermore, survival rates of mice administrated 5-Fu and CP in combination with LC2782 were 226% and 244%, respectively.

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Effect of Neuronal Differentiation Activity of Hot Water Extracts of Marine Alga, Chlorella capsulata (해수 미세조류인 Chlorella capsulata의 열 수 추출물의 신경세포 분화촉진에 관한 연구)

  • 이현용;이현수;이서호;김대호;박진홍
    • Microbiology and Biotechnology Letters
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    • v.31 no.2
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    • pp.165-170
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    • 2003
  • Hot water extracts of Chlorella capsulata(CCE) is a biological response modifier (BRM) which exhibits neuronal differentiation activity. The effect of CCE on the growth of nerve cells, PC12 was observed as follows: The viable cell density in adding CCE was increased up to 2.5 times, compare to that in no addition. The neurite of the cells was also lengthened up to 40 $\mu\textrm{m}$ longer than 5 $\mu\textrm{m}$ in no addition. The number of neurite-bearing cells were about four times higher than that in no addition.

Immunomodulatory Effects of Fructus and Semen from Rosa rugosa on Macrophages (해당화의 과육 및 종자추출물의 대식세포 면역조절작용)

  • Kang, Nam-Sung;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.23 no.5
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    • pp.399-405
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    • 2010
  • Rosa rugosa has been used as a folk medicine with various pharmacological properties for a long time in Asia. Recently, it has been reported that the extract of fractions from different parts of Rosa rugosa have various pharmacological effects on diverse diseases including diabetes, inflammatory diseases and tumor. We investigated effects of fructus extracts of Rosa rugosa(RRF) and semen extracts of this herb(RRS) on macrophage to evaluate the possibilities as a biological response modifier. We showed increased effects on tumoricidal activity, phagocytic activity, TNF-$\alpha$ and NO production in RRF-treated groups without direct tumor cell cytotoxicity. RRS-treated groups increased direct tumor cell cytotoxicity at high dose without tumoricial activity except increasing of TNF-$\alpha$ release. These results provide further possibilities for the beneficial immunomodulating effects of RRF on immune system with relatively larger safety margin rather than RRS.

Compilation of 104 Experimental Theses on the Antitumor and Immuno-activating therapies of Oriental Medicine (한의학의 항종양 면역치료에 관한 연구 -1990년 이후 발표된 실험논문을 중심으로-)

  • Kang Yeon Yee;Kim Tai Im;Park Jong Ho;Kim Sung Hoon;Park Jong Dai;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.1-24
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    • 2003
  • This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

In Vivo Immunological Activity in Fermentation with Black Rice Bran (유색미 미강발효물의 면역활성 효과)

  • Kim, Dong-Ju;Ryu, Su-Noh;Han, Sang-Jun;Kim, Hwa-Young;Kim, Jung-Hak;Hong, Seong-Gil
    • The Korean Journal of Food And Nutrition
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    • v.24 no.3
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    • pp.273-281
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    • 2011
  • Rice bran is byproducts of the hulling of rice, an important food resource in Korea. Various studies have been reported immune-enhancing effects of rice bran cultured with Lentinus edodes. In particular black rice bran contains anthocyanin, and the effects of antioxidant have been reported. The objective of the this study was to investigate the possible immune-enhancing effects of black rice bran substance extracted from a submerged culture of Lentinus edodes with black rice bran (crude fermentation-polysaccharide, CFP) and products(crude fermentation-polysaccharide-S. cerevisiae CFP-S, crude fermentation-polysaccharide-L. gasseri, CFP-L) which are of secondary fermentation of by using Saccharomyces cerevisiae and Lactobacillus gasseri in the Blab/c male mice. We found that supplementation of CFP, CFP-S and CFP-L enhanced macrophage and splenocyte proliferation compared to the control group(NC) in mice. Also, we measured the concentration of cytokines(IFN-${\gamma}$, TNF-${\alpha}$, IL-6) secreted by activated macrophage and splenocyte. The results of the experiment are that supplementation of CFP and CFP-S increased the macrophage and splenocyte proliferation compared to the control group but supplementation of CFP-L decreased the splenoyte proliferation compared to the control group(without mitogen and treated with LPS). When macrophage and splenocyte were stimulated by CFP and CFP-S supplementation, it was increased IFN-${\gamma}$, TNF-${\alpha}$ and IL-6 concentration compared with the control group. These results suggest that the capacity of CFP and CFP-S seem to act as a potent immune modulator causing augmentation of immune cell activity, and enhance the immue function through regulating cytokine production capacity by activated macrophage and splenocyte in mice.