• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.155-162
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• 1999

This study was performed to assess that clinco-therapeutic effect of natural Italian honeybee (Apis mellifera) venom in adjuvant-induced arthritic rat. Ninety Sprague- Dawley rats of male were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of 1 mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hindpaw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. Experimental groups were divided into three groups. When arthritis was developed in the rat hind-paw, tested groups were administrated with prednisolone (10 mg/kg, p.o) and honeybee venom (one bee, s.c) at an interval of two days. Control group was subcutaneously injected with 0.1 ml of physiological saline solution in the rat at an interval of two days. Clinical findings, hematological values and histopathological findings were observed during or after the drugs administration. In tested groups, the development of inflammatory edema and polyarthritis on day 14 after treatment was suppressed. No significant differences of hindpaw edema volume and lameness score between prednisolone and honeybee venom groups were observed during or after therapeutic drugs treatment. WBC counts of prednisolone and honeybee venom treatment groups as compared with the control group were getting remarkably decreased during or after the therapeutic drugs administration(p＜0.01). Erosions of articular cartilage and inflammatory cell infiltrations during or after the therapeutic drugs treatment was effectively suppressed in natural honey venom.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.510-516
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• 2015

In this review, lipid A, from its discovery to recent findings, is presented as a drug target and therapeutic molecule. First, the biosynthetic pathway for lipid A, the Raetz pathway, serves as a good drug target for antibiotic development. Several assay methods used to screen for inhibitors of lipid A synthesis will be presented, and some of the promising lead compounds will be described. Second, utilization of lipid A biosynthetic pathways by various bacterial species can generate modified lipid A molecules with therapeutic value.

• Journal of Gastric Cancer
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• v.19 no.3
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• pp.235-253
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• 2019

Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.

• Clinical and Experimental Vaccine Research
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• v.11 no.2
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• pp.163-172
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• 2022

Purpose: Epithelial ovarian carcinoma (EOC) is the most lethal of all human gynecologic malignancies. We previously reported that vaccination of female mice with the extracellular domain of anti-Müllerian hormone receptor II (AMHR2-ED) in complete Freund's adjuvant (CFA) generates AMHR2-ED specific immunoglobulin G (IgG) that provides prevention and therapy against murine EOCs. Although CFA is the "gold standard" adjuvant in animal studies, it is not approved for human use because it often induces painful granulomas and abscesses. Thus, the objective of this study is to identify an alternative adjuvant to CFA for use in our ovarian cancer vaccine clinical trials. Materials and Methods: Because it has been used successfully without serious adverse effects in numerous human clinical trials, we selected the IgG-inducing squalene-based adjuvant, AddaVax^TM, for evaluation of its ability to facilitate vaccine-induced prevention and treatment of EOC in mice. To this end, we immunized female C57BL/6 mice with recombinant mouse AMHR2-ED emulsified with either AddaVax or CFA as adjuvant and compared the results. Results: We found that formulation of the AMHR2-ED vaccine with AddaVax adjuvant induced high serum titers of IgG and significant inhibition of EOC growth with significantly enhanced overall survival of mice using both prevention and therapeutic protocols. These results were compared favorably with results obtained using CFA as an adjuvant in the AMHR2-ED vaccine. Conclusion: Our data indicate that the AMHR2-ED vaccine formulated with AddaVax may be used in human clinical trials and thereby serve as a novel and effective way to control human EOC.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Herbal Formula Science
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• v.11 no.2
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• pp.1-18
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• 2003

The Theory for Monarch, Minister, Adjuvant and Dispatcher (or the Theory of Principal, Assistant, Adjuvant and Guiding Korean Oriental Herbal Medicines) has served as a standard principle for newly developed prescription formulas as well as established ones. Despite its significance, however, this theory hasn't been thoroughly studied and covered in the academic journals of Korean Oriental Herbal Medicines (KOHM) yet. This paper inquires into the origin of the theory while presenting the definitions and functions of Principal, Assistant, Adjuvant, and Guiding KOHM. In the end, the recommended doses and number of the KOHM comprising each of Principal, Assistant, Adjuvant, and Guiding KOHM are suggested. The compatibility theory of Principal, Assistant, Adjuvant, and Guiding KOHM can be traced back to the Warring States Period during which it was recorded in the treatise of the various schools of thoughts and their exponents. The theory was firmly established as a full system in ${\ulcorner}Shinnong's\;Pharmacopoeia{\lrcorner}\;and\;{\ulcorner}Yellow\;Emperor's\;Cannon\;of\;Internal\;Medicine{\lrcorner}$. While ${\ulcorner}Shinnong's\;Pharmacopoeia{\lrcorner}$ focuses on the classification of the properties of KOHM, ${\ulcorner}Yellow\;Emperor's\;Cannon\;of\;Internal\;Medicine{\lrcorner}$ mainly deals with the principles for writing prescriptions. In this regard, it is ${\ulcorner}Yellow\;Emperor's\;Cannon\;of\;Internal\;Medicine{\lrcorner}$ that systemized the Theory of Principal, Assistant, Adjuvant, and Guiding KOHM in a real sense. Principal KOHM aims at the causes of diseases and treat main symptoms. The doses are greater than Assistant, Adjuvant and Guiding KOHM. With their comprehensive effects, Principal KOHM is a leading ingredient of any prescription formula. Assistant KOHM are similar to Principal KOHM in its natures and flavors. Although its natures, flavors as well as efficacies may slightly differ from those of Principal KOHM, Assistant KOHM strengthens the therapeutic effects, jointly working with Principal KOHM. They mainly treat accompanying diseases and symptoms. Adjuvant KOHM is divided into two types: facilitator and inhibitor. Facilitators with the similar properties to those of Principal and Assistant KOHM help strengthen the therapeutic effects. Since they usually treat accompanying symptoms or secondary accompanying symptoms (minor accompanying symptoms), there are two kinds of facilitators. (1) The first kind of facilitators assists Principal KOHM, targeting accompanying symptoms. (2) The second ones supporting Assistant KOHM are for accompanying or secondary accompanying symptoms (or minor accompanying symptoms). Inhibitors counteract and thereby complement Principal and Assistant KOHM. Some of them inhibit the side effects or toxicity of Principal KOHM for the sake of the safety of the whole prescription formula while the others generate induced interactions. Guiding KOHM can be used for two purposes: guiding and mediating. The Guiding KOHM for the former purpose leads the other KOHM in a prescription formula to the lesion. But, the Guiding KOHM for mediating coodinate and harmonize all the ingredients in a prescription formula. The number of KOHM for those Principal, Assistant, Adjuvant and Guiding KOHM and their doses are different, depending on the types of prescriptions: classical prescriptions, prescriptions after ${\ulcorner}$Treatise of Cold-Induced Diseases${\lrcorner}$ and prescriptions of Sasang Constitutions Medicines. In the case of the prescriptions after ${\ulcorner}$Treatise of Cold-Induced Diseases${\lrcorner}$, it is highly recommended to follow the view of ${\ulcorner}$Thesaurus of Korean Oriental Medicine Doctors in Chosun Dynasty${\lrcorner}$ for the number of KOHM to be used. For the doses, however, ${\ulcorner}$Elementary Course for Medicine${\lrcorner}$, is found to be more accurate. The most appropriate number of KOHM per prescription is 11-13. To be more specific, for one prescription formula, it is recommended to administer one kind of KOHM for Principal KOHM, 2-3 for Assistant KOHM, 3-4 for Adjuvant KOHM and 5 for Guiding KOHM. As for the proportion of the doses, when 10 units are to be administered for Principal KOHM in a formula, the doses for the other three should be 7-8 units for Assistant KOHM, 5-6 for Adjuvant KOHM and 3-4 for Guiding KOHM. The doses of the KOHM added to or taken out of the prescription correspond to those of Adjuvant and Guiding KOHM.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.127-137
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• 2012

Objectives : The purpose of this study is to investigate the effect of $Clematidis$ radix herbal-acupuncture solution, on collagen, adjuvant, lipopolysaccharide and phospholipase A2 induced rheumatoid arthritis in mice. Methods : Arthritis index was measured for mouse that was injected subcutaneously in solution mixed chicken type II collagen with Freund's complete adjuvant. We injected Freund's complete adjuvant into right posterior part of the sole of a ICR mouse foot, which was measured by plethysmometer. The solution mixed $CRHS$ with Tris-HCI, $CaCl_2$, substrate, enzyme was done a chemical action for thirty minutes, and then inhibitory activity of PLA2 enzyme was expressed with inhibition percentage by utilizing isolated arachidonic acid. COX-2 was induced by adding LPS to RAW 264.7 cell, and COX-2 activity was measured by western blot analysis and $PGE_2$ Biotrak kit. Results : $CRHS$ also inhibited Freund's complete adjuvant induced chronic rheumatoid arthritis in mice. $CRHS$ showed significant inhibition of type I and type II $PLA_2$ activities in a dose dependent manner. Furthermore, $PGE_2$ production was decreased with $CRHS$ and lipopolysaccharide-induced COX-2 protein expression was significantly inhibited by $CRHS$. Conclusions : These results suggest that $CRHS$ has an therapeutic effect on drug induced-rheumatoic arthritis by inhibiting $PLA_2$ and COX-2 activities.

• Journal of Acupuncture Research
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• v.19 no.5
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• pp.176-188
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• 2002

Objective : Sono-acupoint (SA) therapy is a new therapeutic technique that combined with acupuncture points, herbal medicine and ultrasound therapy. This study was carried out to investigate the analgesic and anti-inflammatory effects of sono-acupoint therapy. Methods : We performed the tail-flick test with normal rats to examine the tail-flick latency (TFL), and the Freund's adjuvant-induced arthritis rat model to examine the edema, skin temperature and serum concentration of c-reactive protein and rheumatoid factor (RF). Herbal SA (HSA) treatment was performed at bilateral Zusanli (ST36) with the hanbang-gel made of several selected herbal drugs in Sprague-Dawley rats (male, $250{\pm}30g$). General SA (GSA) treatment was performed at bilateral Zusanli (ST36) with the gel used in ultrasound therapy. In arthritis rat model, Freund's adjuvant (50mg/ml) was injected in dorsal part of right foot, and these treatments were performed after 15 days. Results : TFL was lengthened after SA treatments. Skin temperature and RF concentration that were the evidence of arthritis in rats were decreased by HSA treatment (P < 0.05). Conclusion : These results indicate that HSA has the analgesic and anti-inflammatory effects in rats, and further developments will produce the advance of this new therapeutic skill.

• Journal of Ginseng Research
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• v.22 no.1
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• pp.32-42
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• 1998

(Backgrounds) This study was performed to evaluate the usefulness of red ginseng ex rant as adjuvant therapeutic agent improving immune function in immune compromizing gas-trointestinal carcinoma patient. (Material and Methods) We were treated 72 patients with two groups after we were undertaken the curative resection for gastrointestinal carcinoma; 1) only chemotherapy and immunotherapy (control group) 2) chemotherapy and immunotherapy with 4500 mg (15 tablets) red ginseng for 6 months (study group). For investigating the immunologic alternations alongside the numerical changes in peripheral blood Iymphocyte and their subsets in the gastrolntestinal carcinoma patients, Iymphocyte surface markers were determined by monoclonal antibodies on the preoperative day, postoperative 1 months, 3 months, 6 months, 12 months and 18 months in 40 controls and 32 red ginseng groups In gastrointestinal carcinoma patients which was recruited at Korea diversity Hospital from March, 1995 to January, 1997. The patient was measured and compared in both groups with the body weight, total protein and albumin, blood hematocrit and hemoglobin, total leukocyte, lymphocyte and lymphocyte subsets count in peripheral blood through planed schedules. (Couclusion) This data suggests that red ginseng may be useful as a adjuvant therapeutic agent for improving the immune function after curative operation for immune compromizing gastrointestinal carcinoma patients. Key words : Ginseng, Immunity, Gastrointestlnal carcinoma patients.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.91-103
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• 2002

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. characterized by leukocyte infiltration, a chronic inflammation of the joint, a pannus formation and the extensive destruction of the 3Iticular caJ1ilage and bone. Several proinflammatory cytokines such as tumor necrosis factor-${\alpa}$(TNF-${\alpa}$), interleukin-1${\beta}$ (IL-1${\beta}$) and interleukin 6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. In the Korean traditional medicine, Hominis placenta (HP) as an herbal solution of herb-acupuncture has been widely used to treat the inflammatory diseases including RA. In order to study the medicinal effect of HP herb-acupuncture on rheumatoid joint, an adjuvant-induced arthritis (AlA) was generated by the injection of 1.5 mg uf Mycobactelium tuberculusis. emulsified in squalene, 10 the base of the tail of Sprague-Dawley(SD) rats. After onset stage of polyarthritis, HP was daily injected to the Zusanti (ST36) acupuncture points in both of rat lags and the expression pattems of cytokines such as TNF-{\alpa}$, IL-1${\beta}$, and 1L-6 at the knee joint were analyzed using immunostaining and RT-PCR. The HP herb-acupuncture was found to be effective to alleviate the arthritic symptums in adjuvant-induced arthritic rats as regards the joint appearance and the expression profiles of inflammatory cytokines. In conclusion, therapeutic effects of HP herb-acupuncture on the rat with AlA might be related to anti inflammatory activities of the hurb-acupuncture.