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Prospective Study for Korean Red Ginseng Extract as an Immune Modulator Following a Curative Gastric Resection in Patients with Advanced Gastric Cancer

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Prospective Study for Korean Red Ginseng Extract as an Immune Modulator Following a Curative Gastric Resection in Patients with Advanced Gastric Cancer

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Abstract

The aim of this study was to evaluate prospectively the impact of the red ginseng extract on circulating interleukin (IL) 2 and 10 in advanced gastric cancer during chemotherapy after operative treatment. Analysis of circulating IL-2 and 10 was performed in 50 patients with advanced gastric adenocarcinoma who underwent a curative surgery or with an unresectable gastric adenocarcinoma by using ELISA and monoclonal antibodies at preoperative day 1, postoperative months 1, and 3. Twenty-five patients as the control group, twenty-six patients as the non-ginseng (NG) group, and twenty-four patients as the ginseng (G) group were eligible in this study. All plasma IL-2 of the NG and G groups was significantly lower an that of the control group on preoperative 1 day. These values of the G group were more increase than these of the NG group during the postoperative chemotherapy. The mean value of serum IL-10 of the control group (0.608pg/ml) was significantly lower than that of the advanced gastric cancer patients including the NG (12.015 pg/ml) and G group (9.409 pg/ml) (p?0.001). These values of the G group were reduced progressively during the postoperative chemotherapy. The mesh value of the G group were only close to that of the control group on postoperative months 3 (p=0.003). The number of patients who were enrolled in this study was relatively small to fully evaluate the immunologic effects of the red ginseng extract on circulating IL-2 and 10. Despite this limitation, these results suggest that the post-operative intake of the red ginseng extract have potential to improve earlier anti-cancer immunity with recovering IL-2 and reducing IL-10 from the depressed IL-2 and elevated IL-10 by gastric cancer during the postoperative chemotherapy. This study will be based on the future study to evaluate the anti-immunity of the red ginseng extract.

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... Twenty-eight trials originated from Korea , and two trials were conducted in Thailand [26] and the United Kingdom [27]. Sixteen studies [28,[32][33][34][35][36][37][38][39][40][41][44][45][46][47]53] were published in Korean, and 14 trials [26,27,[29][30][31]42,43,[48][49][50][51][52]54,55] were written in English. ...
... The key data from studies in healthy persons are summarised in Table 1 [26][27][28][29][30][31][32][33][34], and the data regarding other various conditions are summarised in Table 2 . The included RCTs used ginseng powder either in raw (4 studies) [35,38,53,55] or in capsules (22 studies) [26][27][28][29]31,32,34,36,37,[39][40][41][43][44][45][46][47][48][50][51][52]54] and extract preparation (2 studies) [33,42], while two studies [30,49] did not report the preparation type of ginseng. They addressed a wide range of conditions: generally healthy (i.e., studies in healthy individuals) [26][27][28][29][30][31][32][33][34], erectile dysfunction [35][36][37][38][39][40], gastric cancer [41,43], colon cancer [42], gastrointestinal carcinoma [44], chronic gastritis [45], diabetes mellitus [46,47], androgenic alopecia [48], coronary artery [49], dry mouth [50], glaucoma [51], obesity [52], metabolic syndrome [53], dyspepsia and indigestion [54] and Alzheimer's disease [55]. ...
... The included RCTs used ginseng powder either in raw (4 studies) [35,38,53,55] or in capsules (22 studies) [26][27][28][29]31,32,34,36,37,[39][40][41][43][44][45][46][47][48][50][51][52]54] and extract preparation (2 studies) [33,42], while two studies [30,49] did not report the preparation type of ginseng. They addressed a wide range of conditions: generally healthy (i.e., studies in healthy individuals) [26][27][28][29][30][31][32][33][34], erectile dysfunction [35][36][37][38][39][40], gastric cancer [41,43], colon cancer [42], gastrointestinal carcinoma [44], chronic gastritis [45], diabetes mellitus [46,47], androgenic alopecia [48], coronary artery [49], dry mouth [50], glaucoma [51], obesity [52], metabolic syndrome [53], dyspepsia and indigestion [54] and Alzheimer's disease [55]. ...
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This systematic review was performed to summarise randomised clinical trials (RCTs) assessing the efficacy and safety of ginseng in the Korean literature. The study involved systematic searches conducted in eight Korean Medical databases. The methodological quality of all of the included studies was assessed using the Cochrane Risk of Bias tool. We included all RCTs on any type of ginseng compared to placebo, active treatment or no treatment in healthy individuals or patients regardless of conditions. In total, 1415 potentially relevant studies were identified, and 30 randomised clinical trials were included. Nine RCTs assessed the effects of ginseng on exercise capacity, cognitive performance, somatic symptoms, quality of life, and sleeping in healthy persons. Six RCTs tested ginseng compared with placebo for erectile dysfunction, while another four studies evaluated the effects of ginseng against no treatment for gastric and colon cancer. Two RCTs compared the effect of red ginseng on diabetes mellitus with no treatment or placebo, and the other nine RCTs assessed the effects of ginseng compared with placebo or no treatment on various conditions. The methodological caveats of the included trials make their contribution to the current clinical evidence of ginseng somewhat limited. However, the 20 newly added trials (66.7% of the 30 trials) may provide useful information for future trials. Ginseng appears to be generally safe, and no serious adverse effects have been reported. The clinical effects of ginseng have been tested in a wide range of conditions in Korea. Although the quality of RCTs published in the Korean literature was generally poor, this review is useful for researchers to access studies that were originally published in languages that they would otherwise be unable to read and due to the paucity of evidence on this subject.
... The ginseng group received 3 g of Korean Red ginseng (Korea Ginseng Corporation, Seoul, Republic of Korea) daily as a pill. The dosage of 3 g/day was decided based on the safety dose from previous reports (13,14). Peripheral blood sampling was performed thrice during the study period: before the initiation of adjuvant chemotherapy, during chemotherapy, and after the end of chemotherapy ( Figure 2). ...
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Background/aim: We aimed to clarify the clinical effect of Korean Red ginseng administered with adjuvant chemotherapy on the immune function of patients with bile duct or pancreatic cancer. Patients and methods: This was a prospective, randomized controlled trial conducted at a single tertiary center. Twenty-six consecutive patients who underwent curative resection for bile duct or pancreatic cancer followed by 5-fluorouracil/leucovorin or gemcitabine chemotherapy were included. They were randomized 1:1 to the ginseng and control groups. Immune and inflammatory markers were assayed in peripheral blood samples during and after chemotherapy. Results: Intergroup differences in immune-related parameters before and during chemotherapy were not significant. After chemotherapy, the percentage of CD4+ T lymphocytes was significantly higher in the ginseng group than in the control group (42.01% vs. 33.69%, p=0.048). The ratio of CD4+/CD8+ T lymphocytes was also higher in the ginseng group (2.03 vs. 1.28, p=0.027). Neutropenia and liver dysfunction prevalence did not differ between the groups. Conclusion: The ginseng group, which received Korean Red ginseng daily during adjuvant chemotherapy, showed higher levels of CD4+ T lymphocytes and CD4+/CD8+ T lymphocyte ratio after chemotherapy.
... They then measured the number of immune cells and cytokines in both groups. The KRG group showed an increase in CD4þ and CD8þ T cell count, B cell count, WBC count, and blood IL-2 contentdwhich improves immune function after cancer surgerydcompared to the placebo group with a decrease in IL-10 [39,40]. ...
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Background Most clinical studies of immune responses activated by Korean Red Ginseng (KRG) have been conducted exclusively in patients. However, there is still a lack of clinical research on immune-boosting benefits of KRG for healthy persons. This study aims to confirm how KRG boosts the immune system of healthy subjects. Methods A total of 100 healthy adult subjects were randomly divided into two groups that took either a 2 g KRG tablet or a placebo per day for 8 weeks. The primary efficacy evaluation variables included changes in T cells, B cells, and white blood cells (WBCs) before and after eight weeks of KRG ingestion. Cytokines (TNF-α, INF-γ, IL-2 and IL-4), WBC differential count, and incidence of colds were measured in the secondary efficacy evaluation variables. Safety evaluation variables were used to identify changes in laboratory test results that incorporated adverse reactions, vital signs, hematological tests, blood chemistry tests, and urinalysis. Results Compared to the placebo group, the KRG intake group showed a significant increase in the number of T cells (CD3) and its subtypes (CD4 and CD8), B cells, and the WBC count before and after eight weeks of the intake. There were no clinically significant adverse reactions or other notable results in the safety evaluation factors observed. Conclusion This study has proven through its eight-week intake test and subsequent analysis that KRG boosts the immune system through an increase in T cells, B cells, and WBCs, and that it is safe according to the study's safety evaluation.
... KRG is one of the common adaptogens considered to be relatively safe even in large amounts and over a long-term administration. KRG can improve the response to stress with its adaptogenic activities, enhancing immune function [5] and antioxidant activity [6], improving memory [7] and blood circulation [8], and fatigue recovery [9]. According to diverse pharmacological research and clinical trials, KRG received approval for 6 claims as a health functional food from the Korean Food and Drug Administration. ...
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Background: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. Methods: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. Results: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. Conclusion: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.
... These results confirm that red ginseng has protective effects against acute respiratory diseases [40]. When type 1 human immunodeficiency virus-infected patients (AIDS patients) either took medication and red ginseng together or took red ginseng alone Red ginseng extract Random (no placebo) 25 healthy individuals and 50 stomach cancer patients 3 g/3 months -IL-2 and decrease rate of IL-10 were higher in the red ginseng group than in the control group [37] Red ginseng extract Random (no placebo) 47 colorectal cancer patients 3 g/3 months -IL-2, IL-8, and IL-10 activity was regulated in the red ginseng group than in the control group [38] Red ginseng powder ...
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Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.
... Also, ginseng takers are reported to have higher non organic-specific anti-carcinogenic effects than non-takers [21]. When 43 patients who required chemotherapy after stomach cancer surgery and 7 patients for whom surgery was impossible due to metastasis took red ginseng extract (3 g/ d) for 3 mo, red ginseng extract takers showed increased interleukin (IL)-2 content in the blood, while the content of decreased IL-10, a cytokine that suppresses anticancer immunity of the host, decreased, implying that red ginseng enabled recovery of immunity during anticancer chemotherapy [22]. ...
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This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without 100 μg/L PMA in the absence or presence of various concentrations (100, 200, or 300 μg/mL) of red ginseng extract. Red ginseng extract treatment caused significant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were significantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity significantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.
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This chapter reviews the factors on immunosuppressive molecules that are elaborated by tumor cells or found in sera and effusions. Immunosuppressive factors can be found in normal sera, but their level is increased in cancer sera. These factors may contribute to the defective cellular responses of patients. Some well-characterized immunosuppressive molecules are transforming growth factor β (TGF-β), lymphocyte blastogenesis inhibitory factor (LBIF), p15E, and suppressive E-receptor (SER). TGF-β is produced by most cells and has an extraordinarily wide range of biological activities. p15E protein possesses a remarkable range of immunosuppressive activities. The SER is isolated from malignant effusions derived from patients with several types of cancer and inhibited several cellular immune responses. The exact mechanism of the immunosuppression is still uncertain, but a multiplicity of factors contributes to its occurrence: suppressor T cells and suppressor macrophages, immune complexes, acute phase proteins, tumor-derived suppressor molecules, suppressor substances in sera and effusion fluids of patients, and chemotherapy and irradiation. The colony-stimulating factors, acute-phase proteins, and miscellaneous molecules are some of the immunosuppressive factors in human cancer.
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A large body of evidence suggests the existence of polarized human T cell responses, reminiscent of Th1 and Th2 subsets described for mouse T cells. Human Th1-like cells preferentially develop during infections by intracellular bacteria, protozoa, and viruses, whereas Th2-like cells predominate during helminthic infestations and in response to common environmental allergens. The cytokine profile of “natural immunity” evoked by different offending agents in the context of different host genetic backgrounds appears to be a critical factor in determining the phenotype of the subsequent specific response. Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, they can also promote different immunopathological reactions. Th1-type responses appear to be involved in organ specific autoimmunity, in contact dermatitis, and in some chronic inflammatory disorders of unknown etiology. In contrast, in genetically predisposed hosts, Th2-type responses against common environmental allergens are responsible for triggering of allergic atopic disorders. Altered profiles of lymphokine production may account for immune dysfunctions in some primary or acquired immunodeficiency syndromes. The role of lymphokines produced by T cells in the pathogenesis of systemic autoimmune disorders is less clear. Further work is also required to better clarify the role of T cell-derived lymphokines in protecting against tumors or in favoring their development.
Article
The water extract of Panax ginseng was fractionated by its solubility in ethanol and then the ethanol-insoluble fraction was tested for immunomodulatory activity. The ethanol-insoluble fraction of ginseng (Fr. 3) proliferated splenocytes and generated activated killer cells in vitro. These activated killer cells killed both NK cell sensitive and insensitive tumor target cells without MHC-restriction. Activation of splenocytes by ginseng was mediated through the endogenously produced IL-2. To investigate the effects of Fr.3 on the autochthonous neoplasm, a single subcutaneous injection of 0.5 mg of benzo[a]pyrene (BP) was given within 24 hours after birth of male N: GP(S) mice, and Fr.3 was administered in drinking water at a concentration of 2 mg/ml, 1 mg/ml, or 0.5 mg/ml for 6 weeks after weaning. The treatment with Fr. 3 significantly inhibited lung tumor incidence (P < 0.05) compared with the BP alone group at a concentration of 2 mg/ml or 1 mg/ml in drinking water at the 9th week after BP treatment. These results suggest that the ethanol-insoluble fraction of ginseng shows antitumor effects as an immunomodulator.
Article
In the three years since its discovery, the pleiotropic cytokine interleukin-10 (IL-10) has been implicated as an important regulator of the functions of lymphoid and myeloid cells. IL-10's ability to block activation of cytokine synthesis and several accessory cell functions of macrophage renders this cytokine a potent suppressor of the effector functions of macrophages, T cells, and NK cells. In addition, IL-10 likely contributes to regulating proliferation and differentiation of B cells, mast cells, and thymocytes. The Epstein-Barr virus genome encodes a homolog of IL-10 (BCFR1, viral IL-10, vIL-10) which shares many of the cellular cytokine's biological activities and may therefore play a role in the host-virus interaction. This article reviews current studies of IL-10's biological activities and discusses its possible roles in regulation of immune responses.
Article
Since their discovery nearly ten years ago, T helper 1 (Th1) and Th2 subsets have been implicated in the regulation of many immune responses. In this article, Tim Mosmann and Subash Sad discuss the increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy.
Article
The role of cytokines was intensively discussed over the course of a two and a half day meeting sponsored by the US-JAPAN Cancer Cooperative Research Program of the Office of International Affairs, National Cancer Institute and held at The National Institutes of Health, Bethesda, Maryland on 15-17 January 1996. Most of the first day was devoted to a discussion of the role of cytokines in modulating angiogenesis and the consequent effect of this on tumor growth and metastases. This was followed by sessions on the effect of various cytokines in enhancing or suppressing immunological responses to tumors. Several presentations focused on the direct inhibitory or growth promoting effects of cytokines on tumor growth. The final session consisted of a comparison of the efficacy of different approaches to tumor vaccination including gene therapy, enhanced antigen presentation, use of polymeric carriers or of DNA vectors. For background information the reader is referred to appropriate chapters on the role of cytokines in neoplastic diseases (Oppenheim JJ, Rossio JL, Gearing AJH, eds. In Clinical Application of Cytokines: Role of Pathogenesis, Diagnosis and Therapy. Oxford University Press, New York, 1993 [1]).
Article
In the present study an acidic polysaccharide ginsan, with a molecular weight of 150,000, devoid of lectin properties, was purified from Panax ginseng C.A. Meyer (Araliaceae). Ginsan induced the proliferation of T cells and B cells. Spleen cells became cytotoxic to a wide range of tumor cells without major histocompatibility complex-restriction after 4 or 5 days culture in vitro with ginsan. For the generation of these ginsan-activated killer (AK) cells adherent macrophages and CD4+ cells were needed as accessory cells. The generation of ginsan-AK cells was blocked in the presence of anti-IL-2, anti-IFN gamma, anti-IL-1 or anti-TNF alpha antibodies, showing the importance of these cytokines in the process. The surface phenotypes of the 4 day-cultured ginsan-AK cells was Thy1+, AsGM1+, CD8+, which is distinct from rIL-2 induced lymphokine activated killer (LAK) cells that were CD8. The ginsan also activated macrophages to produce reactive nitrogen intermediates and become tumoricidal. It also exhibited significant in vivo antitumor activity against B16 melanoma cells lines, and in the benzo(a)pyrene-induced autochthonous lung tumor model, at much lower doses than the maximum tolerate doses. Indeed, no mice died, which injected with ginsan at 1g/kg body weight intraperitoneally. In conclusion, 'ginsan' could potentially be an ideal nontoxic antineoplastic immunostimulator by activating multiple effector arms of the immune system.
Article
Depressed cell-mediated immunity is a frequent event in patients with head and neck cancer and is characterized by impairment of T cell-proliferative responses and natural killer cell and lymphokine-activated killer cell activity. This immunosuppressive effect appears to be mediated by a serum-derived factor. Certain cytokines, including transforming growth factor-beta (TGF-beta) and interleukin (IL)-10 have been shown to induce similar immunosuppressive effects. The present study was designed to examine the putative role of these cytokines in cellular immune suppression induced by patient serum. Serum was collected from multiple patients with newly diagnosed or recurrent squamous cell carcinoma of the head and neck. The serum was heat inactivated for 30 min and frozen in aliquots. Peripheral blood lymphocytes were isolated from normal human blood. Lymphocytes were suspended in RPMI and 15% concentrations of control and patient serum and stimulated with 0.75 mg% phytohemagglutinin. In addition, neutralizing antibodies to TGF-beta and IL-10 were added to lymphocyte cultures. At 24 h, and IL-2 response assay was performed. Finally, the sera were examined for the presence of TGF-beta and IL-10 using an enzyme-linked immunosorbent assay (ELISA). In seven of seven experiments, incubating cells with a neutralizing antibody to TGF-beta failed to counteract the immune suppression and restore proliferative response to IL-2. Also, an ELISA of these sera failed to demonstrate the presence of TGF-beta. In contrast, four of five experiments performed with neutralizing antibody to IL-10 showed significant restoration of proliferation in the presence of this antibody. Also, ELISA showed elevated IL-10 levels in 65% of the patients' sera in comparison to controls. We conclude that TGF-beta is not responsible for the immunosuppressive effects induced by head and neck patient sera. However, the suppressive effect is reversed by blocking the biologic action of IL-10. Further experiments are needed to define the role of IL-10 in inducing the immunosuppressive effect.
Article
Recently we have demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) can be activated by cervical carcinoma cells expressing the costimulatory molecule CD80, which may be used as a therapeutic vaccine for patients with cervical cancer. For activated CTLs to be effective, appropriate amounts of MHC class I expression are required on target tumor cells. In this study, we found that some cervical carcinoma cells expressed only low levels of MHC class I and adhesion molecules such as CD54. We further demonstrated that tumor cells (CaSki and SiHa) expressing low levels of MHC class I were more resistant to lysis by specific CTLs than tumor cells (HeLa) expressing high levels of MHC class I. Treatment of CaSki or SiHa cells with interferon-gamma resulted in an increased expression of MHC class I, MHC class II, and CD54. Expression of CD58 and CD80 was not up-regulated or induced. Treatment of the tumor cells with interferon-gamma significantly enhanced the lysis of the tumor cells by specific CTLs which had been activated by the respective CD80-expressing tumor cells. The enhancement of cytolysis could be blocked by monoclonal antibodies to MHC class I and CD54, but not by that to MHC class II. Furthermore, we found that interferon-gamma induced apoptosis in cervical carcinoma cells but not in tumor-specific CTLs.
Article
A wide variety of human tumors express IL-10 for reasons poorly understood. We have analyzed the effect of spontaneous IL-10 expression by a mouse tumor (J558L) on its immunoparalyzing effect. Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells. GM-CSF-secreting cells were not effective when used for immunization against challenge with the parental tumor. Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response. Since the tumor used for challenge produced IL-10, we conclude that IL-10 interfered primarily with the initiation but not the effector phase of the immune response. Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10. In the presence of IL-10, DC accumulation was completely inhibited. Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
Article
Interleukin 10 (IL-10) has been shown to be elevated in the plasma of cancer-bearing patients. The source of systemic IL-10 may be the tumor microenvironment. We therefore tried to evaluate if ablative surgery for gastrointestinal cancer could affect the levels of circulating IL-10. Plasma IL-10 concentration was measured in 45 patients with adenocarcinoma of the gastrointestinal tract. Forty healthy subjects, 15 women undergoing hysterectomy for uterine fibroma, and 15 patients undergoing palliative operation for pancreatic cancer were used as control groups. Plasma IL-10 was assessed 1 day before surgery (baseline) and 1, 4, and 8 days after operation. The baseline concentration of IL-10 was significantly higher in cancer patients than in healthy subjects and in women with fibroma (8.6 ng/mL, 2.1 and 1.8 respectively; P = 0.015). After radical surgery, the IL-10 levels significantly dropped in cancer patients (from 8.6 ng/mL to 3.8; P = 0.024), whereas in subjects undergoing palliative operation, the concentration remained elevated (8.5 ng/mL baseline versus 7.9 on day + 1). The origin of circulating IL-10 may be the tumor microenvironment.
Article
To determine the immunologic characteristics of tumor infiltrating lymphocytes (TILs) in comparison with the corresponding peripheral blood lymphocytes (PBLs) of patients with ovarian cancer in order to detect specific antitumor-reactive-immunocompetent cells. Tumor infiltrating lymphocytes and PBLs were phenotyped by their surface markers, cytokine pattern, proliferation rate, and cytotoxic ability. The phenotypes of both lymphocyte populations were very heterogeneous. Peripheral blood lymphocytes had a higher proliferative activity and cytotoxicity against natural killer-sensitive tumor cells than the corresponding TILs. Furthermore TILs showed increased interleukin-4 expression whereas in PBLs, interferon-gamma production predominated. Peripheral blood lymphocytes showed more potentially valuable behavioral characteristics than TILs. In the future we need to combine several methods in order to define immune cells with antitumor activity. These cells should be expanded ex vivo and stimulated specifically for use in the immunotherapy of ovarian cancer.
Article
Cancer cells may express proteins recognizable by the individual's immune system as foreign because they are either tumor-specific or not expressed at high levels in normal tissues to which the host is tolerant. There is now much evidence that tumors can be immunogenic, that is, that they frequently express antigens in a form recognizable by the host immune system. This has been shown not only in experimental animals but also for spontaneously occurring human tumors. Tumors therefore may progress by evolving variants that can evade immune responses or by developing other strategies to "escape" the immune response. The purpose of this review is to consider the current status of knowledge concerning these different tumor escape strategies.
Article
A number of studies have reported that increased consumption of natural products reduced the risk of cancer. Our previous case-control studies have shown a significant reduction in the risk of cancer development among those who regularly consumed ginseng. We conducted a prospective cohort study to evaluate the preventive effect of ginseng against cancer on a population residing in a ginseng cultivation area on the basis of the result of case-control studies. This study was conducted in Kangwha-eup from August 1987 to December 1992. We studied 4634 people over 40 years old who completed a questionnaire on ginseng intake. In an attempt to obtain detailed information about ginseng intake, we asked them to specify their age at initial intake, their frequency and duration of ginseng intake, the kind of ginseng, etc. Multiple logistic regression was used to estimate relative risks (RR) when controlling simultaneously for covariates. Ginseng consumers had a decreased risk (RR = 0.40, 95% confidence interval [CI] : 0.28-0.56) compared with non-consumers. On the type of ginseng, the RR was 0.31 (95% CI: 0.13-0.74) for fresh ginseng extract consumers and 0.34 (95% CI: 0.20-0.53) for consumers of multiple combinations. There was no cancer death among 24 red ginseng consumers. There was a decreased risk with a rise in the frequency of ginseng intake, showing a dose-response relationship. The RR of ginseng consumers were 0.33 (95% CI: 0.18-0.57) in gastric cancer and 0.30 (95% CI : 0.14-0.65) in lung cancer. Among ginseng preparations, fresh ginseng extract consumers were significantly associated with a decreased risk of gastric cancer (RR = 0.33, 95% CI: 0.12-0.88). These results strongly suggest that Panax ginseng C.A. Meyer has non-organ specific preventive effect against cancer, providing support for the previous case-control studies.
Article
Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. In this study, the authors investigated the prognostic significance of IL-10 levels in the sera of 58 patients with advanced gastric or colorectal carcinoma. IL-10 serum levels were measured before chemotherapy, on completion of chemotherapy, and at follow-up by means of a commercially available enzyme-linked immunoadsorbent assay kit. The results then were analyzed in comparison with other prognostic variables and a model predicting overall survival (OS) and time to disease progression (TTP) was generated. Elevated levels of serum IL-10 were found in carcinoma patients compared with healthy controls (19.6 +/- 6.8 pg/mL vs. 9.2 +/- 1.5 pg/mL; P < 0.0001), with those patients with metastatic disease showing significantly higher levels than patients with undisseminated disease (21.9 +/- 6. 7 pg/mL vs. 15.5 +/- 3.6 pg/mL; P = 0.0003). Retrospective analysis of prechemotherapy IL-10 serum levels showed a significant difference between responders and nonresponders (15.8 +/- 2.5 pg/mL vs. 21.6 +/- 7.6 pg/mL; P < 0.0001). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.6 +/- 7.6 pg/mL prechemotherapy vs. 31.3 +/- 11.6 pg/mL postchemotherapy; P < 0.0001) whereas no significant differences were observed in responders. Using univariate analysis, both OS and TTP were shown to be affected by the median pathologic levels of IL-10; multivariate analysis related to OS and TTP identified performance status and IL-10 serum level as the relevant prognostic factors, respectively. Finally, stepwise regression analysis identified IL-10 serum level and metastases as the prognostic factors related to both OS and TTP. The results of the current study show that measurement of pretreatment serum levels of IL-10 is of independent prognostic utility in patients with advanced gastrointestinal carcinoma and may be useful for the detection of disease progression.
Recurrent gastric cancer after curative surgery
  • J H Park
  • J Y Byun
  • B K Kim
  • I C Kim
Increased interleukin-10 serum levels in patients with solid tumours
  • C Fortis
  • M Foppi
  • L Gianotti
  • L Galli
  • G Citterio
  • G Conson-Nio