1.Inhibitive effects of gastric cancer cell-dendritic cell fusion vaccine on tumor cell proliferation cycle.
Kun ZHANG ; Pei-wu YU ; Peng-fen GAO ; Yun RAO
Chinese Journal of Gastrointestinal Surgery 2006;9(4):345-348
OBJECTIVETo study the inhibitive effects of gastric cancer cell-dendritic cell fusion vaccine on tumor cells of proliferation cycle.
METHODSPeripheral blood mononuclear cells were separated from gastric cancer patients and co-cultured with granulocyte macrophage colony stimulating factors(GM-CSF), interleukin-4(IL-4) and tumor necrosis factor-alpha(TNF-alpha) to generate mature dendritic cells. The dendritic cells and SGC7901 cells were fused by polyethylene glycol, and the pure fusion cells were screened out by selective culture systems. The inhibitive effects of gastric cancer cell-dendritic cell fusion vaccines on tumor cell proliferation cycle in vivo and in vitro were detected by flow cytometry.
RESULTSTreated with the fusion vaccine in vitro, the percentages of G(0)/G(1), S and G(2)/M cells of tumor cells were (76.77+/- 4.38)%, (16.50+/- 2.90)% and (6.73+/- 1.59)% respectively. There were significant differences in the percentages of different cell cycle tumor cells between the tumor cells treated with the fusion vaccine and those co-cultured with dendritic cell or T cells alone(P< 0.01). The proliferative index of the tumor cells treated with the fusion vaccine was 23.34+/- 3.51, significantly lower than those co-cultured with dendritic cell and controls (P< 0.05).
CONCLUSIONSFusion vaccines can affect cell cycle of the tumor cells, thus inhibit tumor cell proliferation and growth.
Cancer Vaccines ; immunology ; pharmacology ; Cell Cycle ; drug effects ; Cell Fusion ; Cell Proliferation ; drug effects ; Dendritic Cells ; immunology ; Humans ; Stomach Neoplasms ; immunology ; Tumor Cells, Cultured
2.Effect of activated greater omental milky spots and peritoneal macrophages on tumoricidal activity against gastric carcinoma SGC-7901 in mice.
Chinese Journal of Oncology 2003;25(3):225-229
OBJECTIVETo investigate the effect of activated greater omental milky spots and peritoneal macrophages in mice on tumoricidal activity against gastric carcinoma SGC-7901, following intraperitoneal (i.p.) injection of INF-gamma, staphylococcin aureus or NDV-L.
METHODSThe quantitative changes of milky spots were determined by activated carbon, the number of the macrophage in milky spots was assessed by nonspecific esterase stain and the number of peritoneal macrophages was counted by trypan blue exclusion. The morphology of peritoneal macrophages was observed by scanning electron microscope, the amount of TNF-alpha and iNOS mRNA expressed by peritoneal macrophages was measured by fluorescence quantitative PCR and the cytotoxicity of peritoneal macrophages supernatant against SGC-7901 was evaluated by MTT assay.
RESULTSIt was found in the treated groups that: 1. The amount of greater omental milky spots and the macrophages in milky spots increased, 2. The number of peritoneal macrophages increased. The peritoneal macrophages were in activated status. The effect TNF-alpha and iNOS mRNA expression increased and 3. The cytotoxicity against in vitro SGC-7901 increased.
CONCLUSIONIntraperitoneal injection of IFN-gamma, staphylococcin aureus or NDV-L could activate the milky spots of the greater omentum and the macrophages in peritoneal cavity in mice, with IFN-gamma being the best. The supernatant of activated peritoneal macrophages has cytotoxicity against SGC-7901. Administration of LPS to macrophages cultured in vitro could amplify the activation and enhance the cytotoxicity of the supernatant against SGC-7901.
Animals ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Female ; Interferon-gamma ; pharmacology ; Macrophages, Peritoneal ; drug effects ; immunology ; ultrastructure ; Mice ; Nitric Oxide Synthase Type II ; genetics ; Omentum ; drug effects ; immunology ; ultrastructure ; RNA, Messenger ; analysis ; Stomach Neoplasms ; immunology ; Tumor Necrosis Factor-alpha ; genetics
3.Murine Model of Buckwheat Allergy by Intragastric Sensitization with Fresh Buckwheat Flour Extract.
Soo Young LEE ; Sejo OH ; Kisun LEE ; Young Ju JANG ; Myung Hyun SOHN ; Kyoung En LEE ; Kyu Earn KIM
Journal of Korean Medical Science 2005;20(4):566-572
Food allergies affect about 4% of the Korean population, and buckwheat allergy is one of the most severe food allergies in Korea. The purpose of the present study was to develop a murine model of IgE-mediated buckwheat hypersensitivity induced by intragastric sensitization. Young female C3H/HeJ mice were sensitized and challenged intragastricly with fresh buckwheat flour (1, 5, 25 mg/dose of proteins) mixed in cholera toxin, followed by intragastric challenge. Anaphylactic reactions, antigen-specific antibodies, splenocytes proliferation assays and cytokine productions were evaluated. Oral buckwheat challenges of sensitized mice provoked anaphylactic reactions such as severe scratch, perioral/periorbital swellings, or decreased activity. Reactions were associated with elevated levels of buckwheatspecific IgE antibodies. Splenocytes from buckwheat allergic mice exhibited significantly greater proliferative responses to buckwheat than non-allergic mice. Buckwheat-stimulated IL-4, IL-5, and INF-gamma productions were associated with elevated levels of buckwheat-specific IgE in sensitized mice. In this model, 1 mg and 5 mg dose of sensitization produced almost the same degree of Th2-directed immune response, however, a 25 mg dose showed blunted antibody responses. In conclusion, we developed IgE-mediated buckwheat allergy by intragastric sensitization and challenge, and this model could provide a good tool for future studies.
Anaphylaxis/blood/immunology
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Animals
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Cell Proliferation/drug effects
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Comparative Study
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Fagopyrum/*immunology
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Female
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*Flour
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Food Hypersensitivity/blood/*immunology
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Immunoglobulin E/blood/immunology
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Immunoglobulin G/blood/immunology
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Interferon Type II/biosynthesis
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Interleukin-4/biosynthesis
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Interleukin-5/biosynthesis
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Mice
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Mice, Inbred C3H
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Plant Extracts/administration & dosage/immunology
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Research Support, Non-U.S. Gov't
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Spleen/cytology/drug effects/metabolism
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Stomach/drug effects/*immunology
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T-Lymphocytes/cytology/drug effects/metabolism
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Time Factors
4.Meta analysis of compound matrine injection combined with cisplatin chemotherapy for advanced gastric cancer.
Sixia HUANG ; Wenbin FAN ; Peng LIU ; Jinhui TIAN
China Journal of Chinese Materia Medica 2011;36(22):3198-3202
OBJECTIVETo assess the efficacy and safety of compound matrine injection combined with cisplatin chemotherapy for advanced gastric cancer.
METHODIt was searched relevant randomized Controlled trials (RCTs) from Cochrane Library, PubMed, EMBASE, CBM, and CNKI etc. The search was finished in February 11, 2010. And it was traced the related references and experts in this field, besides it was also communicated with other authors in order to obtain some certain information that had not been found. RCTs of compound matrine injection combined with cisplatin chemotherapy versus cisplatin chemotherapy for advanced gastric cancer were included. It was evaluated the quality of these included studies and analyzed data by Cochrane Collaboration's RevMan 5.0 software.
RESULTTen RCTs were included meta analysis results suggested that compared with chemotherapy alone, the combination had a statistically significant benefit in healing efficacy (OR = 1.99, 95% CI: 1.26-3.13, P < 0.05) and improving quality of life (OR = 3.83, 95% CI: 2.38-6.15, P < 0.001). Besides, the combination also had a statistically significant benefit in myelosuppression, white blood cell (OR = 0.44, 95% CI: 0.32-0.62, P < 0.001), hematoblast (OR = 0.40, 95% CI: 0.26-0.60, P < 0.001), liver function (OR = 0.33, 95% CI: 0.15-0.75, P < 0.05) and in reducing the gastroenteric reaction (OR = 0.32, 95% CI: 0.16-0.63, P = 0.001), decreasing the of CD3 ( MD = 2.96, 95% CI: 1.724. 20, P < 0.001), CD4 (MD = 9.04, 95% CI: 7.87-10.20, P < 0.001), CD4/CD8 (MD = 0.47, 95% CI: 0.41-0.54, P < 0.001) and NK cells (MD = 5.90, 95% CI: 4.53-7.26, P < 0.001).
CONCLUSIONCompared with cisplatin chemotherapy, compound matrine injection combined with cisplatin chemotherapy can significantly improve the efficiency, QOL and myelosuppression, and reduce adverse events.
Alkaloids ; administration & dosage ; Bone Marrow ; drug effects ; Cisplatin ; administration & dosage ; Humans ; Injections ; Quality of Life ; Quinolizines ; administration & dosage ; Randomized Controlled Trials as Topic ; Stomach Neoplasms ; drug therapy ; immunology
5.Prostaglandin E2 and Interleukin-1beta Reduce E-cadherin Expression by Enhancing Snail Expression in Gastric Cancer Cells.
Ye Seob JEE ; Tae Jung JANG ; Ki Hoon JUNG
Journal of Korean Medical Science 2012;27(9):987-992
Inflammation is closely related to the progression of cancer as well as tumorigenesis. Here, we investigated the effect of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) on E-cadherin expression in SNU719 gastric cancer cells. E-cadherin expression decreased as the dose or exposure time of PGE2 and IL-1beta increased, whereas Snail expression increased with dose or time of PGE2 and IL-1beta. E-cadherin expression reduced by PGE2 treatment increased after the transfection of Snail siRNA. Neutralization of IL-1beta using anti-IL-1beta antibody blocked the expression pattern of E-cadherin and Snail occurred by IL-1beta treatment. However, there was no synergic effect of IL-1beta and PGE2 on the expression pattern of E-cadherin and Snail. In conclusion, inflammatory mediators reduced E-cadherin expression by enhancing Snail expression in gastric cancer cells. Inflammation-induced transcriptional regulation of E-cadherin in gastric cancer has implications for targeted chemoprevention and therapy.
Antibodies/immunology
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Antineoplastic Agents/pharmacology
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Cadherins/*metabolism
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Cell Line, Tumor
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Dinoprostone/*pharmacology
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Gene Expression Regulation/*drug effects
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Humans
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Interleukin-1beta/immunology/*pharmacology
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RNA Interference
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RNA, Small Interfering/metabolism
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Stomach Neoplasms/metabolism/pathology
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Transcription Factors/antagonists & inhibitors/genetics/*metabolism
6.Study on chromatography-efficacy relationship of anti-inflammatory activity of qizhi weitong particle compound herbs with neural network and gray correlation method.
Wen-Wen XU ; Shuai WANG ; Xian-Sheng MENG ; Yong-Rui BAO
China Journal of Chinese Materia Medica 2013;38(11):1806-1811
OBJECTIVETo establish the chromatography-efficacy relation method for analyzing the anti-inflammatory activity of Qizhi Weitong particles, in order to lay a foundation for quality control and pharmacodynamic evaluation of traditional Chinese medicine compounds.
METHODOn the basis of a full-time multi-wavelength fusion fingerprint of Qizhi Weitong particles, the latin hypercube sampling was used to divide six herbs in Qizhi Weitong particles into groups of different proportions to determine their inhibition ratios of TNF-alpha, IL-6 and NO released by LPS-induced RAW264. 7 cells. Pharmaeodynamic data and chemical information of HPLC fingerprints of each group were analyzed with the gray correlation method to get the anti-inflammatory effect of each chromatographic peak, and then fitted with BP neural network to establish the chromatography-efficacy relation.
RESULTThere were 25 peaks closely related to the anti-inflammatory activity. With the 25 peaks as input items, the 3-BP network was adopted to establish the neural network model for anti-inflammatory effect of Qizhi Weitong particles.
CONCLUSIONWith an error of less than 7%, the model could better fit with the complicated non-linear relation of the compound, and applied in studying the chromatography-efficacy relation. In this study on the chromatography-efficacy relation, a new method is established to evaluate the anti-inflammatory activity of Qizhi Weitong particles. It is of practical significance as an effective approach for controlling quality and exploring the material basis for efficacy of traditional Chinese medicine compounds.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; Cell Line ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Humans ; Interleukin-6 ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; Neural Networks (Computer) ; Quality Control ; Rats ; Rats, Sprague-Dawley ; Stomach Diseases ; drug therapy ; immunology ; Tumor Necrosis Factor-alpha ; immunology
7.Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their clinical significance in gastric cancer patients.
Xiao-ling LIU ; Jun GAO ; Cun-zhi HAN ; Li-juan QIAO
Chinese Journal of Oncology 2008;30(11):844-847
OBJECTIVETo investigate the pre- and post-chemotherapy expression levels of Th1 and Th2 type cytokines in peripheral blood CD4(+) T lymphocytes, the changes of Th1/Th2 ratio and their clinical significance in patients with gastric cancer.
METHODSThe levels of specific cytokines in 60 gastric cancer patients were detected by flow cytometry before and after chemotherapy with FOLFOX4.
RESULTSThe level of IFN-gamma from peripheral blood CD4(+) T lymphocytes after chemotherapy in the whole group of gastric cancer patients was 11.4% +/- 5.0%, significantly higher than that (9.5% +/- 3.4%) before chemotherapy (P < 0.05). The level of IL-10 after chemotherapy was 3.6% +/- 1.2%, significantly lower than that (4.2% +/- 1.8%) before chemotherapy (P < 0.05). The ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 3.4 +/- 1.0 versus 3.4 +/- 1.6 before chemotherapy, without significant difference (P > 0.05). Interestingly, the levels of IFN-gamma and TNF-alpha of peripheral blood CD4(+) T lymphocytes in 15 gastric cancer patients who achieved partial response (PR) after chemotherapy were 14.8% +/- 8.0% and 5.9% +/- 2.0%, respectively, both were higher than that (6.9% +/- 2.5% and 4.2% +/- 1.3%) before chemotherapy (both P < 0.05). Furthermore, the ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 4.0 +/- 1.5, significantly higher than 2.5 +/- 1.2 before chemotherapy (P < 0.01).
CONCLUSIONEffective chemotherapy may reduce the tumor burden and relieve the shift of Th1/Th2 ratio. Improvement in immune function may be a very important therapeutic measure due to poor response of chemotherapy in gastric cancer patients.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD4-Positive T-Lymphocytes ; immunology ; Female ; Fluorouracil ; therapeutic use ; Humans ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-4 ; blood ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Organoplatinum Compounds ; therapeutic use ; Remission Induction ; Stomach Neoplasms ; blood ; drug therapy ; pathology ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Tumor Burden ; drug effects ; Tumor Necrosis Factor-alpha ; blood
8.Effect of jianpi yiqi qingyou decoction on lymphocyte subsets and IL-2 mRNA in gastric tissue in rats with chronic superficial gastritis.
China Journal of Chinese Materia Medica 2011;36(7):926-930
OBJECTIVETo investigate the effect of Jianpi Yiqi Qingyou decoction on lymphocyte subsets and IL-2 mRNA in gastric tissue in rats with chronic superficial gastritis.
METHODWistar rats were randomly divided into 6 groups (11 for each): a blank control groups, the model of the control groups, the treatment groups (low-dose groups of traditional Chinese medicine, moderate-dose groups of traditional Chinese medicine, high-dose groups of traditional Chinese medicine) and lansoprazole groups. The models were made with the method in reference except a blank control groups. These rats are drinking freely with 0. 02% ammonia, continuous 90 days, and made preparations for experimental animal model of superficial gastritis. Making the model were detected by HE dying. The count of CD3+, CD4+ and CD8+ T cells were detected by immunohistochemistry. Using reverse transcriptase polymerase chain reaction (RT-PCR), the expression levels of IL-2 mRNA in gastric tissue were quantified.
RESULTCompared with that in model groups, the content of CD3+ T cells and CD4+ T cells in gastric tissue obviously increased in high dose of traditional Chinese medicine groups , the content of CD8+ T cells in gastric tissue obviously decreased in high dose of traditional Chinese medicine groups and the difference was significant (P < 0.01). The expression levels of IL-2 mRNA in gastric tissue obviously increased in moderate and high doses of traditional Chinese medicine groups, and the difference was significant compared with that in model group (P < 0.01).
CONCLUSIONJianpi Yiqi Qingyou decoction can obviously improve the content of CD3+ T cells and CD4+ T cells and the expression levels of IL-2 mRNA, decrease the content of CD8+ T cells in gastric tissue, improve immunity of rats. So the research results can provide some evidences for the treatment for chronic superficial gastritis.
Animals ; CD4-CD8 Ratio ; Chronic Disease ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gastritis ; genetics ; immunology ; pathology ; Interleukin-2 ; genetics ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach ; drug effects ; immunology ; metabolism ; pathology ; T-Lymphocyte Subsets ; drug effects ; metabolism
9.EGFR-blockade by antibody Cetuximab inhibits the growth of human gastric cancer xenograft in nude mice and its possible mechanism.
Jun ZHANG ; Jun JI ; Fei YUAN ; Tao MA ; Zheng-bao YE ; Ying-yan YU ; Bing-ya LIU ; Zheng-gang ZHU
Chinese Journal of Oncology 2009;31(2):85-89
OBJECTIVEEGFR-mediated tumor proliferation plays an important role in the development of cancer, and is a key candidate for targeted therapy. The aim of this study is to evaluate the impact of EGFR monoclonal antibody Cetuximab (C225) on the growth, proliferation and apoptsis of gastric cancer xenograft in nude mice, and its possible mechanisms.
METHODSA gastric cancer cell line SGC-7901 with high EGFR expression level was screened from 7 gastric cancer cell lines. Gastric cancer xenografts in nude mice were established, and randomly divided into C225 treatment group and PBS control group. Tumor growth curves were calculated, the impact of C225 on the tumor growth, proliferation and angiogenesis was evaluated by immunohistochemical (IHC) staining Ki67 and CD34, respectively. The effect of C225 on apoptosis in the gastric cancer cells was evaluated by TUNEL assay. The expression levels of EGFR and its transcription factor Sp1 were detected by IHC staining and Western blot.
RESULTSAfter C225 treatment, the proliferation and growth of gastric cancer xenograft in nude mice were significantly decreased. In the contrast, the apopotic indexes in C225 treatment group and PBS control group were (16.4% +/- 0.3%) and (3.1% +/- 0.9%), respectively, with a significant difference (P < 0.001). There was no significant difference of the densities of CD34-positive microvessels between C225 treatment group and control group. Elevated expression of EGFR and Sp1 after C225 treatment was observed by IHC staining and Western blot assay.
CONCLUSIONEGFR monoclonal antibody cetuximab (C225) can effectively inhibit the growth of gastric cancer xenografts in nude mice, and trigger its apoptosis. Yet, C225 treatment may upregulate the expression of EGFR and its transcription factor Sp1. A "block-transcription activation-compensation" mechanism may exist to explain the molecular mechanism of acquired resistance of a single target blockade treatment.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cetuximab ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Neovascularization, Pathologic ; prevention & control ; Random Allocation ; Receptor, Epidermal Growth Factor ; immunology ; metabolism ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays
10.Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor.
Chinese Journal of Integrated Traditional and Western Medicine 2002;22(7):515-517
OBJECTIVETo observe the effect of Astragalus membranaceus efficacy enhancing and toxicity reducing on chemotherapy in patients of malignant tumor.
METHODSOne hundred and twenty tumor patients were randomly divided into the treated group and the control group. Both groups were treated with chemotherapy, but to the treated group, Astragalus injection was given additionally by intravenous dripping, 20 ml in 250 ml of normal saline once per day for 21 days as one course and 4 courses were given successively.
RESULTSCompared with the control group, the treated group showed a lower progressive incidence, lesser decrease of peripheral WBC and platelet count (P < 0.05), accompanied with CD8 significantly lowered (P < 0.05), CD4/CD8 ratio significantly increased (P < 0.01), IgG and IgM levels raised (P < 0.05) and Karnofsky scores elevated more than those in the control group. IgA level was unchanged in both groups.
CONCLUSIONAstragalus injection supplemented with chemotherapy could inhibit the development of tumor, decrease the toxic-adverse effect of chemotherapy, elevate the immune function of organism and improve the quality of life in patients.
Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Astragalus membranaceus ; chemistry ; CD4-CD8 Ratio ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Etoposide ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Immunoglobulin G ; blood ; Infusions, Intravenous ; Lung Neoplasms ; drug therapy ; immunology ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Phytotherapy ; Stomach Neoplasms ; drug therapy ; immunology