1.Inflammasomes in cancer: a double-edged sword.
Ryan KOLB ; Guang-Hui LIU ; Ann M JANOWSKI ; Fayyaz S SUTTERWALA ; Weizhou ZHANG
Protein & Cell 2014;5(1):12-20
Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.
Animals
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Carcinoma
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immunology
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pathology
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therapy
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Gastrointestinal Neoplasms
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immunology
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pathology
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therapy
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Humans
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Inflammasomes
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metabolism
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Melanoma
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immunology
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pathology
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therapy
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Neoplasms
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immunology
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pathology
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therapy
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Skin Neoplasms
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immunology
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pathology
;
therapy
2.Effects of electroacupuncture on tumor growth and immune function in the Walker-256 model rat.
Min LAI ; Shu-Mei WANG ; Wen-Liang ZHANG ; Ying WANG ; Si-Qin HUANG ; Wei DONG ; Ao LI
Chinese Acupuncture & Moxibustion 2008;28(8):607-609
OBJECTIVETo study the effect of acupuncture on tumor and its mechanism.
METHODSLiver cancer, gastric cancer and hypodermic tumor rat models were made by implantation of replicated Walker-256 cell strain. The 3 model rats were respectively divided into two groups at random, a model control group and an electroacupuncture group. The electroacupuncture groups were treated with electroacupuncture (EA) at "Zusanli" (ST 36), "Hegu" (LI 4) and "San-yinjiao" (SP 6), once each day, 15 min one session, for 15 days. The gross tumor volume and the tumor inhibitory rate, and the levels of humoral immunity index, including serum 1gG, IgM, IgA and C3, C4, and the levels of cellular immunity index, including CD4+, CD8+ and CD4+/CD8+ in the peripheral blood in each group were detected.
RESULTSThe gross tumor volumes in the EA groups were significantly smaller than those in the model control group (P<0.01). The contents of IgG, IgM and C3 in the EA groups increased significantly compared with those in the model control group (P<0.05 or P<0.01). The contents of IgA and C4 in the EA groups did not significantly change (P>0.05). The content of CD4+ and CD4+/CD8+ in the EA groups are significantly higher than those in the model control group (P<0.05 or P<0.01).
CONCLUSIONAcupuncture at "Zusanli" (ST 36), "Hegu" (LI 4) and "Sanyinjiao" (SP 6) can increase immune function and inhibit tumor growth in Walker-256 liver cancer, gastric cancer and hypodermic tumor rats.
Animals ; Carcinoma 256, Walker ; immunology ; pathology ; therapy ; Electroacupuncture ; Male ; Rats ; Rats, Wistar
3.Redirecting T cells to glypican-3 with 28.41BB.ζ and 28.ζ-41BBL CARs for hepatocellular carcinoma treatment.
Haili MA ; Siye CHEN ; Yan HE ; Jingwei HUANG ; Yanhong XU ; Chao WANG ; Cheng LEI ; Ting LU ; Shengdong XIAO ; Jinming MAO ; Yiyun XU ; Hao GUO ; Bohua LI ; Minghui ZHANG ; Xiaowen HE
Protein & Cell 2018;9(7):664-669
Antineoplastic Agents
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chemistry
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pharmacology
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Carcinoma, Hepatocellular
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drug therapy
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immunology
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pathology
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Cytokines
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immunology
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Drug Screening Assays, Antitumor
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Glypicans
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antagonists & inhibitors
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immunology
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Humans
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Ligands
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Liver Neoplasms
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drug therapy
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immunology
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pathology
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T-Lymphocytes
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drug effects
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immunology
4.Effect of p53 gene therapy on the local immunity and the efficacy of patients with nasopharyngeal carcinoma.
Yangda QIN ; Jingjin WENG ; Guiping LAN ; Haiming WEI ; Bo HUANG ; Jinjie SUN ; Yongfeng SI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(21):980-983
OBJECTIVE:
To investigate the tumor regression and local immune function in nasopharyngeal carcinoma patients treated with p53 gene therapy.
METHOD:
The two-step immunohistochemical was done to detect the expression of tumor-infiltrating lymphocytes (TIL) T-cell receptor-CD3, CD4, CD8 and B cell receptor-CD20 in the primary tumor tissue of nasopharyngeal carcinoma. Nasal endoscopy with MRI or CT was used for evaluation of tumor size.
RESULT:
The expression of CD3, CD4, CD8 was significantly increased after p53 gene treatment (P < 0.05). There was no significant change in expression of CD20 after p53 gene treatment (P > 0.05). In conventional treatment group, CD3, CD4, CD8 and CD20 (P > 0.05) did not show any significant difference. In gene therapy group at 3 months after treatment, 20 patients had achieved CR, 10 PR, 1 SD, 1 PD. In conventional treatment group, 11 patients had achieved CR, 12 PR,5 SD,3 PD. The response rate between treatment group and control group (CR+PR) was different (P < 0.05). CD3 and CD4 expression was correlated with tumor regression rate (P < 0.05, P < 0.01), and CD8 expression was correlated with the CR rate (P < 0.05).
CONCLUSION
T cells are the most proliferative cell of TII. in NPC patients after p53 gene therapy The local cellular immune status is positively correlated with tumor regression rate.
Adult
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Aged
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CD4-Positive T-Lymphocytes
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immunology
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Carcinoma
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Female
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Genes, p53
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Genetic Therapy
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Humans
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Lymphocyte Count
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Lymphocytes, Tumor-Infiltrating
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immunology
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Male
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Middle Aged
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Nasopharyngeal Carcinoma
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Nasopharyngeal Neoplasms
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immunology
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pathology
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therapy
5.Clinical study on cytokine induced killer cells therapy to laryngeal cancer after radiotherapy.
Shiwen ZHANG ; Xiaoguang HE ; Xiaojiang LI ; Yanxin REN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2011;25(2):61-63
OBJECTIVE:
To observe the immunity changes of patients after CIK cells being transfused back, and then to discuss the effects of CIK cells on curing laryngeal cancers.
METHOD:
Forty eight laryngeal cancer patients with low immune function were collected. The immunity index in the peripheral blood of patients before/after radiotherapy and after CIK cells therapy were measured and compared with normal one.
RESULT:
After radiotherapy, the percentage of CD3+, CD4+ cells declined, the percentage of CD8+ cells increased; the rate of CD4+ /CD8+ declined and the rate of Th1/Th2 reversed. There were no significant difference between the immunity indexes before and after radiotherapy (P < 0.05). After CIK cell therapy, the above indexes were improved (P < 0.05), but the values didn't returned to normal. After radiotherapy and after CIK therapy, the value of B cell didn't changed obviously (P > 0.05), while the percentage of NK cells changed obviously (P < 0.05).
CONCLUSION
Radiotherapy can restrain the immune function of the patients with laryngeal cancers. CIK therapy is safe and might improve the recent immune function of the patients.
Aged
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Carcinoma, Squamous Cell
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immunology
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pathology
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radiotherapy
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Combined Modality Therapy
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Cytokine-Induced Killer Cells
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immunology
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Humans
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Immunotherapy, Adoptive
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Killer Cells, Natural
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immunology
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Laryngeal Neoplasms
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immunology
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pathology
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radiotherapy
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Male
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Middle Aged
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Neoplasm Staging
6.Immunoregulatory activity of polysaccharopeptide and Astragalus polysaccharides on EAC tumor-bearing mice.
Jin LI ; Yi-Xi BAO ; Xuan ZHU ; Jing LIU ; Hong-Ping WANG
China Journal of Chinese Materia Medica 2008;33(8):924-927
OBJECTIVETo investigate the immunoregulatory activities of polysaccharopeptide and astragalus polysaccharides on EAC tumor-bearing mice.
METHODEhrlich's ascites carcinoma (EAC) Kunming (KM) mice were used to establish the animal model for solid tumor. Mice were randomly divided into six groups (n = 10): NS group (NS, 10 mL x kg(-1) x d(-1)), AMD group (AMD, 4 mg x kg(-1) x d(-1), 0.2 mL, only for the first 3 days), PSP group (PSP, 250 mg x kg(-1) x d(-1), 0.2 mL), APS group (APS, 250 mg x kg(-1) x d(-1), 0.2 mL), complex prescription group (PSP + APS, 250 mg x kg(-1) x d(-1), 0.1 mL) and combined treat group (AMD + PSP + APS, same dosage as above). After thirty days of treatment, immunocytochemical method was employed to detect the changes of T-lymphocyte subsets in the PBMC of tumor-bearing mice. Subsequently, the organ indexes and tumor inhibition rate were calculated and compared with those of control group.
RESULTPercentage of CD3+, CD4+ T-cell and the ratio of CD4+/CD8+ were obviously prominence in the PSP and PSP + APS groups compared with those of NS group (0.05), percentage of CD8+ T-cell was significantly decreased compared with that of AMD group; percentage of CD3+, CD4+ T-cell were obviously increased in AMD + PSP + APS group relative to that of AMD group; the thymus index of AMD group was significantly decreased compared with that of NS group, but the thymus index of AMD + PSP + APS group was obviously increased compared with that of AMD group; the weight of tumor in each administration group was significantly decreased compared with that of NS group.
CONCLUSIONPSP and PSP + APS complex prescription showed the remarkable immunoregulation on EAC mice with chemotherapy or not.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; Astragalus Plant ; chemistry ; immunology ; Carcinoma, Ehrlich Tumor ; drug therapy ; immunology ; pathology ; Female ; Mice ; Polysaccharides ; administration & dosage ; immunology ; pharmacology ; therapeutic use ; Proteoglycans ; administration & dosage ; immunology ; pharmacology ; therapeutic use ; T-Lymphocyte Subsets ; drug effects ; immunology
7.Significance of changes in local immunity in patients with hepatocellular carcinoma after percutaneous microwave coagulation therapy.
Jing ZHANG ; Baowei DONG ; Ping LIANG ; Xiaoling YU ; Li SU ; Dejing YU ; Xiaolong JI ; Guo YU
Chinese Medical Journal 2002;115(9):1367-1371
OBJECTIVETo assess the local immune response in patients with hepatocellular carcinoma after percutaneous microwave coagulation therapy (PMCT).
METHODSSeventy-eight patients with hepatocellular carcinoma underwent PMCT. Both cancerous and adjacent liver tissue were taken before, and 3, 17 and 30 days after PMCT using ultrasound-guided liver biopsy. Specimens were stained by immunohistochemical techniques for detecting CD3, CD45RO, CD56, CD68, and CD20 positive cells.
RESULTSA few CD3, CD45RO, CD56, CD68 and CD20 positive cells were observed in the cancer stroma and surrounding sinusoids in liver tissue pre-PMCT. The number of immunocytes, except for CD20 positive cells, was significantly increased both within the cancer and the adjacent liver tissue, with a larger increase in tumor tissue at day 3 post-PMCT compared with pre-PMCT. These immunocytes were enlarged in size. The number of CD3, CD45RO and CD56 positive cells peaked at day 17 and CD68 positive cells peaked at days 3 post-PMCT. At day 30 post-PMCT, this increase still existed. These infiltrating immunocytes distributed in the parenchyma of the tumor, and within the lumen of small blood vessels after PMCT. In addition, more infiltrated immune cells were seen in cancer cell spaces.
CONCLUSIONSA change in immunocyte infiltration takes place in number, configuration and location after patients with HCC are treated with percutaneous microwave coagulation, suggesting that local immune function is enhanced post-PMCT.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; analysis ; Carcinoma, Hepatocellular ; immunology ; pathology ; therapy ; Electrocoagulation ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; immunology ; pathology ; therapy ; Male ; Microwaves ; therapeutic use ; Middle Aged ; T-Lymphocytes ; immunology
8.Anti-tumor and immune-modulating effect of decoction in mice bearing hepatoma H22 tumor.
Limei CHEN ; Tong JIN ; Chuntao NING ; Suli WANG ; Lijie WANG ; Jingming LIN
Journal of Southern Medical University 2019;39(2):241-248
OBJECTIVE:
To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model.
METHODS:
Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay.
RESULTS:
Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01).
CONCLUSIONS
decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.
Animals
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Antineoplastic Agents, Phytogenic
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pharmacology
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Carcinoma, Hepatocellular
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drug therapy
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immunology
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metabolism
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pathology
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Drugs, Chinese Herbal
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pharmacology
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Kidney
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drug effects
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Liver
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drug effects
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pathology
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Liver Neoplasms
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drug therapy
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immunology
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metabolism
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pathology
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Mice
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Necrosis
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Neoplasm Proteins
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metabolism
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Random Allocation
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Up-Regulation
9.Progress in studies on anti-hepatoma effect of traditional Chinese medicine by adjusting immune function.
China Journal of Chinese Materia Medica 2007;32(4):281-284
We surveyed the literatures domestic and abroad, and summarized traditional Chinese medicine (single or complex prescription) with anti-hepatoma effects by adjusting immune function. Traditional Chinese medicine showed great advantages in improving the immune system function of the organism in various ways, so they could prohibit the generation and development of tumor, lessen the damage caused by chemotherapeutics, increase the sensitivity of chemotherapeutics, strengthen immune surveillance to tumor cells, elevate living quatity of patients and prolong their living time. It is very promising to exploit much more effective anti-tumor drugs from TCM.
Animals
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Antineoplastic Agents, Phytogenic
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therapeutic use
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Carcinoma, Hepatocellular
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drug therapy
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immunology
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pathology
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Drugs, Chinese Herbal
;
isolation & purification
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therapeutic use
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Humans
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Killer Cells, Natural
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drug effects
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immunology
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Liver Neoplasms
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drug therapy
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immunology
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metabolism
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Lymphocyte Activation
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drug effects
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Phytotherapy
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Plants, Medicinal
;
chemistry
10.Neoadjuvant chemotherapy with paclitaxel and cisplantin or carboplatin for patients with locally advanced uterine cervical cancer.
Rong ZHANG ; Bin LI ; Pin BAI ; Hong-Jun LI ; Shu-Min LI ; Ling-Ying WU ; Wei LI
Chinese Journal of Oncology 2011;33(8):616-620
OBJECTIVETo investigate the efficacy and toxicity of neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin for patients with locally advanced cervical cancer.
METHODSA total of 70 patients with locally advanced cervical cancer were treated with neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin in our department from July 2007 to May 2010. The stage distribution among the patients included 45 stage IB2, 21 stage IIa, and 4 stage IIb. Of the 70 patients, 6 were G1, 26 were G2, 32 were G3, and the rest 6 patients were not histologically classified. Sixty-five patients had squamous cell carcinoma, 3 had adenocarcinoma, and 2 patients had adenosquamous cell carcinoma. The clinicopathological parameters were analyzed, and their impact on tumor response were investigated.
RESULTSOf the 70 patients, 14 (20.0%) showed a complete response, 37 (52.9%) had a partial response to chemotherapy, making an overall response rate of 72.9%. Sixty-eight (95.7%) patients underwent surgery, and among them 12 (17.1%) pathological CR were identified. Eleven (16.2%) patients were found to have lymph node metastasis after surgery. Response rates of stage Ib2 and IIa patients were 73.7% and 52.3%, respectively, P<0.05. Patients with SCC exhibited a better response rate than patients with adenocarcinoma and adenosquamous cell carcinoma (73.8% vs. 60.0%). Initial tumor volume, histological classification and cycles of neoadjuvant chemotherapy were not significantly correlated with the response rate.
CONCLUSIONPaclitaxel and carboplatin or cisplatin regimen is a promising therapy with definite short-term efficacy, can improve the resection rate with tolerable side effects, and is an applicable option of treatment for patients with locally advanced cervical cancer in the neoadjuvant setting.
Adenocarcinoma ; drug therapy ; immunology ; pathology ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Adenosquamous ; drug therapy ; immunology ; pathology ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Remission Induction ; Serpins ; metabolism ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; surgery