Antineoplastic Agents ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; pathology ; Cytokines ; immunology ; Drug Screening Assays, Antitumor ; Glypicans ; antagonists & inhibitors ; immunology ; Humans ; Ligands ; Liver Neoplasms ; drug therapy ; immunology ; pathology ; T-Lymphocytes ; drug effects ; immunology

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 ; Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; Liver ; drug effects ; pathology ; Liver Neoplasms ; drug therapy ; immunology ; metabolism ; pathology ; Mice ; Necrosis ; Neoplasm Proteins ; metabolism ; Random Allocation ; Up-Regulation

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 ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Humans ; Killer Cells, Natural ; drug effects ; immunology ; Liver Neoplasms ; drug therapy ; immunology ; metabolism ; Lymphocyte Activation ; drug effects ; Phytotherapy ; Plants, Medicinal ; chemistry

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.
Animals ; Antibodies, Monoclonal/genetics/*immunology ; Antibody-Dependent Cell Cytotoxicity ; Bile Ducts, Intrahepatic/drug effects/immunology/pathology ; CHO Cells ; Cell Adhesion/drug effects ; Cell Proliferation/drug effects ; Cholangiocarcinoma/*drug therapy/immunology/pathology ; Cricetinae ; Disease Models, Animal ; Endocytosis/drug effects ; Humans ; Immunoglobulin G/genetics/*immunology ; Liver Neoplasms/*drug therapy/immunology/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neural Cell Adhesion Molecule L1/genetics/*immunology/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/immunology/metabolism/*therapeutic use

OBJECTIVETo observe the short-term efficacy and safety of Shenqi mixture (SQM) combined with microwave coagulation in treating primary hepatocellular carcinoma (HCC).

METHODSSeventy-two patients with primary HCC of stage II-III, Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and randomly assigned into two groups, the treated group and the control group, 36 in each. Microwave therapy was applied to both groups by double leads, 60 W, 800 sec once a week for two weeks. To the treated group, SQM was given additionally through oral intake of 20 ml, three times a day for 1 month. The changes in tumor size, main symptoms, serum level of alpha-fetoprotein (AFP), immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group.

RESULTS(1) In the SQM treated group, after treatment 3 patients got completely remitted (CR), 24 partial remitted (PR), 4 unchanged (NC) and 5 progressively deteriorated (PD), the effective rate being 75.00%; while in the control group, 1 got CR, 19 PR, 9 NC and 7 PD, the effective rate being 55.56%. Comparison of the effective rate between the two groups showed significant difference (P < 0.05). (2) AFP level decreased after treatment in both groups, but the decrement in the treated group was significantly higher than that in the control group (P < 0.01). (3) After treatment, in the treated group, CD3(+), CD4(+), CD4(+)/CD8(+) and NK activity were improved, Karnofsky scores increased and liver function bettered, with these improvements significantly superior to those in the control group (P < 0.01). (4) The improvement in symptoms such as hepatic region pain, fever, weakness, poor appetite and jaundice in the treated group after treatment was also superior to that in the control group (P < 0.01). (5) The 12-month, 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group, showing significant difference (P < 0.05).

CONCLUSIONCombined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence, but also enhance the cellular immunity of organism. It is one of the effective therapies for patients with middle-advanced hepatocarcinoma, who have lost the chance of surgical operation. It could improve clinical symptoms, elevate the quality of life, prolong the survival period of patients, but shows no evident adverse reaction.

Adult ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; mortality ; pathology ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Electrocoagulation ; methods ; Female ; Humans ; Leukocyte Count ; Liver Function Tests ; Liver Neoplasms ; drug therapy ; immunology ; mortality ; pathology ; Male ; Microwaves ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; alpha-Fetoproteins ; metabolism

Animals ; Carcinoma, Hepatocellular ; blood supply ; pathology ; therapy ; Cell Line, Tumor ; Cells, Cultured ; Cytotoxicity, Immunologic ; immunology ; Female ; Humans ; Interleukin-12 ; pharmacology ; Interleukin-2 ; pharmacology ; Killer Cells, Natural ; cytology ; drug effects ; immunology ; Liver Neoplasms, Experimental ; blood supply ; pathology ; therapy ; Lymphocyte Activation ; drug effects ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Random Allocation ; Xenograft Model Antitumor Assays

OBJECTIVETo study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells.

METHODSCells culture, flow cytometric analysis, affinity chromatography for protein purification, SDS-PAGE, Western-blotting and animal experiment were used.

RESULTSHSP70-PC immunization rendered protective effect to both naive tumorl-bearing mice. All of the naive mice obtained complete resistance to Hcaf cell attack; 40% of the tumor-bearing mice survived for over 90 days, whereas the mice of control group died within 2 weeks (P < 0.01). CD8+ subset of T lymphocytes in the peripheral blood of immunized mice increased by 12%.

CONCLUSIONHSP70-PC induces anti-tumor immunity via activation of cytotoxic T lymphocytes (CTLs), and it possesses strong tumor vaccine effect. Our research adds more evidence to support the clinical use of HSP70-PC to fight human cancers.

Animals ; CD8 Antigens ; blood ; Cell Membrane ; chemistry ; HSP70 Heat-Shock Proteins ; biosynthesis ; isolation & purification ; therapeutic use ; Liver Neoplasms, Experimental ; chemistry ; drug therapy ; immunology ; pathology ; Mice ; Neoplasm Transplantation ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Cells, Cultured

OBJECTIVETo prepare nanospheres coupled with the anti-human liver cancer monoclonal antibody HAb18 and evaluate its immunoreactivity and antitumor effects.

METHODSThe nanosphere coupled with the antibody was prepared by intermolecular cross-linking the anti-human liver cancer monoclonal antibody, HAb18, with human serum albumin nanospheres containing ADM [termed HAS(ADM)-NS] via a new hetero-bifunctional cross-linker SPDP. Condensation test and immunofluorescence assay were used to evaluate the immunoreactivity of the nanospheres, and specific binding of HAb18-HAS(ADM)-NS with liver cancer cell line SMMC-7721 was observed with optical and electron microscopes. The specific cytotoxic effects on the target cells were evaluated in vitro by MTT assay. HAb18-HAS(ADM)-NS, HAS(ADM)-NS and ADM were injected separately into nude mice bearing human liver carcinoma to evaluate the inhibitory activity of HAb18-HAS(ADM)-NS in vivo.

RESULTSThe immunoreactivity of HAb18-HAS(ADM)-NS was well preserved. HAb18-HAS(ADM)-NS could bind specifically with the SMMC-7721 cells. The IC(50) of HAb18-HAS(ADM)-NS against SMMC-7721 cells was 44.6 microg/ml, lower than that of HAS(ADM)-NS (345.5 microg/ml) and ADM (365.5 microg/ml). The inhibition rate of HAb18-HAS(ADM)-NS on the growth of liver cancer xenografts was significantly higher than that of HAS(ADM)-NS and ADM (P<0.001).

CONCLUSIONHAb18-HAS(ADM)-NS has immunoreactivity and can actively and specifically target the liver cancer cells. The antitumor activity of HAb18-HAS(ADM)-NS is significantly higher than that of HAS(ADM)-NS and ADM.

Animals ; Antibodies, Monoclonal ; administration & dosage ; immunology ; Antibodies, Neoplasm ; immunology ; Antineoplastic Combined Chemotherapy Protocols ; immunology ; therapeutic use ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; immunology ; Female ; Humans ; Immunotoxins ; administration & dosage ; immunology ; Liver Neoplasms ; drug therapy ; immunology ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanospheres ; administration & dosage ; Treatment Outcome ; Xenograft Model Antitumor Assays ; methods

AIMTo study the antitumor effects of an immunoconjugate composed of lidamycin (LDM) and monoclonal antibody 3G11 (3G11-LDM conjugate).

METHODS3G11-LDM conjugate was prepared by using 2-iminothiolane (2-IT) and m-maleimidobenzoyl-N-hydroxy-succimide ester (MBS) as crosslinkers. The molecular weight of the conjugate was measured on non-reduced SDS-PAGE gel. Immunoreactivity of 3G11-LDM conjugate to type IV collagenase or to hepatoma 22 cells was determined by ELISA. The cytotoxicity of the immunoconjugate to hepatoma 22 cells was examined by MTT assay. Antitumor effects of the 3G11-LDM conjugate in vivo were evaluated using subcutaneously transplanted hepatoma 22 tumor model in mice.

RESULTSThe molecular weight of 3G11-LDM conjugate was approximately 160 kDa. 3G11-LDM conjugate retained part of the immunoreactivity of 3G11 to type IV collagenase and hepatoma 22 cells. As compared with free LDM, 3G11-LDM conjugate showed stronger cytotoxicity to hepatoma 22 cells. When administered intravenously (i.v. x 2 on day 1 and 8), 3G11-LDM conjugate, at doses of 0.05 and 0.10 mg.kg-1, inhibited the growth of hepatoma 22 in mice by 87.8% and 97.2% on day 11, respectively, whereas the unconjugated LDM at 0.05 mg.kg-1 inhibited tumor growth by 67.1%. The median survival times for tumor-bearing mice of untreated control, LDM at 0.05 mg.kg-1, 3G11-LDM at 0.05 mg.kg-1, and 3G11-LDM at 0.10 mg.kg-1 were 34, 41.5, 60.5 and 94 d, respectively. Evidently 3G11-LDM was more effective than free LDM in suppressing tumor growth and prolonging the life span of tumor-bearing mice.

CONCLUSION3G11-LDM conjugate shows much stronger antitumor effects than equivalent dose of free LDM and may have promising therapeutic potential in cancer treatment.

Aminoglycosides ; administration & dosage ; therapeutic use ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal ; immunology ; Cell Division ; drug effects ; Disease Models, Animal ; Enediynes ; Female ; Immunoconjugates ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Matrix Metalloproteinase 2 ; immunology ; Matrix Metalloproteinase 9 ; immunology ; Mice ; Neoplasm Transplantation ; Random Allocation ; Tumor Cells, Cultured

OBJECTIVE: To investigate the tumor-suppression effect of PA combined with GM-CSF, TNF-alpha and IL-4 on cord blood mononuclear cells (CBMC). METHODS: The mononuclear cells were isolated from human umbilical cord blood and cultured with polyacttin A (PA), GM-CSF + TNF-alpha + IL-4 (GTI), and GTI + PA (GTIP) respectively. Six days later, surface antigen expression of the cultured cells, including CD1a and CD83, which were the specialized markers of dendritic cell (DC), were analyzed by immunohistochemistry technique. The CBMC were cultured with GTI for 24 h to enhance DC, then were added apoptotic/necrotic Hela/HepG2 tumor cells, and finally PA was co-cultured. The antitumor cytotoxicity of CBMC was measured by MTT assay. RESULTS: After the culture, CD1a and CD83 positive cell rates of the PA group inreased significantly, reaching (19.63 +/- 3.61)%, (9.28 +/- 4.31) % respectively, much higher than that of the control, but lower than that of the GTI group. The killing rate to the tumor cells of CBMC cultured with GTIP increased remarkably, much higher than the control, GTI and PA groups. After tumor antigens were added to the CBMC of GTIP group (GTIP + Tc), the killing rate increased. CONCLUSION PA not only promotes the proliferation and maturation of cord blood derived DC, but also improves the tumor-suppression effect of CBMC cultured with GTI.
Antigens, CD ; biosynthesis ; genetics ; Antigens, CD1 ; biosynthesis ; genetics ; Cells, Cultured ; Fetal Blood ; cytology ; Glycopeptides ; pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; HeLa Cells ; Humans ; Immunoglobulins ; biosynthesis ; genetics ; Immunotherapy ; Interleukin-4 ; pharmacology ; Leukocytes, Mononuclear ; drug effects ; immunology ; Liver Neoplasms ; pathology ; therapy ; Membrane Glycoproteins ; biosynthesis ; genetics ; Neoplasms ; therapy ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; pharmacology