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

Brain metastasis was a common metastasis site and leading cause of death in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors had improved survival of NSCLC patients with positive drive gene. It also brings good news to NSCLC patients with positive drive gene and brain metastases. However, there is still no effective treatment for NSCLC patients with drive gene-negative and brain metastases. In recent years, immunotherapy has made breakthrough progress and become important first and second line treatment options of NSCLC especially in patients with drive gene-negative. The role of immunotherapy in specific populations of NSCLC-brain metastasis patients, especially drive gene-negative patients has become the focus of attention. In this report, we review the research progress of immunotherapy in NSCLC with brain metastases, especially in driver-negative patients, analyze the limitations of existing research and future challenge.
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Brain Neoplasms ; immunology ; secondary ; therapy ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Humans ; Immunotherapy ; methods ; Lung Neoplasms ; genetics ; pathology ; Patient Selection

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

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 ; Carcinoma ; immunology ; pathology ; therapy ; Gastrointestinal Neoplasms ; immunology ; pathology ; therapy ; Humans ; Inflammasomes ; metabolism ; Melanoma ; immunology ; pathology ; therapy ; Neoplasms ; immunology ; pathology ; therapy ; Skin Neoplasms ; immunology ; pathology ; therapy

Adenocarcinoma ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Radiotherapy, Adjuvant ; Retrospective Studies ; Serpins ; metabolism ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery

OBJECTIVETo reveal the different molecular mechanisms between Chinese drugs for activating blood (CDAB) and Chinese drugs for nourishing qi and activating blood (CDNQAB) in the metastasis process of Lewis lung carcinoma, thus providing experimental reliance for Chinese drugs to reverse immune escape.

METHODSThe inhibition rate of lung metastasis was observed in each group. The dynamic percentage and ratio changes of Th17 and Treg cells in spleen CD4+ T lymphocytes were detected using flow cytometry. The dynamic levels of IL-17, IL-23, and gamma interferon (IFN-gamma) in the culture supernatant of CD4+ T lymphocytes were detected by ELISA. The dynamic mRNA expressions of Foxp3 and RORgammat in CD4+ T lymphocytes were detected by RT-PCR.

RESULTSCDNQAB (sapanwood +astragalus) showed better lung metastasis inhibiting rate than CDAB (sapanwood alone) (P<0.05), similar to the effects of cyclophosphamide (P>0.05). Except the CDNQAB group, spleen Th17 and Treg cells showed a rising tendency in mice of each tumor-bearing group. The effectors of Th17 and Treg cells (IL-17, IL-23, and IFN-gamma) and key transcription molecules of Th17 and Treg cells (RORgammat and Foxp3) showed dynamic changes corresponding to Th17 and Treg cells.

CONCLUSIONSThe immune inflammatory reactions of CDNQAB (sapanwood +astragalus) were superior to those of CDAB (sapanwood alone) and of cyclophosphamide during the process of inhibiting tumor immunotolerance and of the formation of tumor. All drugs showed certain inhibition on the mechanisms for neoplasm metastasis. But CD-NQAB was superior to CDAB and chemotherapeutics.

Animals ; Carcinoma, Lewis Lung ; drug therapy ; immunology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; immunology ; Interleukin-17 ; immunology ; Interleukin-23 ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; T-Lymphocytes, Helper-Inducer ; immunology ; T-Lymphocytes, Regulatory ; immunology

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 ; Aged ; CD4-Positive T-Lymphocytes ; immunology ; Carcinoma ; Female ; Genes, p53 ; Genetic Therapy ; Humans ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; immunology ; pathology ; therapy

OBJECTIVETo construct a recombinant plasmid pIRES-GM-CSF-IL-21, and to investigate its antitumor effect on tumors in the mice.

METHODSFifty Bal b/c mice were included in this study. Cultured hepatoma H22 cells were inoculated in the left lobe of the liver to develop orthotopically transplanted liver tumor models. The mice with orthotopically transplanted liver tumor were randomly divided into 5 groups (n = 10): (1) Each mouse received injection of recombinant plasmid pIRES-GM-CSF-IL-21; (2) Received injection of plasmid pIRES-GM-CSF; (3) pIRES-IL-21; (4) Received injection of ampty plasmid pIRES (H22/neo group); (5) Received injection of PBS (H22 group) via the tail vein, respectively. Therefore, the anti-tumor effect was induced by both GM-CSF and IL-21, or by either of them alone. The serum levels of IFN-γ and IL-2 were detected by ELISA, and the cytotoxicity of spleen NK and CTL cells were tested by MTT colorimetry.

RESULTSComparing with the H22 and H22/Neo groups, the tumor weight in the mice of H22/GM-CSF group was (0.603 ± 0.223) g, H22/IL21-treated group (0.583 ± 0.290) g and H22/GM-CSF-IL21-treated group (0.303 ± 0.323) g, significantly lower than that in the H22 group [(1.591 ± 0.280) g] and H22/Neo group [(1.489 ± 0.155) g]. Among them the tumor growth was most significantly inhibited in the H22/GM-CSF-IL-21 group (0.303 ± 0.323) g, compared with that of H22 and H22/neo groups (P < 0.01). But there was no significant difference between the tumor weights of the H22/GM-CSF group and H22/IL-21 group, and between the tumor weights of the H22 and H22/Neo groups (P > 0.05). The levels of IFN-γ and IL-2 in peripheral blood of mouse models treated with H22/GM-CSF-IL-21 were significantly increased than that in the H22/GM-CSF group and H22/IL-21 group (all P < 0.01), but significantly decreased in the H22group and H22/Neo group (P < 0.01). The anti-tumor activity of splenic NK cells and CTLs in the H22/GM-CSF-IL21 group was significantly enhanced (P < 0.01), compared with the significantly decreased in the H22 and H22/Neo groups.

CONCLUSIONSOur results demonstrate apparent antitumor effect of the plasmid pIRES-GM-CSF-IL-21 on the orthotopically transplanted liver tumor in mice. The combination of both pIRES-GM-CSF and IL-21 is more effective than that of pIRES/IL21 or pIRES/GM-CSF treatment alone. In addition, the plasmid pIRES-GM-CSF-IL-21 can also promote the secretion of IFN-γ and IL-2 in vivo, and enhance the cytotoxic activity of splenic NK and CTLs against the transplanted liver tumor.

Animals ; Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Cell Line, Tumor ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; Immunotherapy ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Interleukins ; genetics ; Killer Cells, Natural ; immunology ; Liver Neoplasms ; blood ; pathology ; therapy ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Plasmids ; therapeutic use ; Random Allocation ; Recombinant Proteins ; therapeutic use ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Burden

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

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 ; Carcinoma, Squamous Cell ; immunology ; pathology ; radiotherapy ; Combined Modality Therapy ; Cytokine-Induced Killer Cells ; immunology ; Humans ; Immunotherapy, Adoptive ; Killer Cells, Natural ; immunology ; Laryngeal Neoplasms ; immunology ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging