Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Interferons ; therapeutic use ; Interleukin-2 ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence ; Remission Induction ; Thalidomide ; therapeutic use

Interleukin-2 (IL-2) is one of the most important regulators in immune system, as it plays an essential part both in immune activation and suppression. However, as the first immunotherapy drug approved for the treatment of cancer, IL-2 is limited in clinical application by the serious adverse reactions. The long-felt needs in clinical practice, including prolonged half-lives, T cell subset specificity, and toxicity reduction can be achieved by polyethylene glycol (PEG) modification, Fc fusing, or protein mutation of IL-2. NKTR-214, the most advanced IL-2 pathway-targeted agent in clinical development for oncology, shows exciting results in treatment of melanoma in combination with nivolumab. At the same time, many more other modified molecules against cancer and autoimmune diseases are being tested in clinical research, an exciting future lying ahead for IL-2 therapeutics.
Drug Development ; Humans ; Immunotherapy/methods* ; Interleukin-2/therapeutic use* ; Melanoma/drug therapy* ; Nivolumab/therapeutic use* ; Polyethylene Glycols

The inhibition of the host's natural immune response by tumor cells was widely reported in the early phases of the development of oncology therapy, and the concept of employing the host's immune system to treat cancer, i.e. tumor immunotherapy, is not new. However, as a result of early theoretical constraints, clinical application of immunotherapy did not go smoothly and lagged significantly behind radiation and chemotherapy. The path has been winding, but the future now seems promising. Immunotherapy research has advanced enormously as a result of the maturing of immuno-editing theory and the creation of numerous technologies, despite a number of unsuccessful endeavors and clinical studies. Since around 1998, the US Food and Drug Administration (FDA) has approved a variety of tumor immunotherapies, including cytokines (interleukin-2, interferons), cancer vaccines (Provenge), immune checkpoint inhibitors (ipilimumab), and cellular therapies (chimeric antigen receptor-T (CAR-T)), signaling a boom in the field.
Cancer Vaccines/therapeutic use* ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Interferons ; Interleukin-2/therapeutic use* ; Ipilimumab ; Neoplasms/pathology* ; Receptors, Chimeric Antigen

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.
Ammonia/therapeutic use* ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Cyclooxygenase 2 ; Dendrobium/chemistry* ; Interleukin-17/therapeutic use* ; Interleukin-6 ; NF-kappa B/metabolism* ; Pharyngitis/drug therapy* ; Plant Extracts/chemistry* ; Polysaccharides/pharmacology* ; Rats ; Tumor Necrosis Factor-alpha ; Water

OBJECTIVETo evaluate the safety of enteral rehabilitative therapy in rat small bowel transplantation.

METHODSForty-eight rat recipients of allogeneic heterotopic small bowel transplantation (SD and Wistar) were randomly divided into 4 groups according to the application or not of enteral rehabilitative therapy and cyclosporine A (CsA). The pathological changes of the graft, IL-2 receptor expression in lamina propria lymphocytes, serum IL-2 concentrations, results of spleen lymphocytes transformation test and the IL-2 secretion capacity were determined and compared.

RESULTSEnteral rehabilitative therapy could promote the immune function of the recipient so as to augment the acute rejection. But such effects could be blocked by the commonly used immunosuppressant CsA. Under the immunosuppression of CsA (10 mg.kg(-1).d(-1), i.m.), application of enteral rehabilitative therapy did not induce or aggravate acute rejection.

CONCLUSIONUnder effective immunosuppression, application of enteral rehabilitative therapy is safe in rat small bowel transplantation.

Animals ; Cyclosporine ; therapeutic use ; Immunosuppressive Agents ; therapeutic use ; Interleukin-2 ; blood ; Intestine, Small ; transplantation ; Lymphocyte Activation ; immunology ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Interleukin-2 ; immunology ; Transplantation, Heterotopic ; Transplantation, Homologous

OBJECTIVETo explore the values of autologous cytokine-induced killer cells combined with rhIL-2 for therapy of elderly patients with B-cell malignant lymphoma.

METHODSEighty-five elderly patients with B-cell malignant lymphoma were treated by cytokine induced killer cells combine with rhIL-2 (CIK+IL-2 group), 85 elderly patients with B-cell malignant lymphoma treated without cytokine induced killer cells combined with rhIL-2 were used as the control group. The patients in CIK+IL-2 group and control group were divided into 4 subgroups accerding to lymphoma types: group A: diffuse large B cell lymphoma (DLBCL), group B: mucosa-associated lymphoid tissue type (MALT), group C: lymphoplas macytic lymphoma (LPL) and group D: hodgkin's lymphma (HL). The clinical effects, T-lymphocyte, β2 microglobulin level, quality of life and long-term survival were observed.

RESULTSThe levels of CD3+, CD3+/CD8+, CD3+/CD56+ after treatment in the 4 subgroups of CIK+IL-2 group were higher than levels before treatment and the control group (P<0.05); the levels of β2 microglobulin after treatment for the 4 groups were lower than before treatment and the control group (P<0.05); with 1 case death, 16 cases were turned from CRu and PR to CR; the CR rate was not significantly different among the 4 subgroups (P>0.05); the scores of physical performance, role function, cognitive function, emotional functioning, and social function after treatment in the 4 subgroups were higher than the those before treatment (P<0.05); the survival time of patients in the CIK+IL-2 group lasted for 8-76 months, their median survival time was (22.36±5.38) months; the survival of the control group lasted for 7-55 months, their median survival time was (16.15±3.62) months. The survival time of the CIK+IL-2 group was longer than that of the control group (P<0.05).

CONCLUSIONThe treatment of aged patients with B-cell malignant lymphoma by autologous cytokine-induced killer cells combined with rhIL-2 can effectively improve the T-lymphocyte subsets, β2 microglobulin level and quality of life, and can prolong survival time of patients.

Aged ; Cytokine-Induced Killer Cells ; cytology ; Humans ; Interleukin-2 ; therapeutic use ; Lymphoma, Large B-Cell, Diffuse ; therapy ; Quality of Life ; Recombinant Proteins ; therapeutic use ; T-Lymphocyte Subsets

OBJECTIVE: To explore clinical characteristics of sinonasal malignant melanoma and curative effect of the combined modality therapy. METHOD: Clinical data of 6 cases with sinonasal malignant melanoma was retrospectively analyzed. All patients received surgery and postoperative radiotherapy. In addition, 3 cases received postoperative chemotherapy which scheme was CDBT and bioimmunotherapy consisted of INF-α and IL-2 after surgery, of which, 2 cases received one cycle of preoperative chemotherapy. RESULT: Six cases were followed up. The survival time ranged from 15 months to 98 months. The average survival time was 62.7 months. Analyzed by direct method, the 1-year, 3-year and 5-year survival rates were 100%, 83% and 67% respectively. Three cases which received the combined modality therapy, of whch, 2 cases received preoperative chemotherapy have survived by now. CONCLUSION The combined modality therapy should be adopted in case of sinonasal malignant melanoma with operation indication. For the patients who can not be operated recently Postbiopsy, it was beneficial to improve the efficacy of therapy that one cycle of preoperative chemotherapy and bioimmunotherapy should be implemented.
Combined Modality Therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interleukin-2 ; therapeutic use ; Melanoma ; pathology ; therapy ; Paranasal Sinus Neoplasms ; pathology ; therapy ; Retrospective Studies ; Skin Neoplasms ; Survival Rate

OBJECTIVE: To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H₂₂ cell xenograft. METHODS: We examined the effects of treatment with different concentrations of PNS on H₂₂ cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H₂₂ cells. Mouse models bearing H₂₂ cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate. RESULTS: Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H₂₂ cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05). CONCLUSION PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H₂₂ tumor-bearing mice.
Animals ; Carcinoma, Hepatocellular/pathology* ; Cyclophosphamide/therapeutic use* ; Hemolysin Proteins ; Heterografts ; Humans ; Interleukin-2 ; Liver Neoplasms/pathology* ; Mice ; Panax notoginseng ; Saponins/therapeutic use* ; Tumor Necrosis Factor-alpha

OBJECTIVETo discuss the roles of serum interleukin-18 (IL-18), interleukin-10 (IL-10) and soluble interleukin-2R (sIL-2R) in the pathogenesis of chronic hepatitis C and to observe the effects of interferon (IFN) on the above- mentioned serum cytokines.

METHODSThe levels of above- mentioned cytokines were detected in 10 healthy individuals, 24 asymptomatic hepatitis virus C (HCV) carriers and 27 patients with chronic hepatitis C (before and after IFN treatment) using enzyme linked immunosorbent assay (ELISA).

RESULTSThe levels of the cytokines in patients with chronic hepatitis C are higher than in healthy people (P < 0.05) and in asymptomatic HCV carriers (P < 0.05). The values of the cytokines show a significant positive correlation to ALT (P < 0.05). Levels of tested cytokines decreased observably after IFN treatment (P < 0.05). The grades of the serum levels for sIL-2R and IL-10 before IFN treatment (from high to low) were categorized accordingly: non-response group > partial- response group > complete- response group (P < 0.05).

CONCLUSIONSThe tested cytokines co-participate in the pathogenesis of chronic hepatitis C, and can be used to evaluate the effect of IFN on the immune state of organisms. Furthermore, sIL-2R and IL-10 are important for predicting the anti-viral efficacy of IFN.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Middle Aged ; Receptors, Interleukin-2 ; blood ; Recombinant Proteins

OBJECTIVETo investigate the changes in serum interleukin-2 (IL-2) level in a hamster model bearing cheek pouch carcinoma after heavy ion beams irradiation.

METHODSThe serum levels of IL-2 were detected using enzyme-linked immunosorbant assay in 40 hamsters bearing cheek pouch carcinoma before and after exposure to heavy ion beam irradiation, with 8 normal animals as control.

RESULTSSerum IL-2 level was 0.16∓0.01 in the tumor-bearing hamsters before the irradiation, lower than that in the control group. After heavy ion beams irradiation at 4, 6, 8, and 12 Gy, serum IL-2 levels in the tumor-bearing hamsters were 0.18∓0.04, 0.22∓0.05, 0.15∓0.03, and 0.13∓0.04, respectively, showing a peak level after irradiation at 6 Gy and an obvious decrease following irradiation at greater doses.

CONCLUSIONHeavy ion beam irradiation causes alterations in serum IL-2 level with a dose-effect relation between them in hamsters bearing cheek pouch carcinoma.

Animals ; Cheek ; pathology ; Cricetinae ; Female ; Heavy Ions ; therapeutic use ; Interleukin-2 ; blood ; Male ; Mesocricetus ; Mouth Neoplasms ; blood ; radiotherapy