OBJECTIVE: To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models. METHODS: PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. RESULTS: CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate. CONCLUSION CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Mice ; Osteosarcoma ; drug therapy ; Publication Bias ; Risk Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differentiation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen (BS), a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD₄^-CD₈⁺ T lymphocytes and the secretion of downstream cytokines in mice via down-regulating the expression of programmed death-ligand 1 (PD-L1) on the tumor cells' surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.
Animals ; Antineoplastic Agents/pharmacology* ; B7-H1 Antigen/antagonists & inhibitors* ; Benzene Derivatives/therapeutic use* ; CD8-Positive T-Lymphocytes/drug effects* ; Hep G2 Cells ; Humans ; Liver Neoplasms/pathology* ; Male ; Mice ; Organoselenium Compounds/therapeutic use* ; STAT3 Transcription Factor/physiology* ; Thioredoxin-Disulfide Reductase/antagonists & inhibitors* ; Tumor Burden/drug effects*

OBJECTIVETo explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo.

METHODSThirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively.

RESULTSCompared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05).

CONCLUSIONWCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.

Adenocarcinoma ; drug therapy ; pathology ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fas Ligand Protein ; genetics ; metabolism ; Female ; Fluorescent Antibody Technique ; Humans ; In Situ Nick-End Labeling ; Lung Neoplasms ; drug therapy ; pathology ; Mice, Nude ; RNA, Messenger ; genetics ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays ; fas Receptor ; metabolism

ObjectiveTo analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment.

METHODSWe retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15).

RESULTSThe average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either.

CONCLUSIONSHypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

Adult ; Chorionic Gonadotropin ; therapeutic use ; Follicle Stimulating Hormone ; blood ; Humans ; Hypogonadism ; diagnosis ; etiology ; therapy ; Luteinizing Hormone ; blood ; Male ; Pituitary Neoplasms ; blood ; complications ; pathology ; therapy ; Prolactinoma ; blood ; complications ; pathology ; therapy ; Retrospective Studies ; Sella Turcica ; Spermatogenesis ; Spermatozoa ; Testis ; anatomy & histology ; drug effects ; Testosterone ; analogs & derivatives ; blood ; therapeutic use ; Tumor Burden

OBJECTIVETo explore the effect and safety of topical propranolol hydrochloride gel for treatment of infantile hemangioma. METHODS Thirty nude mice (BALA/c, nu/nu) were divided into three groups, experimental group, control group and normal group. Human hemangioma endothelial cells cultured in vitro were injected subcutaneously in experimental group and control group to establish infantile hemangioma model. Topical propranolol hydrochloride gel was applied on the surface of the hemangioman in experimental group and normal group. Tumor volumn change and the skin situations (edema, erythema, ulceration) were observed at different periods. 45 days after cell injection, the mice were killed and plasma concentration was detected in the experimental group and the control group by high performance liquid chromatography with evaporative light scattering detector, and tumors were subjected to histopathologic examination and immunohistochemistry for CD31 and CD34. The correlation between volumes and plasma concentration was statistically analyzed with SPSS 13.0 paired samples t test with α = 0.05 as statistical standard.

RESULTSAt 45 days, the volume of the tumor in control group was (366.57 ± 17.08) mm³, which has a significant difference as compared to the experimental group (13.36 ± 2.09) mm³ (P < 0.05); and the plasma concentration was (16.83 ± 1.53) ng/ml in experimental group, and (18.42 ± 2.21) ng/ ml in normal group (P > 0.05 ). Topical propranolol hydrochloride gel (3%) has no irritation to nude mice's skin.

CONCLUSIONSTopical application of 3% propranolol hydrochloride gel is effective and safe for the treatment of infantile hemangioma.

Animals ; Gels ; administration & dosage ; Hemangioma ; drug therapy ; pathology ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Propranolol ; administration & dosage ; Skin Neoplasms ; drug therapy ; pathology ; Tumor Burden ; drug effects

OBJECTIVETo discuss the anti-tumor effect of Xihuang pill on tumor-bearing rats and its effect on the immune clearance function of tumor-bearing organisms.

METHODWalker256 tumor cells were adopted to establish the tumor-bearing rat model. The rats were randomly divided into five groups: the normal control group, the model control group, the lentinan group and Xihuang pill low dose, middle dose and high dose groups, with 10 rats in each group, and continuously treated and given drugs for 14 d after modeling. Blood and tumors were collected from abdominal aorta to calculate the tumor inhibition rate. The content of CD3+, CD4+, CD8+ T cells and adhesion molecule B7-1 (CD80) in peripheral blood were detected by flow cytometry (FCM). The expressions of IL-2 and IFN-gamma in were determined by ELISA.

RESULTThe tumor inhibition rate of the Xihuang pill high dose group was 33. 1 percent. Compared with the model group, the Xihuang pill large dose group showed significantly low IL-2, IFN-gamma, CD3+, CD4+, B7-1 in peripheral blood, with statistical significance in their differences (P < 0.05).

CONCLUSIONXihuang pill could show its anti-tumor effect by enhancing the immune clearance function and increasing IL-2, IFN-gamma, CD3+ T, CD4+ T, B7-1 in peripheral blood.

Animals ; Antineoplastic Agents ; administration & dosage ; B7-1 Antigen ; genetics ; immunology ; Breast Neoplasms ; drug therapy ; genetics ; immunology ; CD4-Positive T-Lymphocytes ; drug effects ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Flow Cytometry ; Humans ; Immune System ; drug effects ; Immunologic Factors ; administration & dosage ; Interferon-gamma ; genetics ; immunology ; Interleukin-2 ; genetics ; immunology ; Rats ; Rats, Wistar ; Tumor Burden ; drug effects

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; pharmacology ; Drug Carriers ; chemistry ; Female ; Liposomes ; chemistry ; Male ; Mice ; Nanoparticles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacokinetics ; pharmacology ; Particle Size ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma 180 ; pathology ; Silicon Dioxide ; chemistry ; Tumor Burden ; drug effects

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.
Animals ; Antineoplastic Agents, Alkylating ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclophosphamide ; analogs & derivatives ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms, Experimental ; pathology ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tumor Burden ; drug effects

OBJECTIVETo study the radiosensitizing effect of resveratrol on human hypo pharyngeal squamous cell carcinoma (FaDu) cells in nude mice.

METHODSForty-three nude mice bearing FaDu cell xenografts were randomized into control group, radiotherapy (12 Gy) group, resveratrol treatment (50 mg/kg) group, and radiotherapy plus resveratrol treatment group. After corresponding treatments, the tumor volume in the mice was measured every 3 days, and the microvessel density (MVD) in the tumor was evaluated with CD31 immunofluorescence histochemical staining.

RESULTSThe tumor volume and weight were the smallest in mice receiving radiotherapy plus resveratrol treatment (P<0.05) but comparable between those having resveratrol treatment alone and the control mice. Radiotherapy plus resveratrol treatment resulted in a tumor inhibition rate of 76.64% and a significantly decreased MVD in the tumor compared with the other 3 groups.

CONCLUSIONResveratrol can produce a radiosensitizing effect on human hypopharyngeal carcinoma in nude mice.

Animals ; Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; Cell Line, Tumor ; radiation effects ; Head and Neck Neoplasms ; drug therapy ; radiotherapy ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Mice ; Mice, Nude ; Radiation Tolerance ; Radiation-Sensitizing Agents ; pharmacology ; Stilbenes ; pharmacology ; Transplantation, Heterologous ; Tumor Burden

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
Animals ; Antineoplastic Agents ; pharmacokinetics ; pharmacology ; Area Under Curve ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Guinea Pigs ; Hemolysis ; drug effects ; Humans ; Male ; Mice ; Mice, Nude ; Micelles ; Particle Size ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Prostatic Neoplasms ; drug therapy ; pathology ; Rats ; Rats, Sprague-Dawley ; Taxoids ; chemistry ; pharmacokinetics ; pharmacology ; Treatment Outcome ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays