OBJECTIVETo extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.

METHODSAn MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.

RESULTSThere were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.

CONCLUSIONSTIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".

Animals ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cyclooxygenase 2 ; genetics ; metabolism ; Extracellular Fluid ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Stomach Neoplasms ; metabolism ; secondary ; Telomerase ; genetics ; metabolism ; Tumor Microenvironment ; physiology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo investigate the therapeutic effects of Jiedu granules, a Chinese medicine (CM) compound, plus cinobufacini injection, which was extracted from skin of Bufo bufo gargarizans Cantor, to prevent the recurrence of hepatocellular carcinoma (HCC) after surgical resection.

METHODSIn this case-control trial, a total of 120 patients who stayed in Changhai Hospital were enrolled from December 2001 to December 2006. Sixty patients were treated with Jiedu granules plus cinobufacini injection to prevent tumor recurrence after operation (CM group) and 60 patients were treated with transcatheter arterial chemoembolization (TACE) after operation (TACE group). Progression-free survival (PFS) and overall survival (OS) rates were determined to evaluate the therapeutic effects of post-operative management of patients with HCC.

RESULTSPFS in the CM group was 18.07 months [95% confidence interval (CI): 12.49-23.65] and the 1-, 2-, 3-, 4- and 5-year PFS rates were 61%, 39%, 26%, 22% and 12%, respectively. PFS in the TACE group was 8.03 months (95% CI: 6.63-9.44) and the 1-, 2-, 3-, 4- and 5-year PFS rates were 34%, 11%, 7%, 2% and 0%, respectively. There was significant difference in survival rate between the two groups (P<0.01). The mean survival time (MST) of patients in the CM group was 49.53 months versus 39.90 months of the TACE group. The 1-, 2-, 3-, 4- and 5-year survival rates were 90%, 82%, 80%, 70% and 63%, respectively, in the CM group, and 79%, 70%, 60%, 60% and 36%, respectively, in the TACE group. There was significant difference in survival time between the two groups (P=0.045).

CONCLUSIONSJiedu granules plus cinobufacini injection, a combination that is commonly used for post-operation management of HCC, can postpone tumor recurrence and metastasis, prolong the survival time and increase the survival rate of post-surgical patients with HCC. However, these findings need to be confirmed in a prospective, randomized controlled trial.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amphibian Venoms ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; surgery ; Case-Control Studies ; Chemoembolization, Therapeutic ; methods ; Combined Modality Therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Injections, Intra-Arterial ; Liver Neoplasms ; drug therapy ; mortality ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Retrospective Studies ; Young Adult

Malignant tumors are one of the leading causes of death in the world. Considerable progresses have been made on the treatment of tumors in recent decades, especially in the prevention, early diagnosis and the model changing of therapeutics. But we are still facing tough challenges, including the increasing treatment burden and limited improvement of efficacy. In China, Chinese medicine (CM) provides a powerful arsenal to fight against tumors. CM can be well applied to the onset and progression of tumors in China, bearing the characteristics of multi-target, multi-phase and multi-effect. But there are also many problems demanding urgent attention in the use of CM. Some most debated problems in this field were summarized. We should upgrade our concepts in using CM, find its position scientifically, and establish evidence of its effect by high quality clinical research.
Humans ; Integrative Medicine ; trends ; Medical Oncology ; trends ; Medicine, Chinese Traditional ; trends ; Neoplasms ; diagnosis ; therapy

Humans ; Integrative Medicine ; trends ; Medical Oncology ; trends ; Medicine, Chinese Traditional ; trends ; Neoplasms ; therapy

Chinese medicine (CM) clinical efficacy evaluation research involves the longitudinal multivariate measurement which means that patients are measured repeatedly and each patient is measured by several indicators on each fixed cross-section. Although each indicator can be evaluated separately with a longitudinal linear mixed model, it is important to consider all the endpoints together especially when researchers pay special attention to the change of the conjoint efficacy for several indicators in one patient. In this article, we introduce a latent variable linear mixed model to the CM conjoint efficacy evaluation and discuss why and how to analyze the longitudinal multivariate endpoint data in the clinical CM efficacy evaluation research. It may lead to the new insight of using such methodology in the field of conjoint efficacy evaluating of CM study. And with the definition of syndrome and symptom in the CM theory, the applied discussion brings the insight of CM syndrome evaluating in future. We illustrate this methodology using an example of CM efficacy evaluation from an ischemic stroke research.
Biomedical Research ; methods ; statistics & numerical data ; Data Interpretation, Statistical ; Endpoint Determination ; methods ; statistics & numerical data ; Humans ; Linear Models ; Medicine, Chinese Traditional ; methods ; Multivariate Analysis ; Research Design ; statistics & numerical data ; Stroke ; drug therapy ; epidemiology ; Treatment Outcome

OBJECTIVETo evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).

METHODSTwenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).

RESULTSLeft ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).

CONCLUSIONSGarlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

Allyl Compounds ; pharmacology ; therapeutic use ; Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Contrast Media ; Disease Models, Animal ; Disulfides ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; complications ; diagnostic imaging ; drug therapy ; pathology ; Myocardial Reperfusion ; No-Reflow Phenomenon ; complications ; diagnostic imaging ; drug therapy ; pathology ; Swine ; Swine, Miniature ; Thiazoles ; metabolism ; Ultrasonography

OBJECTIVETo investigate the efficacy and safety of combined common femoral artery (CFA) endarterectomy with superficial femoral artery (SFA) stenting plus Shuxuening Injection infusion in patients with complex multifocal arterial steno-obstructive lesions of the lower extremities.

METHODSFrom March 2006 to March 2011, 104 lower limbs in 96 patients with multilevel peripheral arterial steno-occlusive disease, involving SFA as well as CFA and deep femoral artery (DFA) orifice, were treated by combined surgical with endovascular therapy, such as SFA stenting as an adjunct to CFA endarterectomy and patch angioplasty with the great saphenous vein. Before the end of the operation, 20 mL of Shuxuening Injection was infused through the catheter located in the treated artery. Technical and hemodynamic success, as well as primary and primary-assisted patency, was determined according to the Society for Vascular Surgery Guidelines. During follow-up, clinical status assessment, ankle-brachial index (ABI) test, and duplex Doppler ultrasound were administered every 6 months, and computed tomography angiography or magnetic resonance angiography was performed at 12, 24, and 36 months after discharge.

RESULTSAll patients underwent successful combined CFA endarterectomy with SFA stenting treatment. The average ABI after the combination treatment increased from pretreatment of 0.32±0.21 to 0.82±0.24 (P<0.01). No perioperative death and major limb amputations occurred. The mean duration of follow-up for 104 limbs from 96 patients was 1,180 days (range, 196-2,064 days). During follow-up, 5 patients died due to myocardial infarction, cerebral infarction, or pneumonia, and 5 patients were lost to follow-up. There were 21 cases (21.4%) of restenosis, with 15 that occurred in-stent and 6 near the distal end of the stent. A total of 18 (18.3%) reinterventions were performed, including 6 balloon angioplasty, 8 restenting procedures, 2 bypass surgeries, and 2 major limb amputations. The primary patency rates were 92.2%, 76.8%, and 61.3% at 12, 24, and 36 months, respectively, while the primary-assisted patency rates were 94.4%, 83.2%, and 75.6% at 12, 24, and 36 months, respectively.

CONCLUSIONThe combined CFA endarterectomy with SFA stenting plus Shuxuening Injection infusion appears to offer a safe, less invasive, and effective treatment option to patients with chronic lower extremity ischemia due to complex multifocal peripheral artery disease.

Aged ; Aged, 80 and over ; Chronic Disease ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Endarterectomy ; Female ; Femoral Artery ; drug effects ; physiopathology ; surgery ; Follow-Up Studies ; Hemodynamics ; drug effects ; Humans ; Infusions, Intra-Arterial ; Ischemia ; drug therapy ; physiopathology ; surgery ; Leg ; blood supply ; physiopathology ; Male ; Middle Aged ; Stents

OBJECTIVETo investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill (DHZCP), including drugs with the function of removing blood stasis and promoting blood circulation (FP-I), drugs with the function of expelling heat and moistening dryness (FP-II), and drugs with the function of nourishing yin and replenishing blood (FP-III) of DHZCP, on platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs) proliferation with the method of serum pharmacology.

METHODSVSMCs proliferation of rat was assayed by measuring the cell viability with the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) method. DNA synthesis in VSMCs was examined by detecting 5'-bromo-2'-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKCα, and phosphorylated extracellular signal regulated kinase 1/2 (ERK1/2) was quantified by the Western blotting method.

RESULTSThe FP-I and FP-III containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G phase, downregulated cyclin D1, and upregulated p27 expression (P <0.01 or P <0.05). The FP-I and FP-III containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCα expression (P <0.01 or P <0.05).

CONCLUSIONSFP-I and FP-III of DHZCP are able to inhibit VSMCs proliferation via interrupting PKCα-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.

Animals ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; DNA ; biosynthesis ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Activation ; drug effects ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; MAP Kinase Signaling System ; drug effects ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; enzymology ; Platelet-Derived Growth Factor ; pharmacology ; Protein Kinase C-alpha ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum ; metabolism

OBJECTIVETo evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients.

METHODSA randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data.

RESULTSTen patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000).

CONCLUSIONSilymarin as a natural supplement may be used in UC patients to maintain remission.

Adolescent ; Adult ; Aged ; Colitis, Ulcerative ; drug therapy ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; Silymarin ; therapeutic use

In the past century, as medical research has become increasingly precise, it has become clear that the incidence and progression of many diseases involve multiple factors and pathologies; this is particularly true for the degenerative and metabolic diseases facing industrialized societies. At the same time, it becomes increasingly clear that single-target action drugs cannot effectively treat these diseases. Researchers are looking toward the chemical industry as well as traditional herbal medicines to find multi-target interventions. Thus, a new era in drug discovery has begun. Specifically, three approaches have proven effective in seeking multi-target drugs. These are: (1) designing drugs with multiple components; (2) discovering drugs through the study of synergistic compound-compound interactions in medicinal herbs or among chemical drugs and herbal components; and (3) developing drugs to tackle complex multi-component diseases. The authors conclude that there is an increasing need for multi-component remedies to treat the complex chronic diseases afflicting modern populations. Given this situation and the growing body of evidence that these new approaches are effective, multi-target intervention appears to have great potential for discovering, designing, and developing effective new drugs for today's diseases.
Drug Design ; Drug Discovery ; trends ; Drug Synergism ; Herb-Drug Interactions ; Humans ; Molecular Targeted Therapy ; trends ; Plants, Medicinal