OBJECTIVETo investigate the expressions of human epidermal growth factor receptor 2 (Her-2) and vascular endothelial growth factor (VEGF) in primary and recurrent metastatic breast cancers and explore their relationship.

METHODSThe expressions of Her-2 and VEGF in 60 primary and recurrent metastatic breast cancers were detected using immunohistochemical methods. Their relationship was analyzed.

RESULTSThe positive rates of Her-2 and VEGF in the recurrent metastatic breast cancer were 40.00% and 53.33%, respectively, which were significantly higher than that in the primary breast cancer (18.33% and 31.67%) (P < 0.05). The total diversify rates of Her-2 and VEGF were 28.33% and 35.00%, respectively. Her-2 and VEGF expressions were significantly correlated between the primary and the recurrent metastatic breast cancers( P < 0.05).

CONCLUSIONSHer-2 and VEGF may play synergic roles in the occurrence and development of breast cancer. Over-expressions of Her-2 and VEGF predict poor prognosis.

Adult ; Aged ; Breast Neoplasms ; metabolism ; pathology ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; metabolism ; Prognosis ; Receptor, ErbB-2 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the expression of thymidylate synthase (TS) in patients with advanced lung adenocarcinoma and its relation with the therapeutic effect of pemetrexed.

METHODSThe clinicopathological data of 38 patients with stage IIIIB/IV lung adenocarcinoma receiving pemetrexed treatment were retrospectively analyzed. The tumor samples of the patients were collected for detecting TS expression using RT-PCR, and the therapeutic effect of the treatment was analyzed.

RESULTSTS positivity was found in 26.32 (10/38) of the patients. TS positivity was not correlated to gender, TNM stage or PS score. The total response rate of pemetrexed treatment (CR+PR) was 34.21 (13/38) in these patients, and the rate was 39.29% (11/28) in TS-negative patients, as compared to 20.00% (2/10) in the positive patients (P=0.087). Patients with low TS expression had significantly higher control rate by pemetrexed treatment than those with TS overexpression [89.29% (25/28) vs 40.00% (4/10), P=0.002].

CONCLUSIONTS expression may serve as a potential indicator of chemosensitivity to pemetrexed in patients with advanced lung adenocarcinoma.

Adenocarcinoma ; drug therapy ; enzymology ; Antineoplastic Agents ; therapeutic use ; Female ; Folic Acid Antagonists ; therapeutic use ; Glutamates ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; Male ; Middle Aged ; Pemetrexed ; Retrospective Studies ; Thymidylate Synthase ; metabolism

BACKGROUNDConnective tissue growth factor (CTGF) is a secreted protein containing several domains that mediate interactions with growth factors, integrins and extracellular matrix components. CTGF plays an important role in extracellular matrix production by its ability to mediate collagen deposition during wound healing. CTGF also induces neovascularization in vitro, suggesting a role in angiogenesis in vivo. We herein evaluated whether CTGF was required for extracellular matrix synthesis of meniscal fibrochondrocytes and/or angiogenesis during the repair of meniscal tears.

METHODSMeniscal fibrochondrocytes were isolated from the inner-1/2 of rabbit meniscus by trypsin collagenase treatment and further treated with 100 ng/ml CTGF in vitro. Characterization of fibrochondrocytes was identified by flow cytometry analyzing CD31, CD44, CD45 and CD105, and was further tested by type II collagen immunocytochemistry. Changes in gene expression of meniscal fibrochondrocytes were monitored by quantitative real-time polymerase chain reaction. Histological sections prepared from a 3-mm portion of a longitudinal tearing defect in the middle of the rabbit meniscus were subjected to fluorescence-immunohistochemistry analysis at 1, 4 and 10 weeks following surgical treatment with 1.5 µg of CTGF/fibrin-glue composites.

RESULTSQuantitative RT-PCR assay showed that types I and II collagen and vascular endothelial growth factor mRNA expression in the 100 ng/ml CTGF group were remarkably enhanced as compared to levels in the no-dose group at 14 days ((2.38 ± 0.63) fold, (2.96 ± 0.87) fold, (2.14 ± 0.56) fold, respectively). Likewise, fluorescence-immunohistochemical analysis revealed that in the group implanted with CTGF-fibrin glue, types I and II collagen, as well as the capillaries, completely filled the defect by 10 weeks, postoperatively. In contrast, only soft tissue repair occurred when PBS-fibrin glue was implanted.

CONCLUSIONSThese findings suggest that CTGF can significantly promote extracellular matrix deposition (types I and II collagen) within the meniscal avascular zone; CTGF can greatly heighten the expression of vascular endothelial growth factor activity simultaneously in vivo, further enhancing the repair of meniscal tears in the avascular zone.

Animals ; Cells, Cultured ; Chondrocytes ; cytology ; Collagen Type I ; metabolism ; Collagen Type II ; metabolism ; Connective Tissue Growth Factor ; pharmacology ; Flow Cytometry ; Immunohistochemistry ; Male ; Menisci, Tibial ; cytology ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction ; Tibial Meniscus Injuries ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; drug effects

Objective In this study,we investigated the relationship between oxidative stress,selenoproteins level and onset of Keshan disease (KD) through detecting the expression of 8-hydroxy-2-deoxy guanosine (8-OH-dG),thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 1 (GPx1) in myocardial tissue.Methods Myocardium samples of autopsy patients including 8 cases of KD (KD group included 4 acute KD and 4 chronic KD) and 9 cases of non-KD (control group) were immunohistochemically stained for 8-OH-dG,TrxR1 and GPx1.The staining intensities subsequently quantified by using Olympus Image-Pro Plus 6.0 software.Results The positive rate of 8-OH-dG expression in myocardial nuclei was higher in the case group[(68.6 ± 20.4)％] than that of the control group[(2.4 ± 1.5)％,t =8.515,P ＜ 0.05].In addition,the positive rate of 8-OH-dG expression in acute KD[(91.7 ± 3.7)％] was significantly higher than that of chronic KD[(53.2 ± 7.9)％,t =6.409,P＜0.05].The distribution of TrxR1 and GPx1 was not associated with the distribution of myocardial damage.The expression of these two selenoproteins in KD group (401340 ± 59865,497590 ± 197082) were both lower than that of control group(2790300 ± 379298,1348400 ±615840; t =-28.493,-6.016,respectively,all P＜0.01).Conclusions Oxidative damage is detected in myocardium tissue of KD,and 8-OH-dG expression is associated with the degree of myocardial damage in KD.Selenoproteins,TrxR1 and GPx1,may be closely related to the pathogenesis of KD.

Mesenchymal stem cells (MSC) are characterized by their potent immuno-regulatory activity, however our previous data have shown that MSC have no therapeutic effects on collagen-induced arthritis (CIA). To further clarify the complexity, the effects of tumor necrosis factor-alpha (TNF-α) on the in vitro and in vivo immunoregulatory activity of MSC were investigated in this study, as TNF-α is recognized as the key factor in the development of rheumatoid arthritis. The nuclear translocation of the inflammation-associated factor NF-κB was observed after human umbilical cord MSC were treated with TNF-α and the cell proliferation status was assessed by MTT test. The inhibitory effects of MSC or TNF-α-treated MSC on the mixed lymphocyte reaction, in which Wistar rat spleen mononuclear cells were served as the responders and the splenocytes from SD rat spleens as the stimulators, were also determined by the MTT test. Further, the therapeutic potentials of MSC or TNF-α-treated MSC were observed in a Wistar rat CIA model. The results showed that NF-κB translocated into the nuclei promptly after TNF-α treatment, though TNF-α had little effect on the MSC proliferation. MSC, whether pre-stimulated by TNF-α or not and when different doses were tested, exhibited obviously inhibitory effects on the proliferation of the lymphocytes (P < 0.001 for all groups tested), while MSC-treated by TNF-α displayed more potent suppression especially when low-density were used. Unexpectedly, the infiltration of inflammatory cells into the involved knees was aggravated by cell treatment and the pathological scores were significantly higher than those of controls (P < 0.05). It is concluded that the TNF-α exhibits different effects on immune regulation activity of MSC, and its underlying mechanism needs to further investigate.
Animals ; Arthritis, Experimental ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Humans ; Male ; Mesenchymal Stromal Cells ; cytology ; drug effects ; immunology ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo study anti-atherosclerotic mechanisms of divided functional recipes of Dahuang Zhechong pill (DHZCP) in rabbits.

METHODThe atherosclerotic rabbit model was established by high fat feeding combined with immune endothelial injury. Male New Zealand rabbits were divided into 9 groups: normal control group, model control group, Danshen positive control group, and 6 DHZCP-divided groups including divided functional recipes No. 1, 2, 3 with low and high doses for each divided recipe. After intragastric administration for 60 days, blood lipids and serum MDA and NO levels and SOD activity and plasma ET concentration, and contents of hydroxyproline and proteins in the vascular wall were determined.

RESULTCompared with the model group, the level of blood lipids did not significantly change, serum MDA and ET levels, and the contents of hydroxyproline and proteins in the vascular wall significantly decreased (P < 0.05), and SOD activity and NO level increased in the divided functional recipes (all P < 0.05).

CONCLUSIONThe divided functional recipes of DHZCP can inhibit development of atherosclerosis via a non-lowering lipid mechanisms, including anti-peroxidation of lipids, protection of endothelial function, and decrease of formation of extracellular matrix by reducing synthesis of collage and protein on the vascular wall. Among them, the divided functional recipe No. 1 exhibits the most obvious effect.

Animals ; Aorta ; metabolism ; Atherosclerosis ; blood ; pathology ; prevention & control ; Cockroaches ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelins ; blood ; Hydroxyproline ; metabolism ; Lipids ; blood ; Male ; Malondialdehyde ; blood ; Materia Medica ; isolation & purification ; pharmacology ; Nitric Oxide ; blood ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rheum ; chemistry ; Superoxide Dismutase ; blood

Our previous work has shown that mesenchymal stem cells (MSC) have little therapeutic effect on rat arthritis induced by collagen. This study was aimed to further investigate whether the MSC lysates exhibit beneficial effects on rheumatoid arthritis. Aliquots of cell lysates from 1×10(7) human bone marrow MSC were intraperitoneally injected into collagen-induced arthritis (CIA) Wistar rats weekly for 4 consecutive weeks. Methotrexate at a dose of 1 mg/kg or normal saline was served as positive and negative controls respectively. On week 4 the symptom scores were recorded and the hind joints of the rats were pathologically examined and X-ray examination was performed. The results showed that on week 4, the symptom scores of the rats that received MSC lysates (6.87 ± 0.83) and MTX (6.44 ± 1.13) were significantly lower than that of control rats (7.33 ± 0.77, P < 0.01). Meanwhile, pathological examination on the involved ankle showed that the synovitis and arthritis scores of MSC lysates and control groups were 2.28 ± 0.48 and 2.28 ± 0.55 respectively, significantly higher than that of MTX treatment rats (0.71 ± 0.48, P < 0.05). However, X-ray examination on the ankle joints showed that the injury score of control rats was 4 ± 0.57, greatly higher than those from MSC lysates (2.71 ± 0.75) and MTX treatment groups (2.57 ± 0.78, P < 0.05 for both groups). It is concluded that MSC lysate infusion has beneficial effects on CIA rat, but the effectiveness seems inferior to MTX.
Animals ; Arthritis, Experimental ; chemically induced ; therapy ; Bone Marrow Cells ; cytology ; Cells, Cultured ; Collagen ; Humans ; Male ; Mesenchymal Stromal Cells ; cytology ; Methotrexate ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo explore the etiology, clinical aspects, diagnosis and therapeutic strategies of acute low-tone sensorineural hearing loss (ALHL).

METHODSThirty patients (31 ears) with ALHL were selected for this study. Detailed history collection, otological examination and systematic audiological evaluations were conducted. The hearing tests included pure tone audiometry, acoustic immittance, auditory brainstem response (ABR) and otoacoustic emissions (OAE). All cases received therapeutic trial of corticosteroid for 15 days with 6 to 14 months' following-up.

RESULTSALHL mainly affected young people. Low-tone tinnitus, a sensation of ear fullness and hearing impairment were the frequent complains. Otological examinations showed normal results. Mild to moderate sensorineural hearing loss at low frequencies and type "A" tympanograms were found in all patients. Acoustic stapedial reflexes were elicited in 26 of 31 affected ears, and 14 of them had positive results on the Metz test. ABR responses were normal in all 20 tested ears. In 14 out of 20 ears, TEOAEs were absent and DPOAE grams at low frequencies (0.5, 0.75 kHz) were abnormal on the first visit. After steroid therapy, 24 ears demonstrated complete recovery, but 4 ears showed partial recovery and 3 ears unchanged. The total improvement rate was 90.3%.

CONCLUSIONSALHL patients are clinically characterized by low-tone tinnitus, aural fullness and hearing loss, which mainly involved unilateral ear. Audiological findings indicate a cochlear impairment, which only invades low frequency region. The basic pathological feature may be endolymphatic hydrops involves immune response. Conflicting data exist on whether ALHL is an independent disorder or a subtype of Meniere's disease. Ideal therapeutic strategy has not been established by now and corticosteroid is probably an effective agent.

Acute Disease ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Audiometry, Evoked Response ; Endolymphatic Hydrops ; etiology ; Female ; Hearing Loss, Sensorineural ; diagnosis ; drug therapy ; physiopathology ; Humans ; Male ; Meniere Disease ; diagnosis ; drug therapy ; physiopathology ; Middle Aged ; Otoacoustic Emissions, Spontaneous

OBJECTIVETo evaluate protective effects of Rheum tanguticum polysaccharides (RTP) on traumatic brain injury (TBI) in rats.

METHODThe polysaccharides (RTP) were extracted from Tanguficum Maxim. 120 rats were divided into 15 groups, with 8 rats in each group. RTP at 100, 200 and 400 mg x kg(-1) were administrated orally once a day for five days, and model of brain injury was made by dropping weight method.

RESULTRTP reduced water content and malondialdehyde (MDA) levels, and increased total SOD activity and Na+-K+ ATPase activity after injuried.

CONCLUSIONThe polysaccharides may be one of the effective comptents in Rheum tanguticum, showing significant neuroprotective effects.

Animals ; Brain Injuries ; enzymology ; metabolism ; pathology ; Cerebral Cortex ; enzymology ; ultrastructure ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism

BACKGROUNDPeroxisome proliferator-activated receptor (PPAR) alpha is one of the subtypes of PPARs. It regulates metabolism of lipid and lipoprotein, as well as glucose homeostasis. In addition, PPARalpha influences cellular proliferation, inflammation, differentiation and apoptosis, which plays a vital role in cardiovascular diseases. The purpose of this study was to investigate the role and mechanisms of PPARa activation in relation to acute myocardial damage induced by isoproterenol in rats.

METHODSThirty male Wister rats were randomly divided into control group, isoproterenol (Iso) injured group and fenofibrate (FF) treatment group. Acute myocardial damage caused by isoproterenol intraperitoneal injection induced ischemia was established. We determined the levels of creatine kinase (CK) and lactic dehydrogenase (LDH) in serum as well as the concentrations of free fatty acids (FFA) in serum and myocardium. The mRNA expressions of PPARa, muscular type carnitine palmitransferase (M-CPT-I) and medium chain lipid acetyl coenzyme A dehydrogenase (MCAD) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSCompared with the control group, the levels of serum CK and LDH were significantly increased after FF and Iso treatments. Moreover, the concentrations of FFA in both serum and myocardium were obviously increased in the Iso group and FF group, while the mRNA expressions of PPARalpha, M-CPT-I and MCAD declined, respectively (P < 0.01). When compared with the Iso group, significant decreases in serum CK and LDH were observed in the FF group. The concentrations of FFA both in serum and myocardial tissue were markedly decreased in the FF group, while the expressions of PPARalpha, M-CPT-I and MCAD mRNA were increased (vs. Iso, P < or = 0.01).

CONCLUSIONSThe utilization of FFA was reduced in isoproterenol induced acute myocardial damage. PPARalpha activation by its activator fenofibrate may play a key role in energy metabolism in acute myocardial damage induced by isoproterenol in rats.

Animals ; Creatine Kinase ; blood ; Energy Metabolism ; Fatty Acids, Nonesterified ; metabolism ; Fenofibrate ; pharmacology ; Heart ; drug effects ; Isoproterenol ; toxicity ; L-Lactate Dehydrogenase ; blood ; Male ; PPAR alpha ; physiology ; Rats ; Rats, Wistar