Clinicopathology and Survival in Patients with Gastroesophageal Reflux After Radical Surgery of Proximal Gastric Cancer.

BACKGROUND: Gastroesophageal reflux (GR) after radical resection of proximal gastric cancer (PGC) may influence survival; however, few studies have investigated survival in PGC patients who develop GR following radical resection. This study aimed to correlate the occurrence of GR after proximal gastrectomy (PG) and total gastrectomy (TG) with clinicopathological factors and long-term survival. METHODS: The PGC patient cohort was retrospectively grouped as follows: postoperative patients with and without GR (NGR). Clinicopathological characteristics and survival data were compared between the two groups. RESULTS: A total of 88 patients who underwent PG (53%) experienced postoperative GR; however, only 30 patients who underwent TG (14%) experienced GR (P = 0.000). The incidence of GR was significantly associated with surgical procedure (P < 0.01), tumor size (P < 0.01), infiltration depth (P < 0.01), lymph node metastasis (P = 0.018), postoperative distant metastasis (P < 0.01) and recurrence (P = 0.001). The 5-year overall survival of the GR group was significantly worse than that of the NGR group (39.3 vs. 46.5%, respectively; P = 0.046). The PG and TG groups had significantly different 5-year overall survival (45.2 vs. 50.9%, respectively; P = 0.047), and multivariate analysis revealed GR as an independent risk factor associated with poor overall survival. CONCLUSIONS: Patients who experienced GR after radical resection for PGC were more likely to develop recurrence and metastasis, leading to shorter survival. TG for PGC was associated with a more favorable 5-year overall survival than was PG. Thus, TG should be performed for PGC patients with tumors larger than 5 cm, T3/T4 disease or lymph node metastasis to improve their long-term survival.

Irradiated VEGF164-modified tumor cell vaccine protected mice from the parental tumor challenge.

Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine. T-cells isolated from the vaccinated mice showed cytotoxicity against the parental tumor cells in a dose-dependent manner. Meanwhile, sera from the mice vaccinated with LL/2-VEGF164 showed higher titers of antibodies against parental tumor cells compared with the nonvaccinated groups. Our results indicated that VEGF164-modified tumor vaccine could modulate host antitumor immune response and hold therapeutic potential for cancer.

VEGF-D-induced draining lymphatic enlargement and tumor lymphangiogenesis promote lymph node metastasis in a xenograft model of ovarian carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF)-D has been shown to promote lymph node metastasis in several cancers. Although generally overexpressed in ovarian carcinoma, its role in nodal dissemination of this cancer is unclear. To clarify the role of VEGF-D and the underlying molecular mechanisms, we investigated the function of VEGF-D using a mouse xenograft model of ovarian cancer. METHODS: Human ovarian serous adenocarcinoma SKOV3 cells were transfected with VEGF-D recombinant plasmid DNA, or with control vectors. The cells were injected subcutaneously into the footpads of nude mice. Tumor growth was evaluated weekly. Draining lymphatics were observed grossly with Evan's blue lymphangiography. Tumoral lymphatics were delineated with both Evan's blue and LYVE-1 immunostaining. Tumor metastases to lymph nodes were evaluated by H&E and CA125/CD40 staining. Expression of VEGF-D in primary tumors and levels of CA125 in involved lymph nodes were examined by immunohistochemistry. Tumor cell apoptosis was analyzed by Hoechst dyeing. RESULTS: Mice bearing VEGF-D overexpressing xenografts showed a significantly higher rate of lymph node metastasis and markedly greater tumor volume compared with the controls. The functional lymphatic vessels were denser and enlarged in marginal and central tumor portions. Additionally, higher CA125 expression was observed in the involved lymph nodes. Mice bearing VEGF-D overexpressing xenografts also exhibited a markedly lower apoptotic index compared with the controls. CONCLUSIONS: Our data demonstrate the important role of VEGF-D in promoting lymph node metastasis by increasing tumor lymphangiogenesis, stimulating draining lymphatic vessel formation, and enhancing tumor invasiveness. Our findings show that VEGF-D can be a promising therapeutic target for ovarian cancer.

Gene therapy with beta-defensin 2 induces antitumor immunity and enhances local antitumor effects.

Beta-defensins, small antimicrobial peptides, are involved in host immune responses to tumors. In this study, we used beta-defensin 2 (BD2) to explore the possible role of beta-defensins in cancer gene therapy. A recombinant plasmid expressing a secretable form of BD2 was constructed. The biological activities of BD2 in immature dendritic cells (iDCs) were tested in vitro and in vivo. The antitumor effects were investigated in three established tumor models. The secreted BD2 was detected and exhibited chemotactic activity in iDCs both in vitro and in vivo. Recruitment and activation of iDCs in tumor niches resulted in significant tumor growth inhibition. Adoptive transfer of splenocytes and depletion of immune cell subsets revealed that CD8(+) T lymphocyte responses mediated the increased tumor inhibition. Furthermore, we also found that chemotactic and maturation-inducing activities in iDCs in tumor milieu contributed to enhanced local antitumor effects. Our study indicates that gene therapy with BD2 can mediate specific antitumor immunity and augment local antitumor effects. Our study also suggested that beta-defensins may merit further exploration for cancer immunotherapy as promising immunogenes.

Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis melanoma.

BACKGROUND: The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo. METHOD: We designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis. RESULTS: We found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone. CONCLUSION: The present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers.

Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice.

OBJECTIVE: Mice injected with Bacillus Calmette-Guérin (BCG) were challenged with lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was performed to explore the protective effects of interleukin (IL)-4 against liver injury induced by BCG and LPS in mice. MATERIALS AND METHODS: Mice injected with BCG (125 mg/kg) were challenged with LPS (10 µg/kg) to induce the model of inflammatory liver injury. Half an hour after injection of LPS, mice were subcutaneously administered rmIL-4 at 5 and 0.5 µg/kg, respectively. Liver injury was evaluated by serum transaminase assay and H & E staining. Liver cytokine concentrations were determined by enzyme-linked immunosorbent assay, and intrahepatic cytokine and iNOS mRNA levels by reverse transcriptase polymerase chain reaction. Intrahepatic apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated nick end labeling. NF-κB p65 and ERK signal pathway was detected by Western-blotting. NF-κB signal pathway was also detected by electrophoretic mobility shift assay. RESULTS: IL-4 reduced the serum ALT, AST and LDH, alleviated the inflammatory cells infiltration, down regulated the expression of TNF-α, IL-1ß, IFN-γ, IL-6 and iNOS mRNA in liver, and alleviated hepatic glutathione depletion (GSH). In addition, IL-4 displayed inhibition of extracellular signal-regulated kinase phosphorylation and NF-κB activation. CONCLUSION: IL-4 may protect mice against BCG/LPS-induced immune liver injury, besides ERK and NF-κB signal pathways were involved in the effects.

Improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesions simultaneously with biodegradable micelles.

The two major concerns after cytoreductive surgery of abdominal and pelvic malignancies are residual tumors and peritoneal adhesions, which are inevitable and have great impact on prognosis. Therefore, to improve the intraperitoneal chemotherapeutic effect and prevent postsurgical adhesions simultaneously after surgery, we developed a novel strategy that combines the controlled drug delivery system (CDDS) with an antiadhesion barrier. Biodegradable poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PECE) copolymer formed micelles in water, which turned instantly into a nonflowing gel at body temperature as a result of micellar aggregation. Effectiveness of doxorubicin-loaded PECE micelles (Dox-M) in improving intraperitoneal chemotherapeutic effect and preventing adhesions was investigated. Subsequently, we established a novel mouse model for postsurgical residual tumors and peritoneal adhesions, in which Dox-M could improve intraperitoneal chemotherapeutic effect and prevent postsurgical peritoneal adhesions simultaneously. Thus, it is a promising strategy to combine the CDDS and barrier method to improve the intraperitoneal chemotherapeutic effect and prevent peritoneal adhesions simultaneously after surgery.

Preparation of anti-CD40 antibody modified magnetic PCL-PEG-PCL microspheres.

Antibody modified magnetic polymeric microspheres have potential biomedical application. In this paper, anti-CD40 antibody modified magnetic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) microspheres were prepared. First, PCL-PEG-PCL triblock copolymer was synthesized by ring-opening polymerization, followed by reaction with succinic anhydride, creating carboxylated PCL-PEG-PCL copolymer. Then, magnetite nanoparticles were encapsulated into carboxylated PCL-PEG-PCL microspheres, forming magnetic PCL-PEG-PCL microspheres with carboxyl group on their surface. Catalyzed by EDC/NHS, the anti-CD40 antibody was linked to these magnetic PCL-PEG-PCL microspheres, thus forming anti-CD40 modified PCL-PEG-PCL microspheres. These anti-CD40 antibody modified magnetic PCL-PEG-PCL microspheres may have potential application in cell separation.

A novel drug and gene co-delivery system based on Poly(epsilon-caprolactone)-Poly(ethylene glycol)-Poly(epsilon-caprolactone) grafted polyethyleneimine micelle.

In this paper, we prepared a novel cationic self-assembled micelle from poly(epsilon-caprolactone)-poly(ethyl glycol)-poly(epsilon-caprolactone) grafted polyethyleneimine (PCEC-g-PEI). The PCEC-g-PEI micelles, formed by self-assembly method, had mean particle size of ca. 82 nm and zeta potential of +22.5 mV at 37 degrees C, and could efficiently transfer pGFP into HEK293 cells in vitro. Meanwhile, as a model hydrophobic chemotherapeutic drug, honokiol was loaded into PCEC-g-PEI micelles by direct dissolution method assisted by ultrasonication. The honokiol loaded cationic PCEC-g-PEI micelles could effectively adsorb DNA onto its surface, while it could release honokiol in an extended period in vitro. This study demonstrated a novel DNA and hydrophobic chemotherapeutic drug co-delivery system.

A novel transdermal plasmid-dimethylsulfoxide delivery technique for treatment of psoriasis.

BACKGROUND: Psoriasis is a chronic and relapsing inflammatory skin disease associated with various immunologic abnormalities. Repeated subcutaneous injection of interleukin-4 (IL-4) has been established as an effective treatment to counteract psoriasis. OBJECTIVE: We investigated whether gene therapy using IL-4 expression plasmid (pIL-4) via transdermal delivery was an alternative treatment for psoriasis. In our experiment, dimethylsulfoxide (DMSO) was used as a penetration enhancer. METHODS: At first, the penetration efficiency of the complex of reporter plasmid accompanied by DMSO was investigated both in vitro and in vivo. Then, the antipsoriasis efficiency of the treatment with pIL-4-DMSO was tested in mice. RESULTS: The expression of the reporter gene was detected in epidermis and dermis both in vitro and in vivo. More importantly, the psoriasis symptoms were relieved, and significant reductions in some psoriasis-associated factors were observed after pIL-4-DMSO treatment. CONCLUSION: We conclude that the topical application of pIL-4-DMSO can treat psoriasis to a significant extent.

An N-, C-terminally truncated basic fibroblast growth factor and LPD (liposome-polycation-DNA) complexes elicits a protective immune response against murine colon carcinoma.

Basic fibroblast growth factor (bFGF) is a mitogen for endothelial cells, which participates in tumor angiogenesis. Active immunity against bFGF could be a promising approach for the biotherapy of cancer. Because bFGF is abundant in normal and malignant tissues, it is presumably difficult for normal bFGF to induce immunity due to self-tolerance. In addition, previous studies have shown that a complex consisting of a cationic liposome and a non-coding plasmid DNA can be used to stimulate innate immunity. This stimulation initiates a potent cytokine response, which can inhibit tumor growth. To investigate the effects of immunity against bFGF on murine colon carcinomas, we employed an N-, C-terminally truncated basic fibroblast growth factor (tbFGF, of human origin) as an antigen and a liposome-DNA complex as an adjuvant. After six immunizations, a robust bFGF-specific immune response was elicited. Subsequently, inhibition of tumor growth and a significant reduction in tumor vasculature were observed. The antitumor effect was confirmed by adoptive therapy of activated spleen cells from the immunized mice. In vitro, a CTL assay revealed that bFGF-specific cytotoxic T lymphocytes (CTL) resulted in the lysis of mouse microvascular endothelial cells (MS1) rather than that of the CT26 colorectal cancer cells. These results suggest that anti-angiogenesis treatment induced by a bFGF-specific CTLs against microvascular endothelial cells may be a useful method for cancer therapy.

Retinoic acid and dimethyl sulfoxide promote efficient delivery of transgenes to mouse skin by topically transdermal penetration.

Simple and efficient gene transfer to the skin would facilitate many local and systemic gene therapy applications. This study reports a novel approach that allows expression of plasmid DNA in epidermis and hair follicle cells with dimethyl sulfoxide (DMSO) after pre-treatment with depilation and retinoic acid (RA) for the purposes of gene therapy. This study investigated the transdermal efficacy of gene to mouse skin when utilizing DMSO after RA pre-treatment. Retinoic acid pre-treatment can increase the efficiency of transfection. This finding indicates that one can more effectively and much less expensively make use of genes therapy to treat diseases of the hair and skin.

Suppression of human MDA-MB-435S tumor by U6 promoter-driven short hairpin RNAs targeting focal adhesion kinase.

PURPOSE: Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase implicated in cancer cell survival, proliferation, and in various steps in the metastatic cascade. In the present study, we took advantage of a cationic liposome as gene carrier and targeted FAK function through both in vitro and in vivo approaches. METHODS: We utilized a plasmid-encoded hairpin RNA targeting the human FAK mRNA (pGensil2-shRNA/FAK), as a means to inhibit FAK expression for evaluating its anti-tumor effect in vitro and in vivo. Human MDA-MB-435S breast cancer cells were transfected with pGensil2-shRNA/FAK and examined for apoptosis by propidium iodide staining, DNA ladder, and flow cytometric analysis. For in vivo study, subcutaneous breast carcinomatosis models in nude mice were established to evaluate the therapeutic potential of pGensil2-shRNA/FAK. Assessments of proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31) were done using immunohistochemical analysis. RESULTS: Transcripts expressed from plasmid both in vitro and in vivo were identified by northern blot analysis. pGensil2-shRNA/FAK effectively down-regulated the expression of FAK as demonstrated in vitro by real time RT-PCR and western blot analysis, whereas by real time RT-PCR and IHC staining of MDA-MB-435S tumors growing subcutaneously. Breast cancer cells lacking FAK expression undergo apoptosis in vitro. Systemic delivery of cationic liposome-complexed plasmids targeting FAK, resulted in the diminishment of subcutaneous tumor growth beyond the effects observed with liposomes carrying a non-specific shRNA. This diminishment in growth was associated with elevated levels of apoptosis (TUNEL staining), decreased cell proliferation (Ki-67 staining) and diminished endothelial cell density (CD31 staining). CONCLUSION: These results indicate that the systemic delivery of plasmid DNA targeting FAK function using cationic liposome as a gene carrier, represents a promising avenue for breast cancer therapy.

Safety evaluation of amphiphilic three-armed star-shaped copolymer micelles.

In our previous work, we had prepared a biodegradable amphiphilic three-armed star-shaped copolymers (SPCE) based on poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG), which could form micelles by self-assembly method and it was a potential carrier for hydrophobic drug. For further application, the safety of SPCE micelles was evaluated in vitro and in vivo here. (13)C-NMR was used to confirm the formation of the micelles in aqueous solution, and the morphology was observed on transmission electron microscope (TEM). Also, thermostability of blank SPCE micelles was determined by Malvern Nano-ZS 90 laser particle size analyzer. In vitro toxicity evaluation included hemolytic test and cytotoxicity. In vivo acute toxicity tests and histopathological study of SPCE micelles were carried out on BALB/C mice which were administrated SPCE micelles (1 g/kg b.w.) intravenously. In acute toxicity test, the mice were observed continuously for 7 days, obtained their body weight every day, at last the mice was sacrificed for the following study: the blood of the mice was assigned for blood chemistry and routine analysis, the heart, liver, spleen, lung, and kidneys were used for histopathological study. All results indicated that the biodegradable self-assembled SPCE micelles were nontoxic; therefore, it might be used as a safe candidate for drug delivery system.

Enhanced gene delivery using biodegradable poly(ester amine)s (PEAs) based on low-molecular-weight polyethylenimine and poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone).

In this paper, the poly(ester amine)s (PEAs) were successfully prepared from low-molecular-weight PEI (Mn = 2000) and Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCFC) copolymers using isophorone diisocyanate (IPDI) as cross-linker. The obtained PEAs copolymers are biodegradable and water-soluble. The PEAs/DNA complexes showed effective and stable DNA condensation with the particle size < or = 200 nm and zeta potential > or =10 mV, indicating its potential for intracellular delivery. Compared to the unmodified low-molecular-weight PEI, PEAs displayed similarly low cytotoxicity in all two cell lines (293T: Human kidney carcinoma, HUVEC: Human umbilical vein Endothelial cell) and revealed much higher transfection efficiency in 293T cell lines. Therefore these PEAs might be a novel safe and efficient polymeric gene delivery vectors.

Preparation of MPEG-PLA nanoparticle for honokiol delivery in vitro.

Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by (1)H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG-PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG-PLA nanoparticles in this paper might be a novel formulation for honokiol delivery.

Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity.

In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro. Otherwise, the immunogenicity of bFGF was improved significantly after encapsulated into the hydrogel. Strong humoral immunity created by bFGF-hydrogel was maintained for more than 14 weeks. Therefore, the prepared bFGF loaded PECE hydrogel might have great potential as a novel vaccine adjuvant for protein antigen.

A novel poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone) grafted polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study.

BACKGROUND: Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting. RESULTS: Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-g-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-g-PEI was characterized by 1H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-g-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-g-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD. CONCLUSION: The cytotoxicity and in vitro transfection study indicated that PCFC-g-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).

Downregulation of peroxisome proliferator-activated receptor-gamma expression in hypertensive atrial fibrillation.

BACKGROUND: Numerous evidence has suggested that either hypertension or atrial fibrillation (AF) is associated with systemic inflammation. Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been proved to have anti-inflammatory effects and is implicated as a molecular pathway involved in many cardiovascular diseases, such as hypertension. The correlation between PPARgamma inflammation and AF is still unknown. METHODS: Using a case-control study design, 57 patients with hypertensive AF (persistent AF: 32, paroxysmal AF: 25) were included into the study groups. A total of 32 age-matched patients with hypertension, but without AF were selected as the control group. The expressions of PPARgamma, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) mRNA in monocytes were detected by using a reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1 (IL-1) was measured by immunoenzymetric methods. RESULTS: The PPARgamma mRNA was markedly decreased in the hypertensive AF group as compared with the hypertensive non-AF group, and it was significantly lower in persistent AF than paroxysmal AF (0.222 +/- 0.0702 vs 0.564 +/- 0.0436, P<0.01). TNF-alpha mRNA, IL-6 mRNA, and IL-1 were increased in patients with hypertensive AF compared to the non-AF group and it was even higher in persistent AF than in paroxysmal AF (0.721 +/- 0.0541 vs 0.530 +/- 0.0496, 0.567 +/- 0.044 vs 0.457 +/- 0.0505, 325.61 +/- 88.10 vs 190.65 +/- 59.38, respectively, P<0.01). TNF-alpha, IL-6, and IL-1 were in negative correlation with PPARgamma, the correlation coefficient was -0.854, -0.769, and -0.702, respectively (P<0.01). CONCLUSIONS: In hypertensive patients, increased inflammatory cytokines were associated with increased incidence of AF and atrial remodeling; PPARgamma may be involved in the pathogenesis of AF by regulation of inflammation.

[Experimental study on co-culture of early embryo and cancer cells in vitro].

The co-culture system of early embryos and cancer cells is an important means to observe the biological behavior changes of embryos and cancer cells in vitro. In this study, we co-cultured the 3.5 dpc mouse embryo with malignant tumor cells, investigated the development of blastocyst by observing the hatchment, attachment and outgrowth, observed the biological behavior changes of cancer cells in the embryonic circumstances, and detected the proliferation and apoptosis of cancer cells. Compared with the control, the embryos developed normally in the tumor environments, and the rate of hatchment, attachment and outgrowth increased significantly (P<0.05). However, there was no significant change of cancer cells in morphology, proliferation and apoptosis in the co-culture system (P>0.05). Under the co-culture system, the early embryo developed normally, and the cancer cells also grew well. There may be similarities between the embryos and cancer cell's choice for living. Moreover, the growth of embryos could be promoted by cancer cells in the co-culture system. This might be related to the similarities of gene expression, growth factors and signal transduction mechanisms between embryos and cancer cells.