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Biomedical subjects

Xueying Sun

Publications and source records attributed to Xueying Sun.

17 recordsLinked to original sources
PubMed2007

Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats.

BACKGROUND: Liver ischemia/reperfusion (I/R) results in the release of destructive proinflammatory cytokines and oxygen-derived radicals, which in turn cause injury to liver and other organs such as kidney, lung, and intestine. Splenectomy protects organs from intestinal I/R injury. Therefore, the present study aims to investigate whether splenectomy could also ameliorate multiple organ damage caused by liver I/R. METHODS: Wistar rats randomly assigned into 4 groups underwent sham-operation, splenectomy, hepatic I/R induced by occlusion of hepatic artery and portal vein, and splenectomy plus hepatic I/R, respectively. Blood samples were collected for assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, and tumor necrosis factor-alpha (TNF-alpha) levels. The activity of myeloperoxidase (MPO) in liver tissues was assessed. Livers, kidneys, lungs, and small intestines underwent histopathologic examination for scoring injury severity and TUNEL assay for cell apoptosis. The expression of caspase-3 was evaluated with Western blot analysis. RESULTS: Liver I/R resulted in liver injury as evidenced by morphologic abnormalities, increased serum activities of AST and ALT, and increased percentage of apoptotic cells. The activity of MPO in liver tissues and the serum levels of TNF-alpha were increased after I/R. Splenectomy significantly decreased the histologic severity score, apoptotic index, MPO activity, and serum levels of AST, ALT, and TNF-alpha. Hepatic I/R also caused damage to kidneys, lungs, and small intestines, as evaluated by histologic alterations and increased apoptotic cells; these changes were ameliorated by splenectomy. The expression of caspase-3 was upregulated in the 4 organs by hepatic I/R and inhibited by splenectomy. CONCLUSIONS: Splenectomy protects the liver as well as the kidney, lung, and intestine from injury by hepatic I/R. Although the mechanism needs further investigation, this study demonstrated that splenectomy inhibited leukocyte infiltration in livers, release of TNF-alpha, cell apoptosis, and expression of caspase-3.

Alanine Transaminase↗
PubMed2006

Opposite effects of donor apoptotic versus necrotic splenocytes on splenic allograft tolerance.

BACKGROUND: Apoptotic cells have immunosuppressive activity, whereas necrotic cells activate immune response, indicating they might have different effects on immune rejection against splenic allografts. The aim of this study was to determine whether administration of apoptotic or necrotic splenocytes of donor origin could impact the acute rejection of splenic allografts. MATERIALS AND METHODS: Apoptotic or necrotic splenocytes derived from donor rats were induced by irradiation or freeze thaw, respectively. Heterotopic vascularized spleen transplantation was performed from Wistar-Furth (donor) to Sprague-Dawley (recipient) rats, and splenocytes were intravenously injected into the recipients. At different time points, the recipients were sacrificed and the splenic allografts underwent histological examination. The interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) in sera, spleens of recipients, and donor splenocytes before administration were measured. Mixed leukocyte reaction (MLR) was detected with recipient splenocytes as effectors and donor splenocytes as stimulators. RESULTS: Exposure to gamma-irradiation at dose of 10,000 rad caused over 80% splenocytes to become apoptotic. The levels of TGF-beta1 released by apoptotic splenocytes in vitro were significantly higher than that by untreated splenocytes, whereas there was almost no TGF-beta1 detected in necrotic splenocytes culture medium. Administration of apoptotic splenocytes significantly attenuated acute rejection of splenic allografts, evidenced by less severe splenic histological alteration and reduction of histological scores compared with control; whereas necrotic splenocytes exacerbated the acute rejection. Apoptotic splenocytes inhibited production of IFN-gamma but increased the levels of TGF-beta1, whereas necrotic splenocytes showed opposite activity in production of those cytokines. Administration of apoptotic splenocytes inhibited MLR, and necrotic splenocytes promoted MLR. CONCLUSIONS: The apoptotic and necrotic splenocytes exhibited opposite effects on acute rejection against splenic allografts, and IFN-gamma and TGF-beta1 have been involved in the effects.

Acute Disease↗
PubMed2006

Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy.

BACKGROUND/AIMS: B7H3 immunogene therapy is able to completely eradicate tumors when combined with an anti-vascular agent. The aim of this study was to determine whether vasostatin, a potent anti-angiogenic agent, could synergize with B7H3-mediated immunotherapy to combat hepatocellular carcinoma (HCC). METHODS: Vasostatin and B7H3 expression plasmids were constructed, and the in vitro and in vivo expression and anti-angiogenic activity of recombinant vasostatin were measured. The anti-tumor activities of B7H3 and vasostatin alone and in combination were assessed using single and multiple H22 tumor models. RESULTS: Gene transfer of vasostatin inhibited the proliferation of aortic endothelial cells, and angiogenesis in the chorioallantoic membrane assay. Subcutaneous H22 tumors established in BALB/c mice were completely eradicated in response to intratumoral injection of B7H3-expressing plasmids followed 24h later by vasostatin-expressing plasmids. In contrast, neither vasostatin nor B7H3 monotherapy was effective. Gene transfer of vasostatin inhibited tumor angiogenesis and enhanced infiltration of NK cells, whereas B7H3 therapy activated CD8+ and NK cells and increased their infiltration into tumors, and enhanced the levels of circulating IFN-gamma. B7H3 and vasostatin combination gene therapy was effective in combating a systemic challenge of parental H22 cells, and caused the complete regression of multiple distant tumor nodules. CONCLUSIONS: Combining vasostatin anti-angiogenic therapy with B7H3-mediated immunotherapy warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.

Animals↗
PubMed2006

Antiangiogenesis and damaging blood flow by antisense vascular endothelial growth factor oligodeoxynucleotides to suppress lung cancers.

Angiogenesis plays a key role in the growth and metastasis of lung cancers, and vascular endothelial growth factor (VEGF) is one of the major angiogenic factors. The study aims to investigate whether phosphoro thioate-modified antisense VEGF oligodeoxynucleo tides (ASODN) formulated in cationic liposome could inhibit the growth of Lewis lung carcinoma (LLC) tumors by antiangiogenesis. The study demonstrated that ASODN downregulated the expression of VEGF in LLC cells at levels of protein and mRNA in vitro and in vivo. The conditioned media obtained from LLC cells treated with ASODN significantly inhibited the proliferation of bovine aortic endothelial cells. The ASODN therapy significantly suppressed the growth of established subcutaneous LLC tumors in mice by inhibiting angiogenesis and damaging the blood flow of tumors. In conclusion, our results suggest that ASODN targeting VEGF presents a potent therapeutic strategy to combat lung cancers.

Animals↗
PubMed2006

Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas.

Arsenic trioxide (As(2)O(3)), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As(2)O(3) against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL-4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As(2)O(3) would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7-0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As(2)O(3) was preceded by in situ gene transfer of B7H3. In contrast, neither As(2)O(3) nor B7H3 monotherapy was effective. The antitumor activity of As(2)O(3) was attributed to increased tumor-cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD8(+) and NK cells that was effective in combating a systemic challenge of 1 x 10(7) parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN-gamma and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3-mediated immunotherapy with As(2)O(3) warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.

Animals↗
PubMed2006

Opposing effects of arsenic trioxide on hepatocellular carcinomas in mice.

Arsenic trioxide (As2O3) is a potent antitumor agent used to treat acute promyelocytic leukemia (APL) and, more recently, solid tumors. However, the dose of As2O3 required to suppress human xenographs in mice is markedly higher than that used to treat APL in humans. Paradoxically, low doses of As2O3 stimulate angiogenesis, which might be expected to promote tumor growth. Clearly, appropriate dosages of As2O3 are required to treat human patients to avoid toxicity and undesirable side effects. In the present study, we investigated As2O3 with respect to its toxicity and effects on tumor growth, angiogenesis and cell apoptosis using H22 hepatocellular carcinoma (HCC) cells in a mouse model of HCC. As2O3 inhibited tumor growth and angiogenesis, and enhanced tumor cell apoptosis at doses greater than 1 mg/kg, but mice lost weight and failed to thrive at doses of 4 mg/kg and greater. In contrast, low doses (<1 mg/kg) of As2O3 promoted tumor growth, upregulated the expression of vascular endothelial growth factor and tumor angiogenesis, and had no effect on tumor cell apoptosis. In vitro studies demonstrated that As2O3 inhibited the proliferation of H22 tumor cells and bovine aortic endothelial cells, and induced their apoptosis in a dose- and time-dependent fashion, suggesting that the mechanism of As2O3-mediated inhibition of tumor growth is due to direct effects of the drug on both tumor cells and endothelia. In summary, different doses of As2O3 have opposing effects on tumor growth and angiogenesis. The results demonstrate that As2O3 has a narrow window of therapeutic opportunity with respect to dosage, and that low doses of the drug as used in metronomic therapy should be used with extreme caution.

Animals↗
PubMed2006

Specific COX-2 inhibitor, meloxicam, suppresses proliferation and induces apoptosis in human HepG2 hepatocellular carcinoma cells.

BACKGROUND AND AIMS: Cyclooxygenase-2 (COX-2) is associated with carcinogenesis. The aim of this study was to investigate the expression of COX-2 in four hepatocellular carcinoma (HCC) cell lines, and evaluate the effect of a selective COX-2 inhibitor, meloxicam, in HepG2, a high COX-2 expressing cell line. METHODS: Expression of COX-2 was detected using RT-PCR, Western blotting and immunohistochemical analysis. Cell proliferation was measured using MTT assay. Cell cycle distribution was determined by flow cytometry. Apoptosis was detected with TUNEL method. Expression of proliferating cell nuclear antigen (PCNA), cell cycle regulatory proteins including cyclins A, B1, D1 and E, and apoptosis-related proteins including Fas, Fas ligand and Bcl-2 were examined using Western blotting. RESULTS: Cyclooxygenase-2 was intensely expressed in HepG2, HLE and BEL7402 cells, but weakly expressed in SMMC-7402 cells. Meloxicam suppressed proliferation of HepG2 cells in a dose- and time-dependent manner, resulting in cell cycle arrest in S phase and cell accumulation in G0/G1 phase. Expression of PCNA, cyclin A but not cyclin B1, cyclin D1 or cyclin E was down-regulated by meloxicam. Meloxicam also induced apoptosis of HepG2 cells, with increased expression of Fas ligand, but the expression of Fas and Bcl-2 was not affected by meloxicam treatment. CONCLUSIONS: The present study demonstrates that the specific COX-2 inhibitor meloxicam suppresses proliferation and induces apoptosis in HCC cells that express COX-2, suggesting that COX-2 inhibition may offer a novel chemopreventive and therapeutic approach for HCC.

Animals↗
PubMed2005

Recombinant adeno-associated virus-mediated TRAIL gene therapy suppresses liver metastatic tumors.

To evaluate the tumoricidal activity of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on disseminated liver metastatic tumors, we constructed a recombinant adeno-associated virus (rAAV) expressing the extracellular domain (95-281aa) of human TRAIL (TRAIL(95-281), and the recombinant virus was designated as rAAV-TRAIL) using the 3-plasmid, helper-virus-free, packaging system. Transduction of mouse lymphoma EL-4 cells and Jurkat T cells lead to the expression of TRAIL(95-281) protein in both virus-transduced cells and the culture media, along with apoptosis of these cells in vitro. The therapeutic potential of rAAV-TRAIL was then evaluated in an orthotopic transplanted mouse model mimicking liver cancer metastasis, which was established by injection of EL-4 cells into the liver of C57BL/6 mice via the hepatic portal veins. Subsequent intraportal vein injection of rAAV-TRAIL, not the control virus, into the liver of these mice resulted in significant suppression of tumor growth and prolonged survival, while normal hepatocyte toxicity is undetectable. Histological and biochemical analysis in tumor tissue and serum confirmed that TRAIL(95-281) was stably expressed in relatively high level in hepatocytes and was secreted into the serum in active trimeric form. Futhermore, the mechanism for rAAV-TRAIL to inhibit tumor growth was by inducing apoptosis of the tumor cells metastasizing to the livers. These results strongly suggest that the rAAV-TRAIL-mediated gene delivery could be a promising approach for the treatment of liver metastasis cancer.

Adenoviridae↗
PubMed2005

Vascular endothelial growth factor gene delivery by magnetic DNA nanospheres ameliorates limb ischemia in rabbits.

BACKGROUND: Critical limb ischemia often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote arteriogenesis and angiogenesis in animal models of limb ischemia. However, most of the studies used a nonspecific targeting system. MATERIALS AND METHODS: Magnetic DNA nanospheres containing expression plasmids encoding VEGF were synthesized, and their morphology, magnetropism, and stability were analyzed. The magnetic DNA nanospheres were administrated via an artery into a rabbit limb ischemia model. The expression of VEGF and vascularization were examined by immunohistochemistry. The angiography was taken to evaluate arteriogenesis. RESULTS: Magnetic DNA nanospheres were very stable and showed a high magnetropism. Gene delivery of such nanospheres via artery under a magnetic field led to the overexpression of VEGF in situ. The capillary density and capillary to muscle fiber ratio were doubled compared with those of the control animals. The arteriogenesis also was promoted in VEGF gene therapy group compared with controls but at later interval than capillary angiogenesis. CONCLUSIONS: Our results suggest that intra-arterial VEGF gene delivery by magnetic DNA nanosphere promotes angiogenesis and arteriogenesis and presents a potent therapeutic strategy for critical limb ischemia.

Animals↗
PubMed2005

Anti-angiogenic therapy subsequent to adeno-associated-virus-mediated immunotherapy eradicates lymphomas that disseminate to the liver.

Liver cancer has a very poor prognosis and lacks effective therapy. We have previously demonstrated that intraportal injection of adeno-associated-viral (AAV) particles that express angiostatin lead to long-term expression of angiostatin capable of suppressing the outgrowth of EL-4 tumors in the liver. Here we combine AAV-mediated angiostatin therapy with immunotherapy by employing an AAV vector encoding the T-cell costimulator B7.1. Incubation of EL-4 cells with AAV-B7.1 viruses resulted in the rapid expression of B7.1 on the surface of 80% of EL-4 cells. Mice that were vaccinated with B7.1-engineered tumor cells rejected the tumor cells and resisted a secondary challenge with unmodified parental cells. Splenocytes from the vaccinated mice were highly cytotoxic towards parental EL-4 cells in vitro. However, the vaccinated mice failed to resist the challenge of a heavy burden of EL-4 cells. Intraportal injection of AAV particles that express angiostatin into mice that had been vaccinated 1 month earlier with B7.1-engineered tumor cells protected mice against the challenge of a heavy burden of EL-4 cells and eradicated tumors that had disseminated to the liver. The combinational therapy increased the survival rate of mice with advanced liver cancer. These encouraging results warrant investigation of the employment of anti-angiogenic therapy subsequent to cancer immunotherapy for targeting unresectable disseminated liver metastases.

Angiogenesis Inhibitors↗
PubMed2005

Anti-apoptosis effects of oxymatrine protect the liver from warm ischemia reperfusion injury in rats.

Warm ischemia and reperfusion (WI/R) results in the release of destructive proinflammatory cytokines and oxygen free radicals, which in turn cause injury to the liver. Apoptosis is regarded as the central mechanism of liver injury during WI/R. Oxymatrine, an extract from a traditional Chinese herb, Sophora flavescens Ait, has been widely used for the treatment of chronic hepatitis, by virtue of its anti-inflammatory and anti-apoptotic activity. The objective of this study was to investigate whether administration of oxymatrine could protect livers against WI/R. The experimental design consisted of three groups of rats (each group contained 10 Wistar rats): one group were treated by sham-operation; the second (control) group with WI/R were administrated saline, and the third group, rats with WI/R, were administered oxymatrine). Oxymatrine was intravenously administered before a 30-minute period of ischemia. Blood samples were collected for biochemical assay. Liver samples taken at different time points underwent histological examination for detection of apoptotic cells, and Western blotting analysis for Fas and Fas ligand, the key factors in the upper apoptotic pathways. Histologic alteration of the liver was attenuated in oxymatrine-treated rats, and the serum levels of AST and ALT were significantly (P < 0.01) reduced (73% and 61%, respectively). Oxymatrine significantly inhibited cell apoptosis, as examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), and it reduced the apoptotic index by 65% (P < 0.05%) as detected by flow cytometry. The anti-apoptotic activity of oxymatrine depends mainly on downregulation of Fas and Fas ligand. The results of this study indicate that oxymatrine may represent a potent drug to protect the liver against WI/R injury.

Alkaloids↗
PubMed2005

Intramuscular delivery of antiangiogenic genes suppresses secondary metastases after removal of primary tumors.

The success of surgery to remove primary tumors can be compromised by the subsequent outgrowth of metastases. It is recognized that primary tumors secrete antiangiogenic factors that suppress the outgrowth of their daughter metastases. In accord we show here that surgical removal of primary EL-4 lymphomas led to a marked decrease in the levels of circulating angiostatin and endostatin, and promoted the growth of distant nodular tumors. Expression vectors encoding angiostatin and endostatin, formulated with poly-N-vinyl pyrrolidone (PVP), were injected into the tibialis and gastrocnemia muscles, leading to expression of angiostatin and endostatin in muscle fibers. High levels of biologically active exogenous proteins were secreted into the circulation. Intramuscular gene therapy with angiostatin and endostatin plasmids significantly inhibited tumor vascularity and induced tumor cell apoptosis, and thereby suppressed the growth of secondary subcutaneous and disseminated metastatic tumors in the lung and liver. Simultaneous intramuscular delivery of both angiostatin and endostatin plasmids significantly prolonged the survival of mice after removal of primary tumors. These results suggest that intramuscular gene transfer of angiostatin and endostatin might serve as a prophylactic cancer-prevention strategy to combat the recurrence of cancer after surgical resection of primary tumors.

Angiostatins↗
PubMed2005

Captopril restores endothelium-dependent relaxation induced by advanced oxidation protein products in rat aorta.

To explore whether advanced oxidation protein products (AOPP) can cause endothelial dysfunction in vitro, and whether captopril exerts beneficial effect on impaired endothelium-dependent relaxation induced by exogenous advanced oxidation protein products and to investigate the potential mechanisms. Both the Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation of aortic rings were measured by recording isometric tension after the rings were exposed to AOPP-BSA in the absence or presence of captopril to assess the injury effect of AOPP-BSA and the protective effect of captopril on the aortic endothelium, respectively. Co-incubation of aortic rings with AOPP-BSA (3 mmol/L) for 90 minutes resulted in a significant inhibition of EDR to ACh, but had no effects on endothelium-independent relaxation to SNP. After incubation of the rings in the co-presence of captopril (3 to 30 micromol/L) or enalaprilat (30 micromol/L) with AOPP-BSA (3 mmol/L) for 90 minutes, captopril significantly and enalaprilat only partly attenuated the inhibition of EDR induced by AOPP-BSA. This protective effect of captopril (30 micromol/L) was abolished by N-nitro-L-arginine methyl ester (10 micromol/L), an inhibitor of nitric oxide synthase. Furthermore, the superoxide anion scavenger superoxide dismutase (SOD, 200 U/mL), and the nitric oxide precursor L-arginine (3 mmol/L) also ameliorated the impaired EDR caused by AOPP-BSA. But D-arginine had no effect on the impaired EDR caused by AOPP-BSA. AOPP-BSA can trigger endothelial dysfunction and captopril can protect the endothelium against functional damage induced by AOPP-BSA in rat aorta, increase nitric oxide bioavailability. The mechanisms of endothelial dysfunction induced by AOPP-BSA may include the decrease of NO and the generation of oxygen-free radicals.

Animals↗
PubMed2003

Requirements for ICAM-1 immunogene therapy of lymphoma.

Intercellular cell adhesion molecule-1 (ICAM-1) is a cell-surface glycoprotein capable of eliciting bidirectional signals that activate signalling pathways in leukocytes, endothelial, and smooth muscle cells. Gene transfer of xenogeneic ICAM-1 into EL-4 lymphomas causes complete tumor rejection; however, it is unknown whether the mechanism responsible involves the "foreignness" of the ICAM-1 transgene, bidirectional signalling events, ICAM-1-receptor interaction, or a combination of the latter. To begin to address this question, we constructed four different therapeutic expression vectors encoding full-length ICAM-1, and forms in which the N-terminal ligand-binding domains and cytoplasmic tail had been deleted. Mouse EL-4 tumors (0.5 cm in diameter), which actively suppress the immune response, were significantly inhibited in their growth following injection of expression plasmids encoding either full-length xenogenic (human) ICAM-1, or a functional cytoplasmic domain-deficient form that retains ligand-binding activity. Efficacy of ICAM-1-mediated antitumor immunity was significantly augmented by administration of the antivascular drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA), which suppressed blood supply to the tumor, leading to enhanced leukocyte infiltration, and complete tumor eradication in a gene dosage and CD8(+) T cell and NK cell-dependent fashion. Generation of potent cytotoxic T cell (CTL)-mediated antitumor immunity was reflected by ICAM-1-facilitated apoptosis of tumor cells in situ. In contrast, nonfunctional ICAM-1 lacking the N-terminal ligand-binding Ig domain failed to generate antitumor immunity, even in the presence of DMXAA. These studies demonstrate that ICAM-1-stimulated antitumor immunity can overcome tumor-mediated immunosuppression, particularly when employed in combination with an attack on the tumor vasculature. The ligand-binding domain of ICAM-1 is essential for generating antitumor immunity, whereas the cytoplasmic domain and bidirectional activation of tumor signalling pathways are not essential.

Animals↗
PubMed2003

Long-term expression of angiostatin suppresses metastatic liver cancer in mice.

Metastatic liver cancer has a very poor prognosis and lacks effective therapy. Anti-angiogenic therapies, which starve tumors of blood supply, have proven to be effective in preclinical models because tumor growth is angiogenesis dependent. However, long-term, high-level, and sustained expression of angiogenesis inhibitors, such as angiostatin, is necessary to prevent dormant tumors from becoming active again. To achieve this objective, we engineered a recombinant adeno-associated virus (AAV) vector encoding mouse angiostatin, an endogenous inhibitor of tumor vascularization. After intraportal delivery of this vector, high-level, stable transgene expression of angiostatin lasting for at least 6 months was observed locally in hepatocytes. Gene transfer of AAV-angiostatin via the portal vein led to significant suppression of the growth of both nodular and metastatic EL-4 lymphoma tumors established in the liver and prolonged the survival time of the mice. The growth of neovessels was inhibited significantly, and extensive apoptosis of tumor cells was observed. The anti-angiogenic activity of angiostatin was independent of vascular endothelial growth factor (VEGF). The AAV-angiostatin viruses did not appear to be toxic to mice, and there was no detectable apoptosis of hepatocytes. In conclusion, these encouraging results warrant future investigation of the use of AAV-mediated anti-angiogenic gene therapy for targeting unresectable liver metastases, especially after surgical removal of primary tumors.

Angiogenesis Inhibitors↗
PubMed2002

Beta7 integrins contribute to skin graft rejection.

BACKGROUND: Because integrins alpha4beta7 and alphaEbeta7 contribute to epidermotropism of T-cells during skin inflammation, we sought to study their role in skin allograft rejection. METHODS: Wild-type (WT) (beta7+/+) and beta7 gene knockout (beta7-/-) C57BL/6 (H-2(b)) mice and SJL/J (H-2(s)) mice served as donors and recipients of allogeneic skin grafts. An anti-integrin beta7 subunit mAb (FIB504.64) was used to treat WT beta7+/+ C57BL/6 recipients of skin grafts from SJL/J mice. RESULTS: WT C57BL/6 recipients acutely rejected skin from SJL/J mice in 13 days. In contrast, the survival of SJL/J skin on either beta7-/- gene knockout or WT C57BL/6 recipients treated with anti-beta7 subunit mAb, was prolonged by 6 to 7 additional days (P<0.01). The survival of skin allografts from either beta7-/- or beta7+/+ C57BL/6 mice received by SJL/J recipients was not prolonged (P >0.05). CONCLUSIONS: Beta7 integrins contribute to skin graft rejection, in accord with their role in mediating the epidermotropism of T-cells during skin inflammation.

Animals↗