共查询到20条相似文献,搜索用时 46 毫秒
1.
Li-Jen Kuo Chin-Sheng Hung Wei-Yu Chen Yu-Jia Chang Po-Li Wei 《The Journal of surgical research》2013
Background
Up to 20% of colorectal cancer (CRC) is diagnosed with distant metastasis. The combination of chemotherapy with anti-vascular endothelial growth factor (VEGF) antibody can improve patient survival. Glucose-regulated protein 78 (GRP78) has an important role in cancer progression, but little is known about its role in VEGF production in CRC. The aim of this study was to explore the mechanism of GRP78 in two human colon cancer cell lines.Methods
We first checked the expression of GRP78 in human normal and colon cancer tissues and two colon cancer cell lines. Glucose-regulated protein 78 was knocked down using GRP78 small interfering RNA (siRNA) in HT29 and DLD-1 cells. We examined knockdown cells by the cell growth kinetics in vitro and tumor growth rate in vivo, respectively. We also investigated the effect of GRP78 siRNA on the expression of hypoxia inducible factor (HIF-1α), VEGF, and VEGF receptor 2 (VEGFR2).Results
Compared with their adjacent normal tissue, we detected high expression levels of GRP78 of surgically removed colon cancer tissues. Using GRP78 siRNA, we reduced the expression of GRP78 in HT29 and DLD-1 cells. The GRP78 knockdown cells had a lower proliferation rate with fewer colony-forming units in vitro and produced smaller tumors in vivo. In dissecting the mechanism underlying the reduced cell growth, we found that the down-regulation of GRP78 decreased the production of HIF-1α, VEGF, and VEGFR2 and suppressed angiogenesis.Conclusions
Silencing GRP78 not only inhibits tumor, but also decreases the expression of VEGF and VEGFR2. Collectively, therapy targeting for GRP78 may inhibit the formation of colon cancer tumors via the HIF-1α/VEGF/VEGFR2 pathway. 相似文献2.
Qiang Liu MD PhD Weichang Chen Yang Jiao Jianquan HouQingyu Wu MD PhD Yanli Liu Xiaofei Qi 《The Journal of surgical research》2014
Background
Many natural compounds possess antitumor growth activities. Pulsatilla chinensis is an herb used in traditional Chinese medicine to treat infectious diseases. More recently, extracts from P chinensis have been shown to contain antitumor activities.Materials and methods
In this study, we isolated Pulsatilla saponin A as an active compound from P chinensis extracts and tested its anticancer activity in vitro and in vivo.Results
In cell culture, Pulsatilla saponin A significantly inhibited the growth of human hepatocellular carcinoma SMCC-7721 cells and pancreatic BXPC3 and SW1990 cancer cells. Similar inhibitory activities were observed when the compound was tested in mouse xenograft tumor models using human hepatocellular carcinoma Bel-7402 and pancreatic cancer SW1990 cells. In Comet assay and flow cytometric analysis of cell cycle distribution and annexin V expression, DNA damage, G2 arrest, and apoptosis were identified in Pulsatilla saponin A–treated cancer cells. Based on the results of Western blotting, p53 and cyclin B protein levels were higher, whereas Bcl-2 protein levels were lower in Pulsatilla saponin A–treated cancer cells than in vehicle-treated cells.Conclusions
Pulsatilla saponin A may exert its antitumor effect by inducing DNA damage and causing G2 arrest and apoptosis in cancer cells. Pulsatilla saponin A and its derivatives may be developed as a new class of anticancer agents. 相似文献3.
Swathi Balaji PhD Maria LeSaint Sukanta S. Bhattacharya Chad Moles Mykia KiddLouis D. Le MD Alice King Aimen Shaaban Timothy M. Crombleholme Paul Bollyky Sundeep G. Keswani 《The Journal of surgical research》2014
Background
Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway.Methods
Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal human skin, and 3-mm full-thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8-mm full-thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1 × 108 particle forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n = 4–5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7 for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin; Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary density (CD 31 + CAPS/HPF) were analyzed at day 7.Results
In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1 overexpression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1 overexpression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared with control treatments.Conclusions
In two different models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization. 相似文献4.
Monika Posaric-Bauden Karolin Isaksson Daniel Åkerberg Roland Andersson Bobby Tingstedt 《The Journal of surgical research》2014
Background
Postoperative peritoneal carcinomatosis together with adhesion formation are considered as two major clinical complications after resection of malignant abdominal tumors, jeopardizing the beneficial effect of the curative surgery. Biobarrier is a novel anti-adhesive barrier fulfilling the criteria for a good adhesion preventive agent, possessing biochemical properties that may enable it to function as a dual efficient device, reducing both adhesion and tumor development. This study aims to evaluate the effect of novel anti-adhesive device Biobarrier on intra-abdominal tumor progression.Materials and methods
Cells from cancer cell line BN7005H1D2 were treated with Biobarrier to determine the effect of Biobarrier on cell attachment and viability in vitro. For the in vivo experiments, bilateral peritoneal trauma was inflicted in a reproducible syngeneic rat model. To mimic the clinical situation, the animals received an intraperitoneal injection of BN7005H1D2 cancer cells at the end of surgery, resembling perioperative tumor spill after intraperitoneal instillation of Biobarrier. Animals without given anti-adhesive treatment were used as control.Results
Biobarrier applied in vitro hindered cells from attachment to the wells. In vivo treatment with Biobarrier significantly reduced tumor growth at both sites of surgical trauma (P = 0.001 and 0.015) and other non-traumatized intraperitoneal sites (P = 0.021).Conclusions
Biobarrier maybe effective in reducing intra-abdominal tumor cell implantation with subsequent tumor development in conjunction with peritoneal trauma in a syngeneic rat model. 相似文献5.
Deepika Nehra Amy H. Pan Hau D. Le Erica M. Fallon Sarah J. Carlson Brian T. Kalish Mark Puder 《The Journal of surgical research》2014
Background
To determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein–coupled receptors (GPRs) in mediating this effect.Materials and methods
For in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo.Results
DHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group.Conclusions
DHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo. 相似文献6.
Sanjib Chowdhury Melanie Ongchin Guanghua Wan Elizabeth Sharratt Michael G. Brattain Ashwani Rajput 《The Journal of surgical research》2013
Background
Mutational loss of tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN) is associated with malignant progression in many cancers, including colorectal cancer (CRC). PTEN is involved in negatively regulating the phosphatidylinositol 3-kinase/AKT oncogenic signaling pathway and has been implicated in the metastatic colonization process. Few in vivo models are available to study CRC metastasis. The purpose of this study was to determine the effect of restoring PTEN activity on metastases in an orthotopic murine model.Methods
Green fluorescent protein labeled TENN, a highly metastatic human colon cancer cell line with mutational loss of PTEN gene and TENN clones (with restoration of PTEN gene) tumors were orthotopically implanted onto the colons of BALB/c nude mice and allowed to develop primary and metastatic tumors. Seven weeks post-implantation, mice were euthanized and organs extracted for examination.Results
Both TENN and TENN clone cell lines demonstrated 100% primary invasion. However, compared with the parental TENN cells, which demonstrated 62% metastases to both lungs and liver, TENN clone cells showed an approximately 50% reduction in metastasis, with only 31.6% liver metastasis and no metastasis to the lungs (P = 0.02).Conclusions
Our study shows that reactivation of PTEN tumor suppressor pathway leads to a 50% reduction in CRC metastasis without affecting primary tumor formation. Importantly, PTEN restoration also changed the organotropic homing from liver and lung metastasis to liver metastasis only. This in vivo study demonstrates that PTEN might act specifically as a metastasis suppressor and, thus, efforts to target the phosphatidylinositol 3-kinase/PTEN pathway are legitimate. 相似文献7.
Bin Yang Liuhua Zhou Bo Peng Zeyu Sun Yutian Dai Junhua Zheng 《The Journal of surgical research》2014
Background
To compare the effects of various recombinant growth factors on bladder regeneration and angiogenesis for tissue engineering of bladder in patients with neurogenic bladder through in vitro cellular biological methods.Materials and methods
Human bladder smooth muscle cells (HBSMCs) and human bladder urothelial cells (HBUCs) were cultured from patients with neurogenic bladder and used for comparative evaluations of various growth factors. Human umbilical vein endothelial cells (HUVECs) were also used. Eight potential growth factors, platelet-derived growth factor BB (PDGF-BB), platelet-derived growth factor CC (PDGF-CC), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), and transforming growth factor beta 1 (TGF-β1), were selected and their effects on the proliferation, migration, and wound healing of HBSMCs, HBUCs, and HUVECs were compared.Results
PDGF-BB, PDGF-CC, bFGF, VEGF, IGF-1, or HGF enhanced the proliferation, migration, and wound healing of HBSMCs, whereas TGF-β1 inhibited their proliferation. Proliferation, migration, and wound healing of HBUCs and HUVECs were enhanced by bFGF, VEGF, EGF, IGF-1, or HGF, whereas inhibited by TGF-β1. PDGF-BB failed to enhance cell activity of HUVECs, whereas PDGF-CC could enhance their migration and wound healing. PDGF-BB, EGF, and VEGF were the most potent factors for stimulating the activities of HBSMCs, HBUCs, and HUVECs, respectively.Conclusions
Our findings suggest the potential use of a combination of PDGF-BB, EGF, and VEGF for bladder regeneration and angiogenesis. The synergetic effects of the three growth factors on cell activities in a three-dimensional scaffold and an animal model with neurogenic bladder need to be further evaluated. 相似文献8.
Shinichiro YamadaMitsuo Shimada MD PhD Tohru UtsunomiyaTetsuya Ikemoto MD PhD Yu SaitoYuji Morine MD PhD Satoru ImuraHiroki Mori MD PhD Yusuke ArakawaMami Kanamoto MD PhD Shuichi Iwahashi MD PhD 《The Journal of surgical research》2014
Background
Adipose tissue–derived stem cells (ADSCs), which are widely known as multipotent progenitor cells, release several cytokines that support cell survival and repair. The aim of this study was to investigate whether ADSC-secreted molecules could induce a trophic effect in pancreatic islet culture conditions in vitro.Materials and methods
We cocultured porcine islet cells with ADSCs using a transwell system for 48 h and evaluated the viability of islet cells. We also determined the concentration levels of cytokines and insulin in the supernatant of the culture medium. We used anti-vascular endothelial growth factor (VEGF) and anti-interleukin (IL)-6 receptor antibodies to investigate the effect of VEGF and IL-6 on islet cells.Results
ADSCs improved the viability of islet cells in the absence of cell-cell contact (P < 0.05). VEGF and IL-6 levels in the culture medium increased when islet cells were cocultured with ADSCs (P < 0.05). Furthermore, inhibition of VEGF decreased the viability of islet cells (P < 0.05); however, inhibition of IL-6 did not affect islet cell viability.Conclusions
These results suggested that trophic factors, particularly VEGF, secreted by human ADSCs enhanced the survival and function of porcine islet cells. 相似文献9.
Yong Beom Cho Hye Kyung Hong Yoon-La Choi Ensel Oh Kyeung Min Joo Juyoun Jin Do-Hyun Nam Young-Hyeh Ko Woo Yong Lee 《The Journal of surgical research》2014
Background
Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples.Methods
Primary and metastatic colorectal tumor tissues (1–2 mm3) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts.Results
From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000–1500 mm3 of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor.Conclusions
Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. 相似文献10.
Andreas Thalheimer MD Doreen Korb Lars Bönicke Armin Wiegering Bettina MühlingSimone S. Riedel PhD Christoph Thomas Germer Andreas Beilhack Stephanie Brändlein Christoph Otto 《The Journal of surgical research》2013
Background
Bioluminescence imaging (BLI) is an ideal tool for noninvasive, quantitative monitoring of tumor progression/regression in animal models. The effectiveness of different treatment strategies is displayed by an altered intensity of bioluminescence, demonstrating a change of the tumor burden. The aim of this study was to establish a reliable, reproducible colorectal hepatic metastases cancer animal model.Methods
Cells of the human colon carcinoma cell line HCT-116 Lucpos expressing the firefly luciferase enzyme gene were used. HCT-116 Lucpos cells (2.5 × 106) were injected through the portal vein into the liver of immunoincompetent nude mice. BLI was used to analyze intrahepatic tumor burden and growth kinetic.Results
HCT-116 Lucpos cells demonstrated a progressive and reproducible growth in the liver after intraportal injection. Four days after injection, the animals were analyzed for tumor growth by BLI, and mice without or too low bioluminescence signals were excluded (between 10% and 20% animals). HCT-116 Lucpos intrahepatic tumors responded successfully to different dosages (5 and 10 mg/kg) of 5-fluorouracil.Conclusions
BLI is an important tool with many potential advantages for investigators. The measurement of intrahepatic tumor growth by imaging luciferase activity noninvasively provides valuable information on tumor burden and effectiveness of therapy. Thus, the presented intrahepatic metastases model based on the growth of HCT-116 Lucpos cells is suitable for in vivo testing of different cancer therapy strategies. 相似文献11.
Elizabeth Kiwanuka Florian Hackl Edward J. Caterson Daniel Nowinski Johan P.E. Junker Bengt Gerdin Elof Eriksson 《The Journal of surgical research》2013
Background
CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing.Materials and methods
Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/mitogen-activated protein kinase pathway to human keratinocytes were studied.Results
The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration.Conclusions
CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway. 相似文献12.
Cristina A. Metildi Sharmeela Kaushal Robert M. Hoffman Michael Bouvet 《The Journal of surgical research》2013
Introduction
Kras mutations have been thought to play an important role in pancreatic cancer progression. In this study, we evaluated how serially passaging primary pancreatic tumors with and without Kras mutations, in nude mice, can generate more aggressive variants of human pancreatic cancer.Materials & methods
Orthotopic mouse models of human pancreatic cancer were established by injecting 1 × 106 cells of the Kras wildtype BxPC-3 cell line, expressing red fluorescent protein or the Kras mutant Panc-1 cell line expressing green fluorescent protein, into the pancreas. Pancreatic tumors were harvested from premorbid mice to establish cell lines. One million passaged cells were then orthotopically injected into another set of mice. Serial passaging continued until decreasing lifespan of the implanted mice stabilized, which occurred by six passages. Mice harboring serially-passaged cell lines were followed with weekly imaging.Results
Serially passaging generated more aggressive variants of both human pancreatic cancer cell lines, one of which was Kras wild-type (BXPC-3) and the other Kras mutant, Panc-1, which displayed faster tumor growth and shortened survival time. Overall survival decreased from 18 wk in mice with the parental cell line (passage 0) tumor to ∼6 wk in mice by passage 6. Average time to metastasis was shortened from 14 wk to ∼3 wk or less. At termination, mice with the passaged tumor demonstrated a greater extent of distant metastasis.Conclusions
Serial passaging of tumor creates more aggressive variants of human pancreatic cancer cell lines regardless of Kras mutation. The aggressive variants can be used to study the molecular basis of highly malignant pancreatic cancer and to screen for effective agents against this disease. 相似文献13.
Annette Wunderlich Maryna Khoruzhyk Silvia Roth Annette Ramaswamy Brandon H. Greene Dietrich Doll Detlef K. Bartsch Sebastian Hoffmann 《The Journal of surgical research》2013
Background
Despite various attempts at modifying usual treatment modalities, anaplastic thyroid cancer (ATC) is still associated with unfavorable prognosis. Results of preclinical investigations are often of limited transferability to clinical tumor biology. Individualized multimodal treatment regimens, including novel growth-inhibiting drugs, might be a future option.Methods
Tumor tissue, freshly prepared from a patient operated for ATC, was xenotransplanted to nude mice. While the patient obtained a hyperfractionated external beam radiation, mice carrying xenotransplanted tumors were randomized (n = 6) and treated by multikinase inhibitors (sorafenib [S]: vascular endothelial growth factor receptor [VEGF-R], platelet derived growth factor receptor, RET; vandetanib [V]: VEGF-R, endothelial growth factor receptor [EGF-R]; and MLN8054 [M]: Aurora kinases [AK]). Antiproliferative, antiangiogenic, and proapoptotic effects were evaluated.Results
Treatment of successfully xenotransplanted fresh ATC tumor tissue by multikinase inhibitors and aurora kinase inhibitor reduced the tumor volume up to 61% depending on the drug and time of application (3 wk of treatment: 46% [M], 34% [V], 30% [S]; 5 wk of treatment: 61% [S]). Tumor cell proliferation (BrdU) was reduced between 34% and 58% [S] and [V]. Reduction of tumor vascularity was between 67% [V] and 33% [S] and was accompanied by decreased EGF-R/VEGF-R2 receptor activity [V/V,S]. Tumor cell apoptosis (caspase 3 activity) increased up to 2.4-fold [S].Conclusions
Successful in vivo evaluation of novel drugs in xenotransplanted fresh tumor tissue allows in-time (while patient receives standard treatment) prospective analysis for possible additional clinical application. However, technical specifications have to be taken into account to obtain stable in vivo tumor growth. Based on the individual results, a tailored clinical drug application seems possible. 相似文献14.
15.
Melissa L. Korb Yolanda E. Hartman Joy Kovar Kurt R. Zinn Kirby I. Bland Eben L. Rosenthal 《The Journal of surgical research》2014
Background
Complete surgical resection of breast cancer is a powerful determinant of patient outcome, and failure to achieve negative margins results in reoperation in between 30% and 60% of patients. We hypothesize that repurposing Food and Drug Administration–approved antibodies as tumor-targeting diagnostic molecules can function as optical contrast agents to identify the boundaries of malignant tissue intraoperatively.Materials and methods
The monoclonal antibodies bevacizumab, cetuximab, panitumumab, trastuzumab, and tocilizumab were covalently linked to a near-infrared fluorescence probe (IRDye800CW) and in vitro binding assays were performed to confirm ligand-specific binding. Nude mice bearing human breast cancer flank tumors were intravenously injected with the antibody–IRDye800 bioconjugates and imaged over time. Tumor resections were performed using the SPY and Pearl Impulse systems, and the presence or absence of tumor was confirmed by conventional and fluorescence histology.Results
Tumor was distinguishable from normal tissue using both SPY and Pearl systems, with both platforms being able to detect tumor as small as 0.5 mg. Serial surgical resections demonstrated that real-time fluorescence can differentiate subclinical segments of disease. Pathologic examination of samples by conventional and optical histology using the Odyssey scanner confirmed that the bioconjugates were specific for tumor cells and allowed accurate differentiation of malignant areas from normal tissue.Conclusions
Human breast cancer tumors can be imaged in vivo with multiple optical imaging platforms using near-infrared fluorescently labeled antibodies. These data support additional preclinical investigations for improving the surgical resection of malignancies with the goal of eventual clinical translation. 相似文献16.
Xian-ming Liang Gui-fang Guo Xian-hui Huang Wen-long Duan Zhen-ling Zeng 《The Journal of surgical research》2014
Background
Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo.Methods
In vitro, RAW 264.7 cells were pretreated with different dose of ITD 1 h before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h before LPS.Results
In vitro, the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by ITD. Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by ITD. Furthermore, our data showed that ITD significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model.Conclusions
These results suggested that ITD dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process. 相似文献17.
Teodoro Palomares Ignacio García-Alonso Roberto San Isidro Jaime Méndez Ana Alonso-Varona 《The Journal of surgical research》2014
Background
We previously demonstrated a stimulating effect of hepatectomy on residual tumor cells after resection of liver metastases. The aim of this study was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor effect of hepatectomy and survival of hepatectomized rats bearing liver metastases. We also explored whether ATRA interfered with the tumor promoting effect of hepatotropic growth factors (GFs).Methods
The in vitro effect of ATRA on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo studies, rats were partially hepatectomized on day 10 after metastasis induction, one group being treated with ATRA from day 7 to 14, and a second receiving cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the size and number of liver and lung metastases. Finally, we analyzed the effect of treatments on rat survival.Results
Hepatotropic GFs increased cell proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver and lung metastases, and significantly increased rat survival. Furthermore, adding ATRA to CY significantly increased survival compared with CY alone.Conclusions
In our model, ATRA minimizes the tumor-stimulating effect of hepatectomy, reducing the number and size of liver metastases and improving survival. The results suggest that the ATRA may be useful for blocking the growth-promoting effect of hepatotropic GFs released after liver metastasis resection. 相似文献18.
Fang Liu Guo-quan Sun Hua-yi Gao Rui-sheng Li Lanan-Wassy Soromou Na Chen Yan-Hong Deng Hai-hua Feng 《The Journal of surgical research》2013
Background
Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model.Materials and methods
The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 h after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses.Results
The results showed that pretreatment with angelicin markedly downregulated TNF-α and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IκBα, NF-κBp65, p38 MAPK, and JNK in LPS-induced ALI.Conclusions
These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-κB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic. 相似文献19.
Yunfen GeShuangfei Hu MD Yunlong ZhangWenyuan Wang PhD Qiong XuLeping Zhou MD Hui Mao MD 《The Journal of surgical research》2014
Background
The aim of the study was to investigate whether levobupivacaine (LB) suppressed lipopolysaccharide (LPS)-induced high mobility group box 1 (HMGB1) release in vitro and in vivo, and to determin its molecular mechanisms of action.Materials and methods
RAW264.7 cells were treated with LPS and LB for 24 h. Levels of HMGB1, nuclear factor-kappa B (NF-κB) and phosphorylated p38 mitogen-activated protein kinase (MAPK) were measured by Enzyme-linked immunosorbent assay and Western blotting; the levels of HMGB1 messenger RNA were measured by real-time polymerase chain reaction. In addition, cecal ligation and puncture–induced septic C57BL/6 received LB infusion, and the levels of HMGB1 and functional parameters of multiple organs determined using several detection kits.Results
LB inhibited HMGB1 release in vitro and in vivo. Furthermore, LB inhibited the translocation of NF-κB and phosphorylation of p38 MAPK in vitro. Mice treated with LB infusion improved survival in mice and significantly reduced cecal ligation and puncture–induced dysfunction of organs.Conclusions
LB suppresses LPS-induced HMGB1 release in vitro and in vivo by partially inhibiting NF-κB/p38 MAPK pathways. LB can rescue mice from sepsis and protect against organ dysfunction in septic mice. 相似文献20.
Bocui Song Shuang Guan Jing Lu Zhibao Chen Guoren Huang Gen Li Ying Xiong Shuang Zhang Zhanpeng Yue Xuming Deng 《The Journal of surgical research》2013