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  • American Society of Clinical Oncology (ASCO)  (8)
  • 2010-2014  (8)
  • Medicine  (8)
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  • American Society of Clinical Oncology (ASCO)  (8)
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  • 2010-2014  (8)
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  • Medicine  (8)
RVK
  • 1
    Online Resource
    Online Resource
    In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenografts of gastric cancer using multiphoton microscopy.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e22205-e22205
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e22205-e22205
    Abstract: e22205 Background: Peritoneal metastasis shows an extremely poor prognosis in patients with gastric cancer. Clinically, the tumor response to chemotherapeutics depends on anatomical location of metastasis. Metastatic tumor xenografts have been shown to be more resistant to chemotherapy than subcutaneous non-metastatic tumor xenografts in preclinical murine model. We have reported a method of in vivo optical pathology using multiphoton microscopy (MPM) in colorectal liver metastatic tumor xenograft model. Aim: We established a method of time-series in vivo optical pathology of peritoneal metastatic xenografts of gastric cancer using MPM. Then, we imaged and evaluated paclitaxel efficacy in the tumor microenvironment with regard to both tumor cell itself and intravascular change in tumor vessels. Methods: Red fluorescent protein (RFP) expressing human gastric cancer cell line (NUGC4) was inoculated into the peritoneal cavity of green fluorescent protein (GFP) expressing nude mice. Paclitaxel (10 mg/kg) was administered three times a week for more than three weeks. Intravital MPM was performed before and after paclitaxel treatment for the exteriorized peritoneal metastatic lesion in the same living mouse. Results: Four to six weeks later, RFP-NUGC4 cells formed macroscopic peritoneal metastases. Red-colored cancer cells and green-colored surrounding stroma with tumor vessels were clearly imaged at the cellular level (in vivooptical pathology). Their cross-sectional images were obtained from the tissue surface to the area of depth of 200 μm (z-stacks imaging). After paclitaxel treatment, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed. Within the tumor vessels, platelet aggregation and platelet adhesion to endothelial cells were observed. Conclusions: In vivo optical pathology using MPM provides histopathological information about three-dimensional tissue microarchitecture without tissue shrinkage by fixation and tissue destruction by microtome-sectioning. Our method may become a powerful tool to evaluate the tumor response to new chemotherapeutics on ‘metastatic site’ in preclinical tumor xenograft model.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e22205
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    In vivo real-time imaging of tumor microcirculatory alterations in colorectal liver metastatic xenografts by chemotherapy using multiphoton microscopy.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e21053-e21053
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e21053-e21053
    Abstract: e21053 Background: Tumor endothelium is a distinct target for anticancer treatments of metastatic colorectal cancer. Various chemotherapeutics themselves have anti-angiogenic effects on tumor microenvironment by targeting proliferative endothelial cells during tumor angiogenesis. In this study, we imaged the dynamics of tumor microcirculation of colorectal liver metastasis in living mice in vivo real-time using two-photon laser scanning microscopy (TPLSM), and evaluated the microcirculatory alterations in tumor microenvironment by chemotherapy. Methods: Red fluorescent protein expressing human colorectal cancer cell line (HT29) was inoculated to the spleen of green fluorescent protein expressing nude mice. 5-fluorouracil or irinotecan was administered three times a week for more than three weeks for metronomic scheduling. Intravital TPLSM was performed at multiple time points for time-series imaging of liver metastatic xenografts in the same mice. The alterations in tumor microcirculation during chemotherapy was evaluated by measuring blood flows at tumor vessels of colorectal liver metastasis and hepatic sinusoids of adjacent normal liver. Results: At the first TPLSM imaging, the blood flow, as determined from the movement of platelets, was heterogeneous and non-directional in the tumor vessels of liver metastatic xenografts. The blood flow was relatively slower in tumor vessels than normal hepatic sinusoids. At the second TPLSM imaging after chemotherapy, platelet aggregation was observed in tumor vessels of the same mice. Aggregated platelets were frequently adhered to the tumor endothelium, suggesting tumor vessel damage or intratumoral coagulation abnormality by chemotherapy. There was no difference in chemotherapeutics with regard to these findings. Conclusions: Intravital TPLSM imaging of tumor microcirculation at metastatic tumor xenografts is a useful tool to evaluate anti-angiogenic drugs in preclinical models.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e21053
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Serum angiopoietin-like protein 2 as a novel biomarker of diagnosis and prognosis in gastric cancer.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 9-9
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 9-9
    Abstract: 9 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and is known to act as a causative mediator of chronic inflammation and inflammatory carcinogenesis. Recently, we demonstrated that ANGPTL2 overexpresses in gastric cancer (GC) compared to normal gastric mucosa and high ANGPTL2 is associated with poor prognosis. Therefore, if tumor-derived ANGPTL2 over-secretes systemically, focusing ANGPTL2 in blood is logical to evaluate its ability as a biomarker. Accordingly, we quantified serum ANGPTL2 level and assessed its clinical significance in GC patients. Methods: We screened serum ANGPTL2 levels from 32 GC and 24 normal controls (NC) by ELISA (cohort 1). Next, we validated 194 serum samples from GC and 48 NC (cohort 2). Finally, we examined ANGPL2 expression in matched GC tissues of cohort 2 (n=194) by immunohistochemistry (IHC). The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: In cohort 1,serum ANGPTL2 levels in GC were significantly higher than that in NC (p 〈 0.05). Serum ANGPTL2 differentiated GC from NC with high accuracy (AUC=0.814). Analysis of cohort 2 also indicated that serum ANGPTL2 levels in GC were significantly higher compared to NC (p 〈 0.0001), and increased according to UICC stage progression. In addition, serum ANGPTL2 had a promising AUC (0.831) with high sensitivity (73.0%) and specificity(82.2%) to distinguish GC from NC. High serum ANGPTL2 was significantly associated with lymphatic invasion (p=0.03), vessel invasion (p=0.02), distant metastases (p=0.0002), early recurrence (p=0.004) and poor survival (p=0.01), consequently emerged as an independent predicting recurrence marker (HR=5.06, p=0.0004) and prognostic marker (HR=3.6, p=0.01) in GC. Of interest, ANGPTL2 levels in serum from GC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 at the invasive margin of matched GC tissues (r= 0.16, p=0.02). Conclusions: Serum ANGPTL2 levels, which might be secreted from primary or metastatic site into blood stream, have extremely strong potential as a novel biomarker for diagnosis, predicting recurrence and poor prognosis in GC patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.9
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Intravital imaging of fluorescently labeled therapeutic monoclonal antibody on the surface of tumor cells in metastatic tumor xenografts using a multiphoton microscopy.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e22062-e22062
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e22062-e22062
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e22062
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Effect of brain-derived neurotrophic factor/TrkB axis on cancer progression in colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e14039-e14039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14039-e14039
    Abstract: e14039 Background: Brain-derived neurotrophic factor (BDNF) is one of the member of the neurotropin family known to activate the high affinity tyrosine kinase B (TrkB) receptor together with the pan-neurotropin low-affinity coreceptor p75 (p75NTR). TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however, no reports have shown the clinical and biological effects of BDNF/TrkB axis expression in colorectal cancer(CRC). Methods: A total of 223 consecutive patients undergoing surgery for CRC were enrolled. We analyzed BDNF/TrkB mRNA levels by real-time reverse transcription PCR in CRC tissues, and their relationships with clinicopathological findings including survival were investigated. BDNF and TrkB expression were also evaluated by immunohistochemistry. To investigate the biological role of the BDNF/TrkB axis, recombinant human BDNF and Trk antagonist K252a were used for proliferation, migration, and anoikis assays in CRC cell lines. Results: The mean BDNF level in CRC tissue was 94.3 (0-1326.8). One hundred five of 223 patients (47.1%) showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with undifferenciated histological type, lymph node metastasis, and hepatic metastasis. In addition, increased BDNF/TrkB axis expression associated with lymph node metastasis, hepatic metastasis, and peritoneal disseamination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. These effects were generally inhibited by Trk antagonist K252a. Conclusions: We demonstrated the clinical and biological function of BDNF/TrkB axis in CRC. BDNF/TrkB axis appears to play an important role in cancer progression, and blocking this pathway might be clinically useful in developing therapies for patients with CRC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e14039
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    BDNF expression and systemic dissemination via anoikis resistance in gastric cancer.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e14541-e14541
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14541-e14541
    Abstract: e14541 Background: Anoikis (apoptosis resulting from loss of cell-matrix interaction) has been suggested to act as a physiological barrier to metastasis, and resistance to anoikis is necessary for cancer cell survival during systemic dissemination and metastasis. Brain-derived neurotrophic factor (BDNF) is one of the member of neurotropin family known to activate the high affinity tyrosine kinase (Trk)B receptor as a specific suppressor of anoikis. TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however no reports have shown the clinical and biological effects of BDNF/TrkB axis in gastric cancer. Methods: BDNF expression in gastric cancer tissue and clinicopathological data from 153 consective patients were analyzed by real-time PCR and immunohistochemistry. The extent of target gene expression was calculated from the standard curve, with quantitative normalization of the cDNA in each sample performed using GAPDH gene as an internal control. Recombinant human BDNF and Trk antagonist K252a were used for in vitro assays to evaluate the biological role of the BDNF/TrkB axis in gastric cancer cell lines. Results: The mean BDNF level in gastric cancer tissue was 284.5 (0-2834). One hundred eighteen (77.1%) of 153 patients showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with histological diffuse type (p=0.019), lymph node metastasis (p 〈 0.001), peritoneal dissemination (p=0.028) and poor prognosis (p=0.022). In addition, BDNF expression is an independent risk factor for lymph node metastasis and peritoneal dissemination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. In addition, these effects were generally inhibited by Trk antagonist K252a. Conclusions: BDNF appears to play an important role in gastric cancer progression, and blocking BDNF/TrkB axis might be clinically useful in developing therapies for patients with gastric cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e14541
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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    Online Resource
  • 7
    Online Resource
    Online Resource
    Clinical significance of serum angiopoietin-like protein 2 in colorectal cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 417-417
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 417-417
    Abstract: 417 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family. It has been reported to act as a causative mediator of chronic inflammation and metabolic abnormalities. ANGPTL2 increases inflammatory carcinogenesis in several cancers, and its expression in tumor cells is highly correlated with the frequency of tumor cell metastasis through increased tumor angiogenesis and tumor cell epithelial-to-mesenchymal transitions. However, to our own knowledge, clinical significance of serum ANGPTL2 in cancer patients remains unknown. The aim of this study was to quantify serum ANGPTL2 level using ELISA, and to evaluate its clinical and prognostic significance in patients with colorectal cancer (CRC). Methods: We quantified serum ANGPTL2 levels from 194 CRC patients and normal 48 controls (NC) by ELISA. Next, we investigated ANGPTL2 expression in matched CRC tissues (n=194) by immunohistochemistry (IHC) to identify the source of circulating ANGPTL2. The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: Serum ANGPTL2 levels were significantly higher in CRC than in NC (p 〈 0.01) and gradually increased according to TNM stage progression. Serum ANGPTL2 levels discriminated CRC from NC with high accuracy (AUC=0.837). High serum ANGPTL2 was significantly associated with larger tumor size (p=0.03), undifferentiated adenocarcinoma (p=0.03), advanced T stage (p 〈 0.01), peritoneal metastasis (p 〈 0.01). In addition, Kaplan–Meier curves revealed that high serum ANGPTL2 were significantly associated with poor disease free survival (p=0.01) and overall survival (p=0.03). Interestingly, ANGPTL2 levels in serum from CRC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 expression in matched CRC tissues (r=0.14, p=0.03). Conclusions: Serum ANGPTL2, which might be derived from primary CRC tumor, has strong potential to serve as a noninvasive biomarker for CRC diagnosis and prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.417
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Prediction of lymph node metastasis and prognosis in colorectal cancer patients using slug and vimentin expression.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e14029-e14029
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e14029-e14029
    Abstract: e14029 Background: Slug plays a critical role in regulating the epithelial-mesenchymal transition (EMT) by down-regulation of epithelial markers and up-regulation of mesenchymal markers. The purpose of the present study was to evaluate the clinical significance of Slug and Vimentin expression in colorectal cancer (CRC) and to perform in vitro characterization of Slug’s function. Methods: At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. We next analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Results: Knockdown of Slug in siRNA knockdown studies resulted in induction of EMT markers, inhibited cancer cell proliferation, invasion and migration abilities. Slug and Vimentin expression in cancer tissues was significantly higher in patients with high T stage, lymph node involvement, liver metastasis and advanced TNM stage. We also observed a significant correlation between Slug and Vimentin expression in CRC (rho = 0.467). Increased Slug and Vimentin expression were significantly associated with poor prognosis in Stage I-IV (p 〈 0.0001, p=0.0005, log-rank test) and Stage II (p= 0.04, p=0.012, log-rank test) Furthermore, increased Slug expression was an independent predictive marker of lymph node metastasis (p=0.012) and prognostic factor (p= 0.025). Conclusions: Our data demonstrate that evaluation of Slug and Vimentin could be valuable in the identification of patients with lymph node metastasis or poor prognosis in CRC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e14029
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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