Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

Sun, Jianping; Wang, Yan; Chen, Zhengtang; Wu, Zhuo; Zhu, Bo; Liao, Rongxia; Zhang, Shaoxiang

doi:10.1186/1756-9966-28-21

Cited by 26 publications

(48 citation statements)

References 26 publications

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“…MVD in tumors was assessed by immunohistochemistry as suggested by Weidner (13). Nude mice in Group A were sacrificed by cervical dislocation after the eyeballs were removed.…”

Section: Microvessel Density (Mvd)mentioning

confidence: 99%

Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast cancer in xenograft-bearing mice

Sun

Deng

Duan

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. In the present study, we aimed to investigate the tumor-inhibiting effects of recombinant human endostatin (rhES) combined with paclitaxel-cisplatin (TP regimen) on human breast cancer in xenograft-bearing nude mice. A total of 24 mice bearing human breast cancer xenografts were administered both rhES and TP, TP alone, rhES alone or saline. The tumor growth inhibition was observed. Serum vascular endothelial growth factor (VEGF) levels and microvessel density (MVD) were determined by ELISA and immunohistochemistry, respectively. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Survival time was observed in another 24 nude mice with the same treatment. MVD expression in the group administered rhES and TP was lower than that in the other groups (P<0.05); serum VEGF levels in the combined drug group were lower compared to the other groups; the apoptotic index increased in the combined drug group. We conclude that the effect of the TP regimen combined with rhES on breast cancer is better than that of the TP regimen alone.

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“…MVD in tumors was assessed by immunohistochemistry as suggested by Weidner (13). Nude mice in Group A were sacrificed by cervical dislocation after the eyeballs were removed.…”

Section: Microvessel Density (Mvd)mentioning

confidence: 99%

Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast cancer in xenograft-bearing mice

Sun

Deng

Duan

et al. 2011

Experimental and Therapeutic Medicine

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“…Therefore, Shields et al (2004) suggested that absolute lymphatic vessel-density determination would be more appropriate and facilitate data comparisons. Thus, our aim was to establish a map of lymphatic vessels associated with the lepidic pattern of lung adenocarcinomas, as previous reports on lymphangiogenesis in NSCLC only dealt with invasive carcinomas (Koukourakis et al 2005;Renyi-Vamos et al 2005;Kadota et al 2008;Iwakiri et al 2009;Sun et al 2009). Niki et al (2001) studied a series of pure bronchioloalveolar carcinomas (i.e., adenocarcinoma in situ according to the new classification) but with anti-VEGFR-3 antibody, which does not clearly discriminate between vascular and lymphatic endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…LVD has been associated with poor prognosis of various tumors, notably NSCLC (Renyi-Vamos et al 2005;Kadota et al 2008;Sun et al 2009). Thus, the good prognosis of adenocarcinomas in situ, minimally invasive adenocarcinomas and lepidic-predominant adenocarcinomas (Russell et al 2011;Yoshizawa et al 2011) could be explained, at least in part, by the maintenance of a rather poorly developed lymphatic network, as shown herein.…”

Section: Discussionmentioning

confidence: 99%

“…clearly exhibiting an open lumen were counted, to avoid taking into account cancer-associated myofibroblasts (Kawase et al 2008;Ito et al 2012) that might be recognized by D2-40 antibody, as previously described. In most studies devoted to lymphangiogenesis in carcinomas, only lymphatic vessel "hot spots" were considered (Koukourakis et al 2005;Takanami 2006;Faoro et al 2008;Iwakiri et al 2009;Sun et al 2009) and their density was often demonstrated to be a prognostic factor (Takanami 2006;Iwakiri et al 2009;Sun et al 2009). These so-called hot spots are tumor zones giving the impression, at low magnification, of containing numerous lymphatic vessels but their identification is observer-dependent (Van der Auwera et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In NSCLC, an association between poor prognosis and lymphatic vessel density (LVD) was clearly demonstrated (Renyi-Vamos et al 2005;Kadota et al 2008;Sun et al 2009). …”

mentioning

confidence: 99%

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Morphometry Analysis of Lymphatics in Pulmonary Adenocarcinomas With a Lepidic Growth Pattern

Sannier

Kambouchner

Danel

et al. 2013

J Histochem Cytochem.

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Lymph vessels play an important role in tumor progression. Pulmonary adenocarcinomas, accounting for half of non-small-cell lung carcinomas, compose a spectrum of histological types, exclusively or without a lepidic growth pattern (LGP) along preserved interalveolar septa. In that context, this study was designed to investigate the lymphatic vascular pattern associated with LGP and the concomitant invasive component of pulmonary adenocarcinomas. Using the D2-40 monoclonal antibody as a marker of lymphatic endothelial cells, the lymphatic vessel density (LVD) and vessel-area fraction (LVAF) were morphometrically analyzed in four adenocarcinomas in situ (AIS) and the LGP of eight invasive adenocarcinomas (LPIA), and compared with their invasive pattern (IPIA). LVD in AIS (2.1 ± 0.7 mm−2) and LPIA (2.4 ± 1 mm−2) were significantly lower than that in IPIA (14.9 ± 13.6 mm−2) ( p=0.001). Moreover, the lymphatic vascular pattern in LGP was similar to that of normal lung, with isolated small lymphatic vessels within the interalveolar septa. Our results showing the scarcity of lymphatics in LGP suggest an absence of septal lymphangiogenesis associated with the LGP pattern in lung adenocarcinomas, which could explain, at least partially, the better prognosis observed in tumors with exclusive or predominant lepidic spread compared with other subtypes.

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The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients

et al. 2013

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Angiogenesis has been shown to substantially contribute to the progression of chronic lymphocytic leukemia (CLL). Neuropilin-1 (NRP1) represents a receptor for vascular endothelial growth factor (VEGF), which has been reported to be overexpressed in several malignancies. In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed. Earlier we described the specific Treg reduction during the therapy with thalidomide in vivo. Now we observe the reduction of the NRP1 expression on Tregs in vitro, thereby suggesting a possible target of thalidomide action. In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy.

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Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

Abstract: Background: Our aim was to detect lymphatic endothelial marker podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and vascular endothelial growth factor receptor-3 (VEGFR)-3 and study the prognostic relevance of lymphangiogenesis in non-small cell lung cancer (NSCLC).

Cited by 26 publications

References 26 publications

Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast cancer in xenograft-bearing mice

Inhibitory effect of endostatin combined with paclitaxel-cisplatin on breast cancer in xenograft-bearing mice

Morphometry Analysis of Lymphatics in Pulmonary Adenocarcinomas With a Lepidic Growth Pattern

The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients

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