Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF)-C and VEGF-D influence lymphangiogenesis through the activation of the vascular endothelial growth factor receptor (VEGFR)-3. They have been implicated in lymphatic tumor spread, which is an important prognostic factor in patients with non-small cell lung carcinoma (NSCLC). Whether or not the expression of VEGF-C, -D, and VEGFR-3 correlates with clinicopathological factors in patients with T1 lung adenocarcinoma was analysed. The tumor specimens were homogenized to determine the protein expression of VEGF-C, -D, and VEGFR-3 by enzyme-linked immunosorbent assay (ELISA). RNA fractions extracted from the tumor tissues were subjected to real-time reverse transcription-polymerase chain reaction (RT-PCR) to assess the mRNA levels of VEGF-C, -D, and VEGFR-3. The expression of VEGF-D protein and mRNA levels in patients without lymph node metastasis were significantly higher than those with metastasis (p=0.013, p=0.0494, respectively). However, the protein and mRNA levels of VEGF-C and VEGFR-3 were not significantly different in patients with or without metastasis. The 5-year survival rates of the patients with high VEGF-D levels were significantly higher than those of patients with low levels (p =0.0221). No significant difference in the survival rates was observed for VEGF-C and VEGFR-3. VEGF-D may be downregulated in NSCLC tissues in comparison to adjacent normal tissue, resulting in lymph node metastasis and poor prognosis.
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PMID:Correlation between lymph node metastasis and the expression of VEGF-C, VEGF-D and VEGFR-3 in T1 lung adenocarcinoma. 1797 36

Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.
Lung Cancer 2008 May
PMID:Serum vascular endothelial growth factor is related to systemic oxidative stress in patients with lung cancer. 1939 40

Lung cancer continues to be the leading cause of cancer death in Western countries. The median survival time for advanced non-small cell lung cancer (NSCLC) remains poor and chemotherapy is the treatment of choice for most patients with metastatic NSCLC. Platinum-based chemotherapy has long been the standard of care for advanced NSCLC. The formation of new blood vessels (angiogenesis) is needed for the growth and invasiveness of primary tumours, and plays an important role in metastatic growth. Vascular endothelial growth factor (VEGF) has emerged as a key potential target for the pharmacological inhibition of tumour angiogenesis. This review discusses current data and the future potential of bevacizumab, a recombinant humanized monoclonal antibody that binds VEGF, in the treatment of NSCLC. Results from a phase II study showed that the addition of bevacizumab to the first-line chemotherapy with paclitaxel and carboplatin (CP) may increase the overall survival (OS) and the time to progression in advanced NSCLC. Based on these promising results, a randomized phase III trial compared the combination of bevacizumab with CP versus CP alone in the treatment of advanced non-squamous NSCLC. The combination of CP plus bevacizumab led to a statistically significant increase in median OS and progression-free survival (PFS) compared with CP alone, with a response rate (RR) in the CP arm of 15% compared with 35% in the bevacizumab plus CP arm (p < 0.001). More recently, the randomized AVAIL (Avastin in Lung Cancer) study, which evaluated cisplatin with gemcitabine plus bevacizumab in two different dosages versus chemotherapy alone in 1043 patients with recurrent or advanced non-squamous NSCLC, reported a significant increase of PFS, RR and duration of response for both of the bevacizumab-containing arms. Bevacizumab has also been investigated in combination with erlitonib as second-line treatment in two small early phase trials, with interesting results. Bevacizumab was generally well tolerated in clinical trials; the main treatment-associated adverse events were neutropenia and haemorrhage, especially in the lung, but also at other sites. Several trials that incorporate bevacizumab in combination with new active drugs in NSCLC are ongoing and should further help to define the place of bevacizumab in the therapy of NSCLC.
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PMID:Bevacizumab in non-small cell lung cancer. 1841 83

Malignant pleural effusion (MPE) is associated with advanced-stage lung cancer and is a poor prognostic sign for these patients. Osteopontin (OPN) is a multifunctional cytokine that is involved in the tumor progression and angiogenesis of lung cancer cells. The purpose of this study is to investigate and provide evidence for the role of OPN in the formation of MPE associated with lung cancer. In this study, we established an OPN knockdown murine lung cancer cell line, 3LL cells, utilizing the small interfering RNA (siRNA) technique. To reveal the effect of OPN on the formation of MPE associated with lung cancer, we directly injected OPN knockdown 3LL cells, 3LL/OPN siRNA, or control cells, 3LL/control siRNA, into the pleural space of C57BL/6 mice. OPN knockdown significantly reduced the formation of MPE, but did not inhibit in vivo tumor growth of 3LL cells in mice. Vascular endothelial growth factor (VEGF) concentration in MPE was markedly decreased in the 3LL/OPN siRNA in comparison with that of the 3LL/control siRNA. In vitro, recombinant OPN protein enhanced VEGF secretion from human umbilical vein endothelial cell (HUVEC) or human mesothelial cell line, Met5A cells, in a concentration-dependent manner. These results suggest that OPN is positively involved in the formation of MPE of lung cancer presumably by promoting VEGF secretion from vascular endothelial cells or mesothelial cells. OPN could be an effective target molecule for reducing MPE in lung cancer patients.
Lung Cancer 2009 Mar
PMID:Osteopontin is involved in the formation of malignant pleural effusion in lung cancer. 1875 67

Vascular endothelial growth factor (VEGF) is a positive regulator of angiogenesis, and its expression is up-regulated in many carcinomas. In the present study, we found that a microRNA miR-126 has a binding site in 3'-untranslated region of the VEGF-A mRNA. In eight lung cancer cell lines, expression of miR-126 was down-regulated. Reporter gene assay showed that the co-transfection of mir-126 expression vector with pLuc-VEGF/mir126BS could reduce the activity of luciferase. Transfection experiments showed that miR-126 could decrease the expression of VEGF-A. Three human lung carcinoma cell lines A549, Y-90 and SPC-A1 were investigated as cancer models in vitro, and A549 infected by lentivirus-miR-126 (LV-miR-126) was studied in tumor xenograft model. Infection of LV-miR-126 can down-regulate the expression of VEGF-A in A549, Y-90 and SPC-A1 cell lines and can inhibit the growth of these cells. In addition, flow cytometry analysis revealed that LV-miR-126 infection can induce cell cycle G1 arrest in A549, Y-90 and SPC-A1 cells. Furthermore, in nude mice, the average weight of A549 tumor nodules in experimental group was reduced from 0.8035+/-0.1521 to 0.6235+/-0.0757g, with the inhibitive rate being 22.4%. All these results revealed that miR-126 may have a tumor suppressor function in lung cancer cells and could be a promising treatment in anticancer therapy.
Lung Cancer 2009 Nov
PMID:MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. 1922 90

Vascular endothelial growth factor (VEGF) plays an important role in the growth and metastasis of non-small-cell lung cancer (NSCLC). The aim of this study was to develop an RNA-interference approach that targets VEGF, using a recombinant plasmid, and to explore its antitumor efficacy in NSCLC in vivo. shRNA-targeting VEGF was cloned into pGenesil-2 plasmid vector and then transfected into A549 human lung cancer cells, using cationic liposome. Reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis were used to evaluate the silencing effects of VEGF-shRNA on A549 cells in vitro. Further, the growth-inhibition capacity of VEGF-shRNA on A549 lung carcinoma xenografts was tested in nude mice. Proliferation, apoptosis, and angiogenesis in tumor tissues were measured by PCNA, TUNEL, and CD31 immunohistochemistry, respectively. shRNA-targeting VEGF significantly silenced VEGF expression in A549 lung cancer cells, as confirmed by RT-PCR and ELISA assay (P < 0.01). In vivo, the VEGF-shRNA delayed tumor growth and reduced tumor weight by approximately 61.96%, compared with control groups (P < 0.05), accompanied with angiogenesis inhibition (P < 0.01) and apoptosis induction (P < 0.01). Our data showed that the knockdown of VEGF by shRNA might be a potential therapeutic approach against human NSCLC.
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PMID:Efficient inhibition of non-small-cell lung cancer xenograft by systemic delivery of plasmid-encoding short-hairpin RNA targeting VEGF. 2018 98

Vascular endothelial growth factor VEGF(165) is a critical element for development of the vascular system in physiological and pathological angiogenesis. VEGF isoforms have different affinities for heparan sulphate proteoglycan (HSPG) as well as for VEGF receptors; HSPGs are important regulators in vascular development. Therefore, inhibition of interactions between VEGF and HSPGs may prevent angiogenesis. Here, we demonstrate that an HSPG-binding synthetic peptide, corresponding to exon 6a-encoded domain of VEGF gene, has anti-angiogenic property. This 20 amino acids synthetic peptide prevents VEGF(165) binding to several different cell types, mouse embryonic sections and inhibits endothelial cell migration, despite its absence in VEGF(165) sequence. Our in vivo anti-tumor studies show that the peptide inhibits tumor growth in both mouse Lewis-Lung Carcinoma and human Liposarcoma tumor-bearing animal models. This is the first evidence that a synthetic VEGF fragment corresponding to exon 6a has functional antagonism both in vitro and in vivo. We conclude that the above HPSG binding peptide (6a-P) is a potent inhibitor of angiogenesis-dependent diseases.
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PMID:HSPG-binding peptide corresponding to the exon 6a-encoded domain of VEGF inhibits tumor growth by blocking angiogenesis in murine model. 2037 44

Angiogenesis is essential for cancer growth and progression. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The addition of bevacizumab, an antibody to vascular endothelial growth factor (VEGF), to paclitaxel and carboplatin improves survival compared with chemotherapy alone in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are a new class of drugs that target the TK domain of the VEGF receptors. To evaluate the role of this class of agents in the treatment of NSCLC, some phase II and phase III studies using these agents alone or in combination with other agents have been completed. This review summarizes the currently available data on VEGFR TKIs in the treatment of NSCLC.
Clin Lung Cancer 2010 Sep 01
PMID:Vascular endothelial growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. 2083 56

Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression.
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PMID:Vascular endothelial growth factor receptor-1 signaling promotes mobilization of macrophage lineage cells from bone marrow and stimulates solid tumor growth. 2092 6

Vascular endothelial growth factor (VEGF) has been known as a potential vasculogenic and angiogenic factor and its receptor (VEGFR2) is a major receptor to response to the angiogenic activity of VEGF. The technique that to break the immune tolerance of "self-antigens" associated with angiogenesis is an attractive approach for cancer therapy with T4 phage display system. In this experiment, mouse VEGFR2 was constructed on T4 phage nanometer-particle surface as a recombinant vaccine. T4-mVEGFR2 recombinant vaccine was identified by PCR and western blot assay. Immunotherapy with T4-mVEGFR2 was confirmed by protective immunity against Lewis lung carcinoma (LLC) in mice. The antibody against mVEGFR2 was detected by ELISPOT, ELISA and Dot ELISA. The inhibitive effects against angiogenesis were studied using CD31 and CD105 via histological analysis. VEGF-mediated endothelial cells proliferation and tube formation were inhibited in vitro by immunoglobulin induced by T4-mVEGFR2. The antitumor activity was substantiated from the adoptive transfer of the purified immunoglobulin. Antitumor activity and autoantibody production of mVEGFR2 could be neutralized by the depletion of CD4+T lymphocytes. These studies strongly suggest that T4-mVEGFR2 recombinant vaccine might be a promising antitumor approach.
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PMID:Inhibition of tumor angiogenesis in lung cancer by T4 phage surface displaying mVEGFR2 vaccine. 2148 23


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