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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is a leading cause of death worldwide and, although some progress has been made in its treatment, the results remain poor. Better knowledge in tumour biology has allowed us to design anti-target drugs and incorporate them in the treatment of non-small-cell lung cancer (NSCLC). One of the most widely used targeted approaches in this type of tumour has been the inhibition of angiogenesis. Several strategies blocking the VEGF pathway, either at the ligand or recepor level, have been studied and developed. In this review, we present an up-to-date analysis of the current inhibitors of angiogenesis in the treatment of NSCLC.
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PMID:Angiogenesis inhibitors in the treatment of non-small-cell lung cancer (NSCLC). 1841 Nov 92

To elucidate the determinants of the in vivo anti-tumor efficacy of polyethylene glycol (PEG)-modified liposomal doxorubicin (DOX), we examined its anti-tumor effect against three different tumor cell lines (Lewis lung cancer (LLC), Colon-26 (C26) and B16BL6 melanoma (B16)) in vitro and in vivo. In vitro, LLC was the most sensitive tumor to DOX and liposomal DOX based on the MTT assay. However, the strongest in vivo anti-tumor effect was observed in the C26 tumor-bearing mice. The in vivo accumulation of radiolabelled PEG liposome in the C26 tumor after intravenous injection was significantly larger than in other tumors. The extent of vascularity assessed by immunohistochemical staining of CD31 was not directly related with the tumor accumulation of PEG liposome. On the other hand, Evans blue extravasation and secretion of VEGF in C26 tumors were higher than in LLC tumors, clearly demonstrating that the vasculature permeability was higher within C26 tumors. These results indicated that the vascular permeability within the tumor substantially affects the tumor accumulation of PEG liposome and may be one of the important determinants in the in vivo anti-tumor efficacy of PEG liposomal DOX.
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PMID:Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin: importance of vascular permeability within tumors. 1844 89

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.
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PMID:Curcumin and cancer: an "old-age" disease with an "age-old" solution. 1846 66

Until recently, advances in non-small-cell lung cancer (NSCLC) care have been limited; new chemotherapy regimens have not significantly impacted patient survival. With our improved understanding of tumor biology, novel biological therapies targeting key tumorigenic processes targeting factors essential for tumor growth, such as angiogenesis, have been developed that improve patient outcomes beyond those achieved with chemotherapy alone. One of these, bevacizumab (Avastin), specifically targets VEGF, which is key to the malignant growth and progression of solid tumors. Bevacizumab-based therapy until progression significantly delays disease progression, has a well-characterized and acceptable safety profile in bevacizumab-eligible patients and was the first treatment to improve the overall survival of patients with advanced NSCLC beyond 1 year, a significant breakthrough in advanced NSCLC care. Furthermore, bevacizumab-based therapy significantly delays disease progression and has a well-characterized and acceptable safety profile. Based on these data, bevacizumab has received approval for the first-line treatment of NSCLC in the USA and Europe. A number of ongoing trials will potentially expand the eligible patient population for bevacizumab and further define its role in NSCLC treatment.
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PMID:Bevacizumab for the treatment of advanced non-small-cell lung cancer. 1847 Oct 42

The DPC4 influences tumourigenesis and tumor progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of DPC4 is related to the angiogenesis in lung cancer and whether it could be involved in its clinical behaviour. Immunohistochemistry revealed that DPC4 was expressed at high level in normal broncho-tracheal epithelium, but at low level in tumor tissues, and closely correlated with tumor lymph node metastasis. This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high DPC4 expression demonstrated low VEGF expression and low MVD (microvessel density) labelled with CD34. In addition, DPC4 siRNA in A549 cells also showed that DPC4 could decrease VEGF protein and mRNA expression, and increase TSP1 protein and mRNA expression. Our findings indicated that DPC4 might be an important biomarker for malignant transformation and be involved in preventing the tumor metastasis by inhibiting tumor angiogenesis.
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PMID:Expression of DPC4/Smad4 in non-small-cell lung carcinoma and its relationship with angiogenesis. 1850 44

The aim of the present investigation was to study a role of matrix metalloproteinases and their inhibitors in the pathogenesis of fibrosis and angiogenesis in lung precancer processes, which could be used to develop new pathogenetically substantiated lines in therapy. The investigation was conducted using intraoperative and biopsy specimens of the removed lungs and their parts from 113 patients with lung precancer changes with the diagnoses of lung cancer, chronic abscess, bronchoectatic disease, idiopathic fibrosing alveolitis, tuberculosis, of whom 41 patients had lived from childhood to 2002 in vicinity of a polygon and long exposed to radiation (annual radiation dose was greater than 0.1 Rem) (Group 1). The intraoperative and biopsy specimens from 72 patients who lived in the unchanged radiation areas of Kazakhstan (n = 32) and Moscow (n = 40) (Group 2) were used as a comparison group. The specimens were stained with hematoxylin and eosin, alcian blue, picrofuchsin as descried by van Gieson. The paraffin sections were immunohistochemically studied by the immunoperoxidase technique, by applying mono- and polyclonal antibodies to MMP-1, MMP-2, MMP-9, TIMP-1, VEGF, CD34, chromogranin, CD68, and Ki-67. Thus, lung precancer resulting from increased radiation is of high risk for invasive growth due to the imbalance between the expression of metalloproteinases and their inhibitors and the activation of antiblastomic defense mechanisms. Angionesis in the stroma of the adjacent tissues also creates favorable conditions for invasive epithelial growth. The relatively high level of metalloproteinases in radiation-induced precancer may be indirect evidence for the occurrence of precancer in the presence radiation-associated fibrosis and evidence for its high malignant potential.
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PMID:[Matrix metalloproteinases, their inhibitors and angiogenesis in different morphological types of lung precancer in persons who have long lived in the radioactive substance-polluted area of the Semipalatinsk Region, Kazakhstan]. 1854 Apr 36

Placenta growth factor (PlGF) is a member of the VEGF family and has been implicated in the aggressive capacity of solid tumours, partly via its impact on angiogenesis. The present study determined the direct biological function of endogenous PlGF in lung cancer cells. From the human non-small cell lung cancer cell line A549 which expressed good level of PlGF, we created sublines within which PlGF expression was knockdown by way of anti-PlGF ribozyme transgenes. Remarkable reductions of both PlGF mRNA and protein by the ribozyme transgenes were revealed in A549 transfectants (A549(DeltaPlGF)) using RT-PCR and Western blotting respectively. A549(DeltaPlGF) cells exhibited significantly reduced migration and adhesion compared with the wild-type (A549(WT)) and the empty plasmid control (A549(pEF/His)) cells. Immunocytochemistry and Western blotting further revealed that the expression of ROCK1, Rho associated kinase, was also reduced in A549(DeltaPlGF) cells, in comparison with wild-type and control cells. In addition, A549(DeltaPlGF) cells lost its response to a ROCK inhibitor, which otherwise strongly inhibited the motility of A549(WT) and A549(pEF/His) cells. These data indicate that PlGF directly regulates the motility of human lung cancer cells and that this regulation critically dependent on ROCK-1. The study further indicates that PlGF is a potential therapeutic target in lung cancer.
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PMID:Placenta growth factor, PLGF, influences the motility of lung cancer cells, the role of Rho associated kinase, Rock1. 1861 91

Semaphorins are a large family of secreted, transmembrane and GPI-linked proteins initially characterized in the development of the nervous system and axonal guidance. Semaphorins are expressed in many tissues where they regulate normal development, organ morphogenesis, immunity and angiogenesis. They affect the cytoskeleton, actin filament organization, microtubules and cell adhesion. Semaphorin signaling is transduced by plexins, which in the case of most class-3 semaphorins requires high-affinity neuropilin receptors. The neuropilins also function as receptors for VEGF and other growth factors, and their expression is often abnormal in tumors. In cancer, semaphorins have both tumor suppressor and tumor promoting functions. We review here the current status of semaphorins and their receptors in tumor development with a focus on lung cancer.
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PMID:Semaphorins and their receptors in lung cancer. 1862 44

Cigarette smoking is strongly correlated with the onset of nonsmall cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In this study, we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induces morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the promigratory growth factor VEGF. The proinvasive effects of nicotine were mediated by alpha7-nAChRs on NSCLCs. RT-PCR analysis showed that the alpha7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The proinvasive effects of nicotine were mediated via a nAChR, Src and calcium-dependent signaling pathway in breast cancer cells. In a similar fashion, nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition (EMT), characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers.
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PMID:Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. 1884 24

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p<0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.
Lung Cancer 2009 May
PMID:VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. 1884 57


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