Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Targeted therapies have revolutionized the treatment of cancer in recent years. However, treating elderly patients with these new biological therapies remains a challenge. Bevacizumab, a monoclonal antibody directed toward VEGF, appears to increase cardiovascular events in patients who are aged 65 years and over and increases the toxicity in these patients with lung cancer when added to chemotherapy. Owing to the less significant data available concerning the toxicity of trastuzumab and cetuximab, one cannot consider their use to be too toxic for the elderly patient. Rituximab has revolutionized the treatment of lymphomas with no apparent toxic effects in the elderly population. Small-molecule tyrosine kinase inhibitors and immunomodulators - thalidomide and lenalidomide - are emergent drugs that also appear to be efficient and safe for use in these patients. Few data are available concerning the toxicity of biological drugs in the elderly population, hence their use must be evaluated in each single case, always taking into consideration the risk-benefit ratio for the individual patient.
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PMID:Toxicity of targeted therapies in elderly patients. 1904 16

L-[3-(18)F]-alpha-methyltyrosine ((18)F-FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET-CT with (18)F-FMT provides additional information for the preoperative diagnostic workup as compared with (18)F-FDG PET. PET-CT studies with (18)F-FMT and (18)F-FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L-type amino acid transporter 1 (LAT1), CD98, Ki-67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, (18)F-FMT PET exhibited a sensitivity of 84% whereas the sensitivity for (18)F-FDG PET was 89% (p = 0.736). (18)F-FMT PET-CT and (18)F-FDG PET-CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). (18)F-FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of (18)F-FMT PET for diagnosing thoracic tumors was higher than that of (18)F-FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer.
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PMID:Evaluation of thoracic tumors with (18)F-FMT and (18)F-FDG PET-CT: a clinicopathological study. 1906 57

We have reported that a 10-herbal traditional formula containing Korean Angelica gigas Nakai (AGN) exerts potent anti-cancer efficacy and identified decursin and decursinol angelate (DA) from AGN as novel anti-androgens. Here, we determined whether AGN would exert in vivo anti-cancer activity and whether decursin or DA could account for its efficacy. The AGN ethanol extract was tested against the growth of mouse Lewis lung cancer (LLC) allograft in syngenic mice or human PC-3 and DU145 prostate cancer xenograft in immunodeficient mice. The pharmacokinetics of decursin and DA were determined. The AGN extract significantly inhibited LLC allograft growth (30 mg/kg) and PC-3 and DU145 xenograft growth (100 mg/kg) without affecting the body weight of the host mice. Biomarker analyses revealed decreased cell proliferation (Ki67, PCNA), decreased angiogenesis (VEGF, microvessel density) and increased apoptosis (TUNEL, cPARP) in treated tumors. Decursin and DA injected intraperitoneally were rapidly hydrolyzed to decursinol. Decursinol and decursin at 50 mg/kg inhibited LLC allograft growth to the same extent, comparable to 30 mg AGN/kg. Therefore the AGN extract possessed significant in vivo anti-cancer activity, but decursin and DA only contributed moderately to that activity, most likely through decursinol.
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PMID:In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin. 1922 17

Focus on new drug development over the last few years has yielded new agents that differ from unspecific classical chemotherapeutics and ionizing radiation, while still targeting the cancer cell itself. Antiangiogenesis is a totally distinct approach targeting the tumor's blood vessels. This concept has now found its eligibility for the treatment of several adult solid tumors: the human antivascular endothelial growth factor (VEGF) antibody bevacizumab, as well as the VEGF receptor tyrosine kinase inhibitors, sunitinib and sorafinib, have recently been licensed by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of colorectal, renal, and lung cancer. Other antiangiogenic drugs are under preclinical and early clinical evaluation. However, what do we know of the use of these drugs in pediatric solid tumors, such as sarcomas and embryonal and neuronal tumors? For some time now, neuroblastoma has been shown to be dependent on angiogenesis. However, the first preclinical data on antiangiogenic drugs in neuroblastoma have not been published until recently, and clinical trials with antiangiogenic agents in neuroblastoma treatment protocols are scarce. This review adresses current knowledge on the important role and mechanisms of angiogenesis in neuroblastoma and summarizes available preclinical and clinical results of antiangiogenic agents used to treat neuroblastoma. Our review clearly demonstrates that clinical trials are urgently needed to bring forward promising antiangiogenesis concepts in neuroblastoma therapy.
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PMID:[Potential role of antiangiogenic treatment in neuroblastoma]. 1929 15

Lung cancer is a particular challenge in oncology. More than 1 million new cases occur worldwide every year and despite many clinical trials and modern diagnostic techniques, long-term survival rate has only marginally improved. The aim of the current research is to explore new molecular prognostic factors and identify new targets for anticancer therapy. Current evidence shows that angiogenesis is controlled by several angiogenic factors including VEGF and BMP-2. It has been also demonstrated that VEGF plays a key role in this process that is essential in carcinogenesis. Our study has shown that the expressions of the VEGF, BMP-2 and BMP-4 mRNAs were significantly higher (7.1-fold, 25.6-fold and 2.3-fold, respectively) in lung cancer samples than in adjacent normal lung tissues (real-time RT-PCR). Analysis based on the Pearson's correlation coefficient indicated the positive correlation between VEGF and BMP-2 gene expression, whereas no significant correlation between VEGF and BMP-4 gene expression was found. The mean+/-standard deviation serum level of VEGF was 423+/-136 pg/ml. Significant differences in the serum levels of VEGF between patients with T1 tumors and patients with T2, T3 or T4 tumors were observed. Patients with T2, T3 and T4 tumors, respectively, had 1.6-fold, 1.8-fold and 2.3-fold greater serum levels of VEGF than their peers with T1 tumors. In current study patients homozygous for the 936T allele of the +936C/T VEGF gene polymorphism had 12-fold lower VEGF gene expression and 1.3-fold lower VEGF serum level than patients homozygous for the 936C allele. In conclusion, our findings underline the importance of the two angiogenic factors namely VEGF and BMP-2 as well as +936C/T VEGF gene polymorphism in the evaluation of lung cancer patients.
Lung Cancer 2009 Dec
PMID:The positive correlation between gene expression of the two angiogenic factors: VEGF and BMP-2 in lung cancer patients. 1932 47

Bevacizumab, a humanized monoclonal antibody against vascular endothelial factor (VEGF), is approved for the treatment of metastatic colon cancer, but it has also shown efficacy in first line therapy of non-squamous-cell non-smallcell lung cancer, breast cancer and clear-cell renal cancer. Antiangiogenic therapy severe toxic effects such as stroke, myocardial infraction, angina, arterial thromboembolism, pulmonary embolism or haemorrhage, gastrointestinal perforation, heart failure should be taken into account during treatment with bevacizumab. We describe and discuss two cases of cancer patients who developed fatal arterial thromboembolic episodes after administration of bevacizumab. Due to the recent launch of antiangiogenic agents and the limited experience with their use in clinical practice, their adverse effects and pharmacological toxicities, sometimes fatal, are not well-established and a detailed registration of them is needed.
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PMID:Implication of bevacizumab in fatal arterial thromboembolic incidents. 1936 80

Angiogenesis, the formation of new blood vessels, is closely linked with both the initiation and progression of rheumatoid arthritis (RA). Rheumatoid joints contain elevated levels of proangiogenic molecules, such as VEGF, basic FGF, hypoxia-inducible factor 1 and angiopoietins. Increased angiogenesis is also associated with malignancies and proliferative retinopathies, and targeting this process therapeutically has proven beneficial in treating several of these diseases including colorectal, kidney and lung cancer. Adapting such a therapeutic strategy to the treatment of RA may prove beneficial, as data from preclinical studies have demonstrated that angiogenesis inhibitors reduce pannus formation, inflammation and joint erosion. New therapies that inhibit angiogenesis by blocking VEGFR tyrosine kinase signaling, integrin interactions, microtubule formation and endothelial cell proliferation may be applicable to the treatment of RA. There are several angiogenesis inhibitors that have been approved by the FDA or are currently being assessed in clinical trials which are safe for use in humans, although their effects on RA remain untested. This review discusses the potential of angiogenesis inhibition in the context of treating RA.
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PMID:Angiogenesis inhibitors for the treatment of chronic autoimmune inflammatory arthritis. 1943 Oct 75

Microvesicles (MVs) are shed from cell membranes of several cell types and have an important function in cell-to-cell communication. Exponentially growing lung cancer cells secrete large quantities of MVs and we were interested in their role in tumor progression. We observed that both human and murine lung cancer cell lines secrete more MVs in response to non-apoptotic doses of hypoxia and irradiation. These tumor-derived (t)MVs activate and chemoattract stroma fibroblasts and endothelial cells. Furthermore, they induce expression of several pro-angiopoietic factors in stromal cells such as IL-8, VEGF, LIF, OSM, IL-11 and MMP-9. We also noticed that conditioned media harvested from stroma cells stimulated by tMVs enhanced the metastatic potential of both human and murine lung cancer cells in vivo. Thus, we postulated that tMVs are underappreciated constituents of the tumor microenvironment and play a pivotal role in tumor progression, metastasis and angiogenesis.
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PMID:Lung cancer secreted microvesicles: underappreciated modulators of microenvironment in expanding tumors. 1946 51

Early recognition of lung cancer is a prerequisite for any strategy to improve lung cancer treatment outcome. Here we report a cross-sectional study intended as a proof of principle investigation using breath based detection (exhaled breath condensate, EBC) of angiogenic markers (VEGF, bFGF, angiogenin), TNF-alpha and IL-8 to discriminate 74 individuals, with confirmed presence or absence (X-ray, CT) of non-small lung cancer (NSCLC). Levels of angiogenic markers bFGF, angiogenin and VEGF in EBC significantly discriminated between 17 individuals with newly detected NSCLC versus stable and exacerbated chronic obstructive pulmonary disease (COPD) patients as well as healthy volunteers. Levels of IL-8 and TNF-alpha in EBC indicated acute inflammation, e.g. in acute exacerbated COPD (AECOPD) and were not indicative of lung cancer. In a different group of patients that were already treated with two cycles of chemotherapy and who responded with at least a 25% reduction in primary tumor diameter, levels of angiogenic markers were lower compared to patients with newly diagnosed NSCLC. We suggest that breath based detection of angiogenic markers may help in the early detection of lung cancer.
Lung Cancer 2010 May
PMID:Angiogenic markers in breath condensate identify non-small cell lung cancer. 1964 34

Members of the hypoxia-inducible factor (HIF) family of transcription factors regulate the cellular response to hypoxia. In non-small cell lung cancer (NSCLC), high HIF2alpha levels correlate with decreased overall survival, and inhibition of either the protein encoded by the canonical HIF target gene VEGF or VEGFR2 improves clinical outcomes. However, whether HIF2alpha is causal in imparting this poor prognosis is unknown. Here, we generated mice that conditionally express both a nondegradable variant of HIF2alpha and a mutant form of Kras (KrasG12D) that induces lung tumors. Mice expressing both Hif2a and KrasG12D in the lungs developed larger tumors and had an increased tumor burden and decreased survival compared with mice expressing only KrasG12D. Additionally, tumors expressing both KrasG12D and Hif2a were more invasive, demonstrated features of epithelial- mesenchymal transition (EMT), and exhibited increased angiogenesis associated with mobilization of circulating endothelial progenitor cells. These results implicate HIF2alpha causally in the pathogenesis of lung cancer in mice, demonstrate in vivo that HIF2alpha can promote expression of markers of EMT, and define HIF2alpha as a promoter of tumor growth and progression in a solid tumor other than renal cell carcinoma. They further suggest a possible causal relationship between HIF2alpha and prognosis in patients with NSCLC.
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PMID:HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. 1966 77


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