Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have suggested that the vascular endothelial growth factors (VEGFs)/VEGF receptors (VEGF-Rs) system plays an important role in tumour growth and metastasis. We conducted the present study to clarify whether small cell lung cancer (SCLC) cells express functional VEGF-Rs and VEGFs, and their biological significance in the SCLC progression. We examined expression of VEGF and VEGF-C, and their receptors, VEGFR-2 and VEGFR-3, in five SCLC cell lines, NCI-H82, H209, H510, H526 and H660, by Western blotting. We evaluated whether hypoxic conditions up-regulate these protein expressions. We also examined whether VEGF addition and VEGF-D addition cause phosphorylation of the mitogen-activated protein kinase (MAPK) as well as VEGFR-2 and VEGFR-3. Further, we investigated whether VEGF addition and VEGF-D addition induced the proliferation and migration of the SCLC cells. VEGF, VEGF-C, VEGFR-2 and VEGFR-3 were detectable by Western blotting in all five SCLC cell lines,. The VEGF-Rs and VEGFs expression levels were increased by an incubation under hypoxic conditions in NCI-H82. VEGF addition and VEGF-D addition caused phosphorylation of MAPK as well as the VEGF-Rs themselves, and induced proliferation and migration of the SCLC cells. These results suggested potential of VEGF signal-pathway inhibitors as anti-cancer agents in SCLC treatment disturbing growth and migration of the cancer cells.
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PMID:Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3. 1536 28

To investigate the components of the prostaglandin biosynthetic pathway, the characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane synthase (TXS) were examined for autopsied cases with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The immunostaining scores of the prostaglandin biosynthetic pathway markers were significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition, there were significant correlations between two markers of the prostaglandin biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean immunostaining scores for the prostaglandin biosynthetic pathway markers were significantly higher for cases with high count groups than low count groups for MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic pathway markers may act synergistically and enhance tumor angiogenesis, the expression of angiogenic factors, and metastases in patients with NSCLC.
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PMID:Characterization of the prostaglandin biosynthetic pathway in non-small cell lung cancer: a comparison with small cell lung cancer and correlation with angiogenesis, angiogenic factors and metastases. 1587 Sep 20

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.
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PMID:Serum vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in small cell lung cancer. 1693 57

The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and NCI-H441 (non-small cell lung cancer) tumorigenicity in mouse xenografts by 99% and 75%, respectively. Reduction in tumor size was also observed by magnetic resonance imaging of tumors in mice. PHA665752 inhibited c-Met phosphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non-small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung cancer cell line (NCI-H69). PHA665752 also inhibited angiogenesis by >85% in all the abovementioned cell lines and caused an angiogenic switch which resulted in a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis inhibitor thrombospondin-1. These studies show the feasibility of selectively targeting c-Met with ATP competitive small molecule inhibitors and suggest that PHA665752 may provide a novel therapeutic approach to lung cancer.
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PMID:A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. 1744 59

Angiogenesis is one of the hallmarks of cancer. Among the identified angiogenic factors, vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis in normal and malignant tissue. Increased expression of VEGF has been detected in most tumors of humans, and it is associated with increased risks of recurrence, metastasis, and death. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody targeting VEGF, has been evaluated in various solid tumors. Some pivotal phase III trials demonstrated that the addition of bevacizumab to conventional chemotherapy showed a survival benefit with acceptable toxicity. The United States Food and Drug Administration approved the use of bevacizumab for patients with unresectable colorectal cancer and unresectable non-squamous, non small cell lung cancer. In April 2007, the Japanese Ministry of Health, Labour and Welfare approved bevacizumab for patients with unresectable colorectal cancer. The usage of bevacizumab will be stipulated in combination with 5-fluorouracil containing chemotherapy at a dose of 5 mg/kg or 10 mg/kg given every 14 days. To know its efficacy and safety of bevacizumab is necessary for Japanese patients in the clinical practice.
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PMID:[Bevacizumab (Avastin)]. 1768 99

Since the early 90's, it seems that chemotherapy given alone in non-small cell lung cancer had reached a plateau. Many different pathways have been targeted, with or without chemotherapy, trying to improve the treatment efficacy. Angiogenesis plays an important role in the process of the tumour growth and in metastasis dissemination. Two main ways have been developed to block either directly the most important growth factor (vascular endothelial growth factor) using a humanized monoclonal antibody, or its receptors (using low-molecular-weight anti tyrosine kinases). Some of them are currently available in colorectal cancers or renal cell cancer. Many phase II or III trials have been published in non small cell lung cancer in the last years.
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PMID:[The actual place of anti-angiogenesis in non-small cell lung cancer]. 1823 14

Cediranib (AZD2171; Recentin, AstraZeneca, Wilmington, Delaware) is a once-daily oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1, 2, and 3, c-KIT, and platelet-derived growth factor receptors. In preclinical testing it inhibits tumor angiogenesis and inhibits tumor growth in a wide range of tumor models. Phase 1 studies show cediranib to be generally well tolerated as monotherapy at doses of 45 mg/d or less, with a pharmacokinetic profile that supports once-daily oral administration and toxic effects consistent with those seen in other agents that target the vascular endothelial growth factor pathway. Encouraging results from phase 1 studies as monotherapy or in combination with chemotherapy have prompted further investigation in several thoracic malignancies, including ongoing trials in malignant mesothelioma, small cell lung cancer, and an ongoing phase 2/3 trial in non-small cell lung cancer (NSCLC) in combination with chemotherapy. The NSCLC trials include patients with squamous cell histologic features and treated brain metastases, populations for which bevacizumab is currently not indicated. These trials will determine whether cediranib will join the growing armamentarium of therapeutic options for thoracic malignancies and broaden the number of patients with NSCLC who could potentially benefit from antiangiogenic therapy.
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PMID:The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. 1852 Feb 96

The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX) on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally) 24 hours before human ovarian carcinoma (SKOV3), small cell lung carcinoma (LX-1 SCLC), and glioma (UW28, U87MG, and U251) tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0%) of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive) infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.
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PMID:Cyclophosphamide enhances human tumor growth in nude rat xenografted tumor models. 1917 3

The purposes of this study were to evaluate the treatment outcome of patients with small cell lung cancer (SCLC), focusing on the prognostic factors for response to therapy and overall survival. A retrospective analysis was performed on 116 consecutive patients with SCLC diagnosed from January 1997 to December 2005. Collected data included demographic information, pretreatment clinical assessment, treatment regimen, and outcome information. Prognostic factors were analyzed by log-rank test and Cox regression model. Results showed that performance status (PS) 0-1, limited disease, normal serum carcinoembryonic antigen (CEA), and vascular endothelial growth factor (VEGF) level were associated with improved response rate. The univariate analysis showed that sex, disease extent, PS, serum CEA, and VEGF level significantly influenced overall survival. In multivariate analysis, disease extent, PS, serum CEA, and VEGF level were identified as independent prognostic factors. In addition, prophylactic cranial irradiation (PCI) and number of metastatic sites were independent prognostic factors in limited disease and extensive disease, respectively. We concluded that disease extent, PS, serum CEA, and VEGF level are strong predictors of both response and survival. Female sex was a favorable prognostic factor for survival. Moreover, the prognostic factors for limited disease were good PS, normal serum CEA and VEGF level, and PCI, the prognostic factors for extensive disease were good PS, one metastatic site, normal serum CEA, and VEGF level. The identification of prognostic factors may be useful for the better evaluation of treatment outcome in clinical trials and the use of a targeted and specific treatment.
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PMID:Survival and prognostic factors in small cell lung cancer. 1921 13

Inhibition of specific processes essential for tumour vascular development is one of the key strategies for the treatment of non- small cell lung cancer (NSCLC). Many agents target the Vascular Endothelial Growth Factor (VEGF) pathway, either by preventing VEGF receptor binding or inhibiting VEGF receptor signalling in endothelial cells. Bevacizumab is a monoclonal antibody specific for VEGF-A. Combination of bevacizumab with standard first-line chemotherapy in NSCLC leads to an improvement in response rates and progression-free survival compared to chemotherapy alone and a significant survival advantage with carboplatin- paclitaxel chemotherapy. Toxicity issues are of concern with the possible occurrence of hypertension and an increased risk of arterial thrombo-embolism. The occurrence of fatal pulmonary haemorrhage after necrosis of the primary tumour is a specific toxicity in NSCLC which requires appropriate selection of patients before treatment; excluding squamous cell carcinoma, haemorrhagic tumours and tumour invasion of major blood vessels. The use of bevacizumab combined with chemotherapy represent a first step in the development of antiangiogenic treatments in NSCLC, with the future possibility of using it in earlier stages of disease.
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PMID:[Bevacizumab and non-small cell lung cancer: a new step?]. 1931 8


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