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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretion of prostaglandin E2 (PGE2) by cloned variants of QR fibrosarcoma or of Lewis lung carcinoma (LLC) did not correspond with their in vivo aggressive behavior. However, aggressiveness may be influenced by tumor responsiveness to PGE2. Each of the metastatic LLC or progressor QRpP variants was more motile in an in vitro migration model than were either the nonmetastatic LLC or regressor QR variants. One of the two tested progressor QR variants and all of the metastatic LLC variants were also more responsive to PGE2 in their in vitro migration through a membrane than were either regressor QR or nonmetastatic LLC variants. Thus, responsiveness to PGE2 by tumors may regulate the degree of tumor aggressiveness in vivo.
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PMID:Association of increased tumor cell responsiveness to prostaglandin E2 with more aggressive tumor behavior. 206 Oct 4

In certain experimental tumor models, tumor growth is less pronounced in immune deficient animals. Characteristically, tumors such as the murine B16 melanoma and Lewis lung carcinoma (3LL) are weakly antigenic. We proposed that with such tumors that are weakly antigenic, growth is enhanced by T-cell factors. Young mice were inoculated with irradiated B16 cells in complete Freunds adjuvant (CFA) on three occasions, each separated by 2 weeks. Specific antibody (IgG) to B16 membrane antigens was detected by an enzyme-linked immunosorbent assay (ELISA) after the first injection, and it continued to rise for 6 weeks. B16 growth was compared in 20 mice that had received irradiated B16 in CFA or CFA alone by the same schedule previously. Despite the previous sensitization, the rates of tumor appearance and growth were similar. In an additional experiment involving 23 mice that had received B16 immunization, the period of time in which a palpable tumor developed after the injection of viable B16 cells did not correlate with anti-B16 antibody level. It appeared that detectable antibody to B16 antigens was of little consequence. To explain why B16 primary growth and metastases were reduced in immune deficient hosts, we proposed that lymphocytes might enhance tumor growth. To demonstrate this, splenic lymphocytes from tumor-bearing (B16 or 3LL) or control mice were injected with B16 cells into young, immune competent hosts. Tumors (B16) developed earlier and growth was more rapid in mice that received spleen cells from tumor-bearing (B16) mice. Subsequent cell depletion experiments to determine the mediator of tumor enhancement implicated a T-cell fraction that was neither of T-helper nor T-suppressor cell type phenotypically. Immune deficiency states that are associated with dysfunction of those cells that account for tumor enhancement might explain the reduced tumor aggressiveness that is observed frequently in these conditions.
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PMID:Immunologic enhancement of B16 melanoma growth. 325 40

The expression of the epithelial antigen recognised by the MBr1 monoclonal antibody (CaMBr1) was studied on 161 small cell lung carcinoma (SCLC) biopsies. A correlation between the marker expression and the overall survival of the patients was found. To investigate the possible role of CaMBr1 in tumour aggressiveness, the in vivo and in vitro growth capabilities of different SCLC cell lines, in relation to the antigen expression, were analysed. The CaMBr1-positive cell lines displayed a higher growth potential in comparison to CaMBr1-negative cells. The biochemical nature of CaMBr1 was analysed in terms of enzyme sensitivity, molecular weight and comparison with other glycoproteins expressed by SCLC cells. The results indicated the trypsin sensitivity of the molecule, and sialic acid hiding of the CaMBr1 epitope. The increase of MBr1 reactivity after neuraminidase treatment suggests that the CaMBr1 epitope expressed in the SCLC cell line is carried by a sialoglycoprotein.
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PMID:Study of the expression and function of the tumour-associated antigen CaMBr1 in small cell lung carcinomas. 750 62

Neuroendocrine tumors of lung, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC) constitute a spectrum of malignancies in which the pathologist at times has difficulty in discerning tumor subtype and aggressiveness in a reproducible fashion. Therefore, 59 primary neuroendocrine lung tumors including 10 TCs, 26 ACs, 15 LCNECs, and 8 SCLCs were selected from cases collected from 1976 to 1988 and immunostained for p53 protein. All of these tumors were also genotyped for specific point mutational damage affecting p53 (exons 5, 7, and 8; with ACs additionally sequenced for p53 exon 6); 13 tumors for K-ras-2 (exon 1); and 31 tumors for c-raf-1 (exon 15) growth-regulatory genes. Genotyping was performed on topographically selected, minute tumor samples removed from unstained formalin-fixed, paraffin-embedded tissue sections (topographic genotyping) using polymerase chain reaction and direct sequencing. The distribution of p53 immunohistochemical staining had four patterns: negative in TCs, one-half of ACs, 3 of 15 LCNECs, and 1 of 8 SCLCs; less than 10% but more than five tumor cells per 10 high power fields (focal) in a subset (7 of 26) of aggressive ACs; 10 to 49% of tumor cells (patchy) in a subset (6 of 26) of ACs with a higher grade of aggressiveness; and 50 to 100% of tumor cells (diffuse), exclusively seen in LCNECs (12 of 15) and SCLCs (7 of 8). Three patterns of immunohistochemical staining intensity of p53 protein were seen: negative, weak or mild, and moderate to marked. SCLCs and LCNECs accounted for cases of moderate to marked staining and were the only ones to have mutations in p53 exons 5, 7, or 8. No mutations were found in AC and TC, showing absent to weak staining and no staining, respectively. The difference in distribution and staining intensities between LCNEC and SCLC compared with AC and TC was statistically significant (P < 0.001). Patients having AC with patchy p53 immunostaining usually had survival limited to 3 years, whereas those having AC with focal p53 immunostaining subsequently developed metastatic or recurrence of AC disease (P < 0.05). The absence of point mutations in cases with patchy or focal immunostaining suggests increased expression of wild-type p53 tumor suppressor protein likely in response to growth deregulation in a more aggressive subtype of AC. A novel hypothesis is presented in regard to these findings. K-ras-2 and c-raf-1 gene sequence analysis showed no evidence of point mutational change in any of the tumors studied. The TC and AC categories are therefore genetically distinct from the higher grade neuroendocrine SCLC and LCNEC. Immunohistochemistry for p53 on AC lung tumors may be helpful to delineate cases at higher risk for aggressive behavior. Additionally, although LCNEC is categorized as a non-small-cell carcinoma, it is more akin genetically and immunohistochemically to SCLC.
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PMID:Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. 862 22

Loss of heterozygosity (LOH) on chromosomes 2q, 9p, 18q, and 22q frequently occurs in advanced non-small cell lung carcinoma (NSCLC). The association of p53 mutations with prognosis is still unclear in NSCLC. Therefore, we investigated the prognostic significance of allelic imbalances (AI) on these chromosomes and p53 mutations in 108 cases of stage I NSCLC by PCR amplification of polymorphic dinucleotide repeat-containing sequences and PCR-single strand conformation polymorphism analysis. AI on 2q, 9p, 18q, and 22q was detected in 22, 38, 29, and 15% of cases, respectively, whereas p53 was mutated in 41% of stage I NSCLC. AI on 9p and 22q and p53 mutations were significantly associated with shortened survival of the patients (P = 0.010, 0.024, and 0.022, respectively). Although gender and smoking history showed more significant associations with prognosis than other clinicopathological and molecular parameters, independent prognostic significance for AI on 9p was observed (P = 0.002) in male patients with a positive smoking history. These results indicate that clinical aggressiveness of early-stage NSCLC can be partly defined by the presence of AI on chromosome 9p in cancer cells, and that AI on 9p could be a clinically useful prognostic indicator for early-stage NSCLC patients.
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PMID:Prognostic significance of allelic imbalances on chromosome 9p in stage I non-small cell lung carcinoma. 1035 49

Experimental evidence suggests that tumor growth and progression depend on angiogenesis. In a retrospective study we evaluated the relationship between tumor angiogenesis and survival in patients with NSCLC treated with potentially curative surgery between 1992 and 1997. The study population consisted of 76 patients. An anti-CD34 monoclonal antibody was used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel count (MVC): in each sample the three most intense regions of neovascularization were identified under low microscopic power. A x250 field in each of the three areas was then counted and the highest count of the three fields was recorded. Disease free (DFS) and overall survival (OS) during follow up were evaluated. Gender, age, stage, histologic type and KI-67 were the other factors considered for analysis. The median MVC in our series was 41.5. Among the clinicopathologic parameters examined the microvessel count was the only one to show a significant association with disease free survival in univariate analysis (P = 0.04). MVC value is a new indicator of tumor aggressiveness in patients with NSCLC who underwent potentially curative surgery and should be taken into consideration in selecting patients for adjuvant treatment.
Lung Cancer 1999 May
PMID:Prognostic and predictive value of intratumoral microvessels density in operable non-small-cell lung cancer. 1044 58

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel apoptosis inhibitor gene, antiapoptosis clone 11 (AAC-11), may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of AAC-11 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 94 non-small cell lung carcinomas and adjacent histologically normal lung samples. The data was analyzed in reference to clinicopathological and survival data. AAC-11 transcripts were detected in 12 (12.7%) of the tumor samples, although five of paired normal lung samples showed very weak expression. There was no relationship between AAC-11 gene expression and age, gender, N or T-status. AAC-11 was preferentially expressed in squamous cell carcinoma (26.9% of squamous cell carcinoma vs. 7% of adenocarcinoma). The NSCLC patients with AAC-11 expression had significantly poor survival than the patients without AAC-11 expression (P=0.0360). Although the AAC-11 gene was not expressed in a majority of NSCLC tumors, we suggest that AAC-11 may predict poor survival.
Lung Cancer 2001 Oct
PMID:Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer. 1155 13

Telomerase has been reported to be a novel diagnostic marker for malignant diseases and has been recently proven to be composed of three main components, hTR (human telomerase RNA component), TP1 (telomerase-associated protein 1) and hTERT (human telomerase reverse transcriptase), the last of which plays a key role in telomerase activation. In the present study, quantitative levels of telomerase activity and hTERT gene mRNA (hTERT) expression were analyzed in cancerous and non-cancerous lung tissues of 62 lung cancer patients by telomeric repeat amplification protocol and reverse transcription-PCR, respectively. The telomerase expression levels of each group of tissue samples were compared with clinicopathologic variables. Telomerase activity and hTERT were detected in cancerous tissues (75.8 and 75.8%, respectively), while these parameters were not observed in any non-cancerous tissues. In quantitative assessment of telomerase expression, both telomerase activity and hTERT were significantly correlated with lymph node metastasis (N0 vs. N1+2, P<0.05). Telomerase activity also correlated with tumor cell differentiation and stage classification (P<0.05), but did not correlate with other clinicopathologic variables. The disease-free survival in patients with lung cancer demonstrated that patients with hTERT-positive tumor survived for a significantly shorter period than those with hTERT-negative tumor (P=0.0334). Since hTERT levels are correlated with N factor which represents the true aggressiveness of patients' disease concerning the evaluation of clinical outcome, hTERT was found to be one of the important markers revealing biological malignant potentials for lung cancer.
Lung Cancer 2001 Nov
PMID:Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non-small cell lung cancer. 1167 80

Overexpression of the erbB family of receptor tyrosine kinases has been implicated in a variety of tumors including breast, lung, prostate, and brain. Most solid tumors express one or more of these receptors, which can often be related to tumor aggressiveness and poor patient prognosis. CI-1033, a pan-erbB tyrosine kinase inhibitor, is a clinically promising agent that is active against all four members of the erbB receptor tyrosine kinase family. In vitro studies of human cancer cell lines indicate that CI-1033 results in prompt, potent, and sustained inhibition of tyrosine kinase activity. This inhibition is highly selective for erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Treatment of athymic nude mice bearing xenografts of human A431 epidermoid carcinoma, H125 non-small cell lung carcinoma, and SF-767 glioblastoma results in highly significant suppression of tumor growth. The major toxicity in animals is diarrhea, which is more severe at higher doses. In animal models, all side effects are reversible on cessation of treatment. Thus, CI-1033, which is currently undergoing phase I clinical trials, holds significant potential for use in a broad range of solid tumors.
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PMID:CI-1033, a pan-erbB tyrosine kinase inhibitor. 1170 99

The objective of the present report was to study the expression of the low affinity nerve growth factor (NGF) receptor p75 and of the activated high-affinity NGF receptor TrkA in malignant mesothelioma (MM). In addition, to analyze whether expression of these receptors is site-related (pleural versus peritoneal MM, solid lesions versus effusions). Sections from 81 MM (57 biopsies, 24 effusions) were analyzed. Sixty-one mesotheliomas were of pleural origin, while the remaining 20 were peritoneal. Effusion specimens consisted of 6 peritoneal and 18 pleural effusions, while biopsies consisted of 14 peritoneal and 43 pleural lesions. Specimens were immunohistochemically stained using antibodies against p75 and phospho-TrkA (p-TrkA). Six effusions were additionally analyzed for p-TrkA expression using immunoblotting (IB). p-TrkA membrane expression (66/81 specimens; 81%) was by far more frequent than that of p75 (26/81 specimens; 32%). In addition, p-TrkA expression was significantly higher in peritoneal MM compared to their pleural counterparts (20/20 versus 46/61 positive tumors; P = 0.014). p-TrkA membrane expression was marginally higher in effusions (P = 0.058), while the opposite was true for p75 membrane expression (P = 0.008) and p-TrkA cytoplasmic expression (P = 0.003). In conclusion, our results document for the first time frequent expression of p-TrkA and lower expression of p75 in MM, in agreement with the biological aggressiveness of this tumor. The enhanced expression of p-TrkA in peritoneal MM, tumors that appear in younger patients, and in effusions as compared to solid tumors, suggest that p-TrkA plays a significant role in the biology of this disease and may aid in defining tumor progression in this setting.
Lung Cancer 2004 May
PMID:Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma. 1508 80


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