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

We tested the ability of serum-free media to support the in vitro growth of human non-small cell lung carcinoma. A medium containing insulin, transferrin, sodium selenite, hydrocortisone, epidermal growth factor, and bovine serum albumin (1 mg/ml) with serum precoating of culture dishes (modified LA medium) supported three previously established cell lines of non-small cell lung cancer and prevented fibroblast proliferation in fresh tumor specimens but did not support long term tumor cell growth from fresh specimens. We added triiodothyronine, sodium pyruvate, and additional glutamine, insulin, and epidermal growth factor to modified LA medium, precoated with fibronectin and collagen instead of serum, and deleted bovine serum albumin, defining a new medium called ACL-3. ACL-3 medium alone supported the short term growth of 10 of 12 cell lines and the soft agarose cloning of 9 of 12 cell lines tested, and ACL-3 supplemented by an optimal concentration of bovine serum albumin (5 mg/ml) supported the long term growth of 10 of 12 cell lines tested. Moreover, we have grown tumor cells for more than 6 months from 11 of 33 (33%) consecutive fresh clinical specimens of human lung adenocarcinoma in ACL-3 with bovine serum albumin. ACL-3 medium provides a defined environment for the study of growth factor requirements of human non-small cell lung cancer and enhances our ability to grow human lung cancer, particularly adenocarcinoma, in vitro.
 ...
PMID:Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium. 394 Jun 44

Transforming growth factor (TGF) activities could be detected in the urine of normal, pregnant, and tumor-bearing humans. These acid- and heat-stable polypeptides competed for binding to epidermal growth factor (EGF) membrane receptors and promoted the anchorage-independent growth of nontransformed rodent cells. They differed from human EGF in their apparent molecular weights and soft-agar growth-stimulating activity. The urine from pregnant females contained TGF activities with apparent molecular weight(s) (relative) (Mr) of 10,000 ad 17,000--20,000. In the case of a lung cancer patient, an additional major activity of approximately 30,000--35,000 Mr was found. All urine specimens examined also contained a "common" 8,000-Mr soft-agar growth-stimulating activity, which competed for binding to EGF membrane receptors and which was chromatographically separable from EGF (urogastrone). Thus urine may provide a convenient and readily available source for the biochemical characterization of these TGF-like activities, some of which may be clinically useful biologic markers for certain types of cancer.
 ...
PMID:Transforming growth factors in the urine of normal, pregnant, and tumor-bearing humans. 628 92

Seventeen well-characterized human lung cancer cell lines were examined for the presence of specific membrane receptors for epidermal growth factor (EGF) and nerve growth factor (NGF) as well as for the production of diffusible factors capable of stimulating soft agar growth. These cell lines represented all four major histological types of human lung cancer including small cell carcinoma of the lung (SCCL) and the three types of non-SCCL (epidermoid, large cell, and adenocarcinoma). The SCCL lines included three lines referred to as "converters" because they had lost SCCL morphological and biochemical properties during prolonged passage in vitro. Specific receptors for EGF and NGF were detected by measuring the binding of 125I-radiolabeled growth factor to the cell surface. These assays revealed that EGF receptors are found on five of six non-SCCL cell lines and are not found on any of the SCCL lines. In contract, NGF binding was detected at low levels on three of eight SCCL lines and on all three SCCL converters but was not observed for non-SCCL lines. Thus, SCCL and SCCL converter cell lines are distinguished from non-SCCL by the pattern of membrane receptors for EGF and NGF. Such differences may ultimately prove useful as biological markers for the different histological types of lung cancer. Moreover, the majority of SCCL cells and all of the non-SCCL cells tested were found to produce diffusible growth factors which can stimulate soft agar growth of nontransformed normal rat kidney fibroblasts. Although some correlation between soft agar growth factor production and the absence of EGF receptors may exist for SCCL cells, the production of transforming growth factors appears to be a general property of human lung cancer cells in vitro and is independent of EGF receptor expression.
 ...
PMID:Expression of epidermal and nerve growth factor receptors and soft agar growth factor production by human lung cancer cells. 697 91

Inhibition of growth factor-stimulated DNA synthesis carried out in defined medium is often compared with inhibition of serum-stimulated DNA synthesis so as to assess the selectivity of growth-factor-receptor tyrosine kinase inhibitors such as tyrphostins. We investigated whether protein binding may influence the interpretation of these experiments. Protein binding of tyrphostins was determined by ultrafiltration, equilibrium dialysis or spectrophotometer, and was quantitated by high-performance liquid chromatography (HPLC). For growth factor-stimulated DNA synthesis, we used the non-small-cell lung cancer cell line L23/P stimulated by transforming growth factor alpha (TGF alpha). The epidermal growth factor (EGF)-receptor kinase was assayed by phosphorylation of a peptide substrate or by receptor autophosphorylation. Protein binding of a number of tyrphostins ranged from 64% to 98%. There was a positive correlation (r = 0.995) between the degree of protein binding and the hydrophobicity. Inhibition of the EGF-receptor tyrosine kinase activity by the highly protein-bound tyrphostin B56 [N-(4-phenylbutyl)-3,4-dihydroxybenzylidene cyanoacet-amide] was reduced by bovine serum albumin (BSA), but BSA had less of an effect on inhibition of the EGF-receptor kinase by the weakly protein-bound tyrphostin A47 (RG 50864: 3,4-dihydroxybenzylidene cyanothioacetamide). Tyrphostins B46 [N-(3-phenylpropyl)-3,4-dihydroxybenzylidene cyanoacetamide] and B56 (both highly protein-bound) inhibited DNA synthesis of L23/P cells with approximately 3-fold greater potency in 0.5% serum than in 10% serum, but the inhibition of DNA synthesis in 0.5% serum was reduced by the addition of BSA. Tyrphostins B46 and B56 inhibited DNA synthesis stimulated by TGF alpha in defined medium to a greater extent than DNA synthesis stimulated by serum. However, this apparent selectivity for inhibition of TGF alpha-stimulated DNA synthesis was lost when the protein concentration in the defined medium was made equivalent to that in the serum-containing medium. By contrast, BSA enhanced the selective inhibition of TGF alpha-stimulated DNA synthesis by tyrphostin A47. These results demonstrate that protein binding accounts for the apparent selectivity of some highly protein-bound tyrphostins for TGF alpha-stimulated DNA synthesis of L23/P cells. Therefore, protein binding should be taken into consideration in assessments of the selectivity of tyrphostins.
 ...
PMID:Protein binding modulates inhibition of the epidermal growth factor receptor kinase and DNA synthesis by tyrphostins. 762 51

The metastatic variants of human lung adenocarcinoma cell line DMS4C were established by selection in vivo. Lung, brain, spleen and liver metastatic tumors derived from intracarotid inoculation of athymic BALB/c mice were collected, and their corresponding variant cell lines established. The epidermal growth factor (EGF) receptor expression of the parental cell line as well as the metastatic variant cell lines were investigated. 125I-labeled EGF binding assays showed that there were two types of EGF receptors in both parental and metastatic variants. Compared to DMS4C, the EGF binding capacities were found to be down-regulated by 70, 79, 85 and 89% for lung, spleen, liver and brain variant, respectively. The dissociation constants of spleen, liver and brain EGF receptors were distinct from that of the parental cell line. The EGF receptor autophosphorylation activity of lung variant was shown to be down-regulated as shown by immune complex kinase assay that corresponded to EGF receptor numbers whereas kinase activities of the liver, spleen and brain variants EGF receptors were completely abolished. However, the 170 kilodalton EGF receptor was shown to be unaltered during metastasis. The results indicated that, during metastasis progression, the proliferation of adenocarcinoma cells may have adopted a different growth regulation that is independent of EGF receptor kinase-modulated autocrine pathway. The result also implies that other oncogene may emerge as the major growth regulator for distant metastasis of adenocarcinoma cancer cells. This work provides a model for understanding tumor metastasis progression of human lung cancer.
 ...
PMID:Differential down-regulation of epidermal growth factor receptors expressed in the metastatic variants of human lung cancer adenocarcinoma cell line DMS4C. 777 May 48

Gene expression of growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), oncogenes such as c-myc, N-ras, c-erbB2 and tumor suppressor gene P53 were studied in 4 human lung cancer cell lines using Northern blot technique. Among these cell lines were 2 adenocarcinoma cell lines, one large cell carcinoma cell line and one small cell carcinoma cell line. Expression of EGF and TGF alpha mRNAs were found in all 4 cell lines and EFGR mRNA was seen in 3 out of 4 cell lines. Among these cell lines, 2 cell lines with weaker expression of EGF and TGF alpha, expressed c-myc mRNA. Another 2 cell lines had no c-myc but expressed large amounts of EGF and TGF alpha mRNA. No expression of N-ras, c-erbB2 and p53 were found in these cell lines. The results indicate the presence of autocrine loop of growth factors in these cancer cells. The autostimulation of growth factors may be the main cause for the uncontrolled growth of cancer cells. After treating the cancer cells with EGF, anti-EGF and anti-EGFR antibodies, EGF was found to exert a mild stimulating effect on the growth of one cell line, but no effect on the other cell lines. Anti-EGF and anti-EGFR antibodies inhibited the cell growth on all cell lines. These results provided further evidence for the presence of autocrine loop of growth factors in these lung cancer cell lines.
 ...
PMID:[Gene expression of growth factors, growth factor receptor and oncogenes in human lung cancer cell lines]. 778 Nov 11

A wide range of genetic and phenotypic abnormalities have been identified in lung cancer. However, only a few are known to have an impact on patient outcome and thus may influence choice of therapy. Biologic and molecular factors known in this regard include the epidermal growth factor family and its receptors, markers of neuroendocrine differentiation in non-small cell lung cancer, and mutations of the ras gene family. None of these factors, however, can be considered a standard for selection of patients for therapy until additional information is gleaned from ongoing prospective studies.
 ...
PMID:Biologic and molecular prognostic factors--impact on treatment of patients with non-small cell lung cancer. 778 7

Thrombomodulin (TM) is an anticoagulant endothelial cell surface glycoprotein containing six tandem epidermal growth factor (EGF)-like structures. We prepared a recombinant TM peptide (rTME1-6, from R214GHWA to DSGK466 of native TM) composed of these six EGF-like structures and investigated the effect of rTME1-6 peptide on the growth of the Swiss 3T3 fibroblast cell line. It was found that rTME1-6 induced proliferation of Swiss 3T3 cells and accelerated [3H]thymidine uptake into their DNA. [3H]Thymidine uptake increased in a dose-dependent manner, plateauing at 50 ng/mL rTME1-6, which was 1.8 times the control level. rTME1-6 peptide (50 ng/mL) also accelerated the DNA synthesis of human dermal fibroblasts (HDFs), A549 (a human lung cancer cell line), HepG2 (a human hepatocarcinoma cell line), and U937 cells (a human monocytic cell line) to 1.5, 1.6, 1.4, and 1.2 times the control level, respectively. The magnitude of the acceleration of DNA synthesis in Swiss 3T3 induced by rTME1-6 was approximately 20% of that of EGF on a molar basis. The uptake of [3H]thymidine was accelerated synergistically by coculture of the cells with rTME1-6 and insulin, similar to the coculture with EGF and insulin. The effects of rTME1-6 were abolished by addition of polyclonal antihuman TM IgG, whereas the actions of insulin and EGF were not influenced. Glucose uptake in Swiss 3T3 cells also increased 1.6 times over control levels by culture with 50 ng/mL rTME1-6 (1.25 nmol/L), compared with 2.7 times by 10 ng/mL EGF (1.66 nmol/L). Binding of [125I]EGF (0.5 ng/mL, 0.083 nmol/L) by the cells was inhibited by about 60% by addition of an eight-fold molar excess of nonlabeled EGF (0.664 nmol/L), whereas no inhibition of [125I]EGF binding was observed, even in the presence of a 1,000-fold molar excess (83 nmol/L) of rTME1-6. Specific binding of [125I]rTME1-6 on the cells showed a saturation curve, and the apparent concentration of rTME1-6 required for half maximum binding of the peptide on the cells was calculated to be 31.5 ng/mL. Thus, the overall results indicated that the rTME1-6 peptide had mitogenic activity for Swiss 3T3 cells, accelerated DNA synthesis and glucose uptake, and that the mitogenic activity might be mediated by binding of the peptide to a specific site different from the EGF receptor.
 ...
PMID:The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells. 779 28

We investigated the effects of our synthetic bombesin/gastrin-releasing peptide (GRP) antagonists and somatostatin analogue RC-160 on the growth of human small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (non-SCLC) lines in nude mice. Athymic nude mice bearing xenografts of the SCLC NCl-H69 line or non-SCLC NCl-H157 line were treated for 5 and 4 weeks, respectively, with somatostatin analogue RC-160 or various bombesin/GRP antagonists. RC-160, administered s.c. peritumorally at a dose of 100 micrograms per animal per day, inhibited the growth of H69 SCLC xenografts as shown by more than 70% reduction in tumour volumes and weights, as compared with the control group. Bombesin/GRP antagonists, RC-3440, RC-3095 and RC-3950-II, given s.c. peritumorally at a dose of 20 micrograms per animal per day, also inhibited the growth of H69 SCLC tumours. RC-3950-II had the greatest inhibitory effect and decreased tumour volume and weights by more than 80%. The growth of H-157 non-SCLC xenografts was significantly reduced by treatment with RC-160, but not with bombesin/GRP antagonist RC-3095. In mice bearing either tumour model, administration of RC-160 significantly decreased serum growth hormone and gastrin levels. Specific high-affinity receptors for bombesin and somatostatin were found on membranes of SCLC H69 tumours, but not on non-SCLC H157 tumours. Receptor analyses demonstrated high-affinity binding sites for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the membranes of H69 and H157 tumours. EGF receptors were down-regulated on H69 tumours after treatment with RC-160 and bombesin/GRP antagonists. The concentration of binding sites for EGF and IGF-I on the H157 tumours was decreased after treatment with RC-160, but bombesin/GRP antagonist RC-3095 had no effect. These results demonstrate that bombesin/GRP antagonists inhibit the growth of H-69 SCLC, but not of H-157 non-SCLC xenografts in nude mice, whereas somatostatin analogue RC-160 is effective in both tumour models. This raises the possibility that these peptide analogues could be used selectively in the treatment of various subclasses of lung cancer.
 ...
PMID:Effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonists on the growth of human small-cell and non-small-cell lung carcinomas in nude mice. 794 94

In this lecture, importance of growth factors in reproductive functions and cancer growth are discussed. Among many kinds of growth factors, epidermal growth factor (EGF) and transforming growth factor (TGF)alpha are mentioned; both of these are called as EGF family because these share a common receptor (EGF receptor) and show similar biological activities. It is known that growth factors are important in reproductive fields. They play vital roles in the follicle development and the endometrial proliferation in response to estrogen. We studied the expression and role of EGF and TGF alpha in human fallopian tube. Immunohistochemical and RT-PCR studies revealed the menstrual stages specific synthesis and expression of EGF and TGF alpha in tubal epithelial cells. They were abundant at the late follicular and luteal stages, were little at the early follicular stage, suggesting that these growth factors are expressed in response to estrogen. We, next, examined the role of these factors in early embryo development using mouse embryos. Embryo development was significantly improved when embryos were co-cultured with human tubal epithelial cells. However, the favorable effects of the tubal epithelial cells were almost completely abolished by the addition of anti-EGF and -TGF alpha neutralizing antibodies. These facts suggest that EGF and EGF alpha expressed in human epithelial cells promote embryo development in a paracrine manner. Autocrine mechanisms by growth factors are known to be important on cancer cell growth. Among many kinds of autocrine mechanisms TGF alpha/EGF receptor autocrine mechanism is the most commonly expressed in many kinds of cancers such as lung cancer, esophageal cancer, pancreas cancer and liver cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Growth factors in gynecology]. 808 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>