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

The effects of three different dosage schedules on both therapeutic effect and pulmonary toxicity of bleomycin were studied in mice. Therapy was assessed by both survival and decreased tumor size in mice bearing Lewis lung carcinoma. Lung toxicity was estimated in nontumored mice as increases in lung collagen content by measuring lung hydroxyproline concentrations. In the first set of experiments, bleomycin injections twice daily (low-dose, high-frequency) produced a significant (34%) increase in lifespan over controls, whereas the same total dose given twice weekly did not result in increased survival. Both schedules produced pulmonary toxicity. Continuous sc infusion of bleomycin via an osmotic minipump was compared to these two schedules of intermittent injection. Identical total doses of drug were administered in all three schedules. Continuous infusion for 7 days produced marked inhibition of tumor growth (T/C = 16%), which was significantly better than twice weekly or ten-times weekly injection of the same total dose. Furthermore, at a total dose of 40 mg/kg of bleomycin, continuous infusion did not result in measurable pulmonary toxicity, whereas both schedules of bolus injection produced significant increases in lung collagen content. Thus, continuous infusion of bleomycin improved its therapeutic effect against Lewis lung carcinoma and also reduced its pulmonary toxicity.
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PMID:Improved therapeutic index of bleomycin when administered by continuous infusion in mice. 8 69

Morphological analysis of the sclerotic changes in peripheral lung carcinoma (PLC) and nephrosclerosis in renal-cell carcinoma (RCC) established a promoting role of sclerosis in carcinoma development. The pneumosclerosis role as a background process in the PLC development is proved by the following facts: high proportion (83%) of the carcinoma in the scar among PLC; identity of the scar collagen composition in PLC and that in metatuberculosis and metapneumonic pneumosclerosis foci; detection of metatuberculosis foci in 75% of PLC; the presence of the precancerous changes in the epithelium entrapped in the pneumosclerotic foci, not only with signs of morphological atypia, but with the disturbance of nuclear DNA and cellular oncogene expression as well. The association of RCC with nephrosclerosis is shown by a high proportion (82.7%) of the RCC development against the background of nephrosclerosis; the dependence of the so-called cortical adenoma development on the degree of nephrosclerosis; epithelial proliferation in the nephrosclerotic foci with the appearance of undifferentiated cells with the altered DNA content and the expression of cytokeratins and vimentine. Carcinoma morphogenesis against the background of sclerosis may be described as follows: development of sclerosis (focal and/or diffuse), the appearance of the focal epithelial hyperplasia in the scar, dysplasia or adenoma and finally carcinoma.
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PMID:[Sclerosis and carcinogenesis]. 128 96

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.
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PMID:Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. 154 Mar 82

Tumour basement membrane (BM) is an extracellular matrix produced by tumour cells of epithelial origin. We examined the structure and function of the tumour BM of tumour tissues formed by Lewis lung carcinoma-derived cloned cell lines (P29, LM12-3 and LM60-D6 cells) with low, medium and high metastatic potentials, respectively. Immunohistochemical staining of major BM constituents laminin and type IV collagen demonstrated that all the cell lines produced and deposited these materials extracellularly in vivo. However, the continuity of the tumour BM composed of these materials was much greater in the higher metastatic LM12-3 and LM60-D6 tumours than in those with the low metastatic P29 tumour. Electron microscopic examination revealed that in the higher metastatic tumours, especially the LM60-D6 tumour, the tumour BM had a highly organized structure consisting of lamina densa and lamina rara. Parallel bilayers of BM and their fusion were often observed and tumour cells were in direct contact with the BM. In the vicinity of tumour blood vessels, similar interactions between the tumour BM and the vascular BM were observed, and the tumour cells rested on their own BM, the fused BM or the vascular BM. In contrast, in the low metastatic tumour in which the tumour BM was not clearly defined, this close contact between tumour cells and the vascular BM was not observed. In vitro studies showed that the higher metastatic cells adhered more firmly than the LMP cells to a subendothelial matrix. These results suggest that the adhesiveness of tumour cells to the vascular BM in vivo is correlated with their ability to form an integrated BM in vivo, and that this adhesiveness of the tumour cells may be mediated in part by the tumour BM via BM fusion.
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PMID:Morphological characteristics of tumours formed by Lewis lung carcinoma-derived cloned cell lines with different metastatic potentials: structural differences in their basement membranes formed in vivo. 154 5

A case of bronchiolo-alveolar carcinoma (BAC) developing in the presence of idiopathic fibrosing alveolitis (IFA) in a man of 67 with a long history of pulmonary lesion is described. A honeycomb bung was found at the autopsy. Histologically, multiple foci of BAC of mixed-cell structure and those of mucus-producing cells against the background of fibrosing alveolitis at the stage of honeycomb lung were observed. An increased content of collagen type III, IV and V was found immunohistochemically. The role of sclerotic changes and defected immunological surveillance over the epithelial regeneration in the IFA-affected lung in relevant carcinoma genesis is suggested. The origin of the lung carcinoma in IFA is considered to be the regenerating epithelium of the low respiratory tract.
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PMID:[Idiopathic fibrosing alveolitis and bronchioloalveolar cancer]. 165 Jan 74

Collagen types and ultrastructural features of the stroma and scar extracellular matrix in the peripheral lung carcinoma, post-tuberculosis and post-pneumonia pneumosclerosis foci, fibrosing alveolitis interstitium were studied on the material of operational and transbronchial lung biopsies. It is established that by the collagen composition the scars in the peripheral carcinoma are identical to the pneumosclerosis foci and are distinguished from the carcinoma stroma by a higher concentration of type IV and V collagens (p less than 0.05). Accumulation of type III collagen in the lung carcinoma stroma reflects anaplasia of the tumour as the domination of type III collagen is characteristic of the embryonal tissue. The decrease of collagen type IV in the cancer stroma correlates with an increase of its malignancy. Pneumosclerosis in the fibrosing alveolitis is distinct from the focal forms of pneumosclerosis by a higher content of collagen I and a lower content of collagen V this being probably due to the character of sclerosis morphogenesis in this disease.
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PMID:[The extracellular matrix of peripheral lung cancer in the scar and of pneumosclerosis of different origins (the immunohistochemistry and electron microscopy of the collagens)]. 165 27

The effect of sphingosine (SPH) on the adhesive properties of Lewis lung carcinoma (3LL) cells was investigated using plastic precoated with the extracellular matrix proteins, laminin, fibronectin, or type IV collagen. Treatment of 3LL cells with SPH (0.5-10 microM) resulted in a dose-dependent decrease in the ability to bind to laminin and type IV collagen but had little or no effect on attachment to fibronectin. Phorbol 12-myristate 13-acetate (PMA) selectively enhanced attachment of 3LL cells to laminin and collagen. The inhibitory effect of SPH on attachment to both proteins was competitively antagonized by PMA. These results suggest that SPH acts as a negative effector for cell attachment to laminin and collagen, and that the cell attachment process to both proteins might be regulated in part by protein kinase C.
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PMID:Sphingosine inhibits attachment of murine Lewis lung carcinoma cells to laminin and type IV collagen. 186 77

The capability of the integrin VLA-3 to function as a receptor for collagen (Coll), laminin (Lm), and fibronectin (Fn) was addressed using both whole cell adhesion assays and ligand affinity columns. Analysis of VLA-3-mediated cell adhesion was facilitated by the use of a small cell lung carcinoma line (NCI-H69), which expresses VLA-3 but few other integrins. While VLA-3 interaction with Fn was often low or undetectable in cells having both VLA-3 and VLA-5, NCI-H69 cells readily attached to Fn in a VLA-3-dependent manner. Both Arg-Gly-Asp (RGD) peptide inhibition studies, and Fn fragment affinity columns suggested that VLA-3, like VLA-5, may bind to the RGD site in human Fn. However, unlike Fn, both Coll and Lm supported VLA-3-mediated adhesion that was not inhibited by RGD peptide, and was totally unaffected by the presence of VLA-5. In addition, VLA-3-mediated binding to Fn was low in the presence of Ca++, but was increased 6.6-fold with Mg++, and 30-fold in the presence of Mn++. In contrast, binding to Coll was increased only 1.2-fold with Mg++, and 1.7-fold in Mn++, as compared to the level seen with Ca++. Together, these experiments indicate that VLA-3 can bind Coll, Lm, and Fn, and also show that (a) VLA-3 can recognize both RGD-dependent and RGD-independent ligands, and (b) different VLA-3 ligands have distinctly dissimilar divalent cation sensitivities.
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PMID:Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin binding are differentially influenced by Arg-Gly-Asp peptide and by divalent cations. 198 4

Lewis lung carcinoma cells express a plasma membrane receptor (i.e., IRGpIIb/IIIa) which is immunologically and functionally related to the platelet aggregation receptor complex (i.e., GpIIb/IIIa). Both fluorescence microscopy and flow cytometric analysis reveal that surface expression and/or activation of this tumor cell receptor is enhanced by a phorbol ester [i.e., 12-O-tetradecanoylphorbol-13-acetate (TPA)] and a lipoxygenase metabolite of arachidonic acid; 12-hydroxyeicosatetraenoic acid (i.e., 12-HETE). TPA-enhanced expression appears to be mediated by a lipoxygenase metabolite, as this effect can be reversed by lipoxygenase inhibitors but not by cyclooxygenase inhibitors. In parallel with these results both TPA and 12(S)-HETE [but not 12(R)-HETE] enhance tumor cell adhesion to endothelial cells, subendothelial matrix and fibronectin, but not to type IV collagen. TPA-enhanced adhesion can be reduced by lipoxygenase inhibitors but not by cyclooxygenase inhibitors and in addition, stimulated adhesion can be blocked by pretreatment of tumor cells with specific polyclonal or monoclonal antibodies which react against IRGpIIb/IIIa. 12(S)-HETE-enhanced adhesion can also be inhibited by these same antibodies. In contrast, a lipoxygenase product of linoleic acid, 13(S)-hydroxyoctadecadienoic acid, inhibited TPA and 12(S)-HETE-enhanced tumor cell adhesion to endothelial cells, subendothelial matrix, and fibronectin. These results suggest that (a) IRGpIIb/IIIa is a multifunctional receptor which mediates tumor cell adhesion to a variety of biological substrata, (b) TPA enhances surface expression and/or activation of this receptor possibly via a lipoxygenase metabolite of arachidonic acid, and (c) these effects are opposed by a lipoxygenase metabolite of linoleic acid.
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PMID:Bidirectional control of membrane expression and/or activation of the tumor cell IRGpIIb/IIIa receptor and tumor cell adhesion by lipoxygenase products of arachidonic acid and linoleic acid. 249 4

Metastatic spread of malignant tumor appears to correlate with activation of the fibrolytic system. The role of fibrinolysis in growth and metastasis was examined in Lewis lung carcinoma of mice. The inhibition of fibrinolysis or proteases decreased the primary tumor growth and pulmonary metastasis, whereas the activation of fibrinolysis or proteases increased the number of metastatic foci in the lung. Electronmicroscopically, thrombus formation in the primary site prevented tumor invasion and metastasis formation. Plasminogen activator (PA) content of excised tumors was determined by SDS-PAGE, and major PA was found to be urokinase (UK) type. Immunohistochemical study with specific antisera was done. When tumor cells possessed a high level of UK, laminin and type IV collagen, components of the basement membrane, disappeared from tumor tissues. These findings suggest that PA through protease cascade plays a role in tumor invasion and metastasis. Clinically, patients with advanced cancer are usually in a hypercoagulable state with elevated fibrinogen, and fibrin deposition around tumor mass is a serious problem in cancer chemotherapy. UK infusion prior to 5-fluorouracil increased tissue concentration of antitumor agent. However, development of consumption coagulopathy characterized by progression from hypercoagulable state to disseminated intravascular coagulation has also been found in several cases.
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PMID:[Tumor metastasis and the fibrinolytic system]. 273 23


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