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R Salgia

Publications and source records attributed to R Salgia.

At least 55 records · Page 3Linked to original sources
PubMed1995

CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells.

The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In primary neutrophils from patients with CML, the major novel tyrosine-phosphorylated protein is CRKL, an SH2-SH3-SH3 linker protein which has an overall homology of 60% to CRK, the human homologue of the v-crk oncogene product. Anti-CRKL immunoprecipitates from CML cells, but not normal cells, were found to contain p210BCR/ABL and c-ABL. Several other phosphoproteins were also detected in anti-CRKL immunoprecipitates, one of which has been identified as paxillin, a 68-kDa focal adhesion protein which we have previously shown to be phosphorylated by p210BCR/ABL. Using GST-CRKL fusion proteins, the SH3 domains of CRKL were found to bind c-ABL and p210BCR/ABL, while the SH2 domain of CRKL bound to paxillin, suggesting that CRKL could physically link p210BCR/ABL to paxillin. Paxillin contains three tyrosines in Tyr-X-X-Pro (Y-X-X-P) motifs consistent with amino acid sequences predicted to be optimal for binding to the CRKL-SH2 domain (at positions Tyr-31, Tyr-118, and Tyr-181). Each of these tyrosine residues was mutated to a phenylalanine residue, and in vitro binding assays indicated that paxillin tyrosines at positions 31 and 118, but not 181, are likely to be involved in CRKL-SH2 binding. These results suggest that the p210BCR/ABL oncogene may be physically linked to the focal adhesion-associated protein paxillin in hematopoietic cells by CRKL. This interaction could contribute to the known adhesive defects of CML cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL.

The BCR/ABL oncogene causes chronic myelogenous leukemia (CML) in humans and induces growth factor independence of hematopoietic cell lines in tissue culture. p210BCR/ABL is localized at least in part to the cytoskeleton, and has been shown to interact directly with actin filaments through an actin binding domain located in the C-terminus of ABL. CML cells have reduced adhesion to some extracellular matrix components but the mechanism of this phenomenon is unknown. In this study we examined tyrosine phosphorylation of focal adhesion proteins in cells expressing p210BCR/ABL. An interleukin-3 (IL-3)-dependent cell line, 32Dc13, was transformed with a BCR/ABL cDNA, and the patterns of localization, expression, and tyrosine phosphorylation of focal adhesion proteins were compared among untransformed 32Dc13 cells with and without IL-3 stimulation and BCR/ABL-transformed 32Dc13 cells. Of the focal adhesion proteins examined, only paxillin exhibited tyrosine phosphorylation in response to IL-3; while in cells transformed by p210BCR/ABL, paxillin, vinculin, p125FAK, talin and tensin were constitutively tyrosine phosphorylated. IL-3 induced a transient association between paxillin and vinculin, while in BCR/ABL-transformed cells, several proteins coimmunoprecipitated with paxillin, including vinculin, p125FAK, talin and tensin. Pseudopodia enriched in focal adhesion proteins were transiently detected in 32Dc13 cells in response to IL-3, but constitutively detected in cells expressing p210BCR/ABL. p210BCR/ABL protein was also found concentrated in punctate structures adjacent to the cell membrane in myeloid cell lines, which often contained vinculin and paxillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL.

Paxillin is a 68-kDa focal adhesion protein that is phosphorylated on tyrosine residues in fibroblasts in response to transformation by v-src, treatment with platelet-derived growth factor, or cross-linking of integrins. Paxillin has been shown to have binding sites for the SH3 domain of Src and the SH2 domain of Crk in vitro and to coprecipitate with two other focal adhesion proteins, vinculin and focal adhesion kinase (p125fak). After preliminary studies showed that paxillin was a substrate for the hematopoietic oncogene p210BCR/ABL, we investigated the role of this protein in hematopoietic cell transformation and signal transduction. A full-length length cDNA encoding human paxillin was cloned, revealing multiple protein domains, including four tandem LIM domains, a proline-rich domain containing a consensus SH3 binding site, and three potential Crk-SH2 binding sites. The paxillin gene was localized to chromosome 12q24 by fluorescence in situ hybridization analysis. A chicken paxillin cDNA was also cloned and is predicted to encode a protein approximately 90% identical to human paxil-lin. Paxillin coprecipitated with p210BCR/ABL and multiple other cellular proteins in myeloid cell lines, suggesting the formation of multimeric complexes. In normal hematopoietic cells and myeloid cell lines, tyrosine phosphorylation of paxillin and coprecipitation with other cellular proteins was rapidly and transiently induced by interleukin-3 and several other hematopoietic growth factors. The predicted structure of paxillin implicates this molecule in protein-protein interactions involved in signal transduction from growth factor receptors and the BCR/ABL oncogene fusion protein to the cytoskeleton.

3T3 Cells↗
PubMed1995

The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases.

Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocyte-lineage cells. The receptor for TPO, c-MPL, is a member of the hematopoietic cytokine receptor family and has previously been shown to rapidly activate one or more cytoplasmic tyrosine kinases after ligand binding. In this study, we found that activation of the TPO receptor rapidly induced tyrosine phosphorylation of two members of the Jak tyrosine kinase family, JAK2 and TYK2, but not JAK1 or JAK3, in two different factor-dependent hematopoietic cell lines. The activation of both JAK2 and TYK2 was dose- and time-dependent and was associated with rapid tyrosine phosphorylation of a series of STAT proteins including STAT1, STAT3, and STAT5. Gel-shift assays indicated that one or more of these STATs is likely to participate in the formation of specific DNA-binding complexes. The activation of tyrosine kinases and signal propagation through tyrosine phosphorylation are likely to represent important initial steps in mediating the activities of TPO in myeloid cells.

Animals↗
PubMed1994

Changes in Tc-99m radionuclide bone scan images and peripheralization of marrow hematopoietic activity associated with the administration of granulocyte colony stimulating factor as an adjunct to dose-intensified chemotherapy for breast cancer. A case report.

Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy-associated neutropenia. Very little is known about the manner in which pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic changes on bone scan associated with the administration of G-CSF used to support dose-intensified combination chemotherapy in a patient with metastatic breast carcinoma are described. The scintigraphic findings were correlated histologically with increased hematopoietic activity in the bone marrow located in peripheral bones.

Adult↗
PubMed1994

Shc phosphorylation in myeloid cells is regulated by granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor and is constitutively increased by p210BCR/ABL.

Granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor induce proliferation of hematopoietic cells through binding to specific, high affinity, cell surface receptors. However, little is known about post-receptor signal transduction pathways. Here we report that an SH2 domain containing protein previously implicated in the activation of p21ras, Shc, is transiently tyrosine phosphorylated in myeloid cells after stimulation with granulocyte macrophage colony-stimulating factor, interleukin-3, or steel factor. Also, Shc was found to be constitutively tyrosine phosphorylated in myeloid cell lines made factor independent by expression of p210BCR/ABL. A Shc-associated 140-kDa protein was identified, which was phosphorylated on tyrosine residues transiently after cytokine stimulation and constitutively after expression of p210BCR/ABL. These findings suggest that Shc could play an important role in a signal transduction pathway, which leads to the proliferation of myeloid cells.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Factor independence of human myeloid leukemia cell lines is associated with increased phosphorylation of the proto-oncogene Raf-1.

The proliferation of normal hematopoietic cells is strictly factor dependent, while leukemic cell lines and primary leukemic cells are frequently factor independent. Although autocrine growth stimulation of human leukemias is occasionally observed in vitro, it is possible that mutations of signal-transduction or cell-cycle control genes may also be important in the development of factor independence. We have previously shown that the proto-oncogene Raf-1, a 70-kd serine/threonine protein kinase, is rapidly phosphorylated and activated by hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and Steel factor and is likely to be an important intermediate in mitogenic signal transduction pathways in hematopoietic cells. In an effort to better understand the possible role of abnormal signal transduction in the development of factor independence, we compared the state of phosphorylation and associated kinase activity of Raf-1 between a series of factor-dependent human and murine-myeloid normal cells or cell lines and a series of factor-independent myeloid cell lines. In factor-dependent myeloid cells (normal neutrophils; monocytes; and the cell lines MO7, 32Dc13, and FDC-P1), Raf-1 phosphorylation and associated kinase activity was strictly regulated by the supply of growth factor. In contrast, each of eight factor-independent leukemic cell lines examined, HL-60, KG-1, K562, U937, JOSK-S, JOSK-M, JOSK-K, and JOSK-I, expressed hyperphosphorylated Raf-1 with increased Raf-1 associated kinase activity in the absence of growth factor addition. To further explore the relationship of Raf-1 to factor-independent growth, factor-independent sublines were derived from two factor-dependent cell lines, MO7 and FDC-P1, by culture in CSF-deprived medium. Also, several factor-independent sublines were derived by transfection of a cDNA encoding p210BCR/ABL into three different cell lines: MO7, 32Dc13, and FDC-P1. In each case, the new sublines expressed constitutively hyperphosphorylated and activated Raf-1. The correlation of hyperphosphorylation of Raf-1 with factor independence was also observed with primary acute myeloblastic leukemia cells. The rate of "spontaneous" proliferation of primary acute myeloblastic leukemia (AML) cells in vitro correlated with the extent of Raf-1 phosphorylation. These results suggest that the evolution of myeloid leukemic cells to factor independence is associated with phosphorylation and activation of Raf-1, implicating Raf-1 and signal transduction pathways which activate RAf-1 in this process.

Bone Marrow↗
PubMed1993

Altered membrane fluidity in rat hepatocytes during endotoxic shock.

Steady-state fluorescence anisotropy measurements of the fluorescent hydrocarbon probe 1,6-diphenyl-1,3,4-hexatriene (DPH) were carried out in isolated hepatocytes of saline control and Salmonella enteritidis endotoxin (20 mg/kg) injected rats. Statistically significant differences were observed in the fluorescent anisotropy (rs) and membrane microviscosity (eta) values of control (rs = 0.107 +/- 0.004 (SEM), eta = 0.98 +/- 0.08, n +/- 6) versus endotoxin injected rat hepatocytes (rs = 0.134 +/- 0.005, eta = 1.43 +/- 0.08, n = 6, p < 0.001) at 37 degrees C. Fluidity was similarly lower in the isolated plasma membrane preparations from endotoxin-injected rat livers relative to control livers. When endotoxin-injected rats were treated with the calcium channel-blocker diltiazem, the anisotropy and microviscosity values were comparable to those obtained from control rats (rs = 0.152 +/- 0.003, eta = 1.00 +/- 0.003, n = 6). These measurements were made in animals five hours after endotoxin had been injected, and thus represent the in vivo effects of bacterial endotoxins. Temperature scan studies of DPH from 5-40 degrees C revealed that the membrane fluidity of endotoxin-injected rat hepatocytes was significantly lower than control hepatocytes at all temperatures investigated. The data suggest that endotoxin alters the membrane fluidity of hepatocytes, and that calcium-channel blockers can prevent the alteration. Our previous studies have shown that calcium channel blocker prevented endotoxin induced alterations in hepatic cellular regulation of Ca2+. Thus, cellular calcium homeostasis may be important in the maintenance of membrane fluidity and other membrane-associated transport functions.

Animals↗
PubMed1993

Interleukin-3 and p210 BCR/ABL activate both unique and overlapping pathways of signal transduction in a factor-dependent myeloid cell line.

Chronic myelogenous leukemia (CML) is characterized by a specific chromosomal translocation occurring between the long arms of chromosomes 9 and 22 resulting in a fusion product, p210 BCR/ABL, which has elevated tyrosine kinase activity. Expression of p210 BCR/ABL in murine interleukin-3 (IL-3)--dependent cell lines typically converts these cell lines to factor-independence by a non-autocrine mechanism. The IL-3 receptor is believed to function in part by activating a receptor-associated tyrosine kinase, leading to the hypothesis that p210 BCR/ABL may induce factor-independence of myeloid cells by constitutively phosphorylating some common signal-transducing proteins that normally would be phosphorylated on tyrosine residues in response to IL-3. p210 BCR/ABL subclones were constructed from an IL-3-dependent murine myeloid cell line, 32Dcl3, by transfection of a plasmid containing a full-length p210 BCR/ABL cDNA. Following transfection, the cells became completely factor-independent within 3 weeks. We examined the effects of p210 BCR/ABL and IL-3 on the pattern of tyrosine phosphorylation of cellular proteins in 32Dcl3 cells using one- and two-dimensional antiphosphotyrosine immunoblotting. WEHI-3B conditioned media (WEHI-CM) was used as a source of IL-3. The introduction of p210 BCR/ABL results in constitutively increased levels of tyrosine phosphorylation of more than 20 new proteins, while WEHI-CM induced transient tyrosine phosphorylation of 6 to 10 new proteins. Using two-dimensional immunoblots to examine phosphoproteins, four categories could be identified: (1) proteins that are inducibly tyrosine phosphorylated in response to WEHI-CM in 32Dcl3 cells only, (2) proteins inducibly tyrosine phosphorylated by WEHI-CM only in p210 BCR/ABL+ cells, (3) proteins that are inducibly tyrosine phosphorylated in response to WEHI-CM in both 32Dcl3 cells and p210 BCR/ABL+ cells, and (4) proteins inducibly tyrosine phosphorylated in response to WEHI-CM and constitutively phosphorylated in the presence of p210 BCR/ABL. We have identified one of the proteins in category 4 as p42 mitogen-activated protein (MAP) kinase (ERK2). Overall, however, we found that the signal transduction pathways of IL-3 and BCR/ABL are strikingly different, suggesting that most of the immediate substrates of the IL-3 receptor-activated tyrosine kinase and p210 BCR/ABL kinase are different. Convergence of signaling pathways at p42 MAP kinase is of interest since activation of this kinase has been linked to mitogenesis in many systems. Identification of the overlapping proteins of both IL-3 signal transduction in 32Dcl3 cells and p210 BCR/ABL+ cells may help explain the growth-promoting effects of this oncogene.

Animals↗
PubMed1992

Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines.

The Philadelphia chromosome (Ph1), detected in virtually all cases of chronic myelogenous leukemia, is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c-ABL. This oncogene produces a fusion protein (p210BCR/ABL) in which the ABL tyrosine kinase activity is elevated. This elevated kinase activity is essential for transformation, but the mechanisms involved are unknown. We report here that p21ras GTPase activating protein (rasGAP) or rasGAP-associated proteins p190 and p62 are phosphorylated on tyrosine in Ph1 (+) cell lines. Further, rasGAP coimmunoprecipitates with p210BCR/ABL in these cell lines. These results suggest that rasGAP or associated proteins are potential substrates for p210BCR/ABL kinase and thus directly link p210BCR/ABL with a signal transduction pathway known to be activated by hematopoietic growth factors (p21ras).

Fusion Proteins, bcr-abl↗
PubMed1989

Control of bleeding in patients with immune and nonimmune thrombocytopenia with aminocaproic acid.

Patients with thrombocytopenia have an increased risk of bleeding. We have used 18 courses of aminocaproic acid in 17 patients with either immune or nonimmune thrombocytopenia to successfully control hemorrhage associated with reduced platelet counts. The types of hemorrhage controlled included the following: vaginal, gastrointestinal, intracerebral, cutaneous, mucous membrane, subconjunctival, and renal, as well as that associated with dental extractions, tracheostomy, and sites of Penrose drains. The number of platelet and red blood cell transfusions administered decreased substantially following institution of aminocaproic acid therapy. We conclude that therapy with aminocaproic acid is safe and useful in the management of bleeding in patients with both immune and nonimmune thrombocytopenia.

Adult↗
PubMed1987

Degradation and regurgitation of extracellular proteins by cultured mouse peritoneal macrophages and baby hamster kidney fibroblasts. Kinetic evidence that the transfer of proteins to lysosomes is not irreversible.

The uptake and degradation of bovine serum albumin (BSA), bovine liver catalase, and rabbit muscle enolase have been studied in cultured mouse peritoneal macrophages (MPM) and baby hamster kidney fibroblasts (BHK cells). Rates constant for the uptake of the three proteins by MPM were similar. In addition, BSA accumulation was independent of BSA concentration in the uptake medium and was not inhibited by a large excess of serum, suggesting that protein accumulation was by fluid phase pinocytosis. Following an overnight uptake, 20-30% of the accumulated protein was subsequently regurgitated into the medium in a trichloroacetic acid/phosphotungstic acid-precipitable form. This material co-migrated with the authentic protein during molecular sieve chromatography on Sephadex G-50. The rates of appearance of trichloroacetic acid/phosphotungstic acid-insoluble products were greater than expected for cell death and leakage. The observed first order rate constants, kobs, for the appearance of trichloroacetic acid/phosphotungstic acid-soluble and trichloroacetic acid/phosphotungstic acid-insoluble products in the culture medium were identical, indicating that both products were released in parallel from MPM and BHK cells. The kobs for intracellular BSA degradation and regurgitation were independent of the initial BSA concentration in the uptake medium, but were decreased about 35% when degradation was allowed to proceed in the presence of high concentrations of serum. Degradation was also inhibited by chloroquine and pepstatin. Inhibition of degradation was accompanied by an increase in the total amount of regurgitated protein appearing in the medium. Remarkably, however, these inhibitors also decreased kobs for regurgitation, thereby preserving the similarity in the observed rate constants for the appearance of trichloroacetic acid/phosphotungstic acid-soluble and trichloroacetic acid/phosphotungstic acid-insoluble products. These and other results were inconsistent with desorption of proteins from the surface of the culture dish or the surface of cells as the source of the trichloroacetic acid/phosphotungstic acid-insoluble label appearing in the medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications.

Over a 2-month period, 40 patients with untreated malignancy were studied for protein-C (PRC), antithrombin-III (AT-III), fibrinopeptide A (FPA), routine hemostatic screens, and presence of liver metastases to determine pretreatment changes of hemostasis and relate them to subsequent development of thrombotic or hemorrhagic complications. These patients were observed for a mean period of 18 months. There were 23 males and 17 females with a median age of 64 years. Nine patients had lung carcinoma, 8 colon carcinoma, 7 lymphoma, 5 breast carcinoma, 5 head and neck carcinoma, 2 acute leukemia, 2 prostate carcinoma, 1 adenocarcinoma of unknown primary, and 1 sarcoma. Eight patients had liver metastases. PRC was measured by ELISA, AT-III by radial immunodiffusion, and FPA by RIA. Four patients had decreased AT-III, 28 had decreased levels of PRC, and 39 had elevated levels of FPA. All patients with liver metastases had low PRC. Albumin levels were lower in patients with low PRC (mean 3.3 g/dL v 4.0 g/dL for others). Eight patients, five with liver metastases, developed thrombotic (4), hemorrhagic (3), or both (1) complications. Statistically significant associations were found between (1) presence of liver metastases and development of thrombotic and hemorrhagic complications (P less than .001), (2) presence of liver metastases and decreased PRC (P = .001), and (3) lower albumin levels and decreased PRC (P = .0001). Our study documents early changes of hemostasis in untreated malignancy. We extend previous observations that decreased PRC levels in malignancy may be due to poor synthetic functions of liver. Presence of liver metastases was the only factor associated with subsequent development of thrombotic and hemorrhagic complications. Biochemical markers of hemostatic abnormalities, even though encountered frequently at the time of presentation, are of little predictive value for development of thrombotic and hemorrhagic complications.

Adult↗
PubMed1986

The effects of monensin on membrane lipids of cultured human skin fibroblasts.

We have investigated the effects of monensin, a monovalent cationophore, on the metabolism of neutral lipids, fatty acids, ceramide and phospholipids in cultured human skin fibroblasts. Treatment with 1 microM monensin for 18 h reduced the cellular cholesterol ester content to less than one-third of untreated cells, and incorporation of [3H]acetate into cholesterol ester was also reduced, to less than one-fifth. Concomitantly, a greater conversion of [3H]acetate into free cholesterol occurred. There was a moderate increase in free fatty acids, but no change in triacylglycerol content, although the content of the latter appeared to increase in the presence of fetal calf serum in the culture medium. Phosphatidylcholine decreased in content and phosphatidylserine increased among the phosphatides, but ceramide remained unchanged after monensin treatment. These findings suggest that monensin influences the metabolic interrelationships of structural lipids in fibroblasts.

Acetates↗
PubMedDate not supplied

Activated c-Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive illness with early metastases. There are several receptor tyrosine kinases (RTKs) overexpressed in SCLC, including c-Met. c-Met contains an external semaphorin-like domain, a cytoplasmic juxtamembrane domain, tyrosine kinase domain and multiple tyrosines that bind to adapter molecules. We have previously reported that c-Met is abundantly expressed in the NCI-H69 SCLC cell line and now have determined the downstream effects of stimulating c-Met via its ligand hepatocyte growth factor (HGF). Utilizing unique phospho-specific antibodies generated against various tyrosines of c-Met, we show that Y1003 (binding site for c-Cbl and a negative regulatory site), Y1313 (binding site for PI3K), Y1230/Y1234/Y1235 (autophosphorylation site), Y1349 (binding site for Grb2), Y1365 (important in cell morphogenesis) are phosphorylated in response to HGF (40 ng/ml, 7.5 min) in H69 cells. Since multiple biological and biochemical effects are transduced through the PI3K pathway, we determine the role of PI3K in the c-Met/HGF stimulation pathway. We initially determined that by inhibiting PI3K with LY294002 (50 microM over 72 hours), there was at least a 55% decrease in viability of H69 cells. Since H69 SCLC cells form clusters in cell culture, we determined the effects of HGF and LY294002 on cell motility of the clusters by time-lapse video microscopy. In response to HGF, SCLC moved much faster and formed more clusters, and this was inhibited by LY294002. Finally, we determined the downstream signal transduction of HGF stimulation of c-Met with and without inhibition of c-Met (with geldanamycin, an anisamycin antibiotic that inhibits c-Met in SCLC) or PI3K (with LY294002). We show that association of c-Met with PI3K and GAB2 is diminished by inhibiting c-Met. In summary, activation of the c-Met pathway targets the PI3K pathway in SCLC and this may be an important therapeutic target.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Fibronectin enhances viability and alters cytoskeletal functions (with effects on the phosphatidylinositol 3-kinase pathway) in small cell lung cancer.

Small cell lung cancer (SCLC) is a rapidly progressive disease with ultimate poor outcome. SCLC has been shown to interact closely with the stromal and extracellular matrix (ECM) components of the diseased host. ECM consists of type I/IV collagen, laminin, vitronectin, and fibronectin (FN) among others. Herein, we investigated the behavior of a SCLC cell line (NCI-H446) on FN-coated surface. Over a course of 72 h, FN (10 micro g/ml) caused both increased survival and proliferation of NCI-H446 cells. Survival under serum-starved conditions increased 1.44-fold and proliferation in the presence of fetal calf serum increased by 1.30-fold. The phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 reduced both survival and proliferation of NCI-H446 cells (0.48- and 0.27-fold, respectively), even on FN-coated surface. We next determined the effects of FN on cytoskeletal function such as cell motility/morphology and adhesion. Over a course of 24 h, FN reduced aggregation of NCI-H446 cells and induced flattened cellular morphology with neurite-like projections after 1 h, however, in the presence of LY294002, the cells rounded up. Adhesion of NCI-H446 cells also increased with FN (4.47-fold) which was abrogated with LY294002 treatment. This correlated with phosphorylation of the cytoskeletal protein p125FAK, on Tyr397, Tyr861 and Ser843 residues with FN. Even in the presence of LY294002, these serine/tyrosine residues were still phosphorylated on FN-coated surface. In contrast, the focal adhesion protein paxillin was not phosphorylated at Tyr31 with FN. In summary, FN stimulation of SCLC cells leads to enhancement of viability and changes in cytoskeletal function that are partially mediated through the PI3-K pathway.

Carcinoma, Small Cell↗
PubMedDate not supplied

Role of serum tumor markers CA 125 and CEA in non-small cell lung cancer.

BACKGROUND: CA 125 and CEA are valuable serum tumor markers that can be used to monitor response to therapy in patients with various solid tumors. Systemic studies of CA125 and CEA have not been evaluated in lung cancer. In this study, we report the serum levels of CA 125 and compared it to CEA in newly diagnosed lung cancer and analyzed the serum levels of these markers pre- and post-therapy. MATERIALS AND METHODS: Two hundred and sixteen patients with newly diagnosed non-small lung cancer were evaluated. CA 125 and CEA levels were correlated with stage and histopathology. RESULTS: CA 125 levels and CEA levels were shown to be lower in patients with early stage disease as compared to patients with unresectable or metastatic disease. CEA levels were significantly higher among patients with adenocarcinoma, while there was no statistically significant relationship between histology and CA 125. There was a statistically significant difference in the CEA and CA 125 levels dependent on tumor size. Thirty-seven patients were analyzed for responses to chemotherapy and responders are more likely to have decreases in CA 125 or CEA. CONCLUSION: When abnormally elevated inpatients witlrlung cancer, CA 125 and CEA are useful indicators of disease extent, a useful clinical therapeutic marker, and may potentially have important prognostic value.

Adenocarcinoma↗