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Biomedical subjects

G Jaques

Publications and source records attributed to G Jaques.

36 records · Page 2Linked to original sources
PubMed1991

Human chorionic gonadotropin and related glycoprotein hormones in lung cancer cell lines.

Twenty-five non-small cell lung cancer (NSCLC), 42 small cell lung carcinoma (SCLC), one extrapulmonary small cell carcinoma, 4 carcinoid, and 13 non-lung cancer cell lines were analyzed for human chorionic gonadotropin (HCG) and related glycoprotein hormones. HCG or its subunits were present in 72% of NSCLC, 10% of SCLC, one extrapulmonary small cell carcinoma, 3/4 carcinoids and 2/13 non-lung cancer cell lines. Related glycoprotein hormones were undetectable. These data indicate a frequent production of HCG or its subunits by NSCLC cell lines and cell lines from tumors with carcinoid features. They confirm the clinical inclusion of carcinoids under the broad category of NSCLC rather than SCLC despite their neuroendocrine features. Clinicians should not assume that undifferentiated NSCLC with HCG production represent germ cell tumors.

Biomarkers, Tumor↗
PubMed1991

Insulin-like growth factor binding protein expression in human small cell lung cancer cell lines.

Insulin-like growth factor binding proteins (IGF-BP) are secreted by several human small cell lung cancer cell lines (SCLC). In order to identify the IGF-BPs from SCLC cell lines the RNA from 10 different SCLC cell lines was analyzed by Northern blot analysis with the probes for three different IGF-BPs, IGFBP-1, IGFBP-2, and IGFBP-3. No hybridization signal could be detected with the probes encoding for IGFBP-1 and IGFBP-3. The hybridization with different IGFBP-2-specific oligodeoxynucleotide probes and with the corresponding full-length cDNA showed that all SCLC cell lines which secreted IGF-BPs express IGFBP-2.

Base Sequence↗
PubMed1990

Growth regulation by insulin-like growth factors in lung cancer.

Lung cancer is a major health problem, with over 38,000 new cases expected every year in West Germany. A more complete understanding of the biology of lung cancer will hopefully lead to therapeutic modalities. The possible autocrine growth regulation in small-cell lung cancer and non-small-cell lung cancer has been demonstrated for bombesin/GRP, vasopressin, neurotensin, EGF/TGF alpha, transferrin-related peptides and insulin-like growth factors. This contribution concentrates on recent data concerning binding sites, growth promoting effects and secretion of IGFs in lung cancer cell lines. The production of IGF-binding proteins which were also produced by lung cancer cell lines modifies the autocrine/paracrine model for IGFs since then proteins can either enhance or inhibit the effect of IGFs on tumor growth.

Humans↗
PubMed1989

Androgen receptors, androgen-dependent proliferation, and 5 alpha-reductase activity of small-cell lung cancer cell lines.

We investigated the influence of testosterone on binding to established small-cell lung cancer (SCLC) cell lines and were able to show specific high-affinity and low-capacity binding sites in some cell lines with a typical receptor size, using sucrose density gradient centrifugation. In addition, we demonstrated marked growth stimulation with testosterone and dehydrotestosterone using different androgen-receptor-positive small-cell lung cancer cell lines. This growth stimulation could be counteracted by the addition of anti-androgens like cyproterone acetate or flutamide. The presence of 5 alpha-reductase activity, 17 beta-hydroxysteroid-dehydrogenase and 3 alpha-hydroxysteroid-dehydrogenase activities could be demonstrated, suggesting testosterone metabolism of small-cell lung cancer cell lines.

Androgen Antagonists↗
PubMed1989

Production of insulin-like growth factor binding proteins by small-cell lung cancer cell lines.

Conditioned serum-free media (CM) from small-cell lung cancer (SCLC) cell lines were examined for the presence of insulin-like growth-factor-binding proteins (IGF-BP). 6/9 SCLC cell lines secreted binding proteins with high affinity for IGFs. When [125I]IGF-I or [125I]IGF-II was incubated with the CMs, complexes of tracer with proteins could be demonstrated by gel filtration, by precipitation with polyethylenglycol, and after adsorption of unbound tracer with activated charcoal. Analysis of binding data according to the method of Scatchard resulted in linear plots for IGF-I and IGF-II. The dissociation constants were determined to be 0.106 nM for IGF-I and 0.209 nM for IGF-II binding. Cross-linking of [125I]IGF-I or [125I]IGF-II to the CMs followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions revealed the presence of IGF-BPs with molecular masses in the range 24-32 kDa. The binding was competitively inhibited by addition of cold IGF-I and IGF-II but not by insulin. Northern blot hybridization with an IGF-BP cDNA probe encoding a low-molecular-weight IGF-BP from a human placenta cDNA library and Western blot analysis with a corresponding polyclonal antibody showed no expression of this gene. These data demonstrate that SCLC cell lines release IGF-BPs in culture supernatants, which differ from IGF-BPs detected in liver and placenta. These IGF-BPs might be important mediators in the autocrine/paracrine growth regulation of IGFs in SCLC.

Carcinoma, Small Cell↗
PubMed1988

Prognostic value of pretreatment carcinoembryonic antigen, neuron-specific enolase, and creatine kinase-BB levels in sera of patients with small cell lung cancer.

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and the BB isoenzyme of creatine kinase (CK-BB) were evaluated before therapy in the sera of 195 patients with histologically confirmed small cell lung cancer (SCLC) in a prospective multicenter trial. Forty-four percent (84 of 193) of all patients had CEA levels higher than 5 ng/ml, 66% (111 of 168) had NSE levels higher than 12.5 ng/ml, and 32% (40 of 123) had CK-BB levels higher than 10 ng/ml. Clear pathologic levels were less frequently observed. Significantly higher pretreatment titers for CEA, NSE, and CK-BB were found in patients with bone marrow and/or liver metastases. The most elevated marker levels were observed in the group of nonresponding patients with bone marrow and/or liver metastases. Only a slight correlation between the pretreatment CEA level and survival time could be observed. Patients with pathologic NSE (greater than or equal to 30 ng/ml) levels and, in particular, those with pathologic CK-BB (greater than or equal to 25 ng/ml) levels had a significantly shorter median survival than those with normal or elevated levels. In addition, a positive linear correlation between pretreatment NSE and CK-BB (n = 116, r = 0.54) levels was found, but CEA levels did not correlate with other marker levels. From these data it is concluded that pretreatment CEA, NSE, and CK-BB levels are helpful in the clinical management of a subset of patients with SCLC, i.e., those with bone marrow and/or liver metastases.

Biomarkers, Tumor↗
PubMed1988

Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects.

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.

Amino Acid Sequence↗
PubMed1988

Production of immunoreactive insulin-like growth factor I and response to exogenous IGF-I in small cell lung cancer cell lines.

Small cell lung cancer (SCLC) cell lines were examined for the presence of insulin-like growth factor I-related protein (IGF-I) in cell pellets and culture media. IGF-I immunoreactivity was detected in 11/14 pellets, ranging from 12 to 76 mIU/mg soluble protein. The IGF-I levels in the cell pellets showed a correlation to the corresponding culture media. IGF-I binding sites were found in all tested cell lines. The maximum binding (Bmax) ranged from 131 to 1230 fmol/mg protein and the dissociation constant (KD) from 0.89 to 5.21 nM. The incorporation of [3H]thymidine in the presence of recombinant human IGF-I resulted in a clearly increased DNA synthesis in two of seven cell lines. Thus, IGF-I may be an important growth factor in SCLC.

Animals↗
PubMed1988

Peptide hormones in patients with acute leukaemia.

Paraneoplastic production and secretion of peptide hormones by numerous malignant tumours is a well-known phenomenon. The incidence of the production of six peptide hormones was evaluated in patients with acute leukaemia. Most often the calcitonin gene-related peptides were found to be elevated in sera at the time of diagnosis. The values evaluated for the hormones were: h-CT 46.7%, CGRP 51%, s-CT 20.7%, PTH 15.7%, beta-HCG 15%, and ACTH 11.6%. A significant coincidence of two or more hormones was not observed. In 83.4% of the patients increased concentrations of at least one of the six hormones were found. Clinical and biochemical parameters showed no influence on the serum levels of these peptides. Analysis of elevated hormone serum levels in subtypes of leukaemia revealed that the calcitonin-related hormones were significantly correlated to more immature forms of leukaemia such as AUL and M1. Synthesis of calcitonin gene-related peptides was also seen in established leukaemic cell lines and in buffy coat cells of untreated patients with acute leukaemia. This investigation provides further evidence that peptide hormone production in leukaemic blasts is a common finding. These results further suggest hormone production to be a universal concommitant of neoplasia. A possible influence of these peptide hormones on the biological behaviour of the malignant cells is discussed.

Acute Disease↗
PubMed1988

Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines.

Six new non-small-cell lung cancer (NSCLC) cell lines were established directly from human tissue or indirectly via nude mouse xenografts in serum-supplemented media with success rates of 8% and 13%, respectively. They comprised one adenocarcinoma (ADLC-5M2), two squamous cell carcinomas (EPLC-32M1, EPLC-65H), two large cell carcinomas (LCLC-97TM1, LCLC-103H), and one malignant biphasic mesothelioma (MSTO-211H). All cell lines grew adherent to culture vessels with population doubling times (PDT) of 16-40 h, formed colonies in soft agarose with efficiencies of 0.1%-5.1%, and all grew in athymic nude mice. Xenograft histologies appeared as follows: (a) undifferentiated carcinomas with feeble resemblance to the original tumors in the case of adenocarcinomas and squamous cell carcinomas; (b) large cell carcinoma with high resemblance to the original tumor; (c) an undifferentiated tumor with predominance of large epithelial cells and few fibrous cells in the case of mesothelioma. Human chorionic gonadotropin (HCG) was found by radioimmunoassay and high-affinity binding sites for epidermal growth factor (EGF) by radio-receptor assay in 4/4 cell lines. A very low activity of L-DOPA decarboxylase (DDC) was detectable only in the adenocarcinoma cell line. All cell lines overexpressed the c-myc protooncogene, and no gene rearrangement or amplification was observed. Chromosome analysis revealed modal chromosome numbers of 70-73 in ADLC-5M2, EPLC-32M1, EPLC-65H, and MSTO-211H. Cell lines derived from large cell carcinoma had modal values of 65 and 170 and a wider chromosome distribution than all other cell lines. A NSCLC specific chromosomal aberration has been undetectable until now. These cell lines may aid in elucidating the biology of NSCLC and its interrelationship to other lung tumors.

Animals↗
PubMed1987

Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer.

Two small cell lung cancer (SCLC) cell lines were established from pericardial and pleural effusions of a patient with histopathologically proven SCLC of the oat cell type. Chemotherapy was administered without response during the 148-day period prior to the establishment of the first cell line, SCLC-22H, and some of the same drugs were administered in the 15 days prior to the establishment of the second cell line, SCLC-21H. Both cell lines differed markedly in their biochemical, kinetic, and morphological properties. Although the biomarkers L-Dopa decarboxylase, bombesin, carcinoembryonic antigen, and neurotensin were detectable in SCLC-22H, they were undetectable or low in SCLC-21H. The population doubling time was twice as fast and the colony forming efficiency higher in SCLC-21H than in SCLC-22H. They both expressed high concentrations of the SCLC marker enzymes neuron-specific enolase and the creatine kinase isoenzyme BB and showed no significant differences in their chromosomal characteristics. c-myc was amplified and expressed in both cell lines, and SCLC-21H had an additional rearranged and amplified EcoRI c-myc fragment. Morphological differences were apparent in liquid culture, cytology, and xenograft histology; SCLC-21H grew much more loosely than SCLC-22H, and had more prominent nucleoli and more abundant cytoplasm. Ultrastructurally dense core granules were present in both cell lines. SCLC-21H thus expressed properties of the variant cell type of SCLC, whereas SCLC-22H had mixed classic/variant features. An in vivo progression of the patient's tumor from a pure small cell to a mixed small cell/large cell morphology could be demonstrated, which suggests that cell line SCLC-22H represents a cell type characteristic for the transitional phase of the tumor. The features of this cell line therefore define a new subclass of SCLC called transitional cell type. SCLC-22H may be of use to study the mechanisms involved in the classic to variant transition, which probably has a considerable impact on the prognosis and response to therapy.

Carcinoma, Small Cell↗
PubMed1987

Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines.

Cell lines from SCLC were established with a success rate of 43% from different metastatic sites of treated and untreated patients. All 6 SCLC cell lines grew as floating cell aggregates without substrate adherence. The degree of aggregation ranged from very tight spheroids to very loose sheets and chains. This gross morphological property showed a striking correlation to the PDT, with short PDTs in loose growing cell lines and long PDTs in tight growing cell lines. Cell size and nuclear features, i.e., chromatin pattern and nucleolar prominence, also seemed to correlate with the PDT and gross morphology. All SCLC cell lines had dense core granules by electron microscopical examination. Several different serum-free and serum-supplemented growth media were tested for their feasibility in establishing and permanently growing SCLC. Serum-free SIT medium and SIT2.5 medium provided the best results in liquid culture. For semisolid SCLC cultivation, R 10 medium was superior to all other media tested. These cell lines are currently under intensive biochemical, molecular biological, and cytogenetical investigation in different laboratories and thus provide a tool for studying the biology of lung cancer.

Bone Marrow↗
PubMed1987

Markers and characteristics of human SCLC cell lines. Neuroendocrine markers, classical tumor markers, and chromosomal characteristics of permanent human small cell lung cancer cell lines.

Permanent human small cell lung cancer (SCLC) cell lines established in our laboratory were investigated for their expression of the enzymatic neuroendocrine markers L-DOPA decarboxylase (DDC), neuron-specific enolase (NSE), and creatine kinase (CK), including its BB isoenzyme (CK-BB), the classical tumor markers carcinoembryonic antigen (CEA), the alpha and beta subunits of human chorionic gonadotropin (alpha-HCG, beta-HCG), and alpha-fetoprotein (alpha-FP), and their chromosomal characteristics. DDC activities were detectable in 5/6 SCLC cell lines and absent in non-SCLC. NSE levels ranged from 160 to 1422 ng/mg soluble protein and were less than 290 ng/mg soluble protein in non-SCLC. Activities of CK and levels of CK-BB clearly distinguished SCLC from non-SCLC with CK activities greater than 1000 munits/mg soluble protein and CK-BB levels greater than 3000 ng/mg soluble protein in SCLC and less than 300 munits/mg soluble protein and less than 2000 ng/mg soluble protein in non-SCLC. CEA was detectable in 5/6 SCLC cell lines but absent in non-SCLC, and its level seemed to correlate with those of DDC, NSE, and CK. One cell line, SCLC-16H, lost some of its neuroendocrine properties and CEA after 1 year of in vitro cultivation. Generally, marker levels were low in fast growing cell lines and high in slow growing cell lines. HCG alpha and beta subunit and alpha-FP were not detectable in SCLC cell lines. All SCLC cell lines examined had near diploid DNA indices and modal chromosome numbers. Double minute chromosomes and homogeneously staining regions were found in 2/5 and 4/5 SCLC cell lines respectively. With respect to chromosomal aberrations, we found a deletion of the short arm of at least one chromosome 3 in all SCLC cell lines (5/5). These data show that SCLC expresses neuroendocrine markers and CEA; CK is the most sensitive marker, and DDC and CEA are the most specific markers for SCLC in vitro; individual marker levels correlate with each other and the in vitro malignancy of SCLC; and SCLC cell lines have relatively uniform chromosomal characteristics. Our results suggest that patients whose tumors have high levels of DDC, NSE, CK-BB, and CEA have a better prognosis than those with low marker levels. This hypothesis could be proved by comparing pairs of patients that are matched for all known prognostic parameters, in particular tumor spread, for their serum and tumor marker levels with respect to the patients' outcome and prognosis.

Carcinoembryonic Antigen↗
PubMed1981

Beta 2-microglobulin and other proteins as parameter for tubular function.

Urinary excretion of the low molecular weight protein beta 2-microglobulin and tubular enzymes--alanine aminopeptidase (AAP), gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (AP)--are very sensitive parameters for proximal tubular lesions. In patients with preeclampsia the renal excretion of beta 2-microglobulin allows to differentiate between a primary preeclampsia and a preeclampsia superimposed upon chronic pyelonephritis. In the first group the increase is 3- to 4-fold and in the second group up to 300-fold. In patients with kidney transplantation the urinary excretion of beta 2-microglobulin, AAP, gamma-GT and AP are several times higher than in normals. In case of a rejection episode a further increase of these proteins occur in more than 80% several days before clinical symptoms are present. The application of analgetics (paracetamol, acetylsalicylic acid) in healthy individuals in therapeutical dosages on 3 consecutive days does not show any tubular alteration by the measurement of urinary beta 2-microglobulin. Aminoglycosides (tobramycin, UK 18,892) lead to a cumulative increase of the renal excretion of beta 2-microglobulin and AAP while cephalosporins induce an increase of total proteins in the final urine under the same conditions.

Acetaminophen↗
PubMedDate not supplied

[Molecular pathology of lung cancer and insulin-like growth factors].

Molecular pathology of lung cancer (LC) investigates molecular-genetic rearrangements initiating development and growth of the tumor. The system of insulin-like growth factors (IGF) and binding proteins (IGFBP) regulates cell proliferation in the majority of embryonal and tumor tissues of man and animals in the course of reparation processes and productive inflammatory reaction. A general property of all LC histological types is presence in their cells of various members of IGF-system. Content of IGFII in tumor cells correlated with IGFBP-1, IGFBP-2, IGFBP-5. Location of IGFII and IGFBP in LC was different. IGFBP-1, -2, and -5, blocking IGFII, are detected in large amounts in areas of cell death inducing apoptosis while IGFII accumulates in dividing cells and foci of keratinization. Nuclear deposits of IGFBP-3 in bronchioloalveolar LC create phenomenon of intranuclear inclusion of "owl's eye" type. Synthesis of the majority of IGF occurs in tumor cells. Stromal cells also produce and transport into the tumor some quantity of IGFII and IGFBP.

Adenocarcinoma↗
PubMedDate not supplied

[Morphologic and molecular-genetic characteristics of keratinization and apoptosis in squamous cell lung carcinoma].

46 samples of squamous-cell lung carcinoma (SqCLC) from surgical patients were examined for biomolecular tumor markers (pancytokeratins, c-myc, p53, bcl-2, Bax, Ki-67, IGF-system) and apoptosis. Keratinization appeared an independent from apoptosis type of programmed cell death. It relates to cell death by differentiation, is followed by accumulation of c-fos, c-myc, Bax, IGF-II, IGFBP-2, IGFBP-5 this indicating their involvement in the regulation of this process. High level of apoptosis does not determine positive prognosis of the neoplastic process as it is not a single variant of programmed cell death in SqCLC. Malignant grade of SqCLC depends upon correlation between the proliferative processes and various types of cell death. Better prognosis of well and moderately differentiated SqCLC (as compared to poorly differentiated carcinomas) may be due to the fact that high proliferative activity of the tumor cells is balanced by their death by keratinization.

Apoptosis↗
PubMedDate not supplied

Carcinoembryonic antigen as differentiation marker for small cell lung cancer in vitro and its clinical relevance.

Fifteen small cell lung cancer (SCLC) cell lines and 249 histopathological specimens from patients with SCLC were investigated for carcinoembryonic antigen (CEA) expression. Quantitative determinations of CEA in cell line homogenates correlated significantly (p less than 0.001) with L-DOPA decarboxylase (DDC) activities and population doubling times (PDT). Using monoclonal antibodies specific for CEA (BW 431/31) and crossreactive with non-specific crossreacting antigens (NCA) 55 and 95 (BW 250/183 and BW 374/14), the CEA-reactive moiety in SCLC was immunologically identified as CEA. In vivo studies demonstrated CEA by immunohistochemistry in 57% (141/249) of newly diagnosed SCLC. The presence of CEA and the degree of immunostaining did not correlate with clinical parameters.

Age Factors↗