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J Bergh

Publications and source records attributed to J Bergh.

At least 145 records · Page 8Linked to original sources
PubMed1989

Histopathological and immunohistochemical analysis of lung tumors: description of a convenient technique for use with fine needle biopsy.

In this paper we describe a convenient procedure for use with fine-needle biopsy in the diagnosis of lung and medistinal tumors. Cells obtained from a fine-needle aspiration are suspended in a formaldehyde solution and allowed to sediment onto a polycarbonate filter, using a filtering device specially designed for this purpose. The filter with the aspirated cells is then embedded in paraffin and thereafter sectioned and stained in a routine manner. The main advantages with this technique, instead of cytology, are: 1. the cells are kept mainly intact, mostly in undisrupted clusters, and this increases the possibility of obtaining a specific diagnosis, a prerequisite for the diversified clinical management of malignant tumors: 2. possibilities exist, when necessary, of further immunohistochemical characterization of tumor cells in order to obtain a specific diagnosis without thoractomy. This could be of major importance when the management of certain tumors and infiltrates (i.e. those preferably treated by radio- and chemotherapy) does not require surgical intervention.

Adult↗
PubMed1989

Accumulation of hyaluronic acid in the alveolar interstitial tissue in bleomycin-induced alveolitis.

By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in the lungs of rats at different times (4, 10, and 20 days) after bleomycin injury. Four days after an intratracheal injection of bleomycin, HA was accumulated in the edematous alveolar septa of the focal areas with lung tissue injury. An interstitial cellular infiltrate of mainly lymphocytes was present. In normal rat lung, HA was not seen in the alveolar tissue but confined to peribronchial and perivascular spaces. Ten and twenty days after bleomycin administration, increasing numbers of macrophages were apparent in the alveolar space. Proliferating fibroblasts and deposition of collagen in the alveolar tissue were observed while the diffuse HA accumulation was becoming less prominent in the alveolar interstitial tissue. HA was more distinctly located in the surroundings of proliferating fibroblasts. A few scattered alveolar macrophages showed a positive staining for HA. An increased water content of the lung was most apparent 4 days after bleomycin administration. The accumulation of HA, a glycosaminoglycan with unique qualities to immobilize water, in the alveolar interstitium suggests a role for HA in the alveolar interstitial edema. The appearance of HA in alveolar macrophages might indicate that macrophage phagocytosis contributes to the elimination of HA from inflamed lung tissue.

Animals↗
PubMed1989

The release of chromogranin A and B like activity from human lung cancer cell lines. A potential marker for a subset of small cell lung cancer.

Human small cell lung cancer (SCLC) is in vivo and in vitro characterized by a heterogeneous spectrum of neuroendocrine markers. The non-SCLC group is deprived of these markers, or expresses them in low quantities. In this paper we report on the release to the culture medium of neuroendocrine associated proteins, chromogranin A and B like activity (CABLA). The culture medium from three out of five SCLC cell lines and in one/five non-SCLC cell line contained significant levels of CABLA. Normal diploid foreskin fibroblasts and a histiocytic lymphoma cell line were deprived of CABLA production. The presence of CABLA in both SCLC and non-SCLC further stress their common histogenetic origin. The CABLA values were partly unrelated to other neuroendocrine markers. Determinations of CABLA could thus be a potential and valuable marker for a subset of SCLC.

Biomarkers, Tumor↗
PubMed1988

A randomized study of radiation treatment in small cell bronchial carcinoma treated with two types of four-drug chemotherapy regimens.

Of an unselected series of 133 patients with small cell bronchial carcinoma, 110 patients (54 with extensive disease and 56 with limited disease) were randomly allocated to receive either chemotherapy with cyclophosphamide, doxorubicin, vincristine, and methotrexate, alternating after four cycles with cyclophosphamide, lomustine, vincristine, and methotrexate, or the same chemotherapy combinations together with irradiation at 40 Gy to the primary tumor area and the adjacent mediastinum. In patients with extensive disease the total response rates were 70% and 86% and the median survival 7.6 and 9.2 months, respectively. There were no long-term survivors, and no advantage was gained from radiation combination treatment. The results confirm previously reported findings. In limited disease the complete remission rates were 68% and 64%, the partial remission rates 26% and 28%, and the median survival was 14.8 and 15.4 months, respectively. There were no statistically significant differences favoring either treatment regimen. The disease-free survival exceeding 2 years in the two respective groups was 6.5% and 25%; this difference was not statistically significant. A slight advantage of combined radiation and chemotherapy in the direction of better long-term survival was confirmed by the 4-year disease-free survival rate of 12% as compared with 0% in the nonirradiation group. This difference was statistically significant. There was considerable toxicity with both treatment regimens. The addition of radiation treatment to the chemotherapy most likely benefits patients with limited disease. The overall median survival of all the unselected 133 patients (nonrandomized included) was 10.3 months, and the cure rate was 3%.

Actuarial Analysis↗
PubMed1988

Expression of an estramustine-binding associated protein in human lung cancer cell lines.

Estramustine-binding protein has previously been demonstrated in normal rat prostatic tissue, in normal human prostate epithelium, and in prostatic carcinomas. It binds specifically estramustine and estromustine, the cytotoxic metabolites of estramustine phosphate (Estracyt), a drug which is used in the treatment of prostatic carcinoma. In this study we have examined the presence of an estramustine-binding associated protein in a panel of human cell lines, representing the major histopathological types of lung cancer. A mouse (murine) monoclonal antiserum developed against rat estramustine-binding protein was used for immunohistochemical detection. Fast protein liquid chromatography was used for biochemical characterization. As judged from the immunohistochemical investigation, estramustine-binding protein was present in large amounts in five of six non-small cell carcinoma cell lines, while seven of eight small cell carcinoma cell lines were essentially negative. Fast protein liquid chromatography analyses of lysated cells from the lung cancer cell lines, incubated with [3H]estromustine, concurred with the results from the immunohistochemical stainings. These data strongly indicate a convincing connection between the immunoreactivity and ligand-binding properties of estramustine-binding protein in the cell lines examined. The presence of an estramustine-binding associated protein in human lung cancer cell lines has implications for further investigations into the biological relevance and the potential for eventual therapeutic applications.

Antibodies, Monoclonal↗
PubMed1988

Differential expression of platelet-derived growth factor and transforming growth factor genes in small- and non-small-cell human lung carcinoma lines.

We have investigated a panel of human lung cancer cell lines representing the major groups of lung cancer, i.e., small-cell carcinoma (SCC) and the group of non-SCC, consisting of squamous-cell carcinoma (SQC), adenocarcinoma (ADC) and large-cell carcinoma (LCC), for their expression of certain growth factor genes. Messenger RNA from each cell line was hybridized with probes for platelet-derived growth factor (PDGF) A- and B-chains, insulin-like growth factor (IGF)-I and -II, transforming growth factor (TGF)-alpha and -beta, epidermal growth factor (EGF) as well as a probe for the EGF receptor. All non-SCC cell lines examined showed expression of the PDGF A-chain gene. The PDGF beta-chain and TGF-beta genes were expressed in all non-SCC cell lines but one, H-125 (ADC). TGF-alpha gene expression was demonstrated in the SQC cell line U-1752, in both ADC cell lines (H-23 and H-125) and in one of the 3 LCC cell lines, U-1810. IGF-II was only transcribed in the LCC cell line U-1810. The EGF-receptor was detected in all non-SCC cell lines but one, H-661 (LCC). Neither IGF-I nor EGF transcripts could be seen in any of the 10 cell lines examined. In contrast to the non-SCC cell lines, the 4 SCC lines were constantly negative for the probes employed in this study. The frequent and heterogeneous expression of growth factor transcripts in all non-SCC studied, but not SCC-cell lines, may contribute to the difference in biological behaviour observed in vivo and in vitro between the 2 major lung cancer entities.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Estramustine binding protein and anti-proliferative effect of estramustine in human glioma cell lines.

Four human cell lines derived from malignant gliomas were immunohistochemically examined for their content of estramustine-binding protein (EMBP). EMBP was detected in a large amount in all glioma cells during the entire cell cycle. EMBP has previously been demonstrated to be the major receptor protein in prostatic cancers for the cytostatic drug estramustine-phosphate (EMP). EMP caused a dose-dependent inhibition of exponentially growing cells by increasing the number of cells in G2/M stage of the cell cycle as monitored by flow cytofluorometry. The effect may be coupled to arrest of the glioma cells at metaphase. The presence of EMBP may suggest a selective binding and effect of EMP in glioma cells.

Carrier Proteins↗
PubMed1988

The expression of the platelet-derived and transforming growth factor genes in human nonsmall lung cancer cell lines is related to tumor stroma formation in nude mice tumors.

Human lung cancer could be separated into two major groups, small cell lung cancer (SCLC), or non-SCLC based on morphology, biochemical profile, and clinical management. The SCLC group is characterized by a wide spectrum of neuroendocrine markers, while the non-SCLC group is defined by epithelial markers. The non-SCLC cell lines studied have also been demonstrated to express elevated mRNA levels for platelet-derived growth factors and transforming growth factors, while SCLC cell lines were negative for these genes. Four human SCLC cell lines and six human non-SCLC cell lines were inoculated into seventeen nude mice. All studied tumors from the non-SCLC cell lines demonstrated prominent fibrous stromata, although with variability between the individual cell lines. The SCLC cell lines were deprived of significant stroma reaction. These findings may be of importance in explaining the biologic and clinical differences between non-SCLC and SCLC.

Animals↗
PubMed1987

Expression of multiple growth factors in a human lung cancer cell line.

U-1810, a human large-cell lung cancer line, was found to express a PDGF-like growth factor. 35S-cysteine labelling and immunoprecipitation revealed the synthesis and secretion of a 31-kDa PDGF-like protein. Serum-free conditioned medium contained PDGF-receptor-competing and mitogenic activity when tested on human fibroblasts. Whereas the receptor-competing activity was fully neutralized by anti-PDGF antibodies, the mitogenic activity was only partially affected. We therefore probed U-1810 mRNA with a panel of growth-factor DNA clones. We found expression of the genes for PDGF A- and B-chains, TGF-alpha, TGF-beta and IGF-II but not EGF or IGF-I. U-1810 cells lacked specific binding sites for PDGF but showed specific binding of EGF and expressed EGF-receptor transcripts. Thus, U-1810 is an example of a human tumor cell line that expresses multiple growth factor genes; in the intact tumor the corresponding growth factors may operate in autocrine stimulation of the tumor cells as well as in paracrine growth reactions (i.e. stroma recruitment).

Cell Line↗
PubMed1987

Tachykinin production by carcinoid tumours in culture.

Tissue specimens from 5 patients with metastatic midgut carcinoid tumours were kept in organ culture for up to 6 months. The tumour cells were confined to the suspension in the form of condensed cell clusters and appeared to retain their endocrine characteristics. Radioimmunoassay for tachykinin immunoreactivity showed high concentrations in 4 out of 5 culture media. The concentrations were highest in the beginning of the experiment, but subsequently decreased. The 4 patients from which these tumours were taken had all elevated tachykinin concentrations in extracted plasma. The fifth culture medium had low tachykinin concentration, and the concentration in extracted plasma from this patient was within the normal range. Reversed-phase high-performance liquid chromatography of the culture media with elevated tachykinin concentrations revealed immunoreactive components with the characteristics of synthetic neuropeptide K, neurokinin A and eledoisin, components also found in plasma and tumour tissues of carcinoid patients. Our findings indicate that carcinoid tumour cells produce tachykinins. These peptides are biologically very active, resulting in flush and hypotension when infused intravenously into normals, and might contribute to the clinical symptoms of the carcinoid syndrome.

Carcinoid Tumor↗
PubMed1987

Increased expression of N-myc in human small cell lung cancer biopsies predicts lack of response to chemotherapy and poor prognosis.

Amplified and increased expression of the myc family of protooncogenes (c- and N-myc) has been described to be associated with rapid proliferation in a number of cell lines, including small cell lung cancer (SCLC). In SCLC, c-myc was demonstrated to be amplified in a subset of SCLC cell lines denoted as variant type, which show a more aggressive way of growth in vitro. The N-myc oncogene, which has extensive homology in the second exon with c-myc, has been shown to be implicated in the oncogenesis of several primary tumors, including SCLC. The authors describe, using in situ hybridization, that increased expression of the N-myc oncogenes in primary biopsies from 15 untreated patients with SCLC are strongly associated with poor response to chemotherapy, rapid tumor growth, and short survival.

Adult↗
PubMed1986

Serum deoxythymidine kinase in small cell carcinoma of the lung. Relation to clinical features, prognosis, and other biochemical markers.

Thymidine kinase (s-TK), lactate dehydrogenase (LDH), and carcinoembryonic antigen (CEA) were determined in pretreatment serum from 125 patients with small cell carcinoma of the lung. The distribution of marker levels into three ranges, when including all patients were as follows: s-TK less than 5 units 49%, 5-less than 10 units 25%, greater than or equal to 10 units 26%; LDH less than 6.7 mukat 31%, 6.7-less than 13.4 mukat 48%, greater than or equal to 13.4 mukat 21%; CEA less than 7.5 micrograms/l 51%, 7.5-less than 15 micrograms/l 25%, greater than or equal to 15 micrograms/l 24%. The percentages of patients with limited and with extensive disease within each range were s-TK less than 5 82/18, 5-less than 10 29/71, greater than or equal to 10 9/91; LDH less than 6.7 76/24, 6.7-less than 13.4 51/49, greater than or equal to 13.4 21/79; CEA less than 7.5 70/30, 7.5-less than 15 39/61, greater than or equal to 15 23/77. Analyses in relation to metastases present showed that patients with skeletal and bone marrow metastases had significantly higher s-TK and LDH than those without, while this was not the case for CEA. A strong correlation between s-TK and LDH level, a weaker correlation between CEA and s-TK, and no correlation between CEA and LDH level, was found. Both the level of s-TK and LDH correlated to the patients' performance, as defined by the Karnofsky index. These correlations were mainly confined to the patients with extensive disease. Analyses of the prognostic capacity of variables showed that s-TK, stage, and Karnofsky index could divide the patients into groups with highly significant difference in survival time, while LDH and CEA were of less value. Longitudinal studies showed that the serum markers mirrored the disease activity, with the exception that highly increased s-TK was found during remission induction for some patients. It was concluded that the expression of pathologic levels for the serum markers were dependent on different biological parameters. Of the serum markers, only s-TK was judged useful for estimation of disease spread and prognosis of the individual patient.

Actuarial Analysis↗
PubMed1986

Amplification of the N-myc oncogene in an adenocarcinoma of the lung.

c-myc oncogene is the most extensively studied member of the myc gene family, which now consists of three characterized members, namely the c-myc, N-myc, and L-myc genes. Deregulation owing to amplification and/or rearrangements of the c-myc gene have been described in a variety of human malignancies. Several neuroblastomas have amplifications of the N-myc genes. The c-myc, N-myc, or L-myc oncogenes are also found amplified in different cell lines from small cell carcinomas of the lung. In this study, we have examined the c-myc, N-myc, and c-erbB oncogenes in 34 clinical and autopsy tumor specimens representing various histopathological types of human lung cancer, including nine small cell lung cancers. A 30-fold amplification of the N-myc gene was found in a tumor histopathologically and histochemically verified as a typical adenocarcinoma. No amplifications of the c-myc or c-erbB oncogenes were seen in any of the tumors. In the DNA of one small cell carcinoma, an extra c-myc and N-myc cross-hybridizing restriction fragment was observed, possibly owing to an amplification of a yet uncharacterized myc-related gene.

Adenocarcinoma↗
PubMed1986

Acral lentiginous malignant melanoma. Case report.

We present a case of a regressing acral lentiginous malignant melanoma of the sole with metastases en route and to regional lymph nodes. The histological findings at the primary site were classed as Clark's level I, stressing the difficulty in diagnosing this type of tumours early enough for effective treatment.

Adult↗
PubMed1985

Karyotypic characterization of established cell lines and short-term cultures of human lung cancers.

Karyotypic patterns were analyzed from the four major histopathologic groups of human lung cancer: small cell (SCC), squamous cell (SQC), large cell (LCC), and adenocarcinoma (ADC). The studies were performed on banded chromosomes from direct preparations of pleural fluids (one case of SQC and LCC, respectively) and on cell lines. All metaphases were aneuploid and showed highly rearranged chromosomes, with the exception of the direct preparation of the SQC, which was pseudodiploid. The number of marker chromosomes varied-from tumor to tumor. No consistent aberrations could be detected. Special attention was paid to chromosomes 3p-, which was earlier reported to be a characteristic marker chromosome for SCC. We could confirm the presence of that abnormality in two of our six SCC lines. However, we also found a 3p- in a primary SQC culture, in one LCC cell line, and in one ADC cell line. The breakpoint on 3p was not consistent. In some lines, numerical and structural changes of chromosomes #1, #12, #14, and #22 were also noteworthy, although none of these chromosome abnormalities seemed to be correlated to a certain histopathologic group.

Adenocarcinoma↗
PubMed1985

Immunocytochemical demonstration of neuron-specific enolase (NSE) in human lung cancers.

An anti-serum against human neuron-specific enolase (NSE), raised in sheep, has been characterized and used for immunocytochemical localization of NSE in paraffin sections of normal tissues and lung cancers. Of the small cell carcinomas (SCC), 69 out of 99 (70%) cases stained with the anti-serum. Maltreated biopsies showed a lower frequency of positive staining (19/39), indicating the importance of well-preserved biopsies. There was no clear difference in the staining between the oat cell and intermediate cell type of SCC. A majority (14 out of 21) of the non-SCC:s (large cell, adenocarcinoma and squamous cell carcinoma) were also stained by the anti-serum. Generally, this staining was weak and it could be blocked by preabsorption of the anti-serum by purified NSE. It is concluded that NSE expression, in conjunction with traditional histology, serves as a useful but not exclusive marker for SCC.

Adenocarcinoma↗
PubMed1985

Establishment and characterization of cell lines from human small cell and large cell carcinomas of the lung.

Five new small cell carcinomas (SCC) cell lines and a large cell carcinoma (LCC) cell line were established from human lung cancers. The SCC cell lines had, as a group, common phenotypic properties which distinguished them from non-SCC cell lines. However, the studies also revealed a considerable biological heterogeneity among the individual SCC cell lines. Thus, the SCC cell lines had a typical growth pattern with cell clusters in suspension or partly adherent to the bottom. All the lines examined grew in agarose with variable cloning efficiencies, and all but one line formed tumors subcutaneously in nude mice. The ultrastructure of the SCC cell lines was characteristic with dense core granules at a variable frequency. Neuron-specific enolase was detectable in all SCC cell lines, usually in large amounts, and an inconstant production of a spectrum of polypeptide hormones was found, typical of SCC. The LCC cells proliferated in monolayers, formed colonies in agarose and grew in nude mice. Ultrastructurally, the LCC cell line differed from the SCC cell lines in having intra- and intercellular lumina and tonofilaments. The capacity of the LCC and a previously established squamous cell carcinoma cell line (U-1752) to produce neuron-specific enolase and polypeptide hormones was characteristically much lower than that of the SCC cell lines. We conclude from this study that SCC cell lines, although individually distinct from one another, are quite homogeneous as a group in expressing a set of basic common neuro-endocrine markers. However, these studies also suggest some biological relationship between SCC, LCC and SQC by virtue of their expression of some common neuro-endocrine markers, in support of the concept of a common histogenetic origin of human lung cancers.

Carcinoma, Small Cell↗