Allelotype analysis of adenocarcinoma of the gastric cardia.

To identify chromosomal loci involved in the development of proximal gastric adenocarcinoma, this study delineated the pattern of allelic imbalance in a series of 38 adenocarcinomas arising in the gastric cardia. A total of 137 microsatellite markers covering all autosomal arms, excluding acrocentric arms, were analysed. A mean of 35 out of a total of 39 chromosomal arms studied were informative for each patient.

Processing of [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P in xenograft bearing Nu/Nu mice.

[D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P is a broad-spectrum neuropeptide growth factor antagonist that has exhibited in vitro activity against a range of human cancer cell lines. The fate of this compound in vivo following i.p.

Corticotropin-releasing hormone and calcium signaling in corticotropes.

Corticotropin-releasing hormone (CRH) stimulates ACTH secretion from anterior pituitary corticotropes, largely, but possibly not exclusively, via activation of the adenylyl cyclase cascade. CRH stimulates secretion by increasing Ca(2+) influx and by Ca(2+)-independent mechanisms. As Ca(2+) influx is largely regulated by membrane electrical properties, we review the effects of CRH on membrane excitability and changes in cytosolic Ca(2+).

Expression and activation of protein kinase C isoforms in a human megakaryocytic cell line.

Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. We have shown previously that phorbol 12-myristate 13-acetate (PMA) induces the Dami human megakaryocytic cell line to become polyploid and to express platelet-specific proteins, including von Willebrand factor (vWF) and glycoprotein Ib (GpIb). Phorbol esters are thought to regulate gene expression principally through the activation of protein kinase C (PKC), a family of structurally related kinases with potentially unique activation requirements and substrate specificities.

Effect of Matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines.

The effect of Matrigel, a solubilised tissue basement membrane extract, has been investigated on the tumorigenicity of 3 breast (MCF-7, T47D and MDA.MB.231) and 5 ovarian [PEO1, PEO1 cDDPr, PEO4, PEO14 and OV(hyg)CAR3] carcinoma cell lines.

Corticotropin-releasing hormone stimulates Ca2+ entry through L- and P-type Ca2+ channels in rat corticotropes.

CRH induces corticotrope membrane depolarization and facilitates action potential firing. The increase in electrical excitability causes large oscillatory increases in cytosolic Ca2+ levels. In this study on highly enriched populations of cultured rat corticotropes, inhibitors were used to determine the contribution of the Na+ channel and Ca2+ channel subtypes to membrane excitability and cytosolic Ca2+ levels.

Thrombopoietin suppresses apoptosis and behaves as a survival factor for the human growth factor-dependent cell line, M07e.

Thrombopoietin (TPO) has been demonstrated to have proliferative effects on hematopoietic progenitor cells and maturational effects on more committed populations which express a megakaryocyte lineage-specific phenotype. M07e is a GM-CSF or interleukin 3 (IL-3)-dependent human leukemic cell line having surface markers characteristic of both myeloid progenitors and megakaryocytes. The effects of TPO on the proliferation and survival of M07e cells were investigated.

Widespread microsatellite instability occurs infrequently in adenocarcinoma of the gastric cardia.

Heredity non-polyposis colorectal cancer (HNPCC) is associated with an increased predisposition to colorectal cancer and extra-colonic cancers of the gastro-intestinal, urological and female reproductive tracts. These tumours are characterised by an underlying defect in DNA mismatch repair and exhibit numerous replication errors throughout the genome (RER+ phenotype). HNPCC-associated gastric tumours, and a subset of sporadic, distally-located gastric tumours exhibit this RER+ phenotype.

Pharmacokinetics, metabolism and tumour disposition of 8-chloroadenosine 3',5'-monophosphate in breast cancer patients and xenograft bearing mice.

Background: 8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is undergoing phase I clinical trials as an anticancer drug. However, there is debate as to whether it is a prodrug for its 8-Cl-adenosine metabolite.

Design: Pharmacokinetics, metabolism and tumour disposition studies have been performed in 7 breast cancer patients receiving continuous infusion (28 day) 8-Cl-cAMP (0.

Ubiquitous somatic alterations at microsatellite alleles occur infrequently in Barrett's-associated esophageal adenocarcinoma.

Microsatellite alterations have been documented in a subset of sporadic tumors, including those of the colon, lung, bladder, stomach, and esophagus. This study documented the frequency of microsatellite alterations at 139 loci, comprising predominantly dinucleotide and tetranucleotide repeat units, in 17 cases of primary esophageal adenocarcinoma arising against a background of Barrett's metaplasia. Each tumor demonstrated alterations in at least one locus studied.

Corticotropin-releasing hormone stimulation of Ca2+ entry in corticotropes is partially dependent on protein kinase A.

The modulation of membrane excitability and cytosolic Ca2+ levels by corticotropin-releasing hormone (CRH), (Bu)2cAMP (dBcAMP), and forskolin was examined in enriched populations of cultured rat anterior pituitary corticotropes. CRH (2 or 20 nM), dBcAMP (1 and 5 mM), and forskolin (10 microM) caused a long lasting membrane depolarization accompanied by the onset of cell firing in quiescent cells or by increased firing frequency in spontaneously active cells. All three substances also increased cytosolic Ca2+ levels by increasing the frequency and amplitude of cytosolic Ca2+ transients.

Three high threshold calcium channel subtypes in rat corticotropes.

In this study on highly enriched populations of cultured rat corticotropes, Ca2+ channel inhibitors were used to identify subtypes of the high threshold Ca2+ channel current under voltage clamp conditions. From a holding potential (-50 mV) that eliminated the low threshold T-type current, 52 +/- 4% of the total current in 10 mM Ba2+ was mediated by dihydropyridine-sensitive L-type Ca2+ channels. Blockade of this current was half-maximal at a nifedipine concentration of 187 nM.

NATALI--a model for National Computer Databases in the investigation of new therapeutic techniques.

New medical treatments are often introduced without the benefit of randomized trials. We describe how a national computerized database was produced, by the Thrombolysis Study Group, for monitoring one such new treatment: peripheral arterial thrombolysis. A novel method for transferring angiograms to computer generated arterial maps that can help in the classification and analysis of the outcome of thrombolysis is also described.

Interferon-alpha and survival in renal cell cancer.

Objective: To establish whether the use of interferon-alpha might result in improved survival, using two large series of patients with advanced renal cell cancer treated during studies of chemotherapy and biological therapy, respectively.

Patients And Methods: Patients treated either in the Eastern Cooperative Oncology Group (ECOG) chemotherapy protocols (327 patients) or in protocols employing interferon as part of a European randomized study or phase II studies at the Norwegian Radium Hospital (231 patients) were retrospectively analysed. Groups for comparison were matched by exclusion of those with an ECOG performance status > 2, no prior nephrectomy, brain metastases or prior chemotherapy.

Computerized angiographic analysis of the outcome of peripheral thrombolysis.

Background: Catheter-directed peripheral thrombolysis is used increasingly for the management of acute limb ischemia. The comparison of different agents and techniques has proven difficult because of the variations in patient presentation, vessel involvement, and treatment methods.

Methods: A computerized database in which angiographic information is stored on computerized arterial maps has been designed to record details of thrombolysis.

Base transitions at CpG dinucleotides in the p53 gene are common in esophageal adenocarcinoma.

This study examined the association between 17p allelic loss and p53 gene mutation in a series of 16 esophageal adenocarcinomas arising on a background of Barrett's esophagus. Two highly polymorphic dinucleotide repeat polymorphisms mapping to 17p13 were analyzed to assess the frequency of 17p allelic loss in these tumors. Mutations in the p53 gene were detected by direct DNA sequencing.

Pharmacokinetics, metabolism, tissue and tumour distribution of the neuropeptide growth factor antagonist [Arg6, D-Trp7,9, NmePhe8]- substance P(6-11) in nude mice bearing the H69 small-cell lung cancer xenograft.

Background: [Arg6, D-Trp7,9, NmePhe8]-Substance P (6-11) (codenamed antagonist G) represents the first board spectrum antagonist of a number of neuropeptides shown to act as growth factors in small-cell lung cancer (SCLC) and is shortly to enter clinical trials.

Design: Pharmacokinetics, metabolism, tissue disposition have been studied in mice (nu/nu) bearing the NCI-H69 human SCLC xenograft after systemic drug adminstration at an active dose (45 mg/kg i.p.

Growth inhibition by 8-chloro cyclic AMP of human HT29 colorectal and ZR-75-1 breast carcinoma xenografts is associated with selective modulation of protein kinase A isoenzymes.

Significant dose-related inhibition of growth of HT29 human colorectal cancer xenografts and ZR-75-1 breast cancer xenografts in immune-suppressed mice was induced by the cyclic AMP analogue, 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cyclic AMP) when given by alzet mini-pumps over a 7-day period at doses of either 50 or 100 mg/kg/day. Levels and types of cyclic AMP binding proteins were measured by ligand binding and photoaffinity labelling, respectively, in tumours harvested at the end of the treatment period. Compared with levels in tumours from control animals, values of tumour cyclic AMP binding proteins from treated animals were significantly reduced.

Finite element analysis in the design and characterization of an absorbable cement restrictor.

The benefit of using a cement restrictor to achieve cement pressurization during total hip arthroplasty is well established. An absorbable cement restrictor design has been developed with the use of a finite element model. The non-linear axisymmetric model was used to optimize specific parameters so as to perform within acceptable limits when tested over a specified range of medullary canal sizes.

Effect of human recombinant interferon-alpha on the activity of cis-diamminedichloroplatinum(II) in human non-small cell lung cancer xenografts.

Interferons (IFNs) augment the effect of some antitumor agents, including cis-diamminedichloroplatinum(II) (cDDP), in experimental systems. The effect of human recombinant interferon-alpha 2b (rIFN alpha) on the cDDP-dependent growth delay of a human non-small cell lung cancer established as a xenograft in nude mice (NX002) has been investigated. IFN (10(5) IU/mouse, s.

On the development of the Medical Research Council trial of alpha-interferon in metastatic renal carcinoma. Urological Working Party Renal Carcinoma Subgroup.

This paper describes the steps taken by the British Medical Research Council (MRC) in developing the MRC RE01 trial, a randomized clinical trial for patients with metastatic renal cancer; we discuss the reasons for adopting a triangular sequential design and the impact that this has upon the monitoring of the trial. It had been suggested to the MRC that a trial of biological agents for metastatic renal carcinoma should be initiated. The Cancer Therapy Committee (CTC) of the MRC, through its associated site specific working parties, is responsible for designing and co-ordinating randomized trials of alternative treatments in cancer in solid tumours.

Growth inhibition of oestrogen receptor-positive human ovarian carcinoma by anti-oestrogens in vitro and in a xenograft model.

This paper presents results of the in vitro and in vivo effects of anti-oestrogens on the growth of human ovarian cancer cells. Tamoxifen and the "pure" anti-oestrogens, ICI 164,384 and ICI 182,780, inhibited the oestrogen-stimulated growth of the oestrogen receptor (ER)-positive PE04 and PE01 cell lines grown in culture, the latter two compounds being more potent than tamoxifen. In the absence of 17 beta-oestradiol (E2), tamoxifen, but not the pure anti-oestrogens, produced a small degree of growth stimulation in the PE01 and PE04 lines at concentrations between 10((7) and 10(-9) M.

Mortality from lung cancer in Ontario uranium miners.

Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men.