Use of fluorescence in situ hybridization to determine the relationship between chromosome aberrations and cell survival in eight human fibroblast strains.

A predictive assay of normal tissue radiosensitivity could benefit 'treatment tailoring' of radiotherapy for certain categories of tumour. The use of present clonogenic cell survival assays for this purpose would be impractical in routine clinical practice because of the lengthy assay time. Fluorescence in situ hybridization (FISH) using whole chromosome probes on metaphases was investigated as a potential substitute.

Mechanisms for optimising photodynamic therapy: second-generation photosensitisers in combination with mitomycin C.

Mechanisms for improving photodynamic therapy (PDT) were investigated in the murine RIF1 tumour using meso-tetrahydroxyphenylchlorin (m-THPC) or bacteriochlorin a (BCA) as photosensitisers and comparing these results with Photofrin-mediated PDT. The 86Rb extraction technique was used to measure changes in perfusion at various times after interstitial PDT. Non-curative combinations of light doses with m-THPC and BCA PDT markedly decreased vascular perfusion.

Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer.

Insulin-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity.

Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.

Episialin (MUC1) is a transmembrane molecule with a large mucin-like extracellular domain protruding high above the cell surface. The molecule is located at the apical side of most glandular epithelial cells, whereas in carcinoma cells it is often present at the entire surface and it is frequently expressed in abnormally large quantities. We have previously shown that overexpression of episialin reduces cell-cell interactions.

Assessment of sucralfate coating by sequential scintigraphic imaging in radiation-induced esophageal lesions.

The value of mucosal protection with sucralfate in cases of gastric ulceration is well documented. Although sucralfate is advocated as treatment of esophageal lesions, we found it to be of limited value in the management of radiation-induced esophagitis; in a pilot study of 10 cases, minor relief of symptoms, with analgetics still required, was noted in 4 patients, and no improvement was seen at endoscopy after 6 weeks of treatment in any patient. To see if this might be the result of inadequate mucosal coating, we administered sucralfate labeled with technetium 99m to 26 patients with endoscopically proven esophagitis secondary to irradiation for esophageal carcinoma.

Photosensitizing efficacy of MTHPC-PDT compared to photofrin-PDT in the RIF1 mouse tumour and normal skin.

The new photosensitizer, meso-tetrahydroxyphenylchlorin (mTPHC) was compared with Photofrin in the murine RIF1 tumour and in normal mouse skin. A range of mTHPC or Photofrin doses were given at intervals of 1 hr to 7 days before illumination. mTHPC-PDT resulted in much higher tumour phototoxicity with longer regrowth delays and more cures.

High levels of non-activated receptors in glucocorticoid-sensitive S49wt mouse lymphoma cells incubated with dexamethasone.

Upon agonist binding the heteromeric glucocorticoid receptor complex undergoes a conformational change (receptor activation). This event involves the dissociation of a dimer of 90 kDa heat shock proteins. Whereas receptor activation in cytosolic assays is both rapid and irreversible, less is known about the receptor activation and translocation in intact cells during challenge with an agonist.

Immunocytochemical identification of DNA adducts, O6-methylguanine and 7-methylguanine, in respiratory and other tissues of rat, mouse and Syrian hamster exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The present paper reports about an immunocytochemical inventory of the cell types involved in the metabolic activation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to a DNA methylating metabolite. The formation and distribution of the methylated DNA bases O6-methylguanine (O6-meGua) and 7-methylguanine (7-MeGua) were studied in respiratory tissues, oesophagus, liver, kidneys, pancreas, small intestine, colon and prostate of rat, mouse and hamster 6 h after treatment with a single dose of 30 mg NNK/kg. The tissue- and cell-specific distribution of O6-meGua- and 7-meGua-specific nuclear staining showed the same patterns and were remarkably similar in rat, mouse and hamster in spite of the diverging spectra of NNK-induced tumours in these species.

Quantification of patient to patient variation of skin erythema developing as a response to radiotherapy.

A method is described to determine accurately skin redness during a course of radiotherapy using reflectance spectroscopy utilizing information from across the visible spectrum according to the L*a*b* color coordinate system. The method was used to quantify the development of skin erythema during and after electron beam irradiation of the chest wall following mastectomy. A number of factors were identified which could influence the wide variation in response seen between patients.

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours.

Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.

The epithelial sialomucin, episialin, is sialylated during recycling.

Episialin, the sialomucin encoded by the MUC1 gene is abundantly present at the surface of various epithelial cells. It is a transmembrane molecule that matures through several intermediate forms generated by proteolysis and sequential addition and processing of numerous O-linked glycans. Here we demonstrate that one of the biosynthetic intermediates, the premature form, which is incompletely glycosylated appears at the cell surface.

Photodynamic therapy as an alternative treatment for surgery in a patient with lung cancer undergoing bone marrow transplantation.

We describe a patient who suffered from a bacterial pneumonia and had a left-sided infiltrate on his chest radiograph. He was found to be cytopenic and acute myeloid leukemia was diagnosed. A complete remission was achieved after chemotherapy, and the patient was scheduled to have autologous bone marrow transplantation.

Potentiation of DNA-adduct formation and cytotoxicity of platinum-containing drugs by low pH.

The low interstitial pH of tumor tissue is an important modulator of various anti-tumor modalities. In order to explore the optimal conditions for the potentiating action of low pH on the cytotoxic activities of cis- and carboplatin, we have investigated the temporal aspects of drug activity and pH modulation in L1210 murine leukemia cells in comparison with various other drugs. Extra- and intra-cellular pH of L1210 cells was modulated before, during and after drug exposure and survival of L1210 cells was determined.

Temperature dependence of glucocorticoid binding in sensitive and refractory murine leukaemia cells.

The validity of in vitro assays in predicting the susceptibility of leukaemic cells to glucocorticoid-mediated lysis was evaluated in a panel of six murine leukaemia cell lines. In this panel susceptibility to glucocorticoids ranged from highly sensitive to fully resistant. The panel was screened for specific 3H-dexamethasone binding in whole cells and for activation of cytosolic receptors in cell lysates.

The onset of puberty and the availability of sex steroids in female gymnasts.

Plasma levels of gonadotropins, (sex) steroids, SHBG bound fractions of 17β-estradiol (E2) and testosterone (T), and sex-hormone-binding globulin (SHBG) were compared at the onset of puberty in female gymnasts (n = 7) and two groups of schoolgirls with similar anthropometric characteristics. Ten schoolgirls were matched to the gymnasts on the basis of a sum of skinfolds and the waist/hip ratio, while 12 other girls were selected on the basis of the stature and bicristal breadth of the female gymnasts. All girls were in the second stage of breast development (M2) and were classified as being in the first stage (M1) 6 months earlier.

High dose rate brachytherapy improves resectability in squamous cell lung cancer.

A 44-year old man with squamous cell carcinoma of the left lower lobe extending to the mucosa of the main carina, was treated with high dose rate brachytherapy prior to surgery. A significant reduction of tumor infiltration was achieved allowing a radical pneumonectomy instead of a sleeve pneumonectomy with resection of the main carina. He remains disease-free after a follow-up period of 43 months.

Suppression of cellular aggregation by high levels of episialin.

Episialin is a mucin-like molecule located at the apical surface of most glandular epithelial cells. It is present at increased levels in carcinomas, where the molecule is often distributed over the entire cell surface. We have simulated this overproduction of episialin by transfecting a normal mammary epithelial cell line and a melanoma cell line with full-length complementary DNA encoding episialin.

Cell-associated episialin is a complex containing two proteins derived from a common precursor.

cDNA for the epithelial sialomucin episialin encodes a transmembrane molecule with a large extracellular domain, which mainly consists of repeats of 20 amino acids. Here we confirm the existence of a previously proposed proteolytic cleavage of episialin that occurs in the endoplasmic reticulum (Hilkens, J., and Buijs, F.

Breast cancer: a study into the value of a historical group as comparative material for new methods of treatment.

A large group of consecutive patients were studied who had been treated for a primary breast carcinoma by a radical mastectomy at the Netherlands Cancer Institute, during the period of 1960-1974. One of the objectives of that retrospective study was to record the results of treatment of a historical group of patients in such a way that they could presumably serve as a reference for new methods of treatment of breast cancer. To verify the validity of this presumption, the present study compares the treatment results of patients from the EORTC trial 10801, which addresses the value of breast conserving procedures, with that of matched controls from the historical group mentioned above.

DNA-flow cytometry of head and neck carcinoma: the importance of uniform tissue sampling and tumor sites.

Flow cytometric DNA ploidy measurements using deparaffinized tumor specimens were performed on 46 squamous cell carcinomas of the head and neck, including 22 carcinomas of the oropharynx, 18 carcinomas of the larynx and six carcinomas of the oral cavity. Aneuploidy was found in 14 of these tumors with carcinomas of the larynx and oral cavity showing almost equal percentages of DNA aneuploidy (10/18 and 3/6, respectively). In contrast, only 1 of the oropharyngeal carcinomas was aneuploid.

A single nucleotide polymorphism in an exon dictates allele dependent differential splicing of episialin mRNA.

The episialin gene (MUC1) encodes an epithelial mucin containing a variable number of repeats with a length of twenty amino acids, resulting in many different alleles that can be subdivided into two size classes. The episialin pre-mRNA uses either one of two neighbouring splice acceptor sites for exon 2, which mainly encodes the repeats. Using the genetic polymorphism of the episialin gene to identify different alleles, we show here that the splice site recognition is allele dependent and is based on a single A/G nucleotide difference in exon 2 eight nucleotides downstream of the second splice acceptor site.

Intravenous contrast in spinal computed tomography to identify epidural metastases.

In 16 patients with spinal epidural metastases from various neoplasms the usefulness of intravenous (IV) contrast injection in spinal computed tomography (CT) scanning was analyzed for determining the presence and extent of the epidural lesion. In all cases enhancement of the epidural tumor mass occurred, which effectively showed the outline of the lesion. The extent of the epidural metastases in the spinal canal was equally well visualized as by myelography.

Re-irradiation of mouse kidneys: a comparison of re-treatment tolerance after single and fractionated partial tolerance doses.

Mouse kidneys were bilaterally irradiated with fractionated doses of 15 X 1.2 Gy, 15 X 1.6 Gy or 15 X 2.

Diagnosis and treatment of malignant pheochromocytoma with 131I-meta-iodobenzylguanidine: a case report.

The case of a 67-year-old male patient with metastatic malignant pheochromocytoma is described to illustrate the significant improvement of the diagnosis and treatment of pheochromocytoma since the recent introduction of 131I-meta-iodobenzylguanidine (131I-MIBG). Because of the generally observed tumor heterogeneity as to 131I-MIBG uptake and radiosensitivity in advanced disease, treatment results may be improved further, if 131I-MIBG therapy is initiated when tumor load is still small.

Prostate-specific antigen (PSA). A tissue-specific and sensitive tumor marker.

Noninvasive methods for the diagnosis of prostatic cancer, its staging and evaluation of response to therapy are often not sufficiently sensitive or specific. Prostate-specific antigen (PSA) was identified in 1979 and has been evaluated since then as a marker, both at the serum and the tissue level. A review is presented in this article.