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Biomedical subjects

G Morstyn

Publications and source records attributed to G Morstyn.

At least 73 records · Page 4Linked to original sources
PubMed1988

Therapy of primary diffuse large cell lymphoma of the penis with preservation of function.

Only 7 cases of primary lymphoma of the penis have been described previously. We report a case of diffuse large cell lymphoma of the glans penis. The clinical features, histology and management of these cases are reviewed. The previously reported cases were treated with surgical resection or radiotherapy resulting in some degree of local morbidity. Our patient achieved complete remission after only 1 cycle of chemotherapy. The benefits of chemotherapy over surgery or radiotherapy for primary lymphoma of the penis are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Flare responses in small cell carcinoma of the lung.

Two cases of small cell carcinoma of the lung in which flare responses were demonstrated are discussed. Although the primary tumor and extraskeletal metastases responded to first-line chemotherapy, bone scintigraphs performed 3 months after the start of treatment suggested tumor progression. However, following repeat bone imaging and subsequent clinical evaluation, the interim scintigraphs appeared to represent an unusual flare response, in which the activity of pre-existing hot spots increased and new lesions developed.

Aged↗
PubMed1988

Photoradiation therapy and its potential in the management of neurological tumors.

Photoradiation therapy is a form of local treatment that depends on the selective retention of a photosensitizer, such as hematoporphyrin derivative (HpD), by the tumor followed by treatment with light of an appropriate wavelength to activate the sensitizer in the tumor. The selective uptake of HpD by cerebral tumors has been demonstrated both in laboratory animal model studies and in clinical studies, and selective destruction of intracerebral tumors has been demonstrated in animal glioma models. The biological basis for photoradiation therapy and, in particular, the mechanisms for the selective uptake of the sensitizer into the tumor and the destruction of tumor with photoradiation therapy are discussed. Current evidence suggests that singlet oxygen is the major intermediary leading to cell damage, although other radicals such as hydrogen peroxide and hydroxyl radicals may be involved. Other studies suggest that the initial damage is to the blood vessels, and the tumor subsequently undergoes ischemic changes. Sixty-four patients treated with photoradiation therapy have been reported in the literature. The initial clinical studies were disappointing in their therapeutic effect but these studies often included treatment of recurrent gliomas and low doses of light were used. Technical advances, particularly in laser technology, have enabled more effective photoradiation therapy and the clinical trials are reviewed.

Adolescent↗
PubMed1988

Clinical studies with granulocyte colony stimulating factor (G-CSF) in patients receiving cytotoxic chemotherapy.

Bacterially synthesised human granulocyte colony-stimulating factor (G-CSF) was administered to patients with advanced cancer. The immediate effect of G-CSF was a fall in the level of circulating neutrophils followed by a rise after 4 hours that was sustained during G-CSF administration. The rise in neutrophil level was less in patients who had been treated previously with chemotherapy and/or radiotherapy. G-CSF was also administered to patients following melphalan and this resulted in a reduction in the duration of the neutropenia that invariably follows melphalan. G-CSF was well tolerated and did not have to be stopped in any patient.

Colony-Stimulating Factors↗
PubMed1988

Small cell lung cancer cell lines: pure and variant types can be distinguished by their extracellular matrix synthesis.

Variant subclasses of cell lines derived from small cell lung cancers have previously been characterized, having distinctive biochemical, morphological and growth properties compared to the classic lines. Both types of small cell lung cancer express features suggesting that they are derived from neuroectodermal cells. We compared the capacity of these two types of lung cancer cell lines to synthesize the extracellular matrix glycoproteins, fibronectin and laminin, and also analysed a few other non-small cell lung cancer lines, as controls. We found that the cell lines of the pure type did not produce laminin or fibronectin, whereas the cell lines of the variant type synthesized laminin, and the non-small cell lung cancer lines produced either laminin or fibronectin. These findings suggest that the variant form of small cell lung cancer may be derived from a primitive neuroectodermal cell, with both neural and epithelial features, whereas the classic type is derived from a more mature cell with predominantly neuronal features. The differences in extracellular matrix synthesis, and laminin in particular, may explain some of the in vitro and in vivo characteristics of the tumour.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Pharmacokinetics of human granulocyte-macrophage colony-stimulating factor using a sensitive immunoassay.

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.

Adult↗
PubMed1988

Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients.

Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte-macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.

Bone Marrow↗
PubMed1987

Nature of the tumor-localizing components of hematoporphyrin derivative.

Hematoporphyrin derivative linked by ether bonds (HE) was synthesized by unambiguous procedures in order to compare its properties to hematoporphyrin derivative (HpD). Reverse phase high performance liquid and gel filtration chromatography were used to compare the HE derivatives to HpD. The cellular uptake of HE derivatives was compared to HpD using the WEHI 3B (D+) cell line and was shown to be taken up to a degree and in a manner similar to HpD. The efficiency of HE porphyrins as photosensitizers was compared to HpD using the V79 cell line. HE porphyrins were more efficient in sensitizing the V79 cells than was HpD. The in vivo tumor localizing properties of HE porphyrins were compared to HpD in CBA mice bearing the C6 cerebral glioma, and BALB/c mice bearing the EMT6 mammary tumor. HE derivatives localized in both tumor models as effectively as HpD. We conclude that the properties of ether linked hematoporphyrin derivatives are very similar to properties of HpD.

Animals↗
PubMed1987

Heterogeneous cytogenetic abnormalities in small cell lung cancer cell lines.

Ten cell lines were established from different biopsies from nine patients with small cell lung cancer (SCLC). These were established from metastases in the marrow (7), breast (1), pleural fluid (1), and spinal cord (1) and had been in culture for periods varying from 1 to 11 months. All cell lines exhibited typical cytological features of SCLC, and produced neuron specific enolase. All lines examined (5) contained dense core granules and were tumorigenic when injected intracranially into nude mice. None of the six cell lines tested had an amplified oncogene (c-myc or n-myc) previously reported to be amplified in SCLC. Detailed chromosome analyses were undertaken and showed that a structural abnormality of chromosome 3(p11p23) was a frequent (6 of 10) but not invariable finding. Our study and one other indicate that there is not a unique chromosome abnormality present in all cases of SCLC, although loss of chromosome 13 and structural abnormalities of chromosome 3 were frequently found. A feature of these SCLC cell lines established from metastatic deposits was the complexity of the karyotypes due to numerical and structural chromosomal abnormalities.

Biopsy↗
PubMed1987

Fluctuations in the expression of a glycolipid antigen associated with differentiation of melanoma cells monitored by a monoclonal antibody, Leo Mel 3.

A monoclonal antibody, Leo Mel 3, raised against a melanoma cell line (LiBr), binds to a carbohydrate determinant of cell surface gangliosides, the simplest of which is GD3. This monoclonal antibody was screened for by its capacity to block the recognition and lysis of the melanoma cells by cytotoxic T-lymphocytes with anomalous killer cell function, illustrating a novel approach for identifying monoclonal antibody to biologically relevant tumor-associated antigens. Leo Mel 3 reacted selectively with melanoma cells by indirect immunofluorescent and immunoperoxidase staining; it reacted with tissue from all primary and metastatic melanoma tested, and it bound to cells from all but one of six cultured melanoma cell lines. Leo Mel 3 did not react with a variety of carcinomas, lymphomas, leukemias, and other neuroectodermal tumors, nor with adult or fetal tissues, except fetal liver. Very weak staining of cutaneous basal melanocytes was noted in a minority of skin sections, and 50 to 80% of melanocytes in four of seven benign nevi showed weak to moderate reactivity. The antibody was relatively specific for human adherent melanoma cells, since it did not bind to the adherent murine B16 melanoma line nor to a nonadherent human melanoma cell line (PMC-22). Expression of the Leo Mel 3-defined antigen was unrelated to changes in cell cycle. When cells from an adherent melanoma cell line were detached and maintained briefly in suspension culture, the cells became markedly less reactive with Leo Mel 3 and, after readherence to plastic, they rapidly reexpressed higher levels of the ganglioside antigen; since Leo Mel 3 prevented attachment and growth of melanoma cells in vitro, a functional role for the ganglioside is suggested in cell adhesion and metastasis. Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells.

Antibodies, Monoclonal↗
PubMed1987

Hematoporphyrin derivative and anthracyclines mutually inhibit cellular uptake and toxicity.

Hematoporphyrin derivative (HpD) is a fluorescent photosensitizer which localizes selectively in tumors and is used in photoirradiation therapy of various types of cancer. Photoirradiation is a local form of treatment. There may be advantages in combining it with systemic chemotherapy, and we therefore studied the interaction of HpD and various cytotoxic drugs [daunorubicin (DR), adriamycin (AD), mitozantrone (MI), cis-platinum (CP) and 5-fluorouracil (FU)] with respect to cellular uptake and toxicity. Cultured cells were incubated with HpD and the cytotoxic drugs, either simultaneously or sequentially. The amount of DR, AD and HpD taken up by cells was quantitated by measuring cellular fluorescence and by determining the specific cytotoxic action of the drugs (light-induced cell kill for HpD and loss of proliferative potential for the cytotoxic drugs). The presence of 100 mg/l HpD during drug incubation caused 30-, 12- and 6-fold reductions in the cytotoxicity of DR, AD and MI respectively. HpD-associated fluorescence and photosensitization were reduced upon co-incubation of cells with HpD and AD. When cells were incubated with HpD and AD sequentially, fluorescence was equal to the sum of fluorescence values achieved by treatment with HpD and AD alone, and the cytotoxicity was not reduced. This suggests that the effects were due to an interaction of HpD with the drugs outside the cells, resulting in a reduction of free drug available for cellular uptake. CP and FU did not interact with HpD. The results suggest that protocols which combine photoirradiation therapy and chemotherapy with anthracyclines or similar compounds need to take this interaction into account.

Animals↗
PubMed1987

Pharmacokinetics of unchanged carboplatin (CBDCA) in patients with small cell lung carcinoma.

The disposition of the cisplatin analogue carboplatin was studied in seven patients with small cell lung cancer. Carboplatin 100 mg/m2 was administered without hydration by a 1-h infusion with VP16-213 120 mg/m2 on days 1, 2 and 3 of each course. Plasma and urine collections were made on days 1 and 3 of the first course of treatment. Carboplatin levels in plasma ultrafiltrate and urine were quantitated using a specific and sensitive, high-performance liquid chromatographic assay which involved sample clean-up on a Dowex-2 column prior to injection. Estimates of pharmacokinetic parameters determined using either compartmental or non-compartmental methods were comparable. There was no difference between carboplatin pharmacokinetic parameters determined on days 1 and 3 of treatment. The mean (+/- SD) carboplatin half-life determined from plasma data on day 1 was 105 +/- 30.4 min and was not significantly different from that determined using urinary excretion rate data (107 +/- 51.7 min). Urinary excretion rate plots showed that carboplatin elimination was mono-exponential for up to 14 h after infusion. Total-body clearance was 105 +/- 40.0 ml min-1 m-2, renal clearance 64.3 +/- 44.1 ml min-1 m-2, and volume of distribution 17.3 +/- 4.2 l/m2 on the 1st day of treatment. Of the administered dose, 58.4% +/- 21.2% was recovered in urine over a 24-h period after the start of the infusion. The mean renal clearance of carboplatin was comparable to creatinine clearance. Carboplatin disposition was clearly defined in the patients studied using analytical methodology specific for the unchanged drug.

Adult↗
PubMed1987

Natural killer (NK)-resistant human lung cancer cells are lysed by recombinant interleukin-2-activated NK cells.

Natural killer (NK) cells are active in host defence against tumors. In order to determine if NK cells have the capacity to lyse human lung cancer cells, we evaluated blood NK cell activity against human lung carcinoma lines representing each of the commonest histological types of lung cancer, NCI-H157 (large cell), LICM107 and NCI-H146 (small cell), NCI-H226 (squamous cell), and LICM26 (adeno), and compared the results to their activity against a standard NK-sensitive target, K562, using a 16-hr 51Cr-release assay. At effector to target (E:T) ratios up to 50:1, NK activity was very low against each of the lung cancer cell lines compared to the K562 cells (NCI-H157 10 +/- 2%, LICM107 12 +/- 2%, NCI-H146 14 +/- 5%, NCI-H226 8 +/- 5%, and LICM26 7 +/- 3%, compared to K562 60 +/- 3%, P less than 0.001, for each compared to K562 cells). Recombinant interleukin 2 (IL-2) produced a dose-dependent augmentation of NK activity against each of the lung cancer cell lines, with doses as low as 0.25 U/ml being effective. The highest level of boosting was seen against NCI-H157 cells where NK activity (E:T, 50:1, IL-2, 250 U/ml) increased from 9 +/- 2 to 56 +/- 7%, P less than 0.001). Only brief exposure to IL-2 was necessary for augmentation to occur, with as little as 5 min being required for activation, although increased exposure times produced increased levels of augmentation. NK cells appeared to be the IL-2-responsive lytic cell population in these experiments as Leu 11b-depleted lymphocytes expressed little IL-2-mediated augmentation of activity against these target cells, and most of this IL-2-mediated augmentation of activity was located in the large granular lymphocyte-enriched fraction of the lymphocyte population. We conclude that normal blood NK cell activity against human lung cancer cell lines is low but that this activity can be markedly augmented by brief exposure of NK cells to low doses of recombinant IL-2, suggesting a potential role for IL-2 in the immunotherapy of human lung cancer.

Antibodies, Monoclonal↗
PubMed1987

High-dose photoirradiation of esophageal cancer.

Fifteen patients with locally advanced esophageal cancer were treated with phototherapy. Each patient had dysphagia and weight loss before therapy and could not be operated on because of the extent of the tumor or poor performance status. Patients received a photosensitizer (hematoporphyrin derivative) 72 hours before phototherapy and were then treated by light delivered by an argon pumped dye laser or gold metal vapor laser at powers up to 2.2 W and doses of 337 J/cm2. Fourteen patients received 24 treatments. The results were all patients achieved a tumor response. The depth of response depended on the dose and dose rate of radiation. There were four of 24 local complications (mediastinitis 3, bronchoesophageal fistula 1). These occurred in patients treated with a power of greater than 1.5 W. There were two complete pathologic remissions in patients with locally advanced cancer. In conclusion, phototherapy is an effective alternative to other forms of palliation and potentially may be an alternative to surgery in selected cases of locally advanced esophageal cancer.

Adenocarcinoma↗