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At least 19 recordsLinked to original sources
PubMed1985

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour.

The specific and natural killer (NK)-restricted nature of auto-tumour cytotoxicity of tumour-associated lymphocytes was studied in cancer patients with malignant pleural effusions. Large granular lymphocytes (LGL) and small T lymphocytes were isolated from carcinomatous pleural effusions by centrifugation on discontinuous Percoll gradients. Tumour cells freshly isolated from pleural effusions were classified according to their susceptibility to lysis by Percoll-purified LGL from the blood of normal donors in a 4-h 51Cr release assay. Of 12 NK-sensitive tumour samples, 11 were killed by autologous fresh effusion LGL, whereas only 2 were lysed by autologous T cells. Neither LGL nor T cells were cytotoxic to NK-resistant autologous tumour cells. T cells and LGL were each cultured in vitro with autologous tumour cells for 6 days. Effusion LGL maintained their auto-tumour killing activity in 10 of 12 autologous mixed lymphocyte-tumour cultures (MLTC) with NK-sensitive tumour, while LGL lost the activity when cultured alone. Removal of high-affinity sheep erythrocyte-rosetting cells from Percoll-purified LGL enriched effector cells. Autologous MLTC-derived LGL could also kill NK-sensitive allogeneic effusion tumour cells and K562 cells, as did fresh LGL. In autologous MLTC LGL failed to acquire lytic function to NK-resistant autologous tumour cells. In contrast, in vitro activation of effusion T cells with autologous tumour cells induced auto-tumour killer cells in 9 of 12 NK-sensitive tumour samples and 3 of 6 NK-resistant tumour cases. However, cultured T cells were incapable of killing allogeneic tumour cells and K562 cells. In the autologous MLTC effusion T cells proliferated vigorously in response to autologous tumour cells, whereas LGL showed no proliferation. The enrichment of blasts from cultured T cells on discontinuous Percoll gradients resulted in an enhancement of auto-tumour cytotoxicity, with no reactions recorded in blast-depleted, small, resting T cells. These results indicate that two distinct types of auto-tumour-recognising lymphocytes, LGL and T cells, are present in carcinomatous pleural effusions of cancer patients and that each effector type recognises different membrane moieties of autologous effusion tumour cells.

Adenocarcinoma↗
PubMed1988

Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen consumption and cell survival time under hypoxic stress.

Animals↗
PubMed1976

[Studies on biological characterization of mammary tumours of the sprague-dawley-rat in the syngeneic tumour-host system. I. Spontaneous primary mammary tumours and tumours induced by oral and intravenous application of DMBA (author's transl)].

Spontaneous and DMBA-induced mammary tumours of a Sprague-Dawley inbred line reared in Berlin-Buch are described. The incidence of spontaneous tumours was 14.3%, of chemically induced tumours 43.6% of all the animals tested. 5 different schedules of application proved superior to the oral route with regard to dose, mortality and tumour incidence. 87.2% of the carcinomas and 12.8% of benign tumours following DMBA treatment developed in the region of the mammary glands.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Cell types expressing the Wilms' tumour gene (WT1) in Wilms' tumours: implications for tumour histogenesis.

Wilms' tumour (nephroblastoma), a childhood embryonal kidney tumour, is believed to arise from malignant transformation of abnormally persistent metanephric blastemal cells. At a histological level, tumours show a remarkable mimicry of the normal nephrogenic pathway. There is histological and epidemiological evidence for at least two pathogenetic groupings within Wilms' tumour which may reflect different timings of the tumorigenic insult in this pathway and/or involvement of different genes. Tumorigenesis is thought to result from loss of function of a so-called tumour-suppressor gene which has an essential role in control of normal genitourinary development. Such a candidate, Wilms' tumour gene (WT1) mapping to chromosome 11p13, has been isolated and is known to be mutated in some tumours. We have examined the cell types expressing this gene in 32 Wilms' tumours and in nephroblastomatosis by in situ mRNA hybridization. Our results show that WT1 is expressed only in neoplastic structures whose normal counterparts also express the gene and that abnormally persistent high levels of expression are common in both these lesions. Thus, WT1 expression is a good marker for tumour differentiation and reveals how the normal pattern of differentiation is disrupted in Wilms' tumours. We postulate that mutation of the WT1 gene at the 11p13 locus results in Wilms' tumours associated with intralobar nephrogenic rests, which frequently show stromal-predominant histology. We have used our results and ideas to reinterpret current theories on tumour histogenesis and propose a model which explains how patterns of epithelial differentiation are disrupted in Wilms' tumour and how malignant stroma can result from mutation in WT1.

Antibodies, Monoclonal↗
PubMed1977

Human tumour--lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour-infiltrating, blood and lymph-node lymphocytes with autologous tumour cells.

Lymphocytes prepared from the blood, tumour-draining lymph node and tumour were tested for immune reactivity with freshly isolated autologous tumour cells from biopsies. Reactivity was assessed by the autologous tumour stimulation assay and by lymphocytotoxicity. Activity was found in 6/11 blood preparations, 7/10 lymph nodes and 1/7 tumour-infiltrating lymphocytes in tumour stimulation assays and in 6/19 blood, 8/18 lymph-node and 5/20 tumour-infiltrating lymphocytes in cytotoxicity assays. Tests with material from patients with nasopharyngeal carcinoma showed a higher frequency of cytotoxicity in the tumour-infiltrating lymphocytes than in other solid tumours. There was a correlation between results of the two assays when performed on the same preparations and between the levels of reactivity in lymph node and blood from the same patient. Cytotoxicity in the lymph nodes showed specificity in that cells from a long-term culture (K562) known to be sensitive to natural killer activity and from allogeneic tumour biopsies were only rarely damaged. Cytotoxicity against K562 was more frequently determined in blood lymphocytes. Tumour-infiltrating lymphocytes were non-reactive in patients when the blood and lymph-node lymphocytes were active.

Cytotoxicity, Immunologic↗
PubMed1972

Morphology of tumours induced in hamsters by CELO virus, tumour tissue, and tumour cells grown in culture.

Tumours in hamsters, induced by the chicken-embryo-lethal-orphan (CELO) virus, by tumour tissue transplants, or by tumour cells grown in culture, were well circumscribed solid tumours and covered by a thin capsule-like structure. All were fibrosarcomata. However, tumours produced by the 3 inocula exhibited the following histological differences. Neoplasms induced by CELO virus were generally less differentiated and were composed of cells with polygonal or oval nuclei and indistinct cytoplasmic boundaries. Numerous multinucleated bizarre giant cells were found. Those produced by tumour tissue transplants were more differentiated and were composed of spindle shaped cells with abundant collagen fibre formation. Neoplasms induced by tumour cells grown in culture were generally undifferentiated with many mitotic figures and contained numerous giant cells.Cells from tumours induced by CELO virus or tumour transplants produced similar morphologies when cultured in vitro. The cell cultures consisted of large cells with oval or rounded large nuclei and prominent nucleoli. Multinucleated giant cells, cells in mitosis, and a disorganized growth pattern were also characteristic of the cell cultures. However, mitosis and a piling-up of cells occurred more frequently with cell cultures derived from the CELO virus-induced tumour.

Adenoviridae Infections↗
PubMed1987

Analysis of tumour cell composition in tumours composed of paired mixtures of mammary tumour cell lines.

In order to quantitate the effects of tumour subpopulation interactions, we have devised a method to determine the subpopulation composition of tumours by using paired tumour cell lines able to grow in different selective media. Line 4T07 forms colonies in thioguanine but not in HAT and line 168 forms colonies in HAT but not in thioguanine. An independent technique of determining tumour cell content was used to validate this method: line 168 and 4T07 cells are distinguishable by flow cytometry after staining with propidium iodide for DNA content. Mixtures of cell suspensions prepared from each unmixed tumour, as well as from tumours arising from mixtures of these lines, were analysed by both the colony formation assay and by the DNA content assay. The colony formation assay yielded values in good agreement with the DNA content assay, but was considerably more sensitive in that it was able to quantitate minority subpopulations that constituted less than 10% of the tumour. Both methods revealed that in tumours arising from mixtures, the tumour cells were almost entirely line 4T07, even when the inoculum had contained a high proportion of 168 cells. Since line 168 cells are very tumorigenic per se, these results suggest that line 4T07 cells are capable of interfering with 168 proliferation in mixed tumours, either directly or through a host-mediated mechanism.

Aminopterin↗
PubMed1992

Glutathione S-transferase activity and isoenzyme composition in benign ovarian tumours, untreated malignant ovarian tumours, and malignant ovarian tumours after platinum/cyclophosphamide chemotherapy.

Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4-dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy.

Adenocarcinoma↗
PubMed1990

Testicular tumours in infancy and childhood--a review of 10 germ cell tumours and 10 non germ cell tumours.

Between 1961 and 1989 twenty testicular tumours were treated at the Basel University Children's Hospital. Ten were non germ cell tumours (50%) and a further 10 (50%) were germ cell tumours. Of the germ cell tumours six were benign teratomas, two yolk sac tumours and a further two were teratocarcinomas. In the non germ cell group eight tumours originated from paratesticular structures, one of which was a malignant rhabdomyosarcoma. The remaining two neoplasms originated from the supporting testicular tissues. The clinical presentation, the protocol of treatment and the long-term outcome are discussed. We advocate local tumour excision in benign cases (proven by instant frozen section) if normal testicular tissue can be preserved. In malignant germ cell tumours primary orchiectomy and high spermatic cord ligation is the treatment of choice. Secondary chemotherapy and/or retroperitoneal lymph node dissection is only added if the tumour markers alpha-fetoprotein and beta-human chorionic gonadotropin remain present in high serum levels postoperatively. Rhabdomyosarcomas are treated by surgical excision, primary chemotherapy and radiotherapy. All of the five patients (25%) suffering from malignant testicular tumours survived. A long-term follow-up (mean 12 years) did not show any evidence of recurrent local or metastatic disease.

Adolescent↗
PubMed1989

H-2 antigens and tumour-associated transplantation antigens in clones derived from a methylcholanthrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response.

The methylcholanthrene GR9 tumour is a fibrosarcoma, originated in a BALB/c (H-2d) mouse, composed of different clones (A7, G2, D8, D6, B11, B3, B7, C11, B10, B9) with different class I (Kd Dd Ld) expression. We present data indicating that MHC class I differences observed between the different clones correlated with RNA levels and can be modified with recombinant interferon-gamma. We also studied the presence of tumour-associated antigens in GR9 and their different clones using the monoclonal antibody (MoAb) technology. We produced two syngeneic MoAbs, A7.2 and A7.6, which reacted to GR9 clones. These MoAbs precipitated a 70-kilodalton molecule and did not react with cells positive for the classical Gp70 antigen such as YC-8, LSTRA (H-2d) and RBL-5 (H-2b) lymphomas. A7.2 and A7.6 MoAbs were also negative with normal cells. In this well-characterized tumour model, we analysed the influence of the expression of class I molecules and tumour-associated antigens upon the generation, in vitro and in vivo, of the specific anti-tumour immune response. We produced syngeneic anti-GR9 A7 cytotoxic T lymphocytes (CTLs) which showed significant cytotoxicity against most of the GR9 clones including clones with low or no H-2 class I expression. These CTLs showed no cytotoxic activity against other tumour cells and concanavalin A blasts, neither could the CTL-specific response be inhibited with A7.2 and A7.6 syngeneic MoAbs nor with a panel of anti-class I MoAbs. In vivo experiments have shown that pre-immunization with the immunogenic clone GR9 A7 protects against a challenge of the different GR9 clones, independently of their class I expression and their in vitro susceptibility to lysis by anti-GR9 A7 CTLs. These results demonstrate the existence of cross-reactive tumor-associated transplantation antigens between different clones of the same tumour and the absence of correlation between in vitro susceptibility to lysis and in vivo tumour rejection. Finally, we discuss these results in the context of anti-tumour effector mechanisms generated in chemically induced tumours.

Animals↗
PubMed1990

Proposal for a new carcinoid tumour staging system based on tumour tissue infiltration and primary metastasis; a prospective multicentre carcinoid tumour evaluation study. West German Surgical Oncologists' Group.

In order to evaluate the significance of different prognostic factors, a multicentre prospective carcinoid tumour study was launched in early 1987, under the auspices of CAO (Chirurgische Arbeitsgemeinschaft Onkologie, a West German surgical oncologists' collaboration group) and UICC (Union Internationale Contre le Cancer). Up to March 1990 we received and evaluated clinical data from 94 patients from 16 hospitals. Carcinoid localization was distributed as follows: stomach 4, duodenum 7, pancreas 3, jejunum 5, ileum 21, Meckel's diverticulum 1, appendix 29, colon 5, rectum 14, and 5 cases of tumour metastases of unknown origin. The mean age was 54.7 years, overall sex ratio (m/w) was 1:1.09. Thirty-one patients presented with simultaneous lymph-node metastases and 27 with distant metastases. Based on these data, a metastases staging system (four stages) has been defined for study stratification. This work also aims at evaluating the correlation of tumour diameter and tumour tissue invasion with primary metastases occurrence; primary tumour diameter remains the most important prognosis-related factor for appendiceal location. For other locations, tumour tissue invasion can be markedly better correlated with regional lymphatic and distant spread than is the case with tumour diameter. Tumour tissue invasion has, therefore, been selected to define a local staging (four stages) for further study stratification. Tumour location, metastases stage and local stage combined, best describe the current state of the disease and will serve to evaluate further pathological stratification and to correlate survival data.

Adult↗
PubMed1977

Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ-cell neoplasms: value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour).

Serum alphafoetoprotein (AFP) and serum alpha-1 antitrypsin (AAT) were determined in 24 patients with germ-cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ-cell neoplasms had tumours containing endodermal sinus tumour (yolk-sac tumour) elemetns. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ-cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.

Adolescent↗
PubMed1990

Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction.

The expression of transferrin receptor (Tr) was investigated by means of immunohistochemistry in 101 tumours of the human central and peripheral nervous system. The results were compared with the proliferative activity of the tumours, determined by immunostaining for the proliferation-associated antigen Ki-67. In addition to immunostaining of normal and proliferated blood vessel endothelium and of a fraction of tumour infiltrating lymphocytes, we observed staining for Tr in a variable fraction of neoplastic cells of all histological tumour types. Immunoreactivity in the majority of tumour cells was found only in anaplastic tumours such as glioblastomas. Furthermore, a positive correlation between Tr expression and the Ki-67 growth fraction was established for gliomas. Non-glial tumours strongly expressing Tr included one metastatic rhabdomyosarcoma, one intracerebral malignant lymphoma, two of four plasmocytomas and seven of nine metastatic carcinomas. Our results indicate that immunohistochemistry for Tr and Ki-67 can provide additional information about the biological behaviour of nervous system tumours, thus complementing conventional histopathological criteria for anaplasia.

Antigens, Surface↗
PubMed1991

BW12C: effects on tumour hypoxia, tumour thermosensitivity and relative tumour and normal tissue perfusion in C3H mice.

BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) is an agent which stabilises oxyhaemoglobin and thus reduces oxygen delivery to tissues. It is of interest as a possible potentiator of bioreductive agents and/or hyperthermia. The increases in radiobiological hypoxic fraction of RIF-1 and KHT tumours 30 min after 70 mg kg-1 BW12C i.v. were measured and shown to be similar; factors (+/- 2 s.e.) ranged from 3.87 (2.84-5.29) to 5.92 (1.92-18.2) despite the large variation in initial hypoxic fraction, from 0.30 (0.18-0.50) % for RIF-1 intramuscularly in the leg to 16.3 (14.7-18.1) % for subcutaneous KHT flank tumours. Thermosensitivity of intramuscular KHT leg tumours was not enhanced by 70 mg kg-1 BW12C 30 min before heating at 43 degrees C, 43.5 degrees C or 44 degrees C, assayed by regrowth delay. The effect of 70 mg kg-1 BW12C on relative tissue perfusion (RTP), assayed by 86Rb extraction, was measured from 0.5 h to 6 h after treatment. After 1 h RTP (+/- 2 s.e.) in RIF-1 tumours was reduced to 84 +/- 5.7% and 68 +/- 9.6% of control in leg and flank tumours respectively, and to 86 +/- 6.4% in leg muscle while flank skin RTP was unaltered at 109 +/- 8.6%. There were substantial increases in kidney (149 +/- 10.7%) spleen (173 +/- 22.1%) and lung (128 +/- 10.4%) at 1 h but in liver there was a decrease at 2 h to 85 +/- 8.4%. Dose response studies showed that the threshold dose for reduction of tumour RTP is between 55 and 70 mg kg-1, but perturbations in normal tissue RTP occur at lower doses, e.g. 40 mg kg-1 for spleen. BW12C had minimal effects on renal function measured by 51CrEDTA clearance. The data as a whole indicate that reduction in tumour perfusion is likely to be an important determinant in the increase in tumour hypoxia induced by BW12C.

Animals↗
PubMed1978

Surface membrane changes of T cells induced by syngeneic tumour cells. II. T-cell defects induced by small tumour cell inocula or tumour cell antigens.

Injection of a large number of tumour cells, like other strong immunogenic challenges, is followed within 6 h by the uptake of cytophilic Ig (probably complexes) by a subpopulation of T cells. This phenomenon, known as the "6-hour T-cell response" is abrogated when small tumour cell inocula (10(2)), or small amounts of a preparation from tumour cells, which contains tumour antigens, are injected prior to the immunogenic challenge Abrogation of the "6-hour T-cell response" resulted in a decrease in specific anti-tumour cell immunity as tested in vitro by measuring growth inhibition (cytostasis). It has also resulted in loss of the amplifying function on antibody formation against sheep erythrocytes, normally detected in a T-B cell co-operative system when T cells are used 6 h after priming with sheep erythrocytes. It is postulated that this T-cell defect may represent a mechanism by which tumour cells, in the early stages of their growth, interfere with inductive stages of the immune response for a sufficient period of time to allow the tumour to grow beyond immune control.

Animals↗
PubMed1987

Somatomedins in tumour cyst fluid, cerebrospinal fluid, and tumour cytosol in patients with glial tumours.

In the present study, the levels of the growth-promoting hormones, somatomedins, were analysed in tumour cyst fluid, CSF, and tumour cytosol, collected from 22 unselected patients with intracranial tumours. All samples contained somatomedin activity. 5/7 CSF samples, taken from patients with tumour mass visible on CT, showed elevated concentrations. 6/9 cyst fluid samples, taken from patients with glioma were elevated compared with normal serum somatomedin levels. Tumour cytosol, taken from 7 patients with malignant glioma contained somatomedins in an elevated level compared with values previously analysed from normal adult brains. These preliminary findings demonstrate for the first time the presence of somatomedins in brain tumours and suggest the use of somatomedins as a possible brain tumour marker.

Adult↗
PubMed1991

Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: a new approach to study tumour immunology in vitro.

This paper reports the first example of tumour infiltrating lymphocytes (TILs) and a tumour cell line from the same individual and analyses their characteristics. The tumour cell line (CAT), derived from a patient with well-differentiated (G3pTa) TCC, has been in culture for 24 months and subcultured more than 100 times. Epithelial origin was established by electronmicroscopy and use of a range of monoclonal antibodies (Mabs) against cytokeratins. The TILs isolated from the same tumour expressed all the phenotypic characteristics of normal activated T cells and demonstrated low levels of cytotoxicity against the autologous tumour line (CAT). Comparison of cell surface molecules of these cells revealed the loss of HLA-B7, B44 and Bw6 from the CAT cells whilst maintaining HLA-A2, A3 and Bw4. Karyotypic analysis demonstrated three rearranged chromosomes (between chromosomes 4 and 11, 10 and 13, 11 and 17) on CAT cells. The potential that study of paired autologous tumour cells and TILs in culture offers for studying the role of MHC antigens in tumour rejection and the impact of different approaches to correcting the defect are reviewed.

Antibodies, Monoclonal↗