Showing papers in "British Journal of Cancer in 1981"

Histological Typing of tumours of the Central Nervous System

Abstract: Introduction Histological Classification of CNS Tumours Definitions and Explanatory Notes Tumours of Neuroepithelial Tissue Astrocytic Tumours Ependymal Tumours Mixed Gliomas Choroid Plexus Tumours Neuroepithelial Tumours of Uncertain Origin Neuronal and Mixed Neuronal-Glial Tumours Pineal Parenchymal Tumours Embryonal Tumours Tumours of Cranial and Spinal Nerves Schwannoma Neurofibroma Malignant Peripheral Nerve Sheath Tumor Tumours of the Meninges Tumours of Menigothelial Cells Mesenchymal, Non-menigothelial Tumours Primary Melanocytic Lesions Lymphomas and Haemopoietic Neoplasms Germ Cell Tumours Cysts and Tumour-like Lesions Tumours of the Sellar Region Local Extensions from Regional Tumours Metastatic Tumours Unclassified Tumours Illustrations Subject Index Metat Cy Tu

Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study.

Abstract: A number of men with malignant lymphoma of the histiocytic type and previous exposure to phenoxy acids or chlorophenols were observed and reported in 1979. A matched case-control study has therefore been performed with cases of malignant lymphoma (Hodgkin's disease and non-Hodgkin lymphoma). This study included 169 cases and 338 controls. The results indicate that exposure to phenoxy acids, chlorophenols, and organic solvents may be a causative factor in malignant lymphoma. Combined exposure of these chemicals seemed to increase the risk. Exposure to various other agents was not obviously different in cases and in controls.

Morphological evaluation of cell turnover in relation to the menstrual cycle in the "resting" human breast.

Abstract: This study examines cell turnover within the lobules of the "resting" human breast and correlates it to the stage of the menstrual cycle. The results are based on the morphological identification of both cell multiplication (mitosis) and cell deletion (apoptosis). It is found that these events undergo significant cyclical changes during the menstrual cycle, with raised levels towards the end of the cycle and during menses. However, in relation to a 28-day menstrual cycle, the position of the mitotic and apoptotic peaks, at Days 25 and 28 respectively, are significantly different. The high values are associated with an increase in the number of lobules showing a slight response rather than a large reaction within a few lobules. It appears that the "resting" breast tissue shows a general, rather than a focal reaction to a given hormonal environment. The possible role of oestrogen and progesterone as effectors of these changes is discussed. Our results show that the menstrual cycle influences cell turnover, though different factors may be affecting mitosis and apoptosis.

A marker for hypoxic cells in tumours with potential clinical applicability.

Abstract: ImagesFig. 1Fig. 2Fig. 3Fig. 4

Oral contraceptive use and early abortion as risk factors for breast cancer in young women

Abstract: A case-control study was conducted in Los Angeles County, California, of 163 very young breast-cancer cases (all aged 32 or less at diagnosis) to investigate the role, if any, of oral contraceptives (OC) in the development of the disease. OC use before first full-term pregnancy (FFTP) was associated with an elevated risk, which increased with duration of OC use (relative risk approximately 2.2 at 6 years of use, P < 0.01). This increased risk could not be explained by other risk factors. OC use after FFTP was not associated with any change in risk. A first-trimester abortion before FFTP, whether spontaneous or induced, was associated with a 2.4-fold increase in breast-cancer risk (P < 0.005).

Nutrient intakes in relation to cancer incidence in Hawaii.

Abstract: A representative sample of 4657 adults greater than or equal to 45 years of age from the 5 main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos and Hawaiians) were interviewed during 1977-1979 regarding their diets. Quantitative food-consumption histories were obtained, from which average daily intakes of fat (saturated, unsaturated, cholesterol, meat, dairy, fish, animal, vegetable and total), protein (animal, meat, fish, dairy and total), carbohydrate, and vitamins A and C (including supplements) were calculated using food-consumption data from standard sources. Multiple regression analysis, with sex as a controlled variable, was used to assess the statistical relationship between these ethnic-sex-specific intakes and corresponding population-based cancer incidence rates of 15 selected sites for which nutrient components are suspected to be either causal or protective. Based on pre-set criteria for establishing important relationships, significant positive associations were found for 6 of the cancer sites: breast cancer with fat (saturated, unsaturated, animal, total) and protein (animal), corpus-uteri cancer with the same components as breast cancer, prostate cancer with fat (saturated, animal) and protein (animal, total), stomach cancer with fat (fish only) and protein (fish only), lung cancer with cholesterol, and laryngeal cancer with cholesterol. Breast and corpus-uteri cancers also showed significant negative associations with carbohydrate intake. The implications of these findings for future research are discussed.

Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen

Abstract: We have developed a technique for the immunocytochemical staining of marrow smears using antiserum to epithelial membrane antigen (EMA). This membrane component is confined to, but widely distributed in, epithelial tissues and tumours derived from them, and is strongly expressed by infiltrating breast carcinoma cells. Marrow aspirates from patients with both early and metastatic breast cancer have been examined, and the results of immunocytochemical staining compared with conventional cytology and histology. Staining with antiserum to EMA enabled us to detect small numbers of carcinoma cells, and increased the yield of positive samples. Furthermore, using this technique, we found malignant cells in the marrow of patients with primary breast cancer with no other evidence of metastatic disease. Thus immunocytochemical staining for EMA may be of value in the detection of micrometastases in patients with primary breast carcinoma.

Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck.

Abstract: Ten cell lines of human squamous carcinomas of the tongue and larynx have been established from surgical specimens removed from 36 unselected patients, in order to provide systems for investigating the invasive and tissue-destructive capacity of squamous carcinomas of the head and neck. The morphology, ultrastructure and growth characteristics of the 10 lines are described. Detailed cytogenetic analysis of the first 4 lines indicates that each is karyotypically unique, with no evidence of cross-contamination. Nine of the 10 cell lines secrete immunoreactive beta human chorionic gonadotrophin (beta-hCG) in the culture medium. No correlation was demonstrated between the ability of the cell lines to secrete plasminogen activator and their capacity to grow in soft agar or as xenografts in immune-deficient mice.

Antitumour reactions of monoclonal antibody against a human osteogenic-sarcoma cell line.

Abstract: Monoclonal antibody against an osteogenic-sarcoma cell line (791T) was prepared by production and cloning of a somatic-cell hybrid between the mouse myeloma P3-NS1 and spleen cells from 791T-immunized mice. Three clones of hybridoma producing antibody against 791T, as detected by 125I-labelled Protein A binding, were tested against a range of normal and tumour cell targets to determine the pattern of expression of the antigen detected. The 3 clones had identical activity. They reacted strongly against 791T cells and another osteogenic sarcoma, 788T, and more weakly against a further 2 from a total panel of 10 osteogenic-sarcoma lines. The antibody was negative for fibroblasts from the donor of 791T, and for other fibroblasts, human red blood cells, human peripheral mononuclear cells and sheep red blood cells. When tested against a panel of unrelated tumours, they reacted against individual cell lines derived from carcinomas of colon, lung, bladder and cervix. These cross-reactions were not observed with other colon or lung carcinomas, and it is suggested that the antibody was reacting with a tumour-associated antigen expressed randomly on different tumour types, rather than specifically on osteogenic sarcomas.

Long Term and Short Term Screening Assays for Carcinogens: A Critical Appraisal

Abstract: are well referenced and indexed, and discussions are included. The presentation of the book is of a high standard and is recommended as a detailed and comprehensive treatise on the use of tissue temperature in diagnosis and in therapy. It is unlikely to be bettered until many of the problems discussed have been largely solved. This is definitely one of the more worthwhile appraisals in this series and offers an acceptable foundation for anyone entering the field of carcinogen screening and a useful reference source for those already in the field. The first report is concerned with long-term assays, and details practically every pitfall of such systems. This is so important in assay systems which have so many inherent variables. Everything from the administration of the test substance, through animal caging/bedding selection, to processing of the data is discussed. The reports on 'Mutagenesis Assays in Bacteria', 'Mutagenesis Assays in Mamma-lian Cells', 'Transformation in Cell Culture' and 'Cytogenetic Damage as an end point in short-term Assay systems' are well and enthusiastically presented, detailing the ad-vatages and disadvantages of both, the particular class of screening test and the detailed and varied methods encompassed within each class. Perhaps the most interesting report in the book is that on 'Mutagenesis Assays with Whole Mammals'. This is an area that has been relatively poorly studied and theoretically represents the situation closest to that in real life. Conversely, the Yeast, Drosophila and DNA-repair chapters tend to demonstrate that these areas are outmoded. The expectation that research into neo-plasia in domestic animals would provide new insight into the origins of human cancer, led to the establishment in 1961 of the Epizoology Section within the Epidemiology branch of the National Cancer Institute. Data from 15 veterinary schools in the U.S.A. and Canada have been processed at the National Cancer Institute and the details on neoplastic disease are published in the present volume. Neoplasms in cats were mainly malignant (88%) and horses had the lowest proportion of malignant tumours (400o) with dogs (56%) and cattle (770o) intermediate. The tumours most commonly seen were: Cattle; squamous-cell carcinoma, lym-phoma, leukaemia. Horse; squamous-cell carcinoma, malig-nat melanoma, fibrosarcoma. Cat and Dog; tumours of the skin, haemo-poetic and lymphatic tissues, and mammary gland In many cases the R (summary relative risk) values are given. For all tumours in dogs the Boxer had R 3-4 and the St. Bernard 3 0. The Pekinese R value …

The relationship of malignant melanoma, basal and squamous skin cancers to indoor and outdoor work.

Abstract: An analysis of occupational incidence data for malignant melanomas and squamous-and basal-self carcinomas of the skin in England and Wales from 1970 to 1975 is reported. The occupational pattern for melanomas of the trunk and limbs differed markedly from the pattern for melanomas of the head, face and neck. Office work was associated with a large excess of melanomas of the trunk and limbs. In contrast, outdoor work was associated with an excess of melanomas of the head, face and neck; and was also associated with an excess of squamous-and basal-cell carcinomas of the skin. This suggests that prolonged occupational exposure to sunlight is an important cause of squamous-and basal-cell carcinomas and of melanomas of the head, face and neck, but not of melanomas on other parts of the body. The high rate of lesions on the trunk and limbs in office workers may reflect their sunbathing or other recreational habits; but it contrasts clearly with other indoor work, where there is a generally low rate of all forms of skin cancer.

A case-control study of the possible association between oral contraceptives and malignant melanoma

Abstract: In a case-control study, we investigated 169 women aged 15-49 years with malignant melanoma notified to the Oxford and South Western cancer registries during the years 1971-1976, together with 507 matched controls. Data about medical, reproductive, drug and smoking histories were obtained both by reviewing general practitioner (GP) records and from the women themselves by postal questionnaires. There was no significant evidence of any overall increase in the risk of melanoma in oral contraceptive (OC) users (data from GP records-ever use vs never use, relative risk (RR) 1.34, 95% confidence limits 0.92-1.96; corresponding data from postal questionnaires-RR 1.13, limits 0.73-1.75). However, although not significant, the risk estimated from data in the postal questionnaires was higher in women who had used OCs for 5 years or more (use greater than or equal to 5 years vs never use, RR 1.57, limits 0.83-3.03). Previously demonstrated risk factors for melanoma, such as fair skin, blond or red hair and Celtic origin were found to be commoner in the cases than in the controls. Data from the Oxford/Family Planning Association contraceptive study were also examined. Unexpectedly there was a strong suggestion of a negative association between OC use and melanoma risk, but the analysis was based on only 12 women with the disease.

Localization of human tumour xenografts after i.v. administration of radiolabeled monoclonal antibodies.

Abstract: A mouse monoclonal antibody (LICR-LON/HT13) has been developed to a cell-surface antigen carried on a human germ-cell tumour xenograft (HX39). After radioiodination, the antibody localized in vivo preferentially in xenografted tumours as opposed to normal mouse tissue, whereas tumor uptake did not occur with normal mouse IgG or nonspecific monoclonal IgG. This selective localization could be abolished by simultaneous injection of an excess of the unlabelled LICR-LON/HT13. The kinetics of and factors influencing localization have been examined. Tumour weight was important in that the smaller the tumour the better the localization. LICR-LON/HT13 was found to localize also in other xenografted germ-cell tumours, but not in non-germ-cell tumour xenografts. Thus monoclonal antibodies are capable of selective in vivo localization of human tumours in an animal model, and their clinical value should now be assessed.

Tumour spectrum in the FAMMM syndrome.

Abstract: The Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is characterized by an autosomal dominantly inherited susceptibility to multiple atypical naevi. Patients with this hereditary phenotype show a strong susceptibility to cutaneous malignant melanoma (CMM). Our investigation of an extended Dutch kindred showing the FAMMM phenotype revealed a proband with bilateral intraocular malignant melanoma (IOM) and multiple CMM. The family revealed an array of tumours which included carcinoma of the lung, skin, larynx, and breast in addition to CMM and IOM, which were transmitted vertically through 3 generations. There was male-to-male transmission, and the number of affected males and females was about the same, which was consistent with an autosomal dominant inheritance. Thus the FAMMM syndrome not only indicates a potential for CMM, but a susceptibility to other systemic cancers as well. These observations, though limited to a single kindred, merit a painstaking evaluation of cancer of all anatomical sites in other kindreds showing the FAMMM syndrome. Such studies could yield clues to cancer aetiology, pathogenesis, and control.

Response of Chinese hamster ovary cells to anticancer drugs under aerobic and hypoxic conditions

Abstract: Response of Chinese hamster ovary cells to anticancer drugs under aerobic and hypoxic conditions

Human monoclonal antibodies to lung-cancer antigens

Abstract: Lymphocytes obtained from hilar and bronchial lymph nodes from 23 patients undergoing radical surgery for carcinoma of the bronchus were fused with established rat or mouse myeloma lines. 62% of the resultant hybrids were found to be secreting human Ig detected by a sensitive staphylococcal Protein A-coupled SRBC assay. Immunoglobulins synthesized by such hybrids were internally labelled with 3H-lysine and their antibody activity against a variety of membrane preparations determined. Nine monoclonal antibodies were found which bound to molecules on lung-cancer membranes and not on normal lung membranes from the same patient.

Molecular and Cellular Aspects of Carcinogen Screening Tests

Abstract: review of infectious complications of malignant disease and in the treatment of malignant disease. This is thorough and the different infections are arranged to stress their relevant importance. The self-assessment questions are comprehensive and, in most cases, pose valid and relevant questions. Some questions, however, do not appear to have a definite answer, and it is to be hoped that the American Sub-specialty Boards allow for discussion of controversies in medical oncology in which a simple true-or-false or multiple-choice answer is inappropriate. In summary, this book represents a massive accumulation of data and information. It cannot, however, be fully recommended, because of its, at times, incomprehensible style and its lack of space to discuss objectively different treatment options available for many of the diseases in which chemotherapy is used. Some of the newer information on responses of a variety of short-term tests to mutagens and carcinogens are presented in this volume, and it is evident that a more critical and analytical approach to the vast amount of data being generated is now being adopted. Much more emphasis is now being placed on understanding the scientific basis for the various short-term tests. There is also a shift of emphasis from an exclusive consideration of tests which will detect only initiators to those which will detect promoters and will respond to epigenetic effects now being reconsidered as possibly involved in carcino-genesis; this new approach being exemplified by the contribution from Radman and his co-workers. The interesting section on the scientific basis for short-term tests includes a pertinent paper from Green (Sussex) in which the problems of using the Ames test as even a qualitative index of carcinogenicity are discussed; the main problem being how to define a positive result. When attempts are made to use even the well-validated Ames test quantitatively (i.e. to attempt correlations of muta-genic potency with carcinogenic potency) the problems are compounded, and these are lucidly discussed in this paper. Other papers in the volume deal with inter-laboratory reproducibility of various tests, attempts at a classification of experimental evidence to indicate degrees of carcinogeni-city, and details of various international collaborative schemes for mutagenicity and carcinogenicity. Overall, a useful update of progress in this rapidly expanding field. In the last decade, there has been evidence of a gradual reduction in deaths due to cancer in the under-45 age group. This decrease in the younger age group can be in part …

Elevated levels of prolactin in nulliparous women.

Abstract: Follicular-phase (Day 11) plasma prolactin, and plasma and urinary oestrogen levels of 70 nulliparous nuns were compared with those of 80 of their sisters, of whom 62 were parous. The nuns and their nulliparous sisters did not differ significantly in their prolactin and oestrogen levels. No differences in plasma oestrogens or urinary oestriol ratio were found between the parous and the nulliparous women. However, the mean prolactin level of the nuns and their nulliparous sisters was 35% higher than that of the parous women in the sample taken approximately 1 3/4 h after rising (p less than 0.0005), and 24% higher (P less then 0.01) in the 2nd sample taken 2 h later. The elevation was independent of age, weight, and age at menarche. Age at first full-term pregnancy, at least up to the age of 30, and second or subsequent full-term pregnancies had no further effect on prolactin level. This study suggests that the effect of early first full-term pregnancy in lowering breast cancer risk may be mediated, at least in part, by permanently lowering the level of circulating prolactin.

Tumours of the Pancreas

Abstract: This is No. 21 of the volumes of the WHO International Histological Classification of Tumours. Previous volumes have been reviewed in this journal, and interested readers will be familiar with the aims and achievements of this valuable series. Tumours of the central nervous system have always formed a difficult field of study, divorced from the main corpus of tumour pathology, and shrouded in a mystique which neuropathologists have not always seemed eager to dissipate. But the general principles of tumour classification are as applicable within the CNS as elsewhere, and in recent years less intimidating classifications of CNS tumours have appeared. The present volume follows this more down to-earth trend, and offers a relatively simple scheme. Each tumour type is briefly described, and illustrated by excellent and apposite colour photomicrographs. The dedicated neuro-pathologist may find points to criticise, but the \"occasional\" histopathologist, faced with an intracranial neoplasm, will not go far wrong if he follows this guide. It can also be recommended as a reference book for neuro-surgeons and oncologists. People wAho issue optimistic statements about the progress of the \"fight against cancer\" might do-well to ponder a while on cancer of the pancreas. It is calculated that there are 22,000 new cases of pancreatic cancer per year in the United States. Over 9000, of these are adeno-carcinomas arising in the pancreatic duct system, and for this tumour the overall survival is about 1000 one year from diagnosis , and 20// or less at 5 years. Because of the deep central location of the pancreas, the exocrine pancreatic tumours produce only vague clinical signs in their early stages. By the time that tumour has involved the common bile duct and produced obstructive jaundice, it has spread beyond the possibility of surgical resection, though palliative short-circuit procedures may still be feasible. Radiotherapy has not been successful in this field, and so far the results of chemotherapy have been disapointing. Earlier diagnosis offers the only possible way to improve this grim situation, and the keys to this are, as the authors truly state, (1) early suspicion and (2) immediate access to diagnostic programmes. The core of this book, whose authors are mainly from the University of Chicago, is a critical assessment of the diagnostic procedures currently available for the diagnosis of pancreatic tumours. and drawrbacks of these are all Aell described. Framing these central chapters are good brief reviews of pancreatic anatomy …

Oestrogen-receptor status and sites of metastasis in breast cancer.

Abstract: The oestrogen receptor (RE) status of the primary tumour has been assessed in 466 of a consecutive series of 550 patients with primary operable breast cancer. All patients were followed up (without treatment) until the development of recurrence or metastases. Distant metastases have so far occurred in 124 patients and 82 have had symptomatic local or regional recurrence. A significant correlation exists between the RE status of the primary tumour and subsequent patterns of metastasis. Symptomatic metastases to regional lymph nodes are more common with RE- cancers. There is no significant difference in either time of onset or total incidence of distant metastases between patients with RE+ and RE- tumours. Distribution of distant metastases is influenced by RE status: RE+ tumours tend to recur in bone, RE- tumours show affinity for viscera.

Oestrogen-receptor status and endocrine therapy of breast cancer: response rates and status stability.

Abstract: The concentration of cellular oestrogen receptor (RE) was measured in both the soluble and nuclear-pellet fractions of biopsies from 1,000 breast cancers. Data suggest that functional steroid RE is always in equilibrium between the soluble and nuclear fractions. However, biopsies from only one-third of patients contained detectable amounts of high-affinity RE in both fractions. Thirty patients out of 42 (71%) whose biopsies contained RE in both fractions, showed objective remission after receiving some form of hormonal manipulation as sole treatment. Response rates in the other categories ranged from 9% for those whose biopsies contained no detectable RE to 24% for those who displayed soluble RE alone. The presence of RE in both fractions of primary disease, whereas RE-negativity was maintained during progression from primary to secondary disease. Other aspects of RE status in relation to stage of disease are analysed.

A randomized study of misonidazole and radiotherapy for grade 3 and 4 cerebral astrocytoma.

Abstract: The results are reported of a small clinical trial carried out to assess the potential value of the hypoxic cell radiosensitizer misonidazole in the radiation treatment of Grade 3 and 4 supratentorial astrocytomas. A total of 55 patients were randomly allocated to one of 3 treatment groups. No significant differences were seen between the median survivals of patients in the 2 control radiation groups and that of the third group in which oral misonidazole at a dose of 3 g/m2 preceded each of 4 weekly radiation doses. Possible reasons why no improvement was seen are discussed in detail.

Tumour-necrosis factor from the rabbit. V. Synthesis in vitro by mononuclear phagocytes from various tissues of normal and BCG-injected rabbits.

Abstract: Tumour-necrosis factor (TNF) is an anti-tumour factor released into the serum of BCG-primed rabbits after iv injection of endotoxin Although negligible amounts of TNF are produced in normal, unprimed animals after endotoxin injection, monocytes from these rabbits can produce TNF after endotoxin challenge in vitro This paper (a) establishes the optimal conditions for TNF production in vitro by mononuclear phagocytes from various tissues and (b) compares tissues from normal and BCG-injected rabbits for TNF production in vitro Optimal amounts of TNF are produced by mononuclear phagocytes in the presence of endotoxin The TNF is newly synthesized, mainly in the first 7 h of culture, and has similar gel-filtration and ion exchange behaviour irrespective of its source For both normal and BCG-injected rabbits, alveolar and peritoneal macrophages are the most potent producers, followed by blood monocytes, spleen macrophages and marrow cells The liver is also an important site of TNF synthesis In the tissues of BCG-injected rabbits there are more mononuclear phagocytes than in normal rabbits, and these cells have enhanced capacity to produce TNF Taking both factors into account it can be calculated that, after injection of endotoxin in vivo, over 20 X more TNF would be produced by BCG rabbits than normal rabbits, assuming that the major sources of production are the lungs, blood, spleen and liver

Lymphocytes infiltrating human breast cancers lack K-cell activity and show low levels of NK-cell activity.

Abstract: Lymphocytes infiltrating human primary mammary carcinomas lack ADCC and show low levels of natural cytotoxicity. The peripheral blood lymphocytes, however, show a variable but prominent level of cytotoxicity. Lymphocyte preparations from breast tumours, when mixed with autologous blood lymphocytes, significantly suppress their prominent killer- (K- and NK-) cell activities.

Measurement of self-renewal in culture of clonogenic cells from human ovarian carcinoma.

Abstract: To test the identity of human tumour clonogenic cells and stem cells, a procedure was developed to allow quantitation of self-renewal capacity of human ovarian carcinoma clonogenic cells. Primary colonies grown from malignant effusions of 10 patients were disaggregated and replated; secondary colonies were observed to be similar to primary colonies in size, morphology and culture requirements. Density-gradient separation of tumour-cell populations demonstrated that not all primary clonogenic cells are capable of self-renewal during clonal expansion. Patient-to-patient variation in self-renewal capacity was shown to be significantly correlated with the concentration of the tumour-cell population in the effusion fluid, and preliminary evidence of a progressive increase in self-renewal was found in one patient. It was concluded that some, but not all, ovarian-tumour clonogenic cells have the stem-cell property of self-renewal, and that quantitation of such a property may identify an important prognostic variable.

Cytotoxic and clastogenic effects of soluble and insoluble compounds containing hexavalent and trivalent chromium.

Abstract: Cr(III) and Cr(VI) compounds of varying solubilities have been tested in vitro for their ability to inhibit cell growth and nucleic acid and protein syntheses in BHK cells, to induce alterations in the mitotic cycle in HEp cells, and to increase the frequency of chromosomal aberrations and sister chromatid exchanges (SCE) in CHO cells. All Cr(VI) compounds, and particularly those containing soluble Cr(VI), such as potassium dichromate and zinc yellow, differentially inhibit macromolecular syntheses in BKH cells, that of DNA being always the most affected. Among Cr(III) compounds, which generally have very low cytotoxicity, chromite is particularly active, and inhibits cell growth and DNA synthesis even more than the poorly soluble Cr(VI) compounds. Preincubation in growth medium, with or without metabolizing cell cultures, solubilizes considerable amounts of Cr(VI) from zinc yellow and chromite, but significant amounts are also obtained from the most insoluble Cr(VI) pigments. When BHK cells are treated with such preincubated solutions, reduction of soluble Cr(VI) to Cr(III) by cell metabolites is seen with all Cr(VI) compounds, accompanied by decreased cytotoxicity. The same differences between Cr(VI) and Cr(III) compounds apply to the cytotoxic effects on mitosis of HEp cells and the clastogenic effects on CHO cells. The activity of chromite, the only Cr(III) pigment capable of significantly increasing the frequency of SCE, is due to contamination with soluble Cr(VI). In contrast to the very low cytotoxicity of Cr(III), much higher chromium levels are detected in the cells incubated with soluble Cr(III) than with the same concentrations of soluble Cr(VI). 50% and 75% of chromium accumulated in the cells during treatments with Cr(VI) and Cr(III) respectively remains firmly bound to the cells, even when they are incubated for up to 48 h in normal growth medium. Chromium accumulated in the cells after treatment with Cr(III) is most probably bound to the cell membrane, whereas some of the Cr(VI) is transported through the cell membrane and reduced in the cell nucleus. The results of the present investigation are in agreement with those obtained with the same Cr(VI) and Cr(III) compounds in mutagenicity assays in bacteria and carcinogenicity tests in rodents. A re-evaluation of the mechanisms of chromium carcinogenisis is proposed.

Specific and non-specific lymphocyte cytotoxicity in colon carcinoma.

Abstract: The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.

Prognostic value of preoperative serum CEA level compared to clinical staging. I. Colorectal carcinoma.

Abstract: In a clinical investigation of observed postoperative survival, 563 patients have been registered for primary surgical treatment of colorectal cancer since 1974. The potential prognostic factors examined within the first days of hospitalization for primary resection included age of the patients, operability, location of the tumour, tumour extension and the preoperative serum CEA level. Statistical treatment of the data revealed that each of the clinical parameters except tumour location covers ranges associated with highly significant differences in survival of the patients. The preoperative serum CEA level gave prognostic information in addition to operability or tumour extension. The prognostic significance of the preoperative CEA level was still evident when selected subgroups of patients with distinct resectability and tumour extension were examined. The results indicate that the preoperative serum CEA level is an independent prognostic parameter.

Significance of non-standard Philadelphia chromosomes in chronic granulocytic leukaemia.

Abstract: One hundred and nineteen unselected and similarly treated patients with Ph1-positive chronic granulocytic leukaemia (CGL) had the precise nature of their chromosome rearrangements producing the Ph1 studied to determine whether this had any clinical relevance. Eighteen (15%) did not have the usual 9/22 translocation and these, by life-table analysis, had a significantly shorter benign phase of their disease than the others (P less than 0.01). It further appeared that possession of a non-standard Ph1 was related to age, in that whereas only 24 patients were over 60 at diagnosis, 9 (33%) had a non-9/22 translocation (P less than 0.01). As the duration of the benign phase seemed to be shorter in those over 60 irrespective of Ph1 type (P less than 0.01), the questions arose whether non-standard PhI chromosomes were simply occurring in older patients or whether they were affecting prognosis independently. Their independent effect was suggested by the 11 patients under 60 with a non-9/22 Ph1 who still had a significantly shorter benign phase than the 84 of similar age with a standard Ph1 (P less than 0.01). It is concluded that the myeloid karyotype can provide prognostic as well as diagnostic information in patients with CGL.

Distribution of malignant melanoma on the body surface.

Abstract: The distribution of malignant melanoma among the 4 major body sites (head, upper limb, lower limb and remainder (trunk) was investigated for 37 white populations. Although UV radiation is generally considered to be the major aetiological agent, it was found that approximately 75% of the tumours occurred on the relatively unexposed body sites. However, the sex differences in the incidence of melanoma at the various sites corresponded in direction and magnitude with the patterns of exposures of the sexes. The greatest difference between the sexes was the higher incidence on the female lower limb (the regular wearing of skirts results in a considerable exposure), and the next largest was the higher incidence on the male trunk (men can remove their shirts easily, but do not do so regularly). The results indicate that UV radiation is a major cause of malignant melanoma, but suggest that the mechanism of induction may be complex. Several hypotheses, as well as the types of additional evidence required, are discussed.