Showing papers in "British Journal of Cancer in 1977"

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Abstract: Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Assessment of response to therapy in advanced breast cancer.

Abstract: A system is proposed by the UICC for assessing response to treatment of advanced breast cancers.

Avascular and vascular phases of tumour growth in the chick embryo.

Abstract: The chick embryo was used to study the relationship between the onset of tumour neovascularization and tumour growth. Walker 256 carcinosarcoma was implanted on the chrioallantoic membrane (CAM) of about 600 embryos aged 5-16 days. Tumour diameter and changes in the CAM vasculature in response to the implants were recorded daily. Representative tumours were examined by light microscopy of Epon-embedded tissue and autoradiography after injection of [3H]-thymidine. Tumours remained avascular for 72 h, after which they were penetrated by new blood vessels and began a phase of rapid growth. The rate of growth during this vascular phase was greatest for implants on 5- and 6-day-old embryos and decreased the later the day of implantation. The time of onset of tumour angiogenesis appears to be independent of the immunological state of the chick embryo, although the rate of growth after vascularization may be modified by the onset of immunity. This study suggests that the avascular and vascular phases of tumour growth are separable, and that the avascular tumour population lives under the growth constraints which limit the size of a tumour spheroid growing in soft agar or aqueous humour.

Clinical testing of the radiosensitizer Ro 07-0582: Experience with multiple doses

Abstract: The hypoxic cell radiosensitizer, Ro 07-0582, has now been given in multiple doses to 16 patients. They have received a total of 15-51 g in 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was, however, troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumour concentrations similar to those in plasma were obtained in human tumours, in contrast to the findings in mouse tumours where concentrations are usually below 40% of plasma levels. In the treatment of human tumours, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy.

Prostaglandins from tumours of human large bowel

Abstract: Prostaglandins (PGs) may be important in the growth of tumours (Jaffe, 1974) and their ability to metastasize to bone (Bennett et al., 1975, 1976a, b). Human colon cancer cells in tissue culture release more PGE than normal tissue from the same specimens (see Jaffe, 1974). We now confirm our preliminary report (Bennett and Del Tacca, 1975) that more PG can usually be extracted from human colonic tumours than from normal tissue. Colon resected for cancer (27 patients; 13 male, 14 female) was taken to the laboratory in Krebs' solution within 1 h of surgical removal. Part of the tumour, and macroscopically normal mucosal tissue (mucosa + submucosa) at least 6 cm from the tumour, were cut finely with scissors and washed with Krebs' solution. Weighed samples were homogenized, either in Krebs' solution to indicate synthesizing ability (" synthesized + basal " levels) or in Krebs' solution: ethanol (1 : 1) acidified to approximately pH 3 with formic acid to determine " basal " levels (Bennett, Stamford and Unger, 1973). " Synthesized " levels formed from endogenous precursor during homogenization were obtained by subtracting " basal " from "synthesized + basal " levels. PGs were extracted (Unger, Stamford and Bennett, 1971) and assayed against PGE2 on the rat gastric fundus strip preparation in Krebs' solution containing various antagonists to increase sensitivity and selectivity (Bennett et al., 1973), similar to the method of Gilmore, Vane and Wylie (1968). Tentative characterization of PG-like material extracted from homogenates in Krebs' solution was made, either by alkaline hydrolysis (which inactivates PGE but not PGF compounds; Bennett et al., 1973) or by chromatography using paper impregnated with silica gel, and the solvent system for group separation of PGE and PGF compounds (Stamford and Unger, 1972). Sections (5 ,um) of tumour retained by the Department of Morbid Anatomy were stained with haematoxylin and eosin, and examined histologically. Results (ng PGE2 equivalents/g fresh tissue) are given as median values and semiquartile ranges, and analysed statistically using the Wilcoxon matched-pairs rank test or the Mann-Whitney U test. The Krebs' solution contained (g/l) NaCl 7X1; CaCl2 .6H20 055; KCI 035; KH2PO4 016; MgSO4.7H20 029; NaHCO3 241; dextrose 10. Twenty-five adenocarcinomas of rectum, caecum and colon (13 female, 12 male), one malignant carcinoid, and one anal squamous-cell carcinoma were studied (Table). " Basal " (acid-ethanol) levels were higher than in the corresponding " normal" mucosa in 22/24 adenocarcinomas (1 sample lost), levels in the other 2 being similar. The "basal" values were: tumour 80 (37-125), mucosa 25

Malignant melanoma and oral contraceptive use among women in California.

Abstract: Women who had used oral contraceptives, particularly long-term users, were found to have higher rates of malignant melanoma and of a past history of skin cancer than those who had never used oral contraceptives. This excess was confined to lesions of the lower limb. The association between oral contraceptive use and melanoma was noted in 3 separate sets of data, although it was statistically significant only in one. The possibility that this relationship is indirect because, for example, oral contraceptive users are more likely than never-users to be exposed to sunlight and thus to develop malignant melanoma, cannot be excluded.

Histological Typing of Intestinal Tumours

Abstract: presently represents one of the most suitable models for an interdisciplinary attack on cancer\". Geneva: WHO. 69 pp. 134 colour photographs. Sw,.Fr. 80; US $32. The photographs are also available as a set of colour transparencies, price (complete with book) Sw.Fr. 215; US $86. This is Vol. 15 of the WHO International Histological Classification of Tumours. These volumes have appeared over the past 10 years, and enough have now been published for the quality and scope of the project to be apparent. These are not textbooks or monographs ; their aim is to promote an internationally agreed terminology and classification of human tumour types. Essentially they are collections of colour photomicro-graphs of sections, stained by conventional methods, with a scheme of classification and brief explanatory notes. The importance of achieving an agreed nomenclature for epidemiological purposes or for organizing clinical trials is obvious. These volumes are also of great value to diagnostic histopathologists, specially to those without ready access to specialized reference laboratories. Armed with these volumes, and the U.S. Armed Forces Institute of Pathology's Atlas of Tumor Pathology, the histopathologist should be able to cope effectively with most of the diagnostic problems presented by human neoplasia. Both sets are essential items for the diagnostic laboratory. This volume on intestinal tumours comes from St Mark's Hospital, London, and has all the merits one expects from that renowned centre. This is, in fact, one of the best of the volumes so far in this series. The regions covered are the small intestine, appendix, large intestine, anal canal and anal margin. As well as tumours, valuable sections are devoted to the tumour-like lesions, so often a source of diagnostic difficulty in these regions. Not everyone will agree with the details of the classification adopted, but pathologists should be encouraged to give it a trial. The explanatory notes are brief and pithy. The microphotographs are all of excellent quality and superbly reproduced. The endocrinle tumours of the intestinal tract (a fascinating newr chapter in pathology) are only incidentally mentioned-but a full treatment is promised in the forthcoming volume on endocrine tumours. In summary, an excellently produced, authoritative and invaluable atlas of intestinal tumours. (In the review copy Figs. 121-134 appear twice over, first bound upside dowAn between Figs. 96 and 97, and then in their right place.) Bleomycin (BLM), an anticancer antibiotic was discovered in Japan by Umezawa and his colleagues in 1959 …

Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro.

Abstract: There is now evidence that several classes of nitro compounds which have been used as radiosensitizers also function as cytotoxic agents specific for hypoxic cells The 2-nitroimidazole, Ro-07-0582, (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) is a compound of this type, and its effectiveness as a cytotoxic agent is dependent on drug concentration, contact time and temperature In vitro, Ro-07-0582 in air at 37 degrees C does not cause loss of cell viability at concentrations up to 2 mM, even when in contact for several days In contrast, hypoxic cells do not tolerate much lower concentrations of drugs, even if the contact time is only a few hours When the temperature is raised above 37 degrees C, there is a pronounced increase in the slope of the survival curves; for example, at 41 degrees C (for 1 mM Ro-07-0582, (200 microng/ml), the slope changes by a factor of 2-0 relative to that for 37 degrees C For cells in air at 41 degrees C, as at 37 degrees C, there is no toxic effect at the concentration of drug tested In the absence of drug, there is no cytotoxic effect of hyperthermia alone under these conditions These results are discussed in terms of Arrhenius parameters

Quantification of the role of smoking and chewing tobacco in oral, pharyngeal, and oesophageal cancers.

Abstract: The aetiologic fractions due to smoking and chewing tobacco have been quantified for the first time, for cancers of the oral cavity, oropharynx, hypopharynx, larynx and oesophagus. The overall aetiologic fractions due to smoking and/or chewing tobacco have been found to be 70% for cancer of the oral cavity, 84% for the oropharynx, and about 75% for the hypopharynx and larynx. In cancer of the oesophagus, however, the fraction is only 50%, showing that another factor or factors play an equal role in the aetiology of cancer of this site. At each of the sites studied, it was found that the two factors, smoking and chewing, acted synergistically, though in varying degrees.

Treatment of acute myeloid leukaemia with a triple cytotoxic regime: DAT.

Abstract: Twenty patients with acute myeloid leukaemia (AML) were treated with a combination of chemotherapy which included daunorubicin, cytosine arabino-side and 6-thioguanine (DAT). The complete remission rate was 85% and was achieved, in responsive cases, after an average of 2 courses of therapy. Patients remained in hospital for an average of 37.5 days during remission-induction therapy and 3.7 days per month thereafter. The median remission period was 48 weeks and median survival was 70 weeks. A disappointing feature was the high relapse rate. This feature of the results re-affirms the need for a more effective form of remission therapy.

A method for detecting carcinogenic organic chemicals using mammalian cells in culture.

Abstract: A method for testing organic chemicals for their carcinogenic potential is described Baby hamster kidney cells (BHK-21/C1 13) were exposed to different doses of test compound in liquid tissue culture medium containing rat liver post-mitochondrial supernatant and cofactors (S-9 mix) to aid metabolism, but without serum Survival of cells following exposure to the compound was assessed by cloning in liquid growth medium Transformation was assessed by colony growth in semi-solid agar The dose-response curve for survival was used to determine the LC50 of the compound A dose-response curve for transformation was constructed and a 5-fold increase in transformation frequency at the LC50 was regarded as a positive test result The method may also be used for testing gaseous compounds Cells grown in monolayers and overlaid with serum-free medium and S-9 mix were exposed to vinyl chloride gas mixed with air After exposure, the treated cells were trypsinized, resuspended in growth medium, and survival and transformation assays performed The methods described are illustrated by examples taken from an evaluation study using 120 compounds and found to be more than 90% accurate in distinguishing between carcinogens and non-carcinogens

A combination of chlorambucil, vinblastine, procarbazine and prednisolone for treatment of Hodgkin's disease.

Abstract: Seventy patients with Hodgkin's disease have been treated with a combination of chlorambucil, vinblastine, procarbazine and prednisolone (Ch1VPP). The complete remission rate of 75-7% compares well with that produced by other combinations. The combination is non-toxic, easily administered and can be given safely to outpatients. Its main advantage is that it is far less upsetting to patients than combinations containing nitrogen mustard.

Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice

Abstract: Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582. No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compoinds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective. For Ro-07-0582 and metronidazole, several concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min. The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray. Both metronidazole and Ro-07-0582 gave significant enhancement effect at serum concentrations which can be achieved in man.

Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient

Abstract: One hundred and thirty-nine untreated patients with acute myelogenous leukaemia (AML) were admitted between August 1970 and December 1973 and allocated into two remission treatment regimens: one to receive chemotherapy alone and the other chemotherapy with immunotherapy. Of the patients who attained remission. 22 were in the chemotherapy group and in September 1975 2 remained alive, the median survival time being 270 days and after relapse 75 days. Twenty-eight patients received immunotherapy during remission, and 5 remained alive; the median survival time of the group being 510 days and after relapse 165 days. Ongoing acturial analysis precisely predicted early in the study the median survival of the two groups, but it took a 2-year follow-up after entry of the last patient before it became clear that there were very few long-term survivors. The increase in survival time produced by the immunotherapy is apparently made up of two components: prolongation of the first remission and length of survival after the first relapse. It must be notted that the chemotherapy for this study was devised 6 years ago and the results of the control arm (chemotherapy alone) may be poorer than those obtained in contemporary studies.

Cytotoxicity of Ro-07-0582; enhancement by hyperthermia and protection by cysteamine

Abstract: The selective cytotoxicity which Ro-07-0582 exhibits towards hypoxic cells is strongly temperature-dependent. This cytotoxicity is reduced by the radical scavenger cysteamine, suggesting that nitro radicals or nitroso intermediates are involved in cell killing by the drug. Chromosome aberrations are not induced by Ro-07-0582 even when the surviving fraction is reduced to 0-01.

Influence of tumour size on hypoxic fraction and therapeutic sensitivity of Lewis lung tumour.

Abstract: Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours.

Influence of height, weight and obesity on risk of breast cancer in an unselected Swedish population.

Abstract: A number of recent studies have shown an association between breast-cancer risk and height, weight and dietary habits, especially fat consumption. In the present study, height and weight were determined for 179 consecutive, unselected, breast-cancer patients and age-matched controls selected from a computerized population register. Height and weight for these two groups were compared, including two different indices for overweight (Quetelet's index and Broca's index). Comparisons were repeated after subdivision into pre- and postmenopausal women. In all calculations, the mean values of patients and controls were very similar and without significant difference. It therefore seems improbable that increased height and weight or obesity constitute risk factors for breast cancer. Earlier studies may have shown differences as the result of selection mechanisms not present in this study.

Colorectal cancer and beer drinking

Abstract: Evidence is presented of a significant statistical association between beer drinking and colorectal cancer, particularly rectal cancer. This finding is based on correlations between consumption and cancer mortality and between changes in consumption and changes in cancer mortality for 47 states in the United States of America. Also various secular trends, an urban-rural gradient, socioeconomic gradients and sex ratios in the United States are shown to be generally consistent with a relationship between beer consumption and colorectal cancer, particularly rectal cancer. The limitations on drawing sound aetiological inferences from such data are acknowledged. In particular, several other variables are shown to be associated with both beer drinking and colorectal cancer. Also, a discussion of previous epidemiological studies is given, and it appears there is only a limited amount of direct evidence in humans to support the statistical demographic relationships.

A cell line from an anaplastic transitional cell carcinoma of human urinary bladder.

Abstract: A cell line, TCCSUP, derived from an undifferentiated, Grade IV transitional cell carcinoma is described. The karyotype showed an abnormal distribution of chromosomes, with no obvious modal number. Distinct marker chromosomes were observed in both early and late in vitro passages. These cells have been subcultured over 50 times during a 20-month period. TCCSUP differs in certain morphological and immunological features from other cell lines from transitional cell carcinomas.

Genetics of Human Cancer

Abstract: This volume represents the proceedings of a conference co-sponsored by the Epidemiology Branch of the National Cancer Institute and the National Foundation-March of Dimes. Although the date of the conference is not stated, some of the references are as late as 1976. There are sections dealing with relevant epidemiology, births, defects and cancer, cytogenetics, single gene disorders, cancer families, genetic markers, cell hybridisation, DNA repair, theories and future prospects. The "cause" of common cancers is as elusive as ever. Tumour immunology remains extremely complex and confusing and the role of oncogenic viruses in man is not yet clear. Nevertheless, there is an impressive list ofachievements in fundamental cancer genetics, notably in cytogenetics, in cell fusion studies and in progress in identifying disorders of DNA repair. There are now more than 40 rare cancers which are known to have Mendelian inheritance (but in which pathogenesis is often obscure) and an increasing number of genetic markers appear to be associated with cancer proneness or resistance. The potential importance of genetic marker studies is seen in ankylosing spondylitis. If ankylosing spondylitis were a curable cancer when diagnosed early, it would probably be justified to HLA-B27 type all young males, since those positive would have more than 100 times the risk of those negative. The importance of cancer registers is likely to increase as such genetic markers become available. Scolnick describes his work with the Mormons in which he is "...trying to put together the genealogy of the entire State of Utah ... (linked) to a tumour registry ... so that the familial cases can be studied in the context of other cancer cases in the population". Total ascertainment would largely eliminate the problem of handling bias and if allied to genetic and other marker studies and the computerised recording of all known exposure to environmental carcinogens, might well lead to a clear understanding of the total accumulation of cancer proneness which affects each of us at various ages. However, there is much discussion of and some distaste for the concept of disease registers and many fear to make easily available too much detailed information about ourselves and our weaknesses. If reasonable confidentiality can be guaranteed, as appears to be the case in Utah, the next half century might well see profitable computerisation of medical, genetic and environmental data on a prospective basis for the whole population. Events separated in time and space affecting …

Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma

Abstract: Whole body X-irradiation (400 rad) of C57BL mice, either before or after i.m. implantation of the syngeneic fibrosarcoma, FS6, influenced both the growth of the tumours and their cellular composition, particularly their macrophage content. Pre-irradiation resulted in slower initial growth of tumours, and a concomitant lack of host-cell infiltration, but when tumours began to grow at a rate parallel to controls infiltration by host cells was demonstrable. Similarly, irradiation of the tumour-bearing host resulted in a temporary cessation of growth, and a decrease in the macrophage content, which did not return to control levels for 2-3 weeks after irradiation. The significance of these results is discussed in relation to the possibility that infiltrating host cells, particularly macrophages, may stimulate the growth of this tumour.

Mononuclear Phagocytes in Immunity Infection and Pathology

Abstract: This volume, the fourth in a comprehensive treatise on cancer, is in fact the second of 2 volumes (nos. 3 & 4) devoted to the biology of tumours. It comprises 3 parts concerned respectively with the spread of tumours, im-munology and comparative pathology, to which 17 authors have contributed a total of 12 articles. The first section on the spread of tumours consists of 3 chapters: the properties of the surfaces of normal and transformed cells are dealt with by J. C. Robbins and G. L. Nicolson, and contact inhibition by J. Ponten. I. J. Fidler contributes a chapter on mechanisms of cancer invasion and metastasis. The second section, which is the largest, provides a comprehensive survey of contemporary knowledge of tumour antigens and the hosts' response to them, drawn from experimental models as well as clinical studies. L. W. Law and E. Appella discuss the properties of soluble transplantation and tumour antigens. Antigens expressed by virus-induced tumours are systemically analysed by T. Aoki and L. R. Sibal (Oncorna-viruses) and S. S. and M. J. Tevethia (Oncod-naviruses) while aspects of the immuno-biology and chemically induced tumours are examined Golub, and is a critical appraisal of human tumour immunology, with particular reference to the methodological difficulties which have beset the elucidation of tumour-immune phenomena in man. The third section is devoted to the comparative pathology of cancer in animals, poikilothermics and plants. H. L. Stewart selects common human neoplasms of specific sites and compares them with neoplasms of similar sites in other species, and D. G. Scarpelli describes the distribution and characteristics of some common neoplasms in poikilothermics, and considers various aetio-logical and biological perspectives, such as chemical carcinogens, viruses, immunity and neoplasia etc. Finally, A. C. Braun discusses the contribution which neoplastic diseases of plants have made as models for the study of basic cellular mechanisms underlying the cancerous state. The general style and presentation of the diversified material in this book accords with its intended status as a textbook. As such, it should be readily accessible to experiment-alists and clinicians working in the field. For some time there has been a need to bring together the vast amount of information which is the product of the exponential literature explosion of the last 15 years. Whether the comprehensive treatise, of which this volume is a part, has succeeded will depend on the coverage and quality of the series as a …

Acute-phase reactant protein profiles: an aid to monitoring large bowel cancer by CEA and serum enzymes

Abstract: The profiles of 4 acute-phase reactant proteins (APRPs) (haptoglobin (HPT), alpha1 antitrypsin (AAT), alpha1 acid glycoprotein (AGP) and prealbumin (PALB)) have been studied during the evolution of bowel cancer. Serial measurements of these APRPs can add to the information obtained from measurements of the level of CEA and hepatic enzymes during the monitoring of postoperative patients. There is considerable stability in the profile in a given individual in health, Rises of AAT and AGP are associated with metastases. High levels of HPT may suggest involvement of the bowel wall by recurrent cancer. PALB levels tend to reflect the nutritional status. A discriminant function based on the log CEA, AAT and AGP preoperative blood levels can considerably improve on the predictive value attained using CEA levels alone.

Influence of irradiation and chemotherapy on the ovaries of children with abdominal tumours.

Abstract: The ovaries of children with abdominal tumours were studied in 12 autopsy specimens. Ovaries from 25 children who died in accidents or after a short acute disease served as controls. All ovaries from normal children showed follicle growth, but follicle development was inhibited in 67% of the children with abdominal tumours. The effect of treatment with cytotoxic drugs and/or abdominal irradiation on ovarian morphology was investigated. Normal ovaries were found only in children who had received no chemotherapy or a short course. All patients who had been treated with radiation therapy either alone or in conjunction with chemotherapy had severely damaged ovaries: follicle growth was inhibited in all cases, and the number of small non-growing follicles was markedly reduced in most. It is argued that abdominal irradiation might impair follicle development as well as destroy small follicles.

Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

Abstract: The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY.

Incidence of bone sarcoma in SW England, 1946-74, in relation to age, sex, tumour site and histology.

Abstract: A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours presenting during each hemi-decade did not markedly diverge from the 5-year mean for the period, nor was any significant change found in tumour incidence during the last 20 years of the survey. The age, sex and site distributions correspond with those reported elsewhere. Age-specific incidence rates are compared with those published for Sweden. For osteosarcoma and Ewing's tumour, both commoner in young people, the two series agree closely up to age 55 years, after which the Swedish incidence rates rise and are not exceeded when, for the present cases, Paget's osteosarcomas are included. Whilst Paget's disease may change the age incidence of some types of bone sarcoma, it is uncertain whether it increases the total number which occur. Differences in tumour incidence between males and females, whether for a specific type or for all bone sarcomas, are seldom statistically significant, but the patterns appear to be consistent.

Immunological mechanisms in metastatic spread and the antimetastatic effects of C. parvum.

Abstract: The effects of the host's immune response on metastatic spread was investigated by observing the numbers of pulmonary metastases that developed from an s.c. implant of the Lewis lung carcinoma in C57BL mice in which different cell populations had been suppressed. Macrophage function was impaired by treatment with silica (Si), cortisone acetate (CA), or trypan blue (TB). T-cell function was depressed by adult thymectomy and sublethal irradiation, or by treatment with antilymphocyte serum (ALS). Metastasis was significantly increased and phagocytic activity decreased by Si and CA, but were unaffected by TB. Thymectomy and irradiation had no effect on metastases, whereas ALS when given before, but not after tumour growth, reduced their number. The antimetastatic action of the immunopotentiating agent C. parvum was investigated in these immunologically impaired mice. It was unaffected by Si, CA or TB. However, the inhibiting effect of these agents on phagocytic activity was overcome by treatment with C. parvum. Its antimetastatic action was unaffected in mice which had been thymectomized and irradiated, but could be abrogated by ALS. However, ALS was only able to prevent this activity if given before tumour growth, it was ineffective if given after tumour growth. This study showed that metastatic spread was inversely related to phagocytic activity. The antimetastatic effect of C. parvum appears to be mediated through macrophages in concert with a subpopulation of T lymphocytes, which were considered to be necessary in the sensitization arm of the response as opposed to the effector arm of this response.

Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke.

Abstract: The unusually high relative frequency of cancer in the laryngeal region in males (18% of all histologically diagnosed cancers) and a sex ratio of unity for lung cancer in Northern Thailand were further explored in a hospital-based case-control study in Chiang Mai. This compared patients having cancers of the oral cavity (including oropharynx), larynx, hypopharynx and lung, with controls in relation to smoking and chewing habits. Statistical analysis indicated that chewing betel is strongly associated with the occurrence of oral cancer in both sexes, and with cancer of the laryngeal region in males. No factors were strongly linked to lung cancer in men, but, in women, urban residence and miang chewing were associated with lung cancer. Analysis of smoke from the two main types of cigars smoked in the region showed that both had high tar content, but there were marked differences in pH. Smoking cigars with alkaline smoke and high tar had an increased risk for laryngeal cancer in males, whereas other cigars with acid smoke and high tar together with manufactured cigarettes had increased risks for lung cancer. These increased risks were not, however, statistically significant.

Reduction of tumour cell entry into vessels by bcg-activated macrophages

Abstract: the tumour cell membrane (Evans andAlexander, 1972). It is well establishedthat i.v.-injected macrophages sequesterfirst in the lungs and are later releasedsystemically to accumulate at sites ofinflammation (Roser, 1970; Perper,Oronsky and Sanda, 1976). Thus, it isreasonable to assume that at least somei.v.-infused activated macrophages couldreach the site of tumour transplantationand affect the entry

A test for mutation theory of cancer: carcinogenesis by misrepair of DNA damaged by 4-nitroquinoline 1-oxide.

Abstract: Evidence for a mutation theory of cancer is presented by reviewing the experimental work on 4-nitroquinoline 1-oxide (4NQO) carcinogenesis. 4NQO almost completely mimics u.v. light and produces 4NQO-purine adducts on DNA. When 4NQO-treated cells are held in liquid medium under appropriate conditions, the 4NQO adducts disappear from DNA, in parallel to decrease of premutational damage in Escherichia coli, or pretransformational damage in cultured mouse cells. Post-treatment with caffeine greatly diminishes the yields by 4NQO of mutants in E. coli, malignant transformants in cultured mouse cells and tumour nodules in the lung of mice. Potentially tumourigenized stem cells in the lung remain sensitive to selective killing by caffeine for at least 5 days after 4NQO treatment, in spite of their DNA being apparently replicated, an indication that carcinogen-damaged DNA in the stem cell can be transmitted to its successive daughter stem cells for many generations. This peculiar characteristic is discussed as a possible lead to the crux of the mutation theory of cancer in vivo, and a model for carcinogenesis is proposed.