Showing papers in "British Journal of Cancer in 1979"

Radiobiology for the Radiologist

Abstract: The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.

Case-control study: soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols.

Abstract: In 1977 a number of patients with soft-tissue sarcomas and previous exposure to phenoxyacetic acids were described. Following from these observations a matched case-control study was made. Exposure to chlorophenols was also included in this study. The results showed that exposure to phenoxyacetic acids or chlorophenols gave an approximately 6-fold increase in the risk for this type of tumour. It was not possible to determine, however, whether the carcinogenic effect was exerted by these compounds or by impurities such as chlorinated dibenzodioxins and dibenzofurans that in almost all cases were part of the commercial preparations.

Describing the validity of carcinogen screening tests.

Abstract: SEVERAL issues pertinent to the validation of screening tests and to the evaluation of screening programmes have evolved, largely in the epidemiological and general medical literature (Vecchio, 1966; Holland, 1974; Henderson, 1976). For this reason, laboratory scientists interested in the development and validation of carcinogen screening tests may not be fully aware of some useful concepts. The paper reviews several such concepts and their relationships. These relationships explain, for example, why the \"predictive value\", although frequently used as an index of the utility of a screening test, is not well suited for that purpose. A carcinogen screening test is usually evaluated by applying it to a group of substances, each of which is considered to be, or not to be, a carcinogen according to some selected criteria (i.e. animal or human carcinogenesis). The specific criteria chosen are beyond the scope of this discussion; however, the validity measures of a screening test are meaningful only in the context of these criteria. After some number, N, of substances has been tested, the results may be described using the format of the Table. (Terms used to describe screening tests and screening programmes are defined below the Table.) A screening test is expected to designate carcinogens as \"positive\" and to designate non-carcinogens as \"negative\". Each of these 2 distinct functions has its own measure of validity. The proportion of carcinogens which give a positive result in Accepted 16 October 1978

Prognostic significance of modal DNA value and other factors in malignant tumours, based on 1465 cases

Abstract: The modal DNA values of 1465 tumours, together with other factors of possible prognostic importance, were related to the survival of the patients, using regression models (Kay, 1977). For most tumour sites except the testis, the distributions of modal DNA values were bimodal, with peaks at the diploid level and in the triploid-tetraploid range. For all tumour sites except the cervix uteri, patients in the low (near-diploid) range showed better survival; the reverse was true for squamous-cell carcinoma of the cervix uteri. Other variables showed the following effects: for all sites except the testis, younger patients showed a better survival; for the cervix and corpus uteri, breast and ovary, increasing clinical stage was associated with poorer survival. Where evaluated, histological grade appeared to be associated with survival rate, the less well differentiated tumours having a worse prognosis, except for the breast, where the reverse correlation was noted. For carcinoma of the bladder, females and a poorer survival rate than males.

The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin

Abstract: The photosensitizing effect of haematoporphyrin (HP) on human cells of the established line NHIK 3025 has been studied. Fluorescence measurements show that HP is bound to these cells. Serum proteins also bind HP, and the presence of 10% human serum during incubation with HP (3 X 10(-4)M) reduces the cellular uptake of HP by 75% or more. The photosensitized inactivation is enhanced when the cells are suspended in D2O-buffer during irradiation. This indicates that singlet oxygen is involved in the inactivation. Two findings indicate that the photoinduced damage is repairable: firstly, the fraction of cells surviving a given light dose decreases with decreasing irradiation temperature, and secondly, the survival curves have a shoulder at low exposures of light.

Oesophageal cancer studies in the Caspian Littoral of Iran: results of a case-control study.

Abstract: The results are presented of a case-control study conducted in the north of Iran. The main aim was to study factors identified in a previous study as potentially causally related to cancer of the oesophagus. Other tumours (lung, stomach, breast, large bowel, larynx and pharynx) were included to distinguish findings specific for oesophageal cancer from general characteristics of cancer patients, due for example to ascertainment bias, and to verify that expected associations, such as between lung cancer and cigarette smoking, would emerge under the prevailing field conditions. Two controls were chosen per case, matched for village of residence, age, sex and language group, Reinterviewing was performed to a limited extent to assess the accuracy of replies to questionnaires. The following were found not to be associated with oesophageal cancer: consumption of sheep's milk and yoghurt, sesame oil, chewing of nass, making of carpets, use of pregnancy diets, salting and sun-drying of meat and use of wild spinach. The use of opium, bread and tea could not be assessed in the retrospective framework. Strongly associated with risk of oesophageal cancer were low socio-economic status and low intake of fresh fruit and vegetables. The two factors each had an independent effect, and were more marked for oesophageal cancer than for the other tumours.

Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices.

Abstract: Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well.

A new theory of carcinogenesis

Abstract: Although many carcinogens are mutagens, there is no direct evidence that the cancer-cell phenotype is the result of gene mutation. Transplantation experiments have strongly indicated that malignant cells can arise or revert to the normal phenotype in the absence of mutation. It is suggested that damage to DNA followed by repair triggers the epigenetic changes in gene expression which are responsible for malignancy. We previously proposed that methylation of specific DNA sequences adjacent to structural genes determines whether or not transcription will occur. Specific methylases are required for the switching on of genes and for the stable maintenance of the methylated state, which provides a basis for the control of gene expression in differentiated cells. It is now seen that damage to DNA followed by repair, just before or just after DNA replication, can lead to the loss of methyl groups. This can induce a switch in gene activity which is heritable, but potentially reversible. The known large difference in the probability of malignant transformation in cells of rodents and large mammals is hard to explain if mutation is responsible. On the other hand, this new theory provides an explanation for this difference, since the probability of epigenetic changes in gene activity will depend on the activity of methylating enzymes and the rate of excision repair. The theory is supported by the evidence that excision repair is more efficient in cultured fibroblasts from large long-lived animals than from small short-lived ones.

Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) in rats.

Abstract: Ethyl-alpha-p-chlorophenoxyisobutyrate), a hypolipidaemic drug which induces hepatomegaly and proliferation of peroxisomes in liver cells of rats and mice, was fed to 15 male F344 rats at a dietary concentration of 0.5% (v/w) for up to 28 months. Hepatocellular carcinomas developed in 10/11 (91%) rats killed between 24 and 28 months. Other tumours included carcinoma of the pancreas (2 rats), leiomyoma of the small intestine (1 rat) and a large dermatofibrosarcoma (1 rat). Clofibrate is the third hypolipidaemic peroxisome proliferator demonstrated to be hepatocarcinogenic in rats. These studies suggest that hypolipidaemic agents which are capable of producing a sustained hepatomegalic and peroxisome-proliferative effect also induce liver tumours.

Low natural-killer-cell activity in familial melanoma patients and their relatives.

Abstract: Patients with melanoma who had one or more close relatives with melanoma were studied for their natural-killer-cell (NK) activity against cultured melanoma cells and Chang cells. A high proportion of the patients and their relatives were found to have low NK activity against these target cells. In most of the patients this could not be attributed to general depression of their immune function, since B- and T-cell numbers and the mitogenic response to PHA were within normal limits. The levels of NK activity of the patients and their relatives were found to be significantly correlated, suggesting that the NK activity in these families may have been genetically (or environmentally) determined. Several genetic markers were examined in the patients and their relatives for association with the disease state and NK activity. No association with HLA antigens or ABO blood groups was detected, but there was a low incidence of the Rhesus negative phenotype in the patients (the Rh phenotype had previously been associated with high NK activity). The present results indicate that NK activity has a familial association in families with a high incidence of melanoma, and raise the question whether low NK activity may be one of the predisposing factors in the development of familial melanoma.

Dietary fibre and regional large-bowel cancer mortality in Britain.

Abstract: The relationship between food intake and cancer of the large bowel was assessed by calculating the average intakes of foods, nutrients and dietary fibre in the different regions of Great Britain and relating these to the regional pattern of death from colon and rectal cancers between 1969 and 1973. No significant associations were found with the consumption of fat, animal protein or beer, nor with current estimates of total dietary fibre intake. Average intakes of the pentose fraction of total dietary fibres, and of vegetables other than potatoes, were negatively correlated with the truncated age- and sex-standardized death rates from colon cancer (r = -0.960 and -0.940). Specific components of dietary fibre may therefore inhibit colon carcinogenesis.

Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan.

Abstract: In a Phase I study, melphalan 140 mg/m2 was administered to 8 patients with disseminated malignant melanoma. Marrow was removed from the patients immediately before melphalan administration and returned i.v. 8 h later. Studies on marrow culture and melphalan pharmacokinetics predicted that this was a safe time to administer non-cryopreserved marrow. Four patients received lower doses of i.v. melphalan without autologous marrow. In the group receiving autologous marrow the time for recovery of peripheral-blood granulocytes to 800/mm2 or greater was significantly less (P = 0.01) than in those not receiving marrow. In 7 patients the tumour showed evidence of response to the drug and there was 1 complete remission. This treatment deserves investigation in patients with tumours more sensitive to drugs than melanoma.

Racial differences in melanoma incidence.

Abstract: The incidences of malignant melanoma recorded by 59 population-based cancer registries were investigated to determine the effects of racial and skin-colour differences. White populations exhibited a wide range of melanoma incidences and females commonly, though not invariably, had a higher incidence than males. Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates. No predominant sex difference emerged among non-whites. Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot. A clear negative correlation between degree of skin pigmentation and melanoma incidence emerged for the exposed body sites. These data provide strong support for the hypotheses that UV radiation is a major cause of malignant melanoma and that melanin pigmentation protects against it. Further research is required to elucidate the aetiology of melanoma of the sole of the foot.

Causes of death of blue-collar workers at a Dublin brewery, 1954--73.

Abstract: The suggested association between high consumption of beer and an increased risk of death from cancer of the colon and rectum was investigated among blue-collar workers at a Dublin brewery, who consume more than average amounts of beer, usually in the form of stout. A study of their mortality between 1954 and 1973 showed that they had as good an expectation of life as all Dublin males, with no increased risk of death from cancer of the oesophagus, pharynx, liver or of cirrhosis of the liver, accidents or suicide, conditions normally associated with the high consumption of alcohol. They had significantly increased risk of death from cancer of the rectum and also from diabetes mellitus. Twenty per cent of the workers, differentiated by their place of work within the brewery, had a much higher risk of death from cancer of the rectum.

An angiogenic factor isolated from tumours: a potent low-molecular-weight compound.

Abstract: ImagesFig. 1

Variation of melanoma incidence with latitude in North America and Europe.

Abstract: The relationship between melanoma incidence and latitude was investigated in North American and Europe, using the data collected by 43 population-based cancer registries. In North America melanoma incidence increased with decreasing latitude, supporting the role of UV light in the induction of melanoma. Within England the data from the National Cancer Registration scheme also showed that trend of decreased frequency of melanoma with decreasing latitude. In contrast, across Europe the trend was in the opposite direction, of increasing melanoma incidence with increasing latitude. It is suggested that across Europe there is a range of skin colour from dark in the south to light in the north, which gives rise to a range of susceptibility to the induction of melanoma by UV. The effect of this susceptibility must be large enough to overwhelm the opposing effect of decreased UV intensity at higher latitudes, and this emphasizes the dangers of excessive solar exposure to fair-skinned individuals. The populations of England may be a sufficiently random mix of skin colour, owing to repeated invasions, for the effect of UV intensity to be observed.

Microenvironmental arginine depletion by macrophages in vivo.

Abstract: Since the tumour-selective cytotoxic activity of activated macrophages in vitro can be attributed to depletion of the culture medium of L-arginine by macrophage arginase, a series of experiments was designed to determine whether such a mechanism could operate in vivo. Extracellular fluid obtained from Gullino chambers within established tumours contained high levels of arginase, no detectable arginine and high levels of ornithine. When tumours were disaggregated into single-cell suspensions, arginase was readily detected within tumour macrophages but not within malignant cells. Inflammatory ascites induced in mice by Corynebacterium parvum was rich in arginase, depleted of L-arginine and cytotoxic in vitro to L5178Y and V79 cells. High levels of arginase in the ascites fluid were associated with resistance to challenge with syngeneic L5178Y cells. Lymph collected from the cisterna chyli in rats bearing a macrophage-rich sarcoma on the small bowel contained elevated levels of arginase, was depleted of arginine and contained increased concentrations of ornithine. We conclude that in sites of macrophage infiltration there is microenvironmental arginine depletion due to the action of arginase, and that arginase release could represent an important macrophage effector mechanism against a variety of targets, including malignant cells, virus-infected cells, fungi and parasites.

Descriptive epidemiology of testicular and prostatic cancer in Los Angeles

Abstract: Data from the Los Angeles County Cancer Surveillance Program (CSP) from 1972 to 1975 were used to study the descriptive epidemiology of testicular cancer and prostatic cancer. The very high black/white ratio and late age peak of cancer of the prostate contrasted sharply with the very low ratio and early age peak of testicular cancer. However, both sites had higher rates among upper occupational and social class groupings. Avalable descriptive and analytical research suggests that the etiology of prostatic cancer is most probably related to hormonal influences rather than to a horizontally transmitted agent, while the etiology of testicular cancer is most probably related to endogenous or exogenous hormonal influences in utero or in infancy, or to in utero exposure to other exogenous agents.

Evidence that cells from experimental tumours can activate coagulation factor x.

Abstract: The procoagulant activity of cells from some experimental tumours isolated in culture or in single-cell suspensions from ascitic fluid was investigated. Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, Factor VIII- and Factor VII-deficient but not of Factor X-deficient human plasma. The same cells generated thrombin when mixed with a source of prothrombin and Factor X, absorbed bovine serum (as a source of Factor V), phospholipid and calcium chloride. Thrombin formation was not influenced by the presence of Factor VII. Cells from Sarcoma 180 ascites were completely inactive in both test systems. It is concluded that cells from some experimental tumours have the capacity to activate Coagulation Factor X directly. These findings suggest the existence of an alternative "cellular" pathway in the initiation of blood clotting distinct from both the intrinsic and extrinsic mechanisms.

Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast

Abstract: Activities of some enzymes associated with carbohydrate and lipid metabolism were determined in 48 human breast carcinomas and compared with those found in 35 nonmalignant breast tumours and also in 13 normal breast tissues. In fibrocystic disease only the activity of citrate lyase was markedly higher (14-fold) than in normal tissue. The activities of the remaining enzymes did not differ significantly from those in normal tissue. Enzyme activities in breast carcinoma were 4--160 x those determined in normal tissue according to the following sequence : phosphofructokinase less than malate NADP dehydrogenase less than hexokinase less than lactate dehydrogenase less than isocitrate NADP dehydrogenase less than ATP citrate lyase. Activity of citrate lyase, very low in normal breast (0.0017 mumol/min/g of tissue) rose gradually to 0.039, 0.072 and 0.258 mumol/min/g of tissue in localized fibrocystic disease, fibroadenomas and carcinomas respectively. These data support the idea that citrate lyase may play an important role in lipogenesis in hyperplastic human breast tissues.

Vitamin A, zinc and lung cancer.

Abstract: Serum vitamin A concentration were measured in 26 newly diagnosed lung-cancer patients and found to be significantly lower than those of patients of similar age with either non-malignant lung or non-lung diseases. The levels of vitamin A in the lung-cancer patients, but not in the controls, were significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver.

Surface phenotyping, histology and the nature of non-Hodgkin lymphoma in 157 patients

Abstract: In a study of 157 patients with lymphoid malignancy, the phenotype of the tumour cells was correlated with the histological classification of the tumour using the Rappaport and the Kiel classifications. The markers used included E, Fc gamma, Fc micron (IgM) and C3d rosetting, estimation of SIg and CyIg, and tests for the expression of HTLA, Ia and ALL. Repeat biopsy specimens were studied in 23 of these patients. The phenotypic features of lymphoblastic malignancy indicated B-cell, T-cell and ALL-positive null-cell tumours in this group. Immunoblastic lymphomas were predominantly of non-capping B-cell type, but T-cell immunoblastic lymphoma occurred in 2 patients. Immunoblastic lymphomas of receptor-silent cells occur, and are ALL- and HTLA-negative. In the category of diffuse, poorly differentiated lymphocytic lymphomas, most cases are of centroblastic and centrocytic tumour of diffuse type, but pure centrocytic tumours and centroblastic tumours occur. The dominant phenotype in this group is of B cells expressing C3d receptors. Nodular poorly differentiated lymphocytic lymphomas (Rappaport) are classified as centroblastic and centrocytic follicular (Kiel) and most express SIg+ C3d+ phenotype. The frequency of this phenotype appeared the same in both diffuse and nodular poorly differentiated lymphocytic neoplasms. The Rappaport group of diffuse well-differentiated lymphocytic lymphoma includes 2 Kiel categories, malignant lymphoma lymphocytic, and malignant lymphoma lymphoplasmacytoid. Cells of the former tumour were considered to be immature B cells resembling those seen in CLL, and characteristically expressing SIg weakly, with a high frequency of single kappa light chain. Cells of the latter tumour are by contrast mature, and are related to the centroblastic and centrocytic follicular tumour by their histogenesis and phenotypic features. Repeat biopsy examinations indicate that T-cell predominance occurs in the prodromal phase of B-cell-predominant tumours of SIg+ C3d+ phenotype. It is concluded that non-Hodgkin lymphoma can be divided into 2 categories: (1) tumours of immature immunologically incompetent cells of lymphoblastic histology and with phenotypic features akin to T, B and Null-cell ALL, and (2) tumours of differentiated lymphocytes expressing the phenotypic features of B lymphocytes, with maturation arrested at one of several stages of an antigen-dependent immune response.

Serum testosterone and dihydrotestosterone in carcinoma of the prostate.

Abstract: Serum testosterone (T) and dihydrotestosterone (DHT) were measured by a sensitive and reliable radioimmunoassay in 42 normal subjects and 33 age-matched patients with carcinoma of the prostate. The mean +/- s.e. for serum testosterone in normal subjects was 16.74 +/- 0.76nM and the corresponding value for patients with carcinoma was 20.94 +/- 1.48nM. Statistical analysis of the results showed a significant increase in T level in patients with carcinoma of the prostate (P less than 0.01). In contrast, there was no difference in DHT concentration between the two groups, values being 2.43 +/- 0.09 and 2.06 +/- 0.09nM for normal subjects and patients respectively. The means +/- s.e. for T/DHT ratio in controls and patients were 6.8 +/- 0.2 and 12.8 +/- 1.3 respectively. The difference was highly significant (P less than 0.001). The wide range of variation for T in patients with carcinoma would suggest that although mean T is higher in these patients, this measurement alone is of little practical value, whereas T/DHT ratio is a more reliable parameter in evaluating the androgen changes in these patients. The significance of these findings in relation to the aetiology of the disease is discussed.

Carcinogenicity of betel quid ingredients: feeding mice with aqueous extract and the polyphenol fraction of betel nut

Abstract: Male mice of inbred strains Swiss and C17 were fed daily 5 times a week by intragastric tube 0.1 ml of betel-nut aqueous extract, betel-leaf aqueous extract and the polyphenol fraction of betel nut. Male mice of corresponding strains fed 0.1 ml of distilled water served as controls. Treated and control mice were kept under observation and killed when moribund. Betel-nut aqueous extract induced tumours of the gastrointestinal tract in 58% Swiss mice and 25% C17 mice. The polyphenol fraction by the same route induced tumours at other sites in 17% of the mice. Betel-leaf aqueous extract failed to induce any tumour in the treated mice, which supports an earlier report of the lack of any carcinogenic principle in betel leaf, an essential constituent of betel quid. Results are discussed in relation to the relevant literature.

Thromboplastic and fibrinolytic activities of cultured human cancer cell lines.

Abstract: Thromboplastic and fibrinolytic activities of 14 lines of cultured human cancer cells were estimated by modified Astrup's methods. High tissue thromboplastic activity was found in one line of urinary-bladder cancer, 2 lines of gastric cancer and one line of lung cancer, but no activity was found in 6 lines of lung cancer. High fibrinolytic activity was noted in one line of gastric cancer and 2 lines of lung cancer, but no activity was seen in 6 lines of lung cancer and one line of gastric cancer. No plasmin activity was found. The tumour cell lines could be classified into 3 groups on the basis of the 2 activities. Cancer cell lines could also be classified into 2 groups: with high or low release of thromboplastin into culture media. Fibrinolytic activity was found in the culture media of all cell lines with high fibrinolytic activity. Fibrinolytic activity, but not thromboplastic activity, seemed to be influenced by the constituents of culture media. No definite correlation was found between the 2 activities and the histological types of the parent tumours of the cultured cells.

Cancer of the prostate: early diagnosis by zinc and hormone analysis?

Abstract: Zinc, testosterone and dihydrotestosterone concentrations have been measured in normal prostatic tissue and in specimens obtained from untreated patients with benign prostatic hyperplasia (BPH) and carcinoma of the prostate (CaP). The metal--androgen relationship was examined and related to the pathological condition of the patients. The evidence suggests that discriminant analysis combining the hormonal data into a single variable is a reliable test for distinguishing between BPH and CaP patients. We have observed that the high Zn values found in BPH specimens were always associated with a DTH:T ratio greater than 1. Androgen tissue ratios less than 1 were characteristic of all CaP specimens, and these were usually preceded by a reduction in prostatic Zn concentration. Since these patterns, particularly those associated with neoplasia, precede the clinical manifestations, they may be used as an index for predicting the onset of carcinoma in the prostate gland. They may also be of value in monitoring the progress of the disease.

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients.

Abstract: The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label.

Asbestos and Disease

Abstract: Anthracycline analogues, such as adria-mycin, have been studied in many countries since its original discovery in Italy, and the U.S. contribution to this field by R. S. Benamin reviews the more recent work. The clinical use of adriamycin is not as frequent in Japan as in Europe and the U.S., being replaced to some extent by mitomycin C. However , H. Furue and T. Komita have reviewed the Japanese application of this agent. Specialized papers of macromomycin aclacino-mycin and neocarzinostatin also appear. A paper by Y. Sakurai, apparently out of context with the main theme of the book, discusses some of the synthetic analogues of nitrosoureas, alkylating agents, antimetabo-lites and platinum complexes under present study in Japan. The whole book is a most useful addition to the library of both students and practitioners of oncology. As with many such books, however , the lack of an index is inexcusable. Its value could have been immensely enhanced by even the shortest listing, of drug and tumour data contained within it. This is the second edition of an already highly regarded text. The subjects presented are wide-ranging, in order to cover material relevant to Diagnostic Radiology and Nuclear Medicine, as well as to Radiotherapy. Modifications in this edition include an expansion of the section on carcinogenesis and genetic effects, with a discussion of risk versus benefit which is similar to the ideas embodied in the new ICRP recommendations. Also, for the radiotherapist, sections on sensitizers and hyperthermia have been expanded in the light of much new information, and the sections on high LET and human tumour kinetics have been updated. On the radiotherapy sections, the reviewer has a few comments. The mathematical reason why 37% survival is chosen as a parameter for defining the slope of cell-survival curves is not given, and it could help students in their understanding. In discussing LD50 endpoints, e.g. for mouse lung, the rather ambiguous statement that a dose-response curve is not obtainable may surprise many radiotherapists who recognize such curves for the incidence of complications or recurrence. The rationale for low-dose-rate radiotherapy includes reoxygenation and overall time, but the still-controversial facet of a reduced cellular \"oxygen effect\" is not mentioned. The phrase \"thermal tolerance\" is used here and widely by others to denote acquired resistance to heat after prior heating. This conflicts with the accepted meaning of tolerance in radiotherapy, and can be a source of …

Histological grade and other prognostic factors in relation to survival of patients with breast cancer.

Abstract: Records of 3085 patients registered with breast cancer at the Mersey Regional Cancer Registry have been analysed to evaluate the relative importance of possible prognostic factors. In a subgroup of 1759 patients, clinical stage and histological grade are shown to be strongly related to survival after treatment. In addition histological grade is related to the distribution of times to death after treatment. The results of this and 3 other studies have implications for the design and analysis of clinical trials in the primary treatment of breast cancer.