Showing papers in "International Journal of Cancer in 1987"

A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth.

Abstract: An immortal line of pigmented melanocytes, "melan-a", has been derived from normal epidermal melanoblasts from embryos of inbred C57BL mice. The conditions favouring proliferation of these cells largely resemble those for normal, non-established mouse melanoblasts and melanocytes, and include a low extracellular pH and the presence of a tumour promoter, tetradecanoyl phorbol acetate (TPA) or teleocidin. Melan-a cells have the diploid chromosome number and do not form tumours in syngeneic or nude mice. They are therefore the first known line of non-tumorigenic mouse melanocytes, although an aneuploid melanocyte line of untested tumorigenicity has been reported (Sato et al., 1985). Melan-a cells are syngeneic with the B16 melanoma and its sublines, and provide an excellent parallel non-tumorigenic line for studies of the cellular and molecular basis of melanoma malignancy.

Lung cancer among Chinese women

Abstract: A case-control stud/involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smok- ing was a strong risk factor, but accounted for only about one- fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also re- ported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

Characterization of human ovarian carcinoma‐associated antigens defined by novel monoclonal antibodies with tumor‐restricted specificity

Abstract: Three new monoclonal antibodies (MAbs) (MOv16, MOv18 and MOv19) were raised against human ovarian carcinoma. To obtain more specific reagents than those produced so far, we adopted the following experimental approach which consisted of: the selection of a poorly differentiated ovarian carcinoma which was unreactive with all the MAb previously selected in our laboratory; and the application of a particular immunization protocol. The reactivity of the selected MAbs was studied by solid-phase RIA on live and fixed cells from tumor cell lines and by immunofluorescence on frozen sections from surgical specimens. The MAb MOv16 reacted with 60% of ovarian carcinomas as well as with a high percentage of other carcinomas and with some normal tissues. In contrast, MOv18 and MOv19 appeared to have restricted specificities for ovarian carcinomas and cystadenomas. Reactivity on other carcinomas was only observed in a few cases and no reactivity was found on non-epithelial tumors or normal tissues. Immunoprecipitation experiments indicated that MOv16 recognizes a 48-50-kDA protein, whereas MOv18 and MOv19 both identify a 38-40 kDA glycoprotein band. Cross-competition experiments, together with a double-determinant immunoradiometric assay which uses MOv18 as catcher and MOv19 as tracer, suggested that they recognize different epitopes carried by the same molecule. The affinity constants of MOv18 and MOv19 were estimated to be in the range of 10(8)-10(9) M-1. Taken together, the properties of these antibodies, their restricted ovarian tumor specificities and relative high affinity constants, suggest that they could represent promising tools for in vivo applications.

A classification scheme for childhood cancer.

Abstract: The International Agency for Research on Cancer (IARC) is sponsoring a worldwide study of childhood cancer incidence. Cancers in children are highly specific and differ in many ways from cancers found in adults. Data for the international study will be presented according to the classification scheme described below which has been devised specifically for use with paediatric cancers. The features of this scheme are: (1) it is based on the International Classification of Diseases for Oncology (ICD-O); (2) diagnostic groups are defined mainly in terms of morphology; (3) the common types of childhood cancer are individually specified; (4) certain other rare conditions of interest are distinguished; (5) it provides for flexibility of data presentation with respect to amount of detail; (6) all possible combinations of ICD-O morphology and topography codes are included; and (7) the maximum number of codes has been allocated to specific categories. There is a great need for standardization in the classification of childhood cancers and we propose that the scheme be used for presentation of incidence data for results of aetiological and other related studies of cancer in children.

Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international collaborative study among cancer registries.

Abstract: Eleven population-based cancer registries tabulated second cancers among 133,411 patients diagnosed with testicular cancer, ovarian cancer or Hodgkin's disease between 1945 and 1984 Overall, 3,157 second cancers were observed, as compared with 2,420 expected at least one year after the first cancer Survivors of testicular and ovarian cancer experienced 30% and 20% more cancers respectively than the general population comparison group, and patients previously diagnosed with Hodgkin's disease had an 80% excess of cancer No information was available either on treatment for the first cancer, or other risk factors However, temporal patterns in the risk of specific second cancers were analysed, with particular reference to the possible role of therapy for the first cancer Leukaemia of the acute or non-lymphatic type, which has been previously linked to alkylating agent therapy, occurred in excess following all 3 first cancers, as did non-Hodgkin's lymphoma (overall relative risks of 61 and 18 respectively, with considerably higher relative risks following Hodgkin's disease) Other cancers for which important and plausibly therapy-induced excesses occurred were lung cancer following Hodgkin's disease (relative risk 19), breast cancer following Hodgkin's disease (relative risk 14) and bladder cancer following ovarian cancer and Hodgkin's disease (relative risks 17 and 22 in women, respectively) Rarer sites at which striking excesses occurred were the salivary gland, thyroid, bone and connective tissue There were smaller, but clear excesses for cancers of the rectum and colon following ovarian cancer and testicular cancer, skin cancer following Hodgkin's disease, and kidney cancer following ovarian cancer Overdiagnosis, misclassification of metastases and confounding by other risk factors were all considered as explanations of observed excesses Nonetheless, it appeared that there are clear excess risks for cancers other than acute leukaemia which must be ascribed to therapy for the first cancer, especially in view of the possible under-reporting in registry material Case-control studies are under way to provide information on the role of specific aspects of therapy

Increased prevalence of human papillomaviruses in the lower genital tract of pregnant women

Abstract: In order to evaluate the influence of pregnancy on the presence of human papillomavirus (HPV) in the lower female genital tract, cervical smears of 92 pregnant and 96 non-pregnant women, matched by age, were examined for the presence of HPV-DNA by means of Southern blot hybridization. All patients had negative PAP smears. Twenty-six (28%) of the pregnant women and 12 (12.5%) of the non-pregnant women were positive for HPV. HPV 16 accounted for 42% of all positive pregnant cases and only 25% of the positive non-pregnant cases. Smears of pregnant patients contained more than 10 pg viral DNA in 45% of the cases against 20% in the non-pregnant group. HPV 16 showed the most active replication in both groups. This study demonstrates an increased prevalence of HPV (preferentially of HPV 16) and a higher replication rate of viral DNA during pregnancy.

The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA.

Abstract: Immunologic studies of Epstein-Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non-keratinizing nasopharyngeal carcinoma (NPC). Patients with the well-differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well-differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well-differentiated specimens was cloned into a cosmid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.

Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland.

Abstract: A study was carried out in Swaziland to assess the relationship between aflatoxin exposure, hepatitis B infection, and the incidence of liver-cell carcinoma, which is the most commonly occurring malignancy among males in Swaziland. Levels of aflatoxin intake were evaluated in dietary samples from households across the country, and crop samples taken from representative farms. Prevalence of hepatitis B markers was estimated from the serum of blood donors, and liver cancer incidence was recorded for the years 1979-83 through a national system of cancer registration. Across 4 broad geographic regions, there was a more than 5-fold variation in the estimated daily intake of aflatoxin, ranging from 3.1 to 17.5 micrograms. The proportion of HBV-exposed individuals was very high (86% in men), but varied relatively little by geographic region; the prevalence of carriers of the surface antigen was 23% in men, and varied from 21 to 28%. Liver cancer incidence varied over a 5-fold range, and was strongly associated with estimated levels of aflatoxin. In an analysis involving 10 smaller subregions, aflatoxin exposure emerged as a more important determinant of the variation in liver cancer incidence than the prevalence of hepatitis infection. Aflatoxin estimates from crop samples appeared to be a reasonable surrogate for dietary measurements. A comparison with dietary aflatoxin levels measured in an earlier survey in Swaziland suggested that programmes aimed at reducing contamination levels had had some success.

Production of stable cytolytic T-cell clones directed against autologous human melanoma.

Abstract: We have attempted to optimize the production of stable human cytolytic T lymphocyte clones directed against autologous melanoma cell lines. MLTC were restimulated every week with irradiated melanoma cells in medium containing human serum and IL-2. After 21 to 35 days, in 5 out of 6 patients, these cultures expressed a preferential cytolytic activity against the autologous melanoma cells, as compared to autologous EBV-B cells or NK target K562. Limiting dilution of MLTC responder cells was performed at times varying from days 7 to 28, in medium containing IL-2 and allogeneic EBV-B cells as feeders. Approximately 1% of these responder cells gave rise to CTL clones that lysed the autologous melanoma cells, but did not lyse K562 or autologous B cells. It was possible to maintain in culture for several months a large number of CTL clones that retained this specificity with high activity, and multiplied more than 5-fold every week. Some of these CTL clones were dependent on the presence of the autologous melanoma cells for their growth. With one melanoma, the use of autologous CTL clones made it possible to identify 3 different antigens on the tumor cells.

Epidemiological and environmental evidence of the health effects of exposure to erionite fibres: a four-year study in the cappadocian region of Turkey

Abstract: An environmental and epidemiological study has been carried out in Central Cappadocia, Turkey, aiming at investigating the relationship between exposure to naturally occurring erionite fibres and the reported high incidence of malignant mesotheliomas. Airborne fibre levels are generally low but show a higher proportion of erionite fibres in the villages affected by malignant disease than in a control village. The same pattern is confirmed by analysis of the fibre content in lung tissues of sheep from several villages, both affected and unaffected by malignant disease. The 3 villages with the highest proportion of erionite fibres have high rates of malignant pleural mesothelioma, malignant peritoneal mesothelioma and lung cancer. No case of malignancy for the same sites has been reported during the study period from the control village. The relationships between these findings and their consistency with the results from experimental studies indicate erionite fibres as a carcinogenic agent, although some aspects of the exposure are not fully clarified.

A case-control study of diet and gastric cancer in northern Italy.

Abstract: Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for giistric cancer. Dietary histories concerned the frequency of consumption per week of 29 selected food Items (including ttie major sources of starches, proteins, fats, fibres, vitamins A and C, nitrates and nitrites in the Italian diet) and subjective stores for condiments and salt intake. Pasta and rice (the rajor sources of starch), polenta (a porridge made of maize) and ham were positively related with gastric cancer risk, whereas green vegetables and fresh fruit as a whole (and specifically citrus fruit) and selected fibre-rich aliments (such aii whole-grain bread or pasta) showed protective effects on giistric cancer risk. Allowance for major identified potential distorting factors (chiefly indicators of socio-economic status) reduced the positive association with pasta or rice consumption, but did not appreciably modify any of the other risk estimates. When a single logistic model was fitted including all food items significant in univariate analysis, the 3 items remaining statistically significant were green vegetables (rel-acive risk, RR = 0.27 for upper vs. lower tertile), polenta (f;R = 2.32) and ham (RR = 1.60). Indices of beta-carotene and ascorbate intake were negatively and strongly related with giistric cancer risk, but the association with these micronu-trients was no longer evident after simultaneous allowance for various food items. An approximately 7-fold difference in risk was found between extreme quintiles of a scale measuring major positive and negative associations.

Expression of the c‐erbB‐2 protein in normal and transformed cells

Abstract: Two synthetic peptides from the predicted sequence of the human c-erbB-2 protein were synthesized and used to raise antisera in rabbits. The sequences chosen were identical to those in the homologous rat c-neu protein. The antibodies produced reacted with the immunizing peptides in ELISA but showed little or no cross-reaction with the partly homologous peptides found in equivalent positions in the human EGF receptor. Both antipeptide antibodies, and a monoclonal antibody (MAb) specific for the rat new protein, immuno-precipitated a 185-kDa protein from 35S-methionine-labelled lysates prepared from a rat cell line known to express high levels of the c-neu protein. The antipeptide antibodies also recognized a protein of the same size in Western blots. In addition, both antipeptide antibodies immunoprecipitated a 190-kDa protein from labelled cell lysates prepared from human and monkey cells. Antibodies to one of the peptides, which showed no detectable cross-reaction with human, rat or monkey EGF receptor, were used to examine the expression of the c-erbB-2 protein on a variety of cultured cell types. Eleven transformed, I non-established and 2 immortalized cell types were examined by immunoprecipitation for their level of expression of the c-erbB-2 protein and of the EGF receptor. The numbers of EGF receptors varied widely between different cell lines, whereas the level of the c-erbB-2 protein, which was found on all of the cell types examined, was more constant. The number of c-erbB-2 molecules present was estimated by autoradiography to be about 100,000 per cell. The antibodies were then used to examine the location and level of expression of the human c-erbB-2 and rat c-neu proteins in normal tissues. Immunohistochemical staining showed that the c-erbB-2 protein was highly expressed in rat kidney proximal tubules and loop of Henle. The c-enbB-2 protein was also present on normal human epithelial cells but in some cases with a different distribution to that of the EGF receptor.

Pretreatment prognostic factors and scoring system in 407 small‐cell lung cancer patients

Abstract: In 407 patients with small-cell lung cancer (SCLC), 61 pretreatment variables were evaluated in a Cox multiple regression analysis to assess their prognostic value. All patients received short-term intensive regimens (cyclophosphamide, etoposide and methotrexate or ifosfamide and etoposide, both followed by thoracic irradiation if complete response was noted). Lactate dehydrogenase (p = 0.0001), tumour stage (p = 0.0001), serum sodium (p = 0.0009), pretreatment Karnofsky performance score (p = 0.0121), alkaline phosphatase (p = 0.0186) and serum bicarbonate (p = 0.0321) were the important prognostic factors. Once these variables were taken into account no other variable provided additional prognostic information. A simple scoring system (“Manchester Score”) using these variables was established and shows little loss of information compared to the Cox analysis. The score distinguishes 3 prognostic groups, the best of which contains all long-term survivors, whereas the bad prognostic group contains no patient surviving longer than one year. The scoring system may help to design new treatment strategies and may also facilitate the comparison of different studies.

Specific chromosome aberration in human renal cell carcinoma

Abstract: Using G-banding technique, the chromosomes were studied in short-term cultures of 25 primary renal-cell carcinomas (RCC). Phytohaemagglutinin-stimulated peripheral blood lymphocytes or normal kidney cells of the same patients growing in primary cultures were analysed to define the constitutional karyotype. The modal chromosome number of 23 RCC's was found to be pseudo-diploid or near-diploid with only few structural rearrangements, 22 of the RCC's showed an aberration of chromosome 3, deletion of 3p, or translocation of different chromosome segments to the deleted chromosome 3, leading to the loss of variable segments of chromosome 3. The break-points in rearrangements of chromosome 3 clustered in the region 3p11.2-p13. Shortest-region overlap analysis localized a consistent change to a small area of 3p13-pter. In 8 of the 25 RCCs, the rearrangement of chromosome 3 was the only karyotype change determined, and 4 other tumours had only one chromosomal rearrangement in addition to the aberration of chromosome 3. These results suggest that the aberration of chromosome 3 is the first cytogenetic event in the clonal evolution of RCCs. Translocation 3;5 was preferentially involved in the rearrangements between chromosome 3p and other chromosomes. The breakpoint on chromosome 3 was constant at p13, but the breaks on chromosome 5 varied between bands q11.2 and q22. Monosomy 14 was observed in 10 cases and loss of Y chromosome was detected in 6 of 14 tumours obtained from male patients. Since the normal somatic cells were free of chromosomal aberrations, one may conclude that the loss of 3p13-pter segment is an acquired, consistent chromosomal aberration which marks human RCCs.

Analysis of the inhibition of tumour metastasis by sulphated polysaccharides

Abstract: Lung metastases resulting from the intravenous (i.v.) injection of cells from the rat mammary adenocarcinoma 13762 MAT were significantly reduced by a variety of sulphated polysaccharides, the most effective being heparin, fucoidan and Carrageenan lambda. Although all the inhibitory polysaccharides were anticoagulants, it is unlikely that anticoagulation is the total explanation of their antimetastatic effect because: (i) heparin preparations from 2 different suppliers, although exhibiting comparable anticoagulant activities, differed 10-fold in their antimetastatic capability; (ii) certain sulphated polysaccharides consistently gave a 30% difference in the number of metastatic lesions, yet exhibited identical anticoagulant activity; and (iii) the entrapment of 13762 MAT cells in the lung was not impaired by heparin or fucoidan. It was more probable that the sulphated polysaccharides were interfering with the passaging of tumour cells across the capillary wall as heparin significantly inhibited metastasis when injected up to 3 hr after lodgement, and heparin and fucoidan caused a gradual loss of tumour cells from the lung which only became apparent greater than 1 hr following cell lodgement. The data did not eliminate the possibility that tumour cell adhesion to the endothelium occurred via sulphated polysaccharide recognition. A negative correlation existed between the sulphated polysaccharides that bound to the surface of the tumour cells and those that inhibited metastasis.

Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour-cell-derived heparanases

Abstract: Recent studies in this laboratory demonstrated that several sulphated polysaccharides can inhibit metastasis of the rat mammary adenocarcinoma 13762 MAT, probably by preventing the passage of tumour cells through the walls of blood vessels. In order to directly test this possibility, 13762 MAT cells were cultured with (35S)O4(=)-labelled subendothelial extracellular matrices (ECM) and ECM degradation was monitored in either the presence or absence of different sulphated polysaccharides. Degradation products were detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis and subsequent autoradiography. The 5 sulphated polysaccharides that had previously been shown to possess anti-metastatic activity were potent inhibitors of the degradation of subendothelial ECM by 13762 MAT cells. In contrast, of the 4 polysaccharides tested that failed to inhibit metastasis, 3 had no effect on ECM breakdown and one (carrageenan-kappa) was substantially less effective at inhibiting ECM degradation than the anti-metastatic preparations. It was also shown that 13762 MAT cells produce a heparan sulphate-specific glycosidase (heparanase) that degrades the heparan sulphate side-chains of the ECM, the action of this enzyme rather than that of other ECM-solubilizing enzymes being inhibited by the antimetastatic sulphated polysaccharides. Additional experiments indicated that the anti-coagulant activity of the polysaccharides probably plays a minor role in their anti-metastatic effects since heparin, almost completely depleted (98-99.5%) of heparin molecules with anti-coagulant activity by passage over an anti-thrombin III column, retained its ability to inhibit 13762 MAT heparanases and was almost as effective as unfractionated heparin at inhibiting tumour-cell metastasis. Collectively, these data suggest that sulphated polysaccharides inhibit the metastasis of 13762 MAT cells by inhibiting tumour-cell-derived heparanases involved in the penetration of the vascular endothelium and its underlying basement membrane by tumour cells.

Tumor progression in human malignant melanoma: Five stages defined by their antigenic phenotypes

Abstract: The antigenic profile of melanocytic cells in the course of local and systemic tumor progression of human malignant melanoma was investigated by the reactivity of a panel of monoclonal antibodies (MAbs) in frozen sections of histologically defined melanocytic lesions. Specific antigenic phenotypes made it possible to distinguish 5 groups of lesions which could be ranked in relation to each other due to the sequential acquisition or loss of progression markers. On this basis, a scheme of antigenic changes which accompany the stepwise transformation of normal skin melanocytes into highly malignant metastatic melanoma cells is proposed. The steps of tumor progression identified solely by phenotyping with MAbs were in complete concordance with the concept of melanoma progression derived from histological, statistical and clinical analyses. Furthermore, our finding that the expression of gp89 as well as HLA-DR antigens can be induced by interferon-gamma in vitro provides evidence that immune interferon may play a role in the regulation of genes leading to phenotypic changes in progressing melanoma cells.

Hot beverages and oesophageal cancer in southern Brazil: a case-control study

Abstract: There is a cluster of high-incidence areas of oesophageal cancer in south-eastern South America, including Southern Brazil, Uruguay and parts of Argentina. The present case-control study investigated the hypothesis that this may be due to the drinking of mate, a traditional beverage drunk at a very high temperature, and also studied the role of other known risk factors such as alcohol and tobacco. Cases (171) and age- and sex-matched controls (342) were recruited from hospitals in the State of Rio Grande do Sul in Southern Brazil. The crude odds ratio for daily mate drinkers was 1.92 relative to those drinking less frequently than daily (p = 0.006). Other risk factors included the drinking of cachaca (a sugar cane spirit), smoking, rural residence, low fruit consumption and high intake of meats. After adjustment for these variables through conditional logistic regression, the odds ratio associated with daily mate drinking was reduced to 1.47 (90% CI = 0.87-2.50). Although the study failed to provide evidence of a strong association between mate and oesophageal cancer, the cluster of high rates could be explained by relative risks of the magnitude observed. This is due to the fact that approximately 70% of adult males and 50% of females are daily drinkers. In addition, this study revealed that alcohol, tobacco smoking and rural residence are the main risk factors for oesophageal cancer in this population and the fruit consumption confers some degree of protection.

Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors.

Abstract: Five out of 6 cell lines derived from metastatic melanoma lesions grew in a chemically defined base medium consisting of a mixture of calcium-supplemented MCDB 153 and L 15 media in the absence of any polypeptide growth factors. In contrast, under these conditions no growth was seen in any of 5 primary melanoma cell lines tested, including 2 cell lines from patients whose metastatic cells proliferated well in base medium. Growth stimulation of all 11 melanoma cell lines by epidermal growth factor (EGF), transferrin, insulin, and insulin-like growth factor (IGF)-1 alone and in various combinations was studied. Insulin represented the strongest single growth factor for primary and metastatic melanoma cell lines. The metastatic cell lines remained growth-responsive to EGF, insulin and transferrin and responded more vigorously to these exogenously provided mitogens than the primary cell lines. No synergistic or additive growth effects of insulin, transferrin, or EGF for primary and metastatic cell lines were observed. Cross-linking studies with 125I-IGF-1 demonstrate surface expression of the type-I IGF receptor on melanoma cells. Growth stimulation by insulin and IGF-1 was inhibited by adding to the culture medium a monoclonal antibody to the type-I IGF receptor. Our studies indicate that IGF-1 and insulin are major growth factors for melanoma cells and act via the type-I IGF receptor.

Presence of circulating antibodies against cellular protein p53 in a notable proportion of children with B-cell lymphoma.

Abstract: Serum samples taken from children bearing a wide variety of tumors were screened for the presence of circulating antibodies against the cellular tumor antigen p53. There was a significant correlation (p less than 0.001, n = 119) between the presence of such antibodies and the occurrence of cancer; 12% of the sera tested were positive. These sera were derived from children with a wide range of tumor types. In particular, 21% of the sera obtained from children suffering from a B-cell lymphoma contained anti-p53 antibodies. We were not able to establish a correlation between the secretion of p53-reactive antibodies and any other parameters, such as the age or sex of the child, presence of metastasis, stage or prognosis of disease, or treatment regimen. These results therefore show that the development of p53 immunogenicity is associated with a wide range of neoplastic diseases in children, and in particular with the presence of a B-cell lymphoma.

Colorectal polyps and diet: a case-control study in Marseilles.

Abstract: This study investigates the differences in usual past diet between 252 subjects with newly diagnosed adenomatous or villous polyps of the colon and rectum and a group of 238 hospital controls. Cases and controls were interviewed in hospital by 3 nutritionists using a dietary history questionnaire focused on the diet during the preceding year. Nutrient intake was estimated by means of ad hoc food tables adapted from French and British tables. Out of 16 food groups considered in the analyses, the cases reported lower consumption of oil and potatoes and higher consumption of sugar added to food and drink. Among nutrients, we found that cases had a lower consumption of carbohydrates (not taking into account added sugar), potassium, magnesium and vitamin B6. We found a slightly lower intake of fibre and a slightly higher intake of saturated fat among cases, though neither was statistically significant. Intake values for fibre and for carbohydrates were highly intercorrelated and, due to measurement errors, the effect of one may be masked by the other and vice versa. The hypothesis that some components of carbohydrates (starches, fibre and natural sugars but not added sugar) play a protective role in relation to the biology of tumours of the intestinal tract is considered in further multivariate analyses and in the "Discussion".

In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells.

Abstract: The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.

Cellular heterogeneity and drug resistance in two ovarian adenocarcinoma cell lines derived from a single patient.

Abstract: Two ovarian cell lines were derived from the ascites of a patient before and after the onset of resistance to chemotherapy involving cis-platinum, chlorambucil and 5-fluorouracil. Characterization of these lines shows them to have various features in common and some significant differences. Cytologically the lines cannot be distinguished and they both contain high concentrations of oestrogen receptor. However, they do differ with respect to their growth characteristics, karyotype, glutathione content and sensitivity to cis-platinum. The karyotypes of the 2 lines show several marker chromosomes in common but the resistant line contained a chromosome 8 and a 17 which were absent from the earlier sensitive line. This suggests a clonal origin with subsequent divergence to a heterogeneous population.

High incidence of EGF receptor hyperproduction in esophageal squamous-cell carcinomas.

Abstract: EGF receptor levels were investigated in esophageal squamous-cell carcinoma tissues from 31 patients. Twenty-two (71%) of these cancer tissues exhibited significantly higher 125I-EGF binding activity than normal mucosa in the adjacent non-cancerous tissues. These EGF receptor levels were then compared on the basis of pathological findings including lymph-node metastasis, depth of invasion, differentiation type, vascular invasion, infiltration and location of the lesion. Unlike previous reports on breast and bladder cancers, our study showed no obvious correlation between these pathological characteristics and the EGF receptor levels in esophageal carcinomas. Immunohistochemical staining with the anti-EGF receptor monoclonal antibody detected EGF receptors in squamous cells of the cancer tissues as well as in the basal cells of nearby normal epithelium. Since the basal cells have proliferative potential in the esophagus, the increase in EGF receptor levels in these cells may possibly be associated with the development of human esophageal squamous-cell cancer.

Monoclonal integration of HTLV-I proviral DNA in patients with strongyloidiasis

Abstract: The relationship between strongyloidiasis and HTLV-I was investigated in Okinawa, an area where both conditions are endemic. Thirty-six patients with strongyloidiasis were seropositive for HTLV-I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV-I proviral DNA in their blood lymphocytes, a condition designated as "smouldering" adult T-cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV-I could predispose to hyperinfestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co-factors leading to the development of ATL.

Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3

Abstract: Monoclonal antibody (MAb) B72.3 has been previously shown, by in vitro assays, to have a high degree of specificity for carcinomas of the colon, ovary and breast versus normal adult tissues. B72.3 IgG was labelled with 131I and injected i.v. into 20 patients with known or suspected colorectal cancer. All patients subsequently underwent surgical exploration, with tumor and selected normal tissues removed for staging purposes. The selective localization of 131I-MAb B72.3 IgG was demonstrated in biodistribution studies in which the % ID/g of each tumor was compared with that of the normal tissues, thus providing a relative RI for each lesion. Of the tumor lesions, 70% (99/142) had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues), and 31% of the tumor lesions had RIs of over 10. Only 12 of 210 (6%) histologically normal tissues had RIs of > 3; either these tissues were adjacent to or draining tumor masses or, as in the case of 2 patients, the high RI values were apparently due to deposition of immune complexes in the splenic tissues. Several parameters were studied to determine factors that might influence MAb localization. Whereas tumors of all histologic types localized the MAb, 31% of the well-differentiated mucinous carcinomas displayed tumor-to-normal ratios greater than 10, while less than 5% of the lesions of other tumor types demonstrated similar localization. The expression of the antigen (TAG-72) detected by MAb B72.3 in these tumors, as studied by immunohistochemical techniques using tissue sections, did not always correlate with the outcome of the MAb distribution. No differences in MAb uptake were observed among the carcinoma lesions from numerous anatomic locations, demonstrating the ability of i.v. administered B72.3 to reach all the tumor sites. Furthermore, autoradiographic studies of tumors showed good penetration of the MAb into the medial areas of the tumors, regardless of their size.

Shedding of GD2 ganglioside by human neuroblastoma.

Abstract: Substantial concentrations of the cell-surface glycosphingolipid, the disialoganglioside GD2, are uniformly present in human neuroblastoma tumors. This ganglioside can also be detected in the plasma of patients with neuroblastoma by direct thin-layer chromatographic analysis. Among 32 neuroblastoma patients in all clinical stages studied prior to the initiation of treatment, 27 (84%) showed measurably elevated plasma concentrations of GD2 (greater than or equal to 50 pmol/ml). The mean level (545 +/- 108 pmol/ml) was more than 50 times the normal plasma GD2 concentration of less than or equal to 10 pmol/ml. Circulating GD2 was not detected in the plasma of patients with the related, more differentiated tumors, ganglioneuroblastoma and ganglioneuroma, indicating an association of the shedding of this ganglioside with the undifferentiated phenotype. Circulating GD2 diminished in patients in response to therapy, and reappeared in patients whose disease recurred. The results suggest that the sequential determination of circulating GD2 will be of value in monitoring individual patients with neuroblastoma.

Influence of pregnancy and lactation on serum and breast fluid estrogen levels: implications for breast cancer risk.

Abstract: We investigated estrogen (estrone and estradiof) levels in serum and in nipple aspirates of breast fluid in relation to reproductive and menopausal characteristics in 104 normal women. In general, breast fluid and serum estrogen levels were not correlated and breast fluid estrogen levels were approximately 5 to 45 times higher than serum levels. Serum estrogen levels were lower in post-menopausal than in premenopausal women. In contrast, breast fluid estrogen levels were approximately the same in pre- and post-menopausal women. Breast fluid estrogen mean levels were lower in premenopausal parous women than in nulligravidous or nulliparous women whereas serum estrogen levels did not differ in these 3 groups. Breast fluid estrogen levels were positively correlated with months since last birth or since last breastfeeding. Estrogen levels were low in nipple aspirates of breast milk but gradually increased in breast fluid of non-lactating women over a period of several years after cessation of lactation. Serum estrogen levels did not increase with months since last breast-feeding. We were unable to evaluate the postpartum effect of pregnancy without lactation due to the small numbers of these subjects. The high concentrations of estrogen in breast fluid and the absence of a relationship to serum estrogen levels may explain why prior serum studies have I failed to link variations in serum estrogens with breast cancer risk. The prolonged low levels of breast fluid estrogens following full-term birth and lactation may, in part, provide a mechanism by which parity reduces breast cancer risk.

A new animal model for human colon cancer metastasis

Abstract: An animal model for human colon cancer metastasis is described in which spontaneously metastasizing colonic tumors are formed after injection of human colon cancer cells into the cecal wall of young athymic nude mice. Lymphatic and vascular invasion were demonstrated histologically after injection of both well- and poorly-differentiated cell lines, and metastases were found in a pattern similar to that of naturally occurring human colonic cancer. In contrast, little or no visceral organ involvement could be demonstrated after s.c. injection. Cells with increased liver-metastasizing potential were obtained by serial selection in this system. These cells had an enhanced ability to penetrate a reconstituted basement membrane in the presence of partially purified liver extract when compared to lung or brain extracts in a modified Boyden chamber assay. These results demonstrate the ability of human epithelial tumor cells to metastasize reproducibly in an animal model system, which may be useful for studying many aspects of the pathogenesis of cancer metastasis. In addition, it is suggested that local invasion by colon cancer cells may be influenced in part by tissue-specific factors.

Purified colony stimulating factors (G‐CSF and GM‐CSF) induce differentiation in human HL60 leukemic cells with suppression of clonogenicity

Abstract: Purified recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF) and purified native murine granulocyte-CSF (G-CSF) both induced differentiation in HL60 cells as evidenced by expression of granulocyte and macrophage membrane antigens, although this was not accompanied by morphological evidence of differentiation. Both types of CSF suppressed clonogenic HL60 cells with evidence of complete clonal extinction. The suppression of clonogenic HL60 cells was preceded in some experiments by CSF-stimulated proliferation of HL60 cells, and this was most evident in cultures containing low concentrations of fetal calf serum (FCS).