Showing papers on "Cancer published in 1976"

The clonal evolution of tumor cell populations

Abstract: It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.

Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer.

Abstract: Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days). Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with acvanced cancer.

Estrogens and Endometrial Cancer in a Retirement Community

Abstract: All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1), and that for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer. (N Engl J Med 294:1262–1267, 1976)

Liver-cell adenomas associated with use of oral contraceptives.

Abstract: During the past six years an increasing number of liver-cell adenomas in women were diagnosed, and we undertook a study of possible etiologic faciors, including use of oral contraceptives, in 42 women. There was a significant difference between cases and matched controls in mean months of oral-contraceptive use: 73.4 as compared to 36.2 (P<0.001). The women with adenomas look mestranol-containing pills much more commonly than the controls (P<0.0001). Hemorrhage into the tumor was often associated with the onset of menstruation in women taking oral contraceptives. Long-term use of oral contraceptives, especially those containing a high total dose of steroids or mestranol as the synthetic estrogen, should be balanced against risks of side effects of the drugs. (N Engl J Med 294:470–472, 1976)

A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin

Abstract: Extensive experience with isotransplants of 27 different tumours (leukaemias, sarcomata, carcinomata), all of strictly spontaneous origin in laboratory bred mice of low cancer strains CBA/Ht and WHT/Ht, has revealed no evidence of tumour immunogenicity. Of approximately 20,000 maintenance transplants, none failed and none regressed; of almost 10,000 carefully observed tumours arising from small or minimal inocula of tumour cells, none spontaneously regressed. The number of injected viable tumour cells required to give a 50% probability of successful transplantation (the TD50) ranged from approximately 1 cell to greater than 10,000 cells among the 27 tumours; high TD50 values, which were dramatically reduced by various procedures having no immunological significance, did not signify active "resistance" of the hosts. In the case of all of 7 randomly selected tumours, prior "immunization" of recipients with homologous lethally irradiated cells increased their tumour receptivity. Several experiments using various tumours failed to give evidence that immunity could be non-specifically induced or that a massive preponderance of lymphocytes from specifically sensitized mice could inhibit tumour transplantation or growth in vivo; no trace of "resistance" to tumour was adopted by isogeneic recipients of lymphocytes from regional nodes of tumour bearers. A limited review of the recent literature on tumour immunity shows that practically all the animal data presented in support of a general theory of tumour immunogenicity or to provide a basis for active clinical immunotherapy have been obtained from transplanted tumour systems which entail artefactual immunity associated with viral or chemical induction of the tumours or their allogeneic transplantation. It is suggested that isotransplants of spontaneously arising tumours are the only appropriate models of human cancer and that any genuine rapport between the animal laboratory and the clinic requires their exclusive use.

Melanomas of the eye and other noncutaneous sites: epidemiologic aspects.

Abstract: The Third National Cancer Survey, 1969-71, reported 432 patients with noncutaneous melanoma, 79% originating in the eye. As with skin melanoma, ocular tumors were more common in whites than blacks and predominated in females at younger ages and males after middle life. On the other hand, ocular melanoma did not show the strong North-South gradient seen with skin melanoma; this suggested no relation to sunlight exposure.

Morphological lesions associated with human primary invasive nonendocrine pancreas cancer.

Abstract: In 227 cases of human pancreas cancer (100 pancreatectomy specimens and 127 autopsies), pancreas duct epithelium not involved by invasive cancer was examined. Pancreas duct epithelium from 100 autopsies of patients with nonpancreatic cancer, matched by age and sex to the pancreas cancer autopsy cases, was used for control studies. The prevalence of squamous metaplasia, pyloric gland metaplasia, mucous hypertrophy, and focal epithelial hyperplasia was not greatly different in the two groups. Ductal papillary hyperplasia was three times more prevalent in pancrease cancer than in controls. Marked atypia occurred in 20%, and carcinoma in situ, in 18% of the pancreas cancer cases, but neither change was seen in the control cases. It is possible that focal epithelial hyperplasia was a precursor change but that it was overgrown by the cancer. Papillary hyperplasia could not be properly evaluated as a precursor lesion because of duct obstruction, but practically all cases of marked atypia and carcinoma in situ occurred in papillary lesions. Marked atypia and carcinoma in situ, by analogy to other cancers, would appear to be precursor lesions, and their presence in association with invasive cancer lends hope to the possibility that there is a significant, recognizable, in situ phase of the disease before invasive cancer occurs.

Antioxidants and cancer. Part VI. Selenium and age-adjusted human cancer mortality.

Abstract: The possible epidemiologic relationship between selenium occurrence and cancer mortality was studied in cities and states located in areas with different levels of selenium bioavailability. Statistically significant differences were found in age-specific cancer death rates among states with high, medium, and low selenium levels. The death rates for specific types of cancer showed a larger difference in males than in females in the states with high selenium levels. The greater difference between males and females may be related to sex difference or to the fact that males are heavier smokers and are aslo more likely to be exposed to industrial pollution. In the states with high selenium levels, there was significantly lower mortality in both males and females from several types of cancer, particularly the environmental problem indicators, such as gastrointestinal and urogenital types of cancer.

Menopausal Estrogens and Breast Cancer

Abstract: 1891 women given conjugated estrogens for the menopause were followed for 12 years (mean) for incidence of breast cancer. Overall, 49 cases were observed; 39.1 were expected on the basis of rates in the general population (relative risk = 1.3, P = 0.06). The relative risk increased with follow-up duration, progressing to 2.0 after 15 years (13/6.6, P = 0.01). The excess risk after 10 years was not due simply to prolonged estrogen use, since there was no clear dose-response relation to accumulated years of use. However, higher risk accrued to women using higher-dose tablets and those taking the medication on an other than daily basis. In addition, after 10 years of follow-up observation, two factors related to low risk of breast cancer, multiparity and oophorectomy, were no longer so related. Finally, estrogen use was related to an especially high risk of breast cancer among women in whom benign disease developed after they had started the drug.

Gastric cancer in Colombia. III. Natural history of precursor lesions.

Abstract: The premalignant process in the gastric mucosa was studied by gastroscopic surveys of Colombian populations, and the prevalence of superficial gastritis, chronic atrophic gastritis, and intestinal metaplasia was calculated for population samples having a very high gastric cancer risk (Narino), very low risk (Cartagena), and intermediate risk (Cali). The prevalence of individuals with normal mucosa in successive age groups was used to estimate "depletion" curves, which were taken as indicators of the dynamics of the premalignant process in each community. Differences corresponding to the geographic variation in stomach cancer risk were found: In the high-risk areas of Narino, around 75% of the population developed some type of gastritis by 45 years of age, whereas in the low- and intermediate-risk population of Cartagena and Cali, the proportion of such lesions did not exceed 50% at age 45 or thereafter. The effect of environmental factors in early life seemed to be important in determining the prevalence of lesions in each population.

Transplantation of human tumors in nude mice.

Abstract: Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.

Quantification of combined radiation therapy and chemotherapy effects on critical normal tissues

Abstract: In order to determine the modification of radiation effects on critical normal tissues which occurs with combinations of radiation and cancer chemotherapy, a review of laboratory and clinical data has been carried out. Information on 10 different normal tissues is available. It is clear that the antibiotic cancer chemotherapeutic agents are the most likely to enhance radiation injury, with increased levels reported in all tissues except the central nervous system. The second most common type of injury with combination therapy appears to occur with drugs causing injury to the normal tissue on their own, such as adriamycin in the heart and methotrexate in the central nervous system. Quantification of the dose-effect factor is only available on a limited number of tissues, and, primarily, in experimental animals. From these limited data, it is clear that dose-effect factors between 1.1 and 1.8 are seen, indicating that radiation doses must be reduced by 10-80% for the same level of injury when combined with chemotherapy. The augmentation of radiation damage by cancer chemotherapeutic agents is a serious problem in a wide range of tissues, but a problem which can be dealt with by accurate knowledge as to the dose-effect factor and appropriate modification of the radiation treatment.

Predicting response to endocrine therapy in human breast cancer: a hypothesis

Abstract: We hypothesize that the presence of progesterone receptors in human breast tumors may be a sensitive marker for predicting response to endocrine therapy. Progesterone receptors were found in 56 percent of tumors with estrogen receptors, but were absent in tumors without estrogen receptors. Preliminary clinical correlations show that only those breast tumors with progesterone receptors regressed after endocrine therapy.

Gastric cancer in Colombia. I. Cancer risk and suspect environmental agents.

Abstract: A case control study of patients discharged from hospitals revealed fourfold differences in geographic variation in stomach cancer risk within the Department of Narino (Colombia). Data from gastroscopic surveys of population groups, samples of water supplies, and urine and saliva in Narino also indicated a generally positive correlation among the following parameters: 1) gastric cancer risk, 2) prevalence of chronic atrophic gastritis and intestinal metaplasia, 3) nitrate content of well waters, and 4) nitrate excretion by the population. Urinary excretion reflected the ingestion of nitrates, and this implied a higher average intake of nitrates in the populations at high risk for stomach cancer. The Narino data could be construed as presumptive epidemiologic evidence for the role of nitrate availability in the etiology of stomach cancer.

Coeliac disease, gluten-free diet, and malignancy.

Abstract: Two hundred and two patients with coeliac disease or idiopathic steatorrhoea previously reported from this unit have been reviewed after a further 10 years of follow-up. Of 20 more deaths, 10 were due to malignancy. A separate study was made of all patients with histologically confirmed coeliac disease seen to the end of 1972 and followed up to the end of 1974. Twenty-one of the 43 deaths in this series were due to malignant tumours, of which 13 were reticulum cell sarcomas. There was no evidence that patients showing sub-optimal clinical response to gluten withdrawal or persisting falt jejunal biopsies were more prone to die of cancer. A gluten-free diet did not appear to be effective in preventing malignant complications, but a longer follow-up of patients will be necessary to provide a final answer to this question.

Environmental factors in cancer of the larynx. A second look

Abstract: During a retrospective case-control study of recent laryngeal cancer patients, several associated factors were studied to determine possible changes in the epidemiology of laryngeal cancer between 1956 and 1974. The large sex difference noted in the early survey (male: female ratio of 14.9:1) diminished considerably in the present sample (4.6:1) because more women are cigarette smokers in the cancer age group today than was the case 20 years ago. Laryngeal cancer patients tended to be less educated than the controls and included a smaller proportion of Jews and more Catholics than the control group. The risk for developing laryngeal cnacer was considerably lower for exsmokers and long-term (10+ years) filter cigarette smokers as compared with non-filter smokers. At each level of alcohol consumption, the risk increased as exposure to tobacco increased. Occupations associated with wood exposure were found to affect the development of laryngeal cancer, independently of smoking status. Future studies should include an extensive study of nutritional deficiencies associated with alcoholism to determine if a correlation exists between such deficiencies, socioeconomic status, and an increased risk of laryngeal cnacer.

Chemotherapy of gastrointestinal cancer.

Abstract: IN this country, and, indeed, the world over, gastrointestinal cancer causes more deaths than cancer taking origin in any other organ system. Although management of these diseases has traditionally...

Drinking water and cancer mortality in Louisiana.

Abstract: Multivariant regression analysis indicates a statistically significant relation between cancer mortality rates in Louisiana and drinking water obtained from the Missippi River. This is true for total cancer, cancer of the urinary organs, and cancer of the gastrointestinal tract.

Association of cadmium with renal cancer.

Abstract: Sixty-four cases of renal cancer in white males were compared with controls (197 cases of nonmalignant diseases of the digestive system and 72 cases of colon cancer) for past exposures to cadmium. Controls were also white males, and were group-matched to the cases on age for the analyses. Data on the three main sources of exposure to cadmium--diet, cigarette smoking and occupation--were obtained by interview. The results showed a significant association of renal cancer with exposure to cadmium, and favored a synergistic effect between occupational exposure and smoking. The relative risk for men who both smoked and worked in high-risk occupations was more than four times that for men who did neither. The apparent synergism, however, suggests that the agent in cigarette smoke contributing to this association may not be cadmium.

Aspergillus Infections in Cancer Patients: Association With Fireproofing Materials in a New Hospital

Abstract: INFECTION is the major cause of mortality in patients with acute leukemia and lymphoma. 1-3 Among infections in patients with altered host defenses, an increasing incidence of such fungal complications is well established. 4-6 Fungal infections caused by Aspergillus spp are second in frequency only to candidiasis in these patient populations. 3-5,7 When present, Aspergillus infections are the major contributory factor to their demise, 6,8 and are of serious consequence in patients receiving immunosuppressive therapy for other circumstances, such as collagen vascular diseases, 9 renal transplants, 10 and cardiac transplants. 11 The Baltimore Cancer Research Center admits for intensive therapy patients with acute and chronic leukemia, lymphoma, multiple myeloma, brain tumors, metastatic sarcomas, and metastatic carcinomas. In the past six years there has been essentially no change in either the basic patient population or in treatment philosophy. The necropsy rate has remained consistently high. Shortly after relocation of the Center to

The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens

Abstract: The hypothesis that liver carcinogenesis may have as an important facet the early selection of carcinogen-resistant cells was tested in animals in which putative premalignant hepatocyte populations, hyperplastic nodules, were induced by 2-acetylaminofluorene or by ethionine. Hyperplastic nodules were observed to be resistant to the acute necrogenic effects of 2 hepatotoxins, CCl4 and dimethylnitrosamine, under conditions in which liver cell necrosis occurred in the liver surrounding the nodules. In addition, although [methyl-3H]dimethylnitrosamine was taken up to an equal degree in nodules and normal liver, the interactions with DNA, RNA, and protein in hyperplastic nodules were found to be about 50% less than in control liver. Hyperplastic nodules showed a marked decrease in uptake of [9-14C]-2-acetylaminofluorene, a finding that could account for the large decrease in labeling of DNA, RNA, and protein by [9-14C]-2acetylaminofluorene observed in the nodules. The results are consistent with and support the hypothesis that new hepatocyte populations that appear prior to cancer, during liver carcinogenesis, have as an important biological property a resistance to the cytotoxic effect of hepatocarcinogens. The basis for this resistance might be a decrease in uptake and/or a reduction in the level of activation of carcinogens.

Inhalation of benzpyrene and cancer in man.

Abstract: Both cigarette smoke and polluted urban air contain very small amounts of benzo[a]pyrene, or BaP, a substance which is carcinogenic to experimental animals if relatively large amounts are applied in certain ways such as skin painting or subcutaneous injection. This suggested the possibility that the BaP in cigarette smoke might account for the high degree of association between cigarette smoking and lung cancer, and it suggested the possibility that BaP poliution of urban air might perhaps increase the risk of lung cancer. Some years ago Wynder and Hoffman found an average of 2.5 pg of BaP in the smoke from 100 American cigarettes smoked mechanically.' The average amount has dropped considerably in more recent years. Based upon this, it would appear that even during a lifetime of heavy cigarette smoking, the concentration of BaP per square centimeter of bronchial tissue over which it might be spread would be extremely small as compared with the dose required to produce skin cancer in mice. The concentration of BaP in the air of large American cities is reported to vary from about 0.3 to 6.0 pgl1,OOO cubic meters in summer and from 6.0 to as high as 74.0 in winter.* The air of British cities is more heavily contaminated with BaP. In some British cities, in winter it varies from 73.0 to as high as 170.0 pgl1,OOO cubic meters of air.g During the course of a year, nonsmokers living in some of these cities probably inhale far more BaP than do heavy cigarette smokers living in rural areas of America. Even so, the amount is extremely low as compared with the amount required to produce skin cancer in susceptible strains of mice, surface area being taken into consideration, Largely because of interest in the possible effects of small amounts of BaP in cigarette smoke and in urban air, we decided to study mortality from lung cancer and other causes among people with very heavy occupational exposure to BaP in air. Roofers and waterproofers are such a group. Sawicki collected air samples in the vicinity of men working in pitch roofing operations and found 14,000 pg of BaP/ 1,000 cubic meters of air (see TABLE 1 ) . Even higher amounts were found in air samples collected close to where a roofer was attending a kettle of hot pitch. Thus it would appear that roofers working with hot pitch are exposed to far greater amounts of BaP than are heavy cigarette smokers living in urban areas.

Breast Parenchymal Patterns and Their Changes with Age

Abstract: The appearance of the breast parenchyma was studied in 955 women to determine whether it changed with age. It was found that women initially classified as being at either a low risk or a very high risk of cancer do not demonstrate changes in the breast parenchyma pattern with age. However, breasts in young women which exhibit dysplastic changes on the initial examination (QDY) frequently do change, occasionally to a relatively lower-risk category but often to a normal or near-normal appearance. Such changes generally occur between the ages of 35 and 50.