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Showing papers in "Journal of the National Cancer Institute in 1982"


Journal ArticleDOI
TL;DR: Results from the randomized trial conducted by the Health Insurance Plan (HIP) to determine the efficacy of breast cancer screening with mammography and palpation are reported for longer periods than previously available.
Abstract: Results from the randomized trial conducted by the Health Insurance Plan (HIP) to determine the efficacy of breast cancer screening with mammography and palpation are reported for longer periods than previously available. By the end of 10 years after entry, the study group's mortality due to breast cancer was about 30% below the control group's. Arithmetic gains due to screening were maintained through year 14; relative gains declined. With increases in the period of follow-up, cumulative survival rates among cases detected by mammography alone (palpation negative during screening), decreased more rapidly than rates among other subgroups, but survival rates for mammography cases remained relatively high. Study women aged 40-49 years at entry began to show lower breast cancer mortality than those in the control group as duration of follow-up increased. Reservations are advanced about the acceptance of this finding as evidence of the efficacy of screening under age 50 under the conditions of the HIP study. The reservations are based on the observation that the decrease of mortality among the study group aged 45-49 at entry is concentrated entirely among cases diagnosed after they reached 50 years of age.

912 citations


Journal ArticleDOI
TL;DR: The experiments are interpreted to indicate that angiogenesis is the end result of a sequence of events, two of which are PGE1 production and copper mobilization in the tissue where neovascularization occurs.
Abstract: The interstitial fluid of MTW9A and Walker carcinomas and their ethanol extract induced strong angiogenic response in the rabbit (New Zealand White) corneal test. The fluid collected in vivo was rich in E-type prostaglandins, and prostaglandin E1 (PGE1) in particular was strongly angiogenic at the lowest dose as compared with the angiogenic responses of prostaglandins E2, I2, and F2 alpha. Neoplastic fibroblasts also induced a strong angiogenic response, but in indomethacin-treated rabbits neovascularization failed to occur. Copper was concentrated in the cornea during PGE1-induced neovascularization, and copper-deficient rabbits were unable to mount an angiogenic response in the corneal test. Ceruloplasmin, the copper carrier of plasma, was found to be angiogenic at high doses. In indomethacin-treated rabbits, however, ceruloplasmin at the same high doses failed to induce angiogenesis. The experiments are interpreted to indicate that angiogenesis is the end result of a sequence of events, two of which are PGE1 production and copper mobilization in the tissue where neovascularization occurs.

417 citations


Journal ArticleDOI
TL;DR: It is suggested that RA promoted the differentiation of LA-N-1 neuroblastoma cells, resulting in an altered expression of the malignant phenotype.
Abstract: Retinoic acid (RA) induced concentration-dependent morphologic differentiation and growth inhibition in the LA-N-1 human neuroblastoma cell line. Time course studies demonstrated a significant increase in the formation of long neurites in LA-N-1 cultures within 48 hours of RA addition; maximum expression of differentiation occurred at approximately 4 days. This differentiation profile corresponded to a detectable decrease in [3H]thymidine incorporation at 48 hours and complete inhibition of cell growth after 3-4 days. The RA-induced morphologic differentiation and growth inhibition persisted despite removal of the drug. A soft agar assay system showed that RA also inhibited the ability of LA-N-1 cells to form anchorage-independent colonies and induced morphologic differentiation in colonies that did develop. These findings suggest that RA promoted the differentiation of LA-N-1 neuroblastoma cells, resulting in an altered expression of the malignant phenotype.

408 citations


Journal ArticleDOI
TL;DR: Observations suggest that the determination of DNA distribution in colon carcinomas may prove to be of prognostic value, although lymph node metastases and vascular invasion were more often observed in the nondiploid tumors.
Abstract: Striking differences in outcome of surgically treated colon adenocarcinomas were observed in 33 patients according to the DNA distribution patterns in tumor nuclei, measured by flow cytometry. As discussed and defined in the text and confirmed by appropriate control studies, the tumors were classified into 2 groups: predominantly diploid (20 tumors) and predominantly nondiploid (13 tumors). During the follow-up period of 3-5 years, 12 of the 13 patients with "nondiploid" tumors died of disease within 4-34 months, and the 1 patient still alive after 59 months has extensive metastases. Only 6 of the 20 patients with "diploid" tumors died of disease, sometimes after a slow, protracted clinical course. There were 14 patients with no evidence of disease for periods ranging from 30 to 60 months; 1 of these patients died of other causes. Histologic grading and Dukes' staging appeared to play a relatively limited role in the outcome, although lymph node metastases and vascular invasion were more often observed in the nondiploid tumors. These observations suggest that the determination of DNA distribution in colon carcinomas may prove to be of prognostic value.

367 citations


Journal ArticleDOI
TL;DR: It was concluded that carotenoid pigments function as protective agents by quenching triplet sensitizers, singlet oxygen, and radical intermediates.
Abstract: Dye-sensitized photo-oxidations of liposomes are inhibited by the presence of carotenoids in the membrane. Some carotenoid bleaching occurs during the reaction. It was shown that carotenoids are capable of inhibiting free-radical-induced lipid peroxidation in liposomes as well as singlet oxygen-induced lipid peroxidation. There is little direct effect of lipid peroxides on carotenoid bleaching during the photo-oxidative reactions. The carotenoid bleaching observed during the dye-photosensitized oxidations of the liposomes appears to be due to interactions between the carotenoid pigments and either radical intermediates from type I reactions or direct chemical reaction with singlet oxygen in a type II reaction. It was concluded that carotenoid pigments function as protective agents by quenching triplet sensitizers, singlet oxygen, and radical intermediates.

350 citations


Journal ArticleDOI
TL;DR: The results of the present study indicated that the composition of the diet can alter the activity of an important enzyme system having the capacity to detoxify chemical carcinogens.
Abstract: Benzyl isothiocyanate, beta-naphthoflavone, coumarin, alpha-angelicalactone, disulfiram, indole-3-carbinol and indole-3-acetonitrile induced increased glutathione (GSH) S-transferase activity in the liver and small intestine in female ICR/Ha mice. All seven compounds are inhibitors of chemical carcinogenesis. In additional work, several dietary constituents increased GSH S-transferase activity. Consumption of diets containing dried powdered preparations of brussels sprouts, cabbage, coffee beans, or tea leaves resulted in increased GSH S-transferase activity. Mice fed an unrefined diet (Purina Rat Chow) had a higher GSH S-transferase activity than those fed a semipurified diet. The results of the present study indicated that the composition of the diet can alter the activity of an important enzyme system having the capacity to detoxify chemical carcinogens.

336 citations


Journal ArticleDOI
TL;DR: It is demonstrated that hepatocytes obtained from human liver by the described modified collagenase technique can be used for in vitro studies in chemical carcinogenesis.
Abstract: The in situ two-step collagenase perfusion technique used for the isolation of hepatocytes from rat liver was adapted into a procedure applicable to pieces of human liver obtainable from surgical procedures. Human hepatocytes obtained by this method were maintained in primary culture for 10 days. The cellular changes observed at the light microscopic and electron microscopic levels are described. The changes in microsomal enzymes as a function of the age of the cultures were also measured. Exposure of the human hepatocytes to procarcinogens known to be metabolized by rodent liver resulted in unscheduled DNA synthesis. The isolated hepatocytes were also transplanted into two-thirds partially hepatectomized athymic nude mice. The transplanted cells formed nodules with characteristic hepatic architecture. These studies demonstrate that hepatocytes obtained from human liver by the described modified collagenase technique can be used for in vitro studies in chemical carcinogenesis.

299 citations


Journal ArticleDOI
TL;DR: An animal model for spontaneous mammary tumor metastasis was developed using the rat 13762 mammary adenocarcinoma tumor and several individual parental tumor-derived and lung metastasis-derived clones were compared, indicating that tumor cell populations from metastases are more metastatic than are cells from the parental tumor.
Abstract: With the use of the rat 13762 mammary adenocarcinoma tumor, an animal model for spontaneous mammary tumor metastasis was developed. The parental tumor implanted sc into the mammary fat pads of female Fischer 344 rats metastasized at low frequency to lymph nodes and lung and did not metastasize to other organs. Oophorectomy did not modify the metastatic properties of the parental 13762 tumor. Cell lines were adapted to tissue culture from lymph node or lung metastases, and these were compared to parental tumor transplants in spontaneous metastasis assays. Only the cell lines established from metastases were spontaneously metastatic within 23 days after sc implantation, indicating that tumor cell populations from metastases are more metastatic than are cells from the parental tumor. Several individual parental tumor-derived and lung metastasis-derived clones were compared for spontaneous metastatic potentials, cell culture morphologies, histologic structures at primary implant and secondary metastatic sites, and growth characteristics in vivo and in vitro. There was no correlation between any of these tumor and cellular properties and metastatic potential. The parental mammary tumor-derived, lymph node metastasis-derived, and lung metastasis-derived cell lines and clones with differing spontaneous metastatic properties should prove useful in studies on the roles of tumor cell and host properties in lymphatic and blood-borne metastasis.

260 citations


Journal ArticleDOI
TL;DR: The data are interpreted to indicate that copper ions are involved in the sequence of events leading to angiogenesis and that the carrier molecules may be of quite a different nature.
Abstract: The ability to induce new formation of capillaries in the cornea was tested for ceruloplasmin, the copper carrier of serum, for fragments of the ceruloplasmin molecule with and without copper, for heparin, and for glycyl-L-histidyl-L-lysine, bound or not bound to copper ions. Male or female 2- to 3-kg New Zealand White rabbits were used. These experiments were prompted by the previous observation of copper accumulation in the cornea during angiogenesis and by the inability of copper-deficient rabbits to mount an angiogenic response. The results showed that the three different molecules were all able to induce angiogenesis provided that they were bound to copper. Fragments of the ceruloplasmin molecule also induced angiogenesis but only when copper was bound to the peptides. The data are interpreted to indicate that copper ions are involved in the sequence of events leading to angiogenesis and that the carrier molecules may be of quite a different nature.

253 citations


Journal ArticleDOI
TL;DR: Observations suggest that the fraction of Wilm's tumors that is due to an inherited mutation may be substantially smaller than previously supposed and support the concept that the disease arises from a variety of pathogenetic pathways.
Abstract: Nearly 2,000 children with Wilm's tumor registered in a national clinical trial during 1969-81 showed high rates of aniridia, hemihypertrophy, cryptorchidism, hypospadias, and other genitourinary anomalies. Patients with bilateral disease, who constituted 5% of the total, had younger ages at diagnosis and an increased incidence of congenital anomalies and renal blastemal rests. Those with multicentric unilateral lesions had more blastemal rests but were otherwise indistinguishable from the unicentric cases. The 20 familial cases had none of the features usually associated with genetic tumors: neither younger ages nor an increase in bilaterality nor associated congenital anomalies. These observations suggest that the fraction of Wilm's tumors that is due to an inherited mutation may be substantially smaller than previously supposed and support the concept that the disease arises from a variety of pathogenetic pathways.

207 citations


Journal ArticleDOI
TL;DR: HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl, and induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl.
Abstract: The carcinogenic response to the combined and separate exposures to formaldehyde (HCHO) and hydrochloric acid (HCl) was investigated in male inbred SD rats. The rats were exposed to gaseous HCHO, 14 ppm, and HCl, 10 ppm, in two experiments. In one experiment the gases were premixed at high concentrations before being diluted in the exposure chamber air to maximize the formation of the carcinogen bis(chloromethyl)ether (BCME). In the second experiment exposure was repeated to HCl and HCHO premixed at high concentrations, and not premixed (to minimize BCME formation), as well as to HCHO alone and HCl alone. The second experiment is being reported on at an interim stage. HCHO alone induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl. No carcinogenic response was observed with HCl alone. HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl.

Journal ArticleDOI
TL;DR: A number of distinct processes of the angiogenic response to tumors are discussed which suggest that several families of angiogenesis-inducing factors may mediate each of these processes.
Abstract: Tumor fragments implanted in the mouse cornea induce a neovascular reaction characterized by the penetration of new blood vessels into the avascular cornea that ultimately reach the tumor to permit its further rapid growth. A method to achieve angiogenesis in the mouse cornea was studied, as well as the histologic and gross manifestations of the neovascular reaction and the effect of tumor cells or host irradiation on the observed angiogenic response. Sequential stages of tumor-induced neovascularization are described and documented for sarcoma 180- and C755 mammary adenocarcinoma-induced angiogenesis. A number of distinct processes of the angiogenesis response to tumors are discussed which suggest that several families of angiogenesis-inducing factors may mediate each of these processes. The importance of the development of a mouse model for the study of angiogenesis is stressed.

Journal ArticleDOI
TL;DR: Positive UEA-I binding in many rectal cancerous and adenomatous lesions suggested that a neoplastic glycoprotein with alpha-L-fucosyl residue was produced or that the terminal carbohydrate structure of glycoproteins present in the nonneoplastic mucosa was altered to bind easily with U EA-I after the neoplastics transformation had occurred.
Abstract: Cancerous lesions and nonneoplastic mucosa of surgically extirpated specimens from 94 patients with colorectal carcinoma (of the right colon, 31 patients; of the left colon, 29 patients; and of the rectum, 34 patients) and endoscopically polypectomized specimens from 18 patients with rectal adenoma were examined with fluorescein isothiocyanate-conjugated or horse-radish peroxidase-conjugated Ulex europaeus agglutinin-I (UEA-I) specific to a certain terminal alpha-L-fucosyl residue in glycoconjugates. Of the 31 patients with right colon cancers, 22 showed positive UEA-I binding in the neoplastic cell apexes, apical luminal borders, and luminal secretions. The adjacent nonneoplastic mucosa of all 31 patients, however, demonstrated positive UEA-I binding in the goblet cell mucus. UEA-I binding was positive for 23 of the 29 left colon cancers and for 28 of the 34 rectal cancers, although UEA-I binding was not revealed in the adjacent nonneoplastic mucosa for most of the cases. Of the 18 rectal adenomas, 12 specimens showed positive UEA-I binding in the apical secretions of their adenoma cells. Marked regional differences of UEA-I binding in the nonneoplastic mucosae indicated that the constituents of glycoprotein with UEA-I binding sites in goblet cell mucus differed significantly between the human right and left large bowels. Positive UEA-I binding in many rectal cancerous and adenomatous lesions suggested that a neoplastic glycoprotein with alpha-L-fucosyl residue was produced or that the terminal carbohydrate structure of glycoprotein present in the nonneoplastic mucosa was altered to bind easily with UEA-I after the neoplastic transformation had occurred. A possible relation of this UEA-I binding to blood group H(O) substance is discussed.

Journal ArticleDOI
TL;DR: A population-based case-control study involving interviews with 577 female breast cancer patients and 826 controls in northern Alberta revealed that some determinants of breast cancer varied according to age, and the link to oral contraceptives among among younger women and the inverse relation to breast feeding at all ages may not be causal.
Abstract: A population-based case-control study involving interviews with 577 female breast cancer patients and 826 controls in northern Alberta. Canada, revealed that some determinants of breast cancer varied according to age. Among women under age 45, risk factors included a younger age at menarche, late age at last birth, high parity, and recent use of oral contraceptives. At older ages risk was related to natural as opposed to surgical menopause, late age at first birth, low parity, late age at natural menopause, and tonsillectomy. At all ages there was an increased risk of breast cancer associated with difficulty in conceiving, benign breast disease, not having breast fed, and a history of breast cancer among mothers or sisters. For some variables the age differences were pronounced; the combination of low parity and late age at first birth was associated with a sevenfold increase in breast cancer risk at risk at ages 55-80 but a slight decrease at ages under 45. The effect of tonsillectomy steadily increased with age and represents a new lead, but certain features of the data suggest that the link to oral contraceptives among among younger women and the inverse relation to breast feeding at all ages may not be causal. Even though design limitations (cases interviewed in a different setting from controls) appeared not to influence conclusions, the results may have been subjected to interview bias and thus should be interpreted cautiously.

Journal ArticleDOI
TL;DR: It is demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cellsPopulating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random.
Abstract: These studies demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cells populating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random. The tumors used in these studies were the UV-2237 fibrosarcoma, an in vitro cloned line (C-40) from the UV-2237 tumor, and the K-1735 melanoma, all of which are syngeneic to the C3H/HeN (mammary tumor virus-negative) mouse strain; the M5076 reticulum cell sarcoma and the Lewis lung carcinoma 3LL, which are syngeneic to the C57BL/6 mouse strain, were also used. All tumors were implanted sc into the footpads of syngeneic mice, and several resulting spontaneous metastases were isolated and established in culture as individual cell lines. For each tumor system, comparison was made of the ability of parent tumor cells and cells isolated from several spontaneous metastases to produce either experimental or spontaneous metastases. Cells populating spontaneous metastases produced by heterogeneous and poorly metastatic tumors were significantly more metastatic than the cells of their respective parent tumors. In contrast, cells populating metastases produced by previously selected tumors did not differ significantly in metastatic potential from cells populating their parent tumors. In such systems, metastasis appeared to be random.

Journal ArticleDOI
TL;DR: The hypothesis that collagenolytic metalloproteinases play a necessary role in tumor cell invasion of native connective tissue is supported.
Abstract: The effect of natural protease inhibitors and a chemoattractant on tumor cell invasion were studied with the use of a new in vitro quantitative assay of tumor cell penetration of native connective tissue. Human amnion membrane denuded of its epithelium is composed of a continuous basement membrane (BM) attached to a dense avascular collagenous stroma. M5076 reticulum sarcoma cells, known to be highly invasive in vivo, were placed on the BM side of the amnion connective tissue. Tumor cells penetrating the full thickness of the connective tissue barrier were collected on the stromal side with a Millipore filter. N-Formylmethionyl-leucyl-phenylalanine (FMLP) at an optimal concentration of 10(-7) M stimulated the penetration of up to 600% more tumor cells into the connective tissue after 20 hours in comparison to the number of tumor cells spontaneously penetrating in serum-free media. Natural protease inhibitors blocked both FMLP-stimulated and spontaneous invasion. A bovine cartilage extract containing inhibitors of both serine proteinases and metalloproteinases caused a 500% decrease in invasion. Furthermore, a 500% inhibition of invasion was produced by a purified collagenase (metalloproteinase) inhibitor. In contrast, soybean trypsin inhibitor and bovine serum albumin did not significantly alter the invasion rate. The protease inhibitors were nontoxic and did not reduce tumor cell proliferation, attachment to the amnion, and the rate of tumor cell migration through Nuclepore filters. These data support the hypothesis that collagenolytic metalloproteinases play a necessary role in tumor cell invasion of native connective tissue.

Journal ArticleDOI
TL;DR: In a case-control study of childhood rhabdomyosarcoma, families of 33 cases and 99 controls were interviewed and findings imply that environmental factors may play an important role in the etiology of childhood RMS.
Abstract: In a case-control study of childhood rhabdomyosarcoma (RMS), families of 33 cases and 99 controls were interviewed. A relative risk (RR) of 3.9 was found associated with fathers' (but not mothers') cigarette smoking (P = 0.003). Cases had had fewer immunizations than controls, particularly smallpox vaccination (RR = 0.2; P = 0.001), and conversely had more preventable infections. An RR of 3.2 (P = 0.03) was found associated with exposure to chemicals and and RR of 3.7 (P = 0.004) was found associated with diets that included organ meats. Mothers of cases were more likely to be over age 30 years at subject's birth, to have used antibiotics preceding or during pregnancy, and to have had an overdue and/or assisted delivery. Other findings suggest that low socioeconomic status is associated with an increased risk of RMS. These aggregate findings imply that environmental factors may play an important role in the etiology of childhood RMS.

Journal ArticleDOI
TL;DR: Multivariate examination of demographic and clinical characteristics showed patients with anticipatory side effects to report more severe post treatment emesis, to report their most severe posttreatment nausea as occurring later after treatment, and to be more likely to be taking cisplatin than patients without anticipatorySide effects.
Abstract: Forty-seven of 225 (21%) consecutive cancer patients were found to experience nausea and/or vomiting prior to a chemotherapy treatment. Multivariate examination of demographic and clinical characteristics showed patients with anticipatory side effects to report more severe posttreatment emesis, to report their most severe posttreatment nausea as occurring later after treatment, and to be more likely to be taking cisplatin than patients without anticipatory side effects. Seventy percent of the patients with anticipatory nausea and/or vomiting attributed the side effects to a psychologic etiology.

Journal ArticleDOI
TL;DR: In group 2 animals receiving vitamin E, tumor formation was significantly delayed, so that by 14-16 weeks there were fewer tumors and their average size was smaller than that of tumors in group 1 animals that were painted with DMBA but received no vitamin E supplement.
Abstract: Eighty young adult male and female Syrian golden hamsters (Mesocricetus auratus) were divided into 4 equal experimental groups. In group I animals the left buccal pouch was painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil. In group 2 animals the left buccal pouch was similarly painted with DMBA, but the animals also received orally 10 mg vitamin E (dl-alpha-tocopherol) in peanut oil twice weekly on alternate days with DMBA painting. Group 1 animals received a similar amount of peanut oil vehicle, group 3 animals received only vitamin E (vitamin E controls) in peanut oil, and group 4 animals served as untreated controls receiving only peanut oil. Four animals in each group (2 males and 2 females) were killed at 8, 10, 12, 14, and 16 weeks. Buccal pouches were photographed and excised, and tumors were noted and measured in the left buccal pouches. In group 2 animals receiving vitamin E, tumor formation was significantly delayed, so that by 14-16 weeks there were fewer tumors and their average size was smaller than that of tumors in group 1 animals that were painted with DMBA but received no vitamin E supplement. In group 2 there was also less invasion of underlying tissues and less surface necrosis.

Journal ArticleDOI
TL;DR: Female residents of six counties in Washington and Utah in whom ovarian cancer was diagnosed during 1975-79 were interviewed concerning prior use of noncontraceptive estrogens, finding no evidence of increased risk from estrogen use in the small group of women with clear cell tumors.
Abstract: Female residents of six counties in Washington and Utah in whom ovarian cancer was diagnosed during 1975-79 were interviewed concerning prior use of noncontraceptive estrogens. Interviews with a random sample of women drawn from these counties were obtained for comparison. Taken as a whole, women with epithelial ovarian tumors reported estrogen use for 1 year or more somewhat more often than did controls [relative risk (RR) = 1.3, 95% confidence interval (CL) = 0.9-1.8]. The proportion of women who had used estrogens varied according to the histology of their tumor; notably, of 17 women with endometrioid tumors, 12 had used estrogens (RR = 3.1, 95% CL = 1.0-9.8). The excess risk of endometrioid carcinoma related to estrogen use was not further increased when these hormones were taken for long durations, in high doses, or proximate to the time of diagnosis. Neither was there any evidence of increased risk from estrogen use in the small group of women with clear cell tumors, a histologic tumor type believed to be closely related to endometrioid carcinoma. Thus the observed association between menopausal estrogen use and the occurrence of ovarian endometrioid tumors should be interpreted cautiously until the results of additional studies are available.

Journal ArticleDOI
TL;DR: This study demonstrates that a multiple marker test of tissue-specific antigens can be of an additive value in the immunodiagnosis of cancer and may be a logical and effective approach at this time, in light of the unavailability of human tumor-specific markers.
Abstract: Serum prostate-specific antigen and prostatic acid phosphatase were simultaneously evaluated in 22 healthy males, 29 patients with benign prostatic hypertrophy, and 192 patients with prostate cancers at various stages as well as in 30 patients with cancers other than prostate cancer. Both markers were quantitated by specific sandwich-type, enzyme-linked, immunosorbent assays with the use of specific antiserum reagents. Serum assays revealed a discordance between these two markers; thus expressions of these two biochemically and immunologically distinct prostate-specific proteins may reflect different aspects in the biology of prostate cancer. A combination test with the use of 7.5 ng of prostate antigen and 15.5 ng of prostatic acid phosphatase/ml of serum, respectively, as cutoff values resulted in a positive detection rate of 58% for prostate cancers of stages A (7/12) and B (21/36) each, 68% for prostate cancer of stage C (19/28), 92% for prostate cancer of stage D (106/116), and only 10% for benign prostatic hypertrophy (3/29). None of 52 other cancers or healthy controls was registered as positive. This study demonstrates that a multiple marker test of tissue-specific antigens can be of an additive value in the immunodiagnosis of cancer and may be a logical and effective approach at this time, in light of the unavailability of human tumor-specific markers.

Journal ArticleDOI
TL;DR: The findings suggest that familial susceptibility to breast cancer may be mediated through hormonal factors that operate early in a woman's life, and a synergistic relationship was observed between family history of breast cancer and the occurrence of multiple biopsies for benign breast disease.
Abstract: A case-control study, conducted among participants in the Breast Cancer Detection Demonstration Project, obtained detailed information on family history of breast cancer and other risk factors from 1,362 breast cancer patients and 1,250 control subjects. An affected first-degree relative was reported by 22.4% of the patients and 12.2% of the control subjects. This finding was associated with a twofold increased risk of breast cancer, although greater elevations in risk were seen in younger study subjects and in those reporting both an affected mother and a sister. Analysis of other risk factors showed that, compared to women without a family history of breast cancer, control subjects with a family history of breast cancer tended to have early or late menarche, were older at first childbirth, and were younger at oophorectomy. In addition, the effect of family history on breast cancer risk was modified by age at menarche, but not by age at first birth or type of menopause. These findings suggest that familial susceptibility to breast cancer may be mediated through hormonal factors that operate early in a woman's life. A synergistic relationship was also observed between family history of breast cancer and the occurrence of multiple biopsies for benign breast disease, although the mechanisms for this relationship remain to be elucidated.

Journal ArticleDOI
TL;DR: The familial findings are generally consistent with a two-step mutation model of the development of hereditary and nonhereditary CBT; apparent deviations from the model might be clarified with additional data on this rare neoplasm.
Abstract: Genetic factors in the etiology of carotid body tumors (CBT) were sought in a medical record review of 222 histologically diagnosed cases at 12 U.S. medical centers. Patients in the series, which had a marked female predominance (146 females:76 males), usually developed tumors between the fourth and seventh decades of life (mean, 44.7 yr). In 16 patients who also had other extra-adrenal paragangliomas, suggesting a multiple primary tumor syndrome, CBT were diagnosed significantly earlier (mean, 35.4 yr; P less than 0.01). The occurrence of thyroid cancer in 5 other patients appeared to be excessive. Familial CBT was recognized in 16 patients from 13 affected families, including 9 newly ascertained kindreds. Compared with non-familial lesions, familial CBT tended to develop bilaterally (38% vs. 8% unilaterally) and at slightly earlier ages (41.6 vs. 44.9 yr). CBT was reported to occur in an autosomal dominant pattern in some families and within sibships in others; relatives were not examined for confirmation. The familial findings are generally consistent with a two-step mutation model of the development of hereditary and nonhereditary CBT; apparent deviations from the model might be clarified with additional data on this rare neoplasm.

Journal ArticleDOI
TL;DR: Indirect immunofluorescence analysis with cryostat thin sections of human tissues showed that this antigen is absent from a large variety of normal tissues but is readily detectable on melanomas, nevi, and several different carcinomas.
Abstract: The IgG2a monoclonal antibody (MoAb) 376.96S, secreted by a hybridoma derived from a mouse immunized with cultured human melanoma cells COLO 38, reacts with a single 94,000-dalton glycoprotein that is peripherally associated with the plasma cell membrane of cultured melanoma cells. Indirect immunofluorescence analysis with cryostat thin sections of human tissues showed that this antigen is absent from a large variety of normal tissues but is readily detectable on melanomas, nevi, and several different carcinomas. The MoAb 376.96S binds with cultured melanoma and carcinoma cell lines to a similar extent and can mediate both complement-dependent and cell-dependent lysis of these cells. The 94,000-dalton glycoprotein detected by MoAb 376.96S is distinct in its tissue distribution, antigenicity, and molecular profile from several structures previously identified with monoclonal antibodies that have similar molecular weights.

Journal ArticleDOI
TL;DR: A human cell line (SCL-1) from a poorly differentiating cutaneous squamous cell carcinoma (SCC) ws studied through 20 passages during 2 years, and two stable marker chromosomes strongly indicated a monoclonal origin of this cell line.
Abstract: A human cell line (SCL-1) from a poorly differentiating cutaneous squamous cell carcinoma (SCC) ws studied through 20 passages during 2 years. Cells maintained their original morphology with low degree of keratinization, as indicated by light and electron microscopy. The keratin peptide pattern resembled the type in SCC tumors, and the corresponding filaments were detected by immunofluorescence at all passage levels. Cells did not grow in soft agar but formed tumor-like nodules in an "organotypic" culture assay (on lifted collagen gels) and grew invasively after transplantation to immunosuppressed inbred C3H mice. After injection into BALB/c nu/nu mice, tumors of SCC morphology were formed. The hypodiploid tumor stem-line was maintained for about 10 passages, when a shift to hyperploidy started, as determined by chromosome and DNA flow microfluorometric analyses. Two stable marker chromosomes (in 100 and 70% of the metaphases, respectively), involving chromosomes 7 and 9, strongly indicated a monoclonal origin of this cell line.


Journal ArticleDOI
TL;DR: The data were interpreted to support the hypothesis that acquisition of angiogenic capacity by a cell population normally devoid of this capacity indicates an increased risk of neoplastic transformation.
Abstract: In vivo cell populations at high risk of neoplastic transformation have been shown to acquire the ability to induce new formation of vessels. The present experiments tested whether the same change occurred during neoplastic transformation in vitro. In four cell populations (human HBL 100 mammary epithelium, BALB/c fibroblasts, C57BL-MG epithelium, and Syrian golden hamster embryo cells), angiogenic capacity appeared during their cultivation in vitro and was evident long before a neoplastic transformation could be recognized. The data were interpreted to support the hypothesis that acquisition of angiogenic capacity by a cell population normally devoid of this capacity indicates an increased risk of neoplastic transformation.

Journal ArticleDOI
TL;DR: Urine may provide a convenient and readily available source for the biochemical characterization of these TGF-like activities, some of which may be clinically useful biologic markers for certain types of cancer.
Abstract: Transforming growth factor (TGF) activities could be detected in the urine of normal, pregnant, and tumor-bearing humans. These acid- and heat-stable polypeptides competed for binding to epidermal growth factor (EGF) membrane receptors and promoted the anchorage-independent growth of nontransformed rodent cells. They differed from human EGF in their apparent molecular weights and soft-agar growth-stimulating activity. The urine from pregnant females contained TGF activities with apparent molecular weight(s) (relative) (Mr) of 10,000 ad 17,000--20,000. In the case of a lung cancer patient, an additional major activity of approximately 30,000--35,000 Mr was found. All urine specimens examined also contained a "common" 8,000-Mr soft-agar growth-stimulating activity, which competed for binding to EGF membrane receptors and which was chromatographically separable from EGF (urogastrone). Thus urine may provide a convenient and readily available source for the biochemical characterization of these TGF-like activities, some of which may be clinically useful biologic markers for certain types of cancer.

Journal ArticleDOI
TL;DR: Longevity of granulopoiesis in mouse continuous bone marrow cultures varies significantly among strains, and generation of permanent WEHI-3 dialyzed conditioned medium (DCM)-dependent hematopoietic progenitor cell lines were evaluated.
Abstract: Longevity of granulopoiesis in corticosteroid-supplemented continuous bone marrow cultures and generation of permanent WEHI-3 dialyzed conditioned medium (DCM)-dependent hematopoietic progenitor cell lines were evaluated for 28 inbred mouse strains and outbred stocks. Cultures from AKR/J, NZW, C58/J, DBA/2J, and C57BL/KsJ mice generated granulocytes for 45-58 weeks and released more than 10(5) murine sarcoma virus (MuSV) rescue units of endogenous retrovirus; nonadherent (NA) cells from 50% or more cultures produced permanent WEHI-3 DCM-dependent cell lines. Cultures from 129/J, BALB/cJ, SJL/J, RF/J, CD-1 Swiss, C57BR/cdJ, C57BL/Ka, CBA/J, RFM/Sn, NZB, C3H/HeJ, NIH Swiss [N:NIH(S)], C57BL/10J, C57L/J, SWR/J, HRS/J, and C57BL/6J mice generated granulocytes for 12-38 weeks; some released 10(1)-10(2) MuSV rescue units of retrovirus, and NA cells from less than 50% of cultures from all but SWR/J and C57L/J mice produced WEHI-3 DCM-dependent cell lines. Thus longevity of granulopoiesis in mouse continuous bone marrow cultures varies significantly among strains.

Journal ArticleDOI
TL;DR: The findings strongly suggest that elevated microvascular resistance, intratumor tissue pressure, and widening of intercapillary distances in the melanoma might significantly diminish the impact of chemotherapeutic treatment.
Abstract: Transparent chambers and permanent indwelling catheters were implanted in the dorsal skin flaps of 24 inbred golden Syrian hamsters. After 48 hours, 4 x 10(4) amelanotic melanoma cells (A-Mel-3) were transplanted sc (12 hamsters) in areas exposed for intravital microscopy. A platinum multiwire electrode and techniques for a quantitative analysis of television images were used for measurements of local oxygen pressure (PO2), capillary blood cell velocity, capillary density, and capillary diameter and length, whereas capillary morphology was evaluated by electron microscopy. Compared to the mean local PO2 of the skin flaps of controls (12 hamsters), the mean local PO2 on the tumor surface of melanoma-bearing hamsters decreased with tumor size. Although capillary density of the melanoma was elevated 4 days after tumor transplantation, it decreased significantly until day 12. Of hemodynamic significance were huge platelet conglomerates in short, dilated capillaries. Electron microscopy revealed endothelial hyperplasia, open endothelial junctions, and disintegration of the capillary endothelium. These findings strongly suggest that elevated microvascular resistance, intratumor tissue pressure, and widening of intercapillary distances in the melanoma might significantly diminish the impact of chemotherapeutic treatment.