Neon-20 ion- and X-ray-induced mammary carcinogenesis in female rats.
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We briefly review some biochemical aspects of benign breast disease (BBD), mainly focusing on free and conjugate estrogen content of breast cyst fluid (BCF), also in relation to cyst type. Evidence is reported that high K(+)-type I-cysts clearly associate with low Cl- levels and accumulate significantly higher quantities of dehydroepiandrosterone sulfate (DHAS) and estrone-3-sulfate (E1S). In spite of the limited number of cases, both increasing DHAS and E1S levels correlate with the increment of K+ to Na+ ratio. A positive correlation was also found between DHAS and E1S. Using electrochemical detection (ECD) on-line to high performance liquid chromatography (HPLC) in the reverse phase mode, we also studied the free estrogen profile. We observed that in type I BCF there are significantly increased amounts of free estrone (E1). The E1S to E1 ratio was significantly different in the two cyst subpopulations; again, a positive correlation was found between free and sulfated E1 (r = 0.820, p less than 10(-6). This last, together with other experimental observations, allows us to hypothesize that in BCF a main pathway of steroids should be E1S----E1. Besides, high specific activity of sulfatase, as well as beta-glucuronidase enzymes, has been demonstrated for BBD. Preliminary information is also reported concerning the BCF pattern of free estrogens, including the highly polar ones, i.e., catecholestrogens (CCE) and the parent methoxy (MeO) conjugates, which represent, in BCF, a predominant portion of all free estrogens. Both CCE levels and ratios appear unevenly distributed in the two different cyst types. In addition, some BCFs show very high concentrations of 16 alpha-OH-E1. Further studies are needed to answer the main question: whether estrogen patterns could represent additive parameters to further categorize breast cystic disease (BCD) or whether they are of minor interest to determine patients' risk of developing breast cancer.
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The scanning electron microscope reveals structural differences between the apical microvilli of duct cells from cancerous and noncancerous human breasts. The alterations in the microvilli from carcinomatous breasts appear to be highly specific, to extend throughout the affected breast, and may be pathognomonic for this condition.
Spin echo nuclear magnetic resonance measurements may be used as a method for discriminating between malignant tumors and normal tissue. Measurements of spin-lattice (T(1)) and spin-spin (T(2)) magnetic relaxation times were made in six normal tissues in the rat (muscle, kidney, stomach, intestine, brain, and liver) and in two malignant solid tumors, Walker sarcoma and Novikoff hepatoma. Relaxation times for the two malignant tumors were distinctly outside the range of values for the normal tissues studied, an indication that the malignant tissues were characterized by an increase in the motional freedom of tissue water molecules. The possibility of using magnetic relaxation methods for rapid discrimination between benign and malignant surgical specimens has also been considered. Spin-lattice relaxation times for two benign fibroadenomas were distinct from those for both malignant tissues and were the same as those of muscle.
The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.
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Basal prolactin levels were measured before operation in 113 patients undergoing surgery for a lump in the breast. Prolactin concentrations were not significantly higher in those patients with breast cancer than in those with benign lumps. Prolactin concentrations were, however, found to be higher in premenopausal women than in postmenopausal ones, regardless of tumour histology.
Twenty-three out of 28 patients with metastatic breast carcinoma and one out of 13 patients with localised disease had raised levels of plasma immunoreactive calcitonin. Monolayer cultures of breast carcinomas maintained for up to 10 weeks released immunoreactive calcitonin, and a primary breast carcinoma passaged in "nude" mice for over a year contained material immunologically and chromatographically resembling the monomeric form of human calcitonin. These studies indicate that breast carcinomas can produce calcitonin and that plasma calcitonin measurements may be useful in staging patients with breast carcinomas.
Thirty-nine sarcomas of breast are described. The patients' ages ranged from 26 to 78 years but most patients were middle-aged or elderly. Evidence is adduced that 16 of the tumours arose from pre-existing fibroadenomas and others very probably did so. Many tumours were adenosarcomas and one was a carcinosarcoma which preserved its structure in a lymph-node metastasis. Recurrences were mostly local, but a small group had a much graver prognosis. A pleomorphic and giant-cell structure usually meant a high degree of malignancy but the significance of cartilaginous or bony metaplasia, present in seven tumours, was less certain. It is wise to regard all ;fibroadenomas' of the breast occurring in patients over 40 years of age as at least potentially malignant, and these should be examined histologically with care, particularly since sarcomatous change may be present in one part only and therefore easily overlooked.
Five cases of extensive infarction of lymph nodes were traced in just over 16 years' surgical material. All presented with painful swelling in a superficial lymph node chain. None was diagnosed clinically; two were interpreted as fibroadenoma of the axillary tail of the breast, and two as a femoral hernia. Microscopically the lymph nodes in the first three weeks after infarction were characterized by extensive necrosis of medullary and cortical lymphoid cells, but the central reticulin architecture and a narrow, incomplete rim of viable subcapsular lymphoid tissue were preserved. Reactive perinodal inflammation and the formation of granulation tissue resembled the reaction to myocardial infarction. The late stage of the lesion was characterized by incomplete regeneration of lymphoid tissue in the lymph nodes. The lesions appeared attributable to thrombosis of veins within the substance and the hila of the nodes.
Rapid diagnoses were made on 510 breast lumps by three methods in sequence and the results compared with those obtained by paraffin histology.Naked-eye examination of the excised lumps correctly distinguished between benign and malignant tumours in 95.1% of cases with 23 (4.5%) false negative and two (0.4%) false positive results.Rapid imprint cytodiagnosis was correct in 96.9% of the 391 lumps imprinted with 12 (3.1%) false negatives and no false positive results. Frozen sections gave the correct diagnosis in 99.4% of the 510 cases with three (0.6%) false negative and no false positive results. The use of cytology in the diagnosis of breast tumours is discussed.
Fine needle aspiration cytology is an inexpensive, atraumatic technique for the diagnosis of disease sites. This paper describes the technique and illustrates how it may be applied to the management of tumours throughout the body. The limitations of the method, the dangers of false positive reports, and the inevitability of false negative diagnoses are emphasised. In a clinical context the method has much to offer by saving patients from inappropriate operations and investigations and allowing surgeons to plan quickly and more rationally. It is an economically valuable technique and deserves greater recognition.