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Biomedical subjects

S Swain

Publications and source records attributed to S Swain.

At least 55 records · Page 3Linked to original sources

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Actuarial Analysis↗

Birthweight: its relationship with maternal and newborn skinfold thickness.

Two hundred and forty seven pregnant women at term and their offsprings were studied. Maternal skinfold thickness was measured from ten different sites and newborn skinfold thickness was measured from four different sites in each set of cases. Maternal skinfold thickness was positively correlated with the birthweight and skinfold thickness of the offspring. The birthweight was also positively correlated with the skinfold thickness of offspring. The maternal axillary sites and offspring's subscapular site had higher inter correlation as well as with the birthweight of offspring.

Birth Weight↗

Preliminary correlations of clinical outcome with in vitro chemosensitivity of second passage human breast cancer cells.

These studies describe the clinical correlations of 63 in vitro chemosensitivity assays on breast cancer cells after short-term monolayer culture. Forty-five of the assays were single agent correlations. Based on cut-off values determined empirically, the test accurately predicted resistance for 36 of 41 patients (88%) who did not respond to the drug. It also predicted sensitivity with a high degree of accuracy: 21 of 22 patients (95%) who responded to the drug tested had a sensitive assay. In five cases, two biopsies were evaluated from the same patient. Whenever assays were performed before and after treatment with a given drug, tumor cells from the second biopsy were more resistant in vitro if the patient failed on therapy. If the patient did not fail, but stopped therapy for other reasons, or if there was no intervening therapy with the tested drug, the two biopsies remained similar in drug sensitivity. These results suggest that in vitro chemosensitivity assays which accurately predict both sensitivity and resistance can be obtained with breast cancer cells after short-term culture and that further prospective trials are warranted.

Antineoplastic Agents↗

8th San Antonio Breast Cancer Symposium--Plenary lecture. Autocrine and paracrine growth regulation of human breast cancer.

We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGF alpha, TGF beta, a PDGF-like competency factor, and at least one new epithelial colony stimulating factor). Some of these are estrogen-regulated in hormone dependent cells, and are constitutively increased in cells which acquire independence either spontaneously or by ras transfection. Collectively, the secreted growth factors are capable of promoting tumor formation by MCF-7 cells in nude mice, though not to the same extent as estrogens. There would seem to be potential for clinical intervention in the autocrine and paracrine control of breast cancer cells, including some cells which are no longer dependent on estrogens.

Breast Neoplasms↗

Autocrine and paracrine growth regulation of human breast cancer.

Previous work from our laboratory has demonstrated that human breast cancer (BC) cells in culture can be stimulated by physiologic concentrations of estrogen. In an effort to further understand this process, we have examined the biochemical and biological properties of proteins secreted by human BC cells in vitro. We have developed a defined medium system which simultaneously allows the collection of factors secreted by the BC cells, facilitates their purification and allows for an unequivocal assay of their effect on other BC cells. By both biochemical and radioimmunoassay procedures, MCF-7 cells secrete large quantities of IGF-I-like activity. The cells contain receptors for IGF-I and are stimulated by physiologic concentrations of IGF-I. Multiple additional peaks of growth stimulatory activity can be obtained by partial purification of conditioned media from human BC cells by sequential dialysis, acid extraction and Biogel P60 chromatography. These peaks are induced up to 200-fold by physiologic concentrations of estrogen. Several of these peaks cross-react in a radioreceptor assay with EGF and are thus candidates for transforming growth factors. Monoclonal antibodies (MCA) have been prepared which react with secreted proteins from the MCF-7 cells. One of these MCAs binds to material from MCF-7 and ZR-75-1 hormone-dependent BC cells only when these two lines are treated with estrogen but reacts with conditioned medium from several other hormone-independent cell lines in the absence of estrogen stimulation. This MCA is currently undergoing further characterization and evaluation of its biological potency. We conclude that with estrogen stimulation, hormone-dependent human BC cells secrete peptides which when partially purified can replace estrogen as a mitogen. Their role as autocrine or paracrine growth factors and their effects on surrounding nonneoplastic stroma may suggest a means of interfering with tumor proliferation.

Animals↗

Isolation of fibrinogen-fibrin related antigen from human plasma by immuno-affinity chromatography: its characterization in normal subjects and in defibrinating patients with abruptio placentae and disseminated cancer.

Highly purified fibrinogen-fibrin related antigen (FR-antigen) was isolated with good recovery from 1.0--2.0 ml of human plasma, by immuno-affinity chromatography with antibody specific for fibrinogen and fibrin, and plasmin degradation products X, Y, D and D-D dimer. In FR-antigen from defibrinating patients there was evidence for thrombin activity alone (mainly disseminated cancer) or both plasmin and thrombin (mainly abruptio placentae). Thus, the molar ratio of N-terminal Gly-Tyr in the FR-antigen of 18 of 20 patients strongly suggested thrombin activity (95th percentile). In addition, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) on unreduced samples frequently showed bands similar in mol wt to fragments X, Y and D, and in the reduced samples A alpha and B beta chain degradation, both indicating plasmin activity. 'N-terminal beta chain Ala' was elevated in the antigen of four of 20 patients, also suggesting plasmin activity (99th percentile). Combined thrombin, plasmin and factor-XIII activity, as shown with high levels of serum FR-antigen (greater than 10 mg/dl). In some defibrinating patients, especially those with disseminated cancer, heterogeneity of unreduced FR-antigen and A alpha chain degradation, both indicators of mild plasmin-like activity which are commonly seen in normals, were absent.

Abruptio Placentae↗

Effects of temperature treatments on the heat production of starving chickens.

1. Heat production was measured for about 24 h at six temperatures from 2 to 35 degrees C on individually starved broilers that had been subjected to four treatments; these were acclimated or unacclimated to these temperatures, or to these temperatures for 12 h and to 22 degrees C for 12 h (alternated) during each 24-h period. 2. Response curves relating heart production and environmental temperature for the four different treatments differed significantly. Only the unacclimated birds subjected to the alternated temperatures increased heat production at 35 degrees/22 degrees C. Major effects of acclimation were observed mainly in the cold. 3. The relationship between daily endogenous nitrogen (N) excretion and heart production (mg N/kJ) was constant at the different temperatures, but acclimation and alternating temperature increased N excretion. 4. Evaporative heat loss was reduced by alternating temperature at the high temperatures, and by maintaining temperature constant in the cold.

Acclimatization↗

Characterization of T and B antigen-binding cells for beta-galactosidase. II. T antigen-binding cells.

The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.

Animals↗

Characterization of T and B antigen-binding cells for beta-galactosidase. III. Independence of antigen-binding cells in normal animals from antigenic stimulation.

Antigen-binding cells to beta-galactosidase were enumerated in thymus and spleen of mice of different ages and found to remain at a constant frequency throughout life. Thymic beta-galactosidase-binding cells (ZBCs),6 representing T-binding cells, showed no appreciable fluctuation, whereas splenic ZBCs, a mixture of T- and B-binding cells, were slightly depressed at birth but found at normal frequencies by 1 week of age. In addition, germfree mice, both within the 1st week after birth and after maturity, had nearly as many binding cells as did conventionally reared age-matched mice. These results considered together suggest that the ability of cells of both T and B origin to recognize antigen, as revealed by their ability to bind beta-galactosidase, arise independently of specific or nonspecific antigenic stimulation, as part of the normal ontogenic sequence of steps of differentiation. This is consistent with the theory of clonal precommitment of T and B cells.

Aging↗