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Biomedical subjects

C K Osborne

Publications and source records attributed to C K Osborne.

At least 199 records · Page 11Linked to original sources
PubMed1981

Correlation of primary breast cancer histopathology and estrogen receptor content.

We studied the association of estrogen receptor (ER) with several histologic variables that correlate with breast tumor differentiation and with patient prognosis. Contingency table analysis revealed highly statistically significant correlations between ER content and histologic and nuclear grades, tumor necrosis, and the degree of elastosis and lymphoid cell infiltration. ER positive tumors were more likely than ER negative tumors to demonstrate histological evidence of tumor differentiation. All tumors with histologic grade 1 or nuclear grade 1 (best differentiated) were ER positive or borderline positive. Eighty-nine percent of ER negative tumors were histologic grade 3 and 78.4% were nuclear grade 3 (poor differentiation). ER positive tumors were also correlated with absent tumor necrosis, higher elastic content, and absent lymphoid cell infiltration, all features of good differentiation. Medullary carcinomas were frequently (73%) ER negative, but no relationship between ER and other morphologic types of breast cancer or 9 other morphologic variables was found. ER appears to be a biochemical marker for the degree of differentiation of human breast cancer providing a rationale for the observed differences in biological behavior between receptor positive and negative tumors.

Axilla↗
PubMed1981

Antagonism between epidermal growth factor and phorbol ester tumor promoters in human breast cancer cells.

It has been suggested that the phorbol ester tumor promoters act via the receptor-effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [(3)H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [(3)H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation.

Breast Neoplasms↗
PubMed1980

The value of estrogen and progesterone receptors in the treatment of breast cancer.

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50 to 60 percent are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of clinical relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of Er and an assay for progesterone receptor (PgR) are two methods for increasing the accuracy of selecting or rejecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be a better marker of tumor hormone dependence than quantitative ER.

Breast Neoplasms↗
PubMed1980

Hormone receptors in primary and advanced breast cancer.

The use of cytoplasmic ER is an integral part of the management of patients with metastatic breast cancer. Tissue from the primary tumour should be routinely assayed for ER and, when feasible, metastatic tissue should be obtained for assay. In addition, ER is an important prognostic variable for recurrence and overall survival and may be useful in the design of adjuvant therapy trials. Whether knowledge of receptor status correlates with chemotherapy response has yet to be conclusively determined. Whether PgR will ultimately add to the clinical usefulness of ER has also yet to be clearly defined; however, it is known that patients whose tumour contains both receptors have a high response rate to hormone therapy. These questions, and others await confirmation in prospective clinical trials.

Acute Disease↗
PubMed1980

Epidermal growth factor stimulation of human breast cancer cells in culture.

Epidermal growth factor (EGF), a polypeptide found in human and animal blood and secretions, has been found to stimulate a variety of tissues in vitro including normal and malignant rodent mammary epithelium and human breast epithelial cells and fibroadenoma. We have studied the influence of EGF on malignant human breast tissue with a model system comprising human breast carcinoma cells growing in tissue culture. EGF stimulated growth of MCF-7 cells in serum-free medium. After 7 days in culture, a 2-fold increase in cell number and DNA content and a 3-fold increase in total protein were observed in cells incubated with EGF (10 ng/ml). As little as 0.01 ng/ml of EGF stimulated growth; 10 ng/ml was maximal. EGF effects on growth were noted for cells plated at a high as well as sparse (cloning) density. EGF also stimulated the rates of thymidine, uridine, and leucine incorporation into macromolecules in a dose- and time-dependent fashion. Stimulation of uridine and leucine incorporation was evident by 3 hr, whereas EGF stimulation of thymidine incorporation was delayed until 12 to 18 hr. EGF increased the proportion of cells active in DNA synthesis by nearly 2-fold. The combination of optimal concentrations of insulin (also a growth factor for these cells) and EGF did not stimulate growth above that seen with either hormone alone, suggesting a common step in their mechanism of action. The EGF effect was not dependent on the presence of serum and was not enhanced by dexamethasone as reported for other types of cells. EGF had no effect on another human breast cancer cell line, the MDA-231. These studies suggest that growth of some human breast cancers may be influenced by EGF.

Animals↗
PubMed1980

Nodular histiocytic lymphoma: an aggressive nodular lymphoma with potential for prolonged disease-free survival.

Nodular histiocytic lymphoma (NH) is uncommon, and its natural history is not well defined. Of 473 patients with non-Hodgkin's lymphoma, we found 16 (3.4%) with NH. Most patients (13/16) presented with pathologic stage (PS) III or IV disease, including 7 with liver involvement. One patient (PS III) was initially treated with cyclophosphamide alone, and 4 patients received only radiotherapy, and none were long-term survivors. Eleven patients received combination chemotherapy, and 8 achieved complete remission. Only one of these patients relapsed and died at 19 mo; the other 7 continue in complete remission without maintenance therapy with a minimum followup of 4.5 yr. The survival of the entire group of patients with NH is intermediate between that of the other nodular lymphomas and diffuse histiocytic lymphoma. Nine of 16 patients had either a repeat lymph node biopsy during the course of their disease or lymph node examination at autopsy. Lymph node histology in the majority converted to a diffuse, less differentiated subtype of lymphoma. NH has a natural history similar to that of diffuse histiocytic lymphoma and should be approached with the same therapeutic strategy.

Humans↗
PubMed1980

Steroid hormone receptors in the management of human breast cancer.

Recent insight into the mechanism of steroid hormone receptors in human breast cancer has led to new approaches in treatment strategy. Estrogen receptor (ER) has now replaced clinical criteria in the selection of patients for endocrine therapy. Patients whose tumors do not contain ER should not be subjected to hormonal manipulation. In addition, ER measured on the primary tumor has been found to be an independent prognostic factor for both recurrence and survival. Patients with ER negative primary tumors have a poorer prognosis. This information may be useful in the design and selection of therapy for future adjuvant clinical trials. In metastatic breast cancer, the absolute ER value may provide valuable information regarding endocrine responsiveness. In addition, the measurement of progesterone receptor (PgR) may provide additional insight for predicting with confidence those patients likely to respond.

Breast Neoplasms↗
PubMed1980

Modern approaches to the treatment of breast cancer.

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.

Breast Neoplasms↗
PubMed1979

The use of steroïd hormone receptors in the treatment of human breast cancer: a review.

Basic research into the mechanisms of steroid hormone action in breast cancer has led to significant advances in our understanding and treatment of this disease. The hypothesis that measurement of estrogen receptor (ER) in breast cancer tissue might be useful in predicting the endocrine dependence of a tumor has been proven to be correct. The absence of ER connotes hormone independence and precludes a trial of endocrine therapy. Tumors selected for hormonal treatment on the basis of a positive ER respond to endocrine therapy at nearly twice the rate of those chosen by clinical criteria alone. However, a third of ER positive tumors fail to respond. Recently, research has been directed toward increasing the accuracy of the assay in the ER positive group. The concentration of ER in the tumor and the measurement of progesterone receptor (PgR) appear to improve the predictive accuracy of the test. The ER status of primary breast cancer is also a marker for the length of time to recurrence after mastectomy and for ultimate patient survival. Thus, in addition to its importance in the selection of treatment for advanced disease, the ER assay may also prove valuable in planning new adjuvant treatment strategies.

Breast Neoplasms↗
PubMed1979

Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture.

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.

Acetates↗
PubMed1979

Therapy for cancer of the breast. Current status of steroid hormone receptors.

Estrogen receptor (ER) assays in human breast cancer tissue have proved useful in selecting patients for endocrine therapies. The absence of ER indicates hormone independent tumors and precludes the use of endocrine therapy. Patients with positive tumor ER respond to endocrine therapy at nearly twice the rate of those patients chosen by clinical criteria, although about a third of ER positive tumors in patients still do not respond. Recently, research has been directed toward increasing the accuracy of the ER assay in the ER positive group. The absolute tumor ER value and the presence of progesterone receptor appear promising in this regard. The significance of nuclear estrogen receptor is being studied. Finally, the ER status of a primary breast tumor appears to be a marker for the length of time until recurrence after mastectomy, and for survival. The ER assay may prove valuable in planning new adjuvants in the treatment of breast cancer.

Breast Neoplasms↗
PubMed1979

Breast cancer mortality and diet in the United States.

Internationally, breast cancer mortality is correlated with intestinal lactase sufficiency and dairy product consumption beyond childhood. Within the United States, age-adjusted breast cancer mortality is positively associated with consumption of milk, butter, and total milk fat in regional analyses, and it is associated with milk demand in state-based analyses. Breast cancer mortality is also positively associated with demand for total calories, protein, fat, beef, and table fats (butter and margarine), and it is negatively associated with egg demand. Only the associations with milk and egg demand, however, survive when the Southern states are eliminated from the analyses or when either age of first marriage or income is controlled. The associations with milk and egg demand persist despite multiple controls for other dietary and demographic variables, although the association with milk demand loses statistical significance in some second- and third-order partial correlations. The inverse correlation with egg demand is strong but in the opposite direction from what might have been expected from previous studies. The correlation between milk demand and breast cancer mortality, although weaker, is consistent with results from previous studies, and it suggests a possible special role for dairy products in the etiology of breast cancer.

Adult↗
PubMed1977

Insulin stimulation of fatty acid synthesis in human breast cancer cells.

Four human breast cancer cell lines were tested for their response to hormones with respect to the lactational function, fatty acid synthesis. Physiologic concentrations of insulin enhanced the incorporation of [14C]acetate into fatty acids in two of four cell lines tested. All cell lines had specific, high-affinity insulin receptors; therefore, the failure of two lines to respond could not be attributed to the absence of receptor. The effect of insulin involved an increase in the maximun velocity of incorporation rather than a decrease in the Michaelis constant.

Acetates↗
PubMed1976

Extranodal presentation of non-Hodgkin's lymphomas in the testis.

The clinical and pathologic features of six patients, each of whom exhibited a testicular mass as the first sign of a lymphoma, are discussed. All underwent extensive staging procedures. Retroperitoneal lymph nodes and bone were frequent sites of extratesticular involvement early in the disease. Later widespread dissemination to multiple organs occurred in five of six patients. CNS involvement was a prominent feature of advancing disease. One patient was apparently cured by orchiectomy alone. Although the others exhibited partial responses to chemotherapy and radiation, the disease was fatal to all of them within a year of orchiectomy. Early, aggressive systemic treatment of these patients appears necessary.

Aged↗
PubMed1976

Hormone responsive human breast cancer in long-term tissue culture: effect of insulin.

The mechanisms of steroid and peptide hormone action in human breast cancer are poorly understood. We have previously characterized a cell line of human breast cancer in long-term tissue culture that possesses various steroid hormone receptors and responses, providing a model for the study of steroid hormone action. The present studies describe a human breast cancer in vitro that responds to physiologie concentrations of insulin with an increased rate of macromolecular synthesis and growth. Thymidine and uridine incorporation in cells in serum-free medium are stimulated by 10(-11) M insulin and are maximal with 10(-8) M. Leucine incorporation is stimulated by 5 X 10(-11) M insulin and is maximal with 10(-9) M. Significant stimulation of uridine and leucine incorporation is evident by 3 hr and maximal by 10 hr. A 10-hr lag period exists for insulin stimulation of thymidine incorporation, which is maximal form 14 to 24 hr. The effect of 10(-8) M insulin on macromolecular synthesis is accompanied by a 69% increase above controls in the number of cells after 24 hr. The effect on macromolecular synthesis is observed in glucose-free medium. Insulin's effect on protein synthesis is not blocked by inhibition of RNA synthesis with actinomycin D. Glucocorticoids partially inhibit the action of insulin in these cells. This system provides a model for studying insulin action, and suggests that some human breast cancer may show growth regulation by insulin.

Breast Neoplasms↗