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K R Stone

Publications and source records attributed to K R Stone.

At least 37 records · Page 2Linked to original sources
PubMed1986

A proposed classification of breast cancer based on kinetic information: derived from a comparison of risk factors in 168 primary operable breast cancers.

Flow cytometric DNA analysis was performed on 168 consecutive primary operable breast cancers and the results correlated with thymidine labeling, estrogen receptor (ER) and progesterone receptor values, and various histologic parameters. Seventy-five cancers (45.0%) were diploid and 93 (55.0%) aneuploid. In 83.9% of aneuploid cancers, the DNA index fell between 1.1 and 2.0. Thirteen cancers were hypertetraploid and three hypodiploid. The percent of S-phase cancers (SpF) varied from 1.1% to 24.4%, with a mean of 8.0% and a median of 7.1%. The mean SpF of diploid cancers was 5.2%; of aneuploid cancers, 10.3%. There was no significant correlation between SpF or ploidy and tumor size or axillary lymph node status. The thymidine labeling index (TLI) varied from 0.2 to 23.1, with a mean of 7.5 and a median of 6.1. There was good correlation between TLI and SpF (r = 0.892, P = 0.0001). ER-negative tumors had a significantly higher mean SpF (10.3%) than did ER-positive tumors (6.7%), but there was no significant correlation between ploidy and receptor positivity or negativity. There was a good correlation between invasive tumor necrosis, poor cytologic differentiation, aneuploidy, and above-median SpF. Only a fair correlation was observed between mitotic rate and SpF. A classification of invasive breast cancers based on ploidy and SpF is proposed.

Breast Neoplasms↗
PubMed1986

Reversibility of vitamin D-induced human leukemia cell-line maturation.

HL-60 cells are induced to differentiate along a monocytic pathway by the active metabolites of vitamin D3, e.g. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. All such differentiated cells share a number of features in common but are heterogeneous in their ability to adhere to solid substrates and to resorb devitalized bone matrix. Here, we show that, in addition, as compared to the nonadherent, adherent cells are smaller, less likely to be in the S phase, more enriched in the human monocyte-specific cell surface antigen, 63D3, and contain less cmyc messenger RNA (mRNA). In addition, we document that removal of the hormone leads to dedifferentiation. For these susceptible mononuclear cells, removal of 1,25-(OH)2D3 results in a reversion to a more myeloblastic phenotype, renewed cell proliferation, and the rapid appearance of elevated levels of cmyc mRNA. Finally, we report that the cells that do not revert upon 1,25-(OH)2D3 removal are those that became multinucleated during treatment.

Antigens, Surface↗
PubMed1985

Short-term cryopreservation of human breast carcinoma cells for flow cytometry.

A procedure is described for short-term cryopreservation of primary human tumor cells and tissue slices for later analysis by flow cytometry. Cells were mechanically dispersed into a freezing medium, which was then frozen at either -20 degrees C or -70 degrees C for delayed cell cycle analysis. The results show that a correlation coefficient of greater than 0.95 exists between cell cycle kinetic analyses performed immediately after surgical excision of the tumor and on cells frozen from 1 to 30 days at -70 degrees C in this freezing solution. Somewhat lower levels of correlation exist for cells frozen at -20 degrees C in this freezing medium. This procedure has also been successfully used to preserve freshly isolated breast carcinoma cells shipped from distant laboratories for analysis in the flow cytometer, thus expanding the data base on certain types of breast carcinoma.

Breast Neoplasms↗
PubMed1985

Heterogeneity of breast carcinomas determined by flow cytometric analysis.

Eight cases of primary breast carcinoma were studied for evidence of heterogeneity by flow cytometry using propidium iodide staining of DNA. Tumors ranged from 2.5 to 8.0 cm in greatest dimension, mean 4.2 cm. Five to 11 samples, determined by tumor size, were analyzed from each primary tumor in addition to 4 axillary lymph nodal metastases from 3 of the 8 cases. The presence of carcinoma was demonstrated histologically in each flow cytometric sample. Three of the carcinomas showed only diploid DNA content. Three showed the same single hyperdiploid population in each sample. Two carcinomas (2.5 and 3.5 cm) were heterogeneous and demonstrated 2 or 3 hyperdiploid populations. The 2 or 3 distinct hyperdiploid populations were present singly or sometimes in combination in one sample. Five of the 11 samples from 1 of the heterogeneous tumors and its axillary metastasis contained a single diploid population. Therefore, flow cytometric analysis of a single sample from a breast carcinoma may not be representative of the entire tumor. The study of multiple samples of breast carcinomas by flow cytometry is necessary for full characterization of the tumors.

Adult↗
PubMed1985

A comparison of human breast cancer cell kinetics measured by flow cytometry and thymidine labeling.

Flow cytometric determination of tumor ploidy and S-phase fraction following collagenase dissociation and thymidine labeling was performed on 75 consecutive breast cancers. Estrogen and progesterone receptor levels and routine histologic examination also were obtained on each tumor. Cell viability following collagenase dissociation varied from 13 to 95% with a mean of 71%. Thirty-six tumors were diploid, four tetraploid, and four hypertetraploid, and the remainder had DNA indices between 1.1 and 1.9. There was no significant correlation between tumor ploidy and tumor size or estrogen receptor positivity or negativity. The percentage of cells in S-phase varied from 1.2 to 20.0% with a mean of 6.0% utilizing a rectilinear model for histogram analysis that integrated a 10-contiguous channel sample containing the lowest number of cells in S-phase (S-pFL). The mean S-pFL of diploid carcinomas (3.43%) was significantly lower than that of hyperdiploid carcinomas (8.38%). There was good correlation between S-phase fraction determined by thymidine-labeling index (TLI) and S-pFL (r = 0.772, p = 0.0001). S-pFL predicted whether a tumor would be above or below median TLI with an accuracy of 90.5%. Estrogen receptor-negative cancers tended to have higher TLIs and S-pFLs than estrogen receptor-positive cancers; however, there was no correlation between progesterone receptor positivity or negativity and TLI and S-pFL.

Breast Neoplasms↗
PubMed1984

Practical breast carcinoma cell kinetics: review and update.

The S-phase fraction (SP) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100) the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50-80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.

Aneuploidy↗
PubMed1984

Glucocorticoids modulate macrophage surface oligosaccharides and their bone binding activity.

The circumstantial evidence that indicates that glucocorticoids (GC) may stimulate osteoclastic resorption in vivo has recently found support in observations that demonstrate that these compounds effectively increase the activity of isolated resorptive cells (osteoclasts, macrophage polykaryons, and elicited macrophages [MO] ) in vitro. Data are presented here that indicate that this stimulation by GC is due to an enhancement of the initial stage of the resorption process, the attachment of cells to bone, and that this is caused by alterations of cell surface oligosaccharides. Specifically, dexamethasone and cortisol enhance by 80% the attachment of MO to bone surfaces in a dose dependent manner but do not alter or reduce the binding of these cells to other surfaces (plastic, collagen, and hydroxyapatite crystals). The effect of GC on cell-bone attachment is blocked by the glycosylation inhibitor, tunicamycin, and the glycosylation modifier, swainsonine; this demonstrates that asparagine-linked oligosaccharides are involved in the stimulatory process. Flow cytometric analysis of GC-treated cells using a panel of fluoresceinated lectins confirms this by indicating a selective, enhanced exposure of plasma membrane-associated N-acetylglucosamine and N-acetylgalactosamine residues, sugars we have previously shown to be pivotal in MO-bone binding. Finally, progesterone, a known GC antagonist, blocks GC-stimulated resorption, macrophage-bone binding, and membrane oligosaccharide modification, presumably by competing for the GC receptor. Progesterone alone alters none of these processes. Thus, GC stimulates the resorptive activity of macrophages by enhancing the initial events in the degradative process (cell-bone binding) and does so, apparently, via receptor-mediator alteration of cell surface glycoproteins.

Animals↗
PubMed1984

A method for dissociation of viable human breast cancer cells that produces flow cytometric kinetic information similar to that obtained by thymidine labeling.

Collagenase dissociation, performed on 40 human breast cancers, yielded between 1 million and 50 million cells from less than 1 g of tissue from each tumor. Approximately 60% of cells (mean) was considered viable as judged by trypan blue exclusion and phase microscopy. On subsequent flow cytometric analysis, 20 cancers (50%) were considered diploid, three were tetraploid, and the remainder, hyperdiploid. Thymidine labeling (TLI) and flow cytometry following mechanical dissociation also were performed on 23 of these 40 tumors. Among this group of 23 cases, the median percentage of S-phase cells obtained by collagenase dissociation was 5.4, by TLI was 5.7, and by mechanical dissociation was 9.7. There was excellent correlation between the percentage of S-phase cells obtained by collagenase and TLI (r = 0.847, p = 0.0001) but only fair correlation between the percentage of S-phase cells obtained by mechanical dissociation and TLI (r = 0.597, p = 0.0027). The percentage of S-phase cells obtained by either collagenase or mechanical dissociation predicted whether a tumor was above or below median TLI in 19 of 23 cases (p = 0.0018). Estrogen receptor positivity or negativity did not predict whether a tumor was above or below median TLI (r = 0.283, p = 0.130) or above or below median S-phase fraction following collagenase dissociation (r = 0.218, p = 0.182), nor did quantitative estrogen receptor correlate significantly with TLI (r = 0.283, p = 0.13) or S-phase fraction (r = 0.218, p = 0.18).

Breast Neoplasms↗
PubMed1980

Transglutaminase activity of cultured human prostatic epithelium.

A transglutaminase was extracted from cultured human prostatic adenocarcinoma cells. The enzyme did not exist as a zymogen and had an apparent molecular weight of 72,000 +/- 4,000 by gel filtration. Although the role of this transglutaminase in the human prostate is uncertain, it may be a useful marker for prostatic cells in vitro.

Adenocarcinoma↗
PubMed1980

An in vitro assay procedure to test chemotherapeutic drugs on cells from human solid tumors.

An in vitro assay was developed to measure the chemotherapeutic drug susceptibility of cells from human tumors. The assay utilized live cells, freshly isolated from tumor tissue, which were incubated for a short period in vitro. The drug-induced inhibition of incorporation of radiolabeled precursor into DNA, RNA, and protein was measured. The assay is sensitive to concentrations of chemotherapeutic drugs in the therapeutic range and is reproducible when tested with replicates of the same tumor cell population.

Animals↗
PubMed1980

Activation of cyclophosphamide for in vitro testing of cell sensitivity.

Two methods are described for the activation of cyclophosphamide by a liver microsome preparation. These procedures were applicable to an assay in vitro which tests the sensitivity of tumor cells to the drug. Satisfactory results were obtained either by pretreatment of the cyclophosphamide and removal of the microsomes before testing or by the somewhat simpler procedure of mixing drug, microsomes, and test cells for the assay. Microsome treatment of bleomycin gave a smaller increase in activity, and much smaller effects were seen on some other drugs.

Animals↗
PubMed1978

Isolation of a human prostate carcinoma cell line (DU 145).

A long-term tissue culture cell line has been derived from a human prostate adenocarcinoma metastatic to the brain. The cell line, DU 145, has been passaged 90 times in vitro over a period of 2 years. The cells are epithelial, grow in isolated islands on plastic Petri dishes, and form colonies in soft agar suspension culture. Karyotypic analysis demonstrates an aneuploid human karyotype with a modal chromosome number of 64. Distinctive marker chromosomes (a translocation Y chromosome, metacentric minute chromosomes and three large acrocentic chromosomes) have been identified. Electron microscopy of the original tumor tissue and of the tissue culture cell line show a remarkable similarity in cell organelle structure.

Acid Phosphatase↗
PubMed1978

Investigation of human urogenital tract tumors of papovavirus etiology: brief communication.

Cells cultured from human urogenital cancer and other cancers as well as cells from noncancerous tissues were examined by immunofluorescent staining with antibodies to T-antigens and capsid antigens of papovaviruses BK virus (BKV), JC virus, and simian virus 40(SV40), and to capsid antigens of herpes simplex virus types 1 and 2 and human cytomegalovirus (CMV). Cells from early passage cultures of 123 primary tissues and from 14 continuous lines derived from transitional or renal cell carcinoma were tested. None of the cell preparations was specifically stained with any of the antisera. A serologic comparison of patients with bladder cancer, patients with prostate cancer, and normal control groups of BKV hemagglutination-inhibiting and SV40-neutralizing antibodies showed no differences among the 3 groups. None of the sera in the 3 groups had SV40 or BKV T-antibodies. In tests of supernatants of 35 primary cultures for presence of virus, a single isolation, that of a cytomegalovirus, was made. The study revealed no evidence that infection with papovaviruses of the SV40-polyoma subgroup has any part in the production of bladder and prostate cancer.

Animals↗
PubMed1977

Scanning and transmission electron microscopy of human prostatic acinar cells.

Benign hyperplastic and neoplastic human prostate tissue samples were obtained by needle biopsy, transurethral resection or open prostatectomy. Acinar cells of both types of tissues were examined in the scanning electron microscope. It had been reported previously that adenocarcinoma acinar cells were more heterogeneous in size and shape than BPH acinar cells; the purpose of this study was to determine if there were surface morphology differences between the two types of tissues. Acinar cells were found to be extremely heterogeneous in their surface morphologies; three major types of surface morphologies were present - microvillous, ruffled, and bare. Within each class of surface morphology there was heterogeneity, both in size and density, of surface structures present. Microvillous, ruffled, and bare cells appeared to be present in normal, BPH, and neoplastic acini with no significant qualitative or quantitative differences in surface morphologies. Infrequently, it was possible to distinguish between well-differentiated and poorly-differentiated carcinomas because cells of the latter tissues were present in sheets rather than acini and appeared flat and totally devoid of surface detail. The SEM studies also sought to determine a marker to establish the origin of prostate tissue culture cells as normal, BPH or cancerous. Surface morphologies from tissues could be traced into the tissue cultures; again, three types of cells are present - bare, microvillous, and ruffled. However, since surface morphology does not appear to be a distinguishin feature of the pathology of the tissue it cannot provide a distinguishing marker for the origin of tissue culture cells. Scanning electron microscopy also provided an opportunity to observe possible secretory mechanisms and products in the prostate acinar cells.

Adenocarcinoma↗