Biomedical subjects

M M Lieber

Publications and source records attributed to M M Lieber.

At least 163 records · Page 9Linked to original sources

PubMed1988

A nuclear binding assay for measurement of biologically active androgen receptors in animal tissues and human prostate cancer.

A nuclear binding (NB) assay has been developed for the measurement in intact viable cells of biologically active (functional) estrogen and progesterone receptors, i.e. those capable of binding to nuclear acceptor sites [Spelsberg et al., Endocrinology 121: 631 (1987)]. This paper describes the application of this assay to analyses of androgen receptors in the guinea pig seminal vesicle and in human prostatic carcinoma. Cells from fresh animal seminal vesicles or human prostate carcinoma are isolated using collagenase and are incubated with [3H]R1881 for 1 h at 22 degrees C, after which nuclei are isolated at 4 degrees C and assayed for DNA and radioactivity. This NB assay demonstrates a saturable, temperature dependent, steroid and tissue specific nuclear binding of [3H]R1881 for the guinea pig-seminal vesicle system. The nuclear binding is of high affinity and low capacity. The NB assay reveals several important aspects of the androgen and estrogen receptors in target tissues: (1) the nuclear acceptor sites for androgen receptor (AR) are steroid receptor specific; (2) there are different concentrations of the androgen and estrogen receptors between the epithelium and the fibromuscular components of the guinea pig seminal vesicle; and finally (3) some biopsies of human prostate cancer appear to contain biologically inactive AR. This assay may be useful in the analyses of functional receptors in biopsies of human cancer cells.

Animals↗

PubMed1988

Magnetic resonance imaging of renal oncocytoma.

Two cases of renal oncocytoma studied by magnetic resonance imaging (MRI) suggest that this new imaging modality may prove useful in the preoperative diagnosis of oncocytoma and its differentiation from renal cell carcinoma.

Adenoma↗

PubMed1988

Transitional cell carcinoma of the renal pelvis: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Nuclear deoxyribonucleic acid ploidy analysis by flow cytometry was performed successfully on 109 formalin-fixed paraffin-embedded tissue specimens of transitional cell carcinoma of the renal pelvis. Tumor tissues were from patients who were operated upon between 1960 and 1975, so that long-term clinical followup was available. There were good correlations among deoxyribonucleic acid ploidy pattern and histological grade, pathological stage and clinical outcome. For high grade, high stage tumors deoxyribonucleic acid ploidy pattern provided no additional prognostically important information. However, for the more common low grade, low stage tumors the occasional detection of deoxyribonucleic acid aneuploidy patterns identified an important subgroup of patients who experienced significantly poorer survival.

Actuarial Analysis↗

PubMed1988

Embryonal rhabdomyosarcoma of bladder and prostate: nuclear DNA patterns studied by flow cytometry.

Nuclear deoxyribonucleic acid ploidy studies with paraffin-embedded archival tumor specimens were performed by flow cytometry on extracted nuclei from 13 embryonal rhabdomyosarcomas of the bladder and prostate. Preparation of embedded tissue specimens into single dissociated nuclei was by the Hedley technique and they were stained with propidium iodide according to the Vindeløv method. Before the era of chemotherapy, 6 of 7 patients died of disease at a median of 5.5 months post-treatment. All 6 deaths occurred in patients with deoxyribonucleic acid aneuploid patterns that were stage II or greater. The 1 survivor had a deoxyribonucleic acid aneuploid pattern and stage I disease and is alive at 12 years of followup. Since 1971, 6 patients were treated with primary polychemotherapy and surgery. All 6 patients are alive without evidence of disease at a mean followup of 75 months (range 12 to 180 months). All 6 patients had deoxyribonucleic acid aneuploid tumors. One patient was stage I and 5 patients were stage III. Thus, all patients with pediatric embryonal rhabdomyosarcoma of the bladder and prostate had deoxyribonucleic acid aneuploid tumors. These patients responded well to treatment with the combination of chemotherapy and surgery.

Aneuploidy↗

PubMed1988

Primary squamous cell carcinoma of the male urethra: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Flow cytometry analysis was performed on 30 primary male urethral squamous cell carcinoma specimens. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Bulbomembranous urethral tumors had a higher incidence of abnormal deoxyribonucleic acid ploidy patterns than penile urethral tumors (69 and 29 per cent, respectively). Of the tumors exhibiting a deoxyribonucleic acid diploid pattern and an abnormal (deoxyribonucleic acid tetraploid or aneuploid) histogram 18 and 93 per cent, respectively, showed tumor progression (p less than 0.001). None (0 per cent) of the low grade (grade 1 or 2) tumors with a deoxyribonucleic acid diploid pattern developed local recurrence or distant metastases, whereas 90 per cent of the low grade tumors with an abnormal deoxyribonucleic acid pattern progressed (p less than 0.002). Patients with tumors exhibiting deoxyribonucleic acid diploid ploidy had 5 and 10-year rates free of disease of 85 per cent. In contrast, patients with tumors with abnormal deoxyribonucleic acid ploidy patterns had 5 and 10-year rates of 20 and 0 per cent, respectively (p less than 0.001). Determination of deoxyribonucleic acid ploidy pattern by flow cytometry provides important prognostic information for male patients with primary squamous cell carcinoma of the urethra.

Adult↗

PubMed1988

Stage D1 prostatic adenocarcinoma: significance of nuclear DNA ploidy patterns studied by flow cytometry.

Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 91 samples of prostatic adenocarcinoma from patients with stage D1 disease (metastatic deposits in pelvic lymph nodes). All patients had undergone radical retropubic prostatectomy and bilateral pelvic lymphadenectomy. Clinical follow-up ranged from 5 to 19 years. Nuclei were extracted from paraffin-embedded archival material. Isolated nuclei were stained with propidium iodide. The DNA ploidy pattern was diploid (normal) in 42% of tumors, tetraploid in 45%, and distinctly aneuploid in 13%. Only 15% of DNA diploid tumors progressed locally or systemically, whereas 75% of tumors with an abnormal DNA ploidy pattern (tetraploid or aneuploid) subsequently progressed (P less than 0.0001). Among low-grade tumors, ploidy analysis detected a subgroup associated with a poor prognosis; among high-grade tumors, a subgroup associated with a favorable prognosis was detected. None of the patients with a DNA diploid tumor died of prostatic cancer during the period of observation. In contrast, 43% of patients with DNA tetraploid tumors and 44% of those with DNA aneuploid tumors had died of prostatic cancer 10 years after surgical treatment (P less than 0.001). Determination of nuclear DNA ploidy pattern by flow cytometry provides objective, highly significant, prognostic information for patients with stage D1 prostatic carcinoma.

Adenocarcinoma↗

PubMed1988

Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry.

Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas.

Adult↗

PubMed1987

Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern.

Flow cytometric DNA histograms of colorectal carcinomas from 264 patients were evaluated for the association of tumor site, Dukes' stage, tumor grade, and preoperative carcinoembryonic level with patient survival. The DNA nondiploid carcinomas were significantly more common from the left (descending and sigmoid) colon and the rectum. A poorer prognosis was found for patients with DNA nondiploid cancers than for patients with DNA diploid cancers. This was particularly true for patients with Dukes' stages B2 and C tumors with a small number (one to three) of lymph nodes with metastatic deposits. The DNA nondiploid cancers also had a relatively poorer prognosis in patients with unresectable disease. In a Cox multivariate analysis model, the DNA pattern was an independent prognostic variable for this group of 264 patients with resected colorectal carcinoma.

Carcinoembryonic Antigen↗

PubMed1987

The relative prognostic value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma.

The DNA histograms of resected rectal carcinomas from 121 patients were compared, along with a detailed clinicopathologic assessment of the same tumors, with the incidence of postresection tumor recurrence and patient survival over an extended period of 15-year follow-up. A poorer prognosis was found for patients with DNA aneuploid and DNA tetraploid rectal cancers as compared with patients with DNA diploid cancers. In addition, local tumor recurrence was twice as common among patients with DNA nondiploid rectal carcinomas. The DNA pattern of a rectal carcinoma was an independent prognostic variable in a Cox's multivariate analysis model. DNA nondiploid rectal carcinomas had a statistically significant increased incidence of vascular invasion, tumor fibrosis, and high Dukes' stage.

Aged↗

PubMed1987

In vitro chemotherapy sensitivity testing of human ovarian carcinoma: comparison of optical colony counting and [3H]thymidine incorporation assays.

Optical colony counting was used for assessing drug sensitivity of 87 samples (from 51 primary solid tumors, 19 metastatic solid tumors, and 17 ascites fluids) from 83 common epithelial type ovarian carcinomas. The evaluability rate by the optical counting method was 26.4%. Fifty of these samples were also assessed by a tritiated thymidine ( [3H]dThd) incorporation assay (evaluability rate by incorporation assay, 74%). In the 12 cases fully evaluable by both methods, the correlation coefficients for regression of drug sensitivity data between the methods ranged from 0.503 to 0.976 (mean, 0.745); for the combined data of these cases, the correlation coefficient was 0.707. The new [3H]dThd assay appears useful and efficient for performing in vitro chemotherapy sensitivity testing of human ovarian cancer.

Antineoplastic Agents↗

PubMed1987

Wilms tumors: relationship of nuclear deoxyribonucleic acid ploidy to patient survival.

Nuclear deoxyribonucleic acid ploidy studies with paraffin-embedded archival tumor specimens were performed by flow cytometry on extracted nuclei from 56 Wilms tumors. Before the era of chemotherapy 9 patients had a 33 per cent survival rate at 5 years. No significant correlation between deoxyribonucleic acid ploidy pattern and survival was seen in this early group of patients. Since 1960, 47 patients underwent radical nephrectomy and received chemotherapy. Deoxyribonucleic acid histograms in this group were normal in 13 tumors, while 23 tumors exhibited a tetraploid pattern (greater than 10 per cent nuclei in the G2 peak) and 11 showed an aneuploid pattern. Survival rates according to deoxyribonucleic acid ploidy pattern showed that 100 per cent of the patients with a normal or aneuploid histogram pattern were alive at 2 and 5 years. Patients with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 74 and 69 per cent at 2 and 5 years (p less than 0.02 and less than 0.01), respectively. Tumors with a normal or aneuploid histogram pattern for all stages and a deoxyribonucleic acid tetraploid pattern for pathological stage I or II were associated with a 2 and 5-year survival rate of 100 and 97 per cent, respectively. However, patients with stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern had a significantly worse survival of 25 per cent at 2 and 5 years (p less than 0.0001). Measurement of nuclear deoxyribonucleic acid ploidy identifies a patient group who are at high risk for treatment failure, that is stages III and IV tumors with a deoxyribonucleic acid tetraploid pattern.

Actuarial Analysis↗

PubMed1987

Well differentiated clear cell renal carcinoma: significance of nuclear deoxyribonucleic acid patterns studied by flow cytometry.

Nuclear deoxyribonucleic acid ploidy was determined in 206 samples of well differentiated clear cell renal carcinoma via a previously described technique on paraffin-embedded archival material. Grade 2 tumors had a higher incidence of abnormal deoxyribonucleic acid patterns than grade 1 tumors. Of stage 1 well differentiated clear cell renal tumors 60 per cent had a normal deoxyribonucleic acid histogram pattern, whereas 67 per cent of higher stage tumors had an abnormal pattern. The existence of abnormal nuclear deoxyribonucleic acid histogram patterns in the primary tumor tissue had a significant correlation with subsequent development of metastatic disease, independent of tumor grade and stage. The 10-year actuarial survival rate was 62 per cent for patients with normal deoxyribonucleic acid histograms and 37 per cent for patients with abnormal patterns. These results demonstrate that nuclear deoxyribonucleic acid ploidy measured by flow cytometry is an important variable in the classification and determination of prognosis for patients with clear cell renal carcinoma.

Adult↗

PubMed1987

Leiomyosarcomas and benign smooth muscle tumors of the stomach: nuclear DNA patterns studied by flow cytometry.

Paraffin-embedded archival tissue samples were used for determination of DNA ploidy by flow cytometry on 117 surgically resected gastric smooth muscle tumors (44 leiomyosarcomas, 53 leiomyomas, and 20 benign leiomyoblastomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 53 leiomyomas, the DNA ploidy pattern was diploid in most tumors (87%), except for 2 DNA tetraploid/polyploid and 5 DNA aneuploid samples. In comparison, the 20 benign leiomyoblastomas had more frequent abnormal DNA histograms: DNA tetraploidy/polyploidy in 5 (25%) and DNA aneuploidy in 2 (10%). The DNA histograms of the 44 leiomyosarcomas (including 4 epithelioid leiomyosarcomas) were classified as follows: 20 cases (45%) exhibited a DNA diploid pattern, 14 cases (32%) had a DNA tetraploid/polyploid pattern, and 10 cases (23%) had DNA aneuploid peaks. For the patients with leiomyosarcomas, the DNA ploidy pattern was significantly correlated with survival (P less than 0.001), as were tumor grade (P less than 0.001) and tumor size (P less than 0.05). Furthermore, both benign and malignant gastric smooth muscle tumors with DNA tetraploid/polyploid patterns were significantly larger than those with a DNA diploid histogram (P less than 0.05). DNA ploidy pattern cannot be used for diagnosis--that is, to distinguish malignant from benign gastric smooth muscle tumors. For gastric leiomyosarcomas, however, nuclear DNA ploidy pattern is an easily measured objective determination with important prognostic significance.

Adolescent↗

PubMed1987

Flow cytometric DNA patterns from colorectal cancers--how reproducible are they?

The heterogeneity of DNA ploidy patterns within individual colorectal carcinomas was investigated by analyzing 261 different samples from 30 fresh colorectal cancers. The results of DNA analysis of multiple superficial cup biopsy specimens, of multiple full-thickness fresh tumor slices, and of nuclei extracted from paraffin-embedded pathologic archival specimens with use of the Hedley technique were compared. The same DNA ploidy pattern was found in all specimens of 19 (63%) of the 30 tumors studied. Minimal heterogeneity for DNA ploidy pattern was noted in seven carcinomas (23%), and moderate to marked heterogeneity was found in an additional four tumors (13%). The DNA pattern of a full-thickness specimen from 79% of the carcinomas studied was the same when samples were obtained from any one of five possible sites. In addition, the DNA ploidy pattern of the majority of the carcinomas could have been accurately predicted by flow cytometric DNA analysis of superficial cup biopsy specimens. These results demonstrate that most colorectal carcinomas are DNA ploidy homogeneous. Therefore, measurement of this tumor property can be used in future clinical research studies with some degree of confidence.

Colonic Neoplasms↗

PubMed1987

Adrenocortical carcinoma: nuclear deoxyribonucleic acid ploidy studied by flow cytometry.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with use of paraffin-embedded specimens were performed by flow cytometry on 52 adrenocortical carcinomas. Specimens were prepared by the combined techniques of Hedley and Vindeløv. Clinical course was obtained by chart review and follow-up examination. Nine (17%) tumors had a normal (diploid) DNA pattern, 13 (25%) were DNA tetraploid, and 30 (58%) were DNA aneuploid. The DNA aneuploid group was subdivided: 18 tumors with one stemline and 12 tumors with two stemlines of abnormal DNA cells. For tumors that were resected for cure, the 5-year Kaplan-Meier disease-free survival rates of the five patients with DNA diploid tumors and of the six patients with DNA tetraploid tumors were 80% and 33%, respectively. For 21 patients of whom 12 had one-stemline and nine had two-stemline DNA aneuploid tumors, the survival was 67% and 0%, respectively. Following palliative resection, the 4-year survival rates of the four patients with DNA diploid, seven with DNA tetraploid, five (omitting one with short follow-up) with one-stemline DNA aneuploid, and three with two-stemline DNA aneuploid tumors were 0%, 0%, 0%, and 33%, respectively. Although adrenocortical carcinoma is in general markedly aggressive, the addition of nuclear DNA ploidy studies may help to identify certain groups of patients who have a relatively favorable prognosis.

Adrenal Gland Neoplasms↗

PubMed1987

Surgery vs radiation for localized prostate cancer.

With the increased incidence of prostate cancer, decisions regarding its treatment are now both complex and frequent. Accurate staging is crucial. Then appropriate treatment can be decided on, using nondogmatic common sense.

Aged↗

PubMed1987

Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in resected hepatic metastases from colorectal carcinoma.

Nuclear deoxyribonucleic acid (DNA) ploidy studies of paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 101 surgically resected hepatic metastases from colorectal cancer. In 28 patients, the corresponding primary carcinoma of the metastases was also studied. Tumor clinicopathology and clinical course of the patients were reviewed. Preparation of paraffin-embedded tissue specimens was performed by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindelov et al. Eighty-eight of 101 metastatic tumors and 26 of 28 primary tumors yielded evaluable DNA histograms. Twenty-six metastases showed a DNA diploid pattern, 25 showed a significantly increased 4C peak (DNA tetraploid/polyploid), and 37 had a DNA aneuploid peak. Ploidy pattern was constant between primary and metastases in 84.6% of tumors. No significant relationship between host and tumor characteristics and ploidy pattern was found except for a correlation between grade 3 metastases and DNA aneuploid. Survival of patients with DNA aneuploid metastases was significantly less than that of patients with DNA diploid metastases (p = 0.03). However, among DNA nondiploid metastases, survival was significantly less for low DNA index metastases (less than or equal to 1.5) than for high DNA index (greater than 1.5) metastases (p less than 0.05). Flow cytometric DNA ploidy measurements may have prognostic value for patients with resected hepatic metastases from colorectal carcinoma.

Colonic Neoplasms↗

PubMed1986

Metabolic stability of experimental chemotherapeutic agents in hepatocyte:tumor cell co-cultures.

A U.S. National Cancer Institute screening program for new anticancer drugs, based on the growth of primary human tumor cells in an in vitro soft agar colony formation assay, has resulted in the identification of a number of compounds that have cytotoxic activity against primary human tumor cells in vitro but are inactive in the conventional in vivo murine P388 leukemia animal model pre-screen. To investigate whether metabolic inactivation ov the compounds might be a factor in the lack of in vivo cytotoxicity we have co-cultured rat hepatocytes with A204 rhabdomyosarcoma and murine P388 leukemia cell lines in the soft agarose colony formation assay for 24 h during exposure to the compounds. Twenty compounds with a range of in vitro activities were studied. Thirteen compounds exhibited cytotoxicity against A204 cells in culture; nine of them were less active when co-cultured with hepatocytes, two were activated by hepatocyte co-culture, and two showed no effect of hepatocyte co-culture. P388 cells were more sensitive to the antiproliferative effects of the compounds than A204 cells. Two compounds that were not active against A204 cells exhibited cytotoxicity against P388 cells. One compound was inactivated by hepatocyte co-culture and one showed no effect. Five compounds showed no cytotoxicity toward either A204 cells or P388 cells. Two of the compounds showing hepatocyte inactivation in vitro possess activity in one or more in vivo tumor models. Thus, evidence for metabolic inactivation in hepatocyte co-culture is not always an indication for lack of in vivo antitumor activity. Hepatocyte co-culture methodology provides a simple and objective means, amenable to large-scale screening, of distinguishing metabolic activation or inactivation of a given compound from other pharmacokinetic and pharmacodynamic factors with a minimum of material.

Animals↗