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Biomedical subjects

M L Friedlander

Publications and source records attributed to M L Friedlander.

At least 55 records · Page 3Linked to original sources
PubMed1987

Brenner tumours of the ovary: a study of the histology, immunohistochemistry and cellular DNA content in benign, borderline and malignant ovarian tumours.

Brenner tumours are now generally regarded as being of ovarian epithelial origin. Most have a limited growth potential and are benign. For this reason they are usually found incidentally at hysterectomy. In common with other epithelial ovarian tumours there is a histopathological spectrum of appearances ranging from benign through borderline to invasive malignancy. In this series all 54 tumours were graded according to the degree of cytological atypia, presence of mitoses and tumour necrosis. Heterogeneity of DNA content was observed in the higher grade tumours, two of the four being diploid and two being aneuploid (all benign tumours being diploid). The presence of aneuploidy correlated with the histological features and a poor clinical prognosis. Immunohistochemical staining for keratoprotein was found to be of limited value in the diagnosis of Brenner tumours and their metastases.

Brenner Tumor↗
PubMed1986

Molecular evidence for the clonal origin of blast crisis in chronic myeloid leukaemia.

Cytogenetic and enzymatic studies have shown that chronic myeloid leukemia (CML) represents the clonal proliferation of a pluripotent stem cell. The Philadelphia chromosome (Ph') is the characteristic karyotypic abnormality seen in this disease, although the exact role of this clonal marker in the pathogenesis of CML is uncertain. At a molecular level, the Ph' has recently been shown to represent the translocation of c-abl to a limited (breakpoint cluster region, bcr) on chromosome 22. We have used probes for the bcr gene to obtain molecular evidence for the clonal origin of blast crisis in 2 patient with CML. In both cases, the first with myeloid and the second with lymphoid blast crisis, there was rearrangement of the bcr gene. The patterns of rearrangement varied between patients but were identical when comparing acute and chronic phases within the same individual. As the Ph' translocation is thought to represent a random recombination event these data not only provide further evidence for the clonal origin of blast crisis in CML, but also suggest that in the second patient this translocation event had already occurred at the pluripotent stem cell.

Adult↗
PubMed1985

Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance.

By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease-free survival. This influence of DNA content on disease-free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more tumor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors.

Aneuploidy↗
PubMed1985

Metastasizing placental site trophoblastic tumor: a case study.

The clinicopathologic features of placental site trophoblastic tumor (PSTT), a rare form of trophoblastic disease, were systematically described only relatively recently. Previously, in endometrial curettage and hysterectomy specimens, PSTT was not distinguished from choriocarcinoma or sarcoma, although in most cases the natural history had been benign. A case of biopsy-proved metastasis to para-aortic lymph nodes with radiologic evidence of lung metastasis is reported. Histologically, the tumor appeared similar to the tumors in other reported cases of PSTT. The mitotic rate was variable, being very high in a few small fragments obtained by curettage. Flow cytometric analysis of the tumor showed cells with diploid DNA content and a relatively low proliferative fraction. The tumor maintained its morphologic and functional characteristics following xenotransplantation into Balb/c nu/nu mice. In spite of a treatment regimen that included hysterectomy and multiagent chemotherapy, the patient continued to have evidence of persistent trophoblastic disease 15 months after presentation.

Adult↗
PubMed1985

Ovarian tumour xenografts in the study of the biology of human epithelial ovarian cancer.

Human epithelial ovarian tumours were successfully established as xenografts in nude mice in 54% of cases. An evaluation of the biological characteristics of tumours propagated in nude mice was carried out and the functions investigated included morphology, growth kinetics, cellular DNA content, cell surface antigen expression and sensitivity to chemotherapy. To allow a more detailed study of the influence of ploidy on biological behaviour, xenografted tumour with varying degrees of aneuploidy and tumours with a common ancestry but different ploidies were also established. Although this is a highly selective model system favouring the growth of biologically aggressive tumours the xenografts, in general, reflect many of the characteristics of the tumours from which they were derived and are likely to provide a useful model for investigating the biology of ovarian cancer.

Animals↗
PubMed1985

Selective toxicity of a new lipophilic antifolate, BW301U, for methotrexate-resistant cells with reduced drug uptake.

Three methotrexate (MTX)-resistant cell lines and their MTX-sensitive counterparts have been used to examine 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW301U), a novel lipophilic antifolate, and compare its cytotoxicity with MTX and metoprine. Collateral sensitivity for both BW301U and metoprine was observed in CCRF-CEM/MTX R-cells, where MTX resistance appeared to be primarily due to a deficiency in drug uptake. This was particularly pronounced with BW301U which proved to be as effective in killing CCRF-CEM/MTX R as was MTX with the parental CCRF-CEM cell line. This effect was not seen in other cell lines, L5178Y/MTX or L1210/MTX R, where resistance to MTX was correlated with either an overproduction of 5,6,7,8-tetrahydrofolate:nicotinamide adenine dinucleotide phosphate oxidoreductase EC 1.5.1.3 (DHFR) or with combined uptake defect and increased DHFR levels, respectively. In each case, however, BW301U and metoprine, especially at high concentrations, were more effective than MTX in treating MTX-resistant cells.

Antineoplastic Agents↗
PubMed1984

The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study.

Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Cellular DNA content--a stable feature in epithelial ovarian cancer.

Detailed flow cytometric analysis of cellular DNA content was performed on neoplastic tissue from 33 patients with malignant common epithelial ovarian tumours in order to investigate the intratumoral stability of ploidy and proliferative fraction. There was a remarkable stability, both spatial and temporal, in the DNA pattern for any particular tumour. Of 24 tumours that were analysed in multiple areas tumour ploidy was found to be a stable marker in all but 3 cases where regional variations were evident. In 9 patients serial analyses were performed on tumour obtained either at initial diagnosis (6 patients) or second look laparotomy (3 patients) and then some time later (7-17 months) at relapse or death and in all cases the tumour ploidy remained unchanged. In addition, 10 ovarian carcinomas established in nude mice have maintained a DNA content during serial passage similar to that of the original implanted tumour. In contrast in 50% of tumours that were evaluable for S-phase analysis we demonstrated a considerable intratumoral variability in the S-phase fraction. We conclude that cellular DNA content is a stable feature of ovarian carcinoma while S-phase fraction is commonly subject to intratumoral variation.

Animals↗
PubMed1984

Clinical and biological significance of aneuploidy in human tumours.

Aneuploidy is a well recognised feature of human tumours, but the investigation of its biological and clinical significance has been hampered by technological constraints. Quantitative DNA analysis reflects the total chromosomal content of tumour cells and can now be determined rapidly and reliably using flow cytometry; this has resulted in renewed interest in its potential clinical applications. This article reviews the accumulating evidence that tumour ploidy reflects the biological behaviour of a large number of tumour types and that diploid tumours in particular have a relatively good prognosis. The measurement of tumour ploidy is likely to become a valuable adjunct to the clinical and histopathological assessment of cancers.

Aneuploidy↗
PubMed1984

Abortion: predicting the complexity of the decision-making process.

This study sought to test a conflict theory model of decision-making in abortion. Complex, or conflicted, abortion decisions were defined as those occurring when the woman had desired pregnancy, when the abortion alternative was considered later, and when the decision process was lengthier and subjectively more difficult. Sets of personal and social variables, identified from previous research, were expected to require a more complex decision process. A second objective was to determine whether these variables would also predict previous contraceptive behavior. A large sample of abortion patients completed a survey of attitudes and behaviors related to the abortion decision and contraceptive usage. Results indicated that strong involvement with one's sexual partner tended to encourage contraception but complicated the abortion decision. Strong work commitment likewise encouraged contraception but appeared to simplify the abortion decision. While concern for personal health was significantly associated with contraceptive behavior, it was not related to the decision process in abortion. Interpretation suggested that prevention of unwanted pregnancy and the abortion decision are independent processes, both of which are affected by love and work but in opposite directions.

Abortion Applicants↗
PubMed1984

Flow cytometric analysis of cellular DNA content as an adjunct to the diagnosis of ovarian tumours of borderline malignancy.

Flow cytometric analysis of cellular DNA content was performed on tissue from 44 borderline ovarian tumours (tumours of low malignant potential). Forty-two tumours (95%) were diploid and associated with both an indolent biological behaviour and good prognosis. Aneuploidy was identified in only 2 tumours (5%), and one of the associated patients died of progressive disease within months of the initial diagnosis. Careful review of the histopathology of these 2 aneuploid tumours revealed areas of invasion in the omental and peritoneal "implants" of each. This study has reinforced the currently advocated separation of so-called borderline tumours from invasive ovarian carcinomas and the interpretation of the pathological criteria used to categorize such neoplasms. Our results indicate that flow cytometric analysis of cellular DNA content may complement conventional histopathological diagnosis by providing an objective parameter which correlates with biological behaviour and may identify the few genuine borderline ovarian epithelial neoplasms which show clinical progression.

Adult↗
PubMed1984

Influence of cellular DNA content on survival in advanced ovarian cancer.

Tumor cellular DNA content was measured by flow cytometry in 91 patients with advanced ovarian cancer, using a new and simple technique which allows archival paraffin-embedded tissue to be studied; 69% of the tumors were aneuploid, and 31% were diploid. Tumor ploidy was shown by multivariate Cox model analysis to be an independent prognostic variable and the major determinant of survival. Patients with diploid tumors survived significantly longer than did those with aneuploid tumors (p much less than 0.0001; X2 = 25.44; d.f. = 1).

DNA, Neoplasm↗
PubMed1983

Anchoring and publicity effects in clinical judgment.

Extrapolation from the literature of social-cognitive bias suggested testing anchoring and publicity effects in clinicians' (N = 46) successive judgments of detailed interview notes, five per case. If anchoring occurs, Ss' estimates of a client's pathology and prognosis at the final judgment point would be related differentially to the time (early/late) that they had received salient, pathognomonic case material. The publicity effect would be a tendency toward more conservative estimates on the part of Ss who are asked to justify their ratings in writing. Results among an experienced sample of clinicians indicated significant anchoring in one case but not the other, which suggests a clinical bias to disregard pathognomonic data about a client who is seen initially as less disturbed. Public justification was related neither to Ss' ratings, to reported confidence in their ratings, nor differentially by case. Implications and limitations are suggested.

Adult↗
PubMed1983

The influence of age on the DNA ploidy levels of breast tumours.

Primary tumour DNA content and estimates of cell cycle kinetic parameters were analysed by flow cytometry in 114 cases of breast cancer. Tumours were classified as: near-diploid, single aneuploid, tetraploid and greater, and multiploid (defined as having more than one aneuploid tumour cell population). No significant correlations were found between ploidy and histologic type, tumour size, lymph node involvement or receptor (oestrogen and progesterone) status. a highly significant correlation between ploidy and proliferative activity (as assessed by the percentage of cells in S phase) was observed, with near-diploid and diploid tumours being associated with a low (less than or equal to 10%) S phase fraction (P = 0.0001). A marked relationship between ploidy and patient age was also seen, with increased DNA content being associated with older patients (P = 0.025). In contrast, no patients with multiploid tumours were over 60 yr, and their age distribution was significantly different from the population as a whole (P less than 0.05), suggesting that multiploidy might be a phenomenon associated with the menopause.

Adult↗