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Biomedical subjects

C J Rodenburg

Publications and source records attributed to C J Rodenburg.

At least 37 records · Page 2Linked to original sources

Prognostic value of pS2 protein and receptors for epidermal growth factor (EGF-R), insulin-like growth factor-1 (IGF-1-R) and somatostatin (SS-R) in patients with breast and ovarian cancer.

The prognostic value of EGF-R, IGF-1-R and SS-R, and of cytosolic estrogen-regulated pS2 protein, was studied in patients (pts) with primary breast and advanced ovarian cancer. Ovarian cancer tissues were negative for pS2 (by immunoradiometric assay) IGF-1-R and EGF-R contents (by ligand binding assay, LBA) were of no or moderate prognostic value for breast cancer pts (n = 214). For advanced ovarian cancer pts, EGF-R content determined by LBA (n = 55) showed no prognostic value, whereas EGF-R status (n = 35) determined by immunohistochemistry (MoAb 2E9) significantly correlated with progression of disease (P less than 0.05). In breast cancer pts, both SS-R and pS2 showed no association with tumor size, nodal status and grade. For pS2 the best cut-off level with respect to relapse-free (RFS) and overall survival (OS) was found to be 11 ng/mg protein. Both SS-R (1 g% SS-R+, n = 135; P less than 0.04) and pS2 (27% pS2+, n = 197; P less than 0.001), which were mainly positive in ER+ tumors, were of prognostic value, especially within the subgroups with ER+/PgR+ tumors. Also within N+ and No pts the 5-yr RFS and OS showed a difference between pS2+ and pS2- (33 and 54% for N+, and 31 and 13% difference for No pts). In summary, SS-R and pS2 are valuable prognosticators in breast cancer pts, and prognostic significance of EGF-R in ovarian cancer pts needs further study.

Biomarkers, Tumor↗

Carcinoma of unknown primary: identification of a treatable subset?

We initiated a phase II study with combination chemotherapy consisting of cisplatin, etoposide and bleomycin in a subset of patients with carcinomas of unknown primary site characterized by the presence of at least one of the following criteria: 1) age below 50 years; 2) clinical evidence of rapid tumour growth; 3) tumour located predominantly in a midline distribution; 4) good response to previous administered radiotherapy. In 34 evaluable patients an objective response rate of 53% (95% confidence limits 35%-70%) was achieved. For patients with poorly differentiated adenocarcinomas the response rate was 35%, and, in most instances, of short duration. A response rate of 79% including complete responses and long-term survivals was achieved in patients with undifferentiated carcinomas. This difference in response rate was statistically significant (p = 0.02). No supplementary prognostic factors predicting response to chemotherapy could be identified. One patient with an initial diagnosis of undifferentiated carcinoma proved to have a malignant lymphoma after additional immunohistochemical investigation. Until a better characterization of this syndrome is possible patients with undifferentiated carcinomas of unknown primary site should be challenged with cisplatin-based chemotherapy.

Adenocarcinoma↗

Antiprogestins, a new form of endocrine therapy for human breast cancer.

The antitumor, endocrine, hematological, biochemical, and side effects of chronic second-line treatment with the antiprogestin mifepristone (RU) 486) were investigated in 11 postmenopausal patients with metastatic breast cancer. We observed one objective response, 6 instances of short-term stable disease, and 4 instances of progressive disease. Mean plasma concentrations of adrenocorticotropic hormone (P less than 0.05), cortisol (P less than 0.001), androstenedione (P less than 0.01), and estradiol (P less than 0.002) increased significantly during treatment accompanied by a slight decrease of sex hormone binding globulin levels, while basal and stimulated gonadotropin levels did not change significantly. The increased basal cortisol levels could not be further stimulated by synacthen, nor suppressed by 1 mg of dexamethasone. Plasma estradiol concentrations were significantly correlated with both androstenedione (P less than 0.05) and cortisol levels (P less than 0.01). The percentage of eosinophilic white blood cells (P less than 0.02) and mean plasma creatinine concentration (P less than 0.05) increased significantly. Side effects frequently occurred during long-term treatment and appeared to be caused mainly by the antiglucocorticoid properties of the drug. It is concluded that antiprogestins form a new treatment modality in the endocrine treatment of human breast cancer. New antiprogestins with less antiglucocorticoid side effects might be especially of value as an adjunct to antiestrogenic treatment in view of our finding that combined antiestrogenic and antiprogestational treatment caused additive growth-inhibitory effects in rat mammary tumors.

Aged↗

Clinical relevance of various microscopical features of the second-look specimen in advanced ovarian cancer.

The second-look specimens of 70 patients with advanced ovarian cancer (FIGO 2B, 3, and 4) were reviewed and classified according to four categories: no response to chemotherapy (category a), predominantly histologically viable tumor with some necrotic and/or fibrotic tissue (category b), predominance of fibrosis and recrosis (category c), and no evidence of tumor, i.e., pathologically proven complete response (PCR) (category d). All of the patients in categories a and b had died because of ovarian cancer at the end of the observation period. In category c, 17/25 patients eventually achieved a PCR as established at a third-look procedure. The median survival of 56 months in this group was lower than that of the patients in category d (64 months), although this difference was without statistical significance. These observations underscore the importance of the microscopical features of the second-look specimen for the treatment of advanced ovarian cancer.

Female↗

DNA flow cytometry and morphometry as prognostic indicators in advanced ovarian cancer: a step forward in predicting the clinical outcome.

In 74 patients with advanced ovarian cancer, the value of DNA flow cytometry and morphometry was evaluated and compared with histological grading and clinical outcome. By means of both DNA flow cytometry and morphometry a clear distinction was found between a favorable group of 15 patients, with a median survival of more than 60 months, and the remaining patients, of whom the majority died during the same follow-up period. The levels of significance for DNA flow cytometry (P = 0.0002) and morphometry (P = 0.0001) with respect to survival of the favorable and unfavorable groups of patients were higher than for histological grading (P = 0.02). In a multivariate analysis it was demonstrated that morphometry proved to be the factor of most relevance for survival, although the effect of DNA flow cytometry was almost as good. Data such as presence of ascites, the size of the residual tumor mass, choice of chemotherapy, FIGO stage, and histological grade were not of additional prognostic relevance in this analysis. It is concluded that both morphometry and DNA flow cytometry are a step forward in identifying favorable and unfavorable groups of patients with advanced ovarian cancer. For the daily practice of management of ovarian cancer patients, morphometry may be an attractive support of visual grading.

Adenocarcinoma↗

Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome.

The monoclonal antibody RAP 5 immunoreactive with the ras gene product p21 was used in an immunohistochemical study of 57 patients with advanced ovarian cancer and in 28 normal ovaries. The pattern of the staining of various tumor specimens was similar to the germinal epithelium of normal ovaries, whereas the intensity of staining was more enhanced in carcinomas than in normal ovaries. However, we found a lack of correlation among staining intensity of RAP 5 and the histologic type, the histologic grade, the ploidy class, and the clinical outcome.

Adenoma↗

Use of DNA image cytometry in addition to flow cytometry for the study of patients with advanced ovarian cancer.

Forty-five patients with advanced ovarian cancer were studied with both DNA flow cytometry (FCM) and automatic DNA image cytometry carried out with the Leiden Television Analysis System (Leytas). There was a significant difference in survival between the diploid and nondiploid cases as determined by FCM. Furthermore, the presence of nuclei with a high DNA content (defined as a DNA content higher than 5C) as determined by Leytas indicated a poor prognosis. When the combined results of FCM and Leytas were taken into account, three different groups of patients could be distinguished. The group of patients with a diploid malignancy (n = 12) had a median survival of more than 60 months. The group of patients (n = 11) with a nondiploid tumor having fewer than 100 nuclei with a high DNA content per 1600 microscope fields formed an intermediate group (median survival, 42 months), whereas the median survival of the remaining patients (n = 22), who had a nondiploid malignancy combined with more than 100 of these nuclei per 1600 microscope fields, was only 15 months. In addition, comparison of the clinical parameters by means of a multivariate analysis (Cox regression model) showed that the combined results of FCM and DNA image cytometry had the largest influence on survival. It is concluded that DNA image cytometry appears to be supplementary to FCM for the study of DNA ploidy abnormalities and that the combined results of these methods have a major influence on the clinical outcome.

Aneuploidy↗

Tumor ploidy as a major prognostic factor in advanced ovarian cancer.

Tumor ploidy was determined by flowcytometry (FCM) in paraffin-embedded tissue of 74 patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] 2B, 3, 4). Significant differences in survival and progression-free survival were found between classes of tumor ploidy as well as for several clinical parameters, including FIGO stage, histologic grade, diameter of the largest metastases, presence of ascites, peritoneal carcinomatosis, and size of residual tumor. In a Cox regression analysis, tumor ploidy and presence or absence of ascites were the only significant factors for survival, whereas ascites and residual tumor proved to be the significant parameters for progression-free survival. Tumor ploidy was strongly associated with tumor bulk, size of residual tumor, and histologic grade. Tumor ploidy was the same within different tumor sites in the majority of the cases. On the basis of these findings tumor ploidy is considered to be a major prognostic factor for survival in advanced ovarian cancer.

Adult↗

The value of tumour marker CA 125 in surgical pathology.

CA 125 is a tumour marker located primarily on non-mucinous epithelial ovarian tumours and which is recognized by the monoclonal antibody OC 125. In this study the value of CA 125 in surgical pathology was assessed. In fresh frozen material, the expression of CA 125 was demonstrated in 82% of 83 epithelial ovarian neoplasms using the indirect immunoperoxidase technique. In addition, all adenocarcinomas of cervix (n = 5) and endometrium (n = 15) tested expressed CA 125, and 25 of 111 (22%) non-gynaecological malignant tumours were positive. The positive cases included 20 breast carcinomas, one carcinoma of the stomach and one of the colon. Using a commercial kit on routinely fixed, paraffin embedded material, CA 125 positivity was demonstrated in 29 of 36 (80%) serous cystadenocarcinomas after pronase pre-treatment of the sections, in contrast to 100% (n = 25) positivity on frozen tissue sections. CA 125 can, therefore, be demonstrated in routinely fixed paraffin embedded material, although the number of positive results is less than in fresh frozen sections.

Antigens, Neoplasm↗

Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma.

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.

Adolescent↗

Immunohistochemical localization and chromatographic characterization of human chorionic gonadotropin in a bladder carcinoma.

We describe a patient with advanced bladder carcinoma, in which ectopic synthesis and secretion of human chorionic gonadotropinlike immunoreactivity (ihCG) was demonstrated. Concanavalin A-sepharose affinity chromatography of serum revealed that the ihCG differed from placental human chorionic gonadotropin in its carbohydrate moiety. Treatment of the patient with a cisplatin-containing regimen did not result in regression of the tumor. Since immunohistochemistry revealed ihCG in five of 13 additional cases of bladder carcinoma, it is concluded that ectopic production of ihCG by bladder carcinomas is probably not rare.

Carcinoma, Transitional Cell↗