Search PubMed⌕ Search

Biomedical subjects

E Paus

Publications and source records attributed to E Paus.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer.

BACKGROUND: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment prostate-specific antigen (PSA). We evaluated the additional prognostic impact of serum levels of neuron-specific enolase (NSE) and chromograninA (CgA) after curative radiotherapy and the importance of serum PSA, analyzed 3 months after irradiation. METHODS: From 1988 to 1995, 161 patients with localized T1-4, pN0M0, prostate adenocarcinoma were treated with external radiation (66Gy, 2Gy/5 fractions per week). Frozen serum samples were assessed for CgA, NSE, and PSA before and 3 months after radiotherapy. CgA was analyzed in only 100 patients. NSE and CgA were determined by a immunometric assay. Total PSA was measured by a time-resolved fluoro-immunometric assay. RESULTS: Prior to radiotherapy CgA was elevated in 16 of 100 patients, and NSE was elevated in 33 of the 161 patients. There was no association between grade, T category or pretreatment PSA and the levels of neuroendocrine markers. Pretreatment-elevated serum NSE, but not initial CgA, identified patients with an unfavorable prognosis. A < 50% reduction of PSA 3 months after radiotherapy was associated with decreased failure-free 10 years urvival. Multivariate analysis demonstrated an increased risk of failure for patients with elevated pretreatment NSE and PSA values, T3 category, and decline of PSA less than 50% 3 months after radiotherapy. The presence of none or several risk factors (1-4) defined clearly separable groups. CONCLUSIONS: Together with T category and pretreatment serum PSA values, serum NSE values before radiotherapy and decrease of serum PSA 3 months after radiotherapy represent easily assessable prognostic parameters in patients undergoing curative radiation treatment for prostate cancer.

Adenocarcinoma↗
PubMed2000

Identification of nucleolar protein No55 as a tumour-associated autoantigen in patients with prostate cancer.

Four different genes were identified by immunoscreening of a cDNA expression library from the human prostate cancer cell line DU145 with allogeneic sera from four prostate cancer patients. A cDNA encoding the nucleolar protein No55 was further analysed and shown to be expressed at the mRNA level in several normal tissues, including ovaries, pancreas and prostate and in human prostate cancer cell lines PC-3, PC-3m and LNCaP. By reverse transcriptase/polymerase chain reaction, expression of No55 was several-fold higher in two out of nine prostate cancer primary tumours and two out of two metastatic lesions, compared to normal prostate tissue. Antibodies to No55 were detected in sera from seven out of 47 prostate cancer patients but not in sera from 20 healthy male controls. Sequence analysis of the No55 open reading frame from normal and tumour tissues revealed no tumour-specific mutations. The No55 gene was located to chromosome 17q21, a region reported to be partially deleted in prostate cancer. Considering the immunogenicity of the No55 protein in the tumour host, the expression profile and chromosomal localization of the corresponding gene, studies evaluating No55 as a potential antigen for immunological studies in prostate cancer may be warranted.

Antigens, Neoplasm↗
PubMed1999

Cushing's syndrome in prostate cancer. An aggressive course of prostatic malignancy.

We report a case with an initial diagnosis of adenocarcinoma of the prostate in whom Cushing's syndrome developed. The disease did not respond to estrogen treatment and the patient died of severe septicemia. Histopathologic examination of the autopsy specimens revealed a small cell carcinoma intermingled with a moderately differentiated adenocarcinoma in the prostate and widespread metastases of small cell carcinoma. Immunoreactivity for neuroendocrine differentiation was found only in the small cell carcinoma. Determination of different tumor markers in plasma samples showed markedly elevated levels of prostate-specific antigen as well as carcinoembryonic antigen prior to treatment, with no significant changes after treatment. The concentration of the neuroendocrine marker chromogranin A was initially within the normal range, but increased during estrogen treatment, whilst neuron-specific enolase was moderately elevated throughout the observation period.

ACTH Syndrome, Ectopic↗
PubMed1999

Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen.

Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.

Antibodies, Monoclonal↗
PubMed1999

Reactivity of 77 antibodies to prostate-specific antigen with isoenzymes and complexes of prostate-specific antigen.

Seventy-seven antibodies submitted to the ISOBM TD-3 PSA Workshop (TD-3.1 and TD-3.2) were characterized by measuring their reactivity with isoenzymes of free prostate-specific antigen (PSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT) and alpha1-proteinase inhibitor (PSA-API). Antibodies were classified into 15 distinct groups according to their reaction profiles with the various isoenzymes. Some antibodies recognizing both free and complexed PSA were inaccurate in measuring total PSA. Eight of the 9 free PSA-specific antibodies cross-reacted more with PSA-API than with PSA-ACT, while 1 antibody reacted less with PSA-API than PSA-ACT. From the panel of antibodies 39 reacted with both free and complexed PSA and were classified as total PSA antibodies.

Antibodies, Monoclonal↗
PubMed1999

Epitope mapping and affinity estimation of 83 antibodies against prostate-specific antigen.

Eighty-three antibodies submitted to the ISOBM TD-3 Workshop on prostate-specific antigen (PSA) were characterized by cross-inhibition studies, immunometric assay and affinity estimation with free or complexed PSA (PSA-alpha1-antichymotrypsin, PSA-ACT). Nine antibodies did not bind PSA or PSA-ACT when coated onto microtiter plates or in solution. Another 3 antibodies bound the antigens only when in solution and were therefore omitted from the cross-inhibition experiments. Dissociation constants (Kd) were estimated from the concentration of free antibody needed to achieve half-maximal binding of the antigen. Kd values for PSA and PSA-ACT ranged from 2 x 10(-12) to >10(-8) mol/l. Antibodies were classified into 6 main groups according to their reactivity. Group 1 comprised 15 antibodies (#25, 26, 33, 68, 73, 77, 78, 80, 85, 209, 213, 216, 223, 230, and 262) specific for free PSA. These antibodies had >80% cross-inhibition and showed high affinity for PSA with minimal or no affinity for the PSA-ACT complex. Group 2 comprised antibodies that reacted with both free PSA and PSA-ACT. Three subgroups were defined: group 2a (#40), group 2b (#32) and group 2c (#35, 37, 63, 90, 215 and 226). Group 3a antibodies (#31, 36, 37, 57, 64, 66, 72, 82, 84, 212, 224, 229, 257 and 260) were closely related to those of group 2, with two exceptions in group 3b (#88 and 89). Group 4 contains antibodies with binding patterns similar to those represented by groups 3b and 6b. These antibodies could be divided into two subgroups: group 4a (#30, 38, 51, 217, and 220) and group 4b (#74). Group 5 was more heterogeneous, with distinct inhibition patterns: group 5a (#50, 54, 76, 81,207, and 222); group 5b (#41), and group 5c (#28 and 86). Group 6 antibodies bind epitopes on both free PSA and PSA-ACT, but have epitopes unrelated to those represented in groups 1-3: group 6a contains 15 antibodies (#24, 27, 29, 34, 55, 56, 65, 79, 210, 214, 218, 221, 225, 258 and 261), and group 6b 2 antibodies (#67 and 75). These 6 groups represent the major immunodominant regions, one of which is exposed only on free PSA. Our classification could provide a useful guide in choosing antibodies for future PSA assays.

Antibodies, Monoclonal↗
PubMed1998

Stability of free and total prostate specific antigen in serum from patients with prostate carcinoma and benign hyperplasia.

PURPOSE: Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly men without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum. MATERIALS AND METHODS: The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 microg./l. The influence of total PSA levels on in vitro changes in free-to-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 microg./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 microg./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures. RESULTS: We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p=0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p=0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 microg./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001). CONCLUSIONS: In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.

Aged↗
PubMed1998

Specificity and affinity of 30 monoclonal antibodies against alpha-fetoprotein.

Twenty-two antibodies with high affinity for AFP could be classified into groups according to five AFP binding regions, designated A-E, based on cross-inhibition studies and immunometric assay combinations. Antibodies in group A (ISOBM TD2 No. in parentheses): H31 (119), AFP-4-F45 (111), 140/5 (117), K51 (99), K52 (110), AFP-200014A (120) and F2 (118) and in group B: A4-4 (98) and AFP-4-F67 (93) were only inhibited by antibodies belonging to the same groups and could be used in immunometric assay combinations with all other antibodies. Groups C, D and E were inhibited by antibodies in adjacent antibody groups and did not form immunometric assay pairs with antibodies belonging to neighboring groups. Group C comprises: K28 (105), A34-B/B5 (101), AFP-4-F111 (95), AFP100025B (121) and K57 (116), group D: E7 (114) and D10 (92) and group E: H219 (115), K6B1 (103), A34-A/D12 (104), C2 (102), C9 (94) and C10 (97). For six of seven antibodies with low binding to labelled AFP, the specificity could not be determined. Two antibodies were not conclusively assigned to any binding region. Antibody 9A12 (109) may be classified into group E based on immunometric assay combinations, but could not be evaluated in cross-inhibition experiments due to low binding to labelled AFP. Antibody 19F12 (100) functioned as a tracer antibody in combination with all other antibodies, but did not bind AFP when used as solid phase antibody. This antibody could therefore represent a unique binding specificity.

Antibodies, Monoclonal↗
PubMed1997

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study.

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Pharmacokinetics of reboxetine in healthy volunteers. Single against repeated oral doses and lack of enzymatic alterations.

The pharmacokinetics of reboxetine have been investigated in 12 healthy male volunteers after a single 2 mg dose of reboxetine and at steady state, following the last administration of a multiple-dose regimen (2mg twice a day for 5 1/2 d). Reboxetine was analysed in plasma and urine samples collected up to 72 h post-dosing using an HPLC method with UV detection. The urinary excretion rate of 6-beta-hydroxycortisol, used as a marker for cytochrome P450IIIA activity, was also tested, and any possible alteration was correlated to reboxetine plasma levels. The dosing regimen was well tolerated by all subjects. Reboxetine pharmacokinetic parameters, calculated after the single dose using non-compartmental analysis, were in good agreement with those obtained in previous studies. Following the multiple-dosing regimen, no significant deviations from expectation based on linear superposition was observed. The accumulation ratio, based on repeated-dose/single-dose ratios of Cmax, AUC(0-12 h), and C(12 h) was approximately two. A slight rise was recorded for the average excretion rate of 6-beta-hydroxycortisol over 48 h by the end of treatment; however, the difference was not statistically significant and the mean excretion rates were within the normal reference range. Thus a significant induction of P450IIIA was not indicated.

Administration, Oral↗
PubMed1996

Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: first report from the ISOBM TD-1 workshop. International Society for Oncodevelopmental Biology and Medicine.

The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines. Immunometric assays using all possible antibody combinations were used to study the topography of antibody binding sites on the antigen. We conclude that the CA 125 antigen carries only two major antigenic domains, which classifies the antibodies as OC125-like (group A) or M11-like (group B). One antibody, OV 197, showed binding specificity related to some of the OC125-like antibodies, but was classified into a separate group C. The OC125-like group of antibodies has four subgroups with different binding specificities. These are A1 = OC 125 and K 95, A2 = K 93, A3 = B43.13, and A4 = ZS 33, B27.1 and CCD 247. Binding of nonlabelled OC 125 or K 95 to CA 125 caused a marked increase in binding of labelled OV 197 to the complex. This conformational change was not observed with any other antibody combinations. Antibody B43.13 could form immunometric assay combinations particularly with antibodies of subgroup A4, indicating that the B43.13 epitope is in the periphery of the binding area of OC125-like antibodies. The M11-like group of antibodies is more homogenous with strong cross-inhibition between most antibodies. Only one antibody, ZR 38, would form an immunoassay combination with other M11-like antibodies and thus represents a distinct subgroup. The main group of M11-like antibodies are M 11, ZR 45, MA602-6, K 91, OV 185, K 101, K 90, K 96, K 97, K 102, CCD 242, 145-9, and 130-22. Antibody OV 197 binds to a domain designated C and is unique, as stated above. Antibody pairs from any two of the three groups may be used in immunometric assays. Three antibodies were not studied by complete cross-inhibition due to low affinity (OV 198 and K 100) or lack of material (MA602-1). OV 198 and K 100 are most likely OC125-like and MA602-1 is M11-like. Antibody affinity was estimated with labelled antigen in solution or with antigen absorbed on microtiter wells. Western blot analysis showed staining both in the stacking gel and corresponding to a molecule of 200 kDa. There was a marked difference between the antibodies in their ability to bind to CA 125 immobilized on a membrane. Strongest binding was observed with the M11-like antibodies, particularly M 11, K 96, K 97, MA602-6, 145-9. Antibodies belonging to the subgroup A4 were the only OC 125-like antibodies which reacted well with CA 125 in Western analysis. Digestion of CA 125 with proteolytic enzymes showed it to be particularly sensitive to trypsin cleavage. However, no low molecular weight fragments with preserved immunoreactivity were found.

Animals↗
PubMed1996

Expression and interconversion of neuron-specific enolase in patient sera and extracts from small-cell lung cancer cells.

The isoforms of gamma-enolase were characterized in serum from patients with small-cell lung cancer (SCLC) and in extracts from SCLC cell lines and malignant melanoma tumor tissue. Large variations in the expression of the 3 gamma-isoforms of enolase were observed. These forms probably represent the homodimeric gamma gamma-enolase, the heterodimeric alpha gamma-enolase and the monomeric forms of gamma-enolase. Only the dimeric forms are enzymatically active. The predominant gamma-enolase in the cell lines is the heterodimeric alpha gamma-enolase. The SCLC cell lines can be divided into two groups: one with negligible gamma gamma-enolase expression and considerable amounts of the nonneuronal alpha alpha-enolase and a second group with a large fraction of gamma gamma-enolase concomitant with a low expression of alpha-enolase. Similar patterns are observed in tissue extracts from malignant melanoma. When changing buffer conditions by increasing the ionic strength and decreasing the Mg2+ concentration, interconversions between the isozymes occur. In contrast to the predominant alpha gamma-enolase in extracts from cell lines, the multiple forms of gamma-enolase in serum might be caused by a subunit exchange facilitated by the low Mg2+ concentration in plasma. However, there seems to be a stable equilibrium between the isoforms in undiluted patient serum. The induction of subunit exchange by perturbation in ionic strength and/or Mg2+ concentration indicates a need for caution when choosing diluents for use in assays for neuron-specific enolase.

Carcinoma, Small Cell↗
PubMed1996

Immunohistochemical characterization of 22 monoclonal antibodies against the CA125 antigen: 2nd report from the ISOBM TD-1 Workshop.

We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.

Adenocarcinoma, Clear Cell↗
PubMed1995

Dual analyte assay based on particle types of different size measured by flow cytometry.

Simultaneous flow cytometric assays have been developed for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), with internal determination of sample related non-specific binding (NSB). The assays use particles of 7.5, 6.5 and 5.5 microns diameter coated with, respectively, monoclonal antibodies specific for AFP, hCG or an epitope normally not present in serum. The different particle types were identified simultaneously by light-scatter measurements as their specific immunofluorometric responses were determined. The NSB in the simultaneous assay of AFP and hCG was increased by approximately 30% compared to corresponding single analyte assays. The working range of the dual analyte assays was 0.6-2000 kIU/l for AFP and 6-10,000 IU/l for hCG. No significant interference from the presence of the other analyte was observed in the measurement of either AFP or hCG. The 95% confidence interval for the ratio of dual over single analyte assay results was [0.81, 1.11] for AFP and [0.88, 1.16] for hCG.

Acrylates↗
PubMed1995

DNA ploidy, serum prostate specific antigen, histological grade and immunohistochemistry as predictive parameters of lymph node metastases in T1-T3/M0 prostatic adenocarcinoma.

OBJECTIVE: To evaluate whether DNA ploidy and immunohistochemistry performed in primary prostatic carcinoma specimens give predictive information on regional lymph node metastasis in addition to T category, histological grade and serum prostate specific antigen (PSA). PATIENTS AND METHODS: Pre-treatment TURP specimens from 80 patients with prostatic carcinoma T0-T3/M0 disease were retrospectively evaluated by means of DNA ploidy and histological grade, and immunostaining for PSA, prostatic acid phosphatase (PAP), neuron-specific enolase (NSE) and p53 protein. Pelvic lymph node dissection was performed in all patients. Serum PSA was determined in 76 of the 80 patients before pelvic staging lymphadenectomy. Thirty-two (40%) of the 80 patients had pN+ disease. RESULTS: Thirty-six patients (46%) had serum PSA values below the upper reference limit (< or = 10 micrograms/L). By univariate analysis the pN category correlated with the serum PSA level (P < 0.001), histological grade (P < 0.001), tissue PSA (P < 0.001), tissue PAP (P < 0.04), T category (P < 0.005) and DNA ploidy (P < 0.02). Multivariate analysis revealed that the serum PSA level was the most powerful independent prognosticator, followed by the T category, tissue PAP and tissue PSA. Histological grade and DNA ploidy did not reach the level of significance in the multivariate analysis. CONCLUSION: These data suggest that tissue PAP and tissue PSA predict the pN status in patients with T0-T3/M0 prostate carcinoma, in addition to serum PSA and T category. Neuroendocrine differentiation and p53 protein seem to have no predictive ability.

Adenocarcinoma↗
PubMed1995

Increase of serum prostatic specific antigen and clinical progression in pN + MO prostate cancer.

OBJECTIVE: To analyse the increase of serum prostatic specific antigen (PSA) as a means of early detection of progression in hormonally untreated or androgen-deprived patients with T1-T4, pN+ and MO prostate cancer. PATIENTS AND METHODS: From 1986 to 1992 40 patients with T1-T4 pN+ MO prostate cancer were either deprived of androgen at diagnosis (Group 1, 19 patients) or had no immediate hormone manipulation (Group 2, 21 patients) and were followed at 3-6-monthly intervals when determinations of PSA and routine clinical/radiological examinations were performed. A significant increase in PSA was defined as a > or = 50% increase of the baseline PSA value which was the either the lowest PSA value within 6 months from the start of androgen deprivation (Group 1) or the initial PSA value (Group 2). RESULTS: By June 1993 22 of the 40 patients had clinically progressed. In 12 patients the progression was preceded by a significant increase in PSA (Group 1, three of four progressing patients; Group 2, nine of 18 progressing patients). A PSA increase of > or = 50% was observed simultaneously with clinical progression in six patients, whereas clinical progression occurred in four patients with no previous or simultaneous significant increase in PSA. In four of nine hormonally untreated patients > or = 1 year elapsed between antecedent PSA increase and clinical progression. CONCLUSION: In routine clinical practice PSA does not significantly increase (> or = 50% of baseline value and > 10 micrograms/L) before disease progression in about one third of patients with pN+ MO prostate cancer managed with or with no hormone manipulation. Future studies should be carried out to determine whether a lower rate of increase in PSA during follow-up has any clinical significance.

Aged↗
PubMed1995

Detection of c-erbB-2 related protein in sera from breast cancer patients. Relationship to ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour.

The level of a c-erbB-2 related protein was determined in sera from 168 breast carcinoma patients, 12 females with benign breast disease, and 66 female controls using an ELISA (enzyme linked immunosorbent assay) kit. Elevated c-erbB-2 related protein level was detected in one of 13 preoperative sera (8%), two of 62 postoperative sera from patients without recurrent disease (3%), and 55 of 93 sera collected at recurrent disease (59%). Elevated serum levels were detected significantly more often in patients with distant metastases than in patients with recurrent disease restricted to loco-regional areas (68% versus 19%). Presence of elevated serum level was associated with ERBB2 gene amplification and c-erbB-2 protein overexpression in tumour. None of the patients who had normal ERBB2 gene copy number in tumour had elevated serum levels. Although the usefulness in postoperative prediction of the presence of micrometastases is somewhat questionable, the results suggest c-erbB-2 related protein to represent a novel tumour marker in serum and other body fluids from breast cancer patients at the time of diagnosis and during treatment monitoring.

Adult↗