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S Nordling

Publications and source records attributed to S Nordling.

At least 55 records · Page 3Linked to original sources
PubMed1998

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

Analysis of Variance↗
PubMed1998

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence.

We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.

Adult↗
PubMed1998

Characterization and immunological determination of the complex between prostate-specific antigen and alpha2-macroglobulin.

Prostate-specific antigen (PSA) rapidly forms a complex with alpha2-macroglobulin (A2M) in vitro; however, PSA complexed with A2M (PSA-A2M) is not detected by conventional immunoassays for PSA because it is encapsulated by the A2M. In this study, we show that denaturation of PSA-A2M at high pH renders PSA immunoreactive. Part of the complexed PSA is released in free form and part remains bound to denatured A2M. These forms can be measured by a conventional immunoassay for PSA. This finding enabled us to design a dissociation assay for the detection of PSA-A2M, which was based on the removal of immunoreactive PSA in serum by immunoadsorption, denaturation of PSA-A2M at high pH, and measurement of the released PSA immunoreactivity by a conventional PSA immunoassay. This PSA-A2M assay was calibrated with PSA-A2M formed in vitro. The detection limit of the assay was 0.14 microg/L. Inter- and intraassay coefficients variation were 4-9% and 8-14%, respectively. When purified PSA was incubated with A2M, the loss of PSA immunoreactivity was highly correlated with the PSA-A2M formed, as measured by the dissociation assay for PSA-A2M (r = 0.99; P <0.0001). The concentration of PSA-A2M in serum correlated with that of total PSA both in prostate cancer (PCa) and benign prostatic hyperplasia (BPH); however, the ratio of PSA-A2M in relation to total PSA was significantly higher in BPH than in PCa (P <0.0003). ROC curve analysis suggested that measurement of the ratio of PSA-A2M to total PSA in serum improves the diagnostic accuracy for PCa compared with assays for total PSA only.

Aged↗
PubMed1997

Expression and function of the complement membrane attack complex inhibitor protectin (CD59) in human prostate cancer.

Protectin (CD59) inhibits homologous complement-mediated cytolysis by preventing formation of the membrane attack complex at the point of insertion and polymerization of C9 into cell membranes. The present study investigated the expression and function of CD59 on human prostatic tumor cells in situ and on 5 human prostate cell lines in vitro originating from either metastatic tumors or benign prostate hypertrophy epithelial cells. Immunohistochemical staining of prostate carcinoma tissue with monoclonal antibody (MAb) MEM43 revealed weak to moderately strong expression of CD59 by prostate glandular epithelial cells. Flow cytometry with MEM43 demonstrated that the 5 prostate cell lines expressed different relative quantities of CD59. Indirect immunofluorescence analysis revealed uniform membrane staining of DU145 and PC3 cell lines with no membranous granularity in the staining pattern. Western immunoblots with MAb BRIC 229 showed that PC3 and DU145 cells express CD59 with a m.w. of 18-25 kDa. Treatment of DU 145 and PC3 cells with phosphatidylinositol-specific phospholipase C caused a significant decrease of CD59 expression indicating that the CD59 expressed by prostate cancer cells is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) linkage. PC3 and DU145 cells were completely resistant to human complement-mediated cytolysis but became sensitive to killing in the presence of the CD59-neutralizing MAb YTH53.1. We conclude that malignant and benign human prostate cells express CD59 that is GPI-linked to the cell surface and that CD59 may regulate the immunological response to cancerous prostate cells by protecting the cells from the cytolytic activity of complement.

Adenocarcinoma↗
PubMed1997

17q12-21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: a comparative genomic hybridization study.

We studied DNA copy number changes in gastric cancer (GC) using comparative genomic hybridization (CGH) analysis on 35 resected gastric carcinomas (22 of the intestinal type and 13 of the diffuse type). Eighty-three percent of the cases showed DNA copy number changes. Gains were more common than losses (median of 3 and 1 in primary tumors of the intestinal and diffuse type, respectively). The most common gains were detected on 20q [46%; 12 intestinal type (55%) and four diffuse type (31%)], 8q [37%; 10 intestinal type (45%) and three diffuse type (23%)], and 17q12-21 [29%; all but one intestinal type (41%)]. The most frequent losses were detected on 18q [26%; all intestinal type (41%)] and on 4q [23%; all intestinal type (32%)]. High-level amplifications were observed in the intestinal type of tumors at 17q12-21 (three tumors), 20q (three tumors). 2q (one tumor), and 18q (one tumor). In the diffuse type, high-level amplification was detected once at 13q.

Adult↗
PubMed1997

Diagnostic laparoscopy in patients with acute leukemia and suspected hepatic candidiasis.

To assess the value of laparoscopy in the diagnosis of suspected hepatosplenic candidiasis in patients with acute leukemia, a retrospective analysis of 28 laparoscopies was conducted. In all but two cases, imaging of the liver showed focal lesions before laparoscopy. Diagnosis of hepatic candidiasis was established significantly more often when the biopsy was targeted at white nodules (in 12 of 22 laparoscopies) than when targeted randomly or at scars (0 of 6 laparoscopies) (p = 0.017, chi-square test). Yeast was detected more often if the laparoscopy was performed during the three-week period after recovery from neutropenia (in 8 of 12 laparoscopies) than when performed later (in 4 of 16 laparoscopies) (p = 0.028, chi-square test). In addition to the 12 laparoscopically diagnosed patients, eight (29%) patients were diagnosed with disseminated Candida infection by other methods. In another eight (29%) patients the causative agent was not identified. No bleeding or other problems occurred after the laparoscopy. Laparoscopy-guided liver biopsy is most useful if biopsies are targeted to macroscopic lesions and if laparoscopy is performed soon after recovery from neutropenia.

Acute Disease↗
PubMed1997

Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications.

We studied the incidence among, risk factors for, and survival of adult patients with acute leukemia and hepatosplenic candidiasis during the period 1980 to 1993. Of 562 adult patients with acute leukemia, 38 (6.8%) had hepatosplenic candidiasis. The incidence of infection increased fivefold during the study period. The incidence was higher among patients with acute lymphatic leukemia (11.3%) than among those with acute myeloid leukemia (5.1%) (P = .01). The median survival was 9.5 months, and by the end of follow-up, 74% of patients had died. Patients whose leukemia was in remission before the last cytotoxic treatment preceding hepatosplenic candidiasis survived longer than did patients with newly diagnosed or refractory or relapsed leukemia (P = .0065). Eleven patients died within 3 months after the diagnosis of the infection: 7 of 16 with newly diagnosed leukemia, 4 of 10 with refractory or relapsed leukemia, and 0 of 12 with leukemia in remission (P = .028). In all of the patients who died within 3 months, infection was found at autopsy. In conclusion, the incidence of hepatosplenic candidiasis has significantly increased since 1980, and the outcome for patients with this infection is related to the stage of leukemia.

Acute Disease↗
PubMed1997

DNA flow cytometry and the outcome of chemoimmunotherapy in metastatic melanoma.

DNA ploidy and S-phase fraction (SPF) were measured by flow cytometry on tumours from 80 patients with disseminated malignant melanoma. All patients received a four-drug chemotherapy regimen (dacarbazine, vincristine, bleomycin and lomustine) plus interferon. Specimens were taken for analysis from the latest metastases biopsied before the start of the treatment. In 13 patients we also analysed sequential samples taken after the treatment at the time of progression. DNA aneuploidy was observed in 65% of the patients. Among the 40 responders there were 26 with aneuploid tumours (65%). Aneuploidy did not reach statistical significance as a prognostic sign in the unstratified study population, but when stratified by response groups, DNA aneuploidy was a significant prognostic factor for a better response (P = 0.04). SPF could be calculated in 76 tumours. Out of 40 responding patients (complete or partial response), 23 had tumours with an SPF higher than the median. Accordingly, patients with a high SPF survived longer than those with a low SPF, with median survival times of 9.8 months and 8.7 months, respectively (P = 0.18). We conclude that DNA aneuploidy and a high SPF are associated with longer survival in patients with disseminated melanoma treated with a chemoimmunotherapy regimen. Based on our findings we claim that, among patients receiving chemoimmunotherapy, high SPF and aneuploidy are not signs of unfavourable prognosis, which is in contrast to previous observations in melanoma patients receiving heterogeneous therapy.

Adult↗
PubMed1997

Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node negative breast cancer.

The prognostic value of Ki-67, p53 and ER immunohistochemical labelling and flow-cytometric S-phase fraction and ploidy was evaluated in 212 pT1N0M0 breast carcinomas. The mean follow-up time was 8.3 years. Patients with breast carcinomas with high Ki-67 expression (> or = 10%) had a less favourable disease-free survival than those with low Ki-67 expression (< 10%) (p = 0.008). A positive p53 staining and high SPF were associated with a less favourable disease-free survival although it did not reach statistical significance. The subset of patients with ER negative, Ki-67 > or = 10% and p53 > or = 20% tumours, had a shorter disease-free survival compared with that of all the other patients (p = 0.03). We conclude that the potential value of Ki-67 labelling for prognostic evaluation of T1N0M0 breast carcinoma is good.

Adult↗
PubMed1997

Retinoic acid induces signal transducer and activator of transcription (STAT) 1, STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons.

IFNs are antiproliferative cytokines that have growth-inhibitory effects on various normal and malignant cells. Therefore, they have been used in the treatment of certain forms of cancer, such as chronic myelogenous leukemia and hairy cell leukemia. However, there is little evidence that IFNs would be effective in the treatment of acute myelogenous leukemia, and molecular mechanisms underlying IFN unresponsiveness have not been clarified. Here we have studied the activation and induction of IFN-specific transcription factors signal transducer and activator of transcription (STAT) 1, STAT2, and p48 in all-trans-retinoic acid (ATRA)-differentiated myeloid leukemia cells using promyelocytic NB4, myeloblastic HL-60, and monoblastic U937 cells as model systems. These cells respond to ATRA by growth inhibition and differentiation. We show that in undifferentiated NB4 cells, 2',5'-oligoadenylate synthetase and MxB gene expression is not activated by IFN-alpha, possibly due to a relative lack of signaling molecules, especially p48 protein. However, during ATRA-induced differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and corresponding protein levels were elevated both in NB4 and U937 cells, apparently correlating to an enhanced responsiveness of these cells to IFNs. ATRA treatment of NB4 cells sensitized them to IFN action as seen by increased IFN-gamma activation site DNA-binding activity or by efficient formation of IFN-alpha-specific ISGF3 complex and subsequent oligoadenylate synthetase and MxB gene expression. Lack of p48 expression could be one of the mechanisms of promyelocytic leukemia cell escape from growth-inhibitory effects of IFN-alpha.

Acute-Phase Proteins↗
PubMed1997

Comparison of DNA ploidy and S-phase fraction with prognostic factors in gastric cancer.

OBJECTIVE: To assess the value of DNA ploidy and S-phase fraction (SPF) as prognostic factors in gastric cancer. STUDY DESIGN: DNA ploidy and SPF were analyzed in 289 gastric cancer cases using flow cytometry and compared with the clinical and histopathologic features of the tumors. RESULTS: Aneuploidy was found in 36% of the patients; it was more frequent in the intestinal type of cancer (56%) as compared to the diffuse type (15%). Aneuploidy was also related to advanced TNM stage, cardiac location and high mitotic activity. In univariate survival analysis, TNM stage and tumor size were the most important prognostic factors. High SPF was significantly related to inferior survival rates, but DNA ploidy did not have any significant correlation with survival when all patients were analyzed together. However, in diffuse-type cancer, both DNA ploidy and SPF were significant prognostic factors. In multivariate analysis, DNA ploidy proved to be an independent predictor of survival in gastric cancer. CONCLUSION: The results indicate that in addition to TNM stage, flow cytometric analysis of DNA ploidy and SPF are important prognostic factors in gastric cancer.

Adenocarcinoma↗
PubMed1996

Comparison of cytogenetics, interphase cytogenetics, and DNA flow cytometry in bone tumors.

Twenty-three samples of benign and malignant bone tumors were studied with cytogenetic analysis, interphase cytogenetics (IC) using in situ hybridization with (peri)centromeric probes for chromosomes 1, 7, and/or 8, and DNA flow cytometry (FCM). Our aim was to compare these methods in the detection of numerical chromosome aberrations (NCA) and aneuploidy. IC detected aneuploidy in 91%, FCM in 73%, and cytogenetics in 27% of the malignant tumors. In benign tumors IC detected aneuploid by in 4(33%), FCM in 2(17%), and cytogenetic analysis in 1. All of the benign tumors aneuploid by IC, two of which were also aneuploid by FCM, were histologically potentially aggressive. The clonal aberrations detected with cytogenetics usually agreed with the IC and FCM findings. All malignant tumors which had a normal karyotype were aneuploid either by IC or FCM or by both. In conclusion, IC was the most sensitive method in the detection of NCA and aneuploidy even though it was usually performed with only two (peri)centromeric probes. Aneuploidy was detected by cytogenetic analysis alone in 4 samples (17%), by cytogenetic analysis and/or FCM in 11 samples (48%), and by cytogenetic analysis, FCM, and/or IC in 16 samples (70%). Thus, the combined use of all three methods increased the sensitivity of aneuploidy detection.

Aneuploidy↗
PubMed1996

A risk score for predicting outcome in patients with gastric cancer, based on stage, sialyl-Tn immunoreactivity and ploidy--a multivariate analysis.

Twelve variables were studied for possible prognostic value in 242 patients with adenocarcinoma of the stomach. Eight of these had a statistically significant effect on survival in univariate analyses. A multivariate analysis of 196 patients showed that the most significant differences in survival could be explained by 3 independent variables acting simultaneously, namely stage of disease, Sialyl Tn antigen (STn) expression and aneuploidy of the tumour cells. By adding scores for stage (1-4 points), STn expression (0-1 points) and ploidy (0-1 points) a risk score based on these 3 variables defined the patients into 6 different risk groups with statistically highly significant differences in survival (chi 2 = 107.74, DF = 1, p < 0.0001). Application of the risk score improves the prediction of outcome, may help in choosing patients for different treatment modalities, and allows more accurate stratification in clinical trials.

Aged↗
PubMed1996

Sialyl Tn antigen is an independent predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of Sialyl Tn antigen (STn) was evaluated in 242 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody C1282, produced by immunization with ovine submaxillary mucin (OSM). Positive immunoreactivity for STn was observed in 149 (62%) patients. The expression of STn did not correlate with stage of disease (TNM), tumour location, presence of lymph-node or distant metastases, histological type, age or gender. STn immunoreactivity correlated strongly with overall survival in univariate analysis. The median survival in the STn-positive group was 21 months, in comparison to 38 months in the STn-negative group. The difference in survival between STn-negative and STn-positive tumours was significant in patients with stage-I cancer, but not in patients with stage-II -III or -IV disease. STn immunoreactivity emerged as an independent prognostic factor in Cox multivariate analysis. It is concluded that the immunohistochemical expression of STn is a good marker in the prediction of survival in patients with stage-I gastric carcinoma.

Adenocarcinoma↗
PubMed1996

Preoperative assessment of proliferative activity and hormonal receptor status in carcinoma of the breast: a comparison of needle aspiration and needle-core biopsies to the surgical specimen.

The applicability and reliability of estimates of proliferative activity in breast carcinomas using fine-needle aspiration (FNA) and needle-core biopsies (NC) was evaluated in 98 breast carcinoma patients. The Ki-67, Estrogen receptor (ER), and progesteron receptor (PR) immunolabelling of FNA and NC was compared with that of the surgical specimen. A statistically significant consistency between labelling was found in the Ki-67-NC (kappa = 0.474), ER-FNA (kappa = 0.318), ER-NC (kappa = 0.518), and PR-FNA (kappa = 0.404) groups. The consistency in the Ki-67-FNA group was less significant (kappa = 0.182), and there was no consistency in the PR-NC group (kappa = 0.062). There was a positive correlation of Ki-67 labelling in FNA and NC biopsies (Spearman rank, rho = 0.4; P = 0.0007), and also in ER labeling (Spearman rank rho = 0.6; P = 0.0001). These results indicate that NC and FNA can be used for preoperative assessment of proliferative activity and hormonal status in breast carcinoma.

Adult↗
PubMed1996

Expression of MIB-1, mitotic index and S-phase fraction as indicators of cell proliferation in superficial bladder cancer. Finnbladder Group.

Cell proliferation of transitional cell bladder cancer (TCC) was determined by MIB-1 immunolabeling, volume-corrected mitotic index (M/V index) and S-phase fraction measurement in 207 patients with superficial (Ta-T1) bladder cancer. The results were compared to T category, WHO grade and DNA-ploidy. The MIB-1 score was related to T category (P < 0.001), WHO grade (P < 0.001), DNA ploidy (P < 0,0001), M/V index (P < 0.0001) and fraction of cells in S phase (P < 0.0001). The mean MIB-1 score was 6.37% for G1, 14.59% for G2 and 28.59% for G3 carcinomas (P < 0.001). The MIB-1 score for Ta tumors was 9.24% and for T1 tumors 25.34% (P < 0.001). The M/V index was 3.9 for G1, 11.5 for G2 and 25.9 for G3 tumors (P < 0.0001). The M/V index for Ta tumors was 6.4 and 25.3 for T1 tumors (P < 0.0001). WHO grade 1 tumors had 7.7%, grade 2 tumors 13.8% and grade 3 tumors 21.8% of cells in S phase (P < 0.001). Of grade 1 tumors, 97% were diploid and 3% aneuploid, and 78% of grade 2 tumors were diploid and 22% aneuploid. Of grade 3 tumors, 30% were diploid and 70% aneuploid (P < 0.001). Of Ta tumors, 92% were diploid and 8% aneuploid, respectively, whereas 40% of T1 tumors were diploid and 60% aneuploid (P < 0.0001). The results show that quantitative cell proliferation indices are associated with T category and WHO grade in superficial bladder cancer. The prognostic value of the S-phase fraction and mitotic index has been demonstrated in several previous analyses of prognostic factors while the value of MIB-1 score on bladder cancer prognosis remains to be established in further follow-up studies.

Adult↗
PubMed1996

Expression of p53 protein as a prognostic factor in patients with gastric cancer.

The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.

Adenocarcinoma↗