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Biomedical subjects

S Nordling

Publications and source records attributed to S Nordling.

At least 73 records · Page 4Linked to original sources
PubMed1995

Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma.

Bax is a homologue of Bcl-2 that promotes apoptosis. Bax protein levels were assessed by immunohistochemical methods in primary tumors derived from 119 women with metastatic breast cancer. These patients had received combination chemotherapy either with a once a month dosage schedule or in 4 weekly divided doses. The BAX immunostaining results were retrospectively compared with overall survival, time to tumor progression (TTP), and response, as well as several laboratory markers. Normal breast epithelium and in situ carcinomas immunostained positively for Bax. Marked reductions in Bax immunostaining were observed in 40 (34%) of 119 evaluable tumors. Reduced Bax correlated with shorter overall survival (median, 8.1 versus 15.7 months; P = 0.04), faster TTP (median, 2.0 versus 6.3 months; P = 0.009), and failure to respond (complete response, partial responses; 6% versus 42%, P = 0.01) in the subgroup of patients who received divided dose therapy. Reduced Bax immunostaining was not significant in the monthly dose group. When the two groups were combined, however, reduced Bax was significantly correlated in univariate analysis with failure to respond (21 versus 43% achieving complete response or partial response; P = 0.02), faster TTP (median, 3.7 versus 9.0 months; P = 0.02), and shorter survival (median, 10.7 versus 17.1 months; P = 0.04). Bax immunostaining was not significantly correlated with tumor histology, S-phase fraction, aneuploidy, p53 HER2, or cathepsin D, but was positively associated with Bcl-2 (P = 0.005). In multivariate analysis (Bax, tumor grade, and treatment group), reduced Bax was strongly associated with faster TTP (P approximately equal to 0.009) and shorter survival (P approximately equal to 0.001). Although highly preliminary, the finding suggest that loss of Bax immunostaining represents a novel prognostic indicator of poor response to chemotherapy and shorter survival in women with metastatic breast cancer, and raise the possibility that the subgroup of women with Bax-negative tumors may benefit from more aggressive therapy.

Adenocarcinoma↗
PubMed1995

Chondrosarcoma of bone. A clinical and DNA flow cytometric study.

Fifty-two patients with chondrosarcoma were treated in our hospital between 1981 and 1992. Tumours from 21 of the patients were histologically grade I, 19 were grade II, 10 were grade III and two were grade IV. Forty-seven patients were treated surgically and samples for flow cytometric DNA analysis were taken from 38 tumours with a successful measurement in 37 cases. The mean follow-up time was 40 months and during this period 17 of the patients treated surgically developed a local recurrence or metastasis. In one case, a highly anaplastic sarcoma developed after radiation treatment. Only two of the 19 diploid tumours recurred, whereas eight of the 18 aneuploid tumours showed a recurrence. These results indicate that DNA flow cytometry is of prognostic significance in chondrosarcoma and may aid in planning the treatment.

Adult↗
PubMed1995

Do DNA ploidy and S-phase fraction in primary tumour predict the response to chemotherapy in metastatic breast cancer?

The relationship between the response to chemotherapy with cyclophosphamide, epirubicin and fluorouracil as well as the time to progression of metastasised breast cancer and DNA ploidy and S-phase fraction (SPF) of primary tumours was examined using paraffin-embedded tumour tissue from 81 patients. The response to chemotherapy was significantly better in patients with tumours with a high SPF, and in addition the time to progression was longer in the high-SPF group. There was no significant difference when the DNA ploidy and response to treatment were compared.

Adult↗
PubMed1995

Flow cytometric DNA measurements in aspiration biopsies and surgical specimens of breast cancer.

OBJECTIVE: One of the prognostic factors in breast cancer is the proliferation activity of the tumor. This study sought knowledge of this activity before surgery to benefit the design and timing of therapy. STUDY DESIGN: Flow cytometric DNA analysis data from 52 diagnostic fine needle aspirates were compared with data from subsequent surgical specimens. RESULTS: The data showed that the coefficient of variation of the G1 peak was lower in the aspirates. Small, near-diploid peaks were detected more frequently in aspirate histograms than in surgical specimens. DNA analyses by flow cytometry from aspirates, which can be obtained prior to surgical treatment, were as reliable as those obtained from surgical specimens, provided that the cellular material was diagnostic of cancer. CONCLUSION: Our results suggest that flow cytometry DNA analysis from the first preoperative cytologic specimen from a breast tumor will permit faster planning and coordination of breast cancer care.

Biopsy, Needle↗
PubMed1994

Flow cytometric analysis of the cell cycle in polyamine-depleted cells.

Polyamines are found in all cells but their function is not fully understood. We have studied the effect of polyamines on the passage of cells through the cell cycle using a polyamine auxotrophic mutant, CHO-P22, which has no detectable ornithine decarboxylase activity. The ability of these cells to grow without serum allows efficient polyamine depletion. A flow cytometric analysis of DNA content and bromodeoxyuridine labeling showed that without added polyamines the cells accumulated in S-phase, the rate of DNA synthesis was retarded, and the entry into mitosis was blocked. Addition of polyamines to cultures deprived of polyamines induced cells in all phases of the cell cycle to reinitiate cycling. Earlier studies have shown that cells with damaged DNA are blocked from entering into mitosis but caffeine can partly overcome this block and induce premature chromosome condensation. Polyamine-depleted CHO-P22 cells responded to caffeine in the same way as cells with damaged DNA. These results show that polyamine depletion in CHO-P22 cells primarily affects DNA synthesis. The finding that polyamine-starved cells continuously take up bromodeoxyuridine without a corresponding increase in the amount of DNA is compatible with extensive repair of erroneous and/or damaged DNA. Polyamine auxotrophic Chinese hamster ovary (CHO) cells might be useful in studies on the regulation of mitosis in mammalian cells.

Animals↗
PubMed1994

Partial nephrectomy with a combined CO2 and Nd:YAG laser: experimental study in pigs.

Twenty-eight partial nephrectomies were performed on nine pigs with a simultaneous, coaxial CO2-Nd:YAG laser at power settings of 20 W and 40 W, or with a steel scalpel. A vascular pedicle clamp was used without renal cooling. The time for hemostasis was 4.5 +/- 3.2 min (mean +/- SD) with the laser and 6.4 +/- 2.5 min with the steel scalpel (P = 0.064). There was no difference in the total operation time (10.4 +/- 3.5 min with the laser vs. 11.0 +/- 3.2 min with the steel scalpel, P = 0.470). The mean blood loss with the laser was 17.5 +/- 6.7 g and 22.1 +/- 15.2 g with the steel scalpel (P = 0.299). The number of ligatures needed for complete hemostasis was 2.9 +/- 2.1 with the laser and 5.0 +/- 2.3 with the steel scalpel (P = 0.011). The average thermal damage was 0.23 +/- 0.10 mm. It is concluded that the simultaneous CO2-Nd:YAG laser method can be used in partial nephrectomy and it offers better hemostasis than the conventional technique. Further studies with different power levels are needed.

Aluminum↗
PubMed1994

Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy.

Clinical data were reviewed in 325 patients with prostatic adenocarcinoma followed up for a mean of 13 years. Paraffin-embedded tumour biopsy specimens from the primary tumours were available for flow cytometry (FCM) in 273 cases. Intra-tumour heterogeneity in DNA index (DI) was found in 4% of the tumours (54 cases were analysed). S-phase fraction (SPF) and DNA ploidy were significantly interrelated. Aneuploidy and high SPF were significantly related to both a high T category and high Gleason score. The progression in T1-2M0 tumours was related to Gleason score (P = 0.009), DNA ploidy (P = 0.006) and SPF (P = 0.007), while the Gleason score (P = 0.0013), DNA ploidy (P = 0.002) and SPF (P < 0.001) had prognostic value in univariate survival analysis. In the entire cohort, the T category (P < 0.001), M category (P < 0.001), Gleason score (P < 0.001), DNA ploidy (P < 0.001) and SPF (P < 0.001) were significant prognostic factors. In Cox's analysis, the M category (P < 0.001), Gleason score (P < 0.001), T category (P = 0.003), age (P = 0.001) and SPF (P = 0.087) were independently related to prognosis. In the T1-2M0 tumours, Gleason score (P < 0.001), T category (P = 0.022) and SPF (P = 0.058) were independent predictors. A novel classification system in which the DNA ploidy or SPF and the Gleason score were combined was found to be of significant prognostic value in all M0 tumours (P < 0.001). The results suggest that FCM can be used as an adjunct to conventional histological assessments for determination of the correct prognostic category in prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Hepatosplenic yeast infection in patients with acute leukemia: a diagnostic problem.

The occurrence of hepatosplenic candidiasis following prolonged neutropenic periods has emerged as a major problem for patients with leukemia. In order to evaluate the diagnostic value of various available procedures, we analyzed our findings regarding 26 leukemic patients with hepatosplenic candidiasis. A significantly increased level (> 50 mg/L) of serum C-reactive protein (S-CRP) was significantly more common than a daily fever (for which the mean temperature peak was > 37.5 degrees C) or raised levels of liver enzymes (serum alanine transferase, aspartate transferase, or alkaline phosphatase). Focal changes in the liver, spleen, or kidneys were detected in > 90% of the patients examined by computed tomography (CT) but in < 50% of those examined by ultrasonography. Seventeen diagnoses were based on the findings from microscopy of samples obtained invasively, whereas a positive fungal culture was the basis of the diagnosis for only five patients. In conclusion, monitoring the S-CRP level after a patient's recovery from neutropenia is useful in that its elevation is cause for early suspicion of hepatosplenic candidiasis. In detection of the hepatosplenic foci, CT is superior to ultrasonography. For establishing the specific diagnosis, aggressive collection of samples for microscopy is essential.

Acute Disease↗
PubMed1994

In vivo behavior of 111In-labeled monoclonal anti-prostatic acid phosphatase antibody after intraprostatic and intravenous injections.

The 111In-labeled monoclonal anti-prostatic acid phosphatase (PAP) monoclonal antibody F(ab')2 fragment was used for the radioimmunodetection of prostate cancer in two different patient groups: 15 patients with surgically verified T1-2 prostate cancer were imaged prior to staging lymphadenectomy and total prostatectomy using lymphatic administration (intraprostatic (ipr) injection), and 15 patients with verified metastatic prostatic cancer were imaged after intravenous (i.v.) injection. The patients were studied on several occasions (at 0-180 hours) after injecting a 1 mg MoAb fragment labeled with 75-150 MBq111In (DTPA-chelation). The extirpated tissues were counted for radioactivity, and studied immunohistochemically (IHC) and histologically. The anti-PAP MoAb was labeled with high efficiency (87-99%) and it demonstrated good immunoreactivity (90-95%) and a high affinity to the target antigen. In the excised prostates, cut into 12-18 smaller pieces, there was a clear correlation between the PAP content (as detected by IHC) and absolute radioactivity (% ID of 111In anti-PAP/g prostate). However, there was no correlation between radioactivity and the amount of cancer tissue (% of histological slices) inside the removed prostate tissue. In the pharmacokinetic studies, maximum activity in the serum was obtained within 3-5 hours after ipr injection; after that the kinetic behavior was similar to that after i.v. injection. After i.v. injection, two components could be distinguished the pharmacokinetic curves; the half-lives for mean distribution and elimination were 0.62 and 35.6 hours, respectively. The mean distribution half-life as well as the AUC from the pharmacokinetic curves correlated significantly with serum PAP (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1994

Histopathology of localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

Future handling of patients with localized prostate cancer will undoubtedly depend upon a more sophisticated prognostication than that available today. The basis will continue to be the histopathological evaluation of tumor size, grade, localization and distribution within the gland. The aim of this section is to summarize current concepts of the morphological characteristics of localized prostate cancer and their prognostic implications as well as to give guidelines for standardization of the methods involved in morphological evaluation. First, baseline recommendations for the tissue processing procedures are given: Needle core biopsies, taken in a systematic way, potentially contain the information necessary for estimation of grade, size, distribution and extension to seminal vesicles, and could yield material for DNA-measurements, cytogenetic and genetic information. For TUR specimens it is suggested that at least 10 grams should be embedded or 8 to 10 cassettes employed minimally. The prostatectomy specimens should be carefully examined. Material should be frozen both from tumor tissue and from other areas eg by taking 'mapping' biopsies in a standardized way. After fixation (in 10% buffered formalin for at least 24 hours) and appropriate inking of surgical margins, whole mount sections at 2.5-5 mm intervals should be cut. The extension of the tumor should be outlined and at least the two largest tumors should be graded. Capsule penetration and extension to surgical margins and seminal vesicles should be indicated. Grading of malignancy should always include the Gleason grade and where possible Gleason score (ie the sum of the dominant and the secondary grade or pattern). The WHO and the Boecking systems combine a grading of glandular architecture with a grading of the nuclear atypia. It is stressed that in core biopsies the amount of cancer is sometimes scanty, which limits the possibility to find dominant and secondary patterns. In such cases, a grading of glandular differentiation and of nuclear grade seems rational. Also, for comparison with cytological grading, the WHO system is suitable, since in both cases both tissue differentiation and nuclear atypia are judged. The future need for objective techniques is recognized. Prostatectomy pathology includes important features with high correlation to postoperative prognosis: eg capsular penetration. The extent of capsular penetration and the extent of involvement of the surgical margins is of importance. Only focal penetration or focal involvement of the margin carry a relatively low risk of of progression.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1994

DNA analysis in advanced breast cancer.

DNA flow cytometry is frequently used to determine the aggressiveness of breast cancer at the time of primary treatment. Because its role is not as clear in advanced disease, a retrospective investigation was conducted on 132 breast cancer patients with metastases or a subsequent recurrence of the disease. DNA analysis of 96 primary tumors and 53 metastases was performed. The follow-up time was up to 11 years. The mean DNA index of the primary tumors was 1.4 and the mean S-phase fraction (SPF) was 9.4%; 36.5% of the tumors was diploid. The DNA index did not differ significantly among the different stages, but the SPF was significantly higher in stage III than in stage IV. There was no significant difference in ploidy between the stages. There were no significant differences in DNA index and SPF between the primary tumors of the patients with local or distant metastases. The disease-free interval was independent of DNA index, ploidy, and SPF alone. There was no difference in DNA index, ploidy, or SPF between patients with an early or late relapse. Breast cancer-related mortality after metastasis was independent of ploidy alone. In stage I-II, patients with a low SPF had a significantly higher survival rate than other patients. The same was true in patients with a diploid tumor and a low SPF. When the DNA index, SPF, and ploidy of primary tumors and metastases/recurrences were analyzed, no combination of variables yielding an improved prognosis was found. Therefore, it seems that DNA flow cytometry has limited value in determining the prognosis in a patient with metastases or recurrence.

Breast Neoplasms↗
PubMed1994

Giant cell tumours of bone. A DNA-flow cytometric study.

The variable clinical course and locally aggressive growth of giant cell tumours of bone cause problems in planning treatment. Curettage and bone grafting is the commonest form of surgical treatment, but recurrence rates as high as 40 per cent have been reported. Thirty-four patients with a GCT were treated in our clinic between years 1982 and 1990. There were three gr 1, 24 gr II and 7 grade III tumours. Operative treatment was carried out in 31. DNA flow cytometry was performed from the sample in 28 patients. The type of treatment played an important role in tumour prognosis: there were 10 recurrences after 18 intralesional procedures, but only one recurrence after tumour resection. DNA flow cytometry was not helpful in predicting tumour behaviour.

Adolescent↗
PubMed1993

Flow cytometry in comparison with mitotic index in predicting disease outcome in transitional-cell bladder cancer.

The DNA content and S-phase fraction were measured by flow cytometry in 448 tumour biopsy specimens from transitional-cell bladder cancer (TCC). The samples were also analyzed for mitotic index, WHO grade and papillary status, and histological and flow cytometric data were then correlated to clinical behaviour of tumours during a mean follow-up period of 9.9 years. TNM classification, WHO grade, papillary status, mitotic index, DNA ploidy and S phase fraction were significantly interrelated. Twenty-four percent of tumours showed heterogeneous DNA indices when measured from multiple samples (measured in 94 cases). Of the histological parameters, independent predictors of progression in superficial tumours were the S-phase fraction and mitotic index. In superficial tumours, S-phase fraction and the mitotic index included all the available independent prognostic information in survival analysis, whereas in muscle-invasive tumours T category was the most important prognostic factor. The results suggest that DNA ploidy has no independent prognostic value in transitional-cell bladder cancer, whereas proliferation indices (SPF, mitotic index) are important prognostic factors. Accordingly, malignancy classification of papillary bladder tumours can be based on proliferation indices alone. Nodular tumours run an unfavourable course and their malignancy grading by flow cytometry or by mitotic index is not relevant.

Aged↗
PubMed1993

Contact fibre Nd:YAG laser for partial nephrectomy: experimental study in pigs.

Thirty-two partial nephrectomies were performed without renal cooling on 13 pigs with a contact fibre Nd:YAG laser (10 W) or a steel scalpel with or without a vascular pedicle clamp. Nine pigs had a 2-week follow-up with an abdominal ultrasound 1 week postoperatively. The time for haemostasis was 6.9 +/- 5.2 min (mean +/- SD) with the laser and 9.1 +/- 5.8 min with the steel scalpel when the clamp was used (P = 0.028). There was no significant difference in the total operating time (13.2 +/- 4.5 min with the laser vs 12.6 +/- 4.6 min with the steel scalpel, P = 0.203). Intraoperative blood loss was similar in the two groups when the clamp was used. Clamping the renal pedicle decreased the blood loss by 61% in the laser group and 31% in the steel scalpel group. The number of ligatures used was significantly lower in the laser group (3.7 +/- 2.6) compared with the steel scalpel group (6.6 +/- 3.4) (P = 0.013). Five urinomas developed on the laser side and four on the steel scalpel side. These results indicate that the contact fibre Nd:YAG laser method can be used in partial nephrectomy, but it offers no definitive advantage over the conventional technique.

Aluminum↗
PubMed1993

Poor prognosis associated with elevated serum CA 19-9 level in advanced colorectal carcinoma, independent of DNA ploidy or SPF.

DNA ploidy, S-phase fraction (SPF) for the tumours, serum tumour markers such as carcinoembryonic antigen (CEA) and serum CA 19-9 and major clinical parameters were analysed as prognostic factors in 105 patients with advanced colorectal carcinoma. All 105 were treated with a three-drug schedule including low dose epirubicin and sequential methotrexate, 5-fluorouracil, followed by leucovorin rescue. In univariate analysis, gender, Karnofsky index, extent of metastases, presence of abdominal metastases, CEA and CA 19-9 correlated with survival. Age, presence of liver or of lung metastases, DNA ploidy or SPF were not significantly associated with survival. In stepwise multivariate analysis an elevated serum CA 19-9 level, a poor Karnofsky index and multiple sites of metastases were independent adverse prognostic factors. Based on the multivariate analysis, patients were grouped in three categories. Group 1 consisted of 32 patients with Karnofsky > or = 80, with a normal serum CA 19-9 level and a single site of metastases. Group 2 consisted of 48 patients with Karnofsky > or = 80 and with an elevated serum CA 19-9 level or multiple sites of metastases. Group 3 consisted of 14 patients with Karnofsky < or = 70. This classification gave a highly significant correlation with survival (chi 2 = 45.52, P < 0.001, log rank test). The median survival in group 1, group 2 and group 3 was 30.1 months, 13.5 months and 3.9 months, respectively. Based on these results we suggest that trials involving advanced colorectal cancer should include the measurement of serum CA 19-9 levels as one of the most important prognostic factors, but also include documentation of other independent prognostic factors.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Prognostic value of Ki-67 immunolabelling in primary operable breast cancer.

The prognostic value of Ki-67 immunohistochemical labelling was evaluated in 327 operable primary carcinomas of the breast. The follow-up time was up to 4 years (mean 2.7 years). The disease-free survival in Ki-67 positive patients was shorter than in Ki-67 negative patients (P < 0.005). By combining the Ki-67 expression with ER receptors and stage, subgroups with a different disease-free survival were identified. In stage II patients there was a significant difference (P < 0.005) in disease-free survival between Ki-67 positive/ER negative and Ki-67 negative/ER positive patients. In node negative patients there was no such difference. The disease-free survival according to different prognostic factors, stage, ER and node status, were separately examined using a Cox's proportional hazards model. ER (P < 0.0001), the Ki-67 (P < 0.02), tumour size (P < 0.0001) and nodal status (P < 0.006) were independent prognostic factors. We conclude that the potential value of Ki-67 labelling for prognostic evaluation of patients with breast carcinoma is good.

Adult↗