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Biomedical subjects

T Sørlie

Publications and source records attributed to T Sørlie.

At least 19 recordsLinked to original sources
PubMed2001

Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.

The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.

Algorithms↗
PubMed2001

[Microarray technology--potential in cancer research].

BACKGROUND: Researchers have worked for decades to solve the enigma of cancer. We know that essential checkpoints in the life cycle of cells have to be disrupted in order to create a tumour cell, and some of the genes and proteins involved have been identified. Most of the previous work on identifying these genes have been based on "educated guesswork", as the methods and technologies used have been limited to the examination of genes one by one, or a few at a time. MATERIAL AND METHODS: Microarray technology allows tens of thousands of genes to be examined at the same time, without any previous information on the genes. Both expression levels and copy numbers of the genes can be evaluated. Our studies of breast cancer and bone tumours are presented, as well as examples from the literature. RESULTS AND DISCUSSION: Microarray analyses have been used to produce molecular portraits of breast cancer, malignant melanomas and other cancers. These portraits may help in sub-classification of tumours, in prognosis, and in the general understanding of cancer. For example, studies of gene expression patterns of breast carcinomas, similar with respect to classic prognostic markers (such as ER status, grading and morphology), have identified subgroups of patients that show differences in survival.

Bone Neoplasms↗
PubMed2001

Microarrays in primary breast cancer--lessons from chemotherapy studies.

Current development in molecular techniques has extended the opportunities to explore genetic alterations in malignant tissue. There is a need to improve prognostication and, in particular, to understand the mechanisms of treatment resistance in different tumours. Gene analyses by microarrays allow concomitant analyses of several genes in concert, providing new opportunities for tumour classification and understanding of key biological disturbances. This paper outlines our continuing studies exploring prognostic and, we hope, predictive factors in breast cancer therapy.

Breast Neoplasms↗
PubMed2001

A global measure of physical functioning: psychometric properties.

OBJECTIVE: To examine the psychometric properties of a global physical functioning scale (GPFS) developed as a self-report measure and constructed to scale physical functioning from very poor (1) to excellent (100). DATA SOURCES: Data collection took place between January 1997 and September 1999. It consisted of self-ratings of surgical patients and the ratings of clinicians. The setting was the surgical department at a university hospital. STUDY DESIGN: Test-retest reliability and the convergence of the scores of patients and clinicians were examined in 106 patients before elective coronary or gastrointestinal surgery. Inter-rater reliability was tested in 36 hospitalized patients with cardiologic or vascular surgical diseases who were rated by random selection from a pool of 91 clinicians. The patients also rated their physical functioning. Discriminative validity, sensitivity to change, ceiling and floor effects, and influence of emotional state upon the scores were tested in 127 patients in six diagnostic groups who scored the GPFS before and subsequent to surgery. The concurrent validity was examined in 101 patients who scored the GPFS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) before elective coronary surgery. PRINCIPAL FINDINGS: The test-retest correlation (.90), correlation of the scores of the clinicians and patients (.87), and rater intraclass correlation coefficient (.82) were high. The GPFS discriminated among patients with different levels of physical functioning, and it was sensitive to change following coronary surgery. There were moderate ceiling and no floor effects. The correlation with the physical functioning scale of the SF-36 (PF-10) was .67. The GPFS differentiated patients with middle levels of physical functioning better than did the PF-10. CONCLUSIONS: The psychometric properties of the GPFS appeared adequate as a measure of general physical functioning. The scale is easy to use and also appears suitable for outcome studies following substantial changes in physical functioning as after coronary surgery.

Activities of Daily Living↗
PubMed2000

Molecular portraits of human breast tumours.

Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.

Breast Neoplasms↗
PubMed2000

Predictors of satisfaction with surgical treatment.

OBJECTIVE: To investigate prospectively which medical, psychosocial or treatment-related factors predicted treatment satisfaction and to evaluate the adequacy of a preceding retrospective study which had examined the same factors. Furthermore, to examine the predictors and the stability of the major determinants of patient treatment satisfaction. DESIGN: Assessments made before admission, at discharge and 2 and 4 months after discharge were used to predict both the level and the rate of change in satisfaction with different aspects of treatment. SETTING: Three surgical departments at a University Hospital. STUDY PARTICIPANTS: Four-hundred and eighty-two patients electively admitted for several surgical conditions. RESULTS: The central treatment-related measures were the same in the retrospective and prospective studies: global satisfaction with treatment (GS), perceived quality of contact with the nursing (QCN) and medical staff (QCM) and provision of adequate treatment information (INF). More of the variance in GS was explained in the prospective study (48.7% versus 36.3%). GS was most influenced by treatment-related factors with QCN as the strongest predictor in both studies. Only a small portion of the variance in QCN and QCM could be accounted for by the characteristics of the patients. INF was predicted by characteristics of the patients, their illness and life situation and by treatment-related factors. QCN was the strongest predictor of INF. The relationships with the nursing and medical personnel appear to be the major determinants of both patient treatment satisfaction and patients' reception of adequate information about their condition and its treatment.

Adult↗
PubMed1999

Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway.

Malignant peripheral nerve sheath tumors (MPNSTs) are frequently associated with the disease neurofibromatosis type 1. Only few recurrent cytogenetic changes have been reported, including rearrangements of the short arm of chromosome 9. By fluorescence in situ hybridization with a centromere 9 probe, and by allelic imbalance studies with seven 9p21-23 markers in nine familial and three sporadic MPNSTs, we found interstitial deletions that supported CDKN2A as a possible target gene. Nine MPNSTs showed aberrations of CDKN2A by Southern blot analyses, and in four of these, expression of CDKN2A could not be detected by Northern blot analysis. No mutations of CDKN2A were identified by sequencing of the coding region, and gene inactivation by promoter methylation was not found. In the 9p allelic imbalance studies, a novel allele was detected at one locus in one tumor. Analyses of additional markers (n = 8) excluded mismatch repair deficiency as an important mechanism in the genesis of these tumors. The tumors were analyzed further for alterations in other candidate cell cycle-associated genes. In total, 11/12 MPNSTs showed DNA changes in one or more of the genes CDKN2A, CDKN2B, RB1, CDK4, MDM2, and CCND2. The present study suggests that disruption of the pRB pathway is common in MPNST, and that dose reduction of CDKN2A is particularly frequent and contributes to MPNST development. Genes Chromosomes Cancer 26:151-160, 1999.

Adolescent↗
PubMed1998

[Satisfaction and dissatisfaction with surgical treatment].

Using two different methods simultaneously, a surgical department assessed how former patients experienced the treatment they received. One method was based on a specifically designed questionnaire, while the other studied the patients negative experiences with regard to their treatment. The two approaches were compared in 610 respondents. The questionnaire yielded a more differentiated response pattern than did the other approach. While most of the respondents (88%) expressed overall satisfaction, the degree of satisfaction with information and supervision was not so high. The importance of the doctor's role was strongly emphasized, especially in the "negative experiences" approach. The use of this approach is dependent on the questions covering aspects of treatment actually experienced by the patient. The simultaneous use of both approaches will not only provide information about how patients experience essential aspects of their treatment but also what they consider to be the most problematic practical issues. This will encourage greater motivation among the staff to become involved in evaluation and improvement of treatment.

Adolescent↗
PubMed1998

Mutation screening of BRCA1 using PTT and LOH analysis at 17q21 in breast carcinomas from familial and non-familial cases.

Germline mutations in the BRCA1 gene predispose to breast and ovarian cancer. An estimated 45% of families with multiple breast cancer cases and more than 80% of breast-ovarian cancer families are linked to BRCA1. Mutation analyses by collaborative laboratories have revealed around 460 distinct BRCA1 sequence alterations, mostly germline mutations from familial cases. The majority of these alterations were nonsense and frame-shift mutations. In the present study, breast tumors of both sporadic and familial origin were investigated for allelic imbalance (AI) at the BRCA1 locus. AI was observed in 52% of the sporadic cases and in 17% of the familial cases. Furthermore, 104 breast carcinomas from patients with sporadic disease and 77 patients with positive family histories of breast and/or ovarian cancer were examined for translation-terminating mutations in exon 11 of the BRCA1 gene using the protein truncation test (PTT). No somatic mutations were detected in any of the tumors analysed, and only one BRCA1 mutation carrier was found among the familial cases. The result of this study gives no indication that truncating somatic mutations in exon 11 of BRCA1 play a major role in the tumorigenesis of the breast. Furthermore, the frequency of such mutation carriers in breast cancer populations with weak family histories of breast and/or ovarian cancer seems to be low.

Breast Neoplasms↗
PubMed1998

Analysis of p53, p16MTS, p21WAF1 and H-ras in archived bladder tumours from workers exposed to aromatic amines.

Exposure to aromatic amines is considered a major risk factor for the development of bladder cancer. In this study, we have analysed the pattern of point mutations in several tumour genes in 21 cases of bladder cancer arising among western European workers exposed to aromatic amines in an attempt to determine whether this exposure may be associated with a unique spectrum of mutations. Of the four genes analysed (p53, p16MTS1, p21WAF1 and H-ras), only p53 showed a high frequency of mutations (in 8 out of 21 cases, 38%). Two mutations were found in p16, one in H-ras and none in p21 exon 3. All mutations were at G:C base pairs, mostly at non-CpG residues. This spectrum of mutations, which is highly suggestive of an involvement of exogenous carcinogens, is however identical to the spectrum of p53 mutations detected in bladder cancers of the general population. In exposed workers, p53 mutations were associated with tumour grade and with high occupational and tobacco exposure. Taken together, our data suggest that the same carcinogens may be responsible for the development of bladder cancers in workers exposed to aromatic amines and in the general population.

Adolescent↗
PubMed1998

Psychotherapy supervision conducted by videoconferencing: a qualitative study of users' experiences.

Psychiatry residents in Norway have 70 hours of mandatory psychotherapy supervision to develop insights into the therapeutic relationship. Six supervision pairs (six candidates and two supervisors) conducted five videoconferencing-based supervision sessions (384 kbit/s) and five face-to-face sessions alternating weekly for 10 sessions. Following completion of the 10 sessions for candidates and supervisor B, and the 50 sessions for supervisor A, all subjects completed a semi-structured interview within two weeks. The eight subjects reported a wide range of experiences and attitudes. The results suggested that the quality of supervision can be satisfactorily maintained by using videoconferencing for up to half of the 70 hours required. The precondition for this estimate is that the pair in question have met face to face and established a relationship characterized by mutual trust and respect. Further studies, which include supervision pairs not having previously established relationships, are needed in order to indicate the generality of this precondition. The most obvious implication of this study is the potential for implementing decentralized models for recruiting and educating psychiatrists.

Adult↗
PubMed1998

Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online.

Inactivation of the adenomatous polyposis coli (APC) gene is an early event in sporadic colorectal cancer. Somatic mutations have also been detected in cancers of the stomach, pancreas, thyroid, ovary and breast. Over 95% of the mutations reported in the APC gene are frameshift and nonsense mutations. The large exon 15 accounts for 77% of the coding sequence. The APC gene product interacts with cytoplasmic beta-catenin, mediates its degradation and thereby downregulates transcription exerted by the beta-catenin-Tcf complex. In the absence of a functional APC protein, beta-catenin is stabilized and accumulates in the cytoplasm. This results in uncontrolled transcriptional activation of Tcf responsive genes which may contribute to cancer progression. In order to investigate whether this pathway is disrupted by APC mutations in breast carcinoma cells, we screened 227 breast tumors for truncating mutations in exon 15 using the protein truncation test (PTT). Only one mutation, 4678delA, which was shown to be somatic, was detected by this approach. The mutation resided just outside the mutation cluster region (MCR) and resulted in a premature stop in codon 1564. Our findings do not indicate that the suppressive function of APC is commonly abrogated by truncating mutations in human breast carcinomas.

Alternative Splicing↗
PubMed1997

[To what degree can patient satisfaction be explained? An analysis of a retrospective study].

A retrospective survey comprising 1198 randomly chosen former surgical patients was carried out on average ten months after treatment. The goal of the research project was to investigate the associations between global satisfaction with treatment and issues that might influence how the treatment was experienced. There were no significant differences between the 610 responders and the sample of 1198 patients with respect to age, sex, length of treatment and diagnosis. The following five variables explained together 36.2% of the variance in global treatment satisfaction: Subjective health at time of investigation, the personality dimension conscientiousness, the "degree of severity of the illness", "contact with doctors and nurses" and "conveyed information and supervision". "Contact with doctors and nurses" alone explained 25.1% of the variance.

Female↗
PubMed1995

Screening for p53 gene mutations in archived tumors of workers occupationally exposed to carcinogens: examples from analysis of bladder tumors.

Point mutations in the p53 tumor suppressor gene are the most common genetic alterations in human cancers. The nature and location of these mutations can be informative in assessing the importance of putative carcinogenic agents. Potential associations between a given carcinogen and a specific mutation pattern can be substantiated when the exposure history of the patients is known. While the past exposure to environmental risk factors is often difficult to determine, documented occupational exposure to carcinogens presents a unique situation for evaluating this approach. Analysis usually involves working with paraffin-embedded tissues, fixed under conditions suboptimal for genetic analysis and stored for many years, since frozen tissues are not available in sufficient numbers. The particular methodological problems encountered with fixed samples are discussed here, using as illustration an ongoing study of oncogene and tumor suppressor gene mutations in archived bladder tumors of workers exposed to aromatic amines and nonexposed patients.

Base Sequence↗
PubMed1995

[Development of cooperation in a surgical department. A group dynamics approach].

Knowledge of group dynamics is considered as an essential precondition in establishing good functioning teams. In order to develop cooperation within an administrative council at a surgical ward, a training programme primarily based on the participants own experiences in unstructured groups, was established. We present the theoretical background and the practical amplification of the programme and describe the process and the evaluation of it. In a time when the health services are exposed to great demands concerning quality and effectivity, we will recommend long lasting programmes for the development of communication and cooperation.

Communication↗
PubMed1994

Database of p53 gene somatic mutations in human tumors and cell lines.

A data base is described in which over 2,500 mutations in the p53 gene of human tumors and tumor cell lines are compiled from a systematic search of reports published before 1 January 1994. Data from 1994 are being added intermittently, with a systematic search and update scheduled for December, 1994. The compilation has been deposited with the EMBL Data Library and is available in electronic form free of charge. This report contains a rationale for the compilation, a brief summary of the major findings and a description of the data base.

DNA Mutational Analysis↗
PubMed1992

Long-term changes after brief dynamic psychotherapy: symptomatic versus dynamic assessments.

Dynamic change in psychotherapy, as measured by theory-related or mode-specific instruments, have been criticized for being too intercorrelated with symptomatic change measures. In this study, long-term changes after brief dynamic psychotherapy were studied in 45 moderately disturbed neurotic patients by a reliable outcome battery. The factor structure of all the change variables suggested that they tapped 2 distinct and stable sources of variance: dynamic and symptomatic change. The categories of overall dynamic change were different from categories of change on the Global Assessment Scale. A small systematic difference was found between the categories of overall dynamic change and the categories of target complaints change also, due to false solutions of dynamic conflicts.

Adult↗