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I Elomaa

Publications and source records attributed to I Elomaa.

At least 55 records · Page 3Linked to original sources
PubMed1997

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

Adolescent↗
PubMed1997

Concomitant i.v. and oral clodronate in the relief of bone pain--a double-blind placebo-controlled study in patients with prostate cancer.

Fifty-seven patients with advanced prostate cancer resistant to first-line hormonal therapy were treated with estramustine and additionally randomized for treatment with clodronate or placebo. Clodronate treatment was started with 5 days intravenous administration (300 mg day[-1]) and followed by oral treatment (1.6 g day[-1]) for 12 months. Skeletal pain relief was only about 10% better in the clodronate than in the placebo group. The results do not support the superiority of combined intravenous and oral treatment with clodronate compared with oral administration only.

Administration, Oral↗
PubMed1997

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy.

Antineoplastic Agents↗
PubMed1997

Prognostic factors in bone sarcomas.

Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].

Adolescent↗
PubMed1997

Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.

PURPOSE: In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases. MATERIALS AND METHODS: Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years. RESULTS: Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.

Administration, Oral↗
PubMed1997

Gains, losses, and amplifications of DNA sequences evaluated by comparative genomic hybridization in chondrosarcomas.

Comparative genomic hybridization was used to search for previously unknown gains and losses of DNA sequences along all chromosome arms in 29 chondrosarcoma specimens obtained from 23 patients. Extensive genetic aberrations, with a mean of 6 changes per tumor (range, 1 to 24), were detected in 21 of the 29 samples analyzed (72%). The majority of these changes were gains of whole chromosomes or whole chromosome arms. Gains of DNA sequence copy number were most frequent at 20q (38%), 17p (38%), 20p (31%), 1cen-q24 (28%), and 14q23-qter (28%). High-level amplifications of small chromosome regions were sporadic, detected in only 17% of the samples. The only recurrent high-level amplification, seen in two tumors (7%), affected the minimal common region 12cen-q15. Other amplifications, each encountered only once, involved 1p33-p35, 2p23-pter, 4p, 6p22-pter, 18q12-q22, 19p13.2, 19q13.2, and 20q13.1. Losses of DNA sequences were rare and were most commonly observed at 6cen-q22 (17%) and 9p (17%).

Adult↗
PubMed1997

Comparative genomic hybridization of malignant fibrous histiocytoma reveals a novel prognostic marker.

DNA sequence copy number changes were studied by comparative genomic hybridization (CGH) along all chromosomes in 58 samples of malignant fibrous histiocytoma (MFH). The material consisted of 43 primary tumors (9 of myxoid and 34 of storiform-pleomorphic subtype), 13 local recurrences (2 myxoid and 11 storiform-pleomorphic), and 2 metastases (1 myxoid and 1 storiform-pleomorphic). Genetic aberrations, with a mean of 5.5 changes per sample (range, 0 to 22), were detected in 47 of 58 samples (81%). The minimal common regions of the most frequent gains were 1p31 (33%), 9q31 (29%), 5p14-pter (26%), 7q32 (24%), and 7p15-pter (22%). High-level amplifications were detected in 16 of the 58 samples (28%). High-level amplification of 13q31-qter was seen in four tumors (7%); other high-level amplifications were more sporadic. Losses of DNA sequences were less frequent than gains. The minimal common regions of the most common losses were 13q21 (21%) and 13q22 (21%). Statistically significant correlation was found between gain of 7q32 and the rates of worse metastasis-free survival (P = 0.01) and overall survival (P = 0.004). The gain of 7q32 retained its prognostic significance also in a multivariate analysis with tumor size and grade. Gain of 1p31 was associated with a trend to decreased overall survival. Gains of 5p14-pter and 9q31 and losses of 13q21 and/or 13q22 did not have any prognostic value; neither did the total number of aberrations, total number of gains, or total number of losses per sample.

Adult↗
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

Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect and map the regions of gain, high-level amplification, and loss of DNA sequences in 14 liposarcomas. Thirteen tumors showed DNA sequence copy number changes of one or more genomic regions (mean, six aberrations/tumor; range, 0-17). These aberrations were observed in almost every chromosome but some chromosomal regions were affected more often than others. DNA sequence gains were more frequent than losses. The most common gain was seen at 12q14-21 (50% of tumors). Other frequent gains (29%) were of 1q21-24, 8cen-q21.2, 19q, and 20q. High-level amplification was observed in six (43%) tumors and included as minimal common segments bands 12q15, 1q22, and 1q24. In five (36%) tumors, sequences at 1q21-24 and 1q32 were found to be gained simultaneously with 12q14-21, which means that in 71% of the tumors with gain at 12q, an increase of DNA sequence copy number at 1q was also observed. The most common losses of DNA sequences (21%) occurred from regions 9p21-pter and 13q21-qter. Most of the aforementioned regions have not previously been reported to be altered in liposarcomas. The detection of a novel recurring amplicon at 1q21-24 with high-level amplification at 1q22 and frequent simultaneous DNA sequence gain at 12q14-21 (high-level amplification at 12q15) suggests that genes linked to both these regions may play a significant role in the development and progression of liposarcomas.

Adult↗
PubMed1996

Cytogenetic study of extraskeletal mesenchymal chondrosarcoma. A case report.

Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare and highly malignant type of chondrosarcoma of soft tissue origin. We performed a cytogenetic study on a patient with EMC. Cytogenetic analysis revealed the tumor karyotype: 48-49,XX, t(4;9)(q23;q22), add(10)(q?26), +16, ?del(19)(p13), +1-2mar[cp12] / 48-50,idem, t(1;20)(q21;q13), +mar[cp6] / 46,XX [7].

Adult↗
PubMed1996

The importance of a multidisciplinary group in the treatment of soft tissue sarcomas.

In 1987, a multidisciplinary soft tissue sarcoma (STS) group was established and a treatment protocol was set up. By 1993, there were 193 patients with a diagnosis of STS of the superficial trunk or extremities. 134 patients were referred with primary (stage M0) tumours and treated with curative or palliative intention. Nine amputations were performed. 94 (70%) patients were treated with wide or compartment surgery (n = 62) or marginal surgery combined with postoperative radiotherapy (n = 32). According to the protocol, these patients had received adequate treatment. 18 patients have recurred locally (13%) (median follow-up: 36 months). 12 were salvaged. 33 had metastases. The estimated 3-year survival, local control and disease-free survival rates are 79, 87 and 69%, respectively. These results compare favourably with previously published results from this hospital and from a nationwide study. The improved results emphasise the importance of a multidisciplinary STS group.

Adolescent↗
PubMed1996

Monitoring the action of clodronate with type I collagen metabolites in multiple myeloma.

In our previous double-blind trial, we reported that clodronate reduced the incidence of bone lesions, fractures, pain and hypercalcaemia in multiple myeloma. Recently, it has been assumed that the antiresorptive effect of bisphosphonates on the osteoclasts is mediated through the osteoblasts. We therefore determined, in 244 patients of the same trial, serum assays of aminoterminal propeptide of type I procollagen (PINP) and type I collagen degradation product (ICTP). PINP is an early synthesis product of proliferating osteoblasts, in comparison to the alkaline phosphatase (AP) which is secreted by differentiated osteoblasts during the maturation phase of collagen. ICTP circulates in serum when old bone is resorbed. Our results indicate that after 25 months, the PINP levels decreased in the clodronate group (from 68.9 +/- 4.4 micrograms/l to 37.2 +/- 3.5 micrograms/l; P < 0.001) but not in the control group (from 61.5 +/- 3.2 micrograms/l to 69.3 +/- 7.5 micrograms/l; P < NS). The fall in the ICTP levels was markedly steeper in the patients receiving clodronate (from 8.38 +/- 0.80 micrograms/l to 4.58 +/- 0.32 micrograms/l; P < 0.01) than placebo (from 7.84 +/- 0.53 micrograms/l to 6.45 +/- 0.95 micrograms/l; P = NS). A significant difference between the study groups was seen at 4 months in the PINP, at 7 months in the ICTP and at 13 months in the AP levels, suggesting that clodronate affected through the proliferating osteoblasts, the osteoclasts, and through the osteoclasts, the differentiated osteoblasts. High baseline ICTP, PINP and AP levels indicated a poor prognosis. The decrease of the markers by clodronate was more marked in survivors than in non-survivors.

Aged↗
PubMed1996

Type I and type III collagen metabolites in adult osteosarcoma patients.

Three biochemical markers of collagen metabolism were measured in 39 osteosarcoma patients. The pretreatment values did not predict outcome, and the markers showed no consistent change upon development of metastases. Both the age of the patients and the multimodality therapy affected the collagen metabolites. These findings emphasise the need for cautious interpretation of tumour-associated markers.

Adolescent↗
PubMed1996

Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma.

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman's rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.

Antineoplastic Agents↗
PubMed1996

No evidence of microsatellite instability in bone tumours.

Microsatellite instability has recently been reported in sporadic and familial colorectal tumours and can be due to defects in DNA mismatch repair genes. Such instability has subsequently been detected in several other types of sporadic tumours. We studied 29 specimens of bone tumours with different histopathological diagnoses and found no evidence of microsatellite instability. Our results suggest that mismatch repair defects are unlikely to play a significant part in the tumorigenesis of bone neoplasms. Loss of heterozygosity with at least one marker was detected in 11, i.e. in 38% of the tumour samples, most frequently with markers D2S136 at 2p (eight of 28 informative specimens, 29%) and D11S904 at 11p (four of 21 informative specimens, 19%).

Bone Neoplasms↗
PubMed1996

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer.

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.

Antineoplastic Agents, Hormonal↗
PubMed1996

Effects of chemotherapy-induced castration on serum lipids and apoproteins in premenopausal women with node-positive breast cancer.

The purpose of this study was to determine the effect of adjuvant chemotherapy on serum lipids and lipoproteins in premenopausal nonmetastatic breast cancer patients. Fifty-nine premenopausal breast cancer patients were treated with adjuvant chemotherapy comprising cyclophosphamide, methotrexate, and 5-fluorouracil. Levels of serum FSH, LH, and estradiol; fasting plasma levels of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglyceride, and apolipoprotein A-I, A-II, and B levels; and lipoprotein(a) [Lp(a)] were measured before treatment and 12 months after the beginning of chemotherapy. The changes in serum lipids after chemotherapy correlated significantly to changes in menstruation. Total cholesterol, LDL, and HDL cholesterol levels increased significantly only in patients with chemotherapy-induced ovarian dysfunction. Changes in apo B paralleled those in LDL and apo A-I and A-II HDL cholesterol. The serum concentration of Lp(a) increased significantly only in patients who developed permanent amenorrhea. There were no significant changes in triglyceride levels. Chemotherapy per se has no effect on serum lipids unless associated with induction of ovarian dysfunction. Ovarian failure after chemotherapy has an unfavorable effect on serum total and LDL cholesterol, apo B, and Lp(a) levels, but a favorable effect on HDL cholesterol.

Adult↗