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Biomedical subjects

M Nilbert

Publications and source records attributed to M Nilbert.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.

Adolescent↗
PubMed1998

Ewing's sarcoma treatment in Scandinavia 1984-1990--ten-year results of the Scandinavian Sarcoma Group Protocol SSGIV.

A report on the long-term follow up of the first cooperative Scandinavian Sarcoma Group study in Ewing's sarcoma of bone is presented. Fifty-two previously untreated patients entered the study between 1984 and 1990. Half of the tumors were located in the extremities and one quarter in the pelvis. The combined modality treatment consisted of 5 cycles of chemotherapy--including vincristine, methotrexate, doxorubicin, cyclophosphamide, bleomycin and dactinomycin. The first two cycles were followed by local resection or amputation in 35 patients and by radiotherapy alone in 17 patients. When surgery was not performed, was incomplete or yielded poor margins radiotherapy was given at a dose of 40-60 Gy. Local tumor relapses developed in 10 patients and in all but one patient were accompanied by metastatic disease. Five patients had metastasis at diagnosis and distant metastases developed after primary treatment in 27 patients after a median of 14 months. The median follow-up time for the 20 surviving patients is 10 years. At 5 years the tumor-related survival was 46% and the metastasis-free survival 43%. Late tumor relapses occurred in 4 patients, which reduced the 10-year tumor related survival to 41% and the metastasis-free survival to 38%. Histopathological tumour response correlated with survival with 5-year metastasis-free survival rates of 73% for the good responders and 35% for the poor responders.

Adolescent↗
PubMed1998

Transforming growth factor beta1 in the human endometrium. Cyclic variation, increased expression by estradiol and progesterone, and regulation of plasminogen activators and plasminogen activator inhibitor-1.

The purpose of this study was to identify cyclic variations and hormonal regulation of endometrial transforming growth factor beta1 (TGFbeta1) mRNA. Regulation of the plasminogen-activating system was also examined, since it is involved in activation of latent TGFbetas. We measured TGFbeta1 mRNA in 51 normal endometrial samples by Northern blot and densitometric scanning of autoradiograms. Each value was related to the corresponding beta-actin value to allow quantitative evaluation. TGFbeta1 mRNA was higher in the mid and late secretory and menstrual phases than in the earlier parts of the cycle. This pattern implies progesterone dependence. The content of TGFbeta1 mRNA in endometrial tissue explants obtained in the proliferative phase was significantly increased after stimulation for 4 days with estradiol + progesterone in vitro. Both TGFbeta1 and estradiol + progesterone increased the content of plasminogen activator inhibitor-1 mRNA and protein in primary cultures of endometrial stromal cells. Conditioned-medium concentrations of urokinase plasminogen activator (u-PA) were increased by TGFbeta1, but decreased by estradiol + progesterone. This effect of estradiol + progesterone results from increased internalization and degradation of u-PA secondary to up-regulation of the cell surface receptor for u-PA by progesterone (Casslén et al., JCEM 1995; 80: 2776-2784). Increased extracellular u-PA in response to TGFbeta1 exposure was thus in concordance with an unchanged amount of available u-PA receptors on the cell surface. The activation mechanism of latent TGFbeta involves u-PA activity; since u-PA activity is reduced in the secretory endometrium, we suggest that although TGFbeta1 mRNA is increased in the mid and late secretory phase, TGFbetas are mainly in their latent form until the premenstrual rise in u-PA activity stimulates activation. TGFbeta may promote capillary growth during endometrial regeneration.

Adult↗
PubMed1997

Molecular and cytogenetics of soft tissue sarcomas.

Molecular and cytogenetically soft tissue sarcomas are a well-characterized tumor entity with several tumor type specific changes understood also at the molecular level. Most likely, additional characteristic alterations will be detected, recurrent aberrations characterized at the molecular level, new clinical and histopathological correlations will be found, and little is known about how the genetic changes lead to tumor formation, promote progression and sometimes give tumor cells the ability to recur locally or distantly. The possibility to detect cells with these acquired genetic alterations may increase the reproducibility of tumor classification, yields promising possibilities for early diagnosis of tumor recurrences and/or metastasis, and may allow development of therapeutic regimens targeted at the genetically alterated cell.

Chromosome Aberrations↗
PubMed1995

Characterization of the 12q13-15 amplicon in soft tissue tumors.

Amplification of the genes MDM2, SAS, and CDK4, all located on the long arm of chromosome 12, has recently been demonstrated in human soft tissue tumors. To determine the extent of the amplification unit, we examined 16 soft tissue tumor samples, including pleomorphic liposarcoma, malignant fibrous histiocytoma (MFH), and atypical lipoma, by Southern blot analysis using 13 chromosome 12 probes. All tumors had previously been shown to have 3- to 20-fold amplification of MDM2. In five samples, all MFH, only MDM2 was amplified, whereas in the remaining 11 samples, two to five additional genes were amplified. The amplicon included markers both proximal and distal to MDM2, but was in all but one atypical lipoma confined to the chromosome region 12q13-15. Discontinuous amplicons were found in two of the tumors. This study indicates that MDM2, or possibly an as-yet-unidentified gene in its proximity, is the target gene of the 12q13-15 amplification in soft tissue tumors.

Chromosomes, Human, Pair 12↗
PubMed1995

Progesterone stimulates degradation of urokinase plasminogen activator (u-PA) in endometrial stromal cells by increasing its inhibitor and surface expression of the u-PA receptor.

Progesterone stimulates differentiation and inhibits the growth of endometrial tissue. Also, progesterone reduces plasminogen activator (PA) activity, which implies reduced turnover of extracellular matrix proteins in the secretory phase. To elucidate the mechanism responsible for reduced PA activity, primary cultures of human endometrial stromal cells were stimulated with estradiol and progesterone. Conditioned media were assayed for urokinase-type and tissue-type PA (u-PA and t-PA, respectively), PA inhibitor-1 (PAI-1), and PA activity. Binding of [125I]u-PA and [125I]u-PA:PAI-1 complex to the u-PA receptor and clearance of these ligands were studied. The PA activity of conditioned medium decreased after stimulation with progesterone, and this was secondary to a decrease in u-PA, but not t-PA, and an increase in PAI-1. Northern blot analysis showed induction of PAI-1 messenger ribonucleic acid, whereas the content of u-PA messenger ribonucleic acid was not influenced. Furthermore, the number of free u-PA receptor-binding sites was increased by estradiol and progesterone. The stromal cells degraded complexed u-PA more efficiently than free u-PA, and degradation of both ligands was inhibited by colchicine, chloroquine, and methylamine. Degradation was increased after hormone treatment, and this was apparently due to increased ligand binding, because neither ligand affinity nor the relative rate of degradation was increased. Increased expression of u-PA receptor-binding sites was not regulated on the transcriptional level, but may result from posttranslational mechanisms, such as decreased turnover of the receptor. Activation of plasminogen by receptor bound u-PA initiates a cascade of proteolytic events in the extracellular matrix that is important during tissue proliferation. Our data suggest that differentiated endometrial stroma in the secretory phase regulates extracellular proteolysis by increased elimination of u-PA through increased release of PAI-1 and increased u-PA receptor density.

Adult↗
PubMed1995

Pigmented villonodular synovitis. Monoclonality and metastasis--a case for neoplastic origin?

We report a 48-year follow-up of a case of recurrent pigmented villonodular synovitis of the knee. Subcutaneous metastasis to the contralateral thigh was an unusual finding. Histology demonstrated fibroblastic and histiocytic proliferation, as well as increased mitotic activity in recurrent lesions. Cytogenetic analyses demonstrated monoclonality and chromosomal abnormalities. Our findings support a neoplastic origin of this lesion.

Aged↗
PubMed1994

Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation.

Myxoid liposarcomas are cytogenetically characterized by t(12;16)(q13;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA-binding domain of FUS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. In the present study, we have mapped 16 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric FUS/CHOP transcript. The genomic breakpoints were dispersed along a 7.50-kilobase pair region from a SstI cleavage site upstream of the promoter of CHOP to a PstI cleavage site within intron 1. Reverse transcriptase-polymerase chain reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type II) in size. Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts. We cloned and sequenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I transcript. In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP. As a consequence the normally nontranslated exon 2 is translated and in both types there is in the junction between FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA.

Base Sequence↗
PubMed1994

MDM2 gene amplification correlates with ring chromosome in soft tissue tumors.

The human homolog of the murine double minute type 2 gene (MDM2) has been cloned and mapped to 12q13-14. The gene presumably functions as a cellular regulator and mediator of TP53 function. Amplification of the MDM2 gene has recently been observed in soft tissue sarcoma and in osteosarcoma. We studied MDM2 amplification in a series of 94 mesenchymal tumors and found 3-20-fold amplification in 20 tumors: in 10 of 49 malignant fibrous histiocytomas (MFH), in 1 of 2 pleomorphic liposarcomas, in 6 of 7 atypical lipomas, and in 3 of 12 typical lipomas. Normal hybridization patterns were detected in all 16 myxoid liposarcomas, in all 3 leiomyosarcomas, and in all 5 leiomyomas studied. The MDM2 amplification correlated with the presence of marker ring chromosomes; of the 10 MFH with MDM2 amplification, 5 had ring chromosomes, compared to 4 of 39 without MDM2 amplification, and all 9 liposomas with MDM2 amplification had ring chromosomes, in 5 of the tumors as the sole karyotypic anomaly. The correlation between ring chromosomes and MDM2 gene amplification indicates that the marker rings of MFH and of atypical lipoma often harbor genetic material derived from chromosome 12.

Adult↗
PubMed1994

No rearrangements of the CHOP gene in malignant fibrous histiocytoma.

The human transcription factor gene, CHOP, which maps to 12q13, was recently shown to be disrupted by the t(12;16)(q13;p11) in myxoid liposarcoma. The most common soft tissue sarcoma, malignant fibrous histiocytoma (MFH) histopathologically may contain liposarcoma like areas and is often characterized by complex chromosome anomalies, which may include 12q13-15 aberrations, but never as t(12;16). By Southern blot technique, we detected no rearrangements of the CHOP gene in 41 MFH, including five with liposarcoma like areas. Thus, rearrangements of the CHOP gene appear to be specific for myxoid liposarcoma with t(12;16) and are not associated with lipoblastic differentiation.

CCAAT-Enhancer-Binding Proteins↗
PubMed1992

Independent origin of uterine leiomyomas with karyotypically identical alterations.

Cytogenetic investigation of multiple uterine leiomyomas from the same patient revealed karyotypes containing cytogenetically indistinguishable del(7)(q21.2q31.2) in two of the tumors. Since this finding seemed to contradict the conclusion from previous glucose-6-phosphate dehydrogenase studies of multiple uterine leiomyomas in which an independent origin of these tumors was found, we assessed clonal tumor origin by DNA-recombinant X-chromosome inactivation analysis. The two leiomyomas with del(7)(q21.2q31.2) had different inactivated X-chromosomes. This proves that they originated independently and indicates that their cytogenetic similarity was coincidental.

Adult↗
PubMed1990

Characteristic chromosome abnormalities, including rearrangements of 6p, del(7q), +12, and t(12;14), in 44 uterine leiomyomas.

The cytogenetic analysis of 224 leiomyomas from 138 patients is presented. An insufficient number of mitoses was found in 35 tumors, normal karyotypes in 145, and clonal chromosome aberrations were detected in 44. The three previously identified cytogenetic subgroups were all represented in this series: del(7) (q21.2q31.2) was found in 11, trisomy 12 in five, and t(12;14)(q14-15;q23-24) in one leiomyoma. Rearrangements of 6p, including deletions, inversions, and various translocations, were found in eight tumors, thus delineating a new cytogenetic subgroup of uterine leiomyoma. The remaining 21 karyotypically abnormal tumors had nonrecurrent changes. One leiomyoma had two cytogenetically unrelated clones characterized by del(7)(q21.2q31.2) and +12. Karyotypic changes in two separate leiomyomas from the same uterus were identified in five patients; in three of them, different anomalies were found in the two tumors, whereas cytogenetically identical aberrations - del(7q) and dic(21;22) - were detected in two macroscopically discrete tumors. These findings suggest that whereas some multiple leiomyomas originate independently, others may be derived from the same neoplastic clone.

Chromosome Aberrations↗
PubMed1990

Trisomy 12 in uterine leiomyomas. A new cytogenetic subgroup.

Chromosome analysis of short-term cultures from uterine leiomyomas revealed trisomy 12 in six cases. In four of the tumors + 12 was the only karyotypic change. The fifth case also had trisomy 4, whereas the sixth had loss of one X chromosome as an additional aberration. These findings indicate that trisomy 12 characterizes a new cytogenetic subgroup of uterine leiomyoma.

Chromosomes, Human, Pair 12↗
PubMed1990

Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas.

Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.

Aged↗
PubMed1990

Chromosome rearrangements in two uterine sarcomas.

Cytogenetic analysis of short-term cultures from two uterine sarcomas revealed clonal chromosome abnormalities in both cases. A locally recurrent mixed mesodermal tumor had the karyotype 61,XX,+2,+3,+del(5)(q11),+6,+7,+del(7)(q32),+8,+8,+8,+10, -11,-11,+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+del(12)(q14q21),+13,+15,del(17)(q23),+20. The other tumor, a lung metastasis from a uterine leiomyosarcoma, had several karyotypically abnormal clones. Two of them consisted of highly aberrant cells with modal chromosome numbers of 82 and 153, respectively, but because of insufficient quality the complex anomalies could not be identified. Various chromosomal changes that included translocations, deletions, insertions, and numerical rearrangements (always with extra chromosome 7 material) were identified in pseudo- or near-diploid cells, resulting in nine additional cytogenetically abnormal clones.

Aged↗
PubMed1990

Chromosomal evolution and tumor progression in a myxoid liposarcoma.

A myxoid liposarcoma showed macroscopic, histologic, and cytogenetic heterogeneity. In one of three myxoid nodules and in the surrounding lipoma-like tumor tissue, the translocation t(12;16)(q13;p11), known to be specific for myxoid liposarcoma, was found as the sole chromosomal abnormality. In the other two nodules, additional rearrangements involving chromosomes 1, 12, and 16 were found. These aberrations were probably secondary to the primary t(12;16), and are cytogenetic evidence of clonal evolution. The complex chromosome aberrations were present in those tumor parts that had more malignant histology, indicating that the acquisition of secondary chromosomal aberrations parallels the histologic manifestations of tumor progression.

Chromosome Aberrations↗
PubMed1989

Characteristic karyotypic anomalies identify subtypes of malignant fibrous histiocytoma.

Cytogenetic analysis of short-term cultures from 25 malignant fibrous histiocytomas (MFH) revealed clonal chromosome abnormalities in 17 tumors: ten storiform-pleomorphic and seven myxoid MFH. Telomeric associations, rings, and dicentric chromosomes were present in 11 tumors and cytogenetic signs of gene amplification (homogeneously staining regions and double minute chromosomes) in four. The breakpoint distribution of the numerous structural rearrangements was nonrandom. The chromosome bands most frequently affected were 19p13 (in eight tumors; eight rearrangements gave rise to 19p+ markers, some of which looked similar, and an r(19) was found in one case), 11p11 (in seven tumors; three translocations and four deletions), 1q11 (in seven tumors; one translocation and six deletions), and 3p12 (in six tumors; all deletions). Other bands involved at least four times were 1p36, 5p15, and 20q13. Of particular clinical interest was the observation that tumors with 19p+ seemed to have a pronounced tendency to recur locally (local recurrence in five of eight tumors with 19p+ compared to one of nine in tumors without this aberration; observation period 4-16 months).

Aged↗