The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Nils Mandahl - One of the best experts on this subject based on the ideXlab platform.
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fusion of chop to a novel rna binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils MandahlAbstract:HUMAN myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(ql3;pll)1,2, that is associated with a structural rearrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 residing on 12ql3.16. Using a CHOP-specifie complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
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Fusion of CHOP to a novel RNA-binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils Mandahl, Dorit RonAbstract:Human myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
Anne Crozat - One of the best experts on this subject based on the ideXlab platform.
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fusion of chop to a novel rna binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils MandahlAbstract:HUMAN myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(ql3;pll)1,2, that is associated with a structural rearrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 residing on 12ql3.16. Using a CHOP-specifie complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
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Fusion of CHOP to a novel RNA-binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils Mandahl, Dorit RonAbstract:Human myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
Cyril Fisher - One of the best experts on this subject based on the ideXlab platform.
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dedifferentiated Liposarcoma updates on morphology genetics and therapeutic strategies
Advances in Anatomic Pathology, 2016Co-Authors: Khin Thway, Robin L Jones, Jonathan Noujaim, Shane Zaidi, Aisha Miah, Cyril FisherAbstract:Well-differentiated Liposarcoma (WDL) and dedifferentiated Liposarcoma (DDL) form the largest subgroup of Liposarcomas, and represent a morphologic and behavioral spectrum of 1 disease entity, which arises typically in middle to late adult life, most frequently within the retroperitoneum or extremities. DDL is defined as nonlipogenic sarcoma that is juxtaposed to WDL, occurs as a recurrence of WDL or which can arise de novo, and typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma. DDL have a propensity for local recurrence, whereas distant metastasis is rarer, and behavior is related to anatomic site, with retroperitoneal neoplasms showing a significantly worse prognosis. Surgical resection remains the mainstay of treatment, and medical options for patients with aggressive recurrent or metastatic disease are limited. DDL share similar genetic abnormalities to WDL, with high-level amplifications of chromosome 12q14-15, including the MDM2 and CDK4 cell cycle oncogenes, and DDL harbor additional genetic changes, particularly coamplifications of 6q23 and 1p32. Novel therapies targeted at the gene products of chromosome 12 are being tested in clinical trials. We review the pathology and genetics of DDL, discussing morphologic patterns, immunohistochemical and genetic findings, the differential diagnosis, and future therapeutic strategies.
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differential sensitivity of Liposarcoma subtypes to chemotherapy
European Journal of Cancer, 2005Co-Authors: Robin L Jones, Cyril Fisher, Omar Almuderis, I JudsonAbstract:Abstract Liposarcoma is one of the most common soft tissue sarcomas and has a number of different subtypes: well-differentiated; dedifferentiated; myxoid/round cell; and pleomorphic. However, the response of these subgroups to chemotherapy is not well documented. In this study, we have conducted a retrospective analysis of a prospectively maintained database of soft tissue sarcoma patients treated at the Royal Marsden Hospital. Eighty-eight Liposarcoma patients who received chemotherapy between August 1989 and June 2004 were identified. The response rates to chemotherapy of the different histological subtypes and overall and progression free survival were investigated. Survival according to histological grade was also assessed. A statistically significant higher response rate to first-line chemotherapy was observed in patients with myxoid Liposarcoma compared to de- and well-differentiated tumours, 48% (95%CI; 28–69) and 11% (95%CI; 2–29), P = 0.005. Similarly, those with myxoid Liposarcoma had a significantly higher response rate compared to all other Liposarcoma patients, 48% (95%CI; 28–69) and 18% (95%CI; 8–31). Patients with lower grade tumours had better overall survival. This retrospective analysis suggests that myxoid Liposarcoma is relatively chemosensitive in comparison to a combination of other Liposarcomas, and in particular de- and well-differentiated tumours. Further confirmation of these results should be sought by similar analyses of other databases.
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paratesticular Liposarcoma a clinicopathologic study
The American Journal of Surgical Pathology, 2003Co-Authors: Elizabeth A Montgomery, Cyril FisherAbstract:Paratesticular Liposarcoma - A clinicopathologic study. Paratesticular Liposarcomas are rare and typically reported as isolated cases or as components of larger studies of Liposarcomas. We studied a series of these tumors. All cases of paratesticular Liposarcomas were retrieved from the archives of the Royal Marsden Hospital and the Johns Hopkins Hospital. Slides were reviewed and clinical information obtained. There were 30 paratesticular Liposarcomas from men aged 41-87 years (mean 63 years; median 65 years) that involved the spermatic cord (23, 76%), testicular tunics (6, 20%), and epididymis (1, 4%). Tumors ranged from 3 to 30 cm (mean 11.7 cm; median 10 cm). Nineteen were well-differentiated Liposarcomas (WDLs) and 10 were dedifferentiated Liposarcomas (DDLs, five with high-grade and five with low-grade dedifferentiation). One was a myxoid/round cell Liposarcoma with 70% round cell areas. All patients were treated by radical orchiectomy. One patient with WDL received radiation after his second recurrence and the myxoid/round cell Liposarcoma received radiation and chemotherapy. Follow-up information was available for 16 of the patients, including 10 WDLs (range 24-216 months, mean 106 months), 5 DDLs (14-30 months, median 24 months), and for the myxoid/round cell Liposarcoma (14 months) (range for all cases 14 months to 22 years; mean 87 months, median 36 months). Six of the WDLs (60%) recurred at 2, 4, 6, 10, 18, and 21 years (median 8 years). The lesion that recurred at 18 years (case no. 6) displayed foci of high-grade dedifferentiation in the recurrence, although the patient was disease free at 19 years. One patient with WDL had two recurrences at 4 and 7 years, and another had six recurrences over a 17-year period. Only one example of DDL recurred, at 30 months; another patient, who refused therapy for 15 years, had a primary tumor 30 cm in diameter, displayed pulmonary metastases 1 month after excision, and died after 14 months. The patient with MRCL had abdominal metastases after I year and was alive at 14 months. In summary, paratesticular WDL had a prolonged course with recurrences in more than half the cases, sometimes late. There were no metastases and the overall prognosis was good. One DDL recurred and only one of five (20%) developed metastases, but the mean follow-up for DDL was only 24 months.
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pleomorphic Liposarcoma a clinicopathologic analysis of 19 cases
Modern Pathology, 2001Co-Authors: Katharine A Downes, Elizabeth A Montgomery, John R Goldblum, Cyril FisherAbstract:Pleomorphic Liposarcoma is a variant of Liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic Liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33–87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5–31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2–3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1–6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2–129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2–48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3–28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4–48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic Liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.
Dorit Ron - One of the best experts on this subject based on the ideXlab platform.
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Fusion of CHOP to a novel RNA-binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils Mandahl, Dorit RonAbstract:Human myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
Pierre Åman - One of the best experts on this subject based on the ideXlab platform.
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DDIT3 Expression in Liposarcoma Development
Sarcoma, 2014Co-Authors: Christina Kåbjörn Gustafsson, Katarina Engström, Pierre ÅmanAbstract:Liposarcomas are mesenchymal tumors containing variable numbers of lipoblasts or adipocytes. The most common entities, well differentiated/dedifferentiated Liposarcoma (WDLS/DDLS) and myxoid/round cell Liposarcoma (MLS/RCLS), are both characterized by genetic rearrangements that affect the expression of the transcription factor DDIT3. DDIT3 induces Liposarcoma morphology when ectopically expressed in a human fibrosarcoma. The role of DDIT3 in lipomatous tumors is, however, unclear. We have analyzed the expression of DDIT3 in 37 cases of Liposarcoma (WDLS/DDLS n = 10, MLS/RCLS n = 16, and pleomorphic Liposarcomas (PLS) n = 11) and 11 cases of common benign lipomas. Major cell subpopulations of WDLS/DDLS and MLS/RCLS tumors were found to express DDIT3 or the derived fusion protein, whereas PLS cases showed only a few positive cells. The lipomas contained large subpopulations expressing DDIT3. No correlation between numbers of DDIT3 expressing cells and numbers of lipoblasts/adipocytes was found. In vitro adipogenic treatment of two DDIT3 expressing cell lines induced lipid accumulation in small subpopulations only. Our results suggest a dual, promoting and limiting, role for DDIT3 in the formation of lipoblasts and Liposarcoma morphology.
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fusion of chop to a novel rna binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils MandahlAbstract:HUMAN myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(ql3;pll)1,2, that is associated with a structural rearrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 residing on 12ql3.16. Using a CHOP-specifie complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
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Fusion of CHOP to a novel RNA-binding protein in human myxoid Liposarcoma
Nature, 1993Co-Authors: Anne Crozat, Pierre Åman, Nils Mandahl, Dorit RonAbstract:Human myxoid Liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in Liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
