The Experts below are selected from a list of 951 Experts worldwide ranked by ideXlab platform
Benjamin A Alman - One of the best experts on this subject based on the ideXlab platform.
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Molecular Diagnostics
2013Co-Authors: H Hong, P Nadesan, R Poon, Benjamin A AlmanAbstract:www.bjcancer.com Testosterone regulates cell proliferation in Aggressive Fibromatosis (desmoid tumour
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Nefopam inhibits cell viability in cultures from Aggressive Fibromatosis and hypertrophic cutaneous wounds.
2013Co-Authors: Raymond Poon, Helen Hong, Xin Wei, James Pan, Benjamin A AlmanAbstract:Data from the Sulforhodamine B assay. The mean value for the cell culture treated with carrier was arbitrarily defined as 100 for each cell type. A) Data for a dose of 10 µM of Nefopam. There was a significantly lower level of cell viability in the Aggressive Fibromatosis or the hypertrophic scar cultures compared to that seen in normal tissues. B) Data from different doses of Nefopam in cell cultures from Aggressive Fibromatosis or from hypertrophic scars, showing a dose dependent decrease in cell viability. C) Time course data for cell viability after days of treatment with 10 µM of Nefopam in cell cultures from Aggressive Fibromatosis or from hypertrophic scars. Data is given as means and 95% confidence intervals. Control data is generated by treatment with diphenhydramine. Treatment with carrier alone gave identical results as for diphenhydramine. An asterisk over a data point indicates a significant difference form the control cell cultures.
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Aggressive Fibromatosis desmoid tumor is derived from mesenchymal progenitor cells
Cancer Research, 2010Co-Authors: Colleen Wu, Saied Nikamini, Puviindran Nadesan, William L Stanford, Benjamin A AlmanAbstract:The cellular origins from which most tumors arise are poorly defined, especially in mesenchymal neoplasms. Aggressive Fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor that has mesenchymal characteristics. We found that Aggressive Fibromatosis tumors express genes and cell surface markers characteristic of mesenchymal stem cells (MSC). In mice that are genetically predisposed to develop Aggressive Fibromatosis tumors ( Apc wt/1638N ), we found that the number of tumors formed was proportional to the number of MSCs present. Sca-1 −/− mice, which develop fewer MSCs, were crossed with Apc wt/1638N mice. Doubly mutant mice deficient in Sca-1 developed substantially fewer Aggressive Fibromatosis tumors than wild-type (WT) littermates, but Sca-1 deficiency had no effect on the formation of epithelial-derived intestinal polyps. MSCs isolated from Apc wt/1638N mice (or mice expressing a stabilized form of β-catenin) induced aberrant cellular growth reminiscent of Aggressive Fibromatosis tumors after engraftment to immunocompromised mice, but WT cells and mature fibroblasts from the same animals did not. Taken together, our findings indicate that Aggressive Fibromatosis is derived from MSCs, and that β-catenin supports tumorigenesis by maintaining mesenchymal progenitor cells in a less differentiated state. Protecting this progenitor cell population might prevent tumor formation in patients harboring a germline APC mutation, where Fibromatosis is currently the leading cause of mortality. Cancer Res; 70(19); 7690–8. ©2010 AACR.
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Aggressive Fibromatosis desmoid tumor is derived from mesenchymal progenitor cells
Cancer Research, 2010Co-Authors: Saied Nikamini, Puviindran Nadesan, William L Stanford, Benjamin A AlmanAbstract:The cellular origins from which most tumors arise are poorly defined, especially in mesenchymal neoplasms. Aggressive Fibromatosis, also known as desmoid tumor, is a locally invasive soft tissue tumor that has mesenchymal characteristics. We found that Aggressive Fibromatosis tumors express genes and cell surface markers characteristic of mesenchymal stem cells (MSC). In mice that are genetically predisposed to develop Aggressive Fibromatosis tumors (Apc(wt/1638N)), we found that the number of tumors formed was proportional to the number of MSCs present. Sca-1(-/-) mice, which develop fewer MSCs, were crossed with Apc(wt/1638N) mice. Doubly mutant mice deficient in Sca-1 developed substantially fewer Aggressive Fibromatosis tumors than wild-type (WT) littermates, but Sca-1 deficiency had no effect on the formation of epithelial-derived intestinal polyps. MSCs isolated from Apc(wt/1638N) mice (or mice expressing a stabilized form of β-catenin) induced aberrant cellular growth reminiscent of Aggressive Fibromatosis tumors after engraftment to immunocompromised mice, but WT cells and mature fibroblasts from the same animals did not. Taken together, our findings indicate that Aggressive Fibromatosis is derived from MSCs, and that β-catenin supports tumorigenesis by maintaining mesenchymal progenitor cells in a less differentiated state. Protecting this progenitor cell population might prevent tumor formation in patients harboring a germline APC mutation, where Fibromatosis is currently the leading cause of mortality.
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human sterile alpha motif domain 9 a novel gene identified as down regulated in Aggressive Fibromatosis is absent in the mouse
BMC Genomics, 2007Co-Authors: Jeffrey R Macdonald, Robert Y Wei, Jocelyn Ray, Kimberly Lau, Christopher Kandel, Rachel Koffman, Sherilyn Bell, Stephen W Scherer, Benjamin A AlmanAbstract:Neoplasia can be driven by mutations resulting in dysregulation of transcription. In the mesenchymal neoplasm, Aggressive Fibromatosis, subtractive hybridization identified sterile alpha motif domain 9 (SAMD9) as a substantially down regulated gene in neoplasia. SAMD9 was recently found to be mutated in normophosphatemic familial tumoral calcinosis. In this study, we studied the gene structure and function of SAMD9, and its paralogous gene, SAMD9L, and examined these in a variety of species. SAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with β-catenin stabilization, such as Aggressive Fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice. SAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene.
Catherine Li - One of the best experts on this subject based on the ideXlab platform.
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cyclooxygenase two cox 2 modulates proliferation in Aggressive Fibromatosis desmoid tumor
Oncogene, 2001Co-Authors: Raymond Poon, Catherine Li, Ron Smits, Shantie Jagmohanchangur, Michael Kong, Sophia S Cheon, Chunying Yu, Riccardo Fodde, Benjamin A AlmanAbstract:Aggressive Fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or β-catenin genes, resulting in β-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in β-catenin stabilization. Human Aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven Fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2−/− mice resulted in no difference in number of Aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to β-catenin stabilization in Aggressive Fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic Aggressive Fibromatosis (desmoid tumor)
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Aggressive Fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic Aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of Aggressive Fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.
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adenomatous polyposis coli gene mutation alters proliferation through its β catenin regulatory function in Aggressive Fibromatosis desmoid tumor
American Journal of Pathology, 1998Co-Authors: Catherine Li, Bharati Bapat, Benjamin A AlmanAbstract:Aggressive Fibromatosis is a monoclonal proliferation of spindle (fibroblast-like) cells. A subset of lesions contain somatic truncating adenomatous polyposis coli ( APC ) gene mutations, and all of the lesions contain an elevated β-catenin protein level. A major function of APC is to regulate β-catenin protein level. β-Catenin has a dual function in the cell: it is a member of the adherens junction, and it binds transcription factors in the tcf-lef family, transactivating transcription. Cell cultures from Aggressive fibromatoses containing an APC mutation were studied. Transient transfection of the full-length APC gene caused decreased proliferation and β-catenin protein level in these cultures. To determine whether β-catenin protein level was responsible for the change in proliferation rate, stable transfections of ΔN89β-catenin (a stabilized form that is not degraded by APC, but retains all other functions) were achieved in half of the cultures derived from each tumor, whereas the other half were transfected with an empty vector. Transfection of the full-length APC gene in cultures that were stably transfected with ΔN89β-catenin did not result in a change in proliferation. The type I promotor of p56lck contains an HMG consensus region, to which members of the tcf-lef family can bind. p56lck was expressed in cultures not transfected with the full-length APC gene and in cultures transfected with the full-length APC gene and ΔN89β-catenin, but not in cultures transfected with only the full-length APC gene. These data show that APC truncating mutations give Aggressive Fibromatosis cells a proliferative advantage through β-catenin and suggest that β-catenin acts to transactivate transcription.
Sabine Tejpar - One of the best experts on this subject based on the ideXlab platform.
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic Aggressive Fibromatosis (desmoid tumor)
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Aggressive Fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic Aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of Aggressive Fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.
Bharati Bapat - One of the best experts on this subject based on the ideXlab platform.
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic Aggressive Fibromatosis (desmoid tumor)
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predominance of beta catenin mutations and beta catenin dysregulation in sporadic Aggressive Fibromatosis desmoid tumor
Oncogene, 1999Co-Authors: Sabine Tejpar, Friedel Nollet, G Michils, Bharati Bapat, Eric Van Cutsem, Catherine Li, Jay S Wunder, Jean Jacques Cassiman, Benjamin A AlmanAbstract:Aggressive Fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic Aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of Aggressive Fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.
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adenomatous polyposis coli gene mutation alters proliferation through its β catenin regulatory function in Aggressive Fibromatosis desmoid tumor
American Journal of Pathology, 1998Co-Authors: Catherine Li, Bharati Bapat, Benjamin A AlmanAbstract:Aggressive Fibromatosis is a monoclonal proliferation of spindle (fibroblast-like) cells. A subset of lesions contain somatic truncating adenomatous polyposis coli ( APC ) gene mutations, and all of the lesions contain an elevated β-catenin protein level. A major function of APC is to regulate β-catenin protein level. β-Catenin has a dual function in the cell: it is a member of the adherens junction, and it binds transcription factors in the tcf-lef family, transactivating transcription. Cell cultures from Aggressive fibromatoses containing an APC mutation were studied. Transient transfection of the full-length APC gene caused decreased proliferation and β-catenin protein level in these cultures. To determine whether β-catenin protein level was responsible for the change in proliferation rate, stable transfections of ΔN89β-catenin (a stabilized form that is not degraded by APC, but retains all other functions) were achieved in half of the cultures derived from each tumor, whereas the other half were transfected with an empty vector. Transfection of the full-length APC gene in cultures that were stably transfected with ΔN89β-catenin did not result in a change in proliferation. The type I promotor of p56lck contains an HMG consensus region, to which members of the tcf-lef family can bind. p56lck was expressed in cultures not transfected with the full-length APC gene and in cultures transfected with the full-length APC gene and ΔN89β-catenin, but not in cultures transfected with only the full-length APC gene. These data show that APC truncating mutations give Aggressive Fibromatosis cells a proliferative advantage through β-catenin and suggest that β-catenin acts to transactivate transcription.
Alessandro Gronchi - One of the best experts on this subject based on the ideXlab platform.
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tailored beta catenin mutational approach in extra abdominal sporadic desmoid tumor patients without therapeutic intervention
BMC Cancer, 2016Co-Authors: Danique L M Van Broekhoven, Thijs Van Dalen, Dirk J Grunhagenl, Frits Van Coevorden, Han J Bonenkamp, Lukas B Been, Marc H A Bemelmans, Sander D S Dijkstra, Chiara Colombo, Alessandro GronchiAbstract:The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of Aggressive Fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall Aggressive Fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor. GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall Aggressive Fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization. This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression. The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number 4714 .
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isolated limb perfusion using tumour necrosis factor α and melphalan in patients with advanced Aggressive Fibromatosis
British Journal of Surgery, 2014Co-Authors: D L M Van Broekhoven, Jan P Deroose, S Bonvalot, Alessandro Gronchi, Dirk J Grunhagen, A M M Eggermont, C VerhoefAbstract:Background Aggressive fibromatoses (desmoid tumours) may be locally Aggressive, but do not metastasize. Although a conservative approach is advocated for most patients, pain and functional impairment are indications for active treatment. Tumour necrosis factor (TNF) α and melphalan-based isolated limb perfusion (TM-ILP) is a limb-saving treatment modality for soft tissue tumours. This study reports the results of TM-ILP treatment in patients with Aggressive Fibromatosis. Methods Institutional databases of three European centres were searched. All patients who received TM-ILP treatment for Aggressive Fibromatosis between 1990 and 2012 were included. Before therapy, the patients were discussed at multidisciplinary tumour board meetings. Results Twenty-five patients received 28 TM-ILP treatments. The median age of patients was 28 (i.q.r. 19–34) years and median hospital stay was 8 (7–12) days. Median follow-up was 84 (34–114) months. A complete response was achieved after two TM-ILP treatments, and a partial response after 17 treatments in 16 patients. Stable disease was reported after eight treatments in seven patients, including a patient with stable disease after the first treatment and progression after the second TM-ILP. Toxicity was modest after most treatments; Wieberdink grade IV (extensive epidermolysis, and threatening or manifest compartment syndrome) was seen after two TM-ILP treatments. Systemic leakage was reported after one treatment, but did not lead to systemic toxicity. Functional outcome was good; 16 patients had no physical limitations, and six patients had some limitations but did not need medical aids. Amputation was prevented in all but three patients. Conclusion TNF-α-based ILP is effective in patients with Aggressive Fibromatosis.
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Aggressive Fibromatosis in children and adolescents the italian experience
Cancer, 2009Co-Authors: Cristina Meazza, Alessandro Gronchi, Gianni Bisogno, Michela Casanova, Marco Fiore, Giovanni Cecchetto, Rita Alaggio, Giuseppe Maria Milano, Modesto Carli, Andrea FerrariAbstract:BACKGROUND: Aggressive Fibromatosis (AF) is a rare tumor of intermediate malignancy that has a strong potential for local invasiveness and recurrence. To date, there are no general recommendations for the clinical management of pediatric AF. METHODS: The authors retrospectively analyzed 94 patients aged ≤21 years, including 23 patients who underwent complete surgery (Group I), 42 patients who underwent incomplete surgery with microscopic residual tumor (Group II), and 29 patients who underwent either biopsy or macroscopically incomplete surgery (Group III). RESULTS: The 5-year event-free survival (EFS) and overall survival rates were 44% and 99%, respectively. Local recurrences developed in 22% of patients in Group I, in 76% of patients in Group II, and in 76% of patients in Group III. Two of 7 patients with abdominal disease died of tumor progression, whereas none of the patients with extra-abdominal AF died of their disease. Systemic treatment was given to 15 patients as first-line treatment and to 34 patients at time the time they developed recurrent disease: The response rate was 47% in the former patients and 50% in the latter patients. Objective responses were observed in 11 of 19 patients who received combined methotrexate plus vinblastine/vinorelbine, in 7 of 15 patients who received alkylating-agent chemotherapy, and in 4 of 11 patients who received other therapies (tamoxifen, sulindac, interferon alfa). CONCLUSIONS: The current analysis suggested that the clinical course of AF in children may resemble that of AF in adults. Local recurrences did not affect the chance of responding to systemic therapy or the survival rate. The completeness of initial resection was the main factor that influenced EFS, whereas disease control after marginal resection was much the same as that achieved after intralesional surgery/biopsy. Good responses to systemic treatments, and particularly to low-dose chemotherapy, were observed as reported previously in adults. Cancer 2010. © 2010 American Cancer Society.
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quality of surgery and outcome in extra abdominal Aggressive Fibromatosis a series of patients surgically treated at a single institution
Journal of Clinical Oncology, 2003Co-Authors: Alessandro Gronchi, Marco Fiore, P G Casali, Luigi Mariani, Lo S Vullo, Maurizio Colecchia, L Lozza, Rossella Bertulli, P Olmi, Mario SantinamiAbstract:Purpose: To explore prognostic factors in surgically treated Aggressive Fibromatosis (extra-abdominal desmoid tumor). Patients and Methods: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. Results: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did no...