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Abstracts by Bruce Shriver
Soft-tissue masses: Use of a scoring system in differentiation of benign and malignant lesions “Soft-tissue masses: Use of a scoring system in differentiation of benign and malignant lesions”, by Hakan Mutlu, , Emir Silit, Zekai Pekkafali, C. Cinar Basekim, Ersin Ozturk, Onur Sildiroglu, Esref Kizilkaya and A. Fevzi Karsli, Clinical Imaging, Volume 30, Issue 1 , January-February 2006, Pages 37-42. From the abstract, “The purpose of this study was to show the qualitative and quantitative MRI characteristics of soft-tissue masses in differentiation of benign and malignant lesions. A total of 90 soft-tissue lesions were reviewed in this study. The scoring system presents a more objective diagnostic performance in the prediction of benign or malignant masses. With the use of this scoring system, unnecessary biopsy can be precluded in benign lesions.”
Gastrointestinal stromal tumors: CT and MRI findings “Gastrointestinal stromal tumors: CT and MRI findings” , by K. Sandrasegaran, A. Rajesh, D.A. Rushing, J. Rydberg, F.M. Akisik and J.D. Henley, European Radiology, 2005; 215:1407– 1414. "The objective of this study is to report the CT and MRI appearances of primary and metastatic gastrointestinal stromal tumor (GIST). The clinical and imaging findings of 31 patients with histological and immunohistochemical diagnosis of GIST were reviewed. The CT and MRI findings were assessed independently for size, location, enhancement characteristics, and pattern of metastatic disease. The tumors were of enteric (n =13), gastric (n =12), duodenal (n =2), and rectal (n =3) origin. In one case, the primary site was the mesentery, without involvement of bowel. Primary tumors were typically exophytic (79%), larger than 5 cm (84%), and inhomogeneously enhancing (84%). Central necrosis of all tumors (37%) and aneurismal dilation of enteric tumors (33%) were less common. Metastases were most common in mesentery (26%) or liver (32%). Less common findings were ascites (7%) and omental caking (3%). Liver metastases were hypervascular in 92% of patients and rapidly became cystic following therapy with imatinib mesylate (Gleevec; Novartis, East Hanover, NJ, USA). Lung metastases, bowel obstruction, vascular invasion, and significant lymphadenopathy were not seen in any patient. Gastrointestinal stromal tumors have some specific CT findings that could help differentiate them from other gastrointestinal tumors. Liver metastases became cystic following therapy, mimicking simple cysts. MRI was better than single-phase CT for assessing liver metastases, whereas CT was more sensitive for mesenteric metastases."
Osteogenic sarcoma of the jaw bones: A single institution experience over a 21-year period ”Osteogenic sarcoma of the jaw bones: A single institution experience over a 21-year period”, Mobolanle Olugbemiga Ogunlewe, Oluseyi Folake Ajayi, Wasiu Lanre Adeyemo, Akinola Ladipo Ladeinde, and Olutayo James, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, Volume 101, Issue 1 , January 2006, Pages 76-81. From the conclusion, “Osteogenic sarcoma of the jaws is rare in patients who presented with tumor and tumor-like lesions of the jaws in our center, in agreement with previous reports from Africa and other centers around the world. However, the mean age at presentation of our patients was lower than reported in other parts of the world.”
Intensive Therapy With Growth Factor Support for Patients With Ewing Tumor Metastatic at Diagnosis “Intensive Therapy With Growth Factor Support for Patients With Ewing Tumor Metastatic at Diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457—A Report From the Children's Oncology Group”, by Mark L. Bernstein, Meenakshi Devidas, Dominique Lafreniere, Abdul-Kader Souid, Paul A. Meyers, Mark Gebhardt, Kimo Stine, Richard Nicholas, Elizabeth J. Perlman, Ronald Dubowy, Irving W. Wainer, Paul S. Dickman, Michael P. Link, Allen Goorin, Holcombe E. Grier, Journal of Clinical Oncology, Vol 24, No 1 (January 1), 2006: pp. 152-159. From the purpose, “Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy. A randomly assigned proportion of patients received amifostine as a cytoprotective agent.” From the conclusion. “Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Amifostine was not myeloprotective. Overall results showed no improvement compared with previous studies.”
Pre- and post-chemotherapy alkaline phosphatase levels "Pre- and post-chemotherapy alkaline phosphatase levels as prognostic indicators in adults with localised osteosarcoma", by Jos A.M. Bramera, Adesegun A. Abudua, Roger M. Tillmana, Simon R. Cartera, Vaiyapuri P. Sumathia and Robert J. Grimera, European Journal of Cancer Volume 41, Issue 18 , December 2005, Pages 2846-2852. From the abstract, The prognostic value of alkaline phosphatase (AP) measured before and after chemotherapy, but before surgery was established in a retrospective survey of patients. The patients were 18 years or older, with non-metastatic high-grade osteosarcoma. Pre-chemotherapy AP was available in 89 cases, post-chemotherapy AP in 86 patients, and both in 71 cases. AP was classified as Normal (<100% upper limit), High (100% AP < 200%) or Very High (AP 200%). Osteosarcoma subtype was predominantly conventional. No correlation was found between subtype and chemotherapy response, local recurrence or survival. Pre-chemotherapy AP was raised more in the osteoblastic subtype. Post-chemotherapy AP and normalisation were the same among different subtypes. AP was not correlated with local recurrence. Normal or High pre-chemotherapy AP correlated with better survival at 10 years (64% and 70%) than Very High pre-chemotherapy AP (37%, P = 0.005). Post-chemotherapy AP correlated with survival (68%, 39% and 25% in the Normal, High and Very High group, P = 0.0007) and response to chemotherapy (P = 0.049). A pre-chemotherapy AP above twice Normal correlated with worse survival. If AP decreased after chemotherapy, but was still raised, survival was better, but still worse than if AP normalised. A raised post-chemotherapy AP predicts poor chemotherapy response."
Periosteal osteosarcoma – a European review of outcome "Periosteal osteosarcoma – a European review of outcome", by Robert J. Grimera, Stefan Bielackb, Silke Flegeb, Stephen R. Cannonc, Gunnar Folerasd, Ivan Andreeffe, Todor Sokolove, Antonie Taminiauf, Martin Dominkusg, Mikel San-Julianh, Yehuda Kollenderi, Georg Goshegerj and from The European Musculo Skeletal Oncology Society (EMSOS), European Journal of Cancer Volume 41, Issue 18 , December 2005, Pages 2806-2811. From the abstract, "Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study."
Predictors of outcome in children and adolescents with rhabdomyosarcoma of the trunk "Predictors of outcome in children and adolescents with rhabdomyosarcoma of the trunk—the St Jude Children's Research Hospital experience," by Chan Hon Chuia, Catherine A. Billupsb, Alberto S. Pappoc, d, Bhaskar N. Raoe, f and Sheri L. Spuntg, Journal of Pediatric Surgery, Volume 40, Issue 11 , November 2005, Pages 1691-1695. From the results, "Thirty-three patients with a median age of 8 years were identified. Most had advanced Intergroup Rhabdomyosarcoma Study group III (n = 13) or group IV (n = 9) disease. Primary site included 20 (61%) chest wall, 6 (21%) paraspinal, 5 (15%) periscapular, and 1 (3%) abdominal wall. Most tumors were embryonal (n = 21), larger than 5 cm (n = 27), and locally invasive (n = 13); 7 had positive nodes. Tumor size, nodal status, and gross total tumor resection (upfront or delayed) were significant predictors of event-free and overall survival. Tumors 5 cm or smaller were amenable to upfront surgical resection (P = .007). In patients with tumors larger than 5 cm, resection at any time was associated with a 10-year overall survival 57% ± 13% compared with 8% ± 5% in those who had no surgery (P = .003). Tumor recurrence was local in 44% of cases, and survival after local recurrence was rare (1 of 8)." From the conclusion, "Tumor size, nodal status, and gross total resection at any time are significant predictors of outcome in truncal rhabdomyosarcoma. Gross tumor excision should be the goal of surgical intervention in this disease."
Interleukin-12 Up-Regulates Fas Expression "Interleukin-12 Up-Regulates Fas Expression in Human Osteosarcoma and Ewing's Sarcoma Cells by Enhancing Its Promoter Activity", by Zhichao Zhou, Elizabeth A. Lafleur, Nadezhda V. Koshkina, Laura L. Worth, Malisa S. Lester and Eugenie S. Kleinerman, Molecular Cancer Research 3:685-692 (2005). "Interleukin-12 (IL-12) has shown significant antitumor activity in several preclinical animal tumor models. Our previous studies showed that IL-12 inhibited tumor growth in human osteosarcoma and Ewing's sarcoma animal model. Decreased Fas expression in osteosarcoma increased the lung metastatic potential. In this study, we further examined the mechanism of IL-12 antitumor activity and showed that IL-12 significantly increased Fas expression in both human osteosarcoma cells LM7 and Ewing's sarcoma cells TC71. Up-regulation of Fas expression increased their sensitivity to Fas-induced cell apoptosis. Constructs of the Fas promoter linked to a luciferase reporter gene were used to determine the promoter activity. IL-12 increased Fas promoter activity 4.2- and 4.9-fold in TC71 and LM7 cells, respectively. Time course studies have shown that recombinant IL-12 stimulated Fas promoter activity at 2 hours, reached the peak level at 4 hours, and then declined at 24 hours. To investigate whether IL-12 specifically enhanced Fas promoter activity, we determined whether another gene (E1A) was able to stimulate Fas promoter activity. We also evaluated effect of IL-12 on the topoisomerase II promoter. The results indicated that E1A but not IL-12 stimulated topoisomerase II promoter activity. E1A failed to increase Fas promoter activity. We also found that B-Sp1 element at position –295 to –286 in Fas promoter was essential for IL-12-induced activation, and nuclear factor-B transcription factor was activated after IL-12 treatment in TC71 cells. These results indicate that IL-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma by enhancing Fas promoter activity. Understanding this mechanism may lead to new therapeutic approaches for the treatment of sarcoma involving the use of IL-12."
mTOR signaling: implications for cancer and anticancer therapy In the abstract of their paper, “mTOR signaling: implications for cancer and anticancer therapy”, Petroulakis, Mamane, Le Bacquer, Shahbazian and Sonenberg, of McGill Cancer Centre, McGill University state, “Mounting evidence links deregulated protein synthesis to tumorigenesis via the translation initiation factor complex eIF4F. Components of this complex are often overexpressed in a large number of cancers and promote malignant transformation in experimental systems. mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins. The immunosuppressant rapamycin specifically inhibits mTOR activity and retards cancer growth. Importantly, mutations in upstream negative regulators of mTOR cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin treatment. Such mutations lead to increased eIF4F formation and consequently to enhanced translation initiation and cell growth. Thus, inhibition of translation initiation through targeting the mTOR-signalling pathway is emerging as a promising therapeutic option.” See British Journal of Cancer (2006) 94, 195-199.
In the abstract of their article, “Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980-1994”. Stiller1, Passmore1, Kroll1, Brownbill1, and Wallis1 of the Childhood Cancer Research Group, University of Oxford, and Craft of the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, state, “The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980-1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980-1984, 1985-1989 and 1990-1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983-1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980-1986 and 54% in 1987-1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980-1986, 42 vs 30%; 1987-1992, 59 vs 42%; 1993-1994, 54 vs 43%. During 1985-1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985-1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate.” See British Journal of Cancer (2006) 94, 22-29.
In their article, “Rhabdomyosarcoma Lysis by T Cells Expressing a Human Autoantibody-Based Chimeric Receptor Targeting the Fetal Acetylcholine Receptor”, Gattenlöhner, Alexander Marx, and Müller-Hermelink of the Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany and Markfort, Pscherer, Landmeier, Juergens, and Rossig of the Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany and Matthews, Beeson and Vincent of the Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom, state, “Rhabdomyosarcomas are the most frequent malignant soft tissue tumors of childhood; however, because current multimodality treatments fail to improve the poor survival rate of children with metastatic rhabdomyosarcoma, new treatments are required. We previously identified the -subunit of the fetal acetylcholine receptor (fAChR) as a specific cell surface target in rhabdomyosarcoma. Here, we engineered human T lymphocytes to express chimeric receptors composed of the antigen-binding domain of a human anti-fAChR antibody joined to the signaling domain of the human T-cell receptor -chain. The interaction of fAChR-transduced T cells with fAChR-positive rhabdomyosarcoma cell lines, but not with fAChR-negative control cells, induced T-cell activation characterized by strong secretion of IFN- and delayed lysis of tumor cells. Importantly, we found that in six of six rhabdomyosarcoma patients, chemotherapy increased fAChR expression on residual tumor cells in vivo. Our observations suggest that these fully human chimeric fAChR-transduced T cells, which should be well tolerated by the patient, have potential use in vivo both as a primary treatment for rhabdomyosarcoma and as a complementary approach to eradicate residual tumor cells after chemotherapy. See Cancer Research 66, 24-28, January 1, 2006.
Drs. Coffin, Lowichik, and Zhou of the Department of Pathology, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City state, in the abstract of their article, " Treatment Effects in Pediatric Soft Tissue and Bone Tumors: Practical Considerations for the Pathologist", that "Dramatic improvements in survival for children with cancer have led to increased numbers of posttreatment pathologic specimens, particularly in bone and soft tissue sarcomas. Current therapeutic protocols in North America require specific pathologic classification and stratify patients based on clinical, biologic, and pathologic features. For osteosarcoma, the pathologic response to therapy predicts prognosis and modifies the treatment regimen. Ongoing studies aim to assess the response to therapy and outcome in other types of soft tissue and bone tumors. The pathologic evaluation of pretreatment and posttreatment specimens is critical for therapeutic decisions and prognostic assessment. A standardized approach to posttherapy pathologic specimens, with attention to appropriate use of ancillary tests, and assessment of clinical and biologic significance of therapy-induced pathologic changes has significance for patient management and treatment protocols." This article, which deals with osteosarcoma, Ewing sarcoma/Primitive Neuroectodermal Tumor, rhabdomyosarcoma, synovial sarcoma, and infantile fibrosarcoma, is found in The American Journal of Clinical Pathology 123 (1):75-90, 2005.
V3N1 ESUN Copyright © 2006 Liddy Shriver Sarcoma Initiative.
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