Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fusion proteins created by chromosomal translocations in tumors can create neoantigenic determinants at the breakpoint, which are unique to the tumor cells but shared by the vast majority of tumors of that histologic type. If the fusion protein is responsible for the malignant transformation, its expression cannot be lost by the tumor to escape immune responses against this tumor antigen. Here, we identify such a fusion protein breakpoint epitope in the PAX-FKHR fusion protein created by the t(2;13) translocation present in 80% of cases of alveolar rhabdomyosarcoma, a highly aggressive pediatric soft-tissue sarcoma. We use autologous dendritic cells pulsed with the RS10 breakpoint fusion peptide to raise a human CTL line from a normal healthy HLA-B7+ blood donor specific for this peptide. These CTLs are CD8+ (CD4-CD56-) and restricted by HLA-B7. These human peptide-specific CTL lyse human HLA-B7+ rhabdomyosarcoma tumor cells. Therefore, the fusion protein is endogenously processed to produce this natural epitope presented by HLA-B7 and thus this peptide is a bone fide human tumor antigen. We also define a substitution that increases the affinity for HLA-B7 without loss of antigenicity. This epitope-enhanced peptide may serve as a candidate cancer vaccine for HLA-B7+ patients with alveolar rhabdomyosarcoma.
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PMID:Identification and epitope enhancement of a PAX-FKHR fusion protein breakpoint epitope in alveolar rhabdomyosarcoma cells created by a tumorigenic chromosomal translocation inducing CTL capable of lysing human tumors. 1645 43

Isolated primary granulocytic sarcoma is a rare disease that presents as an extramedullary tumor of myeloid lineage cells. Most patients subsequently develop acute myelogenous leukemia (AML) within a short period, and their prognosis is poor. Herein, we report the case of a 33-year-old woman with a primary isolated granulocytic sarcoma which originated in the small intestine. After she recovered from surgery, she received intensive chemotherapy equivalent to that for AML, followed by allogeneic bone marrow transplantation from an HLA-matched, unrelated donor. Four years after the transplantation, she remains in complete remission without graft-versus-host disease or any other symptoms. This case illustrates the effectiveness of our therapeutic strategy for isolated granulocytic sarcoma, not only with surgical resection of the tumor and intensive chemotherapy equivalent to that for AML, but also with allogeneic bone marrow transplantation, performed while no sign of AML is observed.
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PMID:Isolated granulocytic sarcoma of the small intestine successfully treated with chemotherapy and bone marrow transplantation. 1836 39

Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA repertoire suggesting pathogenic features relating to immunological incompatibility may be at the root of disease. Here we review the influence of immune activation on progression to AIDS with particular reference to molecular mimicry and autoimmune phenomenon and highlight the therapeutic potential of non-neutralizing antibodies and strategies designed to diffuse immune activation.
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PMID:HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies. 1905 48

A 72-year-old man was diagnosed with essential thrombocythemia (ET) and was treated with hydroxyurea for approximately 5 years. He was well until April 2007. In May 2007, a slight fall in hemoglobin levels was found. In June 2007, an upper endoscopy performed to investigate the cause of anemia showed multiple polypoid lesions in the body of the stomach. A gastric biopsy showed a diffuse infiltration of very immature cells. Several additional immunohistochemical staining showed that the cells were positive for CD13, CD34, CD117, and HLA DR, but negative for myeloperoxidase, CD42b, glycophorin, B cell marker, T cell marker, cytokeratin and desmin. We finally diagnosed the condition as myeloid sarcoma. Subsequently, the patient's ET transformed into acute myeloid leukemia. To our knowledge, this is an exceedingly rare event involving a patient with essential thrombocythemia.
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PMID:Myeloid sarcoma in essential thrombocythemia that transformed into acute myeloid leukemia. 1917 81

Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from the antigen-presenting cells of the immune system. We report a case of IDCS occurring in a 69-year-old man who presented to an outside institution with a painless mass in his right parotid gland for several months. He presented to our institution after undergoing a superficial parotidectomy. A diagnosis of undifferentiated neoplasm, favoring poorly differentiated carcinoma, was made at that time. He underwent a total parotidectomy and neck dissection at our institution. Microscopically, the tumor was composed of atypical spindle cells involving the parotid gland and an ipsilateral level III lymph node. Immunophenotypic analysis demonstrated positive staining for S100, fascin, vimentin, and HLA-II. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Taken together, the above features were consistent with IDCS. An IDCS of the parotid gland is extremely rare, with only 2 cases reported in the literature. The unusual location and morphological similarity to follicular dendritic sarcoma and other types of soft tissue sarcomas can be a diagnostic challenge. Awareness of this tumor and the use of appropriate markers are crucial in making the diagnosis. The patient did well postoperatively, and he underwent a complete course of postoperative irradiation to the right parotid and neck.
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PMID:Interdigitating dendritic cell sarcoma of the parotid gland: case report and literature review. 1956 39

We assessed the efficacy of WT1 peptide pulsed dendritic cell (DC) therapy for various advanced cancers. All patients were vaccinated 5 times for 10 weeks with autologous monocytes derived DC and activated T lymphocytes. We treated a total of 26 patients who had HLA-A2402 or/and HLA-A0201. We evaluated 20 of the 26 patients who finished 5-time vaccination (10 men and 10 women, aged 48-81 years, Mean 64 years) and were diagnosed as follows: 3-pancreas cancer, 2-colorectal, 2-breast, 2-esophageal, 2-lung, 2-uterus, 2-ovarian and 5 others. In Clinical response (RECIST), the result was assessed as CR/PR/SD/PD, 0/7/8/5, respectively. Furthermore, the 7 PRs were resulted from 2-colorectal, and one of each was lung, laryngeal, axis, pancreas and smooth muscle sarcoma cancer. The 4 of 7 PR patients were treated with chemotherapy.
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PMID:[WT1 peptide pulsed dendritic cell therapy with activated T lymphocytes therapy for advanced cancers]. 2122 34

Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation.
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PMID:Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas. 2189 45

EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.
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PMID:Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. 2192 86

Myeloid sarcoma is a tumor of myoblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of the female genital tract as an isolated initial presentation or isolated relapse is very rare as evidenced from a literature review. We report a case of vulvar myeloid sarcoma presenting as isolated relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT). A 41-year-old female diagnosed with AML M5 achieved remission with chemotherapy and underwent allogeneic HSCT from an HLA-matched sibling donor. The post-transplant period was complicated with chronic graft-versus-host disease. At 10 months post-transplant, she presented with a vulvar mass of six weeks duration. Excisional biopsy of the vulvar mass confirmed the diagnosis of myeloid sarcoma as extramedullary relapse. Bone marrow biopsy was without evidence of leukemia. Involvement of the vulva, vaginal and adjacent cervical area only was confirmed. She received re-induction chemotherapy with clinical regression of both the vulvar, vaginal and the cervical masses; this was followed by radiation therapy to an extramedullary site. The correct diagnosis of myeloid sarcoma, particularly of an isolated mass in the genital area, is important because of its rarity and the need for appropriate institution of therapy.
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PMID:Myeloid sarcoma of the vulva post-bone marrow transplant presenting as isolated extramedullary relapse in a patient with acute myeloid leukemia. 2282 76

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.
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PMID:Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor. 2597 25


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