Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vif gene of the human immunodeficiency virus (HIV-1) is required for productive virus infection of primary blood mononuclear cells (PBMCs) and macrophages in vitro. Replication of HIV-1 vif- mutants in T-lymphoid cell lines varies and is dependent on the cell line used for virus production. To further understand the role of Vif in HIV-1 infection, we constructed to vif deletion mutants from a molecular clone derived from an African patient (HIV-1Zr6). Cell-free Zr6 vif- virus pools made from transfected rhabdomyosarcoma (RD) cells do not replicate when added to cultures of stimulated PBMCs. However, vif mutants were able to spread from transfected RD cells to PBMCs if cell-to-cell contact was permitted. By Western blot analysis, viral structural proteins expressed after transfection of RD cells by wild-type or vif mutant proviruses were indistinguishable. However, binding of vif mutants to PBMCs or to purified CD4 and virus internalization were significantly reduced when compared with wild-type virus. The defects in cell-free infection, CD4 binding, and internalization were rescued by transcomplementation using a vif expression plasmid. Our results suggest a novel level at which the HIV-1 vif gene product acts to enhance cell-free infection and indicate that vif plays an important role in promoting HIV-1 binding and internalization. Combined with the previous reports of vif's effect at other steps in infection, this suggests that vif is a pleuripotent gene product that affects multiple stages of the infective process.
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PMID:Cell-free HIV-1Zr6 vif mutants are defective in binding to peripheral blood mononuclear cells and in internalization. 892 9

Poorly differentiated rhabdomyosarcomas are traditionally distinguished from lymphomas by their absence of lymphoid markers such as immunoglobulin or CD20 expression. We have encountered three alveolar rhabdomyosarcomas that were initially diagnosed as lymphoid neoplasms because of the expression of a lymphocytic phenotype in morphologically undifferentiated tumor cells. Subsequent cytogenetic analysis revealed a t(2; 13) in two cases. All cases recurred in the chest wall and showed positivity for muscle markers, such as muscle-specific actin, myoglobin, MyoD1, and/or desmin on subsequent immunohistochemistry. The findings in these three cases lead us to conclude that the presence of a lymphoid phenotype does not absolutely exclude the diagnosis of rhabdomyosarcoma.
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PMID:Undifferentiated rhabdomyosarcoma with lymphoid phenotype expression. 902 9

Patients with primary metastatic or recurrent rhabdomyosarcoma (RMS) have a very poor prognosis. Since high-dose chemotherapy (HDC) +/- TBI was thought to improve survival, many centers performed this therapy using different types of hematopoietic rescue (auto BM or PBSC, allo BM). This is a retrospective, multi-center analysis of the results of treatment in 36 patients with primary metastatic or relapsed RMS who were given HDC +/- TBI and hematopoietic rescue between 1986 and 1994. The median age was 6 years (< 1-22 years). Primary therapy was given according to either one of the Cooperative German Soft Tissue Sarcoma Studies CWS-81, -86, -91 or the European Study for Stage IV Malignant Mesenchymal Tumors in Childhood. There were 22 alveolar RMS, 13 embryonal RMS and one undifferentiated sarcoma. The indication for HDC was primary metastatic disease (27 patients) or a relapse of a primary localized tumor (nine patients). Thirty-two patients were in 1st or 2nd CR when given HDC and four in VGPR. The median time from last event to HDC was 44 weeks (21-110). HDC consisted of fractionated melphalan ((4 x 30-45 mg/m2), VP16 40-60 mg/kg, carboplatin 3 x 400-500 mg/m2) in 26 patients, 10 of whom received additional FTBI. Seven patients were treated with melphalan alone or in combination with carboplatin. Two patients received cyclophosphamide/busulphan with TLI (total lymphoid irradiation) and one cyclophosphamide with FTBI. Thirty-one patients were given autologous BM or PBSC as hematopoietic rescue and five allogeneic bone marrow from HLA-identical siblings. Fourteen patients received GM-CSF or G-CSF after hematopoietic stem cell transfusion (HSCT). Ten patients received adjuvant IL-2. There was one toxic HDC-related death. Nine patients are alive and free of disease with a median observation time of 57 months (32-108). The median time from HDC to relapse was 4 months (1-17). The tumor recurred in the majority of patients at previously known sites; in three cases new metastatic sites were observed. Patients with primary localized tumors who had been treated with HDC because of relapse did slightly better (four of nine alive with NED) than patients with primary metastatic disease (five of 27 alive with NED). HDC is still of uncertain value in the therapy of poor-risk rhabdomyosarcoma and should be performed only as part of controlled clinical trials.
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PMID:Do patients with metastatic and recurrent rhabdomyosarcoma benefit from high-dose therapy with hematopoietic rescue? Report of the German/Austrian Pediatric Bone Marrow Transplantation Group. 902 50

The PAX genes encode a family of transcription factors that control development within the neural, myogenic, lymphoid, and a variety of other lineages. These proteins are postulated to regulate expression of gene products that function in the control of cellular processes are fundamental to the development of cancer, and thus genetic alterations of these genes may contribute to neoplastic development within these lineages. In support of this premise, several PAX genes have been shown to be targets of consistent chromosomal translocations associated with specific tumor types. The t(2;13) and t(1;13) translocations associated with the myogenic soft tissue cancer alveolar rhabdomyosarcoma fuse portions of the PAX3 or PAX7 gene with a portion of the FKHR gene to generate novel fusion proteins. The t(9;14) translocation associated with the B cell tumor lymphoplasmacytoid lymphoma juxtaposes the PAX5 gene into the vicinity of the IGH locus to deregulate PAX5 expression. This review will examine the molecular basis of these translocations and the role of altered function or expression of paired box transcription factors in the process of tumorigenesis.
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PMID:Chromosomal translocations involving paired box transcription factors in human cancer. 957 Jan 38

We report a case of alveolar rhabdomyosarcoma (AR) with massive infiltration of bone marrow at presentation, and initial diagnosis in bone marrow aspirate. A 35 year old man presented with a submandibular mass, and hematomas after mild traumatisms. Peripheral blood showed thrombocytopenia and a normocytic anaemia. Bone marrow film showed diffuse involvement by undifferentiated blasts with rhabdomyoblastic features. Subsequent biopsy of submandibular lymph node confirmed the diagnosis with positivity for specific muscle actin and desmin, and negativity for lymphoid markers. Initial presentation of AR with extensive bone marrow involvement is extremely rare, and it could lead to wrong diagnosis and treatment of acute leukaemia, with the serious consequences that this would have. Immunohistochemical study and morphologic differential features can be of great diagnostic help.
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PMID:[Alveolar rhabdomyosarcoma with massive infiltration of the bone marrow as its initial manifestation]. 974 Dec 33

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.
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PMID:Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia. 1037 68

Angiomatoid "malignant" fibrous histiocytoma (AMFH) has been considered to be a low-grade sarcoma of childhood, and, with its fibrous pseudocapsule, angiomatoid change, dense lymphoplasmacytic response, and proliferation of spindled or round cells, has been classified as a fibrohistiocytic neoplasm. We wanted to study the clinicopathologic and immunophenotypic features of a large number of these tumors and to especially further explore their myoid differentiation. Cases coded as AMFH from 1979 to 1995 were retrieved from the Soft Tissue Registry of the AFIP. Only cases that met the criteria for AMFH by light microscopy were included, a total of 158 cases. Immunohistochemistry was obtained on 98 cases. Clinical history on 92% of all cases revealed a gender ratio of 1.3 females: males, age range of 2 to 71 years, median size of 2.0 cm, and a distribution of extremities > trunk > head and neck, with 66% lesions occurring in areas of normal lymphoid tissue. All tumors with available margins were well-circumscribed. Eighty percent of cases had some degree of lymphoplasmacytic infiltration; 50% cases had pseudovascular spaces filled with blood. Fifty-two percent had predominantly round cell morphology; 48% had a predominantly spindle cell pattern. Desmin positivity was noted in 51% cases and occurred in both predominantly round cell and spindle cell tumors. Most of the desmin-positive cases with adjacent lymphoid infiltrate (67%) showed scattered similar, desmin-positive cells in the surrounding lymphoid infiltrate, adjacent to the tumor. Muscle-specific and smooth-muscle actins were seen in 14% cases. Heavy-caldesmon was strongly positive in 3%, and calponin was focally positive in 73% and extensively positive in 12% cases. MyoD1, myoglobin, and myogenin (myf4) were negative in all tumors studied. Forty-five percent of cases were positive for CD99; 52% of these had round cell morphology. Fifteen percent of cases were positive for KP-1. All tumors were positive for vimentin and negative for CD21, CD35, S100 protein, CD34, keratins 8/18, and lysozyme. Clinical follow-up on 86 patients indicated that only 1 patient was alive with a local nodal metastasis (1% frequency of metastasis) within 1 year, and 2 others had local recurrence, all over a mean follow-up period of 6 years. The myoid, primarily myofibroblastic, phenotype of these lesions is supported by desmin, calponin, and occasional actin positivity. The occasional heavy-caldesmon and smooth muscle actin additionally suggest rare smooth muscle phenotype; however, lack of skeletal muscle markers indicate no relationship of AMFH to skeletal muscle tumors. The resemblance of these lesions to lymph nodes, clinically and morphologically, the finding of similar desmin positive cells in the adjacent lymphoid infiltrate, and the fact that 66% cases were found in sites of normal lymphoid tissue raise the possibility that some of these lesions may arise from or be related to myoid cells of lymphoid tissue. AMFH has an almost invariably benign behavior, but the 1% metastatic rate warrants its classification as low-grade "malignant." The predominantly round cell, CD99-positive and desmin positive AMFH cases, respectively, should not be confused with Ewing's sarcoma/PNET or rhabdomyosarcoma, respectively.
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PMID:Angiomatoid "malignant" fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. 1057 14

Hypoxia is known to induce extravasation of lymphocytes and leukocytes during ischemic injury and increase the metastatic potential of malignant lymphoid cells. We have recently identified a new adhesion molecule, hypoxia-activated ligand-1/13 (HAL-1/13), that mediates the hypoxia-induced increases in lymphocyte and neutrophil adhesion to endothelium and hypoxia-mediated invasion of endothelial cell monolayers by tumor cells. In this report, we used expression cloning to identify this molecule as the lupus antigen and DNA-dependent protein kinase-associated nuclear protein, Ku80. The HAL-1/13-Ku80 antigen is present on the surface of leukemic and solid tumor cell lines, including T and B lymphomas, myeloid leukemias, neuroblastoma, rhabdomyosarcoma, and breast carcinoma cells. Transfection and ectopic expression of HAL-1/13-Ku80 on (murine) NIH/3T3 fibroblasts confers the ability of these normally nonadhesive cells to bind to a variety of human lymphoid cell lines. This adhesion can be specifically blocked by HAL-1/13 or Ku80-neutralizing antibodies. Loss of expression variants of these transfectants simultaneously lost their adhesive properties toward human lymphoid cells. Hypoxic exposure of tumor cell lines resulted in upregulation of HAL-1/13-Ku80 expression at the cell surface, mediated by redistribution of the antigen from the nucleus. These studies indicate that the HAL-1/13-Ku80 molecule may mediate, in part, the hypoxia-induced adhesion of lymphocytes, leukocytes, and tumor cells.
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PMID:Hypoxia-activated ligand HAL-1/13 is lupus autoantigen Ku80 and mediates lymphoid cell adhesion in vitro. 1124 7

Childhood cancer, like all cancer, is at heart a genetic disease. Consequently, fundamental understanding of the oncogenic process is likely to be beneficially addressed by genetic methodology. Current methods have largely focused on single-gene defects, like chimeric genes, which are present in many sarcomas and leukemias. Real understanding is more likely to derive from a genome-wide analysis of these malignancies. Recent technologic advances have made it possible to simultaneously assess the entire expressed gene profile, or transcriptome, of a given cancer. Foremost among these methods is gene expression profiling using DNA microarrays. Two basic approaches predominate: spotted arrays and photolithography arrays. Regardless of the method, the resulting information can be used to create disease profiles, but only if appropriate bioinformatic solutions are employed. Common analytic approaches include two-way expression comparisons, or scatter analyses; outlier gene analysis, to identify significantly dysregulated genes; dendrogram analyses, as pioneered by Eisen; cluster analyses to identify diagnostic or biologic groups; and various forms of functional analyses to identify relevant genes and biologic pathways. Studies of both adult and pediatric cancer have demonstrated the feasibility of such analyses to identify both diagnostic and prognostic groups of tumors. Acute childhood leukemias have been grouped into myelogenous and lymphoid, and even B- and T-cell subsets. Breast cancer prognostic groups have been identified on the basis of a small subset of expressed genes. In addition, preliminary data on childhood sarcomas appear to identify both diagnostic and prognostic subsets. Specifically, embryonal rhabdomyosarcoma could be distinguished from alveolar rhabdomyosarcoma, and even morphologically mixed embryonal and alveolar rhabdomyosarcoma showed similar gene expression profiles in both histologies. Further, collaborative studies using clustering analyses appear to identify prognostic groups of diverse sarcomas. Larger institutional and cooperative group studies are currently underway to validate these preliminary findings.
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PMID:DNA microarrays in pediatric cancer. 1126 44

The aims of the study are to investigate the characteristic patterns related to different aged subgroups of young Chinese patients with malignant tumors. The subjects were young Chinese patients (defined as age > 1 and < 40 years) who underwent autopsy for malignant tumors in a teaching hospital in Hong Kong from 1970 to 1999. They were divided into four age groups: 1 to 9 years, 10 to 19 years, 20 to 29 years, and 30 to 39 years. The malignant tumors were classified into subgroups according to the pathological classification. The clinicopathologic features of patients with carcinomas and sarcomas were reviewed in depth. Four hundred sixty-three (22%) of 2,080 young patients had malignant tumors detected at autopsies. The male-to-female ratio was 1.5. The two most common malignant tumors were malignant lymphoid tumors and carcinomas, accounting for 49.9% and 29.8%, respectively, of all malignant tumors. In children (ages 1-9 years), 78.9% of malignant tumors found were malignant lymphoid tumors and neuroendocrine tumors. In teenagers (ages 10-19 years), malignant lymphoid tumors were the most important group of malignant tumor, accounting for 69% of malignant tumors in this age group. Carcinomas and malignant lymphoid tumors were seen in more than 80% of malignancies in young adults (ages 20-39). Overall, carcinomas and sarcomas were noted in 29.8% and 4.1%, respectively, of young patients with malignant tumors. The common primary sites of carcinomas were liver, stomach, lung, and nasopharynx. Sarcomas were more common in females (11 females, seven males), and rhabdomyosarcoma was the most common sarcoma found. Compared with other malignant tumors, carcinomas were less often diagnosed before death. In conclusion, malignant tumor is a common cause of death in young patients. Different types of malignant tumors were seen in various groups of young patients.
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PMID:Characteristics of malignant tumors in young people, with particular emphasis on carcinomas and sarcomas. 1142 63


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