Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances of cytogenetics in human hematological malignancies and solid tumors were reviewed. In leukemia and lymphoma, many non-random chromosome aberrations have been found in the last decade. Further specific chromosome aberrations, which existed usually in less than five percent of acute leukemia cases, were recently found, including t (1 ; 3) in MDS or AML M4, +der (1) t (1 ; 7) in MDS, t (1 ; 11) in AML M4 or M5 and +4 in AML M2 or M4. Recurrent chromosome deletions of 17p-, 9q- and 2p- were also found as secondary aberrations in association with tumor development. Accumulation of the data from variant translocation for the 9 ; 22, 8 ; 21 and 15 ; 17 gave us important informations of critical sites of the chromosome in leukemia development. A new trial for the simultaneous analysis of morphology, immunologic phenotype and karyotype on the same metaphase clearly demonstrated stem cell origin of leukemia in some cases, specializing the affected cell lineage. Progress in non-radioactive in situ hybridization techniques now allows approaches to the recognition of particular chromosome abnormality in metaphase and also in interphase cell by means of specific repetitive probes for each chromosome. Though a hypothesis that fragile sites may act as factors predisposing to chromosomal rearrangements have attracted attention in past few years, recent results appear to be conflicting without any direct proof. Cytogenetic studies in solid tumor have been remarkably progressed with advances of methodology. Recurrent chromosome aberrations in solid tumor were found, such as t (X ; 18) in synovial sarcoma, t (12 ; 16) in liposarcoma, and i (12p) in seminoma. Studies on the correlation between specific chromosome changes and histologic subtypes resulted in an useful orientation to the diagnosis and the therapy. Advance in cytogenetics may serve as new concepts for patho-physiology of malignant tumors and contribute to further understandings of molecular genetics in human solid tumors.
 ...
PMID:[Cancer and chromosomes]. 268 17

Antibodies specific for membrane-associated antigens of human osteosarcoma cells were isolated from sera of 12 patients with osteosarcoma (OS). Affinity columns were prepared by coupling purified membrane antigens from cultured human OS cell lines (TE-85 or LM) to CBrN-activated Sepharose 4B. The antigens were prepared by discontinuous sucrose gradient ultracentrifugation, papain digestion, and DEAE column chromatography. Diluted serum was passed over the affinity columns, and the adsorbed proteins were eluted with 2.5 M MgCl2 (pH 6.5). Immunodiffusion, indirect immunofluorescence, and complement fixation were used to assay antibody activity in the eluate. Specific anti-OS activity was found in the immunoglobulin (Ig) fraction isolated from the sera of the 12 OS patients, as confirmed by blocking experiments. No anti-OS antibody activity was found in sera from healthy individuals or patients with breast carcinoma, clear cell liposarcoma, or leukemia in this study. The anti-OS activity of the isolated Ig from OS patients was abolished after absorption with cultured human OS cells from lines LM, TE-85, or G292 but not after absorption with cells from lines WI-38 (embryonic lung), TE-32 (rhabdomyosarcoma), CAMA-1 or SW527 (breast carcinoma), or M-14 (melanoma). Absorption with rabbit antihuman IgG but not with rabbit antihuman IgM immunobeads completely eliminated the antibody activity.
 ...
PMID:Osteosarcoma patients: isolation of serum antibodies by affinity chromatography. 679 43

The t(16;21)(p11;q22) translocation is a recurrent chromosomal abnormality found in several types of myeloid leukemia. We have previously demonstrated that the breakpoints of this translocation are clustered in a specific intron of the ERG gene on chromosome 21, which has recently been reported to be involved in Ewing's sarcoma. We show here that the TLS/FUS gene on chromosome 16 is fused with the ERG gene to produce the TLS/FUS-ERG chimeric transcript by this translocation. The TLS/FUS gene has been identified as a translocated gene in myxoid liposarcoma by the t(12;16)(q13;p11) translocation and encodes an RNA-binding protein that is highly homologous to the product of the EWS gene involved in Ewing's sarcoma. Thus, the TLS/FUS-ERG gene fusion in t(16;21) leukemia is predicted to produce a protein that is very similar to the EWS-ERG chimeric protein responsible for Ewing's sarcoma.
 ...
PMID:An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. 818 69

The association between venous thrombosis and cancer has been known for a long time. Thrombophlebitis often occurs during the course of a known cancer, but sometimes constitutes the presenting sign. Based on a series of 10 cases of deep venous thrombosis (DVT) revealing an underlying cancer, the authors analyse the various aspects of this association and the elements which help to guide the diagnosis towards a cancer. A simple assessment comprising clinical examination, full blood count and differential white cell count, erythrocyte sedimentation rate, protein electrophoresis, chest x-ray and abdomino-pelvic ultrasonography was performed on admission in 75 cases of presumably idiopathic DVT and revealed a cancer in 10 cases: 6 women and 4 men with a mean age of 53 years. Cancers were located in the urogenital tract in 5 cases, in the bronchi in 2 cases, in the stomach in one case, and there was one case of acute myeloblastic leukaemia (AML) and another case of liposarcoma of the left iliac fossa. The histological type most frequently encountered was adenocarcinoma in 6 cases. In 9 out of 10 cases, the cancer was discovered at the stage of metastases. However, a localized cancer was detected in one case, in which surgical treatment allowed cure of the patient. Comparison of the various characteristics of DVT between the group of DVT revealing a cancer and the group of DVT which remained idiopathic did not reveal any statistically significant difference. A simple, inexpensive assessment looking for a cancer must be systematically performed in all cases of idiopathic DVT in patients between the ages of 50 and 85 years. Other more elaborate examinations may be requested on the basis of the results of the preliminary assessment.
 ...
PMID:[Deep venous thromboses and occult cancers]. 918 94

New oncologic treatments have improved survival in osteosarcoma and Ewing's sarcoma. However, these treatments may cause secondary malignancies after radiotherapy. This study evaluated the incidence of secondary malignancies after neoadjuvant chemotherapy. Between April 1972 and December 1990, 518 osteosarcoma and 299 Ewing's sarcoma patients entered neoadjuvant chemotherapy protocols. Follow-up records of all patients were analyzed and malignant tumors were reported. Nine patients developed another malignancy, including 5 leukemias, 1 astrocytoma, 1 liposarcoma, 1 parotid, and 1 breast carcinoma. Four leukemias were found in patients treated for osteosarcoma with chemotherapy, but not radiotherapy. Only one leukemia developed after Ewing's sarcoma treated with chemotherapy and radiotherapy. The incidence of leukemias is high, while the other tumors can be explained as unrelated cases. Incidence densities for leukemia were calculated for both groups of patients. Treated osteosarcoma patients seem to have a predisposition to develop leukemias, but whether this is chemotherapy induced needs to be investigated.
 ...
PMID:Secondary tumors in bone sarcomas after treatment with chemotherapy. 1046 88

The translocation liposarcoma (TLS) gene is fused to the ETS-related gene (ERG) in human myeloid leukemia, resulting in the generation of a TLS-ERG protein. We demonstrate that both TLS and the TLS-ERG leukemia fusion protein bind to RNA polymerase II through the TLS N-terminal domain, which is retained in the fusion protein; however, TLS recruits members of the serine-arginine (SR) family of splicing factors through its C-terminal domain, whereas the TLS-ERG fusion protein lacks the ability to recruit SR proteins due to replacement of the C-terminal domain by the fusion partner ERG. In transient-transfection assays, the TLS-ERG fusion protein inhibits E1A pre-mRNA splicing mediated by these TLS-associated SR proteins (TASR), and stable expression of the TLS-ERG fusion protein in K562 cells alters the splicing profile of CD44 mRNA. These results suggest that TLS fusion proteins may lead to cellular abnormalities by interfering with the splicing of important cellular regulators.
 ...
PMID:TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins. 1077 24

Translocation liposarcoma protein (TLS)-associated serine-arginine (TASR)-1 and -2 are two newly identified serine-arginine splicing factors. Our recent studies suggest that disruption of TASR-mediated pre-mRNA splicing is involved in the pathogenesis of human leukemia and sarcomas. The mRNA transcripts for TASR-1 and -2 share an identical sequence at the 5' untranslated region (5' UTR) and in part of the coding region; however the other regions of the transcripts diverge from each other and it was not clear whether the differences resulted from alternative splicing or transcription from two distinct genes. Here we describe the assignment of both TASR cDNAs to the same 16 kb DNA segment located on chromosome 1. Despite the presence of at least three retroposed products of TASR-1 mRNA in the human genome, only the 16 kb structural TASR gene on chromosome 1 is actively transcribed. In addition, multiple polyadenylation sites and a rare U12-type intron were found within the TASR gene. Transcription initiation site of the TASR gene was determined by primer extension; analysis of the TASR promoter revealed that it lacks the TATA box but contains a GC-rich sequence. When cloned into a luciferase reporter and transfected into human cells, the TASR promoter construct generated luciferase activity that was at least 2000 fold greater than the promoterless plasmid. Northern blot analysis showed that at least five different TASR-1 and -2 transcripts are expressed in a broad range of human tissues.
 ...
PMID:Characterization and expression of the human gene encoding two translocation liposarcoma protein-associated serine-arginine (TASR) proteins. 1189 Oct 55

CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that have been implicated in diverse cellular functions such as cellular differentiation and proliferation, and inflammatory processes. C/EBPzeta, also known as GADD153, CHOP10, and DDIT3 has been found associated with the development of myxoid liposarcoma and the progression of melanoma. To investigate the correlation of C/EBPzeta transcript levels with the development of leukemia, samples from 187 patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) were examined for C/EBPzeta mRNA using real-time quantitative PCR (RQ-PCR). RQ-PCR analysis demonstrated the median levels of C/EBPzeta were significantly decreased in MDS, AML, and CML patients compared with normal controls (1.40, 0.96, 2.60 versus 14.69, P<0.0001). Significant differences were also observed between patients with CML and with AML or MDS. These results suggest that the insufficient dosage of C/EBPzeta might be involved in the development of leukemia.
 ...
PMID:Decreased expression of CCAAT/enhancer binding protein zeta (C/EBPzeta) in patients with different myeloid diseases. 1600 64

Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis. Mean annualized rates of skin malignancy were calculated, and the relative risk was determined using a Poisson model. Malignancy-free survival rates for nonskin malignancies were compared using Kaplan-Meier estimates and the log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST 0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat analysis). The relative risks for both basal and squamous cell carcinomas were significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus 4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma, astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL-based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
 ...
PMID:Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. 1643 6

Survival from soft tissue tumors (STTs) has been improved because of the successful treatment. One of the late sequelae in STT survivors is the development of a second malignancy. The present study aimed at quantifying risks for second malignancies in patients with STTs, and risks for second STTs after other primary malignancies. Adjusted standardized incidence ratios (SIRs), calculated from the Swedish Family-Cancer Database, were used as a measure of risk. Among 6,671 primary STT patients, a total of 650 second malignancies occurred. Besides second STTs, other cancer sites with an increased SIR were the nervous system, endocrine glands, skin (melanoma and squamous cell carcinoma) and prostate; the risk for non-Hodgkin lymphoma (NHL) was also increased. The overall risk of second malignancies decreased in the following order: fibrosarocma (1.63) > myxosarcoma (1.48) > leiomyosarcoma (1.44) > liposarcoma (1.21). An increased risk of second STTs after primary cancers of the bone, ovary, nervous system, cervix, thyroid gland, skin, endometrium, breast, upper aerodigestive tract, and after Hodgkin disease, NHL and leukemia was also noted. This study showed that the incidence of second primary malignancies in patients with STTs was increased, but the SIRs varied among specific cancer sites. Besides therapeutic effects, the associations between STTs and bone and nervous system tumors suggested that cancer syndromes, such as neurofibromatosis type 1 and Li-Fraumeni syndrome, may partly explain the excesses. The associations of STTs with cancers of the skin (squamous cell carcinoma and melanoma) and with NHL may be related to immunodeficiency.
 ...
PMID:Second primary malignancies among patients with soft tissue tumors in Sweden. 1655 72


1 2 3 Next >>