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)

The term "small round-cell tumor" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma ("classic-type"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases. Yet, a clear understanding of their clinicopathologic features usually allows for a confident diagnosis, especially if immunohistochemistry is used. The following is a review of the immunohistochemistry of this small round-cell tumor group.
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PMID:Immunohistochemistry of small round-cell tumors. 1096 7

Ultrasonography (US) is of value in the evaluation and characterization of breast masses in children. Most masses represent either normal breast tissue, cysts, or fibroadenomas. Premature thelarche may be unilateral, and normal breast tissue is found at US. Cysts are commonly retroareolar; when they become infected, they appear sonographically as a complex mass. Fibroadenoma is the most frequent breast tumor in adolescent girls, and it is usually solitary, homogeneous, and hypoechoic. Malignant breast lesions are very rare in children; most are due to metastatic disease secondary to rhabdomyosarcoma, leukemia, lymphoma, and neuroblastoma, and their US appearance is nonspecific. Gynecomastia in boys can be mimicked by general obesity and pectoral hypertrophy; US is helpful in the diagnosis, especially when gynecomastia is asymmetric. Most breast lesions in children and adolescents are benign, and surgery should be avoided to prevent later deformity. US is the ideal imaging modality to evaluate breast lesions and may be used to guide a fine-needle aspiration biopsy. Color Doppler US evaluation is helpful; cysts are avascular, fibroadenomas may be avascular or hypovascular, and abscesses show peripheral increased flow. Bloody nipple discharge is more common in prepubertal patients, may occur in infants, and may be secondary to mammary ductal ectasia. Discharge commonly resolves spontaneously, and findings at US are frequently normal.
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PMID:Breast US in children and adolescents. 1111 14

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme of the mevalonate pathway, the diverse array of end products of which are vital for a variety of cellular functions, including cholesterol synthesis and cell cycle progression. We showed previously that this enzyme holds a critical role in regulating tumor cell fate, including cell death, as its expression is down-regulated in response to retinoic acid, a potent anticancer therapeutic. Indeed, direct inhibition of HMG-CoA reductase with lovastatin, a competitive inhibitor of this enzyme, induced a pronounced apoptotic response in neuroblastoma and acute myeloid leukemic cells. We have now extended this work and evaluated a wide variety and large number of tumor-derived cell lines for their sensitivity to lovastatin-induced apoptosis. These cell lines were exposed to a wide range (0-100 microM) of lovastatin for 2 days and assayed for cell viability using the 3,4,5-dimethyl thiazlyl-2,2,5-diphenyltetrazolium bromide assay and the induction of apoptosis by flow cytometric and ultrastructural analyses. Lovastatin induced a pronounced apoptotic response in cells derived from juvenile monomyelocytic leukemia, pediatric solid malignancies (rhabdomyosarcoma and medulloblastoma), and squamous cell carcinoma of the cervix and of the head and neck. Interestingly, the subset of malignancies that are particularly sensitive to lovastatin-induced apoptosis correspond to those tumor subtypes that are sensitive to the biological and antiproliferative effects of retinoids in vitro. The nature of the biologically active form of lovastatin has been challenged recently as the growth-inhibitory effects of this drug were attributed to its prodrug lactone form that does not inhibit HMG-CoA reductase function. In this report, we demonstrate that the apoptotic properties of lovastatin are triggered by the open ring acid form that is a potent inhibitor of HMG-CoA reductase activity. Thus, we have identified a subset of tumors that are sensitive to lovastatin-induced apoptosis and show HMG-CoA reductase as a potential therapeutic target of these cancers.
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PMID:Differential sensitivity of various pediatric cancers and squamous cell carcinomas to lovastatin-induced apoptosis: therapeutic implications. 1120 4

Each year advances are made in the clinical evaluation and treatment of genitourinary tumors in children. Understanding of cellular, molecular, and genetic processes in tumorigenesis is evolving rapidly. In addition, information is accumulating about the long-term outcome and complications associated with treatment modalities. This article reviews the 2001 literature on pediatric Wilms tumor, other renal tumors, rhabdomyosarcoma of the pelvis, paratesticular rhabdomyosarcoma, and testicular tumors. The emphasis in molecular biology is to identify molecular or genetic markers that predict outcome. The National Wilms' Tumor Study Group reported on the complications of surgery and the decreased complication rate when these procedures are performed by pediatric surgical specialists. Long-term complications of treatment are also discussed, including short stature and leukemia. The Intergroup Rhabdomyosarcoma Study Group reported on the results of treatment for nonmetastatic disease and the goals of the upcoming Study V, reduction of chemotherapy and radiotherapy. They also presented data from Study IV and discussed the findings on improved prognosis.
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PMID:Pediatric genitourinary tumors. 1198 Dec 71

Chest wall lesions in childhood include a wide range of pathologies. Benign lesions include lipoma, neurofibroma, lymphangioma, haemangioma and mesenchymal hamartoma. Malignant lesions include neuroblastoma, rhabdomyosarcoma, Ewings sarcoma, Askin tumour and primitive neuroectodermal tumours. Manifestations of systemic diseases such as leukaemia, lymphoma, Langerhans cell histocytosis and infections such as tuberculosis and actinomycosis may also cause chest wall lesions. The imaging characteristics of the above are reviewed but only a minority of lesions show diagnostic imaging characteristics. Most lesions require biopsy and histopathological examination for definitive diagnosis. The role of different imaging modalities is discussed, with an emphasis on magnetic resonance imaging for demonstrating lesion morphology and local spread, with computed tomography and nuclear medicine being used mainly to assess remote disease.
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PMID:Chest wall lesions. 1245 4

Sixteen children and young adults were treated with high-dose cyclosporin combined with a combination of cytotoxics (epirubicin, vincristine and etoposide) (EVE) known to be influenced by P-glycoprotein-mediated multidrug resistance (MDR). Tumour types were neuroblastoma 3, Ewing's sarcoma 2, rhabdomyosarcoma 5, osteosarcoma 3, desmoplastic small round cell tumour 1, nephroblastoma 1, T-acute lymphoblastic leukaemia (ALL) 1. All had progressed or relapsed following at least two of the drug types included in EVE. Acute reactions to cyclosporin and myelosuppression were the major toxicities documented. Renal and hepatic toxicity was rarely severe and always transient. Partial responses (PR) were observed in 2 patients (1 rhabdomyosarcoma, 1 Ewing's sarcoma). We conclude that this combination is tolerable in heavily pretreated patients and may be suitable for further evaluation in untreated poor risk tumours.
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PMID:EVE/cyclosporin (etoposide, vincristine, epirubicin with high-dose cyclosporin)-chemotherapy selected for multidrug resistance modulation. 1246 Jul 76

We compared the extent to which apoptosis is induced and clonogenicity reduced in three tumour cell lines - the human melanoma Me45 and promyelocytic leukaemia HL-60, and the rat rhabdomyosarcoma R1 - after exposure to the anticancer drugs etoposide and cis-platinum or to gamma radiation; each induces different types of DNA damage. Cells which readily underwent apoptosis did not necessarily show a correlated loss of clonogenicity; for example, Me45 cells showed the highest sensitivity to all three agents in clonogenic assays but much lower levels of apoptotic cells than R1 or HL-60 cells. These results show that the efficiency of the eradication of clonogenic cells by genotoxic agents does not solely depend on the induction of apoptotic processes, and suggest that the induction of apoptosis and suppression of clonogenicity are independent processes.
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PMID:Apoptosis and clonogenic survival in three tumour cell lines exposed to gamma rays or chemical genotoxic agents. 1294 6

In the last few years molecular genetic studies of childhood cancer have acquired great importance. Advances in these techniques have increased knowledge of the various genes involved in tumoral development. Genetic alterations can occur in three large groups of genes: oncogenes, tumor suppressor genes, and DNA repair genes. Cytogenetic analyses (karyotyping) are complemented by various molecular techniques, such as fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and spectral karyotyping (SKY). These are the most reliable techniques and improve the sensitivity of karyotyping. The present article reviews the most representative and best characterized genes involved in the molecular etiology of childhood cancer, both hematologic malignancies (leukemia and lymphoma) and solid tumors (brain tumors, neuroblastoma, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma, Ewing's sarcoma and retinoblastoma). Molecular techniques have enabled more precise diagnosis as well as identification of new prognostic factors and the development of more effective treatments. These techniques can also be useful in identifying minimal residual disease during and after treatment for leukemias, neuroblastomas and sarcomas, with the aim of predicting recurrence.
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PMID:[The role of molecular genetics in childhood cancer]. 1451 4

The authors report a case of a 19-year-old man with alveolar rhabdomyosarcoma with an unusual clinical presentation. The diagnosis was established on lymph node biopsy performed on admission of the patient in a context simulating leukaemia. The patient achieved complete remission in response to high-dose chemotherapy. A recurrence in the form of an intratesticular metastasis demonstrated a periorbital tumour that was probably the primary tumour. The authors present the radiological and histological findings and a molecular biology study of the testicular metastasis, eliminating a primary testicular tumour.
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PMID:[Testicular metastasis of alveolar rhabdomyosarcoma: clinical case of a 19-year-old man]. 1465 Mar 11

BACKGROUND: Chaperones (CH) play an important role in tumor biology but no systematic work on expressional patterns has been reported so far. The aim of the study was therefore to present an analytical method for the concomitant determination of several CH in human tumor cell lines, to generate expressional patterns in the individual cell lines and to search for tumor and non-tumor cell line specific CH expression.Human tumor cell lines of neuroblastoma, colorectal and adenocarcinoma of the ovary, osteosarcoma, rhabdomyosarcoma, malignant melanoma, lung, cervical and breast cancer, promyelocytic leukaemia were homogenised, proteins were separated on two-dimensional gel electrophoresis with in-gel digestion of proteins and MALDI-TOF/TOF analysis was carried out for the identification of CH. RESULTS: A series of CH was identified including the main CH groups as HSP90/HATPas_C, HSP70, Cpn60_TCP1, DnaJ, Thioredoxin, TPR, Pro_isomerase, HSP20, ERP29_C, KE2, Prefoldin, DUF704, BAG, GrpE and DcpS. CONCLUSIONS: The ten individual tumor cell lines showed different expression patterns, which are important for the design of CH studies in tumor cell lines. The results can serve as a reference map and form the basis of a concomitant determination of CH by a protein chemical rather than an immunochemical method, independent of antibody availability or specificity.
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PMID:Expressional patterns of chaperones in ten human tumor cell lines. 1559 46


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