Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A two-year-old boy with a malignant tumor of the brain (medulloblastoma) excreted large amounts of thymine and uracil in his urine. The excretion was related to progress and regress of the disease, and reached a maximum of 3.0 mol of thymine per mole of creatinine and 2.6 mol of uracil per mole of creatinine. The excretion by 20 apparently normal children was less than 0.01 mol/mol of creatinine for each of the two pyrimidines. Three children with brain tumors, two with leukemias, and one with neuroblastoma were also studied; two of them had a moderate increase in urinary pyrimidine excretion, but only up to 0.07 mol/mol of creatinine. The activity of dihydrouracil dehydrogenase (NADP+) (EC 1.3.1.2) in cultured fibroblasts from the patient was somewhat lower than in control fibroblasts. The tumor was considered to be the likely cause of the increased excretion of pyrimidines, but an impaired degradation of pyrimidines in the liver could not be ruled out.
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PMID:Urinary excretion of thymine and uracil in a two-year-old child with a malignant tumor of the brain. 28 71

The C-1300 neuroblastoma tumor which arises spontaneously in the A/J mouse has been maintained in this mouse strain. Two different cell populations have been recognized in cultured C-1300 mouse neuroblastoma (MNB): (1) round, "neuroblast-like" cells, growing in suspension (poorly attached), that have a highly malignant behavior when injected into the A/J mouse (T1 cells); and (2) flat, "epithelioid" cells that attach well to surfaces and show low malignancy towards the inoculated animals (T2 cells). The specific activities of the pyrimidine metabolizing enzymes thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) were examined in both MNB cell lines by a new radiochromatographic method. Enzymatic activities of TP and DPD in the cytosols of T2 (weakly malignant) cells were up to 15 times higher than those of T1 (strongly malignant) cells, whereas the mean TP/DPD activity ratio was 16 in either cell line. TP and DPD activity levels increased with time of growth in culture in T2 cells while no such increase was seen in the T1 cells. Maximal TK activity was similar in both cell lines but dropped more rapidly in the T2 cells as cell densities increased. The enzymatic activity levels of TP and DPD but not of TK correlated inversely with neoplastic expression of MNB cells. The observed patterns of pyrimidine metabolizing enzymes in MNB cells could result in an increased thymidine pool in T1 cells whenever TK activity is suppressed, whereas such conditions would favor the generation of thymine in the T2 cells.
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PMID:Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells. 271 95

The case of a 41/2-year-old girl with disseminated neuroblastoma and concomitant osteomyelitis is reported. Neuroblastoma was detected in the vertebral column, the right suprarenal fossa, the left side of cranium and in bone marrow aspirates. Osteomyelitis was present in the left femur and was due to Salmonella tennessee. For the first time in the literature the two lesions were demonstrated by means of simultaneous 131I-MIBG and 99mTc-DPD scintigraphy. The diagnoses were proved by direct histological and microbiological studies.
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PMID:Coincidence of infectious osteomyelitis and disseminated neuroblastoma: a diagnostic dilemma solved by scintigraphic imaging. 401 73

To diagnose inborn errors of metabolism, it would be desirable to simultaneously analyze and quantify organic acids, purines, pyrimidines, amino acids, sugars, polyols, and other compounds using a single-step fractionation; unfortunately, no such method currently exists. The present article will be concerned primarily with a practical yet comprehensive diagnostic procedure of inborn errors of metabolism (IEM). This procedure involves the use of urine or eluates from urine on filter paper, stable isotope dilution, and gas chromatography-mass spectrometry (GC-MS). This procedure not only offers reliable and quantitative evidence for diagnosing, understanding and monitoring the diseases, but also provides evidence for the diagnosis of new kinds of IEM. In this review, the differential diagnosis for hyperammonemia are described; deficiencies of ornithine carbamoyl transferase, argininosuccinate synthase (citrullinemia), argininosuccinate lyase and arginase, lysinuric protein intolerance, hyperammonemia-hyperornithinemia-homocitrullinemia syndrome, and citrullinemia type II. The diagnosis of IEM of purine and pyrimidine such as deficiencies of hypoxanthine-guanine phosphoribosyl transferase, adenine phosphoribosyl transferase, dihydropyrimidine dehydrogenase, dihydropyrimidinase and beta-ureidopropionase are described. During the pilot study for newborn screening, we found neonates with diseases at a rate of 1 per 1,400 including propionic acidemia, methylmalonic acidemia, orotic aciduria, beta-ureidopropionase deficiency, lactic aciduria and neuroblastoma. A rapid and reliable prenatal diagnosis for propionic acidemia is also described.
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PMID:Diagnosis and monitoring of inborn errors of metabolism using urease-pretreatment of urine, isotope dilution, and gas chromatography-mass spectrometry. 1245 Jun 76

Genome-wide association studies (GWAS) have identified a locus on chromosome 1p21.3 to be highly associated with schizophrenia. A microRNA, MIR137, within this locus has been proposed as the gene causally associated with schizophrenia, due to its known role as a regulator of neuronal development and function. However, the involvement of other genes within this region, including DPYD (dihydropyrimidine dehydrogenase), is also plausible. In this communication, we describe a previously uncharacterised, brain-expressed RNA, EU358092, within the schizophrenia-associated region at 1p21.3. As we observed for MIR137, EU358092 expression was modulated in response to psychoactive drug treatment in the human SH-SY5Y neuroblastoma cell line. Bioinformatic analysis of publically available CNS expression data indicates that MIR137 and EU358092 are often co-expressed in vivo. A potential regulatory domain for expression of EU358092 is identified by bioinformatic analysis and its regulatory function is confirmed by reporter gene assays. These data suggest a potentially important role for EU358092 in the aetiology of schizophrenia, either individually or in combination with other genes at this locus.
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PMID:Novel brain expressed RNA identified at the MIR137 schizophrenia-associated locus. 2791 61

Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the standard of care for patients with Locally Advanced Rectal Cancer (LARC). Current selection for nCRT is based on clinical criteria regardless of any molecular marker. Pharmacogenomics may be a useful strategy to personalize and optimize nCRT in LARC. This review aims to summarize the most recent and relevant findings about the role of germline and somatic pharmacogenomics in the prediction of nCRT outcome in patients with LARC, discussing the state of the art of their application in the clinical practice. A systematic literature search of the PubMed database was completed to identify relevant English-language papers published up to January 2020. The chemotherapeutic backbone of nCRT is represented by fluoropyrimidines, mainly metabolized by DPD (Dihydro-Pyrimidine Dehydrogenase, DPYD). The clinical impact of testing DPYD*2A, DPYD*13, c.2846A > T and c.1236G > A-HapB3 before a fluoropyrimidines administration to increase treatment safety is widely acknowledged. Other relevant target genes are TYMS (Thymidylate Synthase) and MTHFR (Methylene-Tetrahydro-Folate Reductase), whose polymorphisms were mainly studied as potential markers of treatment efficacy in LARC. A pivotal role of a TYMS polymorphism in the gene promoter region (rs34743033) was reported and was pioneeringly used to guide nCRT treatment in a phase II study. The pharmacogenomic analysis of other pathways mostly involved in the cellular response to radiation damage, as the DNA repair and the activation of the inflammatory cascade, provided less consistent results. A high rate of somatic mutation in genes belonging to PI3K (Phosphatidyl-Inositol 3-Kinase) and MAPK (Mitogen-Activated Protein Kinase) pathways, as BRAF (V-raf murine sarcoma viral oncogene homolog B1), KRAS (Kirsten Rat Sarcoma viral oncogene homolog), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog), PIK3CA (Phosphatidyl-Inositol-4,5-bisphosphate 3-Kinase, Catalytic Subunit Alpha), as well as TP53 (Tumor Protein 53) was reported in LARC. Their pharmacogenomic role, already defined in colorectal cancer, is under investigation in LARC with promising results concerning specific somatic mutations in KRAS and TP53, as predictors of tumor response and prognosis. The availability of circulating tumor DNA in plasma may also represent an opportunity to monitor somatic mutations in course of therapy.
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PMID:Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy. 3262 92