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)

Cyclin D1 belongs to a family of proteins that regulate progression through the G1-S phase of the cell cycle by binding to cyclin-dependent kinase (cdk)-4 to phosphorylate the retinoblastoma protein and release E2F transcription factors for progression through cell cycle. Several cancers, including breast, colon, and prostate, overexpress the cyclin D1 gene. However, the correlation of cyclin D1 overexpression with E2F target gene regulation or of cdk-dependent cyclin D1 activity with tumor development has not been identified. This suggests that the role of cyclin D1 in oncogenesis may be independent of its function as a cell cycle regulator. One such function is the role of cyclin D1 in cell adhesion and motility. Filamin A (FLNa), a member of the actin-binding filamin protein family, regulates signaling events involved in cell motility and invasion. FLNa has also been associated with a variety of cancers including lung cancer, prostate cancer, melanoma, human bladder cancer, and neuroblastoma. We hypothesized that elevated cyclin D1 facilitates motility in the invasive MDA-MB-231 breast cancer cell line. We show that MDA-MB-231 motility is affected by disturbing cyclin D1 levels or cyclin D1-cdk4/6 kinase activity. Using mass spectrometry, we find that cyclin D1 and FLNa coimmunoprecipitate and that lower levels of cyclin D1 are associated with decreased phosphorylation of FLNa at Ser2152 and Ser1459. We also identify many proteins related to cytoskeletal function, biomolecular synthesis, organelle biogenesis, and calcium regulation whose levels of expression change concomitant with decreased cell motility induced by decreased cyclin D1 and cyclin D1-cdk4/6 activities.
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PMID:Cyclin D1/cyclin-dependent kinase 4 interacts with filamin A and affects the migration and invasion potential of breast cancer cells. 2017 8

As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((1H-benzo[d]imidazol-2-yl)methylthio)-4-(substituted)-6-phenylpyrimidine-5-carbonitriles was synthesized. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against twelve cell lines namely, Cervical carcinoma (KB), Ovarial carcinoma (SK OV-3), CNS cancer (SF-268), Non small lung cancer (NCI H460), Colonadenocarcinoma (RKOP27), Leukaemia (HL60, U937, K562), Melanoma (G361, SK-MEL-28) and Neuroblastoma (GOTO, NB-1) revealed their marked potency when compared with known anticancer drugs.
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PMID:Novel benzimidazole-pyrimidine conjugates as potent antitumor agents. 2035 55

This article summarizes the phenomenon of cancer overdiagnosis-the diagnosis of a "cancer" that would otherwise not go on to cause symptoms or death. We describe the two prerequisites for cancer overdiagnosis to occur: the existence of a silent disease reservoir and activities leading to its detection (particularly cancer screening). We estimated the magnitude of overdiagnosis from randomized trials: about 25% of mammographically detected breast cancers, 50% of chest x-ray and/or sputum-detected lung cancers, and 60% of prostate-specific antigen-detected prostate cancers. We also review data from observational studies and population-based cancer statistics suggesting overdiagnosis in computed tomography-detected lung cancer, neuroblastoma, thyroid cancer, melanoma, and kidney cancer. To address the problem, patients must be adequately informed of the nature and the magnitude of the trade-off involved with early cancer detection. Equally important, researchers need to work to develop better estimates of the magnitude of overdiagnosis and develop clinical strategies to help minimize it.
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PMID:Overdiagnosis in cancer. 2207 86

The aim of this article is to review the paraneoplastic opsoclonus-myoclonus syndrome (POMS). Opsoclonus is characterized by involuntary, arrhythmic, chaotic, multi-directional saccades with horizontal, vertical and torsional components, and it is commonly accompanied by cerebellar ataxia and myoclonic jerks in the trunk and limbs. Parainfectious brainstem encephalitis, toxic-metabolic disturbances and others condition should be considered as potential causes of these symptoms. In adults, POMS is most commonly associated with small-cell lung cancer, breast cancer, and ovarian cancer. In children, a neuroblastoma is detected in approximately 50% of cases. Many autoantibodies have been detected in patients with POMS: this finding suggests the involvement of a humoral immune mechanism. However, most patients are seronegative for these autoantibodies. This implies that a cell-mediated immune mechanism may also be involved in the pathogenesis of opsoclonus. Although the exact pathophysiology mechanism of opsoclonus remains unclear, recent reports suggest that disinhibition of the fastigial nucleus of the cerebellum is involved. In children, the immunotherapy with corticosteroids, intravenous immunoglobulin, adrenocorticotropic hormone, plasma exchange, cyclophosphamide, or rituximab is used. Although opsoclonus is often responsive to therapy, the high incidence of sequelae related to motor function, speech, behavior, and sleep is an important problem. In adults, POMS is less responsive to immunotherapy and improves only with tumor resection. In order to develop novel and effective therapeutic strategies, further studies on the immunopathogenesis and pathophysiology of POMS are required.
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PMID:[Paraneoplastic opsoclonus-myoclonus syndrome--a review]. 2042 Jan 76

Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.
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PMID:Non-FDG PET in the practice of oncology. 2044 72

The Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase first identified as the product of a gene rearrangement in Anaplastic Large Cell Lymphoma. ALK has subsequently been found to be rearranged, mutated, or amplified in a further series of tumours including neuroblastoma, and Non-Small Cell Lung Cancer. There is strong preclinical evidence that ALK is a driving force for oncogenesis in these cases, and that inhibition of ALK kinase activity results in anti-tumoural efficacy. These observations have sparked the development of small molecule kinase inhibitors, the most advanced of which is currently in clinical testing and which has shown promising preliminary activity in the subset of lung cancer patients whose tumours harbour activated ALK. In this review, we describe the various oncogenic forms of ALK, relevant clinical settings, and give a detailed overview of current drug discovery efforts in the field.
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PMID:Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy. 2093 3

Rho guanosine triphosphatases (GTPases) are a family of small proteins which function as molecular switches in a variety of signaling pathways following stimulation of cell surface receptors. RhoGTPases regulate numerous cellular processes including cytoskeleton organization, gene transcription, cell proliferation, migration, growth and cell survival. Because of their central role in regulating processes that are dysregulated in cancer, it seems reasonable that defects in the RhoGTPase pathway may be involved in the development of cancer. RhoGTPase activity is regulated by a number of protein families: guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhibitors (GDIs). This review discusses the participation of RhoGTPases and their regulators, especially GEFs in human cancers. In particular, we focus on the involvement of the RhoGTPase GEF, Vav1, a hematopoietic specific signal transducer which is involved in human neuroblastoma, pancreatic ductal carcinoma and lung cancer. Finally, we summarize recent advances in the design and application of a number of molecules that specifically target individual RhoGTPases or their regulators or effectors, and discuss their potential for cancer therapy.
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PMID:Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy? 2104 80

The phytochemical investigation of the hexane extract of the Hedychium coronarium led to the isolation and identification of two new labdane diterpenes (1 and 2) along with 10 known metabolites (3-12). The structures of the new compounds were established on the basis of spectroscopic data analysis (1D and 2D NMR and MS). Cytotoxic activities of the isolates were studied against the A-549 (lung cancer), SK-N-SH (human neuroblastoma), MCF-7 (breast cancer) and HeLa (cervical cancer) cell lines.
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PMID:Two new cytotoxic labdane diterpenes from the rhizomes of Hedychium coronarium. 2110 58

Paraneoplastic opsoclonus is well described in neuroblastoma. In the adult oncologic population, opsoclonus is seen usually within the context of opsoclonus-myoclonus ataxia and is associated most strongly with small-cell lung cancer. Patients with paraneoplastic opsoclonus are often seronegative. Patients with gynecologic malignancies are known to be predisposed to paraneoplastic syndromes; however, we describe the first case of paraneoplastic opsoclonus in association with endometrial cancer.
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PMID:Opsoclonus as a suspected paraneoplastic syndrome of endometrial cancer. 2113 58

The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease.
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PMID:Evaluation of the bioactivity of novel spiroisoxazoline typecompounds against normal and cancer cell lines. 2116 84


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