Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in gene expression profiles were investigated in 23 patients with Niemann-Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3, THBS4), cytokine signalling (MMP3), extracellular matrix degradation (MMP3, CTSK), autophagy and apoptosis (CTSK, GPNMB, PTGIS), immune response (AKR1C3, RCAN2, PTGIS) and processes of neuronal development (RCAN2). Downregulated genes were associated with cytoskeletal signalling (ACTG2, CNN1); inflammation and oxidative stress (CNN1); inhibition of cell proliferation, migration and differentiation; ERK-MAPK pathway (COL4A1, COL4A2, CPA4); cell adhesion (IGFBP7); autophagy and apoptosis (CDH2, IGFBP7, COL4A2); neuronal function and development (CSRP1); and extracellular matrix stability (PLOD2). When comparing NPC and Gaucher patients together versus controls, upregulation of SERPINB2 and IL13RA2 and downregulation of CSRP1 and CNN1 were characteristic. Notably, in NPC patients, the expression of PTGIS is upregulated while the expression of PLOD2 is downregulated when compared to Gaucher patients or controls and potentially could serve to differentiate these patients. Interestingly, in NPC patients with (i) jaundice, splenomegaly and cognitive impairment/psychomotor delay-the expression of ACTG2 was especially downregulated; (ii) ataxia-the expression of ACTG2 and IGFBP5 was especially downregulated; and (iii) VSGP, dysarthria, dysphagia and epilepsy-the expression of AKR1C3 was especially upregulated while the expression of ACTG2 was downregulated. These results indicate disordered apoptosis, autophagy and cytoskeleton remodelling as well as upregulation of immune response and inflammation to play an important role in the pathogenesis of NPC in humans.
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PMID:Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann-Pick C disease. 3192 69

Melanoma metastasis from an unknown primary cancer has an incidence of 3.2% among melanoma patients. Furthermore, paraneoplastic neurological syndromes (PNS) are rare, occurring in 1-3% of patients with malignancies. Paraneoplastic cerebellar degeneration (PCD) is one of the classic PNS and is characterized by acute or subacute onset of ataxia and/or presence of onconeural antibodies. A 61-year-old male with ataxia, vertigo, and headache later developed dysarthria, multidirectional nystagmus, hyperactive delirium, auditory hallucinations, psychomotor agitation, and myoclonus. Toxicological, metabolic, infectious, and autoimmune etiologies were assessed and reported negative. An osteolytic lesion was observed in the right iliac crest via computed tomography (CT). A positron emission tomography-CT reported increased fluorodeoxyglucose uptake of a right iliac and right inguinal ganglion. After biopsy of the right inguinal ganglion, a BRAF mutation-positive melanoma metastasis from an occult primary cancer was diagnosed. Dermatologic, ophthalmologic, and endoscopic gastrointestinal assessment did not reveal a primary malignant melanoma. The patient's movement disorders and neuropsychiatric symptoms improved with quetiapine, prednisone, azathioprine, and cyclophosphamide. Oncological management was conducted with MAPK pathway inhibitors (i.e., dabrafenib and trametinib). Movement disorders associated with neuropsychiatric symptoms are complex to diagnose. PNS are rare and often associated with antibodies against neural antigens expressed by the tumor. The case presented above describes a patient with a BRAF-positive malignant melanoma metastasis from an occult primary associated with PCD - to the best of our knowledge, the first reported in the literature.
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PMID:Paraneoplastic Cerebellar Degeneration Secondary to BRAF Mutant Melanoma Metastasis from an Occult Primary Cancer. 3277 48