Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although increased expression of cysteine proteinases has been shown to be correlated with increased metastasis for a wide variety of tumours, the contribution of cysteine proteinases to the metastatic spread of tumour cells is not well understood. In order to examine this question we have overexpressed a specific cysteine proteinase inhibitor, cystatin C, by stable transfection of B16F10 melanoma. Increased expression of cystatin C inhibited motility and in vitro invasiveness of B16 melanoma by 50% in both stimulated (autocrine motility factor, laminin) and unstimulated cells. These results suggest that cysteine proteinases are involved in B16 melanoma motility and invasion.
Melanoma Res 1997 Apr
PMID:Inhibition of motility and invasion of B16 melanoma by the overexpression of cystatin C. 916 74

Progression to metastasis has been correlated with increased cysteine proteinase activity for a number of tumour types. One mechanism of cysteine proteinase regulation in normal cells is by natural protease inhibitors, the cystatins. Here we further characterize a transfected cell line showing increased cystatin C transcription driven by cytomegalovirus (CMV) promoter/enhancer sequences. Properties of this cystatin C altered cell line such as growth in vitro, lung colonization after tail vein injection in mice, production of cystatin, and cysteine proteinase inhibitor activities were examined. Although there was no difference between the growth rate of the cystatin transfected cell line and that of the control, there was a substantial difference in metastatic ability. No increase was noted in cystatin C secretion into the media for the cystatin C transfected cell line compared with the control transfected cell line. There was, however, a difference in cysteine protease inhibitor activity in the cell-free extracts. These results show that alteration of cystatin C levels by overexpression in B16 melanoma alters properties associated with metastasis.
Melanoma Res 1999 Aug
PMID:Inhibition of B16 melanoma metastasis by overexpression of the cysteine proteinase inhibitor cystatin C. 1050 55

Immune-related adverse events (irAEs) are a frequent complication of immunotherapy, but neurological irAEs are rare and varied. Here, we present a case of cerebral amyloid angiopathy-related inflammation (CAA-ri) attributable to nivolumab monotherapy, which has not been previously reported. The context of immunotherapy and availability of serial imaging also provide unique insights into the pathogenesis and evolution of CAA-ri. Routine surveillance neuroimaging in a patient with metastatic melanoma, in remission after treatment with nivolumab, demonstrated progressive microhaemorrhages and associated oedema, suspicious for CAA-ri. These changes progressed despite cessation of nivolumab. The patient was initially asymptomatic, but later developed an acute confusional state, warranting brain biopsy, which confirmed the diagnosis of CAA-ri. Treatment with methylprednisolone resulted in resolution of the oedema, and a marked decrease in the subsequent accumulation of microhaemorrhages. The temporal evolution prior to symptom development and subsequently related to treatment suggests that inflammation may be an important component of the pathogenesis of CAA-ri, rather than simply a secondary response. Given that immunotherapy is in its relative infancy, it is important to consider rare irAEs in patients exhibiting unusual imaging findings.
Melanoma Res 2020 12
PMID:Clinical and radiological evolution of cerebral amyloid angiopathy-related inflammation in the context of anti-PD-1 immunotherapy. 3259 Apr 13