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1.
Oncogene ; 35(43): 5674-5685, 2016 10 27.
Article in English | MEDLINE | ID: mdl-27065329

ABSTRACT

HLJ1 (DNAJB4), a DNAJ/Hsp40 chaperone, has emerged as a novel prognostic marker in lung cancers; however, the molecular contribution and functionality in neoplastic diseases remain to be established. This study demonstrated that HLJ1 inhibits epithelial-mesenchymal transition in vitro and reduces lung cancer metastasis in vivo. Using shRNA silencing and ectopic expression of HLJ1, we found that HLJ1 not only suppresses catalytic activity of Src but also downregulates the formation of oncogenic complexes associated with the EGFR, FAK and STAT3 signaling pathways. A screen of specimens from HLJ1-knockout mice and lung cancer patients validated that HLJ1 expression is inversely correlated with Src activity. Mechanistically, HLJ1 protein directly bound to catalytic and protein-binding domains of Src through its amino acid Y172 and the P301/P304 motif. Following Src-induced HLJ1 phosphorylation at Y172, HLJ1-Src interaction was elevated, resulting in Src inhibition and malignancy suppression. Interestingly, both Src-binding regions also occurred in other DNAJB family members and contributed to anti-invasive activities of DNAJB proteins. We conclude that HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. This HLJ1-Src complex might provide a promising molecular model for developing new anticancer strategies.


Subject(s)
HSP40 Heat-Shock Proteins/metabolism , Neoplasms/metabolism , Neoplasms/pathology , src-Family Kinases/antagonists & inhibitors , Amino Acid Sequence , Animals , Disease Models, Animal , Disease Progression , Enzyme Activation , Gene Expression , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , HSP40 Heat-Shock Proteins/chemistry , HSP40 Heat-Shock Proteins/genetics , HSP40 Heat-Shock Proteins/pharmacology , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, Knockout , Models, Biological , Models, Molecular , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasms/genetics , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , RNA Interference , RNA, Small Interfering/genetics , src Homology Domains , src-Family Kinases/chemistry , src-Family Kinases/metabolism
2.
Opt Lett ; 39(19): 5515-8, 2014 Oct 01.
Article in English | MEDLINE | ID: mdl-25360916

ABSTRACT

We experimentally demonstrate the use of single-photon avalanche photodiode (SPAD) for radiometric temperature measurement. The low dark count rate CMOS SPAD and a commercial InGaAs/InP SPAD can detect the thermal radiation from a blackbody down to the temperatures of 510 and 405 K, respectively. Our work shows that current SPADs are cost-effective thermal sensors for various applications.

3.
Eur J Neurol ; 21(10): 1285-91, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24909847

ABSTRACT

BACKGROUND AND PURPOSE: Orolingual angioedema (OA) is an uncommon but potentially life-threatening complication of treatment with recombinant tissue plasminogen activator (rt-PA; alteplase) during acute ischaemic stroke. This study aimed to determine the incidence of rt-PA-related OA in an Asian stroke population and the risk of pre-stroke anti-hypertensive drug use for development of this complication. METHODS: A multi-center stroke registry was used to identify the pre-stroke medications of acute ischaemic stroke patients receiving intravenous rt-PA from January 2002 to December 2013. The clinical manifestations of rt-PA-related OA were recorded and the incidence of this complication was determined. The risks of pre-stroke use of different anti-hypertensive agents for the occurrence of rt-PA-related OA were determined from this study and from a meta-analysis. RESULTS: A total of 559 patients received intravenous rt-PA over a 12-year period. Five patients (two males) developed OA after rt-PA administration. The incidence of OA amongst these patients was 0.89% (95% confidence interval 0.29%-2.09%), which was lower than that obtained by meta-analysis (1.9%). Amongst pre-stroke anti-hypertensive medications, angiotensin-converting enzyme (ACE) inhibitors were found in this study to have the highest relative risk for rt-PA-related OA (17.1; 95% confidence interval 3.0-96.9). Meta-analysis also revealed that pre-stroke use of ACE inhibitors was associated with a high relative risk of OA after intravenous rt-PA (12.9; 95% confidence interval 4.5-37.0). CONCLUSIONS: The incidence of rt-PA-related OA in the Asian population is lower than that in the Caucasian population. Pre-stroke use of ACE inhibitors significantly increases the risk of this complication.


Subject(s)
Angioedema/chemically induced , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Brain Ischemia/drug therapy , Fibrinolytic Agents/adverse effects , Mouth Diseases/chemically induced , Registries/statistics & numerical data , Stroke/drug therapy , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Aged , Aged, 80 and over , Angioedema/epidemiology , Brain Ischemia/epidemiology , Female , Fibrinolytic Agents/administration & dosage , Humans , Incidence , Male , Middle Aged , Mouth Diseases/epidemiology , Risk , Stroke/epidemiology , Taiwan/epidemiology , Thrombolytic Therapy/statistics & numerical data , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use , Tongue Diseases/chemically induced , Tongue Diseases/epidemiology
5.
BJU Int ; 85(1): 79-82, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10619951

ABSTRACT

OBJECTIVE: To assess in a prospective study the use of a new variable, the residual prostatic weight ratio (RPWR), for evaluating the clinical outcome after transurethral resection of the prostate (TURP). PATIENTS AND METHODS: From April 1996 to June 1997, 40 men (mean age 70.4 years, range 53-85) with symptomatic benign prostatic hyperplasia were evaluated using the American Urological Association (AUA) symptom score, measurements of the mean and maximum urinary flow rate (Qave and Qmax), and by transrectal ultrasonography (TRUS) before and 16 weeks after TURP. The estimated total prostate weight was derived as 0.52 x length x width x height x the specific gravity of the prostate (1.010). The RPWR was calculated as the prostate weight after TURP divided by the initial weight, where the value after TURP was the initial weight minus that of the TURP specimen. The clinical outcome was evaluated by the difference (Delta) in AUA score, Qmax and Qave before and 16 weeks after surgery. RESULTS: There was a close correlation between the estimated prostate weight and the actual weight of the TURP specimen (r = 0.82 and 0.80 for the adenoma and total prostate, respectively). The mean (SD) RPWR, DeltaAUA score, DeltaQmax and DeltaQave were 50.1 (17.1)%, 11.5 (5. 3), 9.0 (4.2) mL/s and 6.2 (2.9) mL/s, respectively. There was a negative correlation between the RPWR and the DeltaAUA, DeltaQmax and DeltaQave (r = -0.81, -0.68, and -0.70, respectively, P < 0.05). The prostate volume estimated by TRUS decreased significantly 16 weeks after TURP. CONCLUSIONS: TRUS is a useful tool for estimating prostate weight before surgery. The smaller the RPWR at 16 weeks after TURP, the better the clinical outcome.


Subject(s)
Prostate/pathology , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Organ Size , Prospective Studies , Prostatic Hyperplasia/pathology , Treatment Outcome
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