Search results for "Serpins"
showing 10 items of 23 documents
The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possibl…
2016
Abstract Breast cancer stem cells seem to play important roles in breast tumor recurrence and endocrine therapy resistance, although the underlying mechanisms have not been well established. Moreover, in some tumor systems the immunosurveillance failure against cancer cells has been related to the presence of the granzyme B inhibitor PI-9. This study explored the status of PI-9 in tumorspheres isolated from estrogen receptor-α positive (ERα+) breast cancer MCF7 cells. Studies were performed in tertiary tumorspheres which possess high levels of stemness markers (Nanog, Oct3/4 and Sox2) and self-renewal ability. The exposure to estrogens (17-β estradiol and genistein) increased the number and…
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
2016
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−…
Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema
2005
BACKGROUND: Abdominal edema attacks in patients with hereditary angioedema are often extremely painful, associated with vomiting and diarrhea, and have a high potential for causing recurrent disability of the patient. STUDY DESIGN AND METHODS: Intraindividual comparison of retrospective data in 75 hereditary angioedema patients comprising 4,834 abdominal attacks treated with C1 inhibitor concentrate versus 17,444 untreated abdominal attacks. RESULTS: The mean duration of abdominal attacks was 92.0 hours (SD, 40.8 hr) when untreated compared to 39.9 hours (SD, 30.0 hr) when treated. Patients reported a mean maximal pain score of 8.6 (SD, 1.7; range, 1-10) for untreated attacks compared to 4.…
Acute Myocardial Infarction and Proinflammatory Gene Variants
2007
We identified four genetic risk sets for acute myocardial infarction (AMI) from information on functional gene variants that favor inflammation or modulate cholesterol metabolism: IL6 -174 G/C, TNF -308 G/A, IL10 -1082 G/A, SERPINA3 -51 G/T, IFNG +874 T/A, HMGCR -911 C/A, and APOE ε2/3/4; 316 patients and 461 healthy subjects, all Italian. Putative risk alleles are shown underlined. The sets were identified using grade-of-membership analysis. Membership scores in the sets are automatically generated for individuals. The ''low intrinsic risk'' set had alleles that downregulate inflammation and cholesterol synthesis (IL6, TNF, ILl0, HMGCR). ''AMI across a broad age range'' carried multiple pr…
Hereditary Angioedema: New Findings Concerning Symptoms, Affected Organs, and Course
2005
Abstract Purpose Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Our aim was to examine a temporal and spatial pattern of the edema episodes by evaluating the long-term course of hereditary angioedema in order to establish a specific swelling pattern. Subjects and methods Data were generated from 221 patients with C1 inhibitor deficiency by asking them about symptoms they experienced during their edema episodes. Documentation was accomplished through the use of standardized questionnaires. Results A total of 131110 edema episodes were observed. Clinical …
Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course.
2007
Abstract Purpose A new type of hereditary angioedema was described recently. It was characterized by recurrent bouts of angioedema in various organs and normal C1 inhibitor and was observed mainly in women. Our aim was to conduct a detailed study of the clinical features of this condition. Methods A total of 138 patients with hereditary angioedema and normal C1 inhibitor who belonged to 43 unrelated families were examined through the use of standardized questionnaires. Results A majority of patients with hereditary angioedema and normal C1 inhibitor had skin swellings (92.8%), tongue swellings (53.6%), and abdominal pain attacks (50%). Laryngeal edema (25.4%) and uvular edema (21.7%) also w…
Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency.
2006
Recurrent abdominal attacks belong to the cardinal and most distressing symptoms of hereditary angioedema (HAE) due to C1 inhibitor deficiency. They are characterized by crampy pain, but may include vomiting, diarrhea, and other features. Detailed clinical data about the symptoms and course of abdominal attacks have not been reported.We retrospectively observed a total of 33,671 abdominal attacks in 153 patients with HAE including a prospectively examined subgroup of 23 patients. Symptoms, course, frequency of attacks, and complications were analyzed.The relation of mild, moderate, and severe attacks was 1:1.4:5.6 in the prospective part of the study. Extra-abdominal symptoms preceded the a…
Targeted SERPIN (TaSER): A dual‐action antithrombotic agent that targets platelets for SERPIN delivery
2021
BACKGROUND Occlusive thrombi are not homogeneous in composition. The core of a thrombus is rich in activated platelets and fibrin while the outer shell contains resting platelets. This core is inaccessible to plasma proteins. We produced a fusion protein (targeted SERPIN-TaSER), consisting of a function-blocking VH H against glycoprotein Ibα (GPIbα) and a thrombin-inhibiting serine protease inhibitor (SERPIN; α1-antitrypsin 355 AIAR358 ) to interfere with platelet-driven thrombin formation. AIM To evaluate the antithrombotic properties of TaSER. METHODS Besides TaSER, we generated three analogous control variants with either a wild-type antitrypsin subunit, a non-targeting control VH H, or …
Tightly bound to DNA proteins: possible universal substrates for intranuclear processes.
2011
Tightly bound to DNA proteins (TBPs) are a protein group that remains attached to DNA after its deproteinization by phenol, chloroform or salting-out. TBP are bound to DNA with covalent phosphotriester or non-covalent ion and hydrogen bonds. They appear to be a vast protein group involved in numerous intranuclear processes. The TBPs fraction co-purified with DNA deproteinized by mild procedures is extremely heterogeneous, tissue and species-specific. The protein fraction co-purified with DNA after harsh deproteinization procedures appears to be formed from few polypeptides common to different species and tissues. Interaction sites between DNA and TBPs depend on the physiological status of t…
Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone.
2009
We sought to address the fundamental question of how stem cell microenvironments can regulate self-renewal. We found that Notch was active in astroglia-like neural stem cells (NSCs), but not in transit-amplifying progenitors of the murine subependymal zone, and that the level of Notch transcriptional activity correlated with self-renewal and multipotency. Moreover, dividing NSCs appeared to balance renewal with commitment via controlled segregation of Notch activity, leading to biased expression of known (Hes1) and previously unknown (Egfr) Notch target genes in daughter cells. Pigment epithelium-derived factor (PEDF) enhanced Notch-dependent transcription in cells with low Notch signaling,…