scholarly journals Emerging Roles of SPINK1 in Cancer

2016 ◽  
Vol 62 (3) ◽  
pp. 449-457 ◽  
Author(s):  
Kati Räsänen ◽  
Outi Itkonen ◽  
Hannu Koistinen ◽  
Ulf-Håkan Stenman
Keyword(s):  
Growth Factor ◽  
Trypsin Inhibitor ◽  
Acute Phase Reactant ◽  
Normal Tissues ◽  
Trypsin Inhibition ◽  
Increased Risk ◽  
Peptidase Inhibitor ◽  
The Many

Abstract BACKGROUND Tumor-associated trypsin inhibitor (TATI) was originally isolated from the urine of a patient with ovarian cancer. It was later shown to be produced by many other tumors and several normal tissues. It had earlier been isolated from the pancreas and was hence called pancreatic secretory trypsin inhibitor (PSTI). It belongs to a family of protease inhibitors presently called serine peptidase inhibitor Kazal type (SPINK). In the SPINK family TATI/PSTI is SPINK1, which is the name used in this review. CONTENT In addition to being a protease inhibitor, SPINK1 also acts as an acute-phase reactant and a growth factor. Furthermore, it has been shown to modulate apoptosis. Overexpression of SPINK1 predicts an unfavorable outcome in several cancers and determination of SPINK1 in serum can be used to identify patients at increased risk of aggressive disease. Thus serum SPINK1 can be used as a prognostic tumor marker. Because SPINK1 acts as a growth factor and an inhibitor of apoptosis in some cancers, it has also been suggested that it can be a therapeutic target in cancer. However, because SPINK1 is the major physiological inhibitor of trypsin, inhibition of SPINK1 may increase the risk of pancreatitis. SUMMARY Taking into account the many functions of SPINK1, assessing the role of SPINK1 in cancer has several potentially important clinical applications ranging from a biomarker to a potential new target for cancer therapy.

The role of hormonal and vascular dysregulation in the genesis of early reproductive losses

2014 ◽  
Vol 63 (4) ◽  
pp. 22-33 ◽  
Author(s):  
Irina Aleksandrovna Gaziyeva ◽  
Guzel Nukhovna Chistyakova ◽  
Irina Ivanovna Remizova
Keyword(s):  
Growth Factor ◽  
Chromosomal Abnormalities ◽  
First Trimester ◽  
Hormonal Control ◽  
Soluble Adhesion Molecules ◽  
Vascular Dysregulation ◽  
Fetoplacental Complex ◽  
Reproductive Losses

The Purpose. To study the role of hormonal and vascular dysregulation for the genesis of early reproductive losses without fetus chromosomal abnormalities. Materials and methods. The study involved 150 pregnant women: 38 women with early reproductive losses in this pregnancy (main group) and 112 women with delivery of live full-term infant (comparison group). Determination of factors characterizing the function of fetoplacental complex, indicators of the endothelial function and regulators of angiogenesis was performed in the first trimester of progressive pregnancy. Results. It is established that the mechanisms of abortion in the first trimester is associated with reduced production of hormones and proteins, which are indicators of the formation and function of fetoplacental complex and mediating immunomodulatory, tolerogens and angiogenic effects: β-HCG, PAPP-A and trophoblastic β-1-glycoprotein. Impair of hormonal control of gestational remodeling of the maternal body is associated with endothelial dysfunction and dysregulation of angiogenesis. Markers of endotheliopathy are: increased levels of endothelin-1, propeptide big-endothelin and homocysteine, decreased production of total and endogenous nitrite, and the changing of release of soluble adhesion molecules. Disbalans of stimulators and inhibitors of angiogenesis is characterized by the increased level of proangiogenic vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) as well as by the reduction of level of antiangiogenic soluble receptor of VEGF (sVEGF-R1), protein 1, binding insulin-like growth factor (IGF-BP1), and placental growth factor (PlGF). Conclusion. The determination of factors of hormonal and vascular dysregulation in the early pregnancy contributes to the timely identification of women with risk of miscarriage.

scholarly journals 1103 Understanding the Role of Sleep as a Risk Factor for Suicidal Ideation in Active Duty Service Members

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A419-A420
Author(s):  
M M Paxton Willing ◽  
T C Pickett ◽  
L L Tate ◽  
C Rhodes ◽  
T DeGraba
Keyword(s):  
Heart Rate ◽  
Suicidal Ideation ◽  
Active Duty ◽  
Service Members ◽  
Health Concern ◽  
Sleep Study ◽  
Increased Risk ◽  
The Many ◽  
Subjective Reports

Abstract Introduction Suicide is an important public health concern with many factors contributing to increased risk. Sleep is one such factor that may elevate risk, yet this association is not well understood. By identifying the strongest sleep-related predictors of suicidal ideation (SI), providers may be able to better intervene and reduce risk of suicide. Methods Data were obtained from the clinical database at the National Intrepid Center of Excellence (NICoE). Patients were active duty service members, predominantly male, and with a mean age of 38. As part of standard care, patients receive a polysomnography sleep study and complete a battery of intake measures offering a comprehensive view of sleep. Individual symptoms were analyzed in an effort to understand the role of each sleep symptom within the context of the many other factors that may contribute to SI in service members. Results Of the many data points collected during polysomnography, only rapid eye movement (REM) sleep latency and minimum sleeping heart rate were related to SI. REM latency was associated with increased odds of SI, while minimum sleeping heart rate was related to decreased odds. Subjective reports of bad dreams, trauma-specific bad dreams, sleepiness, and sleep quality were related to increased odds of SI. Notably, subjective reports of sleep were associated with greater odds than objective measures. Traumatic nightmares had the greatest odds, with these patients being much more likely to have SI. Conclusion These results support the importance of considering sleep factors when evaluating SI in service members. Subjective sleep reports, specifically, appear to be particularly important, as they were associated with increased odds of SI. These findings focus on the role of individual sleep factors in increasing the odds of SI and suggest it is important to evaluate sleep in combination with comorbid conditions when conducting risk assessments. Support N/A

scholarly journals Endocrine Gland-Derived Vascular Endothelial Growth Factor/Prokineticin-1 in Cancer Development and Tumor Angiogenesis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Ana Silvia Corlan ◽  
Anca Maria Cîmpean ◽  
Adriana-Andreea Jitariu ◽  
Eugen Melnic ◽  
Marius Raica
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Malignant Tumors ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Endocrine Glands ◽  
Normal Tissues ◽  
Pathological Conditions ◽  
Endothelial Growth Factor

A lot of data suggests endocrine gland-derived vascular endothelial growth factor (EG-VEGF) to be restricted to endocrine glands and to some endocrine-dependent organs. Many evidences show that EG-VEGF stimulates angiogenesis and cell proliferation, although it is not a member of the VEGF family. At the time, a lot of data regarding the role of this growth factor in normal development are available. However, controversial results have been published in the case of pathological conditions and particularly in malignant tumors. Thus, our present paper has been focused on the role of EG-VEGF in normal tissues and various malignant tumors and their angiogenic processes.

scholarly journals Proving the Mode of Action of Phytotoxic Phytochemicals

Plants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1756
Author(s):  
Stephen O. Duke ◽  
Zhiqiang Pan ◽  
Joanna Bajsa-Hirschel
Keyword(s):  
Mode Of Action ◽  
Molecular Target ◽  
Target Site ◽  
Target Protein ◽  
Physiological Effects ◽  
Secondary Effects ◽  
Resistant Form ◽  
The Many

Knowledge of the mode of action of an allelochemical can be valuable for several reasons, such as proving and elucidating the role of the compound in nature and evaluating its potential utility as a pesticide. However, discovery of the molecular target site of a natural phytotoxin can be challenging. Because of this, we know little about the molecular targets of relatively few allelochemicals. It is much simpler to describe the secondary effects of these compounds, and, as a result, there is much information about these effects, which usually tell us little about the mode of action. This review describes the many approaches to molecular target site discovery, with an attempt to point out the pitfalls of each approach. Clues from molecular structure, phenotypic effects, physiological effects, omics studies, genetic approaches, and use of artificial intelligence are discussed. All these approaches can be confounded if the phytotoxin has more than one molecular target at similar concentrations or is a prophytotoxin, requiring structural alteration to create an active compound. Unequivocal determination of the molecular target site requires proof of activity on the function of the target protein and proof that a resistant form of the target protein confers resistance to the target organism.

scholarly journals Genetic variants of vascular endothelial growth factor predict risk and survival of gliomas

Tumor Biology ◽  
2018 ◽  
Vol 40 (3) ◽  
pp. 101042831876627 ◽  
Author(s):  
Paulo Linhares ◽  
Marta Viana-Pereira ◽  
Mónica Ferreira ◽  
Júlia Amorim ◽  
Rui Nabiço ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Odds Ratio ◽  
Multiple Testing ◽  
Cox Regression ◽  
Vascular Endothelial ◽  
Increased Risk ◽  
Endothelial Growth Factor ◽  
Vegf Polymorphisms

The vascular endothelial growth factor regulates angiogenesis that is increased in glioma. VEGF polymorphisms are thought to modulate vascular endothelial growth factor plasma levels and therefore may be implicated in glioma risk. We aimed to clarify the role of VEGF and von Willebrand factor polymorphisms in glioma susceptibility and prognosis. A case–control study of 126 glioma patients and 180 cancer-free controls was performed. Using Sequenom MassARRAY platform, 11 VEGF and 1 VWF polymorphisms were genotyped. Unconditional multivariate logistic regression models were used to calculate odds ratios and 95% confidence intervals. The associations between polymorphisms and survival were evaluated using a Cox regression model. Bonferroni’s adjustment was used to correct for multiple testing. The VEGF polymorphism rs833061 was strongly associated with increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio = 155.66), confirmed after Bonferroni correction. Also, the VEGF polymorphisms rs3024994, rs2010963, and particularly the homozygous carriers of rs1005230 were associated with a worse prognosis for glioma and glioblastoma. Our data support a role of VEGF and VWF polymorphisms as glioma biomarkers, with additional potential relevance for molecular stratification of patients for anti-angiogenic therapies.

scholarly journals Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Clément Mercier ◽  
Marina Rousseau ◽  
Pedro Geraldes
Keyword(s):  
Growth Factor ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Protein Tyrosine ◽  
Collateral Arteries ◽  
Increased Risk ◽  
Artery Disease

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

scholarly journals Animal insulin-like growth factor binding proteins and their biological functions

2012 ◽  
Vol 47 (No. 2 - 3) ◽  
pp. 75-84 ◽  
Author(s):  
Z. Kostecká ◽  
J. Blahovec
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Receptor Activation ◽  
Differential Diagnostics ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Specific Receptors ◽  
Activate Cell

Insulin-like growth factor (IGF-I, IGF-II) action is influenced by until today known eight forms of insulin-like growth factor binding proteins (IGFBPs). They have been obtained not only from some human and animal tissues and body fluids but also from conditioned medium of cell cultures. An important biological property of the IGFBPs is their ability to increase the circulating half-life of the IGFs. They are able to act as potentiators of cell proliferation. As IGFBPs bind to cell surfaces, they may act either to deliver the IGFs to those surfaces for activation of specific receptors or to activate cell responses independently of receptor activation. Phosphorylation, glycosylation and proteolysis of IGFBPs influence their affinity to IGFs. The IGFBPs in the role of inhibitors may block the activity of the IGFs and be used for antimitogenic therapy. In the last time measuring of IGFBPs levels can be used for diagnosis determination of some endocrine diseases or in differential diagnostics.

scholarly journals Analisa Persespsi Masyarakat Pendatang Terhadap Kearifan Lokal Metode Fuzzy Inference System (FIS) Mamdani

KOMTEKINFO ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 188-197
Author(s):  
Silky Safira ◽  
Wifra Safitri
Keyword(s):  
Fuzzy Logic ◽  
Social Life ◽  
Fuzzy Inference ◽  
Immigrant Communities ◽  
Inference System ◽  
The Public ◽  
Cultural Life ◽  
The Many

Fuzzy logic is considered capable of mapping input into output without ignoring existing factors. Fuzzy logic is very flexible and tolerant of existing data. By using fuzzy logic, a model will be produced from a system that is able to estimate the perceptions of immigrants to local wisdom. The factors that influence the determination of immigrants' perceptions of local wisdom with fuzzy logic are the attitude of immigrant communities. Society's socio-cultural life is shown by the many links to other social life, such as ideology, lifestyle, and economy. This means that changes in one socio-cultural life will affect other social and cultural lives. Therefore this system is made so that the public can know, study and examine the variety of local wisdom, examine the role of indigenous and immigrant people in preserving local wisdom and study the strategies of indigenous and immigrant populations in limiting conflict and so on by applying fuzzy mamdani methods that are expected to provide decisions good in responding to the perceptions of immigrants towards local wisdom in West Kinali Pasaman.

Sign in / Sign up

Export Citation Format

Share Document