scholarly journals Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Ntombikayise Xelwa ◽  
Geoffrey Patrick Candy ◽  
John Devar ◽  
Jones Omoshoro-Jones ◽  
Martin Smith ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Developed Countries ◽  
Individual Growth ◽  
Growth Factor Signaling ◽  
Cancer Cell Survival ◽  
Future Potential ◽  
The Individual ◽  
Cancer Chemoresistance

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

scholarly journals Growth factor signaling predicts therapy resistance mechanisms and defines neuroblastoma subtypes

Oncogene ◽  
2021 ◽  
Author(s):  
Timofey Lebedev ◽  
Elmira Vagapova ◽  
Pavel Spirin ◽  
Petr Rubtsov ◽  
Olga Astashkova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Protective Action ◽  
Mycn Amplification ◽  
Survival Prediction ◽  
Growth Factor Signaling ◽  
Erk Activation ◽  
Multikinase Inhibitors ◽  
Recurrent Mutations

AbstractNeuroblastoma (NB) has a low frequency of recurrent mutations compared to other cancers, which hinders the development of targeted therapies and novel risk stratification strategies. Multikinase inhibitors have shown potential in treating high-risk NB, but their efficacy is likely impaired by the cancer cells’ ability to adapt to these drugs through the employment of alternative signaling pathways. Based on the expression of 48 growth factor-related genes in 1189 NB tumors, we have developed a model for NB patient survival prediction. This model discriminates between stage 4 NB tumors with favorable outcomes (>80% overall survival) and very poor outcomes (<10%) independently from MYCN-amplification status. Using signaling pathway analysis and gene set enrichment methods in 60 NB patients with known therapy response, we identified signaling pathways, including EPO, NGF, and HGF, upregulated in patients with no or partial response. In a therapeutic setting, we showed that among six selected growth factors, EPO, and NGF showed the most pronounced protective effects in vitro against several promising anti-NB multikinase inhibitors: imatinib, dasatinib, crizotinib, cabozantinib, and axitinib. Mechanistically kinase inhibitors potentiated NB cells to stronger ERK activation by EPO and NGF. The protective action of these growth factors strongly correlated with ERK activation and was ERK-dependent. ERK inhibitors combined with anticancer drugs, especially with dasatinib, showed a synergistic effect on NB cell death. Consideration of growth factor signaling activity benefits NB outcome prediction and tailoring therapy regimens to treat NB.

scholarly journals The Chemokine-Based Peptide, CXCL9(74-103), Inhibits Angiogenesis by Blocking Heparan Sulfate Proteoglycan-Mediated Signaling of Multiple Endothelial Growth Factors

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5090
Author(s):  
Alexandra De Zutter ◽  
Helena Crijns ◽  
Nele Berghmans ◽  
Melissa García-Caballero ◽  
Lotte Vanbrabant ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Endothelial Cell Proliferation ◽  
Growth Factor Signaling ◽  
Angiogenic Growth Factors ◽  
Angiogenic Activity

Growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) are important angiogenesis-mediating factors. They exert their effects not only through their respective receptor tyrosine kinases (RTKs), but they also require molecular pairing with heparan sulfate proteoglycans (HSPGs). Angiogenic growth factors and their signaling pathways are commonly targeted in current anti-angiogenic cancer therapies but have unfortunately insufficient impact on patient survival. Considering their obvious role in pathological angiogenesis, HS-targeting drugs have become an appealing new strategy. Therefore, we aimed to reduce angiogenesis through interference with growth factor-HS binding and downstream signaling using a CXCL9-derived peptide with a high affinity for glycosaminoglycans (GAGs), CXCL9(74-103). We showed that CXCL9(74-103) reduced EGF-, VEGF165- and FGF-2-mediated angiogenic processes in vitro, such as endothelial cell proliferation, chemotaxis, adhesion and sprouting, without exerting cell toxicity. CXCL9(74-103) interfered with growth factor signaling in diverse ways, e.g., by diminishing VEGF165 binding to HS and by direct association with FGF-2. The dependency of CXCL9(74-103) on HS for binding to HMVECs and for exerting its anti-angiogenic activity was also demonstrated. In vivo, CXCL9(74-103) attenuated neovascularization in the Matrigel plug assay, the corneal cauterization assay and in MDA-MB-231 breast cancer xenografts. Additionally, CXCL9(74-103) reduced vascular leakage in the retina of diabetic rats. In contrast, CXCL9(86-103), a peptide with low GAG affinity, showed no overall anti-angiogenic activity. Altogether, our results indicate that CXCL9(74-103) reduces angiogenesis by interfering with multiple HS-dependent growth factor signaling pathways.

Optimization of the care model for elderly in Poland

Physiotherapy ◽  
2013 ◽  
Vol 21 (4) ◽  
Author(s):  
Felicja Lwow ◽  
Małgorzata Korzeniowska ◽  
Joanna Dadacz ◽  
Ewa Hladik ◽  
Agata Łukojko ◽  
...  
Keyword(s):  
Health Care ◽  
Chronic Conditions ◽  
Institutional Care ◽  
Developed Countries ◽  
Social Aspect ◽  
Age Group ◽  
Care Needs ◽  
Optimal Health ◽  
Health Care Models ◽  
The Individual

AbstractThe demographic situation of Poland as well as other developed countries shows a growing number of people at retirement age. According to the data from GUS (Central Statistical Office), their number reached 6.5 mln in Poland in 2011, and the prognosis for shows 8,3 mln by the year 2035. The consequence of this fact is a necessity of including the specificity of this age group in the functioning of Polish health care as well as in preventive medicine and health promotion. Unifying the health needs of this age group would be disadvantageous due to the diversification of physical efficiency level in the psychosomatic and social aspect. Nevertheless, the key problem is to distinguish the optimal health care models which include not only chronic conditions and dysfunctions but also the quality of life and socially independent life style that guarantee the lack of isolation and social exclusion. Distinguishing the four action models, namely people considered as healthy by the system, autonomously functioning people with chronic conditions, and people who need other people or institutional care to function in a society, seems to cover the individual needs of this group. Concluding, the National Health Care needs to work out some proceeding algorithms for these models. The optimal program adjustment for the needs of the target group would most certainly improve the effectiveness of the Health Care.

Associations Between Higher-Order Values Vary with Age, Education, and Income

2020 ◽  
Author(s):  
Maksim Rudnev
Keyword(s):  
Cognitive Abilities ◽  
Developed Countries ◽  
European Social Survey ◽  
Higher Order ◽  
Group Differences ◽  
Social Survey ◽  
Value Structures ◽  
Younger Age ◽  
The Individual ◽  
Representative Samples

A theory of basic human values relies on the similarity of value structures across countries. It has been well established that the quasi-circumplex value structure as a whole is indeed universal. However, less attention has been paid to the associations between specific values. This study investigated associations between four higher-order values across age, education, and income groups. We analyzed the data from national representative samples collected in 29 countries as part of the fourth round of the European Social Survey with a series of multilevel regressions. Younger age, higher levels of education and income coincided with higher independence of the four adjacent higher-order values, whereas among older, less educated, and less wealthy groups, values tended to merge into a single dimension of Social versus Person Focus. These differences were slightly weaker in more economically developed countries. The group differences in value associations may follow from corresponding differences in the degree of societal and individual empowerment, cognitive abilities, and socialization experiences. Accounting for the individual differences in relations between values may bring deeper understanding and higher predictive power to the studies of links between values and various behaviors or attitudes. , value structure, value interactions, European Social Survey

Prevalence and distribution of causes of infertility according to women’s age – a cross-sectional study in a tertiary healthcare hospital setup

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Keerthana Dhandapani ◽  
Bhagyalakshmi Kodavanji ◽  
Vinodini Nithyananda Madom Anantharaya ◽  
Nayanatara Arun Kumar
Keyword(s):  
Tertiary Care ◽  
Developed Countries ◽  
Cross Sectional Study ◽  
Female Infertility ◽  
Secondary Infertility ◽  
Cross Sectional ◽  
Female Population ◽  
Infertile Women ◽  
Tertiary Healthcare ◽  
The Individual

Abstract Objectives Infertility has disastrous consequences, particularly for women. Causes of infertility in developed countries have been investigated but there is a significant lack of data among Indian female population. The aim of the present study was to analyze the causes and the proportion of the individual factors contributing to infertility, considering the age factor. Methods The data of 204 infertile women (18–45 years) were collected from the files in tertiary care hospitals. Causes and age of infertile women were grouped. The prevalence of each cause was evaluated. Data analysis was done using SPSS (Statistical Package for Social Sciences) version 17.0. Results Polycystic ovarian syndrome (PCOS) was the most common (14.71%) cause of female infertility. Ovulatory dysfunctions (25.55%) were the foremost cause in primary infertility, whereas in secondary infertility, uterine factors (26.86%) were most common. The incidence of primary and secondary infertility was more evident in patients who were more than 30 years of age. Conclusions Causes of infertility vary according to the age. The causes of female infertility were unexplained infertility, ovulatory disorders and uterine factors most commonly affecting women at ≤30 years.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

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