scholarly journals Brain-Derived Neurotrophic Factor, Neutrophils and Cysteinyl Leukotriene Receptor 1 as Potential Prognostic Biomarkers for Patients with Colon Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5520
Author(s):  
Syrina F. Mehrabi ◽  
Souvik Ghatak ◽  
Lubna M. Mehdawi ◽  
Geriolda Topi ◽  
Shakti Ranjan Satapathy ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Neurotrophic Factor ◽  
Xenograft Model ◽  
Brain Derived Neurotrophic Factor ◽  
Normal Mucosa ◽  
Strong Positive Correlation ◽  
Bdnf Expression ◽  
Mouse Xenograft Model ◽  
Cysteinyl Leukotriene Receptor

The tumor microenvironment has been recognized as a complex network in which immune cells play an important role in cancer progression. We found significantly higher CD66b neutrophil expression in tumor tissue than in matched normal mucosa in the Malmö colon cancer (CC) cohort and poorer survival of stage I-III patients with high CD66b expression. Additionally, mice lacking CysLT1R expression (cysltr1−/−) produce less brain-derived neurotrophic factor (BDNF) compared to WT mice and Montelukast (a CysLT1R antagonist)-treated mice also reduced BDNF expression in a mouse xenograft model with human SW480 CC cells. CD66b and BDNF expression was significantly higher in patient tumor tissues than in the matched normal mucosa. The univariate Cox PH analysis yielded CD66b and BDNF as an independent predictor of overall survival, which was also found in the public TCGA-COAD dataset. We also discovered a strong positive correlation between CD66b, BDNF and CysLT1R expression in the Malmö CC cohort and in the TCGA-COAD dataset. Our data suggest that CD66b/BDNF/CysLT1R expression as a prognostic combined biomarker signature for CC patients.

scholarly journals Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression—Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 688
Author(s):  
Adrian Tiron ◽  
Irina Ristescu ◽  
Paula A. Postu ◽  
Crina E. Tiron ◽  
Florin Zugun-Eloae ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Long Term Effects ◽  
Short Term ◽  
Bdnf Expression ◽  
In Vivo Models

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1α, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.

Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

2019 ◽  
Vol 16 (4) ◽  
pp. 344-352
Author(s):  
Radhika Khosla ◽  
Avijit Banik ◽  
Sushant Kaushal ◽  
Priya Battu ◽  
Deepti Gupta ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurotrophic Factor ◽  
Animal Studies ◽  
Neurodegenerative Disorder ◽  
Indirect Evidence ◽  
Brain Derived Neurotrophic Factor ◽  
Common Disease ◽  
Inverse Association ◽  
Bdnf Expression ◽  
Strong Inverse Association

Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer’s and Parkinson’s disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.

scholarly journals Interferon beta-1a induces expression of brain-derived neurotrophic factor in human T lymphocytes in vitro and not in vivo

2020 ◽  
Vol 15 (1) ◽  
pp. FNL38 ◽  
Author(s):  
Zarlascht Karmand ◽  
Hans-Peter Hartung ◽  
Oliver Neuhaus
Keyword(s):  
T Cell ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Proliferation ◽  
Bdnf Expression ◽  
Healthy Donors

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

scholarly journals Optimization of Taste-Masked (–)-Oleocanthal Effervescent Formulation with Potent Breast Cancer Progression and Recurrence Suppressive Activities

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 515 ◽  
Author(s):  
Tajmim ◽  
Siddique ◽  
El Sayed
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Locoregional Recurrence ◽  
Virgin Olive Oil ◽  
Xenograft Model ◽  
Taste Masking ◽  
Control Group ◽  
Placebo Control ◽  
Her2 Positive ◽  
Mouse Xenograft Model

S-(–)-Oleocanthal (OC), a naturally occurring phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO), is a potential nutraceutical therapeutic for inflammation, neurodegenerative diseases, and many malignancies, especially breast cancer (BC). The oral delivery of OC is challenging because of its irritative, bitter, and pungent taste and exceptional chemistry, including two reactive aldehydes, phenolic, and ester groups. OC irritation did not correlate with CO2-induced irritation, and hence, OC was not exerting generalized acid-sensing irritation. The objective of this study was to develop an effervescent formulation of OC with an effective CO2-induced masked taste maintaining the efficacy against the estrogen receptor (ER) and HER2 positive BC. Several ratios of acid and carbonate sources were screened, and five effervescent formulations EF1-EF5 were selected and prepared based on their pH and effervescence time. OC formulations were characterized using differential scanning calorimetry, FT-IR spectroscopy, and scanning electron microscopy analyses. OC formulations exhibited acceptable flowability and effervescence time. Based on physical characteristics and improved OC release, formulation EF-2 was selected for subsequent studies. EF-2 showed effective OC taste masking, as suggested by electronic artificial tongue and mouse preference tests. EF-2 suppressed more than 70% of the hormone and HER2-positive BT-474 BC cell growth in a nude mouse xenograft model. Furthermore, EF-2 demonstrated significant inhibition of BT-474 tumor cell locoregional recurrence after primary tumor surgical excision. EF-2-treated mouse sera had significantly reduced CA 15-3 levels, the human BC recurrence marker, compared to the placebo control group at the end of the study. These results highlight the potential of the OC formulation EF-2 as a prospective nutraceutical for the control and prevention of ER+/HER+ BC progression and locoregional recurrence.

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