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Apoptosis, angiogenesis, inflammation and oxidative stress: basic interactions in patients with early and metastatic breast cancer.

Research Abstract

Purpose

Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC.

Methods

Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-α were measured by immunosorbent assay kits and LPO and NO by chemical methods.

Results

Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls (P < 0.0001). Bcl-2, IL-8, TNF-α, and NO were significantly higher in benign breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001) versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2, IL-8, TNF-α, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-α, LPO, and NO.

Conclusions

BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-α, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-α, and NO are also angiogenic stimulators.

Research Authors
Enas A. Hamed, Madeha M. Zakhary, Doaa W. Maximons.
Research Date
Research Department
Research Journal
Cancer Res Clin Oncol
Research Member
Research Pages
999–1009
Research Vol
138
Research Website
DOI 10.1007/s00432-012-1176-4
Research Year
2012

Apoptotic versus angiogenic factors in gastric and colorectal cancers.

Research Abstract

Objective: Gastric-colon cancer is a complex, multi-stage disease involving deregulation of different signaling cascades. This study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with gastric-colon cancers. Plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; cathepsin D (CD), calpain I and II as proteolytic, apoptotic indices; nitric oxide (NO), lipid peroxides (LPER) as oxidative stress, angiogenic indices, and tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices were measured in gastric-colon cancer patients. Methods: Thirty gastric-colon cancer patients [colorectal (n=20), gastric (n=10) cancers], 30 with benign gastrointestinal tract (GIT) masses and 30 healthy controls, were recruited. sFas, bcl-2 and TNF-α were measured by immunosorbent assay kits, and CD, calpain I and II, LPER and NO by chemical methods. Results: sFas, bcl-2, CD, calpain I, calpain II, NO, and TNF-α were higher in malignant and benign GIT masses than controls, and in malignant than benign masses. In gastric tumors, calpain I, calpain II, CD, LPER, and NO levels were higher than colorectal. In benign and malignant GIT masses, positive correlations were found between sFas, bcl-2, CD, calpain I, calpain II, LPER, NO and TNF- α. Conclusions: Gastric-colon malignancy patients exhibited decreased apoptosis, as evident by an increase in antiapoptotic indices, i.e. sFas and bcl-2, and increased angiogenic activity, as evident by enhanced proteolytic activity of cathepsin-D and calpain I and II. These parameters were higher in gastric than colorectal cancers reflecting aggressive behavior of the earlier. Thus, decreased apoptosis and enhanced angiogenesis give growth priority in gastric-colon cancers, and the angiogenic factors’ blockage may delay the tumor’s spread.

Research Authors
Enas A Hamed, Madeha M Zakhary, Doaa W Maximous, Nagwa S Ahmed, Amany O Mohamed.
Research Date
Research Department
Research Journal
Archives of Clinical and Experimental Surgery
Research Member
Research Pages
71-84
Research Rank
Q2
Research Vol
1
Research Website
DOI: 10.5455/aces.20120216121853
Research Year
1

Hypoxia and oxidative stress markers in pediatric patients undergoing hemodialysis: cross section study.

Research Abstract

Background

Tissue injury due to hypoxia and/or free radicals is common in a variety of disease processes. This cross-sectional study aimed to investigate effect of chronic kidney diseases (CKD) and hemodialysis (HD) on hypoxia and oxidative stress biomarkers.

Methods

Forty pediatric patients with CKD on HD and 20 healthy children were recruited. Plasma hypoxia induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) were measured by specific ELISA kits while, total antioxidant capacity (TAC), total peroxide (TPX), pyruvate and lactate by enzymatic/chemical colorimetric methods. Oxidative stress index (OSI) and lactate/pyruvate (L/P) ratio were calculated.

Results

TAC was significantly lower while TPX, OSI and VEGF were higher in patients at before- and after-dialysis session than controls. Lactate and HIF-1α levels were significantly higher at before-dialysis session than controls. Before dialysis, TAC and L/P ratio were lower than after-dialysis. In before-dialysis session, VEGF correlated positively with pyruvate, HIF-1α and OSI correlated positively with TPX, but, negatively with TAC. In after-dialysis session, HIF-1α correlated negatively with TPX and OSI; while, OSI correlated positively with TPX.

Conclusions

CKD patients succumb considerable tissue hypoxia with oxidative stress. Hemodialysis ameliorated hypoxia but lowered antioxidants as evidenced by decreased levels of HIF-1α and TAC at before- compared to after-dialysis levels.

Research Authors
Enas A Hamed, Taghrid B El-Abaseri, Amany O Mohamed, Ahmed R Ahmed and Tarek H El-Metwally.
Research Date
Research Department
Research Journal
BMC Nephrology
Research Member
Research Pages
136
Research Rank
Q1
Research Vol
13 
Research Website
doi: 10.1186/1471-2369-13-136
Research Year
2012

Effects of Different Routes of Nicotine Administration on Gastric Morphology and Hormonal Secretion in Rats.

Research Abstract

The aim was to assess the effects of different routes of chronic nicotine administration on gastric morphology and hormonal secretion; mainly gastrin, ghrelin, histamine and prostaglandin E2 (PGE2). Forty adult male albino rats were randomly assigned into four groups (10 rats per group), treated for 21 days as follows: control group (given standard rat pellets and water only); oral nicotine-treated group [50 μg (ml drinking water)−1]; intraperitoneal nicotine-treated group [0.5 mg (kg body weight)−1]; and inhaled nicotine-treated group [0.5 mg (kg body weight)−1]. Concentrations of gastrin, ghrelin, PGE2 and histamine in serum and gastric tissue homogenates were assessed using ELISA kits. Stomach fundus was processed for histopathology and immunohistochemistry using light and electron microscopy. Different routes of chronic nicotine administration resulted in a significant increase in serum and gastric homogenate gastrin and ghrelin concentrations and a significant decrease in serum and homogenate PGE2 concentrations compared with the control group. Moreover, nicotine administration via oral and inhalation routes caused gastric erosion, transformation of peptic cells into the mucous variety, a significant increase in parietal cell numbers and an increase in expression of gastrin. In conclusion, the negative impact of nicotine administration on gastric structure that is associated with an increased concentration of gastrin and decreased concentration PGE2 might be the leading cause of gastric/peptic ulcers in heavy smokers. The increased ghrelin concentration and its effect following nicotine chronic administration needs further investigation. Based on these findings, we suggest that the alteration in gastric structure following chronic administration of nicotine can be prevented by reducing gastrin secretion and/or targeting its receptors.
 

Research Authors
Soad Shaker Ali, Enas Ahmed Hamed, Nasra Naeim Ayuob, Ahmed ShakerAli, Mansour Ibrahem Suliman.
Research Date
Research Department
Research Journal
​​​​​​​ Exp Physiol
Research Member
Research Pages
881–895
Research Rank
Q1
Research Vol
100(8)
Research Website
doi: 10.1113/EP085015.
Research Year
2015

Role of Monocyte Chemoattractant Protein-1, Stromal Derived Factor-1 and Retinoic Acid in Pathophysiology of Neuropathic Pain in Rats

Research Authors
Enas A. Hamed, Hanan S. M. Farghaly, Minerva K. Fahmi, Madiha M. Mohammed Makhlouf, Asmaa F. Abdel Mola and Mohamed A. Balfas.
Research Date
Research Department
Research Journal
J Basic Clin Physiol Pharmacol. 
Research Member
Research Pages
411-24
Research Vol
27(4)
Research Year
2016

Plasma levels of transforming growth factor -β1, connective tissue growth factor; soluble factor related apoptosis and urinary levels of desmosine in childhood interstitial lung diseases.

Research Authors
Mostafa M El-Saied, Khaled Saad, Enas A Hamed, Hazem Abu-Zeid Yousef.
Research Date
Research Department
Research Journal
Assiut  Med. J.
Research Member
Research Pages
89-102
Research Vol
40 (1)
Research Year
2016

Childhood Interstitial Lung Disease: Review on Diagnosis and Management.

Research Authors
Enas A Hamed, Mostafa M El-Saied, Khaled Saad, Hazem Abu-Zeid Yousef.
Research Date
Research Department
Research Journal
International Journal of Clinical and Experimental Medical Sciences
Research Member
Research Pages
78-89.
Research Vol
5 (1)
Research Year
2016

Molecular mechanisms underlying fibrosis and elastin destruction in childhood interstitial lung diseases.

Research Abstract


This study aimed to assess the impact of high-fat diet (HFD) and vitamin D3 supplementation on cardiac apoptosis, inflammation, oxidative stress, and cardiac uncoupling proteins (UCPs) 2&3 expression. Forty rats were fed either (45%) or (10%) fat diet with or without vitamin D3 (500 U/kg/day) for 6 months, then cardiac tissue expression of Bax, Bcl2, Fas, Fas-L (markers for apoptotic pathways), TNF-α, MDA7, GPX1 (inflammatory and oxidative markers) and UCP 2&3 were assessed. Results revealed the enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades and increased inflammatory and oxidative burdens on the heart in HFD rats. Downregulation of UCP2 and upregulation of UCP3 gene expression at 6 months. After vitamin D3 supplementation with HFD, cardiac apoptotic, inflammatory and oxidative markers were mitigated and expression of UCP3 was downregulated and UCP2 was upregulated. This work highlights the novel cardioprotective effect of vitamin D3 in the experimental model of HFD feeding through the downregulation of UCP3.

Research Authors
Enas A. Hamed, Mostafa M. El-Saieda, Khaled Saad, Hazem Abu-Zeid Yousef, Amany O. Mohamed, Dina Sabry.
Research Date
Research Department
Research Journal
Pathophysiology
Research Member
Research Pages
275-283.
Research Rank
Q2
Research Vol
23
Research Year
2016

Efficacy of oral agar in management of indirect hyperbilirubinemia in full-term neonates.

Research Abstract

Aim

This prospective randomized case control study aimed to investigate effect of oral agar administration in reducing total serum bilirubin (TSB) levels in full-term neonates with jaundice in comparison with control.

Materials and methods

One hundred sixty full-term neonates were enrolled with TSB 10–19 mg/dl at first week of age from Assiut University Children’s Hospital. Neonates were divided according to TSB into outpatient group (n = 100) (TSB 10–15 mg/dl) and admitted group (n = 60) (TSB > 15–19 mg/dl). Outpatients group were subdivided into agar group received oral agar and control group received placebo. Admitted group were subdivided into agar group received oral agar plus phototherapy combination and control group received phototherapy alone. Neonates in the agar supplementation received oral agar 600 mg/kg/day dissolved in 10 ml distilled water twice daily till TSB decreased to 7 mg/dl. Daily weight, stool frequency and side effects of treatment were observed for each group. TSB was determined pretreatment then serially every 48 h until TSB level reaching ≤7 mg/dl.

Results

Agar fed was effective in lowering TSB in neonates with TSB 10–15 mg/dl. TSB percentage changes were not significantly lower in agar-fed newborn with TSB >15–19 mg/dl compared with control groups after 24 h and 7 days. Age fed shortened the time required to decrease TSB and increased stooling frequency.

Conclusions

Oral agar supplemented feeding at 600 mg/kg/day is safe for full-term neonates and useful in decreasing TSB and phototherapy duration. The efficacy of phototherapy in decreasing TSB level in neonatal hyperbilirubinemia can be augmented with oral agar usage.

Research Authors
Safwat M. Abdel-Aziz Ali, Shereen Mansour Galal, Shaban M. Sror, Omima, Hussein, Abd-El-Haseeb Osman Abd-El-Haseeb Ahmed & Enas A. Hamed.
Research Date
Research Department
Research Journal
The Journal Of Maternal-Fetal & Neonatal Medicine
Research Member
Research Publisher
Taylor & Francis
Research Rank
Q3
Research Website
https://doi.org/10.1080/14767058.2020.1740674

Behavioral problems in children with primary monosymptomatic nocturnal enuresis.

Research Abstract

Background and objectives

Primary monosymptomatic nocturnal enuresis (PMNE) is a common distressing condition to children and parents. This study aimed to determine frequencies, severities and characteristics of behavioral problems with PMNE.

Methods

This cross-sectional study included 80 children with PMNE (age: 12.58 ± 1.24 yrs.; boys = 58, girls = 22) and 60 healthy children. Behavioral symptoms were assessed by Strength and Difficulties Questionnaire (SDQ).

Results

This study included 80 children (boys/girls ratio = 2.64:1) with PMNE. They had mean age of 12.58 ± 1.24 yrs. The majority (70%) had good response to medical treatment. Compared to controls, children with enuresis had higher frequencies of emotional, conduct and hyperactivity-inattention symptoms and peer relationship and prosocial problems and higher total (P = 0.001) and different subscales' scores of SDQ. There was an overlap of behavioral problems in 52.2% of children with nocturnal enuresis. Compared to children without behavioral symptoms, children with behavioral symptoms were significantly older at age at presentation (P = 0.046) regardless of gender, residence and type or response to medications. Multiple regression analysis showed that emotional [β = 0.053 (95%CI = 0.037–0.084), P = 0.024] and hyperactivity-inattention symptoms [β = 0.063 (95%CI = 0.028–0.097), P = 0.001] were significantly associated with enuresis independent to other problems.

Conclusion

PMNE is associated with higher risk of behavioral problems particularly emotional and hyperactivity-inattention symptoms indicating externalizing and internalizing problems, therefore, the importance of early non-pharmacological or/and drug interventions. The comorbid behavioral disorders should be treated separately according to evidence-based recommendations to prevent persistence of enuresis and the development of psychiatric disorders in the future.

 

Research Authors
Sherifa Ahmed Hamed, Mohamed Fawzy, Enas Ahmed Hamed.
Research Date
Research Department
Research Journal
Comprehensive Psychiatry
Research Member
Research Pages
152208
Research Publisher
Elsaviere
Research Rank
Q1
Research Vol
104
Research Website
Show more Add to Mendeley Share Cite https://doi.org/10.1016/j.comppsych.2020.152208
Research Year
2021
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