Laila Eissa | Mansoura University (original) (raw)
Papers by Laila Eissa
Naunyn-Schmiedeberg's Archives of Pharmacology, 2024
Chemico-Biological Interactions, Oct 1, 2018
Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of copti... more Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of coptis. Liver fibrosis is a worldwide health problem with no established therapy until now. The aim of our study is to investigate the efficacy of BBR on hepatic fibrosis induced in rats and to uncover other mechanisms. Rats were injected with thioacetamide (TAA) (200 mg/kg, i.p) twice per week for 6 weeks to induce fibrosis. Treated groups were gavaged with BBR (50 mg/kg/day, p.o) simultaneously with TAA injection. Hepatic antioxidant enzymes (catalase, SOD, GPx) were assessed in hepatic homogenate. Their activities were attenuated by TAA injection and elevated by BBR administration. Additionally, serum IL-6 and mRNA levels of IL-1β, IL-6, IL-10 and IFN-γ were evaluated as inflammatory markers. Our results showed that BBR suppressed the inflammation induced by TAA injection. Tissue expression of α-SMA (marker of activated HSCs), TGF-β1 and fibronectin were measured by immunohistochemistry as well as mRNA expressions of TGF-β1 and fibronectin were quantified as fibrotic markers. The collagen deposition in hepatic tissues was assessed by Masson's trichome staining. BBR significantly alleviated TGF-β1 production, decreased collagen and fibronectin deposition and consequently attenuated hepatic fibrogenesis. Akt pathway controls cell survival, proliferation, migration and adhesion. The relative phosphorylation of Akt was determined in hepatic homogenates that was increased with TAA injection and decreased by BBR treatment. Inhibition of Akt pathway has been linked to the intrinsic pathway of apoptosis. Caspase-3, caspase-9, Bcl-2 and Bax were quantified as apoptotic markers using qPCR and also caspase-3 by immunohistochemistry. BBR-treated rats showed an increase in the expression of apoptotic markers. Moreover, BBR-treated rats showed restoration of normal liver lobular architecture as shown by H&E staining. In conclusion, BBR is a potential therapeutic candidate for liver fibrosis owing to its antioxidant and anti-inflammatory activities.
International Immunopharmacology, May 1, 2023
Journal of Gastrointestinal and Digestive System, Mar 16, 2015
PubMed, 2018
The aim of this study is to investigate the antitumor activity and possible molecular mechanism o... more The aim of this study is to investigate the antitumor activity and possible molecular mechanism of Phenethyl isothiocyanate (PEITC) against Ehrlich ascites carcinoma in-vivo and in-vitro. In-vivo, ascetic fluid volume, body weight, serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined using Ehrlich ascites carcinoma (EAC) bearing mice. In-vitro, MTT assay was used. RT-PCR was used to investigate role of PEITC in apoptosis by analyzing the expression of Bax, caspase-9, and Bcl-2 genes. The effect of PEITC on caspase-9 enzyme activity was also tested. PEITC and/or Doxorubicin (Dox) treatment significantly suppressed EAC growth as compared to EAC/oil control mice. PEITC treatment showed a dose-dependent inhibition of EAC cells as indicated by MTT assay. We found that significant increase in MDA level and decrease in TAC caused by Dox treatment were significantly reduced by combination with PEITC treatment. Bax, caspase-9 genes' expression and caspase-9 enzymatic activity were significantly increased, while Bcl-2 gene expression was significantly decreased in PEITC treated mice. PEITC may act as a promising anticancer agent either alone or more effectively in combination with Dox through apoptotic cell death induction.
International Immunopharmacology, Jun 1, 2023
Bulletin of Pharmaceutical Sciences, Jun 1, 2023
Liver disease causes about 2 million deaths yearly in the world. Caffeine (Caff) is the most comm... more Liver disease causes about 2 million deaths yearly in the world. Caffeine (Caff) is the most common psychoactive substance utilized around the world. Caff has been demonstrated to possess anti-fibrotic actions in the liver. Silymarin (Sily) is a natural product largely used for its hepatoprotective actions through antioxidant, anti-inflammatory, and anti-fibrotic effects. Aim of the study: The current study aims to investigate the hepatoprotective and antioxidant effects of Caff and Sily alone or in combination in a rat model of liver fibrosis focusing on their effects on lysophosphatidic acid receptor 3 (LPAR3) expression. Materials and methods: 200 mg/kg of thioacetamide (TAA) was injected intraperitoneally twice weekly for 8 weeks to induce liver fibrosis. Caff, Sily, and their combination were orally administered to rats at a dose of 50 mg/kg/day for 8 weeks together with TAA injection. Results: Caff and Sily alone or in combination significantly improved liver function tests compared with fibrotic group. Moreover, they significantly decreased hepatic malondialdehyde (MDA) content and significantly increased the hepatic glutathione (GSH) concentration as compared with the fibrotic group. They significantly decreased fibrosis and necro-inflammatory scores with a superior significant effect in the necro-inflammatory score for the combination group each drug alone. Caff and Sily alone or in combination significantly decreased the hepatic LPAR3 gene and tissue expression, which was significantly correlated to their hepatoprotective effects. Conclusion: Caff and Sily alone or in combination protected against hepatic fibrosis through down-regulation of LPAR3 as well as antioxidant effects.
Prostaglandins Leukotrienes and Essential Fatty Acids, Sep 1, 2018
Journal of Biochemical and Molecular Toxicology, Jun 23, 2023
Diabetic nephropathy (DN) is a worldwide issue that eventually leads to end‐stage renal failure, ... more Diabetic nephropathy (DN) is a worldwide issue that eventually leads to end‐stage renal failure, with limited therapeutic options. Prior research has revealed that gold nanoparticles (AuNPs) have a substantial antidiabetic impact. In addition, sodium‐glucose cotransporter2 (SGLT2) inhibitors, including dapagliflozin (DAPA), had renoprotective impact on DN. Therefore, this research attempted to determine the potential AuNPs and DAPA impacts in ameliorating experimentally DN induction and the underlying mechanisms focusing on miR‐192 and miR‐21, correlating them with autophagy, apoptosis, fibrosis, and oxidative stress. Diabetes induction was through a single intraperitoneal streptozotocin (55 mg/kg) injection, and rats with diabetes received AuNPs (2.5 mg/kg/day) as well as DAPA (2 mg/kg/day) for 7 weeks as a treatment. AuNPs and DAPA treatment for 7 weeks substantially alleviated DN. AuNPs and DAPA significantly increased catalase (CAT) activity as well as serum total antioxidant capacity (TAC), along with a substantial decline in malondialdehyde (MDA). AuNPs and DAPA treatment alleviated renal fibrosis as they decreased transforming growth factorß1(TGF‐ß1) as well as matrix metalloproteinase‐2 (MMP‐2) renal expression, decreased apoptosis through alleviating the proapoptotic gene (caspase‐3) renal expression and increased the antiapoptotic gene (Bcl‐2) renal expression, and increased autophagy as they increased LC‐3 as well as Beclin‐1 renal expression. Autophagy activation, inhibition of apoptosis, and renal fibrosis could be due to their inhibitory impact on miR‐192 and miR‐21 renal expression. AuNPs and DAPA have a protective effect on DN in rats by targeting miR‐192 and miR‐21 and their downstream pathways, including fibrosis, apoptosis, autophagy, and oxidative stress.
Life Sciences, Sep 1, 2019
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide.... more Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Indeed, chemotherapeutic drugs-induced systemic toxicity results in suboptimal cancer treatment. Consequently, there is a need for exploring of a safe and effective therapy for cancer patients. This study aimed to evaluate the hepatoprotective effect of thymoquinone (TQ) against thioacetamide (TAA)-induced HCC. Also, we investigated TQ's ability to sensitize cancer cells toward TRAIL/TRAILR2 apoptotic pathway. Main metods Forty male Sprague Dawely rats were divided into 4 groups (n=10) as follows: control group, CMC group, HCC group and HCC+TQ group. Serum levels of liver function biomarkers and Alpha-Fetoprotein (AFP), as well as hepatic levels of glutathione (GSH) and Alpha-Fetoprotein (MDA) were measured. Transforming growth factorbeta 1 (TGF-β1), TRAILR2, TRAIL, caspase-3, caspase-9, caspase-8 and B cell lymphoma-2 (Bcl-2) mRNA levels were assessed by Quantitative, Real-Time PCR. fibrosis percentage and necroinflammation were quantified by histopathological examination. Key findings Our results indicated improvement in liver functions, decrease in AFP level and attenuation of HCC progression in TQ treated rats. TQ upregulated TRAIL/TRAILR2 and subsequently enhanced apoptosis as hinted by caspase-3 upregulation and Bcl-2 downregulation. Also, TQ decreased TGF-β1 gene expression level. Moreover, HCC+TQ group showed significant increase in hepatic GSH level and marked decrease in hepatic MDA level. Significance This study proved that TQ is able to suppress HCC development via decreasing oxidative stress, suppression of TGF-β1 and induction of TRAIL-mediated apoptosis.
PLOS ONE
Purpose Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis i... more Purpose Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis in breast and colorectal cancer. However, the evidence is still inconclusive for bladder cancer (BC). Herein, we investigated the diagnosis and prognosis roles of serum levels of 25(OHD) in suspected BC patients presented by hematuria. Methods This prospective cohort study involved suspected patients of BC presented with hematuria. Patients were evaluated by CT urogram, office cystoscopy and urine cytology with subsequent inpatient biopsy for positive findings. Baseline blood samples were collected for measurement of 25(OHD) by electrochemiluminescence binding assay at the time of diagnosis. Patients with non-muscle-invasive BC (NMIBC) underwent transurethral resection of bladder tumor (TURBT) and adjuvant intravesical chemotherapy or BCG instillation. Patients were followed up for their recurrence status during 10 to 24 months. Recurrence was defined as the first time of NMIBC pathologic...
The Journal of Urology, 2020
surgical template appears to improve staging and outcome of the disease, there continues to be su... more surgical template appears to improve staging and outcome of the disease, there continues to be substantial variation in the performance of LND. We aimed to evaluate the factors associated with the performance and yield of LND during radical cystectomy and pelvic lymph node dissection in non-muscle invasive bladder cancer. METHODS: We queried the National Cancer Database to evaluate patients with clinical stage II and III urothelial carcinoma of the bladder that were treated with radical cystectomy and lymph node dissection with or without neoadjuvant chemotherapy (NAC). We used multivariable linear regression models to evaluate baseline clinical, sociodemographic and health system factors associated with yield of LND. RESULTS: We identified 17,169 patients with urothelial carcinoma who underwent cystectomy for clinical stage II and III disease. From this cohort, 2,009 (11.7%) did not receive LND. In patients with cystectomy and LND, 75% of patients were male, 87.3% had stage II disease, and 42.3% received NAC. Mean lymph nodes examined for the entire cohort was 15.1 10.9 (Median: 13, IQR: 7-21). After multivariable linear regression analysis, greater lymph node count was independently associated with NAC (beta coefficient: 1.2, p<0.001), higher income (beta coefficient: 2.06; P <0.001), and urban status (beta coefficient: 2.1, p<0.001). There were also regional differences in LND yield: patients in institutions from Middle Atlantic region (NY, NJ, PA) had 3.1 more nodes, from East North Central (IL, IN, MI, OH, WI) 3.9 more nodes, and from Pacific region (AK, CA, HI, OR, WA) 6.3 more nodes than institutions in the East South Central region (AL, KY, MS, TN). Compared to community hospitals, Academic/Research programs had 3.4 more nodes examined (P: <0.001). This study is limited by absent information relating to surgical template or pathological analysis. CONCLUSIONS: Pelvic lymph node dissection is not universal at the time of RC for urothelial carcinoma of the bladder. Several factors were associated with greater lymph node yield including receipt of neoadjuvant chemotherapy, specific regions of the country, as well as sociodemographic factors.
Investigative Ophthalmology & Visual Science, 2016
Egyptian Journal of Basic and Applied Sciences, 2018
Patients were classified according to the American Joint Committee on Cancer (AJCC) TNM system [1... more Patients were classified according to the American Joint Committee on Cancer (AJCC) TNM system [16] to stage 0 (3 patients), stage I (9 patients), stage II (12 patients), stage III (13 patients) and stage IV (38 patients). The patients and controls do not have renal, liver disorders or any other type of malignancies. Recorded clinical and pathological features for each patient were obtained from Oncology Center including age, grade, stage, serum
Life Sciences, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Chemico-biological interactions, Jan 5, 2018
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptim... more Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks. After the 16th week, rats were further divided into different groups (n = 10) and treated for 7 weeks. CQ group (received CQ 25 mg/kg/day; orally), DOX group (received DOX 1 mg/kg; ip; 2 times/week) and CQ/DOX group. Liver function biomarkers, AFP, hepatic levels of MDA and GSH, serum CK-MB and LDH enzymes activity were measured. Quantitative, Real-Time PCR was used to measure TRAIL, TRAIL...
Journal of Neuroimmunology, 2014
Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local pr... more Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local productions of reactive oxygen species and inflammatory mediators from activated microglial cells have been hypothesized to underlie apoptotic processes. We previously demonstrated that the anti-inflammatory effect of adenosine, through A2A receptor activation had profound protective influence against retinal injury in traumatic optic neuropathy. This protective effect is limited due to rapid cellular re-uptake of adenosine by equilibrative nucleotside transporter-1 (ENT1) or break down by adenosine kinase (AK), the key enzyme in adenosine clearance pathway. Further, the use of adenosine receptors agonists are limited by systemic side effects. Therefore, we seek to investigate the potential role of amplifying the endogenous ambient level of adenosine by pharmacological inhibition of AK. We tested our hypothesis by comparing TON-induced retinal injury in mice with and without ABT-702 treatment, a selective AK inhibitor (AKI). The retinal-protective effect of ABT-702 was demonstrated by significant reduction of Iba-1, ENT1, TNF-α, IL-6, and iNOS/nNOS protein or mRNA expression in TON as revealed by western blot and real time PCR. TON-induced superoxide anion generation and nitrotyrosine expression were reduced in ABT-702 treated mice retinal sections as determined by immunoflourescence. In addition, ABT-702 attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells. The results of the present investigation suggested that ABT-702 had a protective role against marked TON-induced retinal inflammation and damage by augmenting the endogenous therapeutic effects of site- and event-specific accumulation of extracellular adenosine.
Cancer Research, 2017
Recent findings have shown that the Heat Shock Protein 90 (Hsp90) co-chaperone UNC45A is overexpr... more Recent findings have shown that the Heat Shock Protein 90 (Hsp90) co-chaperone UNC45A is overexpressed in ovarian and breast cancers. Previously, we have shown that UNC45A is a centrosomal protein essential for cervical tumor cell growth through activation of the checkpoint kinase 1 (ChK1). In this report, we further examined the role of UNC45A in breast tumorigenesis using a variety of biochemical and cell biology techniques and animal models. We confirmed that UNC45A is highly overexpressed in human breast-infiltrating ductal carcinomas as compared to adjacent normal tissues. Silencing UNC45A in vitro blocked the proliferation of all breast cancer subtypes and drastically reduced tumor growth of the triple negative MDA-MB-231 cell line implanted in mammary fat pads of NOD/SCID mice. However, loss of UNC45A did not affect the proliferation of normal mammary cells. Remarkably, UNC45A becomes more nuclear in human cancer tissues and cancer cell lines as compared to normal tissues and...
Russian Chemical Bulletin, 2016
Naunyn-Schmiedeberg's Archives of Pharmacology, 2024
Chemico-Biological Interactions, Oct 1, 2018
Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of copti... more Berberine (BBR) is an isoquinoline alkaloid extracted from the roots, rhizomes and stems of coptis. Liver fibrosis is a worldwide health problem with no established therapy until now. The aim of our study is to investigate the efficacy of BBR on hepatic fibrosis induced in rats and to uncover other mechanisms. Rats were injected with thioacetamide (TAA) (200 mg/kg, i.p) twice per week for 6 weeks to induce fibrosis. Treated groups were gavaged with BBR (50 mg/kg/day, p.o) simultaneously with TAA injection. Hepatic antioxidant enzymes (catalase, SOD, GPx) were assessed in hepatic homogenate. Their activities were attenuated by TAA injection and elevated by BBR administration. Additionally, serum IL-6 and mRNA levels of IL-1β, IL-6, IL-10 and IFN-γ were evaluated as inflammatory markers. Our results showed that BBR suppressed the inflammation induced by TAA injection. Tissue expression of α-SMA (marker of activated HSCs), TGF-β1 and fibronectin were measured by immunohistochemistry as well as mRNA expressions of TGF-β1 and fibronectin were quantified as fibrotic markers. The collagen deposition in hepatic tissues was assessed by Masson&amp;#39;s trichome staining. BBR significantly alleviated TGF-β1 production, decreased collagen and fibronectin deposition and consequently attenuated hepatic fibrogenesis. Akt pathway controls cell survival, proliferation, migration and adhesion. The relative phosphorylation of Akt was determined in hepatic homogenates that was increased with TAA injection and decreased by BBR treatment. Inhibition of Akt pathway has been linked to the intrinsic pathway of apoptosis. Caspase-3, caspase-9, Bcl-2 and Bax were quantified as apoptotic markers using qPCR and also caspase-3 by immunohistochemistry. BBR-treated rats showed an increase in the expression of apoptotic markers. Moreover, BBR-treated rats showed restoration of normal liver lobular architecture as shown by H&amp;amp;E staining. In conclusion, BBR is a potential therapeutic candidate for liver fibrosis owing to its antioxidant and anti-inflammatory activities.
International Immunopharmacology, May 1, 2023
Journal of Gastrointestinal and Digestive System, Mar 16, 2015
PubMed, 2018
The aim of this study is to investigate the antitumor activity and possible molecular mechanism o... more The aim of this study is to investigate the antitumor activity and possible molecular mechanism of Phenethyl isothiocyanate (PEITC) against Ehrlich ascites carcinoma in-vivo and in-vitro. In-vivo, ascetic fluid volume, body weight, serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined using Ehrlich ascites carcinoma (EAC) bearing mice. In-vitro, MTT assay was used. RT-PCR was used to investigate role of PEITC in apoptosis by analyzing the expression of Bax, caspase-9, and Bcl-2 genes. The effect of PEITC on caspase-9 enzyme activity was also tested. PEITC and/or Doxorubicin (Dox) treatment significantly suppressed EAC growth as compared to EAC/oil control mice. PEITC treatment showed a dose-dependent inhibition of EAC cells as indicated by MTT assay. We found that significant increase in MDA level and decrease in TAC caused by Dox treatment were significantly reduced by combination with PEITC treatment. Bax, caspase-9 genes' expression and caspase-9 enzymatic activity were significantly increased, while Bcl-2 gene expression was significantly decreased in PEITC treated mice. PEITC may act as a promising anticancer agent either alone or more effectively in combination with Dox through apoptotic cell death induction.
International Immunopharmacology, Jun 1, 2023
Bulletin of Pharmaceutical Sciences, Jun 1, 2023
Liver disease causes about 2 million deaths yearly in the world. Caffeine (Caff) is the most comm... more Liver disease causes about 2 million deaths yearly in the world. Caffeine (Caff) is the most common psychoactive substance utilized around the world. Caff has been demonstrated to possess anti-fibrotic actions in the liver. Silymarin (Sily) is a natural product largely used for its hepatoprotective actions through antioxidant, anti-inflammatory, and anti-fibrotic effects. Aim of the study: The current study aims to investigate the hepatoprotective and antioxidant effects of Caff and Sily alone or in combination in a rat model of liver fibrosis focusing on their effects on lysophosphatidic acid receptor 3 (LPAR3) expression. Materials and methods: 200 mg/kg of thioacetamide (TAA) was injected intraperitoneally twice weekly for 8 weeks to induce liver fibrosis. Caff, Sily, and their combination were orally administered to rats at a dose of 50 mg/kg/day for 8 weeks together with TAA injection. Results: Caff and Sily alone or in combination significantly improved liver function tests compared with fibrotic group. Moreover, they significantly decreased hepatic malondialdehyde (MDA) content and significantly increased the hepatic glutathione (GSH) concentration as compared with the fibrotic group. They significantly decreased fibrosis and necro-inflammatory scores with a superior significant effect in the necro-inflammatory score for the combination group each drug alone. Caff and Sily alone or in combination significantly decreased the hepatic LPAR3 gene and tissue expression, which was significantly correlated to their hepatoprotective effects. Conclusion: Caff and Sily alone or in combination protected against hepatic fibrosis through down-regulation of LPAR3 as well as antioxidant effects.
Prostaglandins Leukotrienes and Essential Fatty Acids, Sep 1, 2018
Journal of Biochemical and Molecular Toxicology, Jun 23, 2023
Diabetic nephropathy (DN) is a worldwide issue that eventually leads to end‐stage renal failure, ... more Diabetic nephropathy (DN) is a worldwide issue that eventually leads to end‐stage renal failure, with limited therapeutic options. Prior research has revealed that gold nanoparticles (AuNPs) have a substantial antidiabetic impact. In addition, sodium‐glucose cotransporter2 (SGLT2) inhibitors, including dapagliflozin (DAPA), had renoprotective impact on DN. Therefore, this research attempted to determine the potential AuNPs and DAPA impacts in ameliorating experimentally DN induction and the underlying mechanisms focusing on miR‐192 and miR‐21, correlating them with autophagy, apoptosis, fibrosis, and oxidative stress. Diabetes induction was through a single intraperitoneal streptozotocin (55 mg/kg) injection, and rats with diabetes received AuNPs (2.5 mg/kg/day) as well as DAPA (2 mg/kg/day) for 7 weeks as a treatment. AuNPs and DAPA treatment for 7 weeks substantially alleviated DN. AuNPs and DAPA significantly increased catalase (CAT) activity as well as serum total antioxidant capacity (TAC), along with a substantial decline in malondialdehyde (MDA). AuNPs and DAPA treatment alleviated renal fibrosis as they decreased transforming growth factorß1(TGF‐ß1) as well as matrix metalloproteinase‐2 (MMP‐2) renal expression, decreased apoptosis through alleviating the proapoptotic gene (caspase‐3) renal expression and increased the antiapoptotic gene (Bcl‐2) renal expression, and increased autophagy as they increased LC‐3 as well as Beclin‐1 renal expression. Autophagy activation, inhibition of apoptosis, and renal fibrosis could be due to their inhibitory impact on miR‐192 and miR‐21 renal expression. AuNPs and DAPA have a protective effect on DN in rats by targeting miR‐192 and miR‐21 and their downstream pathways, including fibrosis, apoptosis, autophagy, and oxidative stress.
Life Sciences, Sep 1, 2019
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide.... more Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Indeed, chemotherapeutic drugs-induced systemic toxicity results in suboptimal cancer treatment. Consequently, there is a need for exploring of a safe and effective therapy for cancer patients. This study aimed to evaluate the hepatoprotective effect of thymoquinone (TQ) against thioacetamide (TAA)-induced HCC. Also, we investigated TQ's ability to sensitize cancer cells toward TRAIL/TRAILR2 apoptotic pathway. Main metods Forty male Sprague Dawely rats were divided into 4 groups (n=10) as follows: control group, CMC group, HCC group and HCC+TQ group. Serum levels of liver function biomarkers and Alpha-Fetoprotein (AFP), as well as hepatic levels of glutathione (GSH) and Alpha-Fetoprotein (MDA) were measured. Transforming growth factorbeta 1 (TGF-β1), TRAILR2, TRAIL, caspase-3, caspase-9, caspase-8 and B cell lymphoma-2 (Bcl-2) mRNA levels were assessed by Quantitative, Real-Time PCR. fibrosis percentage and necroinflammation were quantified by histopathological examination. Key findings Our results indicated improvement in liver functions, decrease in AFP level and attenuation of HCC progression in TQ treated rats. TQ upregulated TRAIL/TRAILR2 and subsequently enhanced apoptosis as hinted by caspase-3 upregulation and Bcl-2 downregulation. Also, TQ decreased TGF-β1 gene expression level. Moreover, HCC+TQ group showed significant increase in hepatic GSH level and marked decrease in hepatic MDA level. Significance This study proved that TQ is able to suppress HCC development via decreasing oxidative stress, suppression of TGF-β1 and induction of TRAIL-mediated apoptosis.
PLOS ONE
Purpose Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis i... more Purpose Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis in breast and colorectal cancer. However, the evidence is still inconclusive for bladder cancer (BC). Herein, we investigated the diagnosis and prognosis roles of serum levels of 25(OHD) in suspected BC patients presented by hematuria. Methods This prospective cohort study involved suspected patients of BC presented with hematuria. Patients were evaluated by CT urogram, office cystoscopy and urine cytology with subsequent inpatient biopsy for positive findings. Baseline blood samples were collected for measurement of 25(OHD) by electrochemiluminescence binding assay at the time of diagnosis. Patients with non-muscle-invasive BC (NMIBC) underwent transurethral resection of bladder tumor (TURBT) and adjuvant intravesical chemotherapy or BCG instillation. Patients were followed up for their recurrence status during 10 to 24 months. Recurrence was defined as the first time of NMIBC pathologic...
The Journal of Urology, 2020
surgical template appears to improve staging and outcome of the disease, there continues to be su... more surgical template appears to improve staging and outcome of the disease, there continues to be substantial variation in the performance of LND. We aimed to evaluate the factors associated with the performance and yield of LND during radical cystectomy and pelvic lymph node dissection in non-muscle invasive bladder cancer. METHODS: We queried the National Cancer Database to evaluate patients with clinical stage II and III urothelial carcinoma of the bladder that were treated with radical cystectomy and lymph node dissection with or without neoadjuvant chemotherapy (NAC). We used multivariable linear regression models to evaluate baseline clinical, sociodemographic and health system factors associated with yield of LND. RESULTS: We identified 17,169 patients with urothelial carcinoma who underwent cystectomy for clinical stage II and III disease. From this cohort, 2,009 (11.7%) did not receive LND. In patients with cystectomy and LND, 75% of patients were male, 87.3% had stage II disease, and 42.3% received NAC. Mean lymph nodes examined for the entire cohort was 15.1 10.9 (Median: 13, IQR: 7-21). After multivariable linear regression analysis, greater lymph node count was independently associated with NAC (beta coefficient: 1.2, p<0.001), higher income (beta coefficient: 2.06; P <0.001), and urban status (beta coefficient: 2.1, p<0.001). There were also regional differences in LND yield: patients in institutions from Middle Atlantic region (NY, NJ, PA) had 3.1 more nodes, from East North Central (IL, IN, MI, OH, WI) 3.9 more nodes, and from Pacific region (AK, CA, HI, OR, WA) 6.3 more nodes than institutions in the East South Central region (AL, KY, MS, TN). Compared to community hospitals, Academic/Research programs had 3.4 more nodes examined (P: <0.001). This study is limited by absent information relating to surgical template or pathological analysis. CONCLUSIONS: Pelvic lymph node dissection is not universal at the time of RC for urothelial carcinoma of the bladder. Several factors were associated with greater lymph node yield including receipt of neoadjuvant chemotherapy, specific regions of the country, as well as sociodemographic factors.
Investigative Ophthalmology & Visual Science, 2016
Egyptian Journal of Basic and Applied Sciences, 2018
Patients were classified according to the American Joint Committee on Cancer (AJCC) TNM system [1... more Patients were classified according to the American Joint Committee on Cancer (AJCC) TNM system [16] to stage 0 (3 patients), stage I (9 patients), stage II (12 patients), stage III (13 patients) and stage IV (38 patients). The patients and controls do not have renal, liver disorders or any other type of malignancies. Recorded clinical and pathological features for each patient were obtained from Oncology Center including age, grade, stage, serum
Life Sciences, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Chemico-biological interactions, Jan 5, 2018
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptim... more Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks. After the 16th week, rats were further divided into different groups (n = 10) and treated for 7 weeks. CQ group (received CQ 25 mg/kg/day; orally), DOX group (received DOX 1 mg/kg; ip; 2 times/week) and CQ/DOX group. Liver function biomarkers, AFP, hepatic levels of MDA and GSH, serum CK-MB and LDH enzymes activity were measured. Quantitative, Real-Time PCR was used to measure TRAIL, TRAIL...
Journal of Neuroimmunology, 2014
Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local pr... more Traumatic optic neuropathy (TON) is associated with apoptosis of retinal ganglion cells. Local productions of reactive oxygen species and inflammatory mediators from activated microglial cells have been hypothesized to underlie apoptotic processes. We previously demonstrated that the anti-inflammatory effect of adenosine, through A2A receptor activation had profound protective influence against retinal injury in traumatic optic neuropathy. This protective effect is limited due to rapid cellular re-uptake of adenosine by equilibrative nucleotside transporter-1 (ENT1) or break down by adenosine kinase (AK), the key enzyme in adenosine clearance pathway. Further, the use of adenosine receptors agonists are limited by systemic side effects. Therefore, we seek to investigate the potential role of amplifying the endogenous ambient level of adenosine by pharmacological inhibition of AK. We tested our hypothesis by comparing TON-induced retinal injury in mice with and without ABT-702 treatment, a selective AK inhibitor (AKI). The retinal-protective effect of ABT-702 was demonstrated by significant reduction of Iba-1, ENT1, TNF-α, IL-6, and iNOS/nNOS protein or mRNA expression in TON as revealed by western blot and real time PCR. TON-induced superoxide anion generation and nitrotyrosine expression were reduced in ABT-702 treated mice retinal sections as determined by immunoflourescence. In addition, ABT-702 attenuated p-ERK1/2 and p-P38 activation in LPS induced activated mouse microglia cells. The results of the present investigation suggested that ABT-702 had a protective role against marked TON-induced retinal inflammation and damage by augmenting the endogenous therapeutic effects of site- and event-specific accumulation of extracellular adenosine.
Cancer Research, 2017
Recent findings have shown that the Heat Shock Protein 90 (Hsp90) co-chaperone UNC45A is overexpr... more Recent findings have shown that the Heat Shock Protein 90 (Hsp90) co-chaperone UNC45A is overexpressed in ovarian and breast cancers. Previously, we have shown that UNC45A is a centrosomal protein essential for cervical tumor cell growth through activation of the checkpoint kinase 1 (ChK1). In this report, we further examined the role of UNC45A in breast tumorigenesis using a variety of biochemical and cell biology techniques and animal models. We confirmed that UNC45A is highly overexpressed in human breast-infiltrating ductal carcinomas as compared to adjacent normal tissues. Silencing UNC45A in vitro blocked the proliferation of all breast cancer subtypes and drastically reduced tumor growth of the triple negative MDA-MB-231 cell line implanted in mammary fat pads of NOD/SCID mice. However, loss of UNC45A did not affect the proliferation of normal mammary cells. Remarkably, UNC45A becomes more nuclear in human cancer tissues and cancer cell lines as compared to normal tissues and...
Russian Chemical Bulletin, 2016