Piri Keşif Aracı

Ek Bilgiler

Kaydet

Kaynak 1:

http://dx.doi.org/10.3390/cancers8030035 arayıcılığı görüntüle.
Kaynak 2:

http://search.ndltd.org/show.php?id=oai%3Aunion.ndltd.org%3ABRADFORD%2Foai%3Abradscholars.brad.ac.uk%3A10454%2F10859&back=http%3A%2F%2Fsearch.ndltd.org%2Fsearch.php%3Fq%3D%26source_set_names%3D%26year_start%3D%26year_end%3D%26language%255B0%255D%3Denglish%26language%255B1%255D%3Den_us%26start%3D1548590 arayıcılığı görüntüle.
Kaynak 3:

https://doi.org/10.3390/cancers8030035 arayıcılığı görüntüle.

DOI : 10.3390/cancers8030035

ISSN: 2072-6694
Sayı: 3
Cilt: 8
Sayfa: 35

Sınıflandırma :

Biyotıp %98

İlaç Direnci %56

Apoptoz %27

2

Anti-Invasive and Anti-Proliferative Effects of shRNA-Loaded Poly(Lactide-Co-Glycolide) Nanoparticles Following RAN Silencing in MDA-MB231 Breast Cancer Cells

Dergi Makalesi

Kaynak :

Springer Link

Dergi:

Pharmaceutical Research

Yazar(lar) :

Ankur Sharma , Paul McCarron , Kyle Matchett , Susan Hawthorne , Mohamed El-Tanani

Konu :

Pharmacology (medical), Organic Chemistry, Pharmaceutical Science, Pharmacology, Molecular Medicine, Biotechnology

Yıl :

2018

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Overexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays. Biodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down. shRNA-loaded nanoparticles were successfully fabricated and delivered to MDA-MB231 cells in culture, where they effectively released their payload, causing a decrease in both cell invasion and cell migration by knocking down RAN gene expression. Results indicate the anti-RAN shRNA-loaded nanoparticles deliver and release biological payload to MDA-MB231 cells in culture. This works paves the way for further investigations into the possible use of anti-RAN shRNA-loaded NP formulations for the treatment of breast cancer in vivo.

DOI : 10.1007/s11095-018-2555-6

Anahtar Kelimeler : Breast cancer, Intracellular delivery, Nanotechnology, PLGA, shRNA

ISSN: 0724-8741 1573-904X
Sayı: 2
Cilt: 36

3

Nanoencapsulation of sophorolipids in PEGylated poly(lactide-co-glycolide) as a novel approach to target colon carcinoma in the murine model

Dergi Makalesi

Kaynak :

Springer Link

Dergi:

Drug Delivery and Translational Research

Yazar(lar) :

Yusuf Haggag , Mohamed Elshikh , Mohamed El-Tanani , Ibrahim M Bannat , Paul McCarron , Murtaza M. Tambuwala

Konu :

Pharmaceutical Science

Yıl :

2020

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Poly(lactic-co-glycolic acid) nanocapsules containing amphiphilic biosurfactant sophorolipids were formulated using a dispersion-based procedure. Di-block copolymers were used to vary peripheral poly(ethylene glycol) density, and variation in the oil core was used to achieve efficient encapsulation of the sophorolipid payload. Particulate size, zeta potential, encapsulation efficiency, release and stability were characterised. A glyceryl monocaprate core composition had the lowest particulate size, maximum encapsulation efficiency and optimum shelf-life stability compared to other formulations. This core composition was used to deliver sophorolipid to both in vitro and in vivo model tumour cell lines (CT26 murine colon carcinoma) and the effect of peripheral hydrophilicity was evaluated. Formulations with 10% poly(ethylene glycol) density achieved more than 80% reduction in cancer cell viability after 72 h and enhanced cellular uptake in CT26 cells. These formulations exhibited higher tumour accumulation and a longer blood circulation profile when compared to the non-poly(ethylene glycol)-containing nanocapsules. Animals treated with sophorolipid-loaded nanocapsules showed a tumour growth inhibition of 57% when compared to controls. An assessment of tumour mass within the same study cohort showed the biggest reduction when compared control and free drug-treated cohorts. This study shows that hydrophilic poly(lactic-co-glycolic acid) nanocapsules loaded with sophorolipids can address the poor intracellular delivery associated with these biosurfactants and is a promising approach for the treatment of colon neoplasia.

DOI : 10.1007/s13346-020-00750-3

Anahtar Kelimeler : Sophorolipids, Biosurfactant, Drug delivery, Nanocapsule, CT26 cells, Colon cancer

ISSN: 2190-393X 2190-3948
Sayı: 5
Cilt: 10
Sayfa: 1353-1366

4

Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Cellular Signalling

Yayıncı:

Elsevier BV

Yazar(lar) :

Mohamed El-Tanani , Arwa Omar Al Khatib , Safwan Mahmoud Aladwan , Ahmed Abuelhana , Paul A. McCarron , Murtaza M. Tambuwala

Yıl :

2022

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

The Signal Transducer and Activator of Transcription 3 (STAT3) protein is encoded on chromosome 17q21. The SH2 and the DNA binding domains are critical structural components of the protein, together with tyrosine and serine residues that initiate phosphorylation. STAT3 interacts with DNA directly and functions in cells as both a signal transducer and a transcription factor. Its cytoplasmic activation results in dimerisation and nuclear translocation, where it is involved in the transcription of a large number of target genes. STAT3 is hyperactive in cancer cells as a result of upstream STAT3 mutations or enhanced cytokine production in the tumour environment. The STAT3 signalling pathway promotes many hallmarks of carcinogenesis and metastasis, including enhanced cell proliferation and survival, as well as migration and invasion into the extracellular matrix. Recent investigations into novel STAT3-based therapies describe a range of innovative approaches, such as the use of novel oligonucleotide drugs. These limit STAT3 binding to its target genes by attaching to SH2 and DNA-binding domains. Yet, despite these significant steps in understanding the underpinning mechanisms, there are currently no therapeutic agents that addresses STAT3 signalling in a clinically relevant manner.

DOI : 10.1016/j.cellsig.2022.110275

Anahtar Kelimeler : STAT, Cancer & metastasis, Cell invasion, Cell migration, Angiogenesis, STAT3 inhibitors

ISSN: 0898-6568
Cilt: 92
Sayfa: 110275

5

Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

Cancers

Yazar(lar) :

Yusuf A. Haggag , Kyle B. Matchett , Robert A. Falconer , Mohammad Isreb , Jason Jones , Ahmed Faheem , Paul McCarron , Mohamed El-Tanani

Yıl :

2019

Mohamed El-Tanani

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs). A modified double emulsion solvent evaporation technique was used to optimise the physicochemical properties of these peptide-loaded biodegradable NPs. The anti-cancer activity of peptide-loaded NPs was studied in vitro using Ran-expressing metastatic breast (MDA-MB-231) and lung cancer (A549) cell lines, and in vivo using Solid Ehrlich Carcinoma-bearing mice. The anti-metastatic activity of peptide-loaded NPs was investigated using migration, invasion and colony formation assays in vitro. A PEG-PLGA-nanoparticle encapsulating N-terminal peptide showed a pronounced antitumor and anti-metastatic action in lung and breast cancer cells in vitro and caused a significant reduction of tumor volume and associated tumor growth inhibition of breast cancer model in vivo. These findings suggest that the novel inhibitory peptides encapsulated into PEGylated PLGA NPs are delivered effectively to interact and deactivate Ran. This novel Ran-targeting peptide construct shows significant potential for therapy of breast cancer and other cancers mediated by Ran overexpression.

Kaynak 1:

https://doi.org/10.3390/cancers11020222 arayıcılığı görüntüle.
Kaynak 2:

http://dx.doi.org/10.3390/cancers11020222 arayıcılığı görüntüle.

DOI : 10.3390/cancers11020222

Anahtar Kelimeler : Ran-RCC1 peptide, nanoparticle, breast cancer, lung cancer, anti-cancer, anti-metastatic, drug delivery

ISSN: 2072-6694
Cilt: 11
Sayı: 2
Sayfa: 222

Sınıflandırma :

Biyotıp %100

Farmakoloji ve Toksikoloji %94

6

Enhanced cutaneous wound healing in rats following topical delivery of insulin-loaded nanoparticles embedded in poly(vinyl alcohol)-borate hydrogels.

Dergi Makalesi

Kaynak :

PubMed

Dergi:

Drug Deliv Transl Res

Yazar(lar) :

Dalia H Abdelkader , Murtaza M Tambuwala , Christopher A Mitchell , Mohamed A Osman , Sanaa A El-Gizawy , Ahmed M Faheem , Mohamed El-Tanani , Paul A McCarron

Yıl :

2018

Mohamed El-Tanani

Piri Tam Metin Bulucu Özet

Kaydet

Insulin plays an important role in the wound healing process, but its method of delivery to the wound bed and subsequent effect on rate of healing is less well investigated. In this study, we evaluated the therapeutic effectiveness of topical human insulin delivery using a nanoparticulate delivery system suspended in a structured hydrogel vehicle. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) of 202.6 nm diameter and loaded with 33.86 μg insulin per milligram of polymer were formulated using a modified double-emulsion solvent evaporation technique and dispersed in a dilatant hydrogel (poly(vinyl alcohol)-borate). Importantly, this hydrogel formulation was used to achieve ultimate contact with the wound bed. A comparison of wound healing rates following local administration of insulin in the free and nanoencapsulated forms was performed in diabetic and healthy rats. In non-diabetic rats, there was no significant difference between healing observed in control and wounds treated with free insulin (p > 0.05), whereas treatment with insulin encapsulated within PLGA NP showed a significant difference (p < 0.001). In diabetic cohorts, both free insulin and nanoencapsulated insulin induced significant improvement in wound healing when compared to controls, with better percentage wound injury indices observed with the colloidal formulation. At day 10 of the experiment, the difference between percentage wound injury indices of insulin-PLGA NP and free insulin comparing to their controls were 29.15 and 12.16%, respectively. These results support strongly the potential of insulin-loaded colloidal carriers for improved wound healing when delivered using dilatant hydrogel formulations.

Kaynak 1:

https://www.ncbi.nlm.nih.gov/pubmed/19594766 arayıcılığı görüntüle.
Kaynak 2:

http://dx.doi.org/10.1007/s13346-018-0554-0 arayıcılığı görüntüle.

DOI : 10.1007/s13346-018-0554-0

Anahtar Kelimeler : Acute diabetes, PLGA nanoparticles, Recombinant human insulin, Topical delivery, Wound healing

7

Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

Molecular Carcinogenesis

Yazar(lar) :

Haibo Xu , Mella McCann , Zhiyu Zhang , Gary H. Posner , Victoria Bingham , Mohamed El-Tanani , Frederick C. Campbell

Yıl :

2009

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Vitamin D receptor (VDR) can modulate functionally antagonistic growth regulatory pathways, involving β‐catenin/E‐cadherin on one hand and osteopontin (OPN) on the other. This study investigates effects of VDR ligand treatment on the balance of these discordant signals and on associated cell behavior. Treatment of Rama 37 or SW480 cells by 1α,25‐(OH)2 D3 or analogs suppressed β‐catenin/Lef‐1/Tcf signaling and upregulated E‐cadherin, consistent with a cancer‐inhibitory action. Conversely, treatment also increased transcription of OPN that may be implicated in tumor progression. Molecular crosstalk was observed between the antagonistic VDR‐dependent signals, in that β‐catenin/Lef‐1/Tcf molecules modulated VDR activation of OPN. Treatment effects on cell growth were related to a constitutive balance of OPN and E‐cadherin expression. No growth effects were observed in Rama 37 cells that have low OPN and high E‐cadherin expression. Conversely, treatment of Rama 37 stably transfected subclones that had high OPN and/or low level E‐cadherin induced small but significant increases of cell attachment to fibronectin, anchorage‐independent growth or invasion. This study shows that relative expression levels of key VDR downstream genes may influence growth regulation by 1α,25‐(OH)2 D3 or analogs. These findings may be relevant to the cell‐ or tissue‐specificity of vitamin D growth regulation. © 2009 Wiley‐Liss, Inc.

DOI : 10.1002/mc.20520

ISSN: 0899-1987
Sayı: 8
Cilt: 48
Sayfa: 758-772

8

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

International Journal of Pharmaceutics

Yayıncı:

Elsevier

Yazar(lar) :

Yusuf Haggag , Yasser Abdel-Wahab , Opeolu Ojo , Mohamed Osman , Sanaa El-Gizawy , Mohamed El-Tanani , Ahmed Faheem , Paul McCarron

Yıl :

2016

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (dl-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200–400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG–PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 h to 6 days in type I diabetic mice.

DOI : 10.1016/j.ijpharm.2015.12.063

Anahtar Kelimeler : Insulin, PEG-PLGA, Nanoparticles, Stability, Controlled delivery, Diabetes

ISSN: 0378-5173
Sayı: 1-2
Cilt: 499
Sayfa: 236-246

Sınıflandırma :

Kimya %99

Kimya ve Gıda Bilimi %35

Kromatografi %29

Biyokimya Mühendisliği %20

9

BAK and NOXA Are Critical Determinants of Mitochondrial Apoptosis Induced by Bortezomib in Mesothelioma

Araştırma Makalesi

Kaynak :

PLOS - Public Library of Science

Dergi:

Public Library of Science

Yazar(lar) :

Dean A. Fennell , Giovanni Gaudino , V. Courtney Broaddus , Mohamed El-Tanani , Julia J. Gorski , Vignesh K. Gunasekharan , Michael Sheaff , Kenneth Arthur , Astero Klabatsa , Alex D. Chacko , Sara Busacca

Yıl :

2013

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM), two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05–10). However, the potential mechanisms underlying resistance to this targeted drug in MPM are still unknown. Functional genetic analyses were conducted to determine the key mitochondrial apoptotic regulators required for bortezomib sensitivity and to establish how their dysregulation may confer resistance. The multidomain proapoptotic protein BAK, but not its orthologue BAX, was found to be essential for bortezomib-induced apoptosis in MPM cell lines. Immunohistochemistry was performed on tissues from the ICORG-05 phase II trial and a TMA of archived mesotheliomas. Loss of BAK was found in 39% of specimens and loss of both BAX/BAK in 37% of samples. However, MPM tissues from patients who failed to respond to bortezomib and MPM cell lines selected for resistance to bortezomib conserved BAK expression. In contrast, c-Myc dependent transactivation of NOXA was abrogated in the resistant cell lines. In summary, the block of mitochondrial apoptosis is a limiting factor for achieving efficacy of bortezomib in MPM, and the observed loss of BAK expression or NOXA transactivation may be relevant mechanisms of resistance in the clinic.

Kaynak 1:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065489 arayıcılığı görüntüle.
Kaynak 2:

https://journals.plos.org/plosone/article?id=10.1371/annotation/90879c69-ebc5-40b2-9926-4a00e4f9e055 arayıcılığı görüntüle.
Kaynak 3:

https://doi.org/10.1371/annotation/90879c69-ebc5-40b2-9926-4a00e4f9e055 arayıcılığı görüntüle.
Kaynak 4:

https://doi.org/10.1371/journal.pone.0065489 arayıcılığı görüntüle.

DOI : 10.1371/journal.pone.0065489

Anahtar Kelimeler : Apoptosis, Mesothelioma, Mitochondria, Cell staining, Transfection, Protein expression, Cancer treatment, Small interfering RNAs

Sınıflandırma :

Biyotıp %100

Apoptoz %100

10

The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer.

Dergi Makalesi

Kaynak :

PubMed

Dergi:

Oncotarget

Yazar(lar) :

El-Habib Dakir , Adam Pickard , Kirtiman Srivastava , Cian M McCrudden , Stephane R Gross , Stephen Lloyd , Shu-Dong Zhang , Andriana Margariti , Richard Morgan , Philip S Rudland , Mohamed El-Tanani

Yıl :

2018

Mohamed El-Tanani

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Pimozide, an antipsychotic drug of the diphenylbutylpiperidine class, has been shown to suppress cell growth of breast cancer cells in vitro. In this study we further explore the inhibitory effects of this molecule in cancer cells. We found that Pimozide inhibited cell proliferation in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells and A549 lung cancer cells. Furthermore, we found that Pimozide also promoted apoptosis as demonstrated by cell cycle arrest and induction of double-strand DNA breaks but did not result in any effect in the non-transformed MCF10A breast cell line. In order to shed new lights into the molecular pathways affected by Pimozide, we show that Pimozide downregulated RAN GTPase and AKT at both protein and mRNA levels and inhibited the AKT signaling pathway in MDA-MB-231 breast cancer cells. Pimozide also inhibited the epithelial mesenchymal transition and cell migration and downregulated the expression of MMPs. Administration of Pimozide showed a potent in vivo antitumor activity in MDA-MB-231 xenograft animal model and reduced the number of lung metastases by blocking vascular endothelial growth factor receptor 2. Furthermore, Pimozide inhibited myofibroblast formation as evaluated by the reduction in α-smooth muscle actin containing cells. Thus, Pimozide might inhibit tumor development by suppressing angiogenesis and by paracrine stimulation provided by host reactive stromal cells. These results demonstrate a novel in vitro and in vivo antitumor activity of Pimozide against breast and lung cancer cells and provide the proof of concept for a putative Pimozide as a novel approach for cancer therapy.

DOI : 10.18632/oncotarget.26175

Anahtar Kelimeler : DSB, apoptosis, breast cancer, pimozide, xenograft

Sınıflandırma :

Biyotıp %100

Hücre Biyolojisi %71

Apoptoz %23

11

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

International Journal of Pharmaceutics

Yayıncı:

Elsevier

Yazar(lar) :

Yusuf A. Haggag , Kyle B. Matchett , El-Habib Dakir , Paul Buchanan , Mohammed A. Osman , Sanaa A. Elgizawy , Mohamed El-Tanani , Ahmed M. Faheem , Paul A. McCarron

Yıl :

2017

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Ran is a small ras-related GTPase and is highly expressed in aggressive breast carcinoma. Overexpression induces malignant transformation and drives metastatic growth. We have designed a novel series of anti-Ran-GTPase peptides, which prevents Ran hydrolysis and activation, and although they display effectiveness in silico, peptide activity is suboptimal in vitro due to reduced bioavailability and poor delivery. To overcome this drawback, we delivered an anti-Ran-GTPase peptide using encapsulation in PLGA-based nanoparticles (NP). Formulation variables within a double emulsion solvent evaporation technique were controlled to optimise physicochemical properties. NP were spherical and negatively charged with a mean diameter of 182–277 nm. Peptide integrity and stability were maintained after encapsulation and release kinetics followed a sustained profile. We were interested in the relationship between cellular uptake and poly(ethylene glycol) (PEG) in the NP matrix, with results showing enhanced in vitro uptake with increasing PEG content. Peptide-loaded, pegylated (10% PEG)-PLGA NP induced significant cytotoxic and apoptotic effects in MDA-MB-231 breast cancer cells, with no evidence of similar effects in cells pulsed with free peptide. Western blot analysis showed that encapsulated peptide interfered with the proposed signal transduction pathway of the Ran gene. Our novel blockade peptide prevented Ran activation by blockage of regulator of chromosome condensation 1 (RCC1) following peptide release directly in the cytoplasm once endocytosis of the peptide-loaded nanoparticle has occurred. RCC1 blockage was effective only when a nanoparticulate delivery approach was adopted.

DOI : 10.1016/j.ijpharm.2017.02.006

Anahtar Kelimeler : Anti-Ran-GTPase peptide, Double emulsion, PLGA, Nanoparticle, Breast cancer, Drug delivery

ISSN: 0378-5173
Sayı: 1-2
Cilt: 521
Sayfa: 40-53

Sınıflandırma :

Biyotıp %90

Farmakoloji ve Toksikoloji %41

Sitogenetik %26

12

Regarding “Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients”

Dergi Makalesi

Kaynak :

Springer Link

Dergi:

Breast Cancer Research and Treatment

Yazar(lar) :

Hiu-Fung Yuen , Shu-Dong Zhang , Ashley San-Yu Wong , Cian M. McCrudden , Yu-Han Huang , Kelvin Yuen-Kwong Chan , Mohamed El-Tanani , Ui-Soon Khoo

Konu :

Cancer Research, Oncology

Yıl :

2011

Mohamed El-Tanani

Ek Bilgiler

Kaydet

DOI : 10.1007/s10549-011-1831-5

Anahtar Kelimeler : Breast Cancer Patient, Epithelial Mesenchymal Transition, Nuclear Expression, Short Survival Time, Early Breast Cancer Patient

ISSN: 0167-6806 1573-7217
Sayı: 1
Cilt: 131
Sayfa: 351-352

13

Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

Bioscience Reports

Yazar(lar) :

Hiuu2011Fung Yuen , Olga Abramczyk , Grant Montgomery , Kau2011Kui Chan , Yuu2011Han Huang , Takehiko Sasazuki , Senji Shirasawa , Srivastava Gopesh , Kwoku2011Wah Chan , Dean Fennell , Pasi Janne , Mohamed Elu2011Tanani , James T. Murray

Yıl :

2012

Mohamed El‑Tanani

Piri Tam Metin Bulucu Özet Ek Bilgiler

Kaydet

Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy.

DOI : 10.1042/BSR20120050

Anahtar Kelimeler : cancer cell, c-Met, K-Ras, mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)

Cilt: 32
Sayı: 4

Sınıflandırma :

Biyotıp %100

Apoptoz %100

14

Protein deregulation associated with breast cancer metastasis

Dergi Makalesi

Kaynak :

Science Direct

Dergi:

Cytokine & Growth Factor Reviews

Yayıncı:

Elsevier

Yazar(lar) :

Ka Kui Chan , Kyle B. Matchett , Paul M. McEnhill , El Habib Dakir , Mary Frances McMullin , Yahia El-Tanani , Laurence Patterson , Ahmed Faheem , Philip S. Rudland , Paul A. McCarron , Mohamed El-Tanani

Yıl :

2015

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Breast cancer is one of the most prevalent malignancies worldwide. It consists of a group of tumor cells that have the ability to grow uncontrollably, overcome replicative senescence (tumor progression) and metastasize within the body. Metastases are processes that consist of an array of complex gene dysregulation events. Although these processes are still not fully understood, the dysregulation of a number of key proteins must take place if the tumor cells are to disseminate and metastasize. It is now widely accepted that future effective and innovative treatments of cancer metastasis will have to encompass all the major components of malignant transformation. For this reason, much research is now being carried out into the mechanisms that govern the malignant transformation processes. Recent research has identified key genes involved in the development of metastases, as well as their mechanisms of action. A detailed understanding of the encoded proteins and their interrelationship generates the possibility of developing novel therapeutic approaches. This review will focus on a select group of proteins, often deregulated in breast cancer metastasis, which have shown therapeutic promise, notably, EMT, E-cadherin, Osteopontin, PEA3, Transforming Growth Factor Beta (TGF-β) and Ran.

DOI : 10.1016/j.cytogfr.2015.05.002

Anahtar Kelimeler : Breast cancer metastasis, EMT, TGF-β, Osteopontin, PEA3

ISSN: 1359-6101
Sayı: 4
Cilt: 26
Sayfa: 415-423

15

Biomedical applications of three‐dimensional bioprinted craniofacial tissue engineering

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

Bioengineering & Translational Medicine

Yazar(lar) :

Nitin Bharat Charbe , Murtaza Tambuwala , Sushesh Srivatsa Palakurthi , Amol Warokar , Altijana Hromiću2010Jahjefendić , Hamid Bakshi , Flavia Zacconi , Vijay Mishra , Saurabh Khadse , Alaa A. Aljabali , Mohamed Elu2010Tanani , Ãngel Serranou2010Aroca , Srinath Palakurthi

Yıl :

2022

Mohamed El‐Tanani

Ek Bilgiler

Kaydet

DOI : 10.1002/btm2.10333

ISSN: 2380-6761

16

Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion

Dergi Makalesi

Kaynak :

The BMJ

Dergi:

Journal of Clinical Pathology

Yazar(lar) :

Somaia Elsheikh , Ilias Kouzoukakis , Catherine Fielden , Wei Li , Shaimaa Elsaid Lashin , Nadia Khair , Teresa Pereira Raposo , Wakkas Fadhil , Philip Rudland , Mohammed Aleskandarany , Poulam Patel , Mohamed El-Tanani , Mohammad Ilyas

Yıl :

2020

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

AimsRan GTPase is involved in nucleocytoplasmic shuttling of proteins and is overexpressed in several cancers. The expression of Ran in malignant melanoma (MM) and its functional activity have not been described and were investigated in this study.MethodsThe prognostic value of Ran expression was tested in a series of 185 primary cutaneous MM cases using immunohistochemistry. The functional activity of Ran was investigated in the two melanoma cell lines. Ran expression was knocked down using two siRNAs and the effect on the expression of the c-Met oncogene, a potential downstream target of Ran, was tested. Functional effects of Ran knockdown on cell motility and cell proliferation were also assessed.ResultsPositive Ran expression was seen in 12.4% of MM and was associated with advanced clinical stage and greater Breslow thickness. Positive expression was an independent marker of shorter overall survival (p=0.023). Knockdown of Ran results in decreased expression of c-Met and the downstream c-met signalling targets ERK1/2. There was a significant reduction in cell migration (p<0.001) and cell invasion (p<0.001). c-Met knockdown decreased the expression of Ran through MAPK and PI3K-AKT in A375 cell line, inhibited the cell viability and migration of both A375 and G361 melanoma cell lines while invasion was enhanced.ConclusionRan is a poor prognostic marker in cutaneous MM. It upregulates expression of the oncogene c-Met and, possibly through this, it promotes cell motility which may in turn promote metastasis.

DOI : 10.1136/jclinpath-2020-206871

ISSN: 0021-9746
Sayfa: jclinpath-2020-206871

17

Polyomavirus enhancer activator 3 protein promotes breast cancer metastatic progression through Snail-induced epithelial-mesenchymal transition

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

The Journal of Pathology

Yazar(lar) :

Hiu-Fung Yuen , Yuen-Kwong Chan , Claire Grills , Cian M McCrudden , Vignesh Gunasekharan , Zhanzhong Shi , Ashley San-Yu Wong , Terence R Lappin , Kwok-Wah Chan , Dean A Fennell , Ui-Soon Khoo , Patrick G Johnston , Mohamed El-Tanani

Konu :

Pathology and Forensic Medicine

Yıl :

2011

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Polyomavirus enhancer activator 3 protein (Pea3), also known as ETV4, is a member of the Ets‐transcription factor family, which promotes metastatic progression in various types of solid cancer. Pea3‐driven epithelial‐mesenchymal transition (EMT) has been described in lung and ovarian cancers. The mechanisms of Pea3‐induced EMT, however, are largely unknown. Here we show that Pea3 overexpression promotes EMT in human breast epithelial cells through transactivation of Snail (SNAI1), an activator of EMT. Pea3 binds to the human Snail promoter through the two proximal Pea3 binding sites and enhances Snail expression. In addition, knockdown of Pea3 in invasive breast cancer cells results in down‐regulation of Snail, partial reversal of EMT, and reduced invasiveness in vitro. Moreover, knockdown of Snail partially rescues the phenotype induced by Pea3 overexpression, suggesting that Snail is one of the mediators bridging Pea3 and EMT, and thereby metastatic progression of the cancer cells. In four breast cancer patient cohorts whose microarray and survival data were obtained from the Gene Expression Omnibus database, Pea3 and Snail expression are significantly correlated with each other and with overall survival of breast cancer patients. We further demonstrate that nuclear localization of Pea3 is associated with Snail expression in breast cancer cell lines and is an independent predictor of overall survival in a Chinese breast cancer patient cohort. In conclusion, our results suggest that Pea3 may be an important prognostic marker and a therapeutic target for metastatic progression of human breast cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

DOI : 10.1002/path.2859

ISSN: 0022-3417
Sayı: 1
Cilt: 224
Sayfa: 78-89

18

Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

Cancer Science

Yazar(lar) :

Hiu-Fung Yuen , Cian M. McCrudden , Claire Grills , Shu-Dong Zhang , Yu-Han Huang , Ka-Kui Chan , Yuen-Piu Chan , Michelle Lok-Yee Wong , Simon Law , Gopesh Srivastava , Dean A. Fennell , Glenn Dickson , Mohamed El-Tanani , Kwok-Wah Chan

Konu :

Cancer Research, Oncology, General Medicine

Yıl :

2012

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Emerging evidence has indicated a role of the bone morphogenetic proteins (BMP) in the pathogenesis of certain cancers. The signaling of BMP family members is tightly regulated by their antagonists, including noggin and SOST, which are, in turn, positively regulated by BMP, thereby forming a negative feedback loop. Consequently, the expression of these antagonists should be taken into account in studies on the prognostic significance of BMP. In the present paper, we correlated protein and mRNA expression levels of BMP6, noggin and SOST, alone or in combination, with patient survival in various types of cancer. We found that BMP6 alone was not significantly correlated with esophageal squamous cell carcinoma patient survival. Instead, a high level of inhibitor of differentiation 1, a downstream factor of BMP6, was associated with shorter survival in patients whose tumors stained strongly for BMP6. Knockdown of noggin in esophageal cancer cell line EC109, which expresses BMP6 strongly and SOST weakly, enhanced the non‐adherent growth of the cells. Noggin and SOST expression levels, when analyzed alone, were not significantly correlated with patient survival. However, high BMP6 activity, defined by strong BMP6 expression coupled with weak noggin or SOST expression, was significantly associated with shorter survival in esophageal squamous cell carcinoma patients. We further confirmed that BMP6 activity could be used as a prognostic indicator in prostate, bladder and colorectal cancers, using publicly available data on BMP6, noggin and SOST mRNA expression and patient survival. Our results strongly suggest that BMP6, noggin and SOST could be used in combination as a prognostic indicator in cancer progression. (Cancer Sci 2012; 103: 1145–1154)

DOI : 10.1111/j.1349-7006.2012.02252.x

ISSN: 1347-9032
Sayı: 6
Cilt: 103
Sayfa: 1145-1154

19

Recent Advances in Anticancer Activity of Novel Plant Extracts and Compounds from Curcuma longa in Hepatocellular Carcinoma

Dergi Makalesi

Kaynak :

Springer Link

Dergi:

Journal of Gastrointestinal Cancer

Yazar(lar) :

Nighat Gull , Fareeha Arshad , Gowhar A. Naikoo , Israr Ul Hassan , Mona Zamani Pedram , Arif Ahmad , Alaa A. A. Aljabali , Vijay Mishra , Saurabh Satija , Nitin Charbe , Poonam Negi , Rohit Goyal , Ángel Serrano-Aroca , Mazhar S. Al Zoubi , Mohamed El-Tanani , Murtaza M. Tambuwala

Konu :

Gastroenterology, Oncology

Yıl :

2022

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it’s postulated molecular targets of curcumin when used against liver cancers. This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.

DOI : 10.1007/s12029-022-00809-z

Anahtar Kelimeler : Cancer, Curcumin, Hepatocellular Carcinoma, Anticancer

ISSN: 1941-6628 1941-6636

20

Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation

Dergi Makalesi

Kaynak :

Wiley Online Library

Dergi:

British Journal of Haematology

Yazar(lar) :

Perry Maxwell , Florinda Melendez-Rodríguez , Kyle B. Matchett , Julian Aragones , Nathalie Ben-Califa , Heidelinde Jaekel , Ludger Hengst , Herbert Lindner , Andre Bernardini , Ulf Brockmeier , Joachim Fandrey , Fritz Grunert , Howard S. Oster , Moshe Mittelman , Mohamed El-Tanani , Markus Thiersch , Edith M. Schneider Gasser , Max Gassmann , David Dangoor , Robert J. Cuthbert , Alexandra Irvine , Anne Jordan , Terence Lappin , John Thompson , Drorit Neumann

Konu :

Hematology

Yıl :

2014

Mohamed El-Tanani

Özet Ek Bilgiler

Kaydet

Recombinant human erythropoietin (rHuEPO) is an effective treatment for anaemia but concerns that it causes disease progression in cancer patients by activation of EPO receptors (EPOR) in tumour tissue have been controversial and have restricted its clinical use. Initial clinical studies were flawed because they used polyclonal antibodies, later shown to lack specificity for EPOR. Moreover, multiple isoforms of EPOR caused by differential splicing have been reported in cancer cell lines at the mRNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The EpoCan consortium seeks to promote improved pathological testing of EPOR, leading to safer clinical use of rHuEPO, by producing well characterized EPOR antibodies. Using novel genetic and traditional peptide immunization protocols, we have produced mouse and rat monoclonal antibodies, and show that several of these specifically recognize EPOR by Western blot, immunoprecipitation, immunofluorescence, flow cytometry and immunohistochemistry in cell lines and clinical material. Widespread availability of these antibodies should enable the research community to gain a better understanding of the role of EPOR in cancer, and eventually to distinguish patients who can be treated safely by rHuEPO from those at increased risk from treatment.

DOI : 10.1111/bjh.13133

ISSN: 0007-1048
Sayı: 3
Cilt: 168
Sayfa: 429-442

21

Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage

Dergi Makalesi

Kaynak :

Directory of Open Access Journals (DOAJ)

Dergi:

Nutrients

Yazar(lar) :

Hamid A. Bakshi , Mazhar S Al Zoubi , Hakkim L. Faruck , Alaa A A Aljabali , Firas A. Rabi , Amin A. Hafiz , Khalid M Al-Batanyeh , Bahaa Al-Trad , Prawej Ansari , Mohamed M. Nasef , Nitin B. Charbe , Saurabh Satija , Meenu Mehta , Vijay Mishra , Gaurav Gupta , Salem Abobaker , Poonam Negi , Ibrahim M. Azzouz , Ashref Ali K Dardouri , Harish Dureja , Parteek Prasher , Dinesh K. Chellappan , Kamal Dua , Mateus Webba Da Silva , Mohamed El Tanani , Paul A. McCarron , Murtaza M. Tambuwala

Yıl :

2020

Mohamed El Tanani