Hassan Bousbaa

Hassan Bousbaa
Cooperativa de Ensino Superior, Politécnico e Universitário | CESPU · The Institute of Research and Advanced Training in Health Sciences and Technologies (iinfacts)

Associate Professor

About

80
Publications
18,721
Reads
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1,754
Citations
Introduction
Hassan's research focuses on the regulation and control of cell division in somatic cells in order to understand how errors in chromosome segregation arise and lead to genomic instability in cancer. His current interests include exploiting the clinical relevance of mitosis regulation/control mechanisms to identify novel cancer diagnostic and prognostic markers, as well as to develop novel therapeutic strategies to kill cancer cells or to increase their sensitivity to antimitotic agents.
Additional affiliations
September 2003 - present
Cooperativa de Ensino Superior, Politécnico e Universitário
Description
  • http://www.cespu.pt/pt-PT/id/cics/
August 1994 - December 2007
University of Porto
July 1993 - July 1994
Institut de Recherche Scientifique sur le Cancer, Villejuif
Position
  • Centre National de Recherche Scientifique (CNRS)

Publications

Publications (80)
Article
Full-text available
The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies sh...
Article
Full-text available
The BUB3 protein plays a key role in the activation of the spindle assembly checkpoint (SAC), a ubiquitous surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis and, consequently, prevents chromosome mis-segregation and aneuploidy. Besides its role in SAC signaling, BUB3 regulates chromosome attachment to the spindle...
Article
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Cancer is a leading cause of death worldwide and, despite medical advances in the development of new anticancer therapies, drug resistance, complicated side effects and poor efficacy remain a major public health problem. To breakdown the antisuppressive tumour strategies and to improve drug efficiency , nanomedicine is increasingly being used in an...
Article
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Glioblastoma (GBM) is the most common malignant primary brain tumor, with remarkably poor prognosis and survival rates. Existing treatments cannot cure GBM patients, and GBM recurrence remains a clinical bottleneck. To explore new GBM chemotherapeutic targets and new therapeutic strategies , the role of the spindle assembly checkpoint (SAC) protein...
Article
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Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent t...
Article
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Background: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia. Material and methods: We...
Article
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Debulking surgery followed by chemotherapy are the standard of care for high-grade serous carcinoma. After an initial good response to treatment, the majority of patients relapse with a chemoresistant profile, leading to a poor overall survival. Chemotherapy regimens used in high-grade serous carcinomas are based in a combination of classical chemo...
Chapter
A importância da engenharia tecidual e o desenvolvimento de novos biomateriais para a substituição, preenchimento e reparo tecidual é indiscutível no campo da medicina. Os biomateriais aplicados na Implantologia devem ser biocompativeis a fim de que sua aplicação clínica seja previsível e não provoque sequelas ou riscos para a saúde do paciente. Al...
Article
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Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitos...
Article
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Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline–chromene scaffold were obtained. These compounds were studied for their huma...
Article
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Objective This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues. Materials and methods A systematic search was carried out on the PubMed electronic platform using the following key terms: Ti “OR” titanium “AND” dental implants “AND” nanopartic...
Article
Full-text available
Antimitotic drugs arrest cells in mitosis through chronic activation of the spindle assembly checkpoint (SAC), leading to cell death. However, drug-treated cancer cells can escape death by undergoing mitotic slippage, due to premature mitotic exit. Therefore, overcoming slippage issue is a promising chemotherapeutic strategy to improve the effectiv...
Article
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Cancer incidence and mortality continue to increase rapidly worldwide [...]
Article
The spindle assembly checkpoint (SAC) is a surveillance mechanism that prevents mitotic exit at the metaphase-to-anaphase transition until all chromosomes have established correct bipolar attachment to spindle microtubules. Activation of SAC relies on the assembly of the mitotic checkpoint complex (MCC), which requires conformational change from in...
Article
Liquid chromatography enantioseparation and determination of enantiomeric purity of synthetized xanthone and benzophenone derivatives comprising one or more chiral moieties are reported. High enantioselectivity and resolution were observed in (S,S)‐Whelk‐O1 chiral stationary phase (CSP) for the enantiomeric mixtures of compounds comprising an aroma...
Article
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Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper c...
Article
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Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D...
Article
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A new series of thirty‐two new enantiomerically pure derivatives of xanthones (3–34) were synthesized for antitumor evaluation. Two carboxyxanthones (1 and 2) were used as chemical substrates and coupled with selected chiral building blocks (43–62), achieving yields and enantiomeric excess (ee) values higher than 92 and 99 %, respectively. Carboxyx...
Article
Natural products had always be an important source of new hits and leads in drug discovery. The marine environment has been regarded as a significant souce of novel and exquisite bioactive compounds. Yicathins B and C are two marine derived xanthones that have shown antibacterial and antifungal activities. Herein, the total synthesis of these yicat...
Article
The main aim of the present study was to perform a literature review on the use of xenogenic and synthetic bomaterials for tissue healing. Regarding ceramic materials, hybrid hydroxyapatite and β-TCP (60-70/40-30 wt%), apatite carbonate, demineralized bovine bone mineral (DBBM) are ordinary bone graft materials. However, the absorption rate and bio...
Article
This study describes the synthesis of a series of chalcones, including pyrazole and α,β-epoxide derivatives, and evaluation of their cell growth inhibitory activity in three human tumor cell lines, as well as their lipophilicity using liposomes as a biomimetic membrane model. Structure-activity and structure-lipophilicity relationships were establi...
Article
Objectives Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC). Materials and Methods Bub3 and Spind...
Article
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The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4–28) with one or more alkyl side chains was car...
Article
Current microtubule-targeting agents (MTAs) remain amongst the most important antimitotic drugs used against a broad range of malignancies. By perturbing spindle assembly, MTAs activate the spindle assembly checkpoint (SAC), which induces mitotic arrest and subsequent apoptosis. However, besides toxic side effects and resistance, mitotic slippage a...
Article
Full-text available
Natural flavonoids and xanthone glycosides display several biological activities, with the glycoside moiety playing an important role in the mechanism of action of these metabolites. Herein, to give further insights into the inhibitory activity on cell growth of these classes of compounds, the synthesis of four flavonoids (5, 6, 9, and 10) and one...
Article
Statement of significance: Lung cancer remains one of the leading killers in the United States and around the world. Platinum agents, including cisplatin, are the first line treatment in lung cancer, including non-small cell lung cancer (NSCLC), which is the predominant form of lung cancer. In this study, we have evaluated Mad2 cell-cycle checkpoi...
Article
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We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the...
Article
Colorectal cancer (CRC), one of the most common malignancies worldwide, is still diagnosed at an advanced stage, and resistance to chemotherapeutics and existing targeted therapy is a major obstacle to its successful treatment. New targets that offer alternative clinical options are therefore urgently needed. Recently, perturbation of the spindle a...
Article
Background: The present study focuses on biodistribution profile and pharmacokinetic parameters of EGFR-targeted chitosan nanoparticles (TG CS nanoparticles) for siRNA/cisplatin combination therapy of lung cancer. Material & methods: Mad2 siRNA was encapsulated in EGFR targeted and nontargeted (NTG) CS nanoparticles by electrostatic interaction....
Article
Objectives: To analyse the expression of the CD44v6, p63, podoplanin and MMP-9, and their prognostic significance in patients with oral squamous cell carcinomas (OSCC). Material and methods: Immunohistochemistry technique was performed on 60 OSCC for detection of CD44v6, p63, podoplanin and MMP-9 proteins. Extent and intensity of staining were e...
Article
Full-text available
Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines der...
Article
Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest and novel materials for such application are actively sought for such applications. Recent strides in polymer science has led to a combinatorial approach for generating a library of ma...
Article
We previously reported that the spindle assembly checkpoint protein Bub3 is involved in regulating kinetochore–microtubule (KT-MT) attachments. Also, Bub3 was reported to interact with the microtubule motor protein dynein. Here we examined how this interaction contributes to KT-MT attachments. Depletion of Bub3 or dynein induced misaligned chromoso...
Article
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Breast cancer is the most common malignancy in women worldwide and the second leading cause of cancer death after lung cancer. Like in other malignancies, aneuploidy is a common feature of breast cancer and influences its behavior.Aneuploidy has been linked to inappropriate activity of the spindle assembly checkpoint (SAC), a surveillance mechanism...
Article
Objectives BubR1 and Mad2 are central components of the mitotic checkpoint complex that inhibits anaphase onset until all chromosomes are correctly aligned at the metaphase plate. We propose to analyse the combined expression of BubR1 and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC) diagnosis and prognosis.Materials and M...
Article
RNA interference has emerged as a powerful strategy in cancer therapy because it allows silencing of specific genes associated with tumor progression and resistance. Mad2 is an essential mitotic checkpoint component required for accurate chromosome segregation during mitosis, and its complete abolition leads to cell death. We have developed an epid...
Article
A predominant mechanism of spindle assembly checkpoint (SAC) silencing is dynein-mediated transport of certain kinetochore proteins along microtubules. There are still conflicting data as to which SAC proteins are dynein cargoes. Using two ATP reduction assays, we found that the core SAC proteins Mad1, Mad2, Bub1, BubR1, and Bub3 redistributed from...
Article
We previously reported the synthesis and the anti-proliferative action of 2',4'-dihydroxy-3,4,5-trimethoxychalcone. Here we reported its mechanism of action on MCF-7 cells. The compound induced aberrant spindles, and arrested cells at metaphase/anaphase boundary with accumulation of checkpoint proteins Mad2, Bub1 and BubR1. Live cell imaging reveal...
Article
Full-text available
Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic...
Article
Full-text available
Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, most cases are on an advanced and inoperable stage, with limited therapeutic options. Existing therapies have shown to be insufficient and novel strategies are urgently necessary. New advances in understanding the disease at cellular and molecular level...
Article
Full-text available
The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases wi...
Chapter
Full-text available
Article
A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed. According to this approach, thirty CDXs (3-32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building...
Article
Objectives Human Cell Division Cycle 20 (CDC20) homolog is a crucial target of the spindle assembly checkpoint. It is an activator of the Anaphase-Promoting Complex/Cyclosome (APC/C) which promotes anaphase onset and mitotic exit through the ubiquitination of securin and cyclin B1. Overexpression of CDC20 was previously reported in oral squamous ce...
Article
Accurate chromosome segregation relies on activity of the spindle assembly checkpoint, a surveillance mechanism that prevents premature anaphase onset until all chromosomes are properly attached to the mitotic spindle apparatus and aligned at the metaphase plate. Defects in this mechanism contribute to chromosome instability and aneuploidy, a hallm...
Article
Full-text available
Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, missegregation i...
Chapter
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Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders. Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate properly between the two cells. Chromosome abnormali...
Article
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The observation that certain patterns of tooth agenesis occur more frequently in individuals of the same family may suggest the existence of predisposing genetic factors. The aim of this study was to search for mutations in the PAX9 and MSX1 genes and to investigate their potential association with the maxillary lateral incisor agenesis (MLIA) phen...
Article
Full-text available
The spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes accomplish proper bipolar attachments to the mitotic spindle and come under tension, thereby ensuring the fidelity of chromosome segregation. Despite significant advances in our understanding of SAC signalling, a clear link between checkpoint signalling and the mole...
Article
Full-text available
The spindle assembly checkpoint monitors the status of kinetochore-microtubule (K-MT) attachments and delays anaphase onset until full metaphase alignment is achieved. Recently, the role of spindle assembly checkpoint proteins was expanded with the discovery that BubR1 and Bub1 are implicated in the regulation of K-MT attachments. One unsolved ques...
Article
Full-text available
The spindle assembly checkpoint is essential to maintain genomic stability during cell division. We analyzed the role of the putative Drosophila Mad2 homologue in the spindle assembly checkpoint and mitotic progression. Depletion of Mad2 by RNAi from S2 cells shows that it is essential to prevent mitotic exit after spindle damage, demonstrating its...
Article
Full-text available
The spindle checkpoint is a surveillance mechanism that regulates the metaphase-anaphase transition during somatic cell division through inhibition of the APC/C ensuring proper chromosome segregation. We show that the conserved spindle checkpoint protein BubR1 is required during early embryonic development. BubR1 is maternally provided and localise...
Article
Full-text available
The spindle assembly checkpoint detects errors in kinetochore attachment to the spindle including insufficient microtubule occupancy and absence of tension across bi-oriented kinetochore pairs. Here, we analyse how the kinetochore localization of the Drosophila spindle checkpoint proteins Bub1, Mad2, Bub3 and BubR1, behave in response to alteration...