Publications by authors named "Lotfi Chouchane"

Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the "Canary" algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs).

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The isocyanide group is the chameleon among the functional groups in organic chemistry. Unlike other multiatom functional groups, where the electrophilic and nucleophilic moieties are typically separated, isocyanides combine both functionalities in the terminal carbon. This unique feature can be rationalized using the frontier orbital concept and has significant implications for its intermolecular interactions and the reactivity of the functional group.

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UBR5 is a HECT domain E3 ubiquitin ligase that is frequently amplified in breast, ovarian and prostate cancers. Heightened UBR5 expression plays a profound role in tumor growth through immune-dependent mechanisms; however, its mode of action in driving tumor metastasis has not been definitively delineated. Herein, we used a tetracycline (Tet)-inducible RNAi-mediated expression silencing cell system to investigate how UBR5 enables postsurgical mammary tumor metastatic growth in mouse lungs without the continuous influence of the primary lesion.

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(1) Background: Immunosuppression is a key barrier to effective anti-cancer therapies, particularly in triple-negative breast cancer (TNBC), an aggressive and difficult to treat form of breast cancer. We investigated here whether the combination of doxorubicin, a standard chemotherapy in TNBC with glyceryltrinitrate (GTN), a nitric oxide (NO) donor, could overcome chemotherapy resistance and highlight the mechanisms involved in a mouse model of TNBC. (2) Methods: Balb/C-bearing subcutaneous 4T1 (TNBC) tumors were treated with doxorubicin (8 mg/Kg) and GTN (5 mg/kg) and monitored for tumor growth and tumor-infiltrating immune cells.

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A balance between the synthesis and degradation of proteins is referred to as protein turnover, which is crucial for cellular protein homeostasis. Proteome-wide analysis of protein turnover in adipocytes, which are well-known for their role in energy storage and their link to obesity and metabolism disorders, is yet to be conducted. Thus, with this objective in mind, our investigation utilized a comparative analysis of time-dependent SILAC labeling to assess protein turnover in 3T3-L1 adipocytes, spanning a period of 0 to 144 h.

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Article Synopsis
  • Porto-sinusoidal vascular disorder (PSVD) is a liver disease characterized by vascular lesions without cirrhosis, with unknown causes in most cases, although it can be linked to coagulation issues or toxins.
  • Researchers conducted genome sequencing on a Lebanese family affected by PSVD and discovered a harmful genetic variant in the FCHSD1 gene that appears to be inherited in an autosomal dominant manner.
  • The variant likely increases stability of the FCHSD1 mRNA and protein, which in turn activates the mTOR pathway excessively, leading to PSVD symptoms observed in genetically edited mice.
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Background: Mutated and non-mutated genes interact to drive cancer growth and metastasis. While research has focused on understanding the impact of mutated genes on cancer biology, understanding non-mutated genes that are essential to tumor development could lead to new therapeutic strategies. The recent advent of high-throughput whole genome sequencing being applied to many different samples has made it possible to calculate if genes are significantly non-mutated in a specific cancer patient cohort.

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Immunotherapy has allowed major advances in oncology in the past years, in particular with the development of immune checkpoint inhibitors, but the clinical benefits are still limited, particularly in colorectal cancer (CRC). Our scientific approach is based on the search for innovative immunotherapy with a final goal that aims to induce an effective antitumor immune response in CRC. Here, we focused on a multikinase inhibitor, H89.

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Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) are widely used to identify disease-associated SNPs.

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  • The study investigates genetic risk factors for cancer within the Qatari population, focusing on disparities among different ancestry groups due to limited genomic data for Middle Eastern populations.
  • The Qatar Genome Programme collected DNA samples from 6142 native Qataris, which were analyzed for polygenic risk scores related to common cancers such as breast, prostate, and colorectal cancers, revealing significant differences among six ancestry groups.
  • Findings indicate that ancestry impacts cancer risk, with individuals from the Arabian Peninsula showing the lowest risk for colorectal cancer and those of African descent displaying the highest risk for prostate cancer, alongside the identification of rare genetic variants linked to cancer susceptibility.
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Breast cancer (BC) is one of the most diagnosed cancers worldwide and is the second cause of cancer related death in women. The most frequent cause of BC-related deaths, like many cancers, is metastasis. However, metastasis is a complicated and poorly understood process for which there is a shortage of accurate prognostic indicators and effective treatments.

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The development of prophylactic and therapeutic agents for coronavirus disease 2019 (COVID-19) is a current global health priority. Here, we investigated the presence of cross-neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dromedary camels that were Middle East respiratory syndrome coronavirus (MERS-CoV) seropositive but MERS-CoV free. The tested 229 dromedaries had anti-MERS-CoV camel antibodies with variable cross-reactivity patterns against SARS-CoV-2 proteins, including the S trimer and M, N, and E proteins.

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Copy number variation (CNV) is considered as the most frequent type of structural variation in the human genome. Some CNVs can act on human phenotype diversity, encompassing rare Mendelian diseases and genomic disorders. The North African populations remain underrepresented in public genetic databases in terms of single-nucleotide variants as well as for larger genomic mutations.

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Aberrant metabolism is the root cause of several serious health issues, creating a huge burden to health and leading to diminished life expectancy. A dysregulated metabolism induces the secretion of several molecules which in turn trigger the inflammatory pathway. Inflammation is the natural reaction of the immune system to a variety of stimuli, such as pathogens, damaged cells, and harmful substances.

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Recessive mutations in the gene have been reported in thirteen patients to date exhibiting development delay, intellectual disability (ID), seizures, and muscular hypotonia, accompanied occasionally by neuronal migration defects expressed as either cobblestone lissencephaly or periventricular hypertopia. Here, we report a new case of a -related syndrome in a Lebanese family with two affected siblings showing severe psychomotor retardation, intellectual disability, microcephaly, absence of speech, muscular hypotonia, and seizures. Whole exome sequencing revealed a homozygous pathogenic variant c.

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Unlabelled: Prosthetic reconstruction in previously irradiated breasts has been associated with a higher risk of complications. Here we describe the surgical and cosmetic outcome of our breast reconstruction process based on primary fat grafting combined with prosthetic placement.

Methods: In this multicenter retrospective study, 136 patients who underwent mastectomy and external chest wall radiotherapy between 2014 and 2018 were benefited from chest wall lipofilling and silicone implant placement were chosen.

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In 2016, the World Innovation Summit for Health (WISH) published its Forum Report on precision medicine "PRECISION MEDICINE - A GLOBAL ACTION PLAN FOR IMPACT". Healthcare is undergoing a transformation, and it is imperative to leverage new technologies to generate new data and support the advent of precision medicine (PM). Recent scientific breakthroughs and technological advancements have improved our disease knowledge and altered diagnosis and treatment approaches resulting in a more precise, predictive, preventative and personalized health care that is customized for the individual patient.

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Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (MEFV) gene. Despite a typical clinical expression, many patients have either a single or no mutation in MEFV.

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Background: In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies.

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Background: Most mutations in melanoma affect one critical amino acid on BRAF gene, resulting in the V600E substitution. Patient management is often based on the use of specific inhibitors targeting this mutation.

Methods: DNA and RNA mutation status was assessed in 15 melanoma cell lines by Sanger sequencing and RNA-seq.

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Background: An immune active cancer phenotype typified by a T helper 1 (Th-1) immune response has been associated with increased responsiveness to immunotherapy and favorable prognosis in some but not all cancer types. The reason of this differential prognostic connotation remains unknown.

Methods: To explore the contextual prognostic value of cancer immune phenotypes, we applied a multimodal pan-cancer analysis among 31 different histologies (9282 patients), encompassing immune and oncogenic transcriptomic analysis, mutational and neoantigen load and copy number variations.

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UBR5 is a nuclear phosphoprotein of obscure functions. Clinical analyses reveal that amplifications and overexpression occur in over 20% cases of human breast cancers. Breast cancer patients carrying genetic lesions with overexpression have significantly reduced survival.

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Article Synopsis
  • The traditional view of cancer as solely a cell-autonomous disease is shifting, highlighting the crucial role of the tumor microenvironment (TM) in cancer growth and spread.
  • Endothelial cells (ECs), once mainly seen as involved in forming blood vessels, are now recognized for their non-angiogenic functions that influence both normal and pathological tissue development.
  • Recent studies have shown that tumor-associated endothelial cells display unique gene expression and interact closely with tumors, revealing potential new targets for therapies aimed at disrupting these interactions.
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Triple-negative breast cancer (TNBC) accounts for ~15-20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to investigate the susceptibility and prognostic implications of genetic variation in CCL5 signaling genes in TNBC in the present study.

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Nucleotide excision repair is a multistep process that recognizes and eliminates a spectrum of DNA damages. Five proteins, namely XPC, RAD23, Centrin 2, DDB1 and DDB2 act as a heterodimeric complex at the early steps of the NER pathway and play a crucial role in the removal of DNA lesions. Several exonic mutations on genes coding for these proteins have been identified as associated with Xeroderma-pigmentosum (XP), a rare monogenic disorder.

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