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  1. Article ; Online: Biogenesis of Exosomes Laden with Metallic Silver-Copper Nanoparticles Liaised by Wheat Germ Agglutinin for Targeted Delivery of Therapeutics to Breast Cancer.

    Ashraf, Sarmadia / Qadri, Shahnaz / Akbar, Shayista / Parray, Aijaz / Haik, Yousef

    Advanced biology

    2022  Volume 6, Issue 7, Page(s) e2200005

    Abstract: The anticancer property of silver-copper metallic nanoparticles (AgCu-NPs) is of greater interest in cancer therapeutics; however, its off-target toxicity limits its therapeutic application. Exosomes emerge as one of the leading idiosyncratic nanocarrier ...

    Abstract The anticancer property of silver-copper metallic nanoparticles (AgCu-NPs) is of greater interest in cancer therapeutics; however, its off-target toxicity limits its therapeutic application. Exosomes emerge as one of the leading idiosyncratic nanocarrier choices for cancer therapeutics due to their size, stability, and phenotypic diversity; however, to encapsulate NPs in extracellular vesicles (EVs) without disrupting their inherited functions is far from the expectations. Here, the loading strategy of AgCu-NP conjugated with wheat germ agglutinin (AgCu-NP-WGA) in exosomes during biogenesis for the targeted delivery of anticancer therapeutics to breast cancer is reported. Based on the intrinsic mechanism of endocytosis of WGA, results show that internalization of WGA or AgCu-NP-WGA bypasses the lysosomal pathway and recycles in EVs. On the contrary, the transport of naked AgCu-NPs to lysosomes; mechanistically, an acidic environment causes oxidation of AgCu-NP. Next, the analysis of EVs harvested by differential centrifugation shows that only AgCu-NPs-WGA (Exo-NP) retain their metallic state. Furthermore, Exo-NP cytotoxicity results manifest that MCF10A-derived Exo-NPs are toxic to its homologous breast cancer cells (MCF-7 and MDA-MB 231) and nontoxic to heterologous cancers NC1-1975 and MCF 10A. In conclusion, this study shows the self-assembly of AgCu-NP in exosomes to target and deliver therapeutics for breast cancer.
    MeSH term(s) Breast Neoplasms/drug therapy ; Copper/pharmacology ; Exosomes/metabolism ; Female ; Humans ; Metal Nanoparticles/therapeutic use ; Silver/pharmacology ; Wheat Germ Agglutinins/metabolism
    Chemical Substances Wheat Germ Agglutinins ; Silver (3M4G523W1G) ; Copper (789U1901C5)
    Language English
    Publishing date 2022-04-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2701-0198
    ISSN (online) 2701-0198
    DOI 10.1002/adbi.202200005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The dynamic role of immune checkpoint molecules in diagnosis, prognosis, and treatment of head and neck cancers.

    Mestiri, Sarra / El-Ella, Dina Moustafa Abo / Fernandes, Queenie / Bedhiafi, Takwa / Almoghrabi, Salam / Akbar, Shayista / Inchakalody, Varghese / Assami, Laila / Anwar, Shaheena / Uddin, Shahab / Gul, Abdul Rehman Zar / Al-Muftah, Mariam / Merhi, Maysaloun / Raza, Afsheen / Dermime, Said

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2024  Volume 171, Page(s) 116095

    Abstract: Head and neck cancer (HNC) is the sixth most common cancer type, accounting for approximately 277,597 deaths worldwide. Recently, the Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) agents targeting programmed death-1 (PD- ...

    Abstract Head and neck cancer (HNC) is the sixth most common cancer type, accounting for approximately 277,597 deaths worldwide. Recently, the Food and Drug Administration (FDA) has approved immune checkpoint blockade (ICB) agents targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) as a treatment regimen for head and neck squamous cell carcinomas (HNSCC). Studies have reported the role of immune checkpoint inhibitors as targeted therapeutic regimens that unleash the immune response against HNSCC tumors. However, the overall response rates to immunotherapy vary between 14-32% in recurrent or metastatic HNSCC, with clinical response and treatment success being unpredictable. Keeping this perspective in mind, it is imperative to understand the role of T cells, natural killer cells, and antigen-presenting cells in modulating the immune response to immunotherapy. In lieu of this, these immune molecules could serve as prognostic and predictive biomarkers to facilitate longitudinal monitoring and understanding of treatment dynamics. These immune biomarkers could pave the path for personalized monitoring and management of HNSCC. In this review, we aim to provide updated immunological insight on the mechanism of action, expression, and the clinical application of immune cells' stimulatory and inhibitory molecules as prognostic and predictive biomarkers in HNC. The review is focused mainly on CD27 and CD137 (members of the TNF-receptor superfamily), natural killer group 2 member D (NKG2D), tumor necrosis factor receptor superfamily member 4 (TNFRSF4 or OX40), S100 proteins, PD-1, PD-L1, PD-L2, T cell immunoglobulin and mucin domain 3 (TIM-3), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), indoleamine-pyrrole 2,3-dioxygenase (IDO), B and T lymphocyte attenuator (BTLA). It also highlights the importance of T, natural killer, and antigen-presenting cells as robust biomarker tools for understanding immune checkpoint inhibitor-based treatment dynamics. Though a comprehensive review, all aspects of the immune molecules could not be covered as they were beyond the scope of the review; Further review articles can cover other aspects to bridge the knowledge gap.
    MeSH term(s) Humans ; Immune Checkpoint Proteins ; Squamous Cell Carcinoma of Head and Neck ; B7-H1 Antigen/genetics ; Programmed Cell Death 1 Receptor ; Head and Neck Neoplasms ; Immunotherapy ; Biomarkers
    Chemical Substances Immune Checkpoint Proteins ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Biomarkers
    Language English
    Publishing date 2024-01-06
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.116095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.198: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer.

    Raza, Afsheen / Khan, Abdul Q / Inchakalody, Varghese Philipose / Mestiri, Sarra / Yoosuf, Zeenath Safira K M / Bedhiafi, Takwa / El-Ella, Dina Moustafa Abo / Taib, Nassiba / Hydrose, Shereena / Akbar, Shayista / Fernandes, Queenie / Al-Zaidan, Lobna / Krishnankutty, Roopesh / Merhi, Maysaloun / Uddin, Shahab / Dermime, Said

    Journal of experimental & clinical cancer research : CR

    2022  Volume 41, Issue 1, Page(s) 99

    Abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and ... ...

    Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Disease Progression ; Early Detection of Cancer ; Humans ; Liquid Biopsy/methods ; Neoplastic Cells, Circulating/metabolism ; Prognosis
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-03-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-022-02318-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2065: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients.

    Akbar, Shayista / Raza, Afsheen / Mohsin, Reyad / Kanbour, Aladdin / Qadri, Shahnaz / Parray, Aijaz / Zar Gul, Abdul Rehman / Philip, Anite / Vijayakumar, Suma / Merhi, Maysaloun / Hydrose, Shereena / Inchakalody, Varghese Philipose / Al-Abdulla, Rajaa / Abualainin, Wafa / Sirriya, Shaza Abu / Al-Bozom, Issam / Uddin, Shahab / Khan, Omar Muhammad / Mohamed Ibrahim, Mohamed Izham /
    Al Homsi, Ussama / Dermime, Said

    Frontiers in immunology

    2023  Volume 13, Page(s) 1097117

    Abstract: Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. ... ...

    Abstract Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p<0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p<0.0001; Nectin-2, p<0.0001; NT5E, p<0.0001; Siglec-7, p<0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p<0.0001; MICA, p<0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients.
    MeSH term(s) Humans ; Biomarkers ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Cytokines/blood ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Exosomes ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Proteins/blood
    Chemical Substances Biomarkers ; Cytokines ; Immune Checkpoint Inhibitors ; Immune Checkpoint Proteins
    Language English
    Publishing date 2023-01-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1097117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression.

    Raza, Afsheen / Mohsen, Reyad / Kanbour, Aladdin / Zar Gul, Abdul Rehman / Philip, Anite / Vijayakumar, Suma / Hydrose, Shereena / Prabhu, Kirti S / Al-Suwaidi, Aisha Khamis / Inchakalody, Varghese Philipose / Merhi, Maysaloun / Abo El-Ella, Dina M / Tauro, Melissa Annrose / Akbar, Shayista / Al-Bozom, Issam / Abualainin, Wafa / Al-Abdulla, Rajaa / Sirriya, Shaza Abu / Hassnad, Suparna /
    Uddin, Shahab / Mohamed Ibrahim, Mohamed Izham / Al Homsi, Ussama / Demime, Said

    Frontiers in immunology

    2023  Volume 14, Page(s) 1157100

    Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better ... ...

    Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Antineoplastic Agents, Immunological/pharmacology ; Treatment Outcome ; Progression-Free Survival ; Immunologic Factors/therapeutic use
    Chemical Substances Antineoplastic Agents, Immunological ; Immunologic Factors
    Language English
    Publishing date 2023-05-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1157100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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