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  • 1
    In: Viruses, MDPI AG, Vol. 15, No. 5 ( 2023-05-10), p. 1140-
    Abstract: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) patients may experience an acute ischemic stroke; however, risk factors, in-hospital deaths, and outcomes have not been thoroughly investigated. This study investigates the risk factors, comorbidities, and outcomes in patients with SARS-VoV-2 infection and acute ischemic stroke compared to patients without these conditions. The present retrospective study was conducted in the King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard, Health Affairs, Riyadh, Saudi Arabia, during the period from April 2020 to February 2022. This study investigates the risk variables among the individuals who were diagnosed with either SARS-CoV-2 with stroke or patients with stroke alone. A total of 42,688 COVID-19 patients were registered, 187 cases of strokes were listed in COVID-19 patients, however, 5395 cases with stroke without SARS-CoV-2 infection. The results revealed that factors including age, hypertension, deep vein thrombosis, and ischemic heart disease are associated with an increased risk of ischemic stroke. The results also displayed an elevated frequency of in-hospital deaths in COVID-19 patients with acute ischemic stroke. The results also showed that SARS-CoV-2 together predicts the probability of stroke and death in the study sample. The study findings conclude that ischemic strokes were infrequent in patients with SARS-CoV-2 and usually occur in the presence of other risk factors. The risk factors of ischemic strokes in patients with SARS-CoV-2 are old age, male gender, hypertension, hyperlipidaemia, DVT, ischemic heart disease, and diabetes mellitus. Furthermore, the results showed a higher frequency of in-hospital deaths in COVID-19 patients with stroke compared to COVID-19 patients without stroke.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 2
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 11 ( 2024-6-3)
    Abstract: Immune checkpoint inhibitors (ICI) have improved overall survival in patients with different cancer types. However, treatment efficacy varies between patients depending on several factors. Recent research suggested that antibiotic-induced dysbiosis can impair ICI efficacy. Here we review the impact of antibiotic use in clinical outcome of patients with gastrointestinal cancer treated with ICI. Methods This is a systematic review and utilized a thorough search of MEDLINE, Cochrane, Scopus, EB-SCO, Web of Science of studies published till September 2023. The aim of the study is to determine the association between antibiotic use and ICI treatment efficacy in patients with gastrointestinal cancers (GI). We utilized a meta-analysis of the association between the use of antibiotics and overall survival and progression-free survival. Results Nine studies met the inclusion criteria with a total of 2,214 patients. The most common type of cancers was hepatocellular carcinoma (HCC). The majority of the studies were retrospective, and one was collective of clinical trials. The use of antibiotics was associated with decreased both overall survival [haz-ard ratio (HR) 1.92, 95% confidence interval (CI) 1.41, 2.63] and progression-free survival [HR 1.81, 95% CI 1.29, 2.54] . Conclusion The use of antibiotics may affect clinical outcomes in patients with GI cancers treated with ICI. Further prospective studies are needed to improve the understanding of this phenomenon. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462172 .
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2775999-4
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  • 3
    In: European Journal of Immunology, Wiley, Vol. 50, No. 5 ( 2020-05), p. 695-704
    Abstract: CD5 is expressed on T cells and a subset of B cells (B1a). It can attenuate TCR signalling and impair CTL activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti‐tumour activity against tumours (including solid tumours) has not been explored. CD5 knockout mice show increased anti‐tumour immunity: reducing CD5 on CTLs may be therapeutically beneficial to enhance the anti‐tumour response. Here, we show that ex vivo administration of a function‐blocking anti‐CD5 MAb to primary mouse CTLs of both tumour‐naïve mice and mice bearing murine 4T1 breast tumour homografts enhanced their capacity to respond to activation by treatment with anti‐CD3/anti‐CD28 MAbs or 4T1 tumour cell lysates. Furthermore, it enhanced TCR signalling (ERK activation) and increased markers of T cell activation, including proliferation, CD69 levels, IFN‐γ production, apoptosis and Fas receptor and Fas ligand levels. Finally, CD5 function‐blocking MAb treatment enhanced the capacity of CD8 + T cells to kill 4T1‐mouse tumour cells in an ex vivo assay. These data support the potential of blockade of CD5 function to enhance T cell‐mediated anti‐tumour immunity.
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1491907-2
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  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Molecular Cancer Therapeutics Vol. 14, No. 12_Supplement_1 ( 2015-12-01), p. B05-B05
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 14, No. 12_Supplement_1 ( 2015-12-01), p. B05-B05
    Abstract: The Fes protein tyrosine kinase is abundantly expressed in phagocytic immune cells, including tumor associated macrophages. In addition to the C-terminal kinase and central SH2 domains, Fes contains an N-terminal F-BAR domain that confers unique membrane binding and bending properties which implicate it in the regulation of dynamic membrane-cytoskeletal remodeling processes associated with phagocytosis, receptor endocytosis, vesicular trafficking and cross-talk between receptor systems. In addition to roles in signaling downstream from a variety of cytokine receptors, including those for IL-3, -4, -5, and GM-CSF, Fes has also been implicated in regulating signaling downstream from the TLR-4 receptor for LPS. Fes knockout mice display enhanced sensitivity to LPS, and this was shown to be associated with increased NF-κB signaling and TNFα production from Fes-/- macrophages. Recent studies have also implicated Fes in cross-talk between MHC-I and the NF-κB and IRF-3 pathways in macrophages. Activation of these pro-inflammatory NF-κB and IRF-3 pathways so called Signal 3 - in antigen presenting cells (APCs) is associated with more robust activation of T cells. Interestingly, tumor onset in the MMTV-Neu transgenic mouse model of breast cancer is significantly delayed in Fes-/-, and this was associated with increased frequency of T and B lymphocytes in the premalignant mammary glands. These observations suggest that Fes contributes to the regulation of signaling downstream from the MHC-I and TLR receptors such that Fes disruption in TLR-engaged APCs would lead to enhanced activation of CD8+ T cells through increased Signal 3 from the T-cell receptor-engaged APCs. Using a lymphocytic choriomeningitis virus (LCMV) model of immune activation we show that LPS stimulated Fes-/- macrophages promote more robust activation of CD8+ T cells than Fes+/+ macrophages. Furthermore, LPS stimulated Fes-/- macrophages show increased phosphorylation of TBK-1 and IRF-3. We also observed that Fes co-localizes with MHC-I in dynamic vesicular structures within macrophages. These observations are consistent with a model where Fes regulates Signal 3 in APCs through roles in cross-talk between MHC-I and the NF-kB and IRF-3 signaling pathways. This suggests that Fes plays an immune checkpoint role at the level of Signal 3, and that Fes inhibition could promote tumor immunity through increased Signal 3 driven T cell activation. Citation Format: Faizah Mesfer Alotaibi, Connie Zhang, Sam Basta, Peter A. Greer. An immune modulatory role for the Fes protein tyrosine kinase. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B05.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2016
    In:  The Saudi Journal for Dental Research Vol. 7, No. 1 ( 2016-01), p. 51-56
    In: The Saudi Journal for Dental Research, Elsevier BV, Vol. 7, No. 1 ( 2016-01), p. 51-56
    Type of Medium: Online Resource
    ISSN: 2352-0035
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2835648-2
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  • 6
    Online Resource
    Online Resource
    Medknow ; 2019
    In:  Journal of Microscopy and Ultrastructure Vol. 7, No. 4 ( 2019), p. 147-
    In: Journal of Microscopy and Ultrastructure, Medknow, Vol. 7, No. 4 ( 2019), p. 147-
    Type of Medium: Online Resource
    ISSN: 2213-879X
    Language: English
    Publisher: Medknow
    Publication Date: 2019
    detail.hit.zdb_id: 2821816-4
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 938-938
    Abstract: Introduction: Molecular Tumor Boards (MTB) are essential in Precision Oncology Programs. Gaps, however, remain in interpreting comprehensive genomic profiling (CGP) results, and determining their actionability. Our MTB, established in October 2020 and conducted at a tertiary cancer center in Saudi Arabia, focused on discussing patients with complex CGP results and recommending genomic based therapies. Meetings occurred virtually, every month, with oncologists, pathologists and genomicists attending. Methods: This is a retrospective cohort study of patients discussed in our MTB from October 2020 till October 2022. We report the outcomes of these patients who had progressive disease on standard of care (SOC) therapies, and have had non Tier 1 alterations (ESCAT classification) in their CGP reports. We chose an FDA approved, commercially available CGP, which tests 324 genes (FoundationOne CDX). We present the demographics, clinical characteristics, CGP results, recommendations of the MTB, and patient outcomes. Results: Sixty patients fitting the criteria above have been discussed. Median number of prior systemic therapy lines was 2 (range 0-8). The most common primary diagnosis was soft tissue sarcoma (25%), followed by liver and pancreato-biliary cancers (20%), followed by head and neck cancers (15%) and skin cancers (8%). Of the 60 patients, 48 patients had response evaluations. Thirty five patients (out of 48, 73%) have had recommendations for genomic based therapies based on their CGP results. Only 16 patients (out of 35, 46%) received MTB recommended therapies. Eight patients (out of 16, 50%) have remained progression free and on MTB recommended genomic therapy for 6 months and above. The commonest reasons for not receiving MTB recommended therapy were patient clinical deterioration or death (9 patients, 47%) followed by patients responding on current line of therapy (7 patients, 37%). Most common pathogenic targetable alterations were CDKN2A/B mutations (6 patients), followed by alterations in FGFR (5 patients), PTEN (4 patients), BRAF (4 patients), PIK3CA (2 patients) and ERBB2 (2 patients) followed by others (will be presented). Conclusion: Following recommendations, of the first MTB in Saudi Arabia, resulted in improved outcomes of cancer patients who had progressive disease on SOC therapies. Consideration of performing CGP and discussing patients early in their cancer journey may allow them to receive, and benefit from recommended genomic therapies earlier. Citation Format: Kanan Alshammari, Fouad Sabatin, Mehlika Hazar-Rethinam, Faizah Alotaibi, Reham Ajina, Hussam Shehata, Mohammad Alkhayyat, Abdullah Alsaleh, Mohammed Algarni. Outcomes of molecular tumor board recommendations for cancer patients with progression on standard of care therapies in Saudi Arabia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 938.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 917-917
    Abstract: Blockade of programmed cell death protein 1 (PD-1) is approved for treatment of multiple human cancers and is the focus of multiple studies due to its key role in T cell function. However, only patients with ‘'hot'' tumors (i.e. those with increased numbers of tumor-infiltrating CD8+ T cells) respond well to the blockade. This suggests that new strategies to increase infiltration of CD8+ T cells into tumors will increase the number of tumor types and patients benefiting from anti-PD-1 therapy. CD5, a member of the scavenger receptor cysteine-rich (SRCR) superfamily, is expressed on T cells and a subset of B cells (B1a). It can attenuate TCR signaling and impair cytotoxic T lymphocyte (CTL) activation. CD5 knockout mice have increased anti-tumor immunity and reduced homograft tumor growth: reducing CD5 on CTLs may be therapeutically beneficial to enhance the anti-tumor response and increase tumor-infiltrating CD8+ T cells. We report that in vivo administration of anti-CD5 blocking MAb treatment increased primary T cell activation in response to 4T1 tumor cell homografts and ex vivo activation as measured by increased CD69, Fas, Fas ligand, IFNγ, PD-1, and apoptosis. Further, anti-CD5 treatment enhanced the capacity of primary T cells to kill 4T1 tumor cells ex vivo. Mice receiving anti-CD5 and anti-PD-1 in combination exhibited increased overall survival compared to mice treated with either agent alone. These data support the potential of blockade of CD5 function to enhance T cell-mediated anti-tumor immunity and PD-1 blockade treatment. Citation Format: Faizah Alotaibi, Mateusz Rytelewski, Rene Figueredo, Ronak Zareardalan1, Saman Maleki Vareki, Xiufen Zheng, Meng Zhang, Peter Ferguson, Mikal El-Hajjar, Yousef Najajreh, Wei-ping Min, James Koropatnick. Functional blocking of CD5 on T cells to enhance the efficacy of therapeutic PD-1 blockade in treatment of mouse 4T1 breast tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 917.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Veterinary Science Vol. 9 ( 2022-3-8)
    In: Frontiers in Veterinary Science, Frontiers Media SA, Vol. 9 ( 2022-3-8)
    Abstract: Rotavirus, one of the main pathogens causing morbidity and mortality in neonatal dairy calves worldwide, is responsible for 30–44% of cattle deaths. It is considered to be the most common etiologic agent of diarrhea in neonatal dairy calves and children, the dominant type being group A. Two hundred seventy animals from 27 farms from 2 regions of Kuwait were tested for the presence of Rotavirus serogroup A (RVA) using latex agglutination test (LAT) and reverse transcription–polymerase chain (RT-PCR) testing. RVA non-structural proteins NSP1-2, NSP4-5 and capsid protein genes VP1-7 were characterized by next generation sequencing. LAT was positive in 15.56% of the animals, and RT-PCR in 28.89%. Using RT-PCR as a reference method, LAT was 100% specific but only 83.33% sensitive. ANOVA analysis showed correlation only with the location of the farms but no significant correlation with the age and sex of the animals. Although there was a tendency of clustering of RVA positive animals, it did not reach statistical significance ( p = 0.035 for LAT). The phylogenetic analysis showed that Kuwaiti isolates of group A rotavirus clustered with human rotaviruses. Taken together, it seems that rotavirus was present in most of the dairy farms in Kuwait. The high occurrence of the virus in calves in Kuwaiti dairy farms and the close phylogenetic affinity with human isolates warrants urgent action to minimize and control its spread between calves in farms.
    Type of Medium: Online Resource
    ISSN: 2297-1769
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2834243-4
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 11 ( 2021-1-28)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2021-1-28)
    Abstract: CD5, a member of the scavenger receptor cysteine-rich superfamily, is a marker for T cells and a subset of B cells (B1a). CD5 associates with T-cell and B-cell receptors and increased CD5 is an indication of B cell activation. In tumor-infiltrating lymphocytes (TILs) isolated from lung cancer patients, CD5 levels were negatively correlated with anti-tumor activity and tumor‐mediated activation-induced T cell death, suggesting that CD5 could impair activation of anti-tumor T cells. We determined CD5 levels in T cell subsets in different organs in mice bearing syngeneic 4T1 breast tumor homografts and assessed the relationship between CD5 and increased T cell activation and effector function by flow cytometry. We report that T cell CD5 levels were higher in CD4 + T cells than in CD8 + T cells in 4T1 tumor-bearing mice, and that high CD5 levels on CD4 + T cells were maintained in peripheral organs (spleen and lymph nodes). However, both CD4 + and CD8 + T cells recruited to tumors had reduced CD5 compared to CD4 + and CD8 + T cells in peripheral organs. In addition, CD5 high /CD4 + T cells and CD5 high /CD8 + T cells from peripheral organs exhibited higher levels of activation and associated effector function compared to CD5 low /CD4 + T cell and CD5 low /CD8 + T cell from the same organs. Interestingly, CD8 + T cells among TILs and downregulated CD5 were activated to a higher level, with concomitantly increased effector function markers, than CD8 + /CD5 high TILs. Thus, differential CD5 levels among T cells in tumors and lymphoid organs can be associated with different levels of T cell activation and effector function, suggesting that CD5 may be a therapeutic target for immunotherapeutic activation in cancer therapy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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