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  1. Article ; Online: Generation of myoglobin (MB)-knockout human embryonic stem cell (hESC) line (KAIMRCe002-A-1S) using CRISPR/Cas9 technology.

    Alowaysi, Maryam / Al-Shehri, Mohammad / Baadhaim, Moayad / AlZahrani, Hajar / Aboalola, Doaa / Daghestani, Mustafa / Hashem, Heba / Aljahdali, Rawan / Salem, Rayan / Alharbi, Adel / Muharraq, Mohammed / Alghamdi, Khaled / Alsobiy, Fawaz / Zia, Asima / Lehmann, Robert / Tegner, Jesper / Alsayegh, Khaled

    Stem cell research

    2023  Volume 71, Page(s) 103158

    Abstract: Myoglobin (MB) is a cytoplasmic hemoprotein that is predominantly expressed in the heart and oxidative myofibers of skeletal muscle. It has been demonstrated that MB binds to oxygen and promotes its diffusion for energy production in the mitochondria. ... ...

    Abstract Myoglobin (MB) is a cytoplasmic hemoprotein that is predominantly expressed in the heart and oxidative myofibers of skeletal muscle. It has been demonstrated that MB binds to oxygen and promotes its diffusion for energy production in the mitochondria. Recently, MB was found to be expressed in different forms of malignant tumors and cancer cell lines. Further studies using gene disruption technology will enhance the understanding of MB's role in human cardiovascular biology and cancers. Here, we describe the generation of a homozygous MB knockout in human embryonic stem cells (hESC-MB
    MeSH term(s) Humans ; Myoglobin/genetics ; Myoglobin/metabolism ; Human Embryonic Stem Cells/metabolism ; CRISPR-Cas Systems/genetics ; Cell Line ; Technology
    Chemical Substances Myoglobin
    Language English
    Publishing date 2023-06-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2023.103158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Preparation of iron oxide mesoporous magnetic microparticles as novel multidrug carriers for synergistic anticancer therapy and deep tumor penetration.

    El-Boubbou, Kheireddine / Ali, Rizwan / Al-Zahrani, Hajar / Trivilegio, Thadeo / Alanazi, Abdullah H / Khan, Abdul Latif / Boudjelal, Mohamed / AlKushi, Abdulmohsen

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 9481

    Abstract: The preparation of mesoporous iron oxides with controllable physiochemical properties for effective therapeutic drug delivery remains a formidable challenge. Herein, iron oxide mesoporous magnetic microparticles (IO-MMMs) were prepared by a modified ... ...

    Abstract The preparation of mesoporous iron oxides with controllable physiochemical properties for effective therapeutic drug delivery remains a formidable challenge. Herein, iron oxide mesoporous magnetic microparticles (IO-MMMs) were prepared by a modified reverse hard-templating approach using, for the first time, acid-prepared mesoporous spheres (APMS) as the hard silica template. The obtained mesostructures exhibited remarkably high surface area and large pore volumes (S
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Drug Carriers/chemistry ; Drug Carriers/pharmacokinetics ; Drug Carriers/pharmacology ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Porosity ; Silicon Dioxide/chemistry ; Silicon Dioxide/pharmacokinetics ; Silicon Dioxide/pharmacology
    Chemical Substances Antineoplastic Agents ; Drug Carriers ; Silicon Dioxide (7631-86-9)
    Language English
    Publishing date 2019-07-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46007-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: New Born Calf Serum Can Induce Spheroid Formation in Breast Cancer KAIMRC1 Cell Line.

    Ali, Rizwan / Huwaizi, Sarah / Alhallaj, Alshaimaa / Al Subait, Arwa / Barhoumi, Tlili / Al Zahrani, Hajar / Al Anazi, Abdullah / Latif Khan, Abdul / Boudjelal, Mohamed

    Frontiers in molecular biosciences

    2021  Volume 8, Page(s) 769030

    Abstract: Three-dimensional (3D) cell culture systems have become very popular in the field of drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. We have developed a novel and ... ...

    Abstract Three-dimensional (3D) cell culture systems have become very popular in the field of drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. We have developed a novel and easy method to produce spheroids from the newly isolated KAIMRC1 cell line
    Language English
    Publishing date 2021-12-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2021.769030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Discovery of a novel potentially transforming somatic mutation in CSF2RB gene in breast cancer.

    Rashid, Mamoon / Ali, Rizwan / Almuzzaini, Bader / Song, Hao / AlHallaj, Alshaimaa / Abdulkarim, Al Abdulrahman / Mohamed Baz, Omar / Al Zahrani, Hajar / Mustafa Sabeena, Muhammed / Alharbi, Wardah / Hussein, Mohamed / Boudjelal, Mohamed

    Cancer medicine

    2021  Volume 10, Issue 22, Page(s) 8138–8150

    Abstract: The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL-3, IL-5, and GM-CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence ... ...

    Abstract The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL-3, IL-5, and GM-CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence in vitro. To date, no report(s) have been shown for the presence of potentially transforming and oncogenic CSF2RB mutation(s) clinically in cancer patients until the first reported case of a leukemia patient in 2016 harboring a germline-activating mutation (R461C). We combined exome sequencing, pathway analyses, and functional assays to identify novel somatic mutations in KAIMRC1 cells and breast tumor specimen. The patient's peripheral blood mononuclear cell (PBMC) exome served as a germline control in the identification of somatic mutations. Here, we report the discovery of a novel potentially transforming and oncogenic somatic mutation (S230I) in the CSF2RB gene of a breast cancer patient and the cell line, KAIMRC1 established from her breast tumor tissue. KAIMRC1 cells are immortalized and shown to survive and proliferate in ligand starvation condition. Immunoblot analysis showed that mutant CSF2RB signals through JAK2/STAT and PI3K/mTOR pathways in ligand starvation conditions. Screening a small molecule kinase inhibitor library revealed potent JAK2 inhibitors against KAIMRC1 cells. We, for the first time, identified a somatic, potentially transforming, and oncogenic CSF2RB mutation (S230I) in breast cancer patients that seem to be an actionable mutation leading to the development of new therapeutics for breast cancer.
    MeSH term(s) Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cytokine Receptor Common beta Subunit/metabolism ; Female ; Germ-Line Mutation ; Humans
    Chemical Substances CSF2RB protein, human ; Cytokine Receptor Common beta Subunit
    Language English
    Publishing date 2021-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.4106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Generation of induced pluripotent stem cell Line KAIMRCi001-A by reprogramming erythroid progenitors from peripheral blood of a healthy Saudi donor.

    Al-Shehri, Mohammad / Baadhaim, Moayad / Jamalalddin, Shereen / Aboalola, Doaa / Daghestani, Mustafa / AlZahrani, Hajar / Malibari, Dalal / Mubaraki, Mohammad / Aldubayan, Kholoud / AlBalwi, Mohammed / Alsayegh, Khaled

    Stem cell research

    2021  Volume 56, Page(s) 102548

    Abstract: In this study we isolated and enriched erythroid progenitor cells (EPCs) from a 10 ml peripheral blood sample from a 37-year old healthy Saudi donor. After expansion, these EPCs were reprogrammed using episomal plasmids to generate an induced pluripotent ...

    Abstract In this study we isolated and enriched erythroid progenitor cells (EPCs) from a 10 ml peripheral blood sample from a 37-year old healthy Saudi donor. After expansion, these EPCs were reprogrammed using episomal plasmids to generate an induced pluripotent stem (iPS) cell line, KAIMRCi001-A. The pluripotency of this line was confirmed by measuring the expression of typical pluripotency markers and assessing differentiation potential in vitro.
    MeSH term(s) Adult ; Cell Differentiation ; Cellular Reprogramming ; Humans ; Induced Pluripotent Stem Cells ; Saudi Arabia ; Tissue Donors
    Language English
    Publishing date 2021-09-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2021.102548
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Proteomics Profiling of KAIMRC1 in Comparison to MDA-MB231 and MCF-7.

    Alghanem, Bandar / Ali, Rizwan / Nehdi, Atef / Al Zahrani, Hajar / Altolayyan, Abdulelah / Shaibah, Hayat / Baz, Omar / Alhallaj, Alshaimaa / Moresco, James J / Diedrich, Jolene K / Yates, John R / Boudjelal, Mohamed

    International journal of molecular sciences

    2020  Volume 21, Issue 12

    Abstract: Proteomics characterization of KAIMRC1 cell line, a naturally immortalized breast cancer cells, is described in comparison to MCF-7 and MDA-MB-231 breast cancer cells. Quantitative proteomics analysis using the tandem mass tag (TMT)-labeled technique in ... ...

    Abstract Proteomics characterization of KAIMRC1 cell line, a naturally immortalized breast cancer cells, is described in comparison to MCF-7 and MDA-MB-231 breast cancer cells. Quantitative proteomics analysis using the tandem mass tag (TMT)-labeled technique in conjunction with the phosphopeptide enrichment method was used to perform comparative profiling of proteins and phosphoproteins in the three cell lines. In total, 673 proteins and 33 Phosphoproteins were differentially expressed among these cell lines. These proteins are involved in several key cellular pathways that include DNA replication and repair, splicing machinery, amino acid metabolism, cellular energy, and estrogen signaling pathway. Many of the differentially expressed proteins are associated with different types of tumors including breast cancer. For validation, 4 highly significant expressed proteins including S-methyl-5'-thioadenosine phosphorylase (MTAP), BTB/POZ domain-containing protein (KCTD12), Poly (ADP-ribose) polymerase 1 (PARP 1), and Prelamin-A/C were subjected to western blotting, and the results were consistent with proteomics analysis. Unlike MCF-7 and MDA-MB-231, KAIMRC1 showed different phospho- and non-phosphoproteomic phenotypes which make it a potential model to study breast cancer.
    MeSH term(s) Breast Neoplasms/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lamin Type A/metabolism ; MCF-7 Cells ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Protein Interaction Maps ; Proteins/metabolism ; Proteomics/methods ; Up-Regulation
    Chemical Substances KCTD12 protein, human ; Lamin Type A ; Proteins ; prelamin A ; PARP1 protein, human (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30)
    Language English
    Publishing date 2020-06-18
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21124328
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  7. Article ; Online: Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2.

    Ali, Rizwan / Al Zahrani, Hajar / Barhoumi, Tlili / Alhallaj, Alshaimaa / Mashhour, Abdullah / Alshammari, Musaad A / Alshawakir, Yasser A / Baz, Omar / Alanazi, Abdullah H / Khan, Abdul Latif / Al Nikhli, Hassan / Al Balwi, Mohammed A / Al Riyees, Lolwah / Boudjelal, Mohamed

    Cells

    2021  Volume 10, Issue 6

    Abstract: In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the ... ...

    Abstract In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells' expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.
    MeSH term(s) Adult ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Neoplasm Proteins/metabolism ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
    Chemical Substances Biomarkers, Tumor ; Neoplasm Proteins
    Language English
    Publishing date 2021-05-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10061303
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1.

    Ali, Rizwan / Samman, Nosaibah / Al Zahrani, Hajar / Nehdi, Atef / Rahman, Sabhi / Khan, Abdul Latif / Al Balwi, Mohamed / Alriyees, Lolwah Abdullah / Alzaid, Manal / Al Askar, Ahmed / Boudjelal, Mohamed

    BMC cancer

    2017  Volume 17, Issue 1, Page(s) 803

    Abstract: Background: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ... ...

    Abstract Background: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds.
    Methods: Breast cancer tissue sections were minced and cultured in media for several weeks. KAIMRC1 cells were successfully isolated from one of the primary breast tumor tissue cultures without any enzymatic digestion. To study the growth characteristics of the cells, wound healing assay, clonogenic assay, cell proliferation assays and live cell time-lapse microscopy was performed. Karyotyping, Immunophenotyping and molecular pathway specific compound treatment was also performed. A selective breast cancer gene expression panel was used to identify genes involved in the signal transduction dysregulation and malfunction of normal biological processes during breast carcinogenesis.
    Results: These cells are ER/PR-positive and HER2-negative. The epithelial nature of these cells was confirmed by flow cytometry analysis using epithelial cell markers. They are cuboidal in shape and relatively smaller in size as compared to established cell lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell culture conditions these cells showed the capability of growing both in monolayer as well as in 3-D conformation. They showed a doubling time in vitro of approximately 24 h. They exhibit a modal karyotype of 58-63,X with abnormalities in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7 cell lines.
    Conclusions: In conclusion we have isolated and characterized a new naturally immortalized breast cell line, KAIMRC1 with a potential to play a key role in opening up novel avenues towards the understanding of breast carcinoma.
    MeSH term(s) Breast Neoplasms/ethnology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Culture Techniques ; Cell Line, Tumor/cytology ; Cell Line, Tumor/metabolism ; Cell Line, Tumor/pathology ; Cell Proliferation ; Female ; Humans ; MAP Kinase Signaling System ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging
    Language English
    Publishing date 2017-11-29
    Publishing country England
    Document type Journal Article
    ISSN 1471-2407
    ISSN (online) 1471-2407
    DOI 10.1186/s12885-017-3812-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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