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  1. Article ; Online: Protocol for drug screening of patient-derived tumor organoids using high-content fluorescent imaging.

    Larsen, Brian M / Cancino, Andrea / Shaxted, Jenna M / Salahudeen, Ameen A

    STAR protocols

    2022  Volume 3, Issue 2, Page(s) 101407

    Abstract: High-content imaging of tumor organoids (TOs) treated with therapeutic agents provides detailed cell viability readouts at the organoid level. In contrast, most used protocols provide one number per well. While requiring the use of inverted microscopy ... ...

    Abstract High-content imaging of tumor organoids (TOs) treated with therapeutic agents provides detailed cell viability readouts at the organoid level. In contrast, most used protocols provide one number per well. While requiring the use of inverted microscopy with an automated stage, this protocol can provide critical information about heterogeneous responses of TOs to various treatments. This protocol describes a technique for culturing and drug testing TOs using fluorescent indicators of cell viability with high reproducibility. For complete details on the use and execution of this protocol, please refer to Larsen et al. (2021).
    MeSH term(s) Diagnostic Imaging ; Drug Evaluation, Preclinical ; Humans ; Neoplasms/diagnostic imaging ; Organoids ; Reproducibility of Results
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Protocol for drug screening of patient-derived tumor organoids using high-content fluorescent imaging

    Brian M. Larsen / Andrea Cancino / Jenna M. Shaxted / Ameen A. Salahudeen

    STAR Protocols, Vol 3, Iss 2, Pp 101407- (2022)

    2022  

    Abstract: Summary: High-content imaging of tumor organoids (TOs) treated with therapeutic agents provides detailed cell viability readouts at the organoid level. In contrast, most used protocols provide one number per well. While requiring the use of inverted ... ...

    Abstract Summary: High-content imaging of tumor organoids (TOs) treated with therapeutic agents provides detailed cell viability readouts at the organoid level. In contrast, most used protocols provide one number per well. While requiring the use of inverted microscopy with an automated stage, this protocol can provide critical information about heterogeneous responses of TOs to various treatments. This protocol describes a technique for culturing and drug testing TOs using fluorescent indicators of cell viability with high reproducibility.For complete details on the use and execution of this protocol, please refer to Larsen et al. (2021). : Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Cancer ; High Throughput Screening ; Microscopy ; Organoids ; Science (General) ; Q1-390
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Toward recreating colon cancer in human organoids.

    Salahudeen, Ameen A / Kuo, Calvin J

    Nature medicine

    2015  Volume 21, Issue 3, Page(s) 215–216

    MeSH term(s) Adenocarcinoma/genetics ; Adenoma/genetics ; Animals ; Colorectal Neoplasms/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa ; Organoids
    Language English
    Publishing date 2015-02-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm.3818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Integrating pharmacogenomic testing into paired germline and somatic genomic testing in patients with cancer.

    Seligson, Nathan D / Kolesar, Jill M / Alam, Benish / Baker, Laura / Lamba, Jatinder K / Fridley, Brooke L / Salahudeen, Ameen A / Hertz, Daniel L / Hicks, J Kevin

    Pharmacogenomics

    2023  Volume 24, Issue 13, Page(s) 731–738

    Abstract: Precision medicine has revolutionized clinical care for patients with cancer through the development of targeted therapy, identification of inherited cancer predisposition syndromes and the use of pharmacogenetics to optimize pharmacotherapy for ... ...

    Abstract Precision medicine has revolutionized clinical care for patients with cancer through the development of targeted therapy, identification of inherited cancer predisposition syndromes and the use of pharmacogenetics to optimize pharmacotherapy for anticancer drugs and supportive care medications. While germline (patient) and somatic (tumor) genomic testing have evolved separately, recent interest in paired germline/somatic testing has led to an increase in integrated genomic testing workflows. However, paired germline/somatic testing has generally lacked the incorporation of germline pharmacogenomics. Integrating pharmacogenomics into paired germline/somatic genomic testing would be an efficient method for increasing access to pharmacogenomic testing. In this perspective, the authors argue for the benefits of implementing a comprehensive approach integrating somatic and germline testing that is inclusive of pharmacogenomics in clinical practice.
    Language English
    Publishing date 2023-09-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2023-0125
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment.

    McDowell, Anthony / Hill, Kristen S / McCorkle, J Robert / Gorski, Justin / Zhang, Yilin / Salahudeen, Ameen A / Ueland, Fred / Kolesar, Jill M

    Diagnostics (Basel, Switzerland)

    2021  Volume 11, Issue 3

    Abstract: Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and ... ...

    Abstract Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment.
    Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate.
    Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness.
    Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer.
    Language English
    Publishing date 2021-02-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics11030395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Integration of tumor extrinsic and intrinsic features associates with immunotherapy response in non-small cell lung cancer.

    Lau, Denise / Khare, Sonal / Stein, Michelle M / Jain, Prerna / Gao, Yinjie / BenTaieb, Aicha / Rand, Tim A / Salahudeen, Ameen A / Khan, Aly A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 4053

    Abstract: The efficacy of immune checkpoint blockade (ICB) varies greatly among metastatic non-small cell lung cancer (NSCLC) patients. Loss of heterozygosity at the HLA-I locus (HLA-LOH) has been identified as an important immune escape mechanism. However, ... ...

    Abstract The efficacy of immune checkpoint blockade (ICB) varies greatly among metastatic non-small cell lung cancer (NSCLC) patients. Loss of heterozygosity at the HLA-I locus (HLA-LOH) has been identified as an important immune escape mechanism. However, despite HLA-I disruptions in their tumor, many patients have durable ICB responses. Here we seek to identify HLA-I-independent features associated with ICB response in NSCLC. We use single-cell profiling to identify tumor-infiltrating, clonally expanded CD4
    MeSH term(s) Biomarkers, Tumor/genetics ; CD8-Positive T-Lymphocytes ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Immunotherapy ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-31769-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Privacy preserving validation for multiomic prediction models.

    Ahmed, Talal / Carty, Mark A / Wenric, Stephane / Dry, Jonathan R / Salahudeen, Ameen A / Khan, Aly A / Lefkofsky, Eric / Stumpe, Martin C / Pelossof, Raphael

    Briefings in bioinformatics

    2022  Volume 23, Issue 3

    Abstract: Reproducibility of results obtained using ribonucleic acid (RNA) data across labs remains a major hurdle in cancer research. Often, molecular predictors trained on one dataset cannot be applied to another due to differences in RNA library preparation and ...

    Abstract Reproducibility of results obtained using ribonucleic acid (RNA) data across labs remains a major hurdle in cancer research. Often, molecular predictors trained on one dataset cannot be applied to another due to differences in RNA library preparation and quantification, which inhibits the validation of predictors across labs. While current RNA correction algorithms reduce these differences, they require simultaneous access to patient-level data from all datasets, which necessitates the sharing of training data for predictors when sharing predictors. Here, we describe SpinAdapt, an unsupervised RNA correction algorithm that enables the transfer of molecular models without requiring access to patient-level data. It computes data corrections only via aggregate statistics of each dataset, thereby maintaining patient data privacy. Despite an inherent trade-off between privacy and performance, SpinAdapt outperforms current correction methods, like Seurat and ComBat, on publicly available cancer studies, including TCGA and ICGC. Furthermore, SpinAdapt can correct new samples, thereby enabling unbiased evaluation on validation cohorts. We expect this novel correction paradigm to enhance research reproducibility and to preserve patient privacy.
    MeSH term(s) Algorithms ; Confidentiality ; Humans ; Privacy ; RNA ; Reproducibility of Results
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2022-02-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbac110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Rociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions.

    Chuang, Jody C / Salahudeen, Ameen A / Wakelee, Heather A

    Expert opinion on pharmacotherapy

    2016  Volume 17, Issue 7, Page(s) 989–993

    Abstract: Introduction: Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the ... ...

    Abstract Introduction: Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the majority of the patients with such driver mutations, all targeted therapies are limited by the eventual development of resistance mechanisms.
    Areas covered: EGFR T790M mutation is a common resistance mechanism after treatment with first or second generation EGFR tyrosine kinase inhibitors (TKI). Rociletinib is one of the third generation EGFR TKIs with activity against T790M and activating EGFR mutations while sparing the wild-type EGFR. In this review, we discuss the current understanding and available data on rociletinib, including the side effects associated with the medication. We will also review the BEAMing plasma test to detect T790M mutation without the need for repeat biopsy. Lastly, we review the potential resistance mechanisms after progression on rociletinib, and future directions.
    Expert opinion: It is important to note that there are other 3(rd) generation EGFR TKIs with activity against T790M already approved by the US FDA (osimertinib) and many others in development. Future research will focus on figuring out which patients can benefit the most from a particular medication with minimal side effects, and further resistance mechanisms after rociletinib.
    MeSH term(s) Acrylamides/pharmacokinetics ; Acrylamides/pharmacology ; Acrylamides/therapeutic use ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Clinical Trials as Topic ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms/drug therapy ; Mutation ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/pharmacokinetics ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptor, Epidermal Growth Factor/genetics
    Chemical Substances Acrylamides ; Antineoplastic Agents ; Protein Kinase Inhibitors ; Pyrimidines ; rociletinib (72AH61702G) ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1)
    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1517/14656566.2016.1162786
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis.

    Salahudeen, Ameen A / Seoane, Jose A / Yuki, Kanako / Mah, Amanda T / Smith, Amber R / Kolahi, Kevin / De la O, Sean M / Hart, Daniel J / Ding, Jie / Ma, Zhicheng / Barkal, Sammy A / Shukla, Navika D / Zhang, Chuck H / Cantrell, Michael A / Batish, Arpit / Usui, Tatsuya / Root, David E / Hahn, William C / Curtis, Christina /
    Kuo, Calvin J

    Cell reports

    2023  Volume 42, Issue 11, Page(s) 113355

    Abstract: Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid ... ...

    Abstract Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling to evaluate candidate oncogenic loci identified via integrative computational analysis of extreme copy gains overlapping with extreme expression dysregulation in The Cancer Genome Atlas. Subsets of "outlier" candidates were contextually screened as tissue-specific cDNA lentiviral libraries within cognate esophagus, oral cavity, colon, stomach, pancreas, and lung organoids bearing initial oncogenic mutations. Iterative analysis nominated the kinase DYRK2 at 12q15 as an amplified head and neck squamous carcinoma oncogene in p53
    MeSH term(s) Humans ; Tumor Suppressor Protein p53/genetics ; Oncogenes ; Cell Transformation, Neoplastic/genetics ; Neoplasms/genetics ; Carcinogenesis/genetics ; Gene Amplification
    Chemical Substances Tumor Suppressor Protein p53
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition.

    Masood, Ashiq / Christ, Trevor / Asif, Samia / Rajakumar, Priya / Gustafson, Beth A / Shune, Leyla O / Salahudeen, Ameen / Nedvad, Drew / Nanua, Suparna / Paner, Agne / Kuzel, Timothy M / Levy, Mia / Subramanian, Janakiraman / Raza, Shahzad

    NPJ genomic medicine

    2021  Volume 6, Issue 1, Page(s) 23

    Abstract: Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic ... ...

    Abstract Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic landscape, clinical course, and prognosis of NSSM are not well characterized. Here, we report a case of a patient with relapsed and refractory NSMM with brain metastasis harboring a TFG-ALK fusion showing a dramatic and durable (over two years) response to commercially available anaplastic lymphoma kinase (ALK) inhibitors. The case emphasizes the beneficial role of molecular profiling in this target-poor disease.
    Language English
    Publishing date 2021-03-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2813848-X
    ISSN 2056-7944 ; 2056-7944
    ISSN (online) 2056-7944
    ISSN 2056-7944
    DOI 10.1038/s41525-021-00186-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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