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  1. Article ; Online: Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chains Assists in the Differential Diagnosis of Nodular Lymphocyte-predominant Hodgkin Lymphoma.

    Kaseb, Hatem / Wang, Zhen / Cook, James R

    The American journal of surgical pathology

    2022  Volume 46, Issue 8, Page(s) 1078–1083

    Abstract: Establishing a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is often challenging as the differential diagnosis is broad, including classic Hodgkin lymphoma (cHL), progressive transformation of germinal centers (PTGC), and other ... ...

    Abstract Establishing a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is often challenging as the differential diagnosis is broad, including classic Hodgkin lymphoma (cHL), progressive transformation of germinal centers (PTGC), and other lymphoproliferative disorders. In this study, we investigate the utility of a recently described ultrasensitive in situ hybridization assay for kappa and lambda immunoglobulin light chains in distinguishing nLPHL, cHL, and PTGC. A total of 72 cases were examined (21 nLPHL, 33 cHL, and 18 PTGC). In nLPHL, the large neoplastic cells were light chain restricted in 21/21 (100%) cases (16 kappa, 5 lambda). In contrast, Reed-Sternberg cells of cHL were negative for kappa and lambda in all cases (0/33, 0%; P <0.001). In PTGC, polytypic B cells were noted in mantle zones and germinal centers in all cases, with 1 case (5%) also showing focal collections of light chain restricted large B cells. Background monotypic small B cells were identified in 3 cases, including 1 nLPHL and 2 cHL (1 of which arose in chronic lymphocytic leukemia). Ultrasensitive in situ hybridization for kappa and lambda is a useful addition to a standard immunophenotyping panel for the evaluation of suspected nLPHL.
    MeSH term(s) B-Lymphocytes/pathology ; Cell Transformation, Neoplastic ; Diagnosis, Differential ; Hodgkin Disease/diagnosis ; Hodgkin Disease/genetics ; Hodgkin Disease/pathology ; Humans ; Immunoglobulin lambda-Chains/genetics ; In Situ Hybridization ; Lymphoma ; RNA
    Chemical Substances Immunoglobulin lambda-Chains ; RNA (63231-63-0)
    Language English
    Publishing date 2022-02-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 752964-8
    ISSN 1532-0979 ; 0147-5185
    ISSN (online) 1532-0979
    ISSN 0147-5185
    DOI 10.1097/PAS.0000000000001881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1356: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article: Concerning consequences of blocking Notch signaling in satellite muscle stem cells.

    Kaseb, Hatem O / Gollin, Susanne M

    Frontiers in cell and developmental biology

    2015  Volume 3, Page(s) 11

    Language English
    Publishing date 2015-02-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2015.00011
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  3. Article ; Online: The clinicopathologic significance of NPM1 mutation and ability to detect mutated NPM1 by immunohistochemistry in non-AML myeloid neoplasms.

    Kaseb, Hatem / Visconte, Valeria / Socha, Daniel S / Crane, Genevieve M / Durkin, Lisa / Cook, James R / Maciejewski, Jaroslaw P / Hsi, Eric D / Rogers, Heesun J

    Genes, chromosomes & cancer

    2023  Volume 62, Issue 10, Page(s) 573–580

    Abstract: NPM1 mutated non-AML myeloid neoplasms (MN; <20% blasts) are characterized by an aggressive clinical course in a few studies. In this retrospective study, we evaluate the clinicopathologic and immunohistochemical features of non-AML MN patients with NPM1 ...

    Abstract NPM1 mutated non-AML myeloid neoplasms (MN; <20% blasts) are characterized by an aggressive clinical course in a few studies. In this retrospective study, we evaluate the clinicopathologic and immunohistochemical features of non-AML MN patients with NPM1 mutations. We assessed NPM1 mutation by targeted next generation sequencing (NGS). Cytoplasmic NPM1 expression was assessed by immunohistochemistry (IHC) on formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. We evaluated 34 non-AML MN patients with NPM1 mutations comprising MDS (22), MPN (3) and MDS/MPN (9). They commonly presented with anemia (88%), thrombocytopenia (58%) and leukopenia (50%). Bone marrow dysplasia was common (79%). The karyotype was often normal (64%). NGS for MN-associated mutations performed in a subset of the patients showed a median of 3 mutations. NPM1 mutations were more often missense (c.859C > T p. L287F; 65%) than frameshift insertion/duplication (35%) with median variant allele frequency (VAF; 9.7%, range 5.1%-49.8%). Mutated NPM1 by IHC showed cytoplasmic positivity in 48% and positivity was associated with higher VAF. The median overall survival (OS) in this cohort was 70 months. Nine patients (26%) progressed to AML. OS in patients who progressed to AML was significantly shorter than the one of patients without progression to AML (OS 20 vs. 128 months, respectively, log rank p = 0.05). NPM1 mutated non-AML MN patients commonly had cytopenias, dysplasia, normal karyotype, mutations in multiple genes, and an unfavorable clinical outcome, including progression to AML. Our data demonstrated that IHC for NPM1 can be a useful supplementary tool to predict NPM1 mutation in some non-AML MN; however, genetic testing cannot be replaced by IHC assessment.
    MeSH term(s) Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Nucleophosmin ; Leukemia, Myeloid, Acute/pathology ; Immunohistochemistry ; Retrospective Studies ; Myeloproliferative Disorders ; Mutation
    Chemical Substances Nuclear Proteins ; Nucleophosmin (117896-08-9)
    Language English
    Publishing date 2023-04-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1018988-9
    ISSN 1098-2264 ; 1045-2257
    ISSN (online) 1098-2264
    ISSN 1045-2257
    DOI 10.1002/gcc.23139
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2966: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Concerning Consequences of Blocking Notch Signaling in Satellite Muscle Stem Cells

    Hatem Osama Kaseb / Susanne M. Gollin

    Frontiers in Cell and Developmental Biology, Vol

    2015  Volume 3

    Keywords stem cell ; targeted therapy ; Toxicity ; tumor cells ; Notch signalling ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2015-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

    Kaseb, Hatem O / Lewis, Dale W / Saunders, William S / Gollin, Susanne M

    Genes, chromosomes & cancer

    2016  Volume 55, Issue 9, Page(s) 694–709

    Abstract: Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and ...

    Abstract Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc.
    MeSH term(s) Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Differentiation/genetics ; Cell Differentiation/radiation effects ; Cell Division/genetics ; Cell Division/radiation effects ; Chromosome Segregation/genetics ; Chromosome Segregation/radiation effects ; Fluorescent Antibody Technique ; Humans ; Infrared Rays ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Neoplastic Stem Cells/radiation effects ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; Tumor Cells, Cultured
    Chemical Substances Biomarkers, Tumor ; SOX2 protein, human ; SOXB1 Transcription Factors
    Language English
    Publishing date 2016-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1018988-9
    ISSN 1098-2264 ; 1045-2257
    ISSN (online) 1098-2264
    ISSN 1045-2257
    DOI 10.1002/gcc.22371
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2966: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  6. Article ; Online: Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas.

    Kaseb, Hatem O / Fohrer-Ting, Helene / Lewis, Dale W / Lagasse, Eric / Gollin, Susanne M

    Experimental cell research

    2016  Volume 348, Issue 1, Page(s) 75–86

    Abstract: Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell ... ...

    Abstract Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66- is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance.
    MeSH term(s) Aged ; Aged, 80 and over ; Animals ; Antigens, CD/metabolism ; Biomarkers, Tumor/metabolism ; Carcinogenesis/pathology ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Self Renewal ; Cell Separation ; Chromosomal Instability ; Clone Cells ; Feeder Cells/cytology ; Female ; Fluorescent Antibody Technique ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/pathology ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Mice ; Middle Aged ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Radiation Tolerance ; Squamous Cell Carcinoma of Head and Neck
    Chemical Substances Antigens, CD ; Biomarkers, Tumor
    Language English
    Publishing date 2016-09-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2016.09.003
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 563: 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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  7. Article ; Online: (with research data) Fat, fibre and cancer risk in African Americans and rural Africans.

    O'Keefe, Stephen J D / Li, Jia V / Lahti, Leo / Ou, Junhai / Carbonero, Franck / Mohammed, Khaled / Posma, Joram M / Kinross, James / Wahl, Elaine / Ruder, Elizabeth / Vipperla, Kishore / Naidoo, Vasudevan / Mtshali, Lungile / Tims, Sebastian / Puylaert, Philippe G B / DeLany, James / Krasinskas, Alyssa / Benefiel, Ann C / Kaseb, Hatem O /
    Newton, Keith / Nicholson, Jeremy K / de Vos, Willem M / Gaskins, H Rex / Zoetendal, Erwin G

    Nature communications

    2015  Volume 6, Page(s) 6342

    Abstract: Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower ...

    Abstract Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans.
    MeSH term(s) Black or African American/statistics & numerical data ; Aged ; Biomarkers/metabolism ; Colon/metabolism ; Colon/microbiology ; Colonic Neoplasms/etiology ; Diet, Fat-Restricted ; Diet, High-Fat/adverse effects ; Diet, High-Fat/statistics & numerical data ; Dietary Fiber/statistics & numerical data ; Feces/chemistry ; Healthy Volunteers ; Humans ; Inflammation/etiology ; Inflammation/metabolism ; Intestinal Mucosa ; Metabolome ; Microbiota ; Middle Aged ; Rural Population/statistics & numerical data ; South Africa ; Urine/chemistry
    Chemical Substances Biomarkers ; Dietary Fiber
    Language English
    Publishing date 2015-04-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms7342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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