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  1. Article ; Online: High-grade squamous intraepithelial lesion cervicovaginal paps with negative high-risk HPV testing, a prospective study with histological follow-up.

    Agoff, S Nicholas / Brockmeyer, Amy D / Barrie, Allison M / Larson, Julie

    Diagnostic cytopathology

    2023  Volume 51, Issue 8, Page(s) 475–479

    Abstract: Background: High-risk human papillomavirus (hrHPV) testing has become integral in the screening and treatment protocols for cervical neoplasia. Stand-alone HPV testing is advocated as a screening tool for cervical neoplasia. However, negative hrHPV ... ...

    Abstract Background: High-risk human papillomavirus (hrHPV) testing has become integral in the screening and treatment protocols for cervical neoplasia. Stand-alone HPV testing is advocated as a screening tool for cervical neoplasia. However, negative hrHPV tests with diagnosis of high-grade squamous intraepithelial lesion or worse (≥HSIL) have been reported. We report our experience with paps diagnosed as HSIL, negative hrHPV testing, and subsequent follow-up.
    Methods: Of 303 women with HSIL diagnosed on ThinPrep pap between 2019 and 2023, 84 (28%) were tested for hrHPV by Roche Cobas. Repeat testing was performed at a referral center. Immunohistochemistry (IHC) for p16 was performed on follow-up biopsies and hrHPV in-situ hybridization.
    Results: Of 84 HSIL cases, 8 were hrHPV negative. Follow-up biopsies available in 7 cases were ≥HSIL (1 with invasive squamous cell carcinoma, 1 endocervical adenocarcinoma in situ). Follow-up HSIL was found on additional cases of HPV negative atypical glandular cells favor neoplastic and atypical squamous cells favor HSIL. IHC for p16 was positive on all biopsies. hrHPV FISH was negative.
    Conclusions: Our experience with hrHPV testing by Roche Cobas demonstrates that some morphologically diagnostic HSIL paps are hrHPV negative: 8.3% of HSIL paps with subsequent histological HSIL were HPV negative. The index case caused concern among our clinical colleagues. Positive staining for p16 is highly suggestive of HPV induced disease. Possible reasons for negative hrHPV testing could include non-hrHPV types, low HPV DNA levels, or HPV types not included in the Cobas testing panel.
    MeSH term(s) Female ; Humans ; Prospective Studies ; Papanicolaou Test ; Follow-Up Studies ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis ; Papillomavirus Infections/pathology ; Uterine Cervical Neoplasms/pathology ; Squamous Intraepithelial Lesions ; Carcinoma, Squamous Cell/pathology ; Carcinoma in Situ ; Papillomaviridae/genetics ; Uterine Cervical Dysplasia/pathology ; Vaginal Smears
    Language English
    Publishing date 2023-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632710-2
    ISSN 1097-0339 ; 8755-1039
    ISSN (online) 1097-0339
    ISSN 8755-1039
    DOI 10.1002/dc.25146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2117: 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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  2. Article: Dramatic response to Laetrile and cannabidiol (CBD) oil in a patient with metastatic low grade serous ovarian carcinoma.

    Barrie, Allison M / Gushue, Ariane C / Eskander, Ramez N

    Gynecologic oncology reports

    2019  Volume 29, Page(s) 10–12

    Abstract: Complimentary alternative medicine use is common in women with gynecologic cancers.•Cannabinoid receptors are potential therapeutic targets in ovarian cancer.•Communication with patients is critical regarding use of alternative therapies. ...

    Abstract •Complimentary alternative medicine use is common in women with gynecologic cancers.•Cannabinoid receptors are potential therapeutic targets in ovarian cancer.•Communication with patients is critical regarding use of alternative therapies.
    Language English
    Publishing date 2019-05-17
    Publishing country Netherlands
    Document type Case Reports
    ZDB-ID 2818505-5
    ISSN 2352-5789
    ISSN 2352-5789
    DOI 10.1016/j.gore.2019.05.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.

    Ozmadenci, Duygu / Shankara Narayanan, Jayanth S / Andrew, Jacob / Ojalill, Marjaana / Barrie, Allison M / Jiang, Shulin / Iyer, Samhita / Chen, Xiao Lei / Rose, Michael / Estrada, Valeria / Molinolo, Alfredo / Bertotto, Thomas / Mikulski, Zbigniew / McHale, Michael C / White, Rebekah R / Connolly, Denise C / Pachter, Jonathan A / Kuchroo, Vijay K / Stupack, Dwayne G /
    Schlaepfer, David D

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 17, Page(s) e2117065119

    Abstract: High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the ... ...

    Abstract High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.
    MeSH term(s) Animals ; Carcinoma, Ovarian Epithelial ; Female ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Immunosuppression Therapy ; Ligands ; Mice ; Ovarian Neoplasms/pathology ; Receptors, Immunologic/metabolism
    Chemical Substances Ligands ; Receptors, Immunologic ; T cell Ig and ITIM domain protein, mouse ; TIGIT protein, human ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; Ptk2 protein, mouse (EC 2.7.10.2)
    Language English
    Publishing date 2022-04-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2117065119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: 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: Rgnef promotes ovarian tumor progression and confers protection from oxidative stress.

    Kleinschmidt, Elizabeth G / Miller, Nichol L G / Ozmadenci, Duygu / Tancioni, Isabelle / Osterman, Carlos Díaz / Barrie, Allison M / Taylor, Kristin N / Ye, Aaron / Jiang, Shulin / Connolly, Denise C / Stupack, Dwayne G / Schlaepfer, David D

    Oncogene

    2019  Volume 38, Issue 36, Page(s) 6323–6337

    Abstract: Ovarian cancer is the fifth-leading cause of cancer death among women. The dissemination of ovarian tumors and growth as spheroids accompanies late-stage disease. In cell culture, ovarian tumor cell spheroids can exhibit elevated resistance to ... ...

    Abstract Ovarian cancer is the fifth-leading cause of cancer death among women. The dissemination of ovarian tumors and growth as spheroids accompanies late-stage disease. In cell culture, ovarian tumor cell spheroids can exhibit elevated resistance to environmental stressors, such as reactive oxygen species. Homeostatic balance of the antioxidant response is a protective mechanism that prevents anoikis, a form of programmed cell death. Signaling pathways activated by integrin receptors suppress anoikis. Rgnef (ARHGEF28/p190RhoGEF) is a guanine nucleotide exchange factor that is activated downstream of integrins. We find that Rgnef protein levels are elevated in late-stage serous ovarian cancer, high Rgnef mRNA levels are associated with decreased progression-free and overall survival, and genomic ARHGEF28 loss is associated with increased patient survival. Using transgenic and transplantable Rgnef knockout mouse models, we find that Rgnef is essential for supporting three-dimensional ovarian spheroid formation in vitro and tumor growth in mice. Using RNA-sequencing and bioinformatic analyses, we identify a conserved Rgnef-supported anti-oxidant gene signature including Gpx4, Nqo1, and Gsta4; common targets of the NF-kB transcription factor. Antioxidant treatment enhanced growth of Rgnef-knockout spheroids and Rgnef re-expression facilitated NF-κB-dependent tumorsphere survival. These studies reveal a new role for Rgnef in ovarian cancer to facilitate NF-κB-mediated gene expression protecting cells from oxidative stress.
    MeSH term(s) Animals ; Cell Proliferation/genetics ; Cytoprotection/genetics ; Disease Progression ; Female ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/physiology ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; NF-kappa B/metabolism ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Oxidative Stress/genetics ; Signal Transduction/genetics ; Tumor Cells, Cultured ; ras-GRF1/genetics ; ras-GRF1/physiology
    Chemical Substances ARHGEF28 protein, human ; Guanine Nucleotide Exchange Factors ; NF-kappa B ; Rasgrf1 protein, mouse ; ras-GRF1
    Language English
    Publishing date 2019-07-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-019-0881-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2218: 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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  5. Article ; Online: FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

    Diaz Osterman, Carlos J / Ozmadenci, Duygu / Kleinschmidt, Elizabeth G / Taylor, Kristin N / Barrie, Allison M / Jiang, Shulin / Bean, Lisa M / Sulzmaier, Florian J / Jean, Christine / Tancioni, Isabelle / Anderson, Kristen / Uryu, Sean / Cordasco, Edward A / Li, Jian / Chen, Xiao Lei / Fu, Guo / Ojalill, Marjaana / Rappu, Pekka / Heino, Jyrki /
    Mark, Adam M / Xu, Guorong / Fisch, Kathleen M / Kolev, Vihren N / Weaver, David T / Pachter, Jonathan A / Győrffy, Balázs / McHale, Michael T / Connolly, Denise C / Molinolo, Alfredo / Stupack, Dwayne G / Schlaepfer, David D

    eLife

    2019  Volume 8

    Abstract: Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, ... ...

    Abstract Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Cisplatin/pharmacology ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Female ; Focal Adhesion Kinase 1/metabolism ; Humans ; Mice ; Ovarian Neoplasms/drug therapy ; Platinum/pharmacology ; Proto-Oncogene Proteins c-myc/metabolism ; Proto-Oncogene Proteins p21(ras)/metabolism ; Signal Transduction ; Stem Cells
    Chemical Substances Antineoplastic Agents ; KRAS protein, human ; MYC protein, human ; Proto-Oncogene Proteins c-myc ; Platinum (49DFR088MY) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2019-09-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.47327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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