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  1. Article: Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

    Ghezelayagh, Talayeh S / Wu, Emily S / Barber, Emma L / Dao, Minh D / Zsiros, Emese / Urban, Renata R / Gray, Heidi J / Goff, Barbara A / Shah, Chirag A / Neubauer, Nikki L / Dai, James Y / Tanyi, Janos L / Liao, John B

    European journal of gynaecological oncology

    2023  Volume 44, Issue 1, Page(s) 17–25

    Abstract: Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has ... ...

    Abstract Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34,
    Language English
    Publishing date 2023-02-14
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 604589-3
    ISSN 0392-2936
    ISSN 0392-2936
    DOI 10.22514/ejgo.2023.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1679: Show issues Location:
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  2. Article ; Online: Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention.

    Ghezelayagh, Talayeh S / Stewart, Lauren E / Norquist, Barbara M / Bowen, Deborah J / Yu, Vivian / Agnew, Kathy J / Pennington, Kathryn P / Swisher, Elizabeth M

    Familial cancer

    2020  Volume 19, Issue 2, Page(s) 143–151

    Abstract: Salpingectomy with interval oophorectomy has gained traction as an ovarian cancer prevention strategy, but is not currently recommended for high risk women. Nevertheless, some choose this approach. We aimed to understand risk perception and plans for ... ...

    Abstract Salpingectomy with interval oophorectomy has gained traction as an ovarian cancer prevention strategy, but is not currently recommended for high risk women. Nevertheless, some choose this approach. We aimed to understand risk perception and plans for oophorectomy in BRCA1 and BRCA2 (BRCA) mutation carriers choosing salpingectomy for ovarian cancer prevention. This was a longitudinal survey study of BRCA mutation carriers who underwent bilateral salpingectomy to reduce ovarian cancer risk. An initial written questionnaire and telephone interview was followed by annual phone interviews. 22 women with BRCA mutations were enrolled. Median follow-up was three years. The median age at salpingectomy was 39.5 years (range 27-49). Perceived lifetime ovarian cancer risk decreased by half after salpingectomy (median risk reduction 25%, range 0-40%). At final follow-up, five (22.7%) had undergone oophorectomy and five women (22.7%) were not planning to undergo completion oophorectomy. BRCA mutation carriers who had salpingectomy after the recommended age of prophylactic surgery (vs. before the recommended age) were less likely to plan for future oophorectomy (28.6% vs. 66.7%, p = 0.037). All women were satisfied with their decision to undergo salpingectomy with eighteen (81.8%) expressing decreased cancer-related worry. There were no diagnoses of ovarian cancer during our study period. In conclusion, most BRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy in BRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven.
    MeSH term(s) Adult ; Age Factors ; Decision Making ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Health Surveys ; Heterozygote ; Humans ; Middle Aged ; Motivation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/prevention & control ; Ovarian Neoplasms/surgery ; Patient Satisfaction/statistics & numerical data ; Reward ; Risk ; Salpingectomy/psychology ; Salpingectomy/statistics & numerical data
    Language English
    Publishing date 2020-02-24
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1502496-9
    ISSN 1573-7292 ; 1389-9600
    ISSN (online) 1573-7292
    ISSN 1389-9600
    DOI 10.1007/s10689-020-00166-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6099: Show issues Location:
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  3. Article ; Online: Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations.

    Ghezelayagh, Talayeh S / Pennington, Kathryn P / Norquist, Barbara M / Khasnavis, Nithisha / Radke, Marc R / Kilgore, Mark R / Garcia, Rochelle L / Lee, Ming / Katz, Ronit / Leslie, Kimberly K / Risques, Rosa Ana / Swisher, Elizabeth M

    Gynecologic oncology

    2020  Volume 160, Issue 3, Page(s) 786–792

    Abstract: Objectives: Mutations in the TP53 tumor suppressor gene are common in ovarian carcinoma (OC) but their impact on outcomes is controversial. We sought to define the relationship of TP53 mutations to cancer outcomes and their interactions with co- ... ...

    Abstract Objectives: Mutations in the TP53 tumor suppressor gene are common in ovarian carcinoma (OC) but their impact on outcomes is controversial. We sought to define the relationship of TP53 mutations to cancer outcomes and their interactions with co-occurrent BRCA1 or BRCA2 (BRCA) mutations, comparing three different TP53 mutation classification schemes.
    Methods: We performed next generation sequencing on 393 cases of OC prospectively followed for survival. TP53 mutations were classified according to three schemes termed Structural, Functional, and Hotspot. Mutation distribution was compared between cases with and without BRCA mutations. In a subset of 281 cases of high grade serous carcinoma (HGSC), overall survival was compared using Kaplan-Meier curves, logrank testing, and multivariate Cox regression analysis, both stratified and adjusted for BRCA mutation status. Multivariate logistic regression was used to analyze the effects of TP53 mutation type on platinum resistance.
    Results: TP53 mutations were identified in 76.8% of the total cohort (n = 302/393) and 87.9% of HGSC (n = 247/281). Cases with BRCA mutations demonstrated significantly higher TP53 mutation frequency overall (n = 84/91, 92.3% vs. n = 218/302, 72.2%, p < 0.001). TP53 mutations were not associated with overall survival, even when stratified by BRCA mutation. TP53 mutations were associated with platinum sensitivity, even after adjusting for BRCA mutation status (OR 0.41, p = 0.048). The choice of TP53 mutation classification scheme was not found to alter any significant outcome.
    Conclusions: BRCA mutations significantly co-occur with TP53 mutations. After adjusting for BRCA mutations, TP53 mutations are associated with platinum sensitivity, and this effect is not dependent on TP53 mutation type.
    MeSH term(s) Female ; Genes, BRCA1/physiology ; Genes, BRCA2/physiology ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mutation ; Ovarian Neoplasms/genetics ; Prospective Studies ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2020-12-26
    Publishing country United States
    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 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2020.12.007
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 885: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women.

    Bartlett, Thomas E / Evans, Iona / Jones, Allison / Barrett, James E / Haran, Shaun / Reisel, Daniel / Papaikonomou, Kiriaki / Jones, Louise / Herzog, Chiara / Pashayan, Nora / Simões, Bruno M / Clarke, Robert B / Evans, D Gareth / Ghezelayagh, Talayeh S / Ponandai-Srinivasan, Sakthivignesh / Boggavarapu, Nageswara R / Lalitkumar, Parameswaran G / Howell, Sacha J / Risques, Rosa Ana /
    Rådestad, Angelique Flöter / Dubeau, Louis / Gemzell-Danielsson, Kristina / Widschwendter, Martin

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 64

    Abstract: Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone ... ...

    Abstract Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation.
    Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1-T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44).
    Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders.
    Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers.
    Trial registration: Clinical trial 1 Mifepristone treatment prior to insertion of a levonorgestrel releasing intrauterine system for improved bleeding control - a randomized controlled trial, clinicaltrialsregister.eu, 2009-009014-40

    registered on 20 July 2009. Clinical trial 2 The effect of a progesterone receptor modulator on breast tissue in women with BRCA1 and 2 mutations, clinicaltrials.gov, NCT01898312

    registered on 07 May 2013. Clinical trial 3 A pilot prevention study of the effects of the anti- progestin Ulipristal Acetate (UA) on surrogate markers of breast cancer risk, clinicaltrialsregister.eu, 2015-001587-19

    registered on 15 July 2015.
    MeSH term(s) Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Epigenesis, Genetic ; Female ; Humans ; Mifepristone ; Mutation ; Progesterone ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Triple Negative Breast Neoplasms/genetics
    Chemical Substances Receptors, Estrogen ; Receptors, Progesterone ; Mifepristone (320T6RNW1F) ; Progesterone (4G7DS2Q64Y)
    Language English
    Publishing date 2022-06-15
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01063-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Uterine lavage identifies cancer mutations and increased

    Ghezelayagh, Talayeh S / Kohrn, Brendan F / Fredrickson, Jeanne / Manhardt, Enna / Radke, Marc R / Katz, Ronit / Gray, Heidi J / Urban, Renata R / Pennington, Kathryn P / Liao, John B / Doll, Kemi M / Simons, Elise J / Burzawa, Jennifer K / Goff, Barbara A / Speiser, Paul / Swisher, Elizabeth M / Norquist, Barbara M / Risques, Rosa Ana

    Cancer research communications

    2022  Volume 2, Issue 10, Page(s) 1282–1292

    Abstract: Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined ... ...

    Abstract Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with
    MeSH term(s) Humans ; Female ; Therapeutic Irrigation ; Ovarian Neoplasms/genetics ; Mutation/genetics ; Clonal Evolution ; Tumor Suppressor Protein p53/genetics
    Chemical Substances TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2022-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2767-9764
    ISSN (online) 2767-9764
    DOI 10.1158/2767-9764.crc-22-0314
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  6. Article ; Online: Correction: Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women.

    Bartlett, Thomas E / Evans, Iona / Jones, Allison / Barrett, James E / Haran, Shaun / Reisel, Daniel / Papaikonomou, Kiriaki / Jones, Louise / Herzog, Chiara / Pashayan, Nora / Simões, Bruno M / Clarke, Robert B / Evans, D Gareth / Ghezelayagh, Talayeh S / Ponandai-Srinivasan, Sakthivignesh / Boggavarapu, Nageswara R / Lalitkumar, Parameswaran G / Howell, Sacha J / Risques, Rosa Ana /
    Rådestad, Angelique Flöter / Dubeau, Louis / Gemzell-Danielsson, Kristina / Widschwendter, Martin

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 76

    Language English
    Publishing date 2022-07-19
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01086-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma.

    Krimmel-Morrison, Jeffrey D / Ghezelayagh, Talayeh S / Lian, Shenyi / Zhang, Yuezheng / Fredrickson, Jeanne / Nachmanson, Daniela / Baker, Kathryn T / Radke, Marc R / Hun, Enna / Norquist, Barbara M / Emond, Mary J / Swisher, Elizabeth M / Risques, Rosa Ana

    Gynecologic oncology

    2019  Volume 156, Issue 2, Page(s) 407–414

    Abstract: Objective: Pap tests hold promise as a molecular diagnostic for serous ovarian cancer, but previous studies reported limited sensitivity. Furthermore, the presence of somatic mutations in normal tissue is increasingly recognized as a challenge to the ... ...

    Abstract Objective: Pap tests hold promise as a molecular diagnostic for serous ovarian cancer, but previous studies reported limited sensitivity. Furthermore, the presence of somatic mutations in normal tissue is increasingly recognized as a challenge to the specificity of mutation-based cancer diagnostics. We applied an ultra-deep sequencing method with the goal of improving sensitivity and characterizing the landscape of low-frequency somatic TP53 mutations in Pap tests.
    Methods: We used CRISPR-DS to deeply sequence (mean Duplex depth ~3000×) the TP53 gene in 30 Pap tests from 21 women without cancer and 9 women with serous ovarian carcinoma with known TP53 driver mutations. Mutations were annotated and compared to those in the TP53 cancer database.
    Results: The tumor-derived mutation was identified in 3 of 8 Pap tests from women with ovarian cancer and intact tubes. In addition, 221 low-frequency (≲0.001) exonic TP53 mutations were identified in Pap tests from women with ovarian cancer (94 mutations) and without ovarian cancer (127 mutations). Many of these mutations resembled TP53 mutations found in cancer: they impaired protein activity, were predicted to be pathogenic, and clustered in exons 5 to 8 and hotspot codons. Cancer-like mutations were identified in all women but at higher frequency in women with ovarian cancer.
    Conclusions: Pap tests have low sensitivity for ovarian cancer detection and carry abundant low-frequency TP53 mutations. These mutations are more frequently pathogenic in women with ovarian cancer. Determining whether low-frequency TP53 mutations in normal gynecologic tissues are associated with an increased cancer risk warrants further study.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Cohort Studies ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/pathology ; DNA/genetics ; DNA/isolation & purification ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Mutation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Papanicolaou Test ; Tumor Suppressor Protein p53/genetics ; Young Adult
    Chemical Substances Biomarkers, Tumor ; TP53 protein, human ; Tumor Suppressor Protein p53 ; DNA (9007-49-2)
    Language English
    Publishing date 2019-12-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2019.11.124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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