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  • 1
    Online Resource
    Online Resource
    Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 21 ( 2015-05-26)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 21 ( 2015-05-26)
    Abstract: In metazoans, transition from fetal to adult heart is accompanied by a switch in energy metabolism-glycolysis to fatty acid oxidation. The molecular factors regulating this metabolic switch remain largely unexplored. We first demonstrate that the molecular signatures in 1-year (y) matured human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are similar to those seen in in vivo-derived mature cardiac tissues, thus making them an excellent model to study human cardiac maturation. We further show that let-7 is the most highly up-regulated microRNA (miRNA) family during in vitro human cardiac maturation. Gain- and loss-of-function analyses of let-7g in hESC-CMs demonstrate it is both required and sufficient for maturation, but not for early differentiation of CMs. Overexpression of let-7 family members in hESC-CMs enhances cell size, sarcomere length, force of contraction, and respiratory capacity. Interestingly, large-scale expression data, target analysis, and metabolic flux assays suggest this let-7–driven CM maturation could be a result of down-regulation of the phosphoinositide 3 kinase (PI3K)/AKT protein kinase/insulin pathway and an up-regulation of fatty acid metabolism. These results indicate let-7 is an important mediator in augmenting metabolic energetics in maturing CMs. Promoting maturation of hESC-CMs with let-7 overexpression will be highly significant for basic and applied research.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1424042112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes
    Elsevier BV ; 2024
    In:  Gynecologic Oncology Vol. 184 ( 2024-05), p. 31-42
    Details
    In: Gynecologic Oncology, Elsevier BV, Vol. 184 ( 2024-05), p. 31-42
    Type of Medium: Online Resource
    ISSN: 0090-8258
    URL: Article
    DOI: 10.1016/j.ygyno.2024.01.009
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1467974-7
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  • 3
    Online Resource
    Online Resource
    Not immune to inequity: minority under-representation in immunotherapy trials for breast and gynecologic cancers
    BMJ ; 2021
    In:  International Journal of Gynecologic Cancer Vol. 31, No. 11 ( 2021-11), p. 1403-1407
    Details
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 31, No. 11 ( 2021-11), p. 1403-1407
    Abstract: To describe the participation of minority women in clinical trials using immunologic agents for breast and gynecologic cancers. Methods A retrospective review of completed clinical trials involving immunotherapy for breast and gynecologic cancers was performed. Completed trials were examined for data on race, tumor type, and start year. Minority enrollment was stratified by tumor site. Based on Center for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated and compared using Χ 2 testing, p≤0.05. Results A total of 53 completed immunotherapy clinical trials involving 8820 patients were reviewed. Breast cancer trials were most common (n=24) and involved the most patients (n=6248, 71%). Racial breakdown was provided in 41 studies (77%) for a total of 7201 patients. Race reporting was lowest in uterine (n=4, 67%) and cervical cancer trials (n=6, 67%), and highest in ovarian cancer trials (n=12, 86%). White patients comprised 70% (n=5022) of all the patients included. Only 5% of patients involved were black (n=339), and 83% of these patients (n=282) were enrolled in breast cancer trials. Observed enrollment of black women was 32-fold lower for ovarian, 19-fold lower for cervical, 15-fold lower for uterine, and 11-fold lower for breast cancer than expected. While all trials reported race between 2013 and 2015, no consistent trend was seen towards increasing race reporting or in enrollment of black patients over time. Conclusion Racial disparities exist in clinical trials evaluating immunologic agents for breast and gynecologic cancers. Recruitment of black women is particularly low. In order to address inequity in outcomes for these cancers, it is crucial that significant attention be directed towards minority representation in immuno-oncologic clinical trials.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/ijgc-2021-002557
    DOI: 10.1136/ijgc-2021-002557.supp1
    DOI: 10.1136/ijgc-2021-002557.supp2
    DOI: 10.1136/ijgc-2021-002557.supp3
    DOI: 10.1136/ijgc-2021-002557.supp4
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2009072-9
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  • 4
    Online Resource
    Online Resource
    Characteristics, treatment and outcomes of women with immature ovarian teratoma, 1998–2012
    Elsevier BV ; 2016
    In:  Gynecologic Oncology Vol. 142, No. 2 ( 2016-08), p. 261-266
    Details
    In: Gynecologic Oncology, Elsevier BV, Vol. 142, No. 2 ( 2016-08), p. 261-266
    Type of Medium: Online Resource
    ISSN: 0090-8258
    URL: Article
    DOI: 10.1016/j.ygyno.2016.05.024
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 1467974-7
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  • 5
    Online Resource
    Online Resource
    National Trends in Extended Procedures for Ovarian Cancer Debulking Surgery
    BMJ ; 2018
    In:  International Journal of Gynecologic Cancer Vol. 28, No. 1 ( 2018-01), p. 19-25
    Details
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 28, No. 1 ( 2018-01), p. 19-25
    Abstract: Primary cytoreduction for ovarian cancer often requires extended radical procedures and is associated with significant morbidity. In 2010, neoadjuvant chemotherapy was shown to have similar survival to primary cytoreduction but with less need for radical surgery. We hypothesized that the increased use of neoadjuvant chemotherapy would decrease the use of radical cytoreductive procedures and thus examined trends in the performance of radical cytoreductive procedures. Methods We used the Nationwide Inpatient Sample to determine the annual number of extended procedures (colon, small intestine, liver, diaphragm, spleen, and gastric resection, ileostomy, colostomy) performed in women undergoing surgery for ovarian cancer from 1998 to 2013. Estimates were weighted to provide national averages. To account for changes in incidence over time, we used national incidence rates and report procedures performed per 1000 new cases of ovarian cancer. Trends were assessed using Cochrane-Armitage tests. Results We identified 274,639 ovarian cancer patients who underwent surgery, ranging from 15,720 to 18,714 procedures performed each year. We identified a significant increase in the use of extended procedures over this period. These differences were significant for absolute numbers of procedures, rate per 1000 new ovarian cancer cases, and percent per hysterectomy/bilateral salpingoophorectomy for rectosigmoid resection, diaphragm resection, splenectomy, ileostomy, and liver resection. Specifically, the use of these procedures rose from 1998 to 2010, declined in 2011, and rose again in 2012 and 2013. Conclusions Although there was a transient decrease in the use of extended cytoreductive procedures from 2010 to 2011 after the publication of randomized neoadjuvant trial data, use of these procedures again rose in 2012 and 2013.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    URL: Article
    DOI: 10.1097/IGC.0000000000001132
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 2009072-9
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  • 6
    Online Resource
    Online Resource
    Patterns of care and outcomes for women with uterine cancer and ovarian metastases
    BMJ ; 2019
    In:  International Journal of Gynecologic Cancer Vol. 29, No. 2 ( 2019-02), p. 365-376
    Details
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 29, No. 2 ( 2019-02), p. 365-376
    Abstract: For women with uterine cancer with metastases isolated to the adnexa (stage IIIA) optimal adjuvant therapy is unknown. We performed a population-based analysis to examine the use of chemotherapy, vaginal brachytherapy, and external beam therapy (in women with stage IIIA uterine cancer. Methods The National Cancer Database was used to identify women with stage IIIA uterine cancer with ovarian metastasis from 2004 to 2012. We explored the use of chemotherapy, vaginal brachytherapy, and external beam therapy over time. Multivariable models were developed to examine factors associated with survival. Results We identified 4088 women with uterine cancer and ovarian metastases. Overall, 56.2% of women received chemotherapy. Vaginal brachytherapy was used in 11.1%, while 36.6% received external beam therapy. Five-year survival was 64.7 % (95% CI, 62.9% to 66.5%). In a multivariable model, chemotherapy was associated with a 38% decrease in mortality (HR = 0.62; 95% CI, 0.54 to 0.71). Similarly, both external beam therapy (HR = 0.74; 95% CI, 0.65 to 0.85) and vaginal brachytherapy (HR = 0.67; 95% CI, 0.53 to 0.85) were associated with improved survival. When the cohort was limited to women who received chemotherapy, radiation was associated with improved overall survival (HR 0.74, 95% CI 0.61 to 0.90). There was no difference in survival between the use of external beam therapy and vaginal brachytherapy. Conclusions Chemotherapy was associated with a decrease in mortality in women with endometrial cancer and ovarian metastases. The addition of radiation therapy was associated with improved overall survival, although there was no difference between external beam therapy and vaginal brachytherapy.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    URL: Article
    DOI: 10.1136/ijgc-2018-000047
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2009072-9
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  • 7
    Online Resource
    Online Resource
    Molecular profiling of triple-negative endometrial cancers (TNEC) and triple-negative breast cancers (TNBC) to reveal unique expression profiles.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 28_suppl ( 2015-10-01), p. 159-159
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 28_suppl ( 2015-10-01), p. 159-159
    Abstract: 159 Background: “Triple negative” has been used to characterize a subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. They are aggressive cancers with limited treatment options. It’s unknown if similar phenotype found in other cancer types, like endometrial cancer, harbor similar molecular alterations and prognosis. We aim to compare molecular features between TNEC and TNBC. Methods: A total of 3133 endometrial cancer samples were evaluated by Caris Life Sciences (Phoenix, AZ) from Mar, 2011 to Jul, 2014 by multiplatform profiling, which included a combination of sequencing (Sanger or NGS), protein expression (IHC), and/or gene amplification (CISH or FISH). 545 TNEC and 2049 TNBC were identified based on reported pathology and compared using Fisher exact tests. Results: Compared to an incidence of 15-20% TNBC in breast cancer, 17% (545/3133) TNEC was seen in our cohort, of which 13% were endometrioid, 22% serous, 26% carcinosarcoma, 7% clear cell, and 22% other. Compared with TNBC, TNEC showed 1.9 exonic mutations per case while TNBC showed 1.2 mutations per case. As shown in the table, AR expression is lower in TNEC than TNBC. TP53 mutation was common in both but more frequent in TNBC. While BRCA1/2 mutation rates were similar, low MGMT and ERCC1 were more common in TNEC, suggesting increased aberrant DNA repair. DNA synthesis protein expression was higher in TNEC including TS, RRM1, and TOPO2A, although TNBC had higher TOPO1. PD-1 expression was more common in TNEC suggesting immune pathway involvement. PI3K/AKT/mTor, MAPK and Wnt pathways were more involved in TNEC with greater PTEN, PIK3CA, FBXW7, KRAS and CTNNB1 mutations. Conclusions: Our study reveals significantly higher overall mutation rates in TNEC than TNBC, and specifically higher activations of multiple molecular pathways including PI3K/Akt/mTor, MAPK and Wnt. Further studies are warranted to validate these findings in clinical trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.28_suppl.159
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Exploring molecular profiles and survival in hormone receptor-positive uterine serous carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 5579-5579
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 5579-5579
    Abstract: 5579 Background: Hormone receptor (HR) positivity has been reported as a good prognostic indicator in endometrial cancer. This study investigated estrogen receptor (ER) and progesterone receptor (PR) positivity as indicators of platinum response and improved survival in uterine serous carcinoma (USC), and determined differences in molecular profiles between these tumors and hormone receptor negative tumors. Methods: Tumor profiling was done with immunohistochemistry (IHC), next generation sequencing (NGS), and whole transcriptome sequencing (WTS). PD-L1 expression was determined by IHC using SP-142 (cut-off 〉 1%). Microsatellite instability (MSI) status was evaluated with IHC and NGS, and tumor mutational burden (TMB) by totaling somatic mutations per tumor (high if 〉 10 mutations/ MB). Immune-cell fraction was determined with QuantiSeq. We used insurance claims data to calculate Kaplan-Meier estimates for overall survival (OS). Statistical significance was determined with chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. Results: 2806 USC tumors were available for molecular profiling with 717 HR+/966 HR-, 1559 ER+/1059 ER- and 805 PR+/1809 PR-. Median OS for HR+ patients was longer than patients who were HR- regardless of treatment (1152 v 797 days; hazard ratio 0.68, 95% CI 0.58-0.80, p 〈 0.01). This OS benefit of HR positivity remained for patients receiving platinum therapy (1134 v 889 days; hazard ratio 0.75, 95% CI 0.58-0.98, p 〈 0.01). HR+ status trended towards improved OS in those treated with hormone therapy (407 vs 771 days, hazard ratio 0.78, 95% CI 0.59-1.02, p = 0.07). In addition to increased androgen receptor expression (54.2 vs 6.2%, p = 〈 0.001), PTEN mutations were more common in the HR+ group (10.3 vs 5.1%, p = 0.016). This resulted in in more frequent alterations of the PI3K pathway when compared to HR- tumors 64.5 vs 52.2%, p = 〈 0.001). PD-L1, TMB, and MSI status were similar between the two cohorts. Checkpoint inhibitor gene expression was notable for higher IDO expression in the HR+ group, but lower CD80, CD86, HAVCR2, IFNG, and PDC1 expression. The immune micro-environment was notable for less B-cells and M1 macrophages, but more M2 macrophages. Breaking the ER and PR positive cohort down to individual expression of each gene resulted in similar OS and molecular findings. Conclusions: HR positivity is associated with improved survival in allcomers with USC and those treated with platinum therapy, and there was a trend to improved OS with hormone therapy. More data is needed to determine if HR status is a prognostic marker for IO treatment response. This cohort had a distinct molecular profile compared to HR- tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.5579
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Raman Spectroscopy for Rapid Evaluation of Surgical Margins during Breast Cancer Lumpectomy
    Springer Science and Business Media LLC ; 2019
    In:  Scientific Reports Vol. 9, No. 1 ( 2019-10-10)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-10-10)
    Abstract: Failure to precisely distinguish malignant from healthy tissue has severe implications for breast cancer surgical outcomes. Clinical prognoses depend on precisely distinguishing healthy from malignant tissue during surgery. Laser Raman spectroscopy (LRS) has been previously shown to differentiate benign from malignant tissue in real time. However, the cost, assembly effort, and technical expertise needed for construction and implementation of the technique have prohibited widespread adoption. Recently, Raman spectrometers have been developed for non-medical uses and have become commercially available and affordable. Here we demonstrate that this current generation of Raman spectrometers can readily identify cancer in breast surgical specimens. We evaluated two commercially available, portable, near-infrared Raman systems operating at excitation wavelengths of either 785 nm or 1064 nm, collecting a total of 164 Raman spectra from cancerous, benign, and transitional regions of resected breast tissue from six patients undergoing mastectomy. The spectra were classified using standard multivariate statistical techniques. We identified a minimal set of spectral bands sufficient to reliably distinguish between healthy and malignant tissue using either the 1064 nm or 785 nm system. Our results indicate that current generation Raman spectrometers can be used as a rapid diagnostic technique distinguishing benign from malignant tissue during surgery.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-019-51112-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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  • 10
    Online Resource
    Online Resource
    Effects of real-time simulation feedback on design for visual comfort
    Informa UK Limited ; 2019
    In:  Journal of Building Performance Simulation Vol. 12, No. 3 ( 2019-05-04), p. 343-361
    Details
    In: Journal of Building Performance Simulation, Informa UK Limited, Vol. 12, No. 3 ( 2019-05-04), p. 343-361
    Type of Medium: Online Resource
    ISSN: 1940-1493 , 1940-1507
    URL: Article
    DOI: 10.1080/19401493.2018.1449889
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2421062-6
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