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  • 1
    Online Resource
    Online Resource
    Development of a Multi-Institutional Prediction Model for Three-Year Survival Status in Patients with Uterine Leiomyosarcoma (AGOG11-022/QCGC1302 Study)
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 10 ( 2021-05-14), p. 2378-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 10 ( 2021-05-14), p. 2378-
    Abstract: Background: The existing staging systems of uterine leiomyosarcoma (uLMS) cannot classify the patients into four non-overlapping prognostic groups. This study aimed to develop a prediction model to predict the three-year survival status of uLMS. Methods: In total, 201 patients with uLMS who had been treated between June 1993 and January 2014, were analyzed. Potential prognostic indicators were identified by univariate models followed by multivariate analyses. Prediction models were constructed by binomial regression with 3-year survival status as a binary outcome, and the final model was validated by internal cross-validation. Results: Nine potential parameters, including age, log tumor diameter, log mitotic count, cervical involvement, parametrial involvement, lymph node metastasis, distant metastasis, tumor circumscription and lymphovascular space invasion were identified. 110 patients had complete data to build the prediction models. Age, log tumor diameter, log mitotic count, distant metastasis, and circumscription were significantly correlated with the 3-year survival status. The final model with the lowest Akaike’s Information Criterion (117.56) was chosen and the cross validation estimated prediction accuracy was 0.745. Conclusion: We developed a prediction model for uLMS based on five readily available clinicopathologic parameters. This might provide a personalized prediction of the 3-year survival status and guide the use of adjuvant therapy, a cancer surveillance program, and future studies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13102378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 7 ( 2022-03-30), p. 3794-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 7 ( 2022-03-30), p. 3794-
    Abstract: Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23073794
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 2 ( 2022-02-18), p. 311-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 2 ( 2022-02-18), p. 311-
    Abstract: The histological criteria for classifying endometrial hyperplasia (EH) are based on architectural crowding and nuclear atypia; however, diagnostic agreement among pathologists is poor. We investigated molecular biomarkers of endometrial cancer (EC) risk in women with simple hyperplasia or complex hyperplasia without atypia (SH/CH-nonA). Forty-nine patients with EC preceded by SH/CH-nonA were identified, of which 23 were excluded (15 with complex atypical hyperplasia (CAH), six not consenting, one with a diagnosis 〈 6 months prior, and one lost to follow-up). The EH tissues of these patients were compared with those of patients with SH/CH-nonA that did not progress to EC (control) through microRNA (miRNA) array analysis, and the results were verified in an expanded cohort through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). MiRNA arrays analyses revealed 20 miRNAs that differed significantly (p 〈 0.05, fold change 〉 4) between the control (n = 12) and case (n = 6) patients. Multiplex RT-qPCR for the 20 miRNAs in the expanded cohort (94 control and 25 case patients) led to the validation of miR-30a-3p (p = 0.0009), miR-141 (p 〈 0.0001), miR-200a (p 〈 0.0001), and miR-200b (p 〈 0.0001) as relevant biomarkers, among which miR-141, miR-200a, and miR-200b regulate the expression of phosphatase and tensin homolog (PTEN). For the prediction of EC, the area under the curve for miR-30a-3p, miR-141, miR-200a, and miR-200b was 0.623, 0.754, 0.783, and 0.704, respectively. The percentage of complete PTEN loss was significantly higher in the case group than in the control group (24% vs. 0%, p 〈 0.001, Fisher’s exact test). A combination of complete PTEN loss and miR-200a provided optimal prediction performance (sensitivity = 0.760; specificity = 1.000; positive predictive value = 1.000; negative predictive value = 0.937; accuracy = 0.947). MiR-30a-3p, miR-141, miR-200a, miR-200b, and complete PTEN loss may be useful tissue biomarkers for predicting EC risk among patients with SH/CH-nonA.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12020311
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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  • 4
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    Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-11-02), p. 13382-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-11-02), p. 13382-
    Abstract: Embryo–endometrial communication plays a critical role in embryo implantation and the establishment of a successful pregnancy. Successful pregnancy outcomes involve maternal immune modulation during embryo implantation. The endometrium is usually primed and immunomodulated by steroid hormones and embryo signals for subsequent embryo implantation and the maintenance of pregnancy. The roles of extracellular vesicles (EVs) and microRNAs for the embryo–maternal interactions have been elucidated recently. New evidence shows that endometrial EVs and trophectoderm-originated EV cargo, including microRNAs, proteins, and lipids in the physiological microenvironment, regulate maternal immunomodulation for embryo implantation and subsequent pregnancy. On the other hand, trophoblast-derived EVs also control the cross-communication between the trophoblasts and immune cells. The exploration of EV functions and mechanisms in the processes of embryo implantation and pregnancy will shed light on a practical tool for the diagnostic or therapeutic approaches to reproductive medicine and infertility.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232113382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    A Patient-Derived Xenograft Model of Dedifferentiated Endometrial Carcinoma: A Proof-of-Concept Study for the Identification of New Molecularly Informed Treatment Approaches
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 23 ( 2021-11-26), p. 5962-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 23 ( 2021-11-26), p. 5962-
    Abstract: Conventional treatment of dedifferentiated endometrial carcinoma (DEC)–an uncommon and highly aggressive uterine malignancy–is beset by high failure rates. A line of research that holds promise to overcome these limitations is tailored treatments targeted on specific molecular alterations. However, suitable preclinical platforms to allow a reliable implementation of this approach are still lacking. Here, we developed a patient-derived xenograft (PDX) model for preclinical testing of investigational drugs informed by molecular data. The model–termed PDX-mLung was established in mice implanted with lung metastatic lesions obtained from a patient with DEC. Histologic and whole-exome genetic analyses revealed a high degree of identity between PDX-mLung and the patient’s parental lesions (both primary DEC and lung metastases). Interestingly, molecular analyses revealed that PDX-mLung harbored druggable alterations including a FGFR2 mutation and CCNE2 amplification. Targeted combined treatment with the FGFR inhibitor lenvatinib and the cell cycle inhibitor palbociclib was found to exert synergistic therapeutic effects against in vivo tumor growth. Based on the results of RNA sequencing, lenvatinib and palbociclib were found to exert anti-tumor effects by interfering interferon signaling and activating hormonal pathways, respectively. Collectively, these data provide proof-of-concept evidence on the value of PDX models for preclinical testing of molecularly informed drug therapy in difficult-to-treat human malignancies. Further clinical research is needed to examine more rigorously the potential usefulness of the lenvatinib and palbociclib combination in patients with DEC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13235962
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 6
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    The Impact of Multidisciplinary Team Approach on Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 12 ( 2021-12-06), p. 1313-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 12 ( 2021-12-06), p. 1313-
    Abstract: Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) is a therapeutic approach used to achieve curative treatment in intra-abdominal malignancy with peritoneal carcinomatosis (PC). However, it is a complicated procedure with high post-operative complication rates. Thus, we analyzed our preliminary data to establish whether multidisciplinary teamwork (MDT) implementation is beneficial for CRS–HIPEC outcomes. Method: A series of 132 consecutive patients with synchronous or recurrent PC secondary to gastrointestinal or gynecologic cancer who received CRS–HIPEC operation between May 2015 and September 2017 were included. Ninety-nine patients were categorized into the MDT group, with the 33 other patients into the non-MDT group. Results: The mean PCI score was 16.3 ± 8.8. Patients in the MDT group more often presented a higher PCI score (p value = 0.038). Regarding CRS completeness (CCR 0–1), it was distributed 81.8% and 57.6% in the MDT and the non-MDT group, respectively (p value = 0.005). Although post-operative complications were common (n = 62, 47.0%), post-operative complication rates did not differ between the two groups. The cumulative OS survival rate at the first year was 75.5%. Older age (p = 0.030, HR = 4.58, 95% CI = 1.16–18.10), ECOG 2 (p = 0.030, HR = 6.41, 95% CI = 1.20–34.14), and incomplete cytoreduction (p = 0.048, HR = 2.79, 95% CI = 1.04–8.27) were independent prognostic factors for survival. Conclusions: Our experience suggests that the CRS–HIPEC performed under MDT cooperation may result in higher complete cytoreduction rates without increasing post-operative complications and hospital mortalities.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11121313
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 7
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    Effects of Mobile Application Program (App)-Assisted Health Education on Preventive Behaviors and Cancer Literacy among Women with Cervical Intraepithelial Neoplasia
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 21 ( 2021-11-04), p. 11603-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 21 ( 2021-11-04), p. 11603-
    Abstract: Objective: This study aimed (1) to study the effects of health education on preventive behaviors and cancer literacy among women with cervical intraepithelial neoplasia (CIN); (2) to compare the effects of mobile application program (App)-assisted health education with traditional book-form health education. Participants: A total of 132 women ages 20 to 69 years women. Methods: This prospective longitudinal study enrolled 132 CIN women who were evaluated three times. Propensity score matching was used by controlling subjects’ age strata, body mass index, education level, occupation, and type of surgery. Results: The influences of various educational tools were investigated. Four domains were assessed, including health behavior, attitude towards behavior change, self-efficacy of behavior, and cervical cancer (CCa) literacy. Significant improvements in behavior change and CCa literacy due to a health education program were observed (p ≤ 0.002). The App combined with a traditional booklet had the highest score for behavior change and was significantly greater than the booklet-only learning (p = 0.002). The App-assisted form, either App alone or combined with booklet, had a significantly better impact on health promotion when compared to the booklet alone (p = 0.045 and 0.005, respectively). App-only learning had the highest score of CCa literacy (p = 0.004). Conclusion: Health education interventions can have positive effects in terms of change of behavior and CCa literacy. App-assisted learning could be used as a supportive technology, and App learning alone or combined with a traditional booklet may be an innovative model of clinical health promotion for women with CIN.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph182111603
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 8
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    Economic Burden of Cervical and Head and Neck Cancer in Taiwan from a Societal Perspective
    MDPI AG ; 2023
    In:  International Journal of Environmental Research and Public Health Vol. 20, No. 4 ( 2023-02-20), p. 3717-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 4 ( 2023-02-20), p. 3717-
    Abstract: Background: Head and neck cancers (HNC) are increasingly recognized as important human papillomavirus (HPV)-related malignancies in addition to cervical cancer (CC). However, data on the socioeconomic impact of HNC and CC in Taiwan are limited. Methods: A retrospective cohort study was conducted to estimate the total direct medical cost and indirect productivity loss from CC and HNC between 2014 and 2015. Patient data from the Taiwan National Cancer Registry were analyzed, with matched non-cancer controls from the Taiwan National Healthcare Reimbursement Database. Indirect costs due to premature deaths were calculated using public data from Taiwanese government reports. Results: In the direct cost analysis, 2083 patients with newly diagnosed CC and 11,078 with newly diagnosed HNC (10,036 males) were identified between 2014 and 2015 and followed up through the end of 2016 or until death. The total direct medical costs incurred in 2014 and 2015 due to HNC were 11.54 times higher in males than in females, and 4.55 times higher than CC. Indirect cost analysis showed the total annual productivity loss was New Taiwan Dollar (NTD) $12 billion in 2019, and 79.99% was attributed to male HNC. Conclusion: In Taiwan, the socioeconomic burden associated with male HNC is high and greater than that seen with CC. While not all HNCs are attributable to HPV infection, prevention of HNC through HPV vaccination should be considered for both sexes.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph20043717
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 9
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    Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 7 ( 2019-07-20), p. 1025-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 7 ( 2019-07-20), p. 1025-
    Abstract: Endometrial cancer incidence rates are growing, especially in countries with rapid socioeconomic transitions. Despite recent advances in chemotherapy, hormone therapy, and targeted therapy, advanced/recurrent disease remains a clinical challenge. Palbociclib—a selective inhibitor of cyclin-dependent kinases (CDK) 4/6—has therapeutic potential against estrogen receptor (ER)-positive and HER2-negative breast cancer. However, the question as to whether it can be clinically useful in endometrial cancer remains open. Here, we show that combined treatment with palbociclib and megesterol acetate exerts synergistic antiproliferative effects against endometrial cancer cells. Treatment of cancer cells with palbociclib suppressed NPM/B23 phosphorylation at threonine 199 (Thr199). We further demonstrated that CDK6 acts as a NPM/B23 kinase. Palbociclib-induced NPM/B23 dephosphorylation sensitized endometrial cancer cells to megesterol acetate through the upregulation of ERα expression. Immunohistochemistry revealed an overexpression of phospho-NPM/B23 (Thr199) in human endometrial cancer, and phospho-NPM/B23 (Thr199) expression levels were inversely associated with Erα in clinical specimen. In a xenograft tumor model, the combination of palbociclib and megesterol acetate successfully inhibited tumor growth. Taken together, our data indicate that palbociclib promoted NPM/B23 dephosphorylation at Thr199—an effect mediated by disruption of CDK6 kinase activity. We conclude that palbociclib holds promise for the treatment of endometrial cancer when used in combination with megesterol acetate.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11071025
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Development of New Cancer Treatment by Identifying and Focusing the Genetic Mutations or Altered Expression in Gynecologic Cancers
    MDPI AG ; 2021
    In:  Genes Vol. 12, No. 10 ( 2021-10-09), p. 1593-
    Details
    In: Genes, MDPI AG, Vol. 12, No. 10 ( 2021-10-09), p. 1593-
    Abstract: With the advent of next-generation sequencing (NGS), The Cancer Genome Atlas (TCGA) research network has given gynecologic cancers molecular classifications, which impacts clinical practice more and more. New cancer treatments that identify and target pathogenic abnormalities of genes have been in rapid development. The most prominent progress in gynecologic cancers is the clinical efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors, which have shown breakthrough benefits in reducing hazard ratios (HRs) (HRs between 0.2 and 0.4) of progression or death from BRCA1/2 mutated ovarian cancer. Immune checkpoint inhibition is also promising in cancers that harbor mismatch repair deficiency (dMMR)/microsatellite instability (MSI). In this review, we focus on the druggable genetic alterations in gynecologic cancers by summarizing literature findings and completed and ongoing clinical trials.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes12101593
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527218-4
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