Variation in physician-directed immunohistochemistry screening among women with endometrial cancer.

OBJECTIVE: Immunohistochemistry screening is a reliable method for identifying women with endometrial cancer who are at risk for Lynch syndrome, but clinical workflows used to implement immunohistochemistry screening protocols can vary by institution. The goal of this study was to investigate variation in performance of immunohistochemistry screening when a physician order is required. METHODS: Retrospective study from an integrated healthcare system with a risk-based immunohistochemistry screening policy for Lynch syndrome from January 2015 to December 2016. Immunohistochemistry screening was indicated for all women with endometrial cancer aged <60 years and women with endometrial cancer aged ≥60 years who had a personal/family history suggestive of Lynch syndrome. However, a physician order was needed to have immunohistochemistry screening performed on the tumor specimen as our health system did not have reflex screening in the clinical workflow. Demographics and tumor characteristics were reviewed, and patients were stratified by immunohistochemistry screening status. Multivariable regression was performed to identify factors associated with immunohistochemistry performance and reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: There were 1399 eligible patients in the study. With a required physician order, immunohistochemistry screening rates (20% overall, 34% aged <60 years) were significantly lower than previous reports (36% overall, 90% aged <60 years, p≤0.0001 for both comparisons). Significant factors associated with immunohistochemistry screening performance identified by multivariable analysis included age, race, body mass index, personal/family cancer history, diabetes, endometrioid histology, and tumor grade. Asian women were most likely to have immunohistochemistry screening (OR 1.58, 95% CI 1.07 to 2.34) whereas black women were least likely (OR 0.43, 95% CI 0.22 to 0.91). CONCLUSIONS: Immunohistochemistry screening rates in women with endometrial cancer were lower in our health system compared with prior reports in the literature, and there were variations in screening performance according to patient age, race, and body mass index. Requiring a physician order for immunohistochemistry screening likely creates a barrier in screening uptake, therefore automated immunohistochemistry screening is recommended.

Asparanin A from Asparagus officinalis L. Induces G0/G1 Cell Cycle Arrest and Apoptosis in Human Endometrial Carcinoma Ishikawa Cells via Mitochondrial and PI3K/AKT Signaling Pathways.

Asparanin A (AA), a steroidal saponin from Asparagus officinalis L., has anticancer activity: however, its detailed molecular mechanisms in endometrial cancer (EC) have not been studied so far. We evaluated the anticancer activity and underlying mechanism of AA on EC cell line Ishikawa in vitro and in vivo. AA inhibited the Ishikawa cell proliferation and caused cell morphology alteration and cell cycle arrest in G0/G1 phase. Moreover, it could induce apoptosis through mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio which led to the generation of ROS, up-regulation of cytochrome c followed by decrease of Δψm, and activation of caspases, besides inhibition of the PI3K/AKT/mTOR pathway. In vivo data showed that administration of AA significantly inhibited the tumor tissue cell proliferation, reduced the tumor growth, and induced the apoptosis occurrence. AA can be a possible functional food ingredient to cure endometrial cancer followed by clinical trials.

Mechanism of Juglone-Induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells.

The molecular mechanism of Juglone-induced cell cycle arrest and apoptosis in human endometrial cancer cells was investigated. Juglone was purified from the green husk of Carya cathayensis Sarg and identified by HPLC, LC-MS/MS, and NMR. At an IC50 of 20.81 µM, juglone significantly inhibited Ishikawa cell proliferation, as shown by S phase arrest mediated by inactivation of cyclin A protein ( p < 0.05). The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. The expression of Bcl-2 and Bcl-xL was significantly down-regulated, whereas the expression of Bax, Bad and cyto c was up-regulated, and we later confirmed the involvement of the mitochondrial pathway in juglone-induced apoptosis. Our in vitro results stated that juglone can be studied further as an effective natural anticancer agent.

A Mindfulness-Based Lifestyle Intervention for Obese, Inactive Endometrial Cancer Survivors: A Feasibility Study.

BACKGROUND: Mindfulness-based interventions (MBIs) to address self-regulation and lifestyle behaviors (diet, physical activity) may benefit endometrial cancer survivors (ECS), who are at increased risk for morbidity and mortality associated with obesity. However, the acceptability of mindfulness training and whether it can augment behavior change in ECS is unknown. We aimed to examine; 1) the feasibility of the Mindfulness in Motion + Diet (MIM+D) intervention and 2) the preliminary efficacy of MIM+D for improving mindfulness, diet, PA and health-related quality of life (HRQL). METHODS: ECS (Mage=62.4, ±5yrs from diagnosis) completed assessments at baseline, 8 and 14 weeks. Feasibility was determined by intervention completion surveys, attendance and adherence data. We used repeated measures ANOVA's (SPSS 22.0) and effect size estimates (Cohen's d) to examine changes in mindfulness, diet, PA, and HRQL over time. RESULTS: Thirteen ECS (76%) completed the MIM+D program and attendance (≥6/8 sessions) was 90%. Women reported favorably on the overall quality (mean of 4.75/5) and benefits of the MIM+D program; however, would have preferred receiving MIM+D closer to diagnosis. Intention to treat analyses found MIM+D did not significantly improve any outcomes. However, an intervention completers analysis showed significant change in mindfulness (p=.0039) and small to moderate estimates for change in fruits and vegetable intake (d=.23), MVPA (d=.45), RAND SF-36: MCS (d=.46), and sleep quality (d=.68). CONCLUSIONS: Integrating mindfulness training into behavioral interventions is feasible and ECS that adhere to these lifestyle programs may benefit. However, to future research should examine the-long term effects of mindfulness-based behavioral lifestyle interventions.

A brief mindfulness-based cognitive behavioral intervention improves sexual functioning versus wait-list control in women treated for gynecologic cancer.

GOAL: The goal of this study was to evaluate a mindfulness-based cognitive behavioral intervention for sexual dysfunction in gynecologic cancer survivors compared to a wait-list control group. METHODS: Thirty-one survivors of endometrial or cervical cancer (mean age 54.0, range 31-64) who self-reported significant and distressing sexual desire and/or sexual arousal concerns were assigned either to three, 90-minute mindfulness-based cognitive behavior therapy sessions or two months of wait-list control prior to entering the treatment arm. Validated measures of sexual response, sexual distress, and mood, as well as laboratory-evoked physiological and subjective sexual arousal were assessed at pre-, one month post-, and 6-months following treatment. RESULTS: There were no significant effects of the wait-list condition on any measure. Treatment led to significant improvements in all domains of sexual response, and a trend towards significance for reducing sexual distress. Perception of genital arousal during an erotic film was also significantly increased following the intervention despite no change in physiologically-measured sexual arousal. CONCLUSIONS: A brief mindfulness-based intervention was effective for improving sexual functioning. Geographic restrictions permitted only a select sample of survivors to participate, thus, the generalizability of the findings is limited. Future studies should aim to develop online modalities for treatment administration to overcome this limitation.

[Effects of traditional Chinese drugs Shuganyishen, on Ishikawa cell line].

OBJECTIVE: To study the effects of the traditional Chinese drugs, Shuganyishen, on Ishikawa cell line. METHOD: Rat blood serum was prepared by using Chinese drugs serum pharmacology method, in which, Shuganyishen was contained or not contained. Ishikawa cells were subjected into five groups: (1) normal cells group (NCG), (2) rat blood serum without Shuganyishen group (NSGG) as negative control, (3) Shuganyishen group (SGG), (4) Cisplatin group (DDPG) as positive control, and (5) Shuganyishen with Cisplatin group (S&CG). MTT assay was used to evaluate the inhibition effect on cell growth in each group. The mRNA expression of estrogen receptor alpha and beta (ERalpha and ERbeta) in each group was detected by RT-PCR. RESULT: Effective inhibition of cell growth was found in the groups of SGG and S&CG, respectively (P < 0.05), which had no significant difference from positive control by MTT. The mRNA expression of ERbeta was slightly going up, while the expression of ERalpha was hardly effected in SGG by RT-PCR. Interestingly in S&CG, the mRNA expression of ERalpha was significantly down-regulated (P < 0.05), but the mRNA expression of ERbeta remained no change. As the positive control, the mRNA expression of ERalpha and ERbeta was significantly down-regulated in DDPG (P < 0.5). CONCLUSION: Traditional Chinese drugs, Shuganyishen, may inhibit Ishikawa cell growth and had no effects on the expression of ERalpha, furthermore, can reverse the inhibition of ERbeta expression by Cisplatin.

Tumor suppressor effect of follistatin-like 1 in ovarian and endometrial carcinogenesis: a differential expression and functional analysis.

Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primer-based reverse transcription (RT)-polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT-PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G(1) cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor-ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis.

Hormone therapy following breast and uterine cancer.

Cancers of the breast and endometrium, although hormonally-dependent, are not complete contraindications to hormonal replacement therapy. About 70% of women with endometrial cancer will be completely cured of their disease using appropriate surgical techniques and therefore can be given oestrogen without in any way compromising their long-term survival. In fact oestrogen will probably allow such women to survive longer with a higher quality of life. Most postmenopausal women with cancer of the breast should be offered an impeded oestrogen such as tamoxifen as their first line of hormonal treatment. There may be improvement in the vagina and bone calcium content following the use of this 'anti-oestrogen' but some women will continue to suffer from vasovagal symptoms. Women with breast cancer which is small, node-free and relatively non-aggressive may also do well on HRT. Because of the influence of progestogens in reducing oestrogen receptor production, in reducing the expression of various growth factors and in inducing apoptosis, it is wise to administer high-dose progestogens to these women as well as oestrogen. There is no clinical evidence that HRT administered to such women will induce any increase in tumour growth or recurrence. Women with a disease-free survival of 10 or more years can also be regarded as 'cured' and can also be offered oestrogen in conjunction with high-dose progestogens. Finally, those women with known secondary spread but who are severely disadvantaged by their oestrogen deficiency symptoms should be offered high-dose progestogens first and if their symptoms persist, then have oestrogen added to the regimen till the symptoms subside.