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Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies. Methods: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated. Results: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy. Conclusion: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate molecular profiling in HER2-low tumors based on a promising dataset. A total of 615 consecutive HER2-negative breast cancer samples were assayed. The genomic mutations in the two groups with different HER2 expression levels (HER2-0 vs. HER2-low) were compared. The mutation types obtained via next-generation targeted sequencing were correlated with the clinicopathological features of the patients with HER2-0 and HER2-low breast cancer. The results showed that there was a significantly higher percentage of receptor-positive (ER/PR) tumors and more low-level Ki-67 tumors, but a lower incidence of stage I/II tumors in the HER2-low group compared to the HER2-0 group. There was a significantly higher frequency of 17.62% (65/369) for PIK3CA_SNA in the HER2-low group than in the HER2-0 group, which had a frequency of only 9.35% (23/246) (p = 0.006). When the called gene alterations in the triple-negative breast cancer (TNBC) group were compared with those in the luminal-like breast cancer group, there was a significantly high frequency of 28.17% (140/497) for ERBB2_SNA in a luminal-like group than in the TNBC group(16.95% (20/118)).We conclude that the early detection of PIK3CA mutations is likely to be important and might help therapeutic decision making in patients with HER2-low tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: The VGH-TAYLOR study comprised a subgroup of early-stage breast cancer patients. Targeted sequencing was performed for both fresh-frozen paraffin-embedded (FFPE) tumor tissue and plasma. Common genes interrogated by both platforms were identified, and the concordance between paired targeted sequencing results from the same individual is reported. Only one-quarter of breast cancers were concordant between tumor and liquid biopsy from the same subject. Early-stage breast cancer might shed less circulating tumor DNA (ctDNA) from the tumor and compromise the detectability of liquid biopsy. In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ2 test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the role of IL-17A in the cancer microenvironment and the recurrence of triple negative breast cancer (TNBC). Methods: Using human TNBC cell lines, the role of IL17-A was investigated by knocked down of IL-17A (ΔIL-17A) and by administration of IL-17A into the culture medium. Cell proliferation assays, migration assays, as well as Western blot analysis and real-time PCR, were used to evaluate IL-17A-related signaling. Three types of 4T1 cells were implanted into BALB/c mice, namely wild type (WT), ΔIL-17A, and WT + neutralizing IL-17 antibody (WT + Ab) cells. Tumor weight, necrosis area, and the number of circulating tumor cells (CTCs) were measured. Immunohistochemistry and Western blotting were used to analyze expression of CD34, CD8, and TGF-β1 as well as anoikis resistance. The Kaplan–Meier's method was used to correlate IL-17A expression and patient outcome, including disease-free survival (DFS) and overall survival (OS). Results: Our results demonstrated that IL-17A was able to stimulate the migratory activity, but not the growth rate, of MDA-MB-231/468 cells. In vivo, for the ΔIL-17A group, there was an increase in necrosis area, a decrease in tumor CD34 expression and a reduction in the number of CTCs. Furthermore, in WT + Ab group, there was a decreased in tumor expression of CD34, fewer CD8 (+) cells, and fewer CTCs, but an increase in expression of TGF-β1 expression. Both of the above were compared to the WT group. Knockdown of IL-17A also decreased anoikis resistance in human TNBC and the murine 4T1 cell lines. Kaplan–Meier analysis disclosed a negative correlation between tumor expression of IL-17A and OS in TNBC patients. Conclusion: We conclude that IL-17A promotes migratory and angiogenic activity in tumors, enhances anoikis resistance, and modulates the immune landscape of the tumor microenvironment such changes favor cancer metastasis. [ABSTRACT FROM AUTHOR]

An analysis of decisions related to patent eligibility by the US Court of Appeals for the Federal Circuit indicates a way to avoid rejection or invalidation of eligibility. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel.Methods: The study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT).Results: A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%).Conclusion: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board. [ABSTRACT FROM AUTHOR]

Aims: There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. Methods: We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. Results: The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Conclusion: Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in triple negative breast cancer cell. In addition, BDNF can function in either an autocrine or a paracrine manner to increase the migration ability of both MDA-MB-231 cells and HUVEC cells. Finally, overexpression of TrkB, but not of BDNF, is significantly associated with a poor survival outcome for TNBC patients. [ABSTRACT FROM AUTHOR]

Organic light-emitting diodes (OLEDs) have outperformed conventional display technologies in smartphones, smartwatches, tablets, and televisions while gradually growing to cover a sizable fraction of the solid-state lighting industry. Blue emission is a crucial chromatic component for realizing high-quality red, green, blue, and yellow (RGBY) and RGB white display technologies and solid-state lighting sources. For consumer products with desirable lifetimes and efficiency, deep blue emissions with much higher power efficiency and operation time are necessary prerequisites. This article reviews over 700 papers covering various factors, namely, the crucial role of blue emission for full-color displays and solid-state lighting, the performance status of blue OLEDs, and the systematic development of fluorescent, phosphorescent, and thermally activated delayed fluorescence blue emitters. In addition, various challenges concerning deep blue efficiency, lifetime, and approaches to realizing deeper blue emission and higher efficacy for blue OLED devices are also described. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that overexpression of the Multiple Epidermal Growth Factor Like Domains 11 (MEGF11) gene in TNBC cells increases tumor cell survival against anoikis via interaction with platelets. The role of MEGF11 was studied in human TNBC MDA-MB-231 and MDA-MB-468 cells by overexpressing MEGF11 (o/e MEGF11) using non-attached culture. Mouse wild type 4 T1 and Δmegf11-4 T1 cells were implanted into the mammary fat pad of BALB/c mice. Circulating tumor cells were isolated and cultured. Plasma platelets were added to these cell lines to carry out a platelet binding assay by confocal microscopy. Anoikis was observed by Live/Dead staining and a quantitative PBMC-specific cytotoxic assay (with/without platelets) was carried out to measure calcein release. The protein levels of MEGF11, Akt, and caspase 3 were assessed by Western blotting. Reduced number of circulating Δmegf11 4 T1 cells, and 4 T1-platelet clusters and reduced p-Akt expression, accompanied by increased specific calcein release, were observed in the Δmegf11 4T1group compared to the 4 T1 wild type group. There was significant increased cancer-platelet binding using the o/e MEGF11 MDA-MB-231/468 lines. Cell survival, caspase 3 activation and PBMC-specific cytotoxicity in the o/e MEGF11 MDA-MB-468 cells, but not in the MDA-MB-231 cells, could be rescued by platelet binding (+), compared to the platelet (−) group. We conclude that MEGF11 overexpression in TNBC cells rescues tumor cells from anoikis via interaction with platelets in mouse 4 T1 cells and human MDA-MB-468 cells. • MEGF11 plays important roles in the TNBC recurrence through cytokine and chemokine cascades. • O/e MEGF11 in TNBC increases cell survival against anoikis through interaction with platelets. • Caspase 3 activation and PBMC cytotoxicity in o/e MEGF11 MDA-MB-468 are rescued by platelet binding. • These novel findings might provide therapeutic strategy in prevention of TNBC metastasis. [ABSTRACT FROM AUTHOR]

Abstract: A study of the oxygen reduction reaction (ORR) on a screen printed carbon electrode surface mediated by the tricopper cluster complex Cu3(7‐N‐Etppz(CH2OH)) dispersed on electrochemically reduced carbon black, where 7‐N‐Etppz(CH2OH) is the ligand 3,3′‐(6‐(hydroxymethyl)‐1,4‐diazepane‐1,4‐diyl)bis(1‐(4‐ethyl piperazin‐1‐yl)propan‐2‐ol), is described. Onset oxygen reduction potentials of about 0.92 V and about 0.77 V are observed at pH 13 and pH 7 vs. the reversible hydrogen electrode, which are comparable to the best values reported for any synthetic copper complex. Based on half‐wave potentials (E1/2), the corresponding overpotentials are about 0.42 V and about 0.68 V, respectively. Kinetic studies indicate that the trinuclear copper catalyst can accomplish the 4 e− reduction of O2 efficiently and the ORR is accompanied by the production of only small amounts of H2O2. The involvement of the copper triad in the O2 activation process is also verified. [ABSTRACT FROM AUTHOR]

Abstract: A study of the oxygen reduction reaction (ORR) on a screen printed carbon electrode surface mediated by the tricopper cluster complex Cu3(7‐N‐Etppz(CH2OH)) dispersed on electrochemically reduced carbon black, where 7‐N‐Etppz(CH2OH) is the ligand 3,3′‐(6‐(hydroxymethyl)‐1,4‐diazepane‐1,4‐diyl)bis(1‐(4‐ethyl piperazin‐1‐yl)propan‐2‐ol), is described. Onset oxygen reduction potentials of about 0.92 V and about 0.77 V are observed at pH 13 and pH 7 vs. the reversible hydrogen electrode, which are comparable to the best values reported for any synthetic copper complex. Based on half‐wave potentials (E1/2), the corresponding overpotentials are about 0.42 V and about 0.68 V, respectively. Kinetic studies indicate that the trinuclear copper catalyst can accomplish the 4 e− reduction of O2 efficiently and the ORR is accompanied by the production of only small amounts of H2O2. The involvement of the copper triad in the O2 activation process is also verified. [ABSTRACT FROM AUTHOR]

Background: Ultramarathon is a high endurance exercise associated with a wide range of exercise-related problems, such as acute kidney injury (AKI). Early recognition of individuals at risk of AKI during ultramarathon event is critical for implementing preventative strategies. Objectives: To investigate the impact of speed variability to identify the exercise-related acute kidney injury anticipatively in ultramarathon event. Methods: This is a prospective, observational study using data from a 100 km ultramarathon in Taipei, Taiwan. The distance of entire ultramarathon race was divided into 10 splits. The mean and variability of speed, which was determined by the coefficient of variation (CV) in each 10 km-split (25 laps of 400 m oval track) were calculated for enrolled runners. Baseline characteristics and biochemical data were collected completely 1 week before, immediately post-race, and one day after race. The main outcome was the development of AKI, defined as Stage II or III according to the Acute Kidney Injury Network (AKIN) criteria. Multivariate analysis was performed to determine the independent association between variables and AKI development. Results: 26 ultramarathon runners were analyzed in the study. The overall incidence of AKI (in all Stages) was 84.6% (22 in 26 runners). Among these 22 runners, 18 runners were determined as Stage I, 4 runners (15.4%) were determined as Stage II, and none was in Stage III. The covariates of BMI (25.22 ± 2.02 vs. 22.55 ± 1.96, p = 0.02), uric acid (6.88 ± 1.47 vs. 5.62 ± 0.86, p = 0.024), and CV of speed in specific 10-km splits (from secondary 10 km-split (10th – 20th km-split) to 60th – 70th km-split) were significantly different between runners with or without AKI (Stage II) in univariate analysis and showed discrimination ability in ROC curve. In the following multivariate analysis, only CV of speed in 40th – 50th km-split continued to show a significant association to the development of AKI (Stage II) (p = 0.032). Conclusions: The development of exercise-related AKI was not infrequent in the ultramarathon runners. Because not all runners can routinely receive laboratory studies after race, variability of running speed (CV of speed) may offer a timely and efficient tool to identify AKI early during the competition, and used as a surrogate screening tool, at-risk runners can be identified and enrolled into prevention trials, such as adequate fluid management and avoidance of further NSAID use. [ABSTRACT FROM AUTHOR]

Glycoprotein non-metastatic B (GPNMB) is a transmembrane protein overexpressed in numerous cancers including triple-negative breast cancers (TNBC). It has been linked to promote cancer aggressiveness and implicated as a novel target for GPNMB-expressing cancers. In current study, we aimed to explore the clinical significance of GPNMB in TNBC. Among 759 specimens, immunohistochemistry (IHC) exhibited GPNMB expressions were variable in different subtypes and significantly higher in TNBC. Kaplan–Meier analysis revealed GPNMB overexpression in TNBC was associated with worse prognosis especially distant metastasis (P = 0.020, HR = 2.515, CI 1.154–5.480). Multivariate analysis showed GPNMB expression was an independent prognostic factor in terms of recurrence and distant metastasis (P = 0.008, HR = 3.22, CI 1.36–7.61; P = 0.017, HR = 3.08, CI 1.22–7.74). In silico analysis showed high mRNA expression of GPNMB was associated with distant metastasis and GPNMB was overexpressed in TNBC. Furthermore, GPNMB positively correlated with epithelial–mesenchymal transition (EMT) regulators, mesenchymal marker vimentin, MMP and integrins. The protein levels of Twist and MMP2 were upregulated by GPNMB overexpression in TNBC cells. GPNMB-enhanced cell invasion was attenuated by broad spectrum MMP inhibitor (GM 6001) and the selective inhibitor of MMP-2 (ARP100). In summary, GPNMB expression is prevalent in TNBC and may be implicated as a prognostic biomarker in patients with TNBC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to prospectively explore severity and prevalence of chemotherapy-induced peripheral neuropathy (CIPN) and examine the correlation between clinician-assessed (objective) and patient-reported (subjective) CIPN in breast cancer survivors receiving taxane. Methods: This was a prospective, longitudinal study. Purposive sampling was adapted to enroll women newly diagnosed with breast cancer and about to receive taxane. The CIPN was assessed after breast cancer diagnosed and before chemotherapy (T1), before cycle 1 to 4 taxane infusion (T2 to T5), and after chemotherapy completion (T6 to T8). Total Neuropathy Score–clinical version (TNSc), Identification Pain Questionnaire (ID pain), Functional Assessment of Cancer Therapy–Taxane subscale (FACT-Tax), and Peripheral Neuropathy Scale (PNS) were utilized for measuring CIPN. Descriptive statistics, Pearson correlation coefficient, and generalized estimating equation were used to analyze data. Results: A total of 88 participants were included. Both clinician-assessed and patient-reported CIPN gradually increased between T1 and T6 and mildly decreased at T7 and T8. Fifty-five participants (62.5%) experienced CIPN at T8. Weak-to-moderate correlations between subjective and objective CIPN were found at T6 to T8 (r = 0.272–0.533, p < 0.05). The change of TNSc, FACT-Tax, and PNS were significant over time. However, the significant change of neuropathic pain was only found at T6. Conclusion: The change of CIPN prevalence and severity were significant over time in survivors newly diagnosed with breast cancer. Specifically, the severest and highest CIPN was detected at chemotherapy completion. Survivors remained suffering from CIPN 3 months after chemotherapy completion. Besides, mild to moderate correlations between clinician-assessed and patient-reported CIPN were identified. [ABSTRACT FROM AUTHOR]

This study describes the fertility intention and explores factors related to fertility intention in reproductive-age women with breast cancer in Taiwan. In this cross-sectional study, women of childbearing age who had been diagnosed with breast cancer completed a face-to-face survey that included demographic, disease, and symptom-related data, and social support and fertility intention information. The mean fertility intention score among the 223 participants was "medium" (M ± SD = 41.18 ± 12.62). Higher symptom severity, especially for distress, was related to lower fertility intention. Instrumental support from families and friends was positively associated with fertility intention score. Younger women had better fertility intention scores than older women. The Sobel test showed that age mediated menopause and fertility intention. The findings offer the evidence of the needs to control symptoms and provide sufficient instrumental support regarding fertility after completing chemotherapy. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that upregulation of multiple epidermal growth factor-like domains 11 (MEGF11) gene expression is involved in the mechanism by which recurrence of Triple Negative Breast Cancer (TNBC) occurs. Our aim was to elucidate the role of MEGF11 expression in TNBC cells, both in vitro and in vivo, and in human tissue. Following MEGF11 gene knockdown (∆MEGF11) or over-expression in MDA-MB-231 and MB-468 cells, cell growth and chemokine gene expression were evaluated. In vivo, tumour growth of implanted human TNBC cells and the number of circulating 4T1 mouse tumour cells were measured. There was a significant decrease in cell growth via inhibition of AKT, NF-kB, CREB and AP-1 activation in ∆MEGF11 MDA-MB-231 and 468 cells. This also resulted, in vivo, in a suppression of tumour growth and a decrease in the number of mouse circulating 4T1 breast cancer cells. Surprisingly, overexpression of MEGF11 upregulated the expression of various chemokines and proinflammatory cytokines via AKT activation, but there was no increase in cell proliferation. MEGF11 was found to cross-talk positively with IL-17A signalling. Patients with tumours that over-expressed MEGF11 had a poorer prognosis. We conclude that MEGF11 plays an important role in tumour survival and that overexpression of MEGF11 induces both a cytokine and a chemokine cascade, which will favour the tumour microenvironment in terms of distant metastasis. MEGF11 might be a potential therapeutic target for preventing TNBC recurrence. [ABSTRACT FROM AUTHOR]

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen. Unlabelled Image • Plasma tamoxifen levels were positively associated with serum triglyceride levels. • CYP2D6(C100T) and high-serum-cholesterol are risk factors of low endoxifen levels. • Overweight and high-serum-cholesterol increased the risk of ineffective endoxifen. [ABSTRACT FROM AUTHOR]

Aims: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in‐situ hybridisation (ISH) positivity are suitable for anti‐HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. Methods and results: We analysed the clinicopathological information of 886 consecutive cases of HER2‐positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti‐HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut‐off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. Conclusion: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2‐positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Copper nano-catalyst accumulated from [Cu(CH 3 CN) 4 ClO 4 ] in a reaction mixture of H 2 O 2(aq) and CH 3 CN can efficiently catalyze the conversion of benzene to p -benzoquinone (BQ) in high selectivity. The obtained nanoparticles can still be reused for the corresponding oxidation to maintain its high selectivity and efficiency for p -BQ production. Highlights • Copper nano-catalyst (Cu NC) prepared from the Cu(CH 3 CN) 4 ClO 4 salt using H 2 O 2(aq) in CH 3 CN. • Cu NC can efficiently oxidize benzene to p -BQ and PhOH using H 2 O 2(aq). • High p -BQ selectivity can be achieved by tuning the composition of H 2 O 2 -H 2 O-CH 3 CN. • The Cu NC can be separated and recycled for several times. • Cu clusters in Cu NC are essential for benzene-to- p -BQ oxidation. Abstract The molecular copper complex tetrakis(acetonitrile)copper(I) perchlorate [Cu(CH 3 CN) 4 ClO 4 ] (1) was shown to act as a catalyst precursor for the efficient oxidation of benzene to p -benzoquinone (p -BQ) with a percentage selectivity of 60–80% under mild conditions, and produces phenol (PhOH) as a minor product at room temperature. Here, we obtained evidences showing the formation of copper based nanoparticle catalyst (NC) (2) from 1 to be the vital step responsible for its ability to catalyze the conversion of benzene to p -BQ, presumably via double oxidation. Addition of a considerable amount of H 2 O to the reaction mixture improved the selectivity for forming p -BQ to 84% and/or the conversion efficiency to 98%. In addition, the copper NC easily formed in situ through the oxidation of substrate using H 2 O 2 in CH 3 CN. After separating the NC from the reaction mixture and recycling them several times, it still maintained comparable catalytic efficiency and selectivity for the conversion of benzene to p -BQ. [ABSTRACT FROM AUTHOR]

Damage associated molecular patterns (DAMPs), including calreticulin (CRT) exposure, high-mobility group box 1 protein (HMGB1) elevation, and ATP release, characterize immunogenic cell death (ICD) and may play a role in cancer immunotherapy. Triple negative breast cancer (TNBC) is an immunogenic subtype of breast cancer with higher lymphocyte infiltration. Here, we found that regorafenib, a multi-target angiokinase inhibitor previously known to suppress STAT3 signaling, induced DAMPs and cell death in TNBC cells. Regorafenib induced the expression of HMGB1 and CRT, and the release of ATP. Regorafenib-induced HMGB1 and CRT were attenuated following STAT3 overexpression. In a 4T1 syngeneic murine model, regorafenib treatment increased HMGB1 and CRT expression in xenografts, and effectively suppressed 4T1 tumor growth. Immunohistochemical staining revealed increased CD4+ and CD8+ tumor-infiltrating T cells in 4T1 xenografts following regorafenib treatment. Regorafenib treatment or programmed death-1 (PD-1) blockade using anti-PD-1 monoclonal antibody reduced lung metastasis of 4T1 cells in immunocompetent mice. While regorafenib increases the proportion of MHC II high expression on dendritic cells in mice with smaller tumors, the combination of regorafenib and PD-1 blockade did not show a synergistic effect on anti-tumor activity. These results suggest that regorafenib induces ICD and suppresses tumor progression in TNBC. It should be carefully evaluated when developing a combination therapy with an anti-PD-1 antibody and a STAT3 inhibitor. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fe-catalyzed oxidation of aromatics in a H 2 O 2 -H 2 O-CH 3 CN system is developed. • Products of benzene oxidation yield controllable ratios of PhOH vs. BQ. • Products of toluene give controllable ratios at sp 2 vs. sp 3 C H bond oxidations. • The inverse KIEs are obtained for benzene, and high NIH-Shift values for toluene. • Ring oxidation involves an electrophilic oxygenation by oxygenated iron species. Iron(II) perchlorate in an H 2 O-H 2 O 2 -CH 3 CN mixture was used to efficiently carry out C H bond activations of benzene to form phenol and/or hydroquinone, and of toluene to form benzaldehyde, benzyl alcohol, o -cresol, p -cresol, and/or methyl- p -benzoquinone. The reactions were facilely tuned and controlled to selectively yield either a single or double oxygenation of benzene as well as a sp 3 or sp 2 C H bond oxidation of toluene. On the basis of H/D kinetic isotope effect data, we determined the aromatic oxidation to mostly proceed by way of formation of an arene oxide or a σ-complex intermediate from high-valence iron species and to then undergo a 1,2-hydride shift, i.e., NIH-shift rearrangement. [ABSTRACT FROM AUTHOR]

An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes. [ABSTRACT FROM AUTHOR]

Background/aim: Evidence shows that Luminal A breast cancer is likely to undergo bone metastasis, but the mechanisms involved remain unknown. This study's aim was to demonstrate a correlation between estrogen receptor (ER) positivity and bone metastasis as the clinically preferred site of metastasis, as well as investigating the role of ERα-Src signaling in MCF-7 cells using Snail over-expression as an in vivo bone metastasis model.Methods: Clinically, the records of breast cancer with distant metastasis were retrospectively reviewed to correlate breast cancer subtypes and preferential metastatic sites. An in vivo bone metastasis model was created by injection of MCF-7 cells with/without Snail over-expression into the tibia of nude mice. The human MCF-7 cells that over-expressed (o/e) Snail were examined and the expression of epithelial-mesenchymal transitions (EMT) markers, ER-Src signaling proteins and p190 RhoGAP analyzed by Western blotting and real-time PCR. The role of ERα was elucidated using ESR1 silence by transfecting shRNA (∆ESR1) into MCF-7 o/e Snail cells in vitro and in vivo.Results: The clinical results showed that ER ≥1% breast cancers showed a positive correlation with bone metastasis, which was found to be the preferred site of metastasis. An in vivo bone metastasis was successfully established using injection of MCF-7 o/e Snail cells into the tibia of nude mice, but no such metastasis was found using control MCF-7 cells. The proteins expressed in MCF-7 o/e Snail cells showed an EMT pattern, while those of the MCF-7 o/e Snail metastatic tissue showed a mesenchymal-epithelial pattern. There was an increase in cytosolic Src, p190 RhoGAP and nuclear ERα proteins, but not in Snail, in MCF-7 o/e Snail tissue compared to the same cell line in vitro. ESR1 knock down decreased Src and p190 RhoGAP expression in vitro and also decreased the incidence of bone metastasis in vivo.Conclusion: We conclude that ER-Src signaling plays an important role in ER (+) breast cancer, which shows a high potential for bone metastasis. [ABSTRACT FROM AUTHOR]

Engineered bacterial cytochrome P450s are noted for their ability in the oxidation of inert small alkanes. Cytochrome P450 BM3 L188P A328F ( BM3 PF) and A74E L188P A328F ( BM3 EPF) variants are able to efficiently oxidize n-butane to 2-butanol. Esterification of the 2-butanol derived from this reaction mediated by the aforementioned two mutants gives diastereomeric excesses ( de) of −56±1 and −52±1 %, respectively, with the preference for the oxidation occurring at the C−H S bond. When tailored (2 R,3 R)- and (2 S,3 S)-[2-2H1,3-2H1]butane probes are employed as substrates for both variants, the obtained de values from (2 R,3 R)-[2-2H1,3-2H1]butane are −93 and −92 % for BM3 PF and EPF, respectively; whereas the obtained de values from (2 S,3 S)-[2-2H1,3-2H1]butane are 52 and 56 % in the BM3 PF and EPF systems, respectively. The kinetic isotope effects (KIEs) for the oxidation of (2 R,3 R)-[2-2H1,3-2H1]butane are 7.3 and 7.8 in BM3 PF and EPF, respectively; whereas KIEs for (2 S,3 S)-[2-2H1,3-2H1]butanes are 18 and 25 in BM3 PF and EPF, respectively. The discrepancy in KIEs obtained from the two substrates supports the two-state reactivity (TSR) that is proposed for alkane oxidation in cytochrome P450 systems. Moreover, for the first time, experimental evidence for tunneling in the oxidation mediated by P450 is given through the oxidation of the C−H R bond in (2 S,3 S)-[2-2H1,3-2H1]butane. [ABSTRACT FROM AUTHOR]

Healthy light has attracted increasing attentions due to recognizing the hazards that modern light has caused to physiology, human eyes, ecology, and artworks. Hence, studies concentrated on the design and fabrication of hazard-free lighting sources has been significantly increasing. However, issues on light quality and energy-saving are of great importance. Here, we present an original approach to enable the generation of human-eye-friendly and melatonin suppression-less healthy light with high light-quality and energy-saving characters. Taking a three-band organic light-emitting diode (OLED) for example, the suppression threat can be reduced by 83% as the color temperature of the resulting light is decreased from 6000 to 2000 K, while slightly sacrificing its theoretical efficacy limit from 260 to 245 lm/W and spectrum resemblance index (SRI) from 90 to 83. Notably, a comparatively more healthy light can be obtained by incorporating lesser deep-blue and -red emissions even at the same color temperature. The same approach can also apply to other lighting technologies such as light-emitting diode. [ABSTRACT FROM AUTHOR]

• Fe-oxide CNC prepared from Fe(ClO 4) 2 using H 2 O 2(aq) in C 6 H 6 -CH 3 CN. • Fe-oxide CNC composes of Fe 2 O 3 nanoparticles and carbonaceous moiety. • Highly efficient Fe-oxide CNC for highly selective benzene oxidation to phenol. • EPR study shows DMPO-OOH adduct formation on heterogeneous Fe-oxide CNC surface. • Hydrophobic carbonaceous surface assists selective C 6 H 6 oxidation to phenol. Direct benzene hydroxylation under mild conditions using hydrogen peroxide can be essential in producing phenol. A new iron oxide-carbonaceous nanocatalyst (Fe-oxide CNC) is prepared in situ using a precursor of Fe(ClO 4) 2 and H 2 O 2 in benzene and CH 3 CN. The obtained Fe-oxide CNC can efficiently catalyze benzene oxidation to phenol using H 2 O 2(aq) in CH 3 CN. The highest phenol production was achieved with the turnover number (TON) of 122 in unit iron content and selectivity of 96% at 60 °C. The catalyst was characterized by SEM, TEM, XAS, XPS, Raman, XRD, BET, and TGA techniques. Interestingly, materials identification and characterization of the Fe-oxide CNC provided evidence to support the presence of Fe 2 O 3. In addition, the carbonaceous moieties mainly consisted of branched aliphatic hydrocarbons on the iron oxide surface, which enhance the catalytic performance for benzene oxidation to phenol. The Fe-oxide CNC can be recycled three times with comparable catalytic efficiency. Using H 2 18O 2 as an oxidant, the phenol product with highly enriched 18O-atom indicates that the reactive oxygen species (ROS) activated by H 2 O 2(aq) is crucial for aromatic oxidation. Time-resolved spin trapping experiments displayed the formation of the intermediate adducts consisting of 5,5-dimethyl-1-pyrroline N -oxide (DMPO) and reactive oxygenated radicals. For 3‒24 h durations, higher steady-state concentrations of the oxygenated intermediates observed at 25 °C than 60 °C indicate that the catalytic oxidation of benzene mediated by Fe-oxide CNC performs much faster kinetics at 60 °C than the ambient condition. [Display omitted] [ABSTRACT FROM AUTHOR]

The electronic communications betweenchromophores are closelyrelated to distances and orientation of these π-conjugated systems.Reported herein is a collection of well-defined two-dimensional comb-likepolymers containing porphyrin pendants obtained by ring-opening metathesispolymerizations of norbornene and cyclobutene derivatives using rutheniumor molybdenum catalysts. The spacing separating the adjacent pendantsare defined by ring sizes of cycloalkenes and the orientations aredetermined by the stiffness of the polymeric backbone, which is, inturn, discerned by the percentage of Z-double bonds.Both peak widths of the porphyrin radical cation of the EPR spectraand the absorption profiles in the Soret band region reflect the degreeof the spin delocalization and exciton coupling between porphyrinpendants in these polymers and, hence, the stiffness of the polymericbackbone. Our approach offers a useful protocol to align an arrayof chromophores appended onto a rigid polymeric backbone so that theoptoelectronic properties can be tuned. [ABSTRACT FROM AUTHOR]

Objective: This prospective study aimed to investigate the relationships between salivary levels of neurosteroids, including dehydroepiandrosterone (DHEA), cortisol, and DHEA/cortisol ratios, and behavioral symptoms in patients with attention-deficit/hyperactivity disorder (ADHD) during treatment with methylphenidate (MPH). Methods: Fifty-eight ADHD patients (48 boys and 10 girls) were included in the study initially. Forty patients (mean age: 7.77±1.64 years; 32 boys and 8 girls) who completed the study received treatment with oral MPH with a dose range of 5-15 mg/day (mean dose: 12.47±7.74 mg/day.) for 6 months at the discretion of the psychiatrist. DHEA and cortisol levels were determined from saliva samples collected at 0800 h at baseline and 6 months from baseline. ADHD symptoms were evaluated with the Child Behavior Checklist (CBCL). Results: Salivary DHEA levels (mean difference=9.05 pg/mL, p=0.027) and DHEA/cortisol ratios (mean difference=32.42, p=0.007) in ADHD patients were significantly increased, but the cortisol levels did not change significantly. During a 6 month follow-up, all behavioral problems assessed using the CBCL improved significantly. Changes in salivary DHEA levels were positively correlated with changes in salivary cortisol levels ( r=0.44, p=0.004); however, changes in salivary levels of DHEA, cortisol, and the DHEA/cortisol ratio were not significantly correlated with change in any subscales of the CBCL. Mean doses of MPH were not significantly correlated with changes in neurosteroid levels and behavioral symptoms. Conclusions: These findings provide evidence that MPH administration might affect DHEA levels and DHEA/cortisol ratios. Whether levels of neurosteroids are directly associated with brain function or behavioral problems in ADHD patients warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. Patients and Methods: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Results: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36–59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Conclusions: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype. [ABSTRACT FROM AUTHOR]

A VIII thiolate complex activated C–Cl bond in dichloromethane via S-based nucleophilic attack. The reaction products, a VIII-Cl species (major one) and a VIV binding to a CH2 containing ligand (minor one) were obtained. The work demonstrates sulfur donors in the early-transition metal thiolates having strong nucleophilic characteristics. [ABSTRACT FROM AUTHOR]

• Nucleotide excision repair (NER) function is poorly characterized in breast cancer. • We developed a novel DDB2 proteo-probe assay to measure cellular NER. • NER function is interrogated across a panel of breast epithelial and tumor cell lines. • Epigenetic silencing of ERCC4 is identified as a driver of NER deficiency. • Re-expression of ERCC4 (XPF) rescues NER deficiency and UV/cisplatin sensitivity. Homologous recombination deficiency conferred by alterations in BRCA1 or BRCA2 are common in breast tumors and can drive sensitivity to platinum chemotherapy and PARP inhibitors. Alterations in nucleotide excision repair (NER) activity can also impact sensitivity to DNA damaging agents, but NER activity in breast cancer has been poorly characterized. Here, we apply a novel immunofluorescence-based cellular NER assay to screen a large panel of breast epithelial and cancer cell lines. Although the majority of breast cancer models are NER proficient, we identify an example of a breast cancer cell line with profound NER deficiency. We show that NER deficiency in this model is driven by epigenetic silencing of the ERCC4 gene, leading to lack of expression of the NER nuclease XPF, and that ERCC4 methylation is also strongly correlated with ERCC4 mRNA and XPF protein expression in primary breast tumors. Re-expression of XPF in the ERCC4 -deficient breast cancer rescues NER deficiency and cisplatin sensitivity, but does not impact PARP inhibitor sensitivity. These findings demonstrate the potential to use functional assays to identify novel mechanisms of DNA repair deficiency and nominate NER deficiency as a platinum sensitivity biomarker in breast cancer. [ABSTRACT FROM AUTHOR]

In this study, we describe efforts to clarify the role of the copper cofactors associated with subunit B (PmoB) of the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) (M. capsulatus). This subunit exhibits strong affinity toward CuI ions. To elucidate the high copper affinity of the subunit, the full-length PmoB, and the N -terminal truncated mutants PmoB 33–414 and PmoB 55–414 , each fused to the maltose-binding protein (MBP), are cloned and over-expressed into Escherichia coli (E. coli) K12 TB1 cells. The Y374F, Y374S and M300L mutants of these protein constructs are also studied. When this E. coli is grown with the pmoB gene in 1.0 mM CuII, it behaves like M. capsulatus (Bath) cultured under high copper stress with abundant membrane accumulation and high CuI content. The recombinant PmoB proteins are verified by Western blotting of antibodies directed against the MBP sub-domain in each of the copper-enriched PmoB proteins. Cu K -edge X-ray absorption near edge spectroscopy (XANES) of the copper ions confirms that all the PmoB recombinants are CuI proteins. All the PmoB proteins show evidence of a "dicopper site" according to analysis of the Cu extended X-ray absorption edge fine structure (EXAFS) of the membranes. No specific activities toward methane and propene oxidation are observed with the recombinant membrane-bound PmoB proteins. However, significant production of hydrogen peroxide is observed in the case of the PmoB 33–414 mutant. Reaction of the dicopper site with dioxygen produces hydrogen peroxide and leads to oxidation of the CuI ions residing in the C-terminal sub-domain of the PmoB subunit. Subunit B (PmoB) of the particulate methane monooxygenase (pMMO) in Methylococcus capsulatus (Bath) has been cloned and over-expressed in E. coli K12 TB1 cells as a multicopper cytoplasmic membrane protein with ca. 9 CuI ions and shown to produce H 2 O 2 upon reaction of O 2 with the dicopper site. Unlabelled Image • Subunit B (PmoB) of particulate methane monooxygenase (pMMO) is expressed in E. coli. • PmoB and its variants/mutants are expressed in the membranes as CuI proteins. • The PmoB of pMMO contains a CuI sponge with high reduction potentials for the Cu sites. • The PmoB proteins show evidence of a dinuclear copper site. • The PmoB-enriched E. coli membranes produce H 2 O 2. [ABSTRACT FROM AUTHOR]

Catalytic mechanism of cytochrome P450 A high H/D kinetic isotope effect (KIE) (18–25) is observed from the hydroxylation of tailored di‐deuterated butane substrate, (2S,3S)‐[2‐2H1,3‐2H1]butane, mediated by engineered cytochrome P450 BM3. For the first time, the experimental evidence that supports the participation of quantum tunneling at the secondary C–H bond oxidized by P450 BM3 is demonstrated. This mechanistic revelation provides the basis for the development of biomimetic iron based catalysts for small alkane oxidation or the process for “gas‐to‐liquid” (GTL) conversion. For more information, see the Full Paper by S. Yu et al. on page 2571 ff. [ABSTRACT FROM AUTHOR]

An amino-linked nitrogen heterocyclic carbene mediates the carbon-carbon coupling reaction through direct C-H functionalization of benzene (II) and pyridine (IV) with aryl iodides (I) in the absence of a metal catalyst. [ABSTRACT FROM AUTHOR]

: BACKGROUND Decoy receptor 3 (DcR3) is a soluble receptor belonging to the tumor necrosis factor receptor superfamily and can inhibit Fas ligand-induced apoptosis. DcR3 is related to carcinogenesis, but is found in human gestational tissues, where the function is uncertain. We aimed to determine DcR3 expression and regulation in endometrial cells in vitro, and throughout the menstrual cycle and pregnancy in vivo. : METHODS Serum DcR3 levels were measured at various stages of the menstrual cycle (n = 40 women) and pregnancy (n = 20). DcR3 transcript and protein levels were analyzed in RL95-2 endometrial cells after treatment with estradiol (E2) (± anti-estrogen) and/or progesterone (± anti-progesterone). Finally, DcR3 protein and transcript were examined in decidua and chorionic villi from normal (n = 14) and anembryonic (n = 14) pregnancies. : RESULTS We identified a trend towards cyclic changes of serum DcR3 levels in the normal menstrual cycle, peaking at the mid-luteal phase, and relatively lower, more stable serum levels throughout normal gestation. DcR3 protein levels were higher in decidua than chorionic villi in normal pregnancy (P = 0.001), and levels in decidua were significantly lower in anembryonic than in normal pregnancies (P = 0.034). Physiologic concentrations of E2 and/or progesterone stimulated DcR3 transcripts in RL95-2 endometrial cells. : CONCLUSIONS This study suggested that DcR3 expression varies during the menstrual cycle and is regulated by sex steroid hormones in vitro in endometrial cells. Human gestational tissues showed a differential production of DcR3, and decidual DcR3 protein was lower in anembryonic than normal pregnancies, suggesting an active role of DcR3 in the regulation of successful pregnancies. [ABSTRACT FROM AUTHOR]