ER Levels Research Articles

Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma.

Breast cancer (BC) and obesity are two heterogeneous conditions with a tremendous impact on health. BC is the most commonly diagnosed neoplasm and the leading cause of cancer-related mortality among women, and the prevalence of obesity in women worldwide reaches pandemic proportions. Obesity is a significant risk factor for both incidence and worse prognosis in estrogen receptor positive (ER+) BC. Yet, the mechanisms underlying the association between excess adiposity and increased risk/therapy resistance/poorer outcome of ER+, but not ER−negative (ER−), BC are not fully understood. Tumor-promoting action of obesity, predominantly in ER + BC patients, is often attributed to the augmented production of estrogen in ‘obese’ adipose tissue. However, in addition to the estrogen production, expression levels of ER represent a key determinant in hormone-driven breast tumorigenesis and therapy response. Here, utilizing in vitro and in vivo models of BC, we show that macrophages, whose adverse activation by obesogenic substances is fueled by heparanase (extracellular matrix-degrading enzyme), are capable of upregulating ER expression in tumor cells, in the setting of obesity-associated BC. These findings underscore a previously unknown mechanism through which interplay between cellular/extracellular elements of obesity-associated BC microenvironment influences estrogen sensitivity—a critical component in hormone-related cancer progression and resistance to therapy.

EZH2 Protein Expression in Estrogen Receptor Positive Invasive Breast Cancer Treated With Neoadjuvant Endocrine Therapy: An Exploratory Study of Association With Tumor Response.

Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67>10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET. We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET. We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( P <0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant. Our results suggest that EZH2 might be a useful biomarker to predict response to NET.

208P Automated prognosis marker assessment in 2’004 breast cancers using an artificial intelligence-based framework for BLEACH&STAIN mfIHC

Prognostic markers in routine clinical practice of breast cancer are currently assessed using multi-gene panels. However, the fluctuating tumor purity can reduce the predictive value of such tests. Immunohistochemistry (IHC) holds the potential for a better risk assessment. To enable automated prognosis marker detection (i.e. HER2, GATA3, PR, ER, and AR, TOP2A, Ki-67, TROP2), we have developed and validated a framework for automated breast cancer identification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of 11+1 marker BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC) staining in 2′004 breast cancers. The optimal distance between Myosin+ basal cells and benign panCK+ cells was identified as 25 μm and used to exclude benign glands from the analysis combined with several deep learning-based algorithms. Our framework discriminated normal glands from malignant glands with an AUC of 0.96. The accuracy of the approach was also validated by well-characterized biological findings, such as the identification of 13% HER2+, 73% PR+/ER+, and 14 triple negative cases. Furthermore, the automated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI and TROP2 was significantly liked to the tumor grade (p<0.001 each). A high expression level of HER2, GATA3, PR, and ER was associated with a prolonged overall survival (p≥0.002 each). A deep learning-based framework for automated breast cancer identification using BLEACH&STAIN mfIHC facilitates automated prognosis marker quantification in breast cancer.

Intense red up-conversion luminescence and temperature sensing property of Yb3+/Er3+ co-doped BaGd2O4 phosphors

In this study, intense red and extremely weak green up-conversion (UC) luminescence was obtained in BaGd2O4: x mol% Yb3+/y mol% Er3+ phosphors under the excitations of 980 nm and 1550 nm. The corresponding maximum integrated intensity ratios of the red to green UC emissions are 50.3 and 158.7, respectively. The UC luminescence mechanisms upon different excitations were discussed. It was confirmed that two-photon and three-photon processes were responsible for both the red and green UC emissions excited at 980 nm and 1550 nm, respectively. The energy transfer efficiency from Er3+ to Yb3+ was calculated according to the fluorescence lifetime measurement under 1550 nm excitation. Temperature sensing based upon the thermally coupled energy levels 2H11/2/4S3/2 as well as thermally coupled Stark sublevels of 4F9/2 level of Er3+ was investigated under the excitation of 980 nm. The maximum absolute sensitivities were respectively obtained to be 0.42% K−1 at 573 K and 0.18% K−1 at 298 K. Our results indicated that BaGd2O4: Yb3+/Er3+ phosphors might be a kind of promising red UC phosphors with optical temperature measurement function.

COX2 Effects on endometrial carcinomas progression

Uterine corpus cancer is one of the most prevalent gynecologic malignancies, among which endometrial cancers (EC) represent about 90 %. Despite the proven predictive value of several immunohistochemical markers, there remains a need to identify new indicators of EC progression and exploit them for therapeutic purposes. Potential candidates with diagnostic and therapeutic efficacy include cyclooxygenases (COXs). We studied 50 EC cases: 30 endometrioid (EEC), 10 serous (SEC), 10 clear-cell endometrial carcinomas (CCEC) and 10 cases of normal endometrial tissues. We investigated the expression of COX2, ER, PR, Ki-67, EGFR, p53, Bcl-2, VEGF, MMP1, CD31, and CD163 immunohistochemically. COX2 levels in EC tissue are elevated compared to the normal endometrium and depend on tumour histological features and differentiation. Elevated COX2 leads to increased tumour cell proliferation, apoptosis inhibition, increased VEGF expression, microvessel density, and M2 macrophage infiltration, and inhibition of PR expression. ER, EGFR, and MMP1 levels are unaffected by COX2, whose levels are independent of patient age and FIGO stage

Er:YAG/Yb:YAG nanopowders‐derived Er/Yb co‐doped yttrium aluminosilicate (YAS) fibers fabricated by UV‐curable nanocomposites for 1.5‐µm single‐frequency fiber lasers

AbstractThe rare‐earth (RE)‐doped yttrium aluminosilicate (YAS) glass fibers have demonstrated their unique advantages in single‐frequency lasers due to their high solubility of RE ions and high gain per unit length. However, the RE‐doped YAS fiber is usually fabricated by RE:YAG crystal or ceramic rods and melting‐in‐tube method, which depend heavily on RE:YAG crystal or ceramic rods and, thus, cannot adjust the fiber compositions effectively; there is little research on the multiple RE ions co‐doped YAS fiber deriving from RE:YAG crystal or ceramic rods. In present work, we developed a novel method to fabricate Er/Yb co‐doped YAS fibers efficiently. The Er:YAG and Yb:YAG nanopowders were fabricated by the coprecipitation method, and then the nanopowders were dispersed into liquid organic resin to form a novel UV‐curable nanocomposite, after curing, debinding, purifying, and drawing process, an Er/Yb co‐doped YAS fibers was fabricated, the absorption coefficients of the fiber was measured to be 17 dB/cm at 976 nm (2F7/2ground level to2F5/2level of Yb and4I15/2ground level to4I11/2level of Er) and 3.2 dB/cm at 1530 nm (4I15/2ground level to the high states of4I13/2of Er). A 1.5‐µm single‐frequency laser was constructed with the 2‐cm Er/Yb co‐doped YAS fiber. The longitudinal mode spacing was calculated to be 2.2 GHz with an effective cavity length of 4.5 cm, and the spectral signal‐to‐noise ratio was higher than 60 dB. To the best of our knowledge, it is the first time that Er/Yb co‐doped YAS fibers are fabricated using the UV‐curable nanocomposites. It indicates that this proposed technology is critical for the fabrication of various types of RE ions co‐doped YAS fibers and their applications in single‐frequency fiber lasers.

Fluoroaluminate glasses with low phosphate content doped with Er3+/Yb3+ ions for up-conversion luminescence temperature sensors

Fluoroaluminate glasses with low phosphate content doped with Er3+-Yb3+ ions were synthesized and their upconversion luminescence was investigated as a function of temperature. The Judd-Ofelt theory was used to predict the transition probabilities, branching and to calculate fluorescence intensity ratio and thermal sensitivity of the glasses for the excited states of Er3+ions in the glasses. The effect of Er3+and Yb3+ ions concentrations and phosphate content on the upconversion luminescence was studied in the range 300–700 K. The fluorescence intensity ratio of the thermally coupled 2H11/2 and 4S3/2 levels of Er3+ions was studied to determine the thermal sensitivity of the glasses. It was found that the maximum absolute sensitivity Smax of the glasses under study varies in the range of 27–43 × 10−4 K−1. The high values of Smax, high upconversion intensity and the ability of recording up-conversion spectra at low excitation powers make fluoroaluminate glasses with low phosphate content promising materials for optical temperature sensors.

Can granulysin provide prognostic value in primary breast cancer?

BackgroundGranulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer. AimTo evaluate the prognostic value of intratumoral GNLY in primary breast cancer patients and its association with established clinicopathological parameters. Patients and methodsThe study included 69 node-negative breast cancer patients with known clinicopathological parameters, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would interfere with the course of disease. The median follow-up period was 144 months. Steroid hormone receptor status was determined by ligand-binding assay and HER2 status by chromogenic in situ hybridisation (CISH). Intratumoral GNLY mRNA levels were determined by RT-qPCR. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analysis. Classification of patients into GNLYlow and GNLYhigh subgroups was performed by the use of the outcome-oriented cut-off point categorisation approach. ResultsThere was a significant difference between GNLY values of patients without any recurrences and those with local or distant recurrences (Mann-Whitney test, p = 0.05 and p = 0.02, respectively). None of the tested parameters showed prognostic significance for local and distant recurrences when combined. When distant metastases and local recurrences were separated as events, the best prognostic performance was observed for GNLY as compared with any clinicopathological parameter (AUC=0.24 and p = 0.04 for local events; AUC=0.71 and p = 0.03 for distant events). Local recurrence incidence was 0% for the GNLYhigh subgroup and 19% for the GNLYlow subgroup; however distant recurrence incidence was 24% for the GNLYhigh subgroup but only 3% for the GNLYlow subgroup (Kaplan–Meier analysis). A significant positive correlation was found between intratumoral ER and GNLY levels, and a significant negative correlation between tumour grade and GNLY levels. ConclusionHigh levels of granulysin prognosticate low risk of local recurrence but a high risk of distant metastasis in primary, untreated, breast cancer patients.

Activating Ultrahigh Thermoresponsive Upconversion in an Erbium Sublattice for Nanothermometry and Information Security.

Thermal activation of upconversion luminescence in nanocrystals opens up new opportunities in biotechnology and nanophotonics. However, it remains a daunting challenge to achieve a smart control of luminescence behavior in the thermal field with remarkable enhancement and ultrahigh sensitivity. Moreover, the physical picture involved is also debatable. Here we report a novel mechanistic design to realize an ultrasensitive thermally activated upconversion in an erbium sublattice core-shell nanostructure. By enabling a thermosensitive property into the intermediate 4I11/2 level of Er3+ through an energy-migration-mediated surface interaction, the upconverted luminescence was markedly enhanced in the thermal field together with a striking thermochromic feature under 1530 nm irradiation. Importantly, the use of non thermally coupled red and green emissions contributes to the thermal sensitivity up to 5.27% K-1, 3 times higher than that obtained by using conventional thermally coupled green emissions. We further demonstrate that the controllable surface interaction is a general approach to the thermal enhancement of upconversion for a series of lanthanide-based nanomaterials. Our findings pave a new way for the development of smart luminescent materials toward emerging applications such as noncontact nanothermometry, information security, and anticounterfeiting.

Organizational Factors Associated with Evidence-Based Practice Knowledge, Attitudes, and Implementation among Nurses in Saudi Arabia.

Evidence-based practice (EBP) is crucial in keeping nurses aware of the current knowledge and improving clinical decision-making. The integration of nurses’ EBP competencies and organizational support has been suggested to create an effective arena in implementing EBP. The purpose of the study was to examine organizational factors influencing nurses’ EBP knowledge, attitudes, and implementation and identify staff nurses’ perceptions of EBP nursing leadership and hospital supports in Saudi Arabia. Data were collected from a convenience sample of staff nurses (N = 227) working in four hospitals using a cross-sectional, correlational descriptive design. Level of education (p < 0.05), EBP training (p < 0.05), unit type (ICU (p < 0.001) and ER (p < 0.01)), perceived nursing leadership (p < 0.001), and work environment (p < 0.05) supports were found significantly associated with nurses’ knowledge. Magnet recognition (p < 0.01) and knowledge (p < 0.001) had significant influence on nurses’ attitudes. Unit type (ER) (p < 0.05), knowledge (p < 0.001), and attitudes (p < 0.001) were associated with implementation. Encouragement to attend EBP trainings from nursing leadership was perceived by most nurses (51.1%). Nurses reported their hospitals support EBP through training (68.2%). Findings support the need for healthcare systems to create a culture that facilitates EBP implementation to enhance nurses’ EBP competencies and improve patients’ outcomes. Nursing managers may consider preparing nurses through education.

Association of Ki-67 Change Pattern After Core Needle Biopsy and Prognosis in HR+/HER2- Early Breast Cancer Patients.

BackgroundTo investigate the association of Ki-67 change pattern after core needle biopsy (CNB) and prognosis in HR+/HER2− early breast cancer patients.MethodEligible patients were categorized into three groups: Low group, Elevation group, and High group. Chi-square test and logistic regression analysis were used to compare the clinic-pathological characteristics. Kaplan–Meier method was used to estimate the rates of recurrence-free interval (RFI) and breast cancer-specific survival (BCSS), which were compared via the Log-rank test. Cox proportional hazard analysis was performed to investigate independent prognostic factors.ResultsA total of 2,858 patients were included: 1,179 (41.3%), 482 (16.9%), and 1,197 (41.8%) patients were classified into the low, elevation, and high groups, respectively. Age, tumor size, histological grade, lymph-vascular invasion (LVI), and ER level status were associated with Ki-67 change pattern after CNB. With a median follow-up of 53.6 months, the estimated 5-year RFI rates for the low group, elevation, and high groups were 96.4%, 95.3% and 90.9%, respectively (P < 0.001). And 5-year BCSS rates were 99.3%, 98.3% and 96.8%, respectively (P = 0.001). Compared with patients in the low group, patients in the high group had significantly worse RFI (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.16–2.54) in multivariate analysis.ConclusionsKi-67 change after CNB was associated with prognosis in HR+/HER2− early breast cancer. Patients with Ki-67 high or elevation after CNB had an inferior disease outcome, indicating the necessity of re-evaluating Ki-67 on surgical specimens after CNB.

Temperature-dependent photoluminescence and optical thermometry performance in Ca3Bi(PO4)3:Er3+ phosphors

Single phase crystalline Er3+ doped Ca3Bi(PO4)3 (CBP:Er3+) phosphors were prepared using chemical co-precipitation route. The structural, optical, morphological and luminescent characteristics of the CBP:Er3+ phosphors for optical thermometry and optoelectronic applications were examined. The diffraction patterns of the samples were matched well with the standard data with single phase cubic structure and not changed after doping. The reflectance spectrum shows the various absorption peaks owing to Er3+ ions. The field emission scanning electron microscopy (FE-SEM) images disclose that the sample particles have asymmetric and spherical particles with some aggregation. Elemental analysis and mapping confirm the existence of various compositional elements. The PL spectra specifies that the phosphor can be effectively excited by near-ultraviolet (n-UV) LED, which was well-observed from n-UV excitation spectrum. As-prepared phosphor emits the visible emission at 523 (2H11/2 → 4I15/2), 552 (4S3/2 → 4I15/2) and 662 nm (4F9/2 → 4I15/2) under n-UV excitation (376 nm). The calculated color coordinates reveal the green color emission from the phosphor under 376 nm excitation with high color purity. PL variation and fluorescence intensity ratio from the thermally coupled 4S3/2 and 2H11/2 levels of Er3+ ions can be utilized to explore applications in optical thermometry and found the good temperature sensitivity in the range of 300–473 K. Hence, the mentioned structural and optical characteristics of the prepared CBP: xEr3+ phosphors will find fascinating applicability in optical thermometry, and other optoelectronic devices.

Abstract 1934: An artificial intelligence-based framework for BLEACH&amp;STAIN mfIHC facilitates automated prognosis marker assessment in breast cancer

Abstract The assessment of prognostic markers in routine clinical practice of breast cancer is currently performed using multi gene RNA panels. However, the unknown proportion of normal breast tissue in relation to malignant breast tissue can reduce the predictive value of such tests. Immunohistochemistry holds the potential for a better assessment of tumors because tumor cells can be separately analyzed. To enable automated prognosis marker detection (i.e. HER2, GATA3, progesterone receptor [PR], estrogen receptor [ER], androgen receptor [AR], TOP2A, Ki-67, TROP2, Mammaglobin), we have developed and validated a framework for automated breast cancer identification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of 12+1 marker BLEACH&amp;STAIN multiplex fluorescence immunohistochemistry staining, in 2004 breast cancers. The optimal distance between Myosin+ basal cells and benign panCK+ benign cells was identified as 31µm and used to exclude benign glands from the analysis combined with and deep learning-based algorithm for benign gland detection. Our deep learning-based framework discriminated normal glands from malignant glands with an area under receiver-operating characteristic curves (AUC) of 0.96 (95% confidence interval [CI], 0.92 to 0.99). The accuracy of the approach was also validated by several well-characterized biological findings, such as the identification of 13% HER2+, 73% PR+/ER+, and 14% triple negative cases in the study cohort as well as a significant higher Fraction of TOP2A in the HER2+ cases as compared to the HER2- cases (p&amp;lt;0.001). Furthermore, the automated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI, TROP2, and Mammaglobin was significantly liked to the tumor grade (p&amp;lt;0.001 each). Furthermore, a high expression level of HER2, GATA3, PR, and ER was associated with a prolonged overall survival (p≥0.002 each). In conclusion, a deep learning-based framework for automated breast cancer identification using BLEACH&amp;STAIN multiplex fluorescence IHC facilitates automated prognosis marker quantification in breast cancer. Citation Format: Tim Mandelkow, Elena Bady, Magalie C. Lurati, Claudia Hube-Magg, Maximilian Lennartz, Guido Sauter, Niclas C. Blessin, Ronald Simon. An artificial intelligence-based framework for BLEACH&amp;STAIN mfIHC facilitates automated prognosis marker assessment in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1934.

Assessing the interrelation between oestrogen receptor status, heart rate variability and serum nitric oxide in breast cancer patients: Understanding their prognostic relevance.

e12564 Background: Heart Rate Variability (HRV) is a non-invasive procedure to assess cardiac functions and provides an index of autonomic function that intricately controls vascular tone. Studying the alteration in HRV with agents producing oxidative stress will provide useful information about disease progression. Lower HRV indicates low level of Parasympathetic Nervous System activation and dysregulation of cardiac functions. Elements of tumour microenvironment like prostaglandin E2, oestrogen and hypoxia stimulate nitric oxide (NO) production which reacts with free radicals released by tumour tissue forming oxidising agents. NO enhances oxidative stress causing vascular dysfunction. Very few studies have reported an interrelationship between NO and HRV parameters in breast cancer. The aim of the study is to verify the relation between HRV and serum NO levels in ER+ and ER- breast cancer groups. Methods: Study design: Analytical, Cross sectional. Sample Size: 135 women above 20 years of age with and without breast cancer. 69 women with histologically proven breast cancer in different stages and 66 women who were healthy age matched controls were included. Oestrogen Receptor (ER) status was obtained from clinical records. Out of 69 women with breast cancer, 31 were ER- with 15 in stage 1 and 16 in stage 2. 38 women were ER+ with 5 in stage 2 and 33 in stage 3. Serum NO was measured using colorimetry. Heart Rate Variability was measured from lead II ECG using Power Lab 15T and lab chart software. Serum NO levels and HRV parameters were compared between ER groups. Results: ER+ women had higher HRV with parasympathetic predominance compared to ER- with p&lt;0.001. ER+ women also had higher serum NO levels compared to ER- group with p&lt;0.001. Though no direct correlation was noticed between NO and HRV, multiple analysis of variance showed significant (p&lt;0.001) difference of all values across the groups. irrespective of menopausal status. Conclusions: A significant difference was observed in HRV of ER+ and ER- women with breast cancer. Most ER+ women were in stage 3 with significantly higher NO levels. Serum NO is expected to be the factor most responsible for HRV changes particularly in stage 3/ER+. Parasympathetic predominance seen in ER+ women possibly is due to high NO levels.[Table: see text]

The temperature sensing characteristics of Ba0.60Sr0.40TiO3: x% Er3+ powders based on upconversion luminescence

Luminescence thermometers are widely known to provide contactless and the high measurement accuracy. In this paper, the different levels of Er3+ concentration doped Ba0.60Sr0.40TiO3 (BST) powders are prepared by a sol-gel method and their structures and the temperature sensing characteristics have been studied. The temperature dependence of the upper quasi-conversion luminescence of Ba0.60Sr0.40TiO3 (BST): x% Er3+(x = 1, 2, 4, 6, 8) powders is systematically tested in the temperature range of 303 K–543 K under 980 nm excitation. Benefiting from the special energy levels of rare earth ions, for example, Er3+ shows different green emission intensity with increasing temperature due to a pair of thermally coupled energy levels 2H11/2 and 4S3/2. By measuring the fluorescence intensity ratio (FIR) of the green emission peak of Er3+ ion, the prepared sample can be used as a probe to measure the ambient temperature of the inserted Er3+ ion. With the increase of Er3+ concentration, the sensitivity of Ba0.60Sr0.40TiO3 (BST): x% Er3+(x = 1, 2, 4, 6, 8) powders first increases and then decreases, while the maximum sensitivity is obtained at 2% Er3+ concentration. In addition, the relative sensitivity and absolute sensitivity maxima are 0.42% K−1at 383 K and 1.54% K−1 at 303 K, respectively.

167MO Association between ER, PR and HER2 levels and outcome under palbociclib (Pal) + aromatase inhibitors (AIs) as first-line therapy for ER+ HER2- metastatic breast cancer (MBC): An exploratory analysis of the PADA-1 trial

In 1st-line trials, the relative Progression Free Survival (PFS) benefit of adding CDK4/6 inhibitors to AI was consistent across all subgroups of patients (pts), including those with lower ER expression. However, little is known about the absolute PFS obtained under CDK4/6i and AI in pts with low ER expression and whether PR and HER2 expression impact PFS in this setting.

Spectroscopic study of Er-doped Ga2Ge5S13 glass for mid-IR laser applications

We present mid-IR spectroscopic characterization of the low-phonon chalcogenide glass, Ga2Ge5S13 (GGS) doped with Er3+ ions. Under the excitation at ∼800 nm, Er3+:GGS exhibited broad mid-IR emission bands centered at ∼2.7, ∼3.5, and ∼4.5 µm at room temperature. The emission lifetime of the 4I9/2 level of Er3+ ions in GGS glass was found to be millisecond-long at room temperature. The measured fluorescence lifetimes were nearly independent of temperature, indicating negligibly small nonradiative decay rate for the 4I9/2 state, as can be expected for a low-maximum-phonon energy host. The transition line-strengths, radiative lifetimes, fluorescence branching ratios were calculated by using the Judd-Ofelt method. The peak stimulated emission cross-section of the 4I9/2 → 4I11/2 transition of Er3+ ion was determined to be ∼0.10×10−20 cm2 at room temperature.

Spectral and laser properties of Er:Yb:Ba3Gd(PO4)3 crystal at 1.5-1.6 µm

An Er:Yb:Ba3Gd(PO4)3 crystal was grown by the Czochralski method. Spectral properties of the crystal associated with 1.5–1.6 µm laser operation were investigated, including the absorption and fluorescence spectra and the fluorescence decay at room temperature. The fluorescence quantum efficiency of the 4I13/2 level of Er3+ ions and energy transfer efficiency from Yb3+ to Er3+ ions were calculated. A CW diode-pumped Er:Yb:Ba3Gd(PO4)3 laser at 1.5–1.6 µm with output power of about 73.9 mW and slope efficiency of 16.3% was achieved for the first time in the Er3+/Yb3+ co-doped phosphate crystal.

Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis.

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical. We hypothesize that treating ER+ letrozole-resistant T47D breast cancer cells (T47DaromLR) with a combination of 10 μM glyceollin and 0.5 μM lapatinib (a dual EGFR/HER2 inhibitor) will decrease cell proliferation through induction of apoptosis. The T47DaromLR cells were found to overexpress HER2 and MAPK while maintaining aromatase and ER levels compared to their letrozole-sensitive (T47Darom) counterparts. In the absence of estrogen stimulation, glyceollin ± lapatinib had no effect on the proliferation of the T47Darom cells, while glyceollin treatment caused 46% reduction in the proliferation of T47DaromLR cells, which was further diminished when combined with lapatinib. While neither agent influenced cell migration, glyceollin and lapatinib reduced S and G2/M phase cell entry and exclusively induced apoptosis by 1.29-fold in the T47DaromLR cells. Taken together, these results suggest that glyceollins and lapatinib may have potential as a novel combination therapeutic approach for hormone-dependent, letrozole-resistant tumors.

High sensitivity thermometry using Yb3+/Er3+ co-doped LuNbO4 nanoparticles over a wide temperature range

Improving the sensitivity of thermometry systems is an important objective. In this study, the modified molten salt method was used to prepare Yb3+/Er3+ co-doped LuNbO4 nanoparticles with uniform size and morphology. By considering the 2H11/2 and 4S3/2 levels of Er3+ ions as the thermal coupling energy levels, an up-conversion thermometer based on LuNbO4:5 mol% Yb3+ and 1 mol% Er3+ nano-phosphor was implemented with the fluorescence intensity ratio read-out method. The experimental results indicated that the LuNbO4:5 mol% Yb3+, 1 mol% Er3+ nanoparticles exhibited excellent optical thermometric sensitivity. The maximum absolute sensitivity and relative sensitivity were 0.0084 K–1 (at 673 K) and 11.34 %K−1 (at 93 K), respectively. The high absolute sensitivity may be attributed to the relatively high phonon energy of LuNbO4 (−807 cm−1), and the relative sensitivity increased with the difference in the energy level between thermally coupled levels. The temperature measurements obtained using LuNbO4:5 mol% Yb3+, 1 mol% Er3+ nanoparticles exhibited excellent repeatability, and luminescence thermometry could be implemented over a wide temperature range of 93–673 K. Our experimental results indicate that LuNbO4:5 mol% Yb3+, 1 mol% Er3+ nanoparticles have potential applications in high-sensitivity optical thermometry over a wide temperature range, and they are also ideal candidates for use in thermometers.