bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P5-09-02: Tβ4 expression in cancer-associated endothelial cells enhances progression of invasive breast cancer
Authors: Cai J , Jiang W
Published: February 2018

Background: Invasive breast cancer is a highly aggressive primary breast tumour with poor prognosis. As tumour angiogenesis is exhibited by invasive breast cancer, anti-angiogenic therapy has been intensively evaluated over the past decade. However, clinical studies were disappointing. Thymosin β4 (Tβ4), a multi-functional peptide, is associated with induction of angiogenesis, but the role of Tβ4 in tumorigenesis of invasive breast cancer is unknown. We tested whether Tβ4 inhibition could be a new target involved in tumour development and tumour angiogenesis for treatment of invasive breast cancer.

Methods: We have adapted a 3D co-culture system to acquire invasive breast cancer cells-associated endothelial cells (ECs), which is followed by characterising the differential gene expressions by PCR-based subtraction analysis. We performed Western blot analysis on the protein samples obtained from ECs-stimulated by invasive breast cancer cells. Expression of Tβ4 in invasive breast cancer was assessed by qPCR in the breast tissues (tumour, n=119; background, n=55), and protein expression confirmed by immunohistochemical examination in an invasive breast cancer tissue microarray. Finally, mice breast cancer xenografts plus non-invasively photoacoustic microscopy were used to analyse the effect of Tβ4 knockdown on the tumorigenesis of invasive breast cancer.

Results: We found that invasive breast cancer cells could stimulate an increase in Tβ4 expression in microvascular ECs. High Tβ4 levels were strongly associated with high malignant invasive breast cancer and poor clinical outcome. In vivo study showed that siRNA targeting Tβ4 blocked growth of invasive breast cancer in mice. Photoacoustic imaging revealed that knockdown of Tβ4 elicited anti-breast cancer growth, in part, through disruption of tumour vasculature. Our results demonstrate that endothelial cell-derived Tβ4 enhances the progression of breast cancer by up-regulating tumour angiogenesis and it indicates that a high level of tumour stromal Tβ4 is an independent predictor of poor outcome.

Conclusions: Inhibiting endothelial Tβ4 could be a new therapeutic target in anti-angiogenic strategy for treatment of invasive breast cancer.

Citation Format: Cai J, Jiang W. Tβ4 expression in cancer-associated endothelial cells enhances progression of invasive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-09-02.
Abstract P5-14-05: α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro
Authors: Tam K-W , Lee C-H
Published: February 2018

Background: The cancer preventive activity of vitamin E (α-tocopherol, α-TP) has been suggested by many epidemiologic studies. Our previous study showed that Tocopherol-Associated Protein (TAP), a major tocopherol–binding protein, is preferentially detected in normal breast tissues than in tumor regions among 93 clinical breast cancer patients, which postulate its tumor suppressive role in breast cells. Pterostilbene (3,5-dimethoxi-49-hydroxystilbene, PS) is a natural dimethylated analogue of Resveratrol found in different plants. Previous studies have shown that PS has the ability to induce apoptosis in a range of cancer cell lines. The purpose of our study was to assess the effect of TAP and Pterostilbene in tumor suppression of breast cancer cell.

Methods: Cell growth, proliferation, and viability were determined using the MTT assay. TAP protein expression was ablated in MDA-MB-231 breast cancer cell with nine independent siRNA sequences. MDA-MB-231 cells were transfected with pcDNA5 plasmids expressing the firefly luciferase gene. TAP protein expressions for each plasmid transfection were measured by western-blot analysis. Synergic effects of tumor growth and metastasis inhibitions in MDA-MB-231 xenograft animal model by PS and α-tocopherol treatment were evaluated.

Results: TAP served as a key molecular in responding to α-tocopheryl succinate (α-TOS) induced cell cycle regulation. PS has demonstrated the synergic decrease on breast cancer cell growth effects by the combination of α-TOS exposure. In animal model, treatment of PS and high level vitamin E diet not only induced breast tumor growth inhibition, but also suppressed tumor cell invasion by measuring circulation tumor cells in mouse blood.

Conclusions: Upon the evidences showed in this study, we suggest taking vitamin E and PS as supplements may provide both breast tumor preventative and therapeutic benefits in clinic.

Citation Format: Tam K-W, Lee C-H. α-tocopherol succinate enhances the anti-tumor activity of pterostilbene against human breast cancer cells in vivo and in vitro [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-14-05.
Abstract P5-14-06: Towards breast cancer prevention through reduced breast density: Suppressive effects of tamoxifen on normal breast epithelial cells
Authors: Rosendahl AH , Puig Blasco L , Borgquist S
Published: February 2018

Background: Breast density is positively associated with risk of breast cancer and the local microenvironment in the normal breast is known to significantly impact breast cancer initiation and further progression. The selective estrogen receptor modulator tamoxifen, with beneficial clinical effects on breast cancer recurrence, has also been shown to reduce mammographic density potentially explaining the primary preventive effects of tamoxifen. Still, important gaps persist regarding the cellular and molecular basis of how tamoxifen modifies breast density and subsequently breast cancer risk.

Purpose: To investigate the impact by tamoxifen on normal human breast epithelial cells (MCF-10A) with the additional ambition to mimic variations in breast density on the cellular level.

Experimental design: Effects of tamoxifen on MCF-10A cells at different cellular densities were evaluated in vitro. Flow cytometry and the sulforhodamine-B assay were used to assess cell cycle distribution and proliferation. Cell adhesion to extracellular matrix proteins was analyzed using hexosaminidase assay. Modulation of integrin receptor levels was determined by Western immunoblotting.

Results: Tamoxifen exposure resulted in impaired cell cycle progression of human breast epithelial cells with a dose-dependent G2/M-phase arrest and reduced cell proliferation. Irrespective of tamoxifen treatment, the percent cellular adhesion to fibronectin and collagen type I by MCF-10A cells was significantly greater in high-density models compared to low-density models. Following tamoxifen treatment the adhesion was reduced in all density models. Consistent with the tamoxifen-induced lower adhesion, the integrin α1 and β3 levels were reduced in a dose-dependent way.

Conclusion: These data support the hypothesis that tamoxifen affects the normal breast epithelium and its adhesion capacity, which may contribute to the clinically observed decrease in breast density and a potential reduced risk of breast tumor establishment.

Citation Format: Rosendahl AH, Puig Blasco L, Borgquist S. Towards breast cancer prevention through reduced breast density: Suppressive effects of tamoxifen on normal breast epithelial cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-14-06.
Abstract P5-19-03: Factors that influence posttraumatic growth in patients with breast cancer: A longitudinal trial
Authors: Berndt U , Gottschlik Y , Leplow B , Thomssen C
Published: February 2018

Objectives:

The main focus of previous research into coping with breast cancer, have been mostly with regards to the negative impacts such as emotional stress, anxiety, depression or cognitive dysfunction. However, patients also report positive changes that have come about as a result of their struggle with cancer. This is referred to as posttraumatic growth (PTG). The aim of this study was to assess the presence of PTG in breast cancer patients at two measurements and to explore the association between personality traits (resilience, optimism, self-efficacy) and positive emotions on PTG.

Patients and Methods:

The study group comprised of 80 women (with a mean age of 53.6 years, SD=10.2) recently diagnosed with stage I to III breast cancer. They completed self-report measures of PTG, resilience, optimism, self-efficacy and positive emotions up to three weeks after diagnose (t1) and then following by an update six months later (t2). Sociodemographic characteristics, emotional distress, anxiety and depression were also recorded.

Results:

Planned comparison: Breast cancer patients showed an increase of PTG from t1 to t2 (p=.00035). Resilience, optimism, self-efficacy and positive emotions did not change in the total sample from t1 to t2. Emotional distress, anxiety and depression have significantly declined from t1 to t2 (anxiety p=.015, depression p=.029, emotional distress p=.000065). Moreover, we found a significant positive correlation between positive emotions to PTG (r=-.386, p=.0004) and optimism to PTG (r=.334, p=.002) at t2, respectively. Depression t2 correlated negatively to PTG at t2 (r=-.264 p=.018).

Explorative results: We also calculated the difference between PTG t2 and t1. We found 67.5% (n=54) of the patients with an increase of PTG and 32.5% (n=26) without or with negative change. In a subgroup analysis we noticed that patients without benefit of PTG showed a decline of resilience (p=.015), self-efficacy (p=.028) and positive emotions (p=.045) between t1 and t2. Furthermore, anxiety and depression did not improve from t1 to t2 in this group.

Conclusions: Positive emotions and optimism represent indicators of PTG in breast cancer patients. A decline of anxiety and depression is associated with a higher rate of PTG. Psycho-oncological strategies related to these factors may support PTG in breast cancer patients. Future studies are needed to search for effective interventions to support patients in PTG.

Citation Format: Berndt U, Gottschlik Y, Leplow B, Thomssen C. Factors that influence posttraumatic growth in patients with breast cancer: A longitudinal trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-19-03.
Abstract P5-20-16: Not presented
Authors: Ait-Oudhia S
Published: February 2018

This abstract was not presented at the symposium.
Abstract P5-22-05: Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection
Authors: Ozmen T , Lazaro M , Zhou Y , Vinyard A , Avisar E
Published: February 2018

Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure however requires microsurgical techniques. The aim of this study was to assess the efficiency of Simplified-LYMPHA (SLYMPHA) in preventing LE in a prospective cohort of patients.

Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and December 2016 were included in the study. SLYMPHA is a slightly modified and simplified version of LYMPHA. It is performed by the operating surgeon performing the ALND. One or more lymphatic channels identified by reverse arm mapping are inserted using a sleeve technique into the cut end of a neighboring vein. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. Demographic, clinical, surgical and pathologic factors were recorded. The incidence of clinical LE was compared between ALND with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE.

Results: 406 patients were included in the study. SLYMPHA procedure was attempted in 81 patients and was completed successfully in 90% of patients. Early complication rates were similar between patients who underwent SLYMPHA and who did not (4% vs. 4.13%; p = 0.948). Median follow-up time was 15±13.73 [1-32] months. Patients, who underwent SLYMPHA, had a significantly lower rate of clinical LE both in univariate and multivariate analysis (3% vs 19%; p = 0.001; OR 0.12 [0.03-0.5]). Excising > 22 lymph nodes and a co-diagnosis of diabetes were also correlated with higher clinical LE rates on univariate analysis, but only excising > 22 lymph nodes remained to be significant on multivariate analysis.

Conclusions: SLYMPHA is a safe and relatively simple method, which decreases incidence of clinical LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.

Citation Format: Ozmen T, Lazaro M, Zhou Y, Vinyard A, Avisar E. Evaluation of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-05.
Abstract P5-22-22: Breast tumor location in BRCA mutation carriers and implications for prevention
Authors: Hosseini A , Esserman LJ , Wallace AM , Au A , Mukhtar RA
Published: February 2018

Introduction:

Close to 65% of BRCA mutation carriers do not choose prophylactic mastectomy, despite their high breast cancer risk. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk and can be modified to target specific areas of the breast. We wondered if a majority of tumors in BRCA mutation carriers would be confined to one quadrant, allowing for the use of targeted cosmetic mammoplasty as a novel method of risk reduction.

Methods:

We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning >1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squaredtest.

Results:

Mean age at breast cancer diagnosis was 44 years with mean tumor size of 2.2 cm (0.1-7cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant whether or not multicentric tumors were included in the analysis (p<0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p=0.021).

Conclusions:

More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that removing this quadrant through breast reduction mammoplasty could significantly reduce breast cancer risk. For women who are not ready for prophylactic mastectomy, this data supports an intermediate risk reduction step instead of only offering surveillance.

Citation Format: Hosseini A, Esserman LJ, Wallace AM, Au A, Mukhtar RA. Breast tumor location in BRCA mutation carriers and implications for prevention [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-22.
Abstract P6-04-01: Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells
Authors: Chen G , Ding X-F , Bouamar H , Pressley K , Yang J , Sun L-Z
Published: February 2018

Rapamycin analogs (rapalogs) inhibit mammalian target of rapamycin (mTOR) and are known to cause induction of autophagy and G1 cell cycle arrest. However, it remains unknown whether rapalog-induced autophagy plays a critical role in its regulation of cell cycle. We, for the first time, found that rapalog everolimus could stimulate autophagy-mediated Cyclin D1 degradation in breast cancer cells. Inhibiting mTOR with everolimus rapidly increased the degradation of Cyclin D1 in MCF-10DCIS.COM and MCF-7 cells. 3-Methyladenine (3-MA), a classic autophagy inhibitor, could attenuate everolimus-induced Cyclin D1 degradation. Furthermore, knockdown of autophagy related gene 7 (Atg-7) could also repress everolimus-triggered degradation of Cyclin D1 in MCF-10DCIS.COM. Moreover, everolimus-induced autophagy occurred earlier than its induction of G1 arrest and cell death. Blockade of autophagy attenuated everolimus-induced G1 cell cycle arrest. These preliminary data support the conclusion that the autophagy induced by rapalogs in breast cancer cells appears to cause Cyclin D1 protein degradation resulting in G1 cell cycle arrest. Our findings contribute to our knowledge of the interplay between autophagy and cell cycle regulation mediated by mTOR signaling and Cyclin D1 regulation.

Citation Format: Chen G, Ding X-F, Bouamar H, Pressley K, Yang J, Sun L-Z. Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-04-01.
Abstract P6-05-03: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Authors: Zhang X , Chiang H-C , Wang Y , Jin VX , Hu Y , Li R
Published: February 2018

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.

Citation Format: Zhang X, Chiang H-C, Wang Y, Jin VX, Hu Y, Li R. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-03.
Abstract P6-07-08: Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast
Authors: Nakshatri H , Ananappa M , Prasad MS , Kumar B , Liu Y , Storniolo AM , Miller KD , Bhat-Nakshatri P
Published: February 2018

Functional modeling of breast epithelial hierarchy and stromal-epithelial cell interactions has been difficult due to inability to obtain sufficient stem-progenitor-mature epithelial cells and stromal cells. The recently developed epithelial reprogramming assay has partially overcome this limitation, allowing propagation of epithelial cells with stem, luminal progenitor and mature cell features. However, characterizing stromal cells using this assay is difficult because irradiated fibroblasts which can be difficult to distinguish from stromal cells are needed as feeder layer. A recent study demonstrated expansion of airway basal stem cells without a feeder layer through pharmacologic inhibition of TGFβ/BMP/SMAD signaling. We sought to develop this method for culture and expansion of cells from normal and cancerous breast samples. With appropriate modifications to growth media, we were able to obtain normal and stromal cells from breast biopsies of healthy women. The expanded cell population included CD10+/EpCAM- basal/myoepithelial cells, CD49f+/EpCAM+ luminal progenitor cells, CD49f-/EpCAM+ mature luminal cells, CD73+/EpCAM+/CD90- rare endogenous pluripotent somatic stem cells, CD73+/CD90+/EpCAM- mesenchymal stem cells, ALCAM (CD166)+/EpCAM+ cells, CD44+/CD24- cells, CD44+/CD24+ cells and ALDFLUOR+ stem/luminal progenitor cells. Epithelial cells were KRT14+, KRT19+ or both further documenting heterogeneity within epithelial cell population. We have extended this technique to grow breast epithelial cells from high-risk patients including BRCA1 mutant-carriers, tumor-adjacent normal and tumor cells from the same patient, pleural effusions and liver metastasis from breast cancer patients. Phenotypic characterization showed differences in the differentiation state of adjacent-normal and tumor cells. Tumor cells from pleural effusions showed remarkable phenotypic heterogeneity with a fraction of these cells expressing estrogen receptor. The assay described here, therefore, is versatile and provides resources to model epithelial-stromal interactions under normal and cancerous conditions as well as for genomics and screening of drugs to target metastasis on an individual level.

Susan G. Komen for the Cure and Department of Defense supported this work.

Citation Format: Nakshatri H, Ananappa M, Prasad MS, Kumar B, Liu Y, Storniolo AM, Miller KD, Bhat-Nakshatri P. Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-08.
Abstract P6-09-11: Ki67 cut offs and oncotype DX recurrence score in early breast cancer
Authors: Namuche F , Ruiz R , Flores C , Gomez HL , Aguilar A
Published: February 2018

Background: The gene expression profiling assay OncotypeDx (ODX) predicts the likelihood of estrogen receptor (ER) positive breast cancer (BC) recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy. Many clinical scores that estimate the risk category of ODX are being tested. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use.

Methods: We retrospectively reviewed the electronic medical records of 190 patients with early stage ER+ BC for whom ODX recurrence score (RS) was available. Patients were diagnosed and treated at a specialized cancer center between 2014 and 2016. Our objective was to find out the degree to which an optimal ki67 cut-off correlates with ODX risk category. We also aim to determine an association between classical clinicopathological variables (St. Gallen (SG) 2015) could predict ODX risk category. Chi square test was used.

Results: The characteristics of patients according to ODX risk category are shown in Table 2. Mean age at diagnosis was 59 years (range 28-89). Mean tumor diameter was 15mm, 84.2% were intermediate grade and 4.7% patients had lymph node involvement. Mean expression of ER, PR and Ki67 were 87%, 53% and 22%, respectively. According to ODX 62.1% patients were low risk, 30.5% were intermediate risk and 7.4% were high risk. An overall concordance of 46.8% (73/190) was found between SG 2015 and the risk category of ODX (75.7% for low, 33.3% for intermediate and 23.9% for high RS). When changing SG Ki67 cutoffs to ≤20% (for low Ki67) and ≥30% (for high Ki67), an overall concordance of 56.3% (107/190) was found (69.6% for low, 47.3% for intermediate and 23.9% for high RS) and this was statistically significant (p=0.00) (Table 3).

Conclusion: In our population there is no a direct correlation between classical clinicopathological variables and ODX score. Despite being a specialized center, the utility of classical clinicopathological variables for predicting ODX risk category is limited.

Citation Format: Namuche F, Ruiz R, Flores C, Gomez HL, Aguilar A. Ki67 cut offs and oncotype DX recurrence score in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-11.
Abstract P6-13-01: Withdrawn
Authors: Janni WJ , Harbeck N , Rack B , Gluz O , Schneeweiss A , Kates R , Fehm T , Kreipe H , Kümmel S , Würstlein R , Hartkopf A , Clemens M , Reimer T , Friedl T , Häberle L , Fasching P , Nitz U
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P6-13-06: Not presented
Authors: Blumencranz LE , Treece T , Ellis D , Barlowe K , Blumencranz P , Audeh W
Published: February 2018

This abstract was not presented at the symposium.
Abstract P6-15-04: Characterization of tumor infiltrating lymphocytes and its association response in breast cancer
Authors: Galvez M , Castaneda C , Villegas V
Published: February 2018

Background: The magnitude of tumor infiltrating lymphocytes (TIL) is a predictor of good prognosis in the context of neoadyuvant chemotherapy (NAC) in breast cancer, and is expressed in the capacity to achieve a pathological complete response (pCR) and therefore to obtain a major survival. The characteristics of TIL are influenced of different clinical and pathological features as well as its predictive value. The goal of this study is to define the different associations between level of stromal (sTIL) and interstitial (iTIL) tumor infiltrating lymphocytes and pathological and clinical feature of breast cancer. Methods: The level of TIL was analyzed in 483 patients diagnosed with breast cancer of the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. We evaluate patient characteristics such as age, clinical stage, histological subtype and grade, clinical T, N and M, presence of estrogen (ER) and progesterone (PgR) receptors, HER-2 expression and molecular subtype as well as pathological response. Results: We found a positive association between sTIL and iTIL proportion and histological grade (G1-2 vs G3, p<0.05 and p<0.05 respectively), hormone receptor (ER- vs ER+PgR- vs ER+PgR+, p<0.05 and p=0.001 respectively), molecular subtype (Luminal A vs Luminal B vs HER2 vs Triple Negative (TN), p<0.05 and p=0.002 respectively), clinical N (positive vs negative, p=0.006 and p<0.05 respectively). Also we found association between sTIL with lymph nodes after surgery (negative vs positive, p=0.028) and pathological response (pCR vs <pCR, p=0.018), there was no association between sTIL and iTIL with age, histological subtype, clinical T and M. Conclusions: The level of tumor infiltrating lymphocytes are affected by different clinical and pathological features, they are present in both lobular and ductal breast cancer without significant difference; higher level of TIL are associated with high histological grade, ER-, TNBC and high clinical N to diagnosis; and specially sTIL are associated with to achieve a negative lymph node after NAC and obtain a pathological complete response.

Citation Format: Galvez M, Castaneda C, Villegas V. Characterization of tumor infiltrating lymphocytes and its association response in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-04.
Abstract PD2-17: Dual energy: Potentialities of contrast enhanced mammography in breast desease diagnosis and follow-up
Authors: Cossu E , Costano E , Di Trapano R , Pensabene MC , Di Stefano C , Fosi S , Fiaschetti V , Portarena I , Buonomo O
Published: February 2018

Purpose: Contrast-enhanced Dual-Energy digital mammography (DE) is a recently

used investigation that consists in acquiring low and high energy images after

intravenous injection of iodinated contrast medium. The purpose of this study is to describe our experience about the role of DE in the diagnosis and follow-up of breast cancer.

Materials and Methods: 50 patients, with heterogeneous breast pattern, already studied

by mammography and ultrasound, were selected. They underwent DE mammography: 17

for mammographic or ultrasonographic suspicious findings (9/17 also examined with MRI), 21 for loco-regional staging (21/21 studied with MRI), 10 for oncologic follow-up (6/10 also underwent MRI). DE has been interrupted in two cases due to technical problems. Exclusion criteria of the study were: breast implants, pregnancy or lactation and contraindications to administration of contrast medium. DE results were compared with the post-operative or post-bioptical (Tru-cut or Vacuum Assisted Biopsy) histological findings.

Results: DE showed a sensitivity of 76% in evaluation of Patients with mammographic or ultrasonographic suspicious findings: in comparison with MRI (9 patients), DE had a 55 % specificity (vs 22% of MRI). In locoregional staging DE proved to be more accurate than MRI in dimensional evaluation of unifocal cancer: DE accuracy was 91% vs 62% of MRI, which overestimated the size of most of lesions. In the count of tumor foci number in case of multifocal/multicentric disease MRI corresponded in 9/11 cases with histology (vs 3/11 cases of DE). DE showed a sensitivity of 100% and a 85.7% specificity in assessing oncologic follow-up Patients: in the comparison between DE and MRI (6 patients), DE got 1 false positive result, while MRI 3.

Conclusion: DE can be a valuable diagnostic tool to help conventional techniques; it is also a possible alternative to MRI in some selected type of patients or where MRI is not available.

Citation Format: Cossu E, Costano E, Di Trapano R, Pensabene MC, Di Stefano C, Fosi S, Fiaschetti V, Portarena I, Buonomo O. Dual energy: Potentialities of contrast enhanced mammography in breast desease diagnosis and follow-up [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-17.
Simulation der kutanen lymphatischen Sporotrichose durch die kutane Nokardiose
Authors: Secchin Pedro , Trope Beatriz Moritz , Fernandes Larissa Araujo , Barreiros Glória , Ramos-e-Silva Marcia
Published: February 2018

Sporotrichose ist eine subkutane Mykose, die durch verschiedene Gattungen des Schimmelpilzes Sporothrix hervorgerufen wird. Die Infektion tritt weltweit auf, doch ist im Bundesstaat Rio de Janeiro derzeit eine zoonotische Sporotrichose-Epidemie zu beobachten. Die lymphokutane Form der vor allem durch Nocardia brasiliensis verursachten Nokardiose ist selten. Sie manifestiert sich in Form nodulärer oder ulzerierter Läsionen mit multiplen schmerzhaften erythematösen Knoten oder pustulösen Satellitenläsionen entlang der Lymphbahnen und ähnelt damit der lymphokutanen Variante der Sporotrichose. Wir berichten über einen 61-jährigen Mann, der nach einem Insektenstich am linken Bein eine ulzerierte Läsion mit aufsteigender Lymphangitis entwickelte, die auf die vorausgegangenen Antibiotika-Therapien nicht angesprochen hatte. Die stationäre Aufnahme des Patienten zur weiteren Abklärung erfolgte unter dem Verdacht auf eine lymphatische kutane Sporotrichose aufgrund der typischen Morphologie sowie der Angabe zum Wohnort des Patienten in Rio de Janeiro. Während der Wartezeit auf die Ergebnisse zu den Pilzkulturen erhielt der Patient eine antibiotische Versorgung gegen CA-MRSA (community-acquired MRSA) mit Sulfamethoxazol/Trimethoprim, unter der die Läsion vollständig abheilte. Nach der Entlassung wurde aus einer Gewebeprobe des Ulcus eine Actinomyces-Spezies kultiviert und mittels molekularbiologischer Untersuchung als N. brasiliensis identifiziert. Mit dem vorliegenden Bericht möchten wir einen Fall lymphokutaner Nokardiose vorstellen, die durch N. brasiliensis, wahrscheinlich nach Insektenstich, hervorgerufen wurde. Obwohl der Patient im Bundesstaat Rio de Janeiro, einer endemischen Region für Sporotrichose, wohnhaft ist, müssen differentialdiagnostisch auch andere Ursachen einer ulzerierten Läsion mit Lymphangitis in Betracht gezogen werden, um eine möglichst frühzeitige Diagnose und entsprechende Behandlung der Krankheit zu erreichen. Übersetzung aus Case Reports in Dermatology 2017;9:119-129 (DOI: 10.1159/000471788)
Enhanced Visualization: From Intraoperative Tissue Differentiation to Augmented Reality
Authors: Wilhelm Dirk , Vogel Thomas , Ostler Daniel , Marahrens Nils , Kohn Nils , Koller Sebastian , Friess Helmut , Kranzfelder Michael
Published: February 2018

Background: Optimal visualization of the operative field and methods that additionally provide supportive optical information form the basis for target-directed and successful surgery. This article strives to give an overview of current enhanced visualization techniques in visceral surgery and to highlight future developments. Methods: The article was written as a comprehensive review on this topic and is based on a MEDLINE search and ongoing research from our own group and from other working groups. Results: Various techniques for enhanced visualization are described comprising augmented reality, unspecific and targeted staining methods, and optical modalities such as narrow-band imaging. All facilitate our surgical performance; however, due to missing randomized controlled studies for most of the innovations reported on, the available evidence is low. Conclusion: Many new visualization technologies are emerging with the aim to improve our perception of the surgical field leading to less invasive, target-oriented, and elegant treatment forms that are of significant benefit to our patients.
miR-499 Ameliorates Podocyte Injury by Targeting Calcineurin in Minimal Change Disease
Authors: Zhang Kaiyue , Sun Wenjuan , Zhang Lai , Xu Xuefang , Wang Jidong , Hong Yan
Published: February 2018

Background: Podocyte injury is a hallmark of minimal change disease (MCD). Calcineurin inhibitors have been widely used in the current treatment of MCD, and miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD and test whether miR-499 delivery can improve MCD. Methods: An MCD mouse model was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using lentiviruses. Biochemical indicators including serum albumin, triglyceride, cholesterol, and 24-h urine protein were determined. Targets of miR-499 were confirmed using reporter gene activity assays. The ultrastructure of podocytes was analyzed using transmission electron microscopy. Results: MiR-499 significantly improved MCD-related symptoms and signs. Foot-process effacement was caused by PAN and partially reversed by miR-499. We identified that both CnAα and CnAβ were targets of miR-499, and were overexpressed in the presence of PAN. However, miR-499 reduced the expression of CnAα and CnAβ, leading to a decreased activity of calcineurin signaling in mouse podocytes in vitro and in vivo. In addition, miR-499 recovered PAN-induced reduction of cell viability. Conclusions: MiR-499 ameliorated podocyte injury by targeting CnAα and CnAβ in a PAN-induced MCD mouse model. Delivery of miR-499 can be a novel strategy for MCD treatment.
A Case of Vulvar Schwannoma Mimicking Epidermoid Cyst
Authors: Tan Jingwen , Chen Jia , Yang Lianjuan
Published: February 2018

Schwannoma is a generally benign tumor of the peripheral nerve sheath arising from Schwann cells. Most schwannomas are found on the head and neck. Here, we describe a rare case of benign vulvar schwannoma located at the labium majus which was similar to an epidermoid cyst in clinical appearance.
Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension
Authors: Wijeratne D. Thiwanka , Lajkosz Katherine , Brogly Susan B. , Lougheed M. Diane , Jiang Li , Housin Ahmad , Barber David , Johnson Ana , Doliszny Katharine M. , Archer Stephen L.
Published: February 2018

Background:

The World Health Organization recognizes 5 groups of pulmonary hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from group 1, is largely unknown.

Methods and Results:

We describe incidence, prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4 PH from 1993 to 2012. Case definitions are based on hospitalizations and emergency department visits, using the Institute for Clinical Evaluative Sciences data, which comprises linked databases of universal coverage health service records for Ontario residents. This cohort included 50 529 patients with PH. The annual incidence of adult PH increased from 2003 to 2012 from 24.1 to 28.7 cases/100 000 population and the annual prevalence from 1993 to 2012 from 99.8 to 127.3 cases/100 000 population, respectively. The most common form of adult PH was group 2, alone (34.2%) or combined with group 3 PH (29.3%). A diagnosis of PH increased the 1-year standardized mortality ratio 7.2-fold. Mortality in adults with PH was 13.0%, 36.4%, and 62.4%, at 30 days, 1 year, and 5 years, respectively. Mortality was highest in groups 2 and 3 and lowest in group 1. PH was present in only 3.6% of people with left heart disease, 0.7% with lung disease, and 1.4% with thromboembolic disease, suggesting that PH is a relatively rare complication of these common diseases. Children (age<16 years) accounted for 3.6% of the cohort. In children group 1 PH was most common (65.2%), and 5-year mortality was lower (21.4%) than in adults. Group 1–specific PH therapies were increasingly prescribed over time and paradoxically were often used in patients who seemed to have group 2, PH based on diagnostic codes indicating left heart disease.

Conclusions:

The incidence and prevalence of adult PH are increasing. Groups 2 and 3 are the most common and lethal forms of PH. This study identifies an emerging epidemic of PH that likely has substantial adverse health and economic implications.
The Two Hidden Childbearing Periods and the Death of Ximen Qing in the Jin Ping Mei
Authors: Mikli Sandra
Published: February 2018

This essay will consider how some basic concepts of traditional Chinese thought inform the plot of the Jin Ping Mei by analysing the development of two hidden pregnancies and the death of the protagonist, Ximen Qing. Interpreting the Jin Ping Mei means paying close attention to the author’s hidden messages, which can only be understood within the framework of such traditional Chinese concepts as Yin and Yang and the five elements, which are interwoven throughout the novel. There are countless situations in the narrative where traditional Chinese thought plays a significant role and, undoubtedly, much more work needs to be done concerning these features. However, for the purposes of this essay, I will only focus on the pregnancies of Ximen Qing’s first and the sixth wife and on his own death. Both the pregnancies and the death may serve as examples illustrating how traditional Chinese concepts are pervasive in Ming Literature.
Traditional Thought and Utopian Egalitarianism in the Tianyi bao: The Rise of an Anarchist Ideal among Chinese Communities in Tokyo
Authors: Gaudino Emanuela
Published: February 2018

This essay discusses the experience of anarchism among young Chinese intellectuals based in Japan between 1907-1908. The rise of an anarchist ideal among Chinese intellectuals was firstly related to their acquaintance with Japanese radicals. In 1907 division among the Tongmenghui leadership and the conversion of Japanese intellectuals to anarchism made Chinese students and intellectuals based in Tokyo more susceptible to radical political doctrines. Anarchism emerged as a new trend out of this political turmoil. Liu Shipei, He Zhen and Zhang Ji were the central figures of the Tokyo Group and the main supporters of the anarchist propaganda in Japan. Through the acquaintance with the Kinyōkai 金矅会 (Friday Group), the radical socialist faction led by Kōtoku Shūsui, they were able to bring together the Chinese overseas communities in Japan, who were dissatisfied with the principle of Tongmenghui and its leadership.

The close relations with Kōtoku and Japanese socialists, the affiliation with the Tongmenghui and the quarrels within the same Alliance concerning Sun’s leadership, the establishment of societies among Chinese students in Japan and the publication of a journal, all consent to define the contours of anarchist activities in Japan between the years 1907-1908.

My goal in the following pages is to highlight the Japanese route of Chinese anarchism outlining anarchist thinking and propaganda as delineated in the pages of their official organ, the Tianyi bao (Journal of Natural Justice). Overall, I will try to answer these three questions. First, how did Chinese traditional thought become a means to sustain utopian egalitarianism? Second, how did Kōtoku Shūsui and Japanese anarchists influence the rise of an anarchist ideal among Chinese intellectuals based in Japan? And third, how did the Tianyi bao promote a racial, social and political revolution in order to create an ideal society?
Taxonomic revision of Israeli snakes belonging to the Platyceps rhodorachis species complex (Reptilia: Squamata: Colubridae)
Authors: SINAIKO GUY , MAGORY-COHEN TALI , MEIRI SHAI , DOR ROI
Published: February 2018

The Platyceps rhodorachis species complex encompasses a widespread group of morphologically similar colubrid snakes. The number and identities of species from this complex in Israel have recently been debated. Studies from the previous decade concluded that there are two species in Israel and its vicinity (compared with one previously recognized), but their identity remained contested. We estimated the number of species and their taxonomic identity using morphological and molecular data. We found some evidence for clinal variation in many of the characters used to differentiate the species, and a great overlap in traits of putative species. Genetic data revealed very low sequence divergence, with all putative species being paraphyletic. Platyceps rogersi emerged as genetically closer to Platyceps saharicus rather than to its putative conspecific, P. karelini. The phylogenetic and taxonomic results thus indicate that the Israeli populations of the P. rhodorachis complex all belong to a single species, Platyceps saharicus (Schätti & McCarthy 2004).
A review of the genus Prosodes Eschscholtz, 1829 (Coleoptera: Tenebrionidae) of Iran
Authors: CHIGRAY IVAN , NABOZHENKO MAXIM , MERKL OTTÓ , KOVALEV ALEXEY
Published: February 2018

A taxonomic review of the genus Prosodes Eschscholtz, 1829 of Iran is given. Two new species from the subgenus Meropersina Reitter, 1909 are described, both from West Azerbaijan Province: P. kasatkini sp. n. and P. shokhini sp. n. Three new synonymies are proposed: Prosodes (Dilopersina) mithras Reitter, 1904 = Prosodes (Dilopersina) chorassanica G. Medvedev, 1996, syn. n., Prosodes (Dilopersina) neopersis Semenov, 1910 = Prosodes (Dilopersina) exilis Medvedev, 1996, syn. n., Prosodes (Meropersina) cordicollis Allard, 1883 = P. cordicollis v. vermicularis Reitter, 1909, syn. n. Lectotypes are designated for Prosodes calcarata Reitter, 1893, Prosodes cordicollis v. vermicularis Reitter, 1909, Prosodes dentimana Reitter, 1909, Prosodes jakowlewi Reitter, 1909, Prosodes jakowlewi Semenov, 1894, Prosodes laticauda Reitter, 1896, Prosodes mithras Reitter, 1904, Prosodes vermiculosa Reitter, 1909, and Prosodes consanguinea Allard, 1885. The Iranian species Prosodes neopersis Semenov, 1910 is resurrected from the synonymy of Prosodes vestita Allard, 1880 and recorded from Turkmenistan for the first time. Prosodes vestita Allard, 1880 is raised to species level. The distribution of Prosodes kraatzi Reitter, 1893 is corrected: this species is known only from Eastern Afghanistan (not from Iran). Morphology of the two closely related subgenera, Dilopersina Reitter, 1909 and Meropersina Reitter, 1909 is discussed. A key to 17 Iranian species of the genus Prosodes is given (Prosodes kraatzi with doubtful Iranian occurrence is also added).
Pethia poiensis, a new species of cyprinid fish from the Chindwin Basin of Manipur, India
Authors: SHANGNINGAM BUNGDON , VISHWANATH WAIKHOM
Published: February 2018

Pethia poiensis, a new cyprinid species, is described from the Challou River, Chindwin Basin, Manipur, India. The new species is characterised by an incomplete lateral line with 7–9 pored scales, the absence of barbels, 19–20 scales in lateral series, 9–10 pre-dorsal scales, 18 pre-anal scales, 3½ scales between dorsal-fin origin and lateral line, three scales between lateral line and pelvic-fin origin and a unique colour pattern consisting of a humeral spot encompassing the third and fourth lateral-line scales, a caudal spot on the 16th and 17th lateral series scales and a black stripe along the flank. A revised key to the species of Pethia found in the Chindwin-Irrawaddy drainage is presented.
Two new species of Kamimuria (Plecoptera: Perlidae) from Shaanxi Province, China
Authors: LI WEIHAI , MO RAORAO
Published: February 2018

Two new species of the perlid genus Kamimuria Klapálek, K. shaanxinensis sp. nov. and K. yangxiana sp. nov. from Shaanxi Province of northwestern China are described in this paper. The similar characteristics of the new species and related taxa are discussed.
A needle in a haystack: the new genus Bernadottea (Diptera: Cecidomyiidae, Winnertziinae) with four new species in the Old World
Authors: JASCHHOF MATHIAS , JASCHHOF CATRIN
Published: February 2018

A new genus of Winnertziini (Cecidomyiidae: Winnertziinae) named Bernadottea gen. nov. is introduced to absorb four new species from various different parts of the Old World: B. natalensis sp. nov. from South Africa, B. honshuensis sp. nov. from Japan, and B. pahangensis sp. nov. and B. selangorensis sp. nov. from Malaysia. Bernadottea are distinguished from previously known Winnertziini by the unusually complex genitalia of males, and from most members of this tribe by the absence of the fourth medial vein (M4). Another feature of Bernadottea is their rare occurrence in samples of Winnertziini taken by hand or by traps, a circumstance presumably expressing their scarcity in nature, at least at ground level. The new taxa are described based on the morphology of males, while females and larvae remain unknown.
Review of Acangassuini Galileo & Martins, 2001 (Insecta, Coleoptera, Cerambycidae), with description of a new genus and
species, and description of two new species in the tribes Methiini Thomson, 1860 and Oemini Lacordaire, 1868
Authors: NASCIMENTO FRANCISCO E. DE L. , BRAVO FREDDY
Published: February 2018

Acangassuini is reviewed. Acangarana gen. nov. is described for A. santossilvai sp. nov. from Brazil. In addition, two species are newly described from Brazil: Methia flavomera sp. nov. (Methiini) and Stenoeme furca sp. nov. (Oemini).