bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational cell study exploring the role of estrogen receptor β expression as a predictive and/or prognostic factor in breast cancer patients
Authors: Saji S. , Honma N. , Hirose M. , Hayashi S. , Kuroi K. 
Published: August 2020

e22185 Background: We have reported that positive expression of Estrogen receptor β (ERβ) was associated with better prognosis in the early breast cancer patients treated with adjuvant tamoxifen monotherapy (J Clin Oncol. 2008). In addition, this was also true in the ERα-negative/PR-negative/Her-2 negative patients. We explored the biological impact of ERβ in breast cancer cell lines to determine whether these observations were due to its prognostic power or predictive power of response to the therapy. Methods: Since MCF-7 cell was ERβ-negative ERα-positive cell line, we established two stable clones of MCF-7 by introducing ERβ expression vector (β-clone 1, β-clone 2) as the model of ERβ-positive ERα-positive breast cancer. MDA-MB 231 cell was used as ERβ-positive triple-negative cell line. These cells were subjected to proliferation, expression and functional analysis. Results: In western blotting, both β-clone 1 and clone 2 showed decreased expression of PR and Her-2 than parent MCF-7, although there were no differences in ERα expression. Expression of ERβ decreased estradiol (E2) induced proliferation ability and rate of cells in S-phase cycle. PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) did not show any difference in response, and IC 50 for 4 OH-tamoxifen and fulvestrant did not differ among MCF-7, β-clone 1 and clone 2 (0.05–0.1 μM). Whereas, cell death due to deprivation of E2 from 1nM to 1pM was more frequently observed in ERβ-expressing clones than in parent MCF-7 cell. These cell deaths did not involve standard apoptosis pathway with caspase-3/7 activation and PARP cleavage. E2, DPN and PPT did not affect the proliferation of ERβ-positive triple negative MDA-MB 231 cell, and IC 50 for 4-OH tamoxifen was too high (8 μM) to be achieved in clinical pharmacological dose. Conclusions: From our cell study, better prognosis of ERβ-positive breast cancer patient who treated with adjuvant tamoxifen is mainly due to its own favorable biological behavior. However, this prognostic impact may include the favorable response to the treatment, when we use estrogen-deprivation therapy such as aromatase inhibitors (AIs). Additional clinical study in AI users would be required to address this issue. No significant financial relationships to disclose.
Development of a tool for reversed-phase protein microarrays (RPMA) and use in immunoproteomics of breast cancer
Authors: Keller K. , Boehm D. , Lebrecht A. , Schmidt M. , Koelbl H. , Grus F. 
Published: August 2020

e22186 Background: Breast cancer is the most commonly diagnosed cancer type in women and one of the most frequent types of cancer which leads to death. It´s early detection is a key factor for successful treatment of patients. Besides, most of the current biomarkers are still lacking of specificity. In the past decade cancer immunogenicity has been described. A development of a new non-invasive method for the detection of humoral response to cancer would be of great benefit. Methods: The proteins from healthy breast tissue and carcinoma were extracted and separated via sodium dodecylsulfate polyacrylamide gel electrophoresis. The non-stained proteins were cut out of gel, digested with trypsin and spotted on nitrocellulose microarray slides. Each sub array was incubated either with different sera of breast cancer patient or with control sera and afterwards labelled with a cyanine 5-labelled human anti-immunoglobulin G antibody (IgG). Results: The extracted and digested protein fractions from both tissue types showed reproducible antibody profiles after the incubation with sera and labelling with anti-IgG antibody. The intensity of the detected signals varied within different protein fractions. Conclusions: This method provides a stable, simple and reproducible visualization of specific antibody profiles. Further upgrading of this method could facilitate a development of a fast, non-invasive and cost- efficient tool for immunoproteomics of cancer. Moreover, the following subsequent identification of the involved tumor associated antigens (TAA´s) is crucial for an understanding of their role in pathogenesis and cancer development, possibly leading to design of new cancer therapies. No significant financial relationships to disclose.
Dual inhibition of aromatase and epidermal growth factor receptor in non-small cell lung cancer
Authors: Koutras A. , Kritikou I. , Giannopoulou E. , Dimitropoulos K. , Kalofonos H. 
Published: August 2020

e22189 Background: Recent evidence suggests that estrogen signaling is important in the progression of cancers expressing estrogen receptors (ERs) and may also be involved in the pathogenesis of non-small cell lung cancer (NSCLC). Aromatase is an enzyme complex that catalyses the final step in estrogen synthesis and is present in several tissues, including the lung. In view of a possible functional interaction between the ER and the epidermal growth factor receptor (EGFR) pathways in NSCLC, we investigated the dual inhibition of aromatase and EGFR in NSCLC cell lines. Methods: In the current study we used exemestane, an irreversible steroidal aromatase inactivator, and erlotinib, an EGFR tyrosine kinase inhibitor. The in vitroexperiments were performed using H23 and A549, two NSCLC cell lines with low and high levels of aromatase, respectively. Cell proliferation was measured by MTT assay. Metalloproteinase (MMP) levels were detected by zymography and cell migration was determined by boyden chamber assay. EGFR protein levels detection was performed by immunofluorescense assay. Results: Exemestane and erlotinib inhibited H23 and A549 cell proliferation either alone or in combination, 48 hours after their application. However, the combination of exemestane and erlotinib was more effective than each agent alone, in H23 cells. Furthermore, exemestane decreased MMP-2 and MMP- 9 levels in H23 cells, whereas erlotinib did not. The combination of exemestane and erlotinib had the same effect on MMPs, as exemestane alone. The effect on cell migration was in line with the results in MMPs levels. In A549 cells, no changes in MMPs levels or cell migration were demonstrated. In addition, exemestane altered the location of EGFR protein in H23 cells, but not in A549 cells. Conclusions: Our findings suggest an antiproliferative effect of exemestane and erlotinib in both cell lines, as well as synergy for the combination in H23 cells. The activity of the combination in these cells with low levels of aromatase might involve an additional effect of exemestane on EGFR protein location. Erlotinib did not enhance the effect of exemestane on MMPs secretion and migration in H23 cells. No significant financial relationships to disclose.
Effect of endotoxin on COX-2 dependent proliferation of NSCLC cells: Role of CD14, TLRs, and EGFR signaling
Authors: Grandel U. , Banat A. , Savai R. , Eul B. , Fink L. , Seeger W. , Grimminger F. , Sibelius U. , Hattar K. 
Published: August 2020

e22190 Background: Bacterial infections are common in NSCLC and growing evidence indicates that inflammation is contributing to cancer growth. Against this background, we investigated the effect of the bacterial cell wall components LPS on the proliferation of the NSCLC cell line A549. Methods: Proliferation of A549 cells was quantified by MTS-assay. PGE2 production was analyzed by ELISA and COX-2 mRNA was quantified by RT-PCR. Results: Incubation of A549 cells with LPS induced a time- and dose-dependent proliferation of A549 cells. Pro-proliferative effects of endotoxin could be inhibited by neutralizing antibodies targeting CD14 and TLR4, but not by inhibition of TLR2. Interestingly, interference with COX-2 activity by the specific inhibitor NS-398 strongly attenuated the LPS-induced tumor cell proliferation. In parallel, large amounts of COX-2 dependent PGE2were released by LPS-stimulated A549 cells. Moreover, enhanced transcription of COX-2 specific mRNA was detected in LPS-stimulated A549 cells. Interestingly, EGFR signaling was obviously involved in LPS-induced tumor cell proliferation and PGE2 release, as both effects could be inhibited by the neutralizing EGFR-antibody cetuximab. Conclusions: We conclude that LPS induces COX-2 dependent proliferation of A549 cells in a CD14, TLR4, and EGFR dependant manner. These effects might contribute to pathogen induced tumor proliferation in NSCLC. No significant financial relationships to disclose.
Demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population
Authors: Yin W. , Di G. , Liu G. , Wu J. , Lu J. , Shen K. , Han Q. , Shen Z. , Shao Z. 
Published: August 2020

e22204 Background: Breast cancer patients with nipple discharge (ND) may constitute a distinct clinical entity compared to those without ND, which has not been well elucidated in previous reports. We sought to analyze the demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population. Methods: A total of 3234 patients, categorized as ND (2.47%) and non-nipple discharge (NND; 97.53%) according to different initial signs, were retrospectively analyzed. Survival curves were performed with Kaplan-Meier method and annual recurrence hazard was estimated by hazard function. Results: ND group tended to have smaller tumors and less axillary lymph node (ALN) involvement than NND group (P < 0.05). In the univariate analysis, we found significantly different recurrence-free survivals (RFS) between subgroups (P = 0.0182), with the rate of 77.78% for ND group and 72.46% for the other at the 11th year respectively. In Cox proportional hazards regression analysis, we found that tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors for RFS. To further evaluate whether prognostic effect of ND status remained unabated over time, the test for lack of proportionality was performed. However, it was statistically significant (global test, P = 0.039), which hinted at a demand for the employment of Cox non-proportional hazards regression in this analysis. In time dependent Cox model, ND status (P = 0.0495) as well as ERBB2 status (P = 0.017), tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors when ND and ERBB2 status were taken as time-varying covariates. Annual hazard rates for recurrence remained lower on ND group until approximately 4.5 years after surgery, while the situation was just the opposite thereafter. Conclusions: Our findings suggested that demographic features and prognostic profiles were quite different between breast cancers presenting with and without ND in Chinese population, which may indirectly uncover distinct biological behaviors and potentially enlighten novel therapeutic approaches for patients with different initial signs. No significant financial relationships to disclose.
An immunochemical analysis of multidrug resistance gene product P170 glycoprotein in human breast cancer tissues
Authors: Michalaki V. , Gennatas S. , Karvouni E. , Kondi-Pafiti A. , Gennatas C. 
Published: August 2020

e22206 Background: P-glycoprotein (gp170; encoded by the MDR1 gene (also known as PGY1) is a membrane protein capable of exporting a variety of anticancer drugs from cells. MDR1/gp170 expression has been studied in breast cancer, but the prevalence of this expression and its role in breast tumour drug resistance are unclear. To offer more effective and less toxic treatment, selecting therapies requires considering the patient and the clinical and molecular characteristics of the tumour. Our primary goal was to clarify the prevalence and clinical relevance of MDR1/gp170 expression in breast cancer patients in correlation with clinocopathologic features. Methods: In this study the expression of MDR1/gp170 protein has been investigated in a series of 40 human breast carcinomas. The immunoperoxidase antigen detection protocol, was employed using anti-p170 monoclonal antibodies (MoABs), (JSB 1 Monosan). Clinicopathologic findings, grade, and molecular markers (HER2, estrogen receptor (ER)alpha, ER beta, and progesterone receptor were also analyzed. Results: MoAB JSB-1 reacted strongly with the transmembranic antigen epitope. The proportion of breast tumours expressing MDR1/gp170 was 22% in Grade 1, 71% and 45.4% in Grade2 and Grade3 Itumors. There was no correlation with hormone receptor status, lymph node status and ΕΕR-2. Conclusions: The data of MDR-1 product expression by immunohistochemistry in breast cancer might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment. While the functional relevance of this expression remains to be established, it seems likely that MDR1/gp170 is an independent prognostic factor in breast tumours. No significant financial relationships to disclose.
Survival associated with bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark (1999 - 2007)
Authors: Yong M. , Jensen A. Ø. , Jacobsen J. B. , Nørgaard M. , Fryzek J. P. , Sørensen H. T. 
Published: August 2020

e22210 Background: Breast cancer (BrCa) is the most commonly diagnosed cancer for women in the industrialized world. Among women who present with metastatic BrCa, more than half will develop bone metastases. Bone metastases increase the risk for skeletal-related events (SREs) defined as radiation to bone, pathologic fractures, spinal cord compression, surgery to bone, or change in antineoplastic therapy to treat bone pain. These complications are associated with an unfavorable prognosis and have a major impact on patients' quality of life. However, data on survival of BrCa patients who experience SREs are lacking. We evaluated survival among BrCa patients without bone metastases, with bone metastases, and with both bone metastases and SREs. Methods: Using Denmark's National Registry of Patients (NRP) database, we conducted a retrospective cohort study in the North and Mid- Jutland Region. Patients with a diagnosis of BrCa from January 1, 1999 through December 31, 2007 were identified using the International Classification of Diseases, 10th Revision (ICD-10) codes C50.x. SREs after BrCa diagnosis were identified using the ICD-10 code C79.5. Cox proportional-hazards regression was used to estimate the mortality rate ratio (MRR), adjusting for age and comorbidity, to compare survival among three subgroups of BrCa patients: no bone metastases, bone metastases, and bone metastases with SREs. Results: We identified 9,474 BrCa patients from the NRP. Of these, 621 (7%) developed bone metastases and 267 (3%) developed both bone metastases and SREs during the study period. The 5-year mortality rates among BrCa patients without bone metastases, with bone metastases, and with bone metastases and SREs were 50.7 per 1,000 person-years (PYs), 469 per 1,000 PYs, and 712 per 1,000 PYs, respectively. Compared to BrCa patients without bone metastases, the adjusted MRRs among BrCa patients with bone metastases and patients with bone metastases and SREs were 11.6 [95% confidence interval (CI): 10.9 - 13.6] and 18.1 (95% CI: 15.5 - 21.0), respectively. Conclusions: Our results suggest that bone metastases and SREs have a major impact on the overall mortality of BrCa patients in Denmark. [Table: see text]
Micro RNA expression to predict side effects of preoperative chemoradiotherapy in rectal cancer
Authors: Nakao T. 
Published: August 2020

e22211 Background: Preoperative chemoradiotherapy (CRT) in lower rectal cancer is used to prevent from local recurrence and preserve anus by avoiding to rectal amputation. We have reported 17 micro DNAs and micro RNAs can predict effect of CRT in ASCO-GI 2009. In this study we aimed to predict side effect of CRT such as diarrhea using micro RNA2. present 16 micro RNA to predict side effect of CRT. Methods: Rectal cancer patients (n=22) who underwent preoperative CRT (40Gy radiotherapy combined with S- 1) were studied. S-1 is a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and has potent radiosensitizing property. RNA harvested from biopsy specimens of rectal cancer before preoperative CRT was hybridized to miRNA microarrays (821 genes). Side effect of CRT was evaluated by NCI-CTC. Groups were classified as side effect group (grade 3 or over) or non side effect group (group 0, 1, 2), respectively. Results: Fifteen patients had well differentiated adenocarcinoma and 7 patients had poorly differentiated adenocarcinoma. Before CRT, 3 patients are stage I, 1 patient is stage IIA, 7 patients are stage IIIB, 8 patients are stage lllC, 3 patients are stage lV in TMN classification. After CRT, 14 patients had PR (RR 63.6%) in RECIST and 15 patient had down staging in TMN classification. Four patients had side effect. One patient had diarrhea and cytopenia, 2 patients had diarrhea, 1 patient had dermatitis. All of them were grade 3. Sixteen miRNAs(micro RNA23a, 27a, 142–3p, 142–5p, 155, 185, 196a, 221, 223, 224, 374a, 374b, 376a, 378, 424, 452) were significantly lower expressed in side effect group than no side effect group. Conclusions: Sixteen micro RNAs were down-regulated in side effect group. Therefore, profile of micro RNA expression may predict the side effect of CRT. No significant financial relationships to disclose.
Occurrence of BRCA1–2 mutations and overall survival among breast cancer patients from Sardinia
Authors: Palmieri G. , Palomba G. , Loi A. , Uras A. , Budroni M. , Contu A. , Cossu A. , Farris A. , Crisponi L. , Monne M. 
Published: August 2020

e22215 Background: Germline mutations in BRCA1-2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA1–2 mutations on prognosis and survival of breast cancer patients is still debated. In this study, we extensively investigated the prevalence and geographical distribution of BRCA1–2 mutations in the entire genetically-homogeneous Sardinian population as well as tried to clarify the influence of such mutations on breast cancer-specific survival. Methods: Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA1–2 mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan- Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. Results: A lower breast cancer-specific overall survival rate was observed in BRCA1–2 mutation-positive patients after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. The geographical distribution of BRCA1–2 mutations was related to specific three large areas of Sardinia: a) the northern area, linguistically different from the rest of the island (where a BRCA2–8765delAG mutation with founder effect was predominant); b) the central-eastern area, land of the ancient Sardinian population (where BRCA2 mutations are still largely more common thanBRCA1 mutations); and c) the south-western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). Conclusions: In Sardinian breast cancer population, the effects of BRCA1–2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA1–2 mutation carriers and non-carriers. Finally, we identified some probands' phenotypic features which may be predictive for the presence of BRCA1–2 germline mutations and should be therefore considered when counselling patients about undergoing genetic testing. No significant financial relationships to disclose.
The correlation of thrombin-activated fibrinolysis inhibitor (TAFI) levels and clinicopathologic factors in advanced colorectal cancer patients
Authors: Salman T. , Bilici A. , Ustaalioglu B. O. , Seker M. , Sonmez B. , Gumus M. , Salepci T. , Yaylaci M. , Orcun A. , Mayadagli A. 
Published: August 2020

e22217 Background: There are many ongoing researchs for novel prognostic factors in colorectal cancers. Increased thromboembolic events were associated with poor prognosis and survival in cancer patients. Thrombin-activated fibrinolysis inhibitor (TAFI), which has inhibitory effects on fibrinolysis, was proven to play a major role in hypercoagulopathy and was reported to reach high blood levels in cancer patients compared to those in the general population. Methods: TAFI levels were measured. The correlation between those levels and clinicopathologic features were analyzed in 82 patients with advanced stage colorectal cancer receiving treatment in our clinic. Results: Eighty-two patients were evaluated. Patients characteristics included 54 males (65.9%), 28 females (34.1%); median age 56.4 (range:24–76). The mean TAFI levels was 198,36±70,01 Ğer yazali and TAFI levels were found to be high in 70% of patients. High levels of TAFI were more common in rectum cancer patients compared with colon cancer patients. There was no significant correlation between TAFI levels and clinicopathologic factors, such as age, sex, body mass index, performance status, number of metastases, grade, vascular invasion, perineural invasion and CEA levels. The TAFI levels of patients receiving bevacizumab (202.1±66.6) were more higher than those no receiving (191,83±76,21), but this association was not statistically significant (p>0.05). Conclusions: Although the statistical analysis proved insignificant in our study, the effect of thromboembolic events on prognosis and survival is well established. Thus, large scale prospective studies are required to determine prognostic factors. No significant financial relationships to disclose.