bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-cadherin, E-cadherin, ERCC1, and c-kit expression in small cell lung cancer (SCLC) and potential for new therapeutic targets
Authors: Batus M. , Myint R. , Coon J. , Basu S. , Kaiser K. , Fidler M. , Bonomi P. 
Published: August 2020

e22157 Background: Minimal advances have been made in the treatment of SCLC. Molecular markers may allow us to better stratify patients (pts) for new treatment options and drug combinations. The objective of our study was to determine the frequency and potential prognostic significance of N-cadherin (N-cad), E-cadherin (E-cad), ERCC1, and c-kit (CD117) expression in SCLC. Methods: Tissue from 132 pts with SCLC was retrospectively stained for N-cad, E-cad, ERCC1, and c-kit. Frequency of expression (% of tumor cells staining positive) was measured on a scale of 0–4 (freq 0=no expression (<1%), freq 1=1–10%, freq 2=11–35%, freq 3=36–70%, freq 4=71–100%). Charts were reviewed for stage, performance status, date of diagnosis/death, survival, and treatment (type, dates, response). The frequency of molecular markers was correlated with clinical data and overall survival. Results: Age range 42 to 97 years, 65 male:67 female, and 64 had limited and 68 had extensive stage. Of the 132 pts, 75% had tumors that expressed (frequency ≥ 1) N-cad, 58% E-cad, 70% ERCC1, and 55% c-kit. Comparing tumor marker expression with survival using either the Log-Rank Test or the Wilcoxon Test, there was no significant association for N-cad, E-cad, or ERCC1. However, tumors that expressed c-kit with frequency ≥ 3 had a trend toward superior survival compared with frequency < 3. Median survival for c-kit frequency ≥ 3 was 496 days compared to 312 days for frequency < 3 (p = 0.09, Log-Rank Test). Conclusions: In our retrospective study of 132 SCLC pts, we found that all 4 markers were expressed in greater than 50% of specimens, and that higher c-kit expression was associated with marginally significant increase in overall survival. Though previous experience with imatinib alone or with chemotherapy showed limited clinical activity in unselected SCLC pts, given preclinical synergy with cisplatin, it seems reasonable to consider combination therapy with cisplatin/etoposide and imatinib in pts selected for high c-kit expression. [Table: see text] No significant financial relationships to disclose.
Evaluation of estrogen receptor expression as a prognostic factor for very young women (below 35 years) with breast cancer in Taiwan
Authors: Lin C. , Huang C. , Lu Y. , Laiu J. , Huang S. , Kuo W. , Kuo W. , Chang K. , Cheng A. 
Published: August 2020

e22163 Background: In the past two decades, the incidence of very young (<35 years) breast cancer in Taiwanese has been rapidly increasing to quite close to that of Caucasian Americans. However, the clinicopathological features of this group of patients appear to be different from their Western counterpart. Here, we sought to determine the prognostic value of ER expression for this newly emerging population in Taiwan. Methods: We retrospectively collected information on all consecutive very young patients (age <35 years) with stage I-III breast cancer treated at National Taiwan University Hospital between 1997 and 2005. ER expression was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tissue sections. Tumor with more than 10% positive nuclei was considered ER positive. Results: A total of 178 patients with a median age of 32 (range: 21–35) years were included. The median follow-up time was 62.5 (95% confidence interval, 42.0–64.2) months. Univariate analysis showed that ER expression was significantly associated with favorable OS (HR=0.48, P=0.03), but not with DFS (hazard ratio [HR]=0.79, P=0.42). Multivariate analysis showed that stage and ER were independent prognostic factors. Conclusions: In contrast to the findings in Caucasians, ER expression was an independent prognostic factor for favorable overall survival in Taiwanese patients with very young breast cancer. No significant financial relationships to disclose.
Breast cancer ErbB2 status in Asian women: A review of local literature
Authors: Tan Y. , Han S. , Lu Y. , Yip C. H. , Sunpaweravong P. , Jeong J. , Caguioa P. B. , Aggarwal S. , Yeoh E. M. , Moon H. 
Published: August 2020

e22164 Background: Breast cancer incidence is increasing throughout Asia. However, the characteristics of Asian breast cancer are not always well understood due to the limited availability of local data and their inadequate inclusion in global literature databases. Effective breast cancer treatment in this region requires a better understanding of Asian breast cancer biology, including ErbB2 status. Methods: We performed a literature search in seven Asian countries on breast cancer studies in which tumour ErbB2 overexpression was assessed. The keywords erbB2 OR HER2 OR ErbB-2 OR HER-2 AND breast cancer AND (country) were used to search PubMed, international and local conference abstracts and local-language journals from the year 2000 onwards. Where available, we selected up to five representative studies from each country on the basis of population size, multi-institution patient populations, institution reputation and journal impact factor. We excluded studies containing only mRNA, serum, or cell line data or those conducted on biased populations or in western countries on Asian populations. Results: ErbB2 data from 26 Asian breast cancer studies are summarized in the table . The mean or median age of the study populations ranged from 46–56 years, with one exception. In most studies that evaluated tumour ErbB2 and hormone status, ErbB2 over-expression correlated negatively with ER positivity. Conclusions: The larger studies in particular confirm that the proportion of ErbB2-positive breast cancer in Asia is generally similar to the 20–30% reported for western women. Definitions of ErbB2 positivity using IHC vary between institutions and FISH is not routinely performed in several Asian countries. This may contribute to the fact that reliable, representative data on breast tumour ErbB2 status is scarce in Malaysia, the Philippines, India and Thailand. The increased availability of accurate ErbB2 testing and data would aid improved treatment of ErbB2-positive breast cancer in these countries. [Table: see text] [Table: see text]
COX-2 expression and clinical outcome in early-stage breast cancer patients treated with adjuvant chemotherapy: A prospective study
Authors: Kargi A. , Ozdogan M. , Bozcuk H. , Pestereli E. , Artac M. , Coskun H. S. , Mutlu H. , Uysal M. , Karaveli S. , Savas B. 
Published: August 2020

e22165 Background: To evaluate the association of cox-2 expression with the outcome after adjuvant chemotherapy in patients with early breast cancer. Methods: This was planned as a prospective study recruiting consecutive patients receiving adjuvant anthracycline based chemotherapy and with available tissue blocks permitting all immunohistochemical analyses. Cox-2 expression, in addition to other classical biological factors, was evaluated with immunohistochemistry. Disease and patient related, and biological predictors of both overall survival (OAS) and relapse free survival (RFS) were analyzed by Cox regression analysis. Median and mean survival times were calculated according to the Kaplan Meier method. Results: A total of 88 patients were recruited over a period of 24 months. Median age was 45 (29 to 70), and 60% of subjects were premenapausal. Median tumour diameter and number of axillary lymph nodes involved were 2 cm (1 to 6 cm), and 2 (0 to 15), respectively. Median follow up is 74.2 months. Univariate analysis revealed menopausal status and estrogen receptor expression as predictors of OAS, and menopausal status as the correlate of RFS. Multivariate analysis confirmed the independent predictive value of both menopausal status and estrogen receptor expression for OAS (P=0.009, HR=4.18, and P=0.014, HR=0.20, respectively). No multivariate analysis could be performed for RFS. Cox-2 expression was not associated with OAS or RFS (P=0.208, HR=1.92, and P=0.132, HR=1.89, respectively). Interestingly, Cox-2 expression was correlated with Estrogen receptor (ER) and Progesteron receptor (PR) expression (P=0.006, R=-0.303, and P=0.004, R=-0.312, respectively). Conclusions: Cox-2 expression fails to predict clinical outcome of early breast cancer patients treated with adjuvant chemotherapy. However, Cox-2 expression seems to negatively correlate with ER and PR expression. It should be tested in this patient population whether Cox-2 may play a part in hormonal resistance. No significant financial relationships to disclose.
Comparison of three different methods for the detection of human papillomavirus infected in cervical lesions
Authors: Ahn W. , Shin J. , Park D. , Lee S. , Wen L. , Kim K. , Kim Y. 
Published: August 2020

e22166 Background: Several techniques are in use for HPV DNA detection: Hybrid Capture IIR(HCIIR) assay, PCR-based DNA microarray and Luminex-based assay. This study was aimed to examine the performances of three validated HPV assays. We compared the concordance between the three methods for detecting HPV in cervical specimen. Methods: Cervical samples of 189 Korean women (21∼77 ages, average 41.2 age) were tested for HPV detection in this study. We examined the performances of three validated HPV assays according to each method's instructions : 1) Hybrid Capture IIR (HCIIR) assay (HCIIR; Digene Corporation, USA) was used to test for detection of 18 types of HPV (high-risk types: HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and low-risk types types: HPV 6, 11, 42, 43, 44). 2) HPV DNA Chip, PCR-based DNA microarray system (MyGene Co., Seoul, South Korea) was used to test for genotyping of 24 types of HPV: 15 types of high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and 9 types of low-risk types (HPV6, 11, 34, 40, 42, 43, 44, 54, 70). 3) Luminex-based HPV test (YBT, Seoul, Korea) was performed for genotyping 26 types of HPV including 15 high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and 11 low-risk types (HPV-6, 11, 34, 40, 42, 43, 44, 54, 55, 67, 70). Results: We compared HPV detection results obtained by the HC II assay with those from the Luminex assay. 51 cases were discordant: 29 samples were HC II negative/Luminex positive and 22 samples were HCII positive/Luminex negative. We also compared HPV detection results obtained by the DNA chip assay with those from the Luminex assay. 37 cases were discordant: 5 samples were DNA chip negative/Luminex positive and 32 samples were DNA chip positive/Luminex negative. Conclusions: The distribution of the HPV detection results obtained for 91 samples using three different methods suggested that the results of DNA chip assay are more often discordant (17.9% instead of 5.1% for Luminex assay and 5.1% for the HC II assay). No significant financial relationships to disclose.
Effect of CCL2 on survival of breast cancer MDA-MB-231 cells via inhibition of apoptosis
Authors: Alva A. S. , Varsos Z. , Roca H. , Pienta K. 
Published: August 2020

e22176 Background: The cytokine CCL2 (Chemokine (C-C) motif ligand 2 or monocyte chemo attractant protein-1 MCP-1) has been shown to play an important role in breast cancer progression by promoting angiogenesis and migration. CCL2 is over-expressed by breast cancer cells as well as by macrophages and mesenchymal stem cells in the tumor micro-environment. We studied the effects of CCL2 and IL-6 on survival of breast cancer MDA-MB-231 cells. Methods: Cytokine expression including of CCL2 and IL- 6 were analyzed in supernatants from MDA-MB-231 cells using cytokine antibody array (Human Antibody Array 3; Ray Biotech, Inc). Serum starved MDA-MB-231 cells were treated with CCL2 (75 ng/mL) and IL-6 (100 ng/mL; both from Apollo Cytokine Research). Cell viability in response to treatment was analyzed at serial time points by cell proliferation assay WST-1 (Roche Applied Science). Protein expression of genes of interest was studied by Western blot. Results: In contrast to primary breast tumor cells, MDA-MB-231 cells express minimal CCL2 at baseline. MDA-MB-231 cells also exhibit low expression of IL-6. Stimulation of MDA-MB-231 cells with either exogenous CCL2 or exogenous IL-6 did not increase levels of the other cytokine. In MDA-MB-231 cells, CCL2, alone and in combination with IL-6, promotes survival in serum starved conditions. Treatment of MDA-MB-231 cells with CCL2 leads to survivin up-regulation beginning at 48 hours as determined by immunoblotting analysis. CCL2 in combination with IL-6 inhibits the cleavage of PARP, lamin and caspase3. Conclusions: There is minimal endogenous expression of CCL2 in MDA-MB-231 cells. CCL2 from the tumor micro-environment promotes survival of MDA-MB-231 cells associated with up-regulation of survivin. IL-6 may play a syngeristic role with CCL2 in promoting survival of MDA-MB-231 cells. We plan to explore the role of survivin up-regulation in protecting cells from cell death. Our findings raise the possibility of utilizing neutralizing antibodies against CCL2 in therapy of breast cancer. No significant financial relationships to disclose.
Evaluation of the association of CXCR4 expression with HER2 status or mTOR expression levels
Authors: Smith M. H. , Li B. D. , Sun G. , Chu Q. D. 
Published: August 2020

e22192 Introduction: CXCR4 is a chemokine receptor that is linked to breast cancer metastasis. The putative mechanism involves activation of the HER-2/PI3K/PTEN/Akt/mammalian target of rapamycin (mTOR) pathway, resulting in enhanced synthesis of downstream proteins such as CXCR4 and eukaryotic initiation factor 4E (eIF4E). Overexpression of eIF4E has been shown to be an independent predictor of breast cancer outcome. Because HER-2/mTOR/CXCR4 pathway has mainly been observed in vitro, it deserves scrutiny to determine whether it is also seen in human breast cancers. We hypothesize that HER-2/mTOR axis is not significantly associated with CXCR4 regulation in human breast cancers. Method: 107 stages 1 - 3 breast cancers from a prospective breast cancer database were analyzed. Samples were quantified for mTOR, CXCR4, and eIF4E levels by Western Blot. mTOR, and eIF4E levels were quantified as fold-over benign breast tissues and CXCR4 levels were quantified as fold-over Hela cells. CXCR4 overexpression was defined as low (< 6.0 fold) or high (≥ 6.0 fold), and eIF4E expression level was separated into tertiles. Primary end points were cancer recurrence and death. Statistical analyses performed were independent student t-test, Spearman correlation, Kaplan-Meier survival curves, log-rank test, and Cox proportional hazard model. Results: All 59 HER-2 (-) and 48 HER-2 (+) breast cancer specimens overexpressed CXCR4 (mean=6.18 ±4.4), mTOR (mean=1.24 ±1.58), and eIF4E (mean=9.53 ±6.42). Unlike in vitro data, there was no difference in mean CXCR4 expression level between HER-2 (-) and HER-2 (+) tumors (mean=6.55, 5.72, respectively) (p=0.33). While mTOR correlated significantly with eIF4E level (p=0.0006, r = 0.34), it did not correlate with CXCR4 level (p=0.713, r=0.036). Only nodal status (p=0.04) and eIF4E level (p=0.03) were independent predictors of breast cancer death. Conclusions: We demonstrate that CXCR4 regulation in human breast cancers is more complex than previously thought. There was no correlation between mTOR and CXCR4 levels, nor was there a difference in mean CXCR4 overexpression levels between HER-2 (+) and HER-2 (-) tumors. Pathways regulating CXCR4 expression warrant further investigation. No significant financial relationships to disclose.
Establishment and molecular characteristics of PC-9 derived erlotinib resistant cell lines
Authors: Jida M. , Yamamoto H. , Kubo T. , Hayashi T. , Otani H. , Sano Y. , Toyooka S. 
Published: August 2020

e22193 Background: EGFR mutation is closely associated with tumor responsiveness to EGFR tyrosine kinase inhibitors (TKIs), gefitinib or erlotinib. However, many non-small cell lung cancer (NSCLC) cases with EGFR mutation that had responded to EGFR-TKIs finally acquire resistance to EGFR-TKIs. It has been reported that T790M mutation and MET amplification caused resistance to EGFR-TKIs . Recent study suggested that overexpression of HGF was also related to resistance to EGFR-TKIs. However, the whole mechanism of acquired resistance to TKIs is still not fully known. Methods: We established 5 clones of elrotinib resistant PC-9 cell line (harboring EGFR exon 19 deletion) (designated as PC-9ER1–5) by exposing PC-9 to low-dose erlotinib. The protein expression of EGFR-related molecules was examined by Western blotting. Array comparative genomic hybridization (aCGH) or real time quantitative PCR (qPCR) assay was performed to examine copy numbers of EGFR-related genes. Results: In MTS assay, the IC50 value for the parental PC-9 cells was 0.02 μmol/L. By contrast, those for PC-9ER1–5 were more than 33μmol/L. All 5 resistant cell lines retained exon19 deletions and did not obtain T790M mutation. The qPCR assay and aCGH showed no MET amplification in PC-9 or PC-9ER1–5. HGF protein was not overexpressed in PC-9ER1–5 by ELISA. The protein expressions of several molecules in the EGFR-Akt signaling pathway were examined by western blotting after erlotinib treatment. Although phospho-EGFR was suppressed in both PC-9 and PC-9ER1–5 with 2-μmol/L erlotinib, phospho-Akt was not suppressed in PC-9ER1–5. PTEN expression was not down-regulated in PC-9ER1–5. The combination of erlotinib and PHA-665752, MET tyrosine kinase inhibitor, did not suppress phospho-Akt or cell proliferation in PC-9ER1–5. Conclusions: As common molecular features of our EGFR-TKI resistant cell lines, phospho-Akt was not suppressed with exposure to erlotinib. These cell lines did not show previously reported features of resistant cell lines including T790M mutation, MET amplification or HGF overexpression. Our results indicated that other mechanisms leading to Akt activation caused resistance to EGFR-TKIs. No significant financial relationships to disclose.
Proteome analysis of malignant pleural effusion
Authors: Lee K. , Bang J. , Kim K. 
Published: August 2020

e22194 Background: Because pleural effusion contains proteins of potential diagnostic value, a comprehensive proteomic analysis of the pleural effusion is worthy to discover a new biomarker. Malignant pleural effusion and tuberculous pleural effusion are sometimes diagnositc challenge due to their similarity like lymphocyte-dominant effusion. Herein, we tried to identify differentially expressed proteins in both effusion using proteomic anlaysis. Methods: Twenty microliters of pleural effusions(PEs) from 3 patients with non-small cell lung cancer(NSCLC) and 3 patients with tuberculous pleurisy(TBC) were used for proteome analysis. After depletion of high abundant proteins including albumin, IgG with MARS Hu-6(Agilent), proteins were separated by SDS-PAGE and subject to in-gel tryptic digestion. The resulting peptides were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The MS/MS spectra were analyzed by Spectrum Mill against normal and reversed human protein databases. Results: In the total of 6 samples, 90 proteins were identified with more than 2 peptides and less than 1% of false positive rate. Among the identified pleural proteins, 57 proteins were detected both in PEs of NSCLS and TBC, 19 and 14 proteins were identified only in the PE of NSCLC and TBC, respectively. We analysed molecular functions, molecular composition and molecular processes of identified proteins with FindGo software. Among the identified proteins, we found the biomarker candidates that significantly have different expression levels in malignant effusion; apolipoprotein B precursor, vitronectin, complement factor B, histidine-rich glycoprotein precursor, coagulation factor II precursor variant. Conclusions: We found that several pleural effusion proteins may serve as potential biomarker candidates for differential diagnosis between maligant and tuberculous pleural effusion. We'll confirm these proteins through the proteomic method(MRM) and immunological method(Western bolt). No significant financial relationships to disclose.
Candidate treatments of brain metastases suggested fromin silico gene expression analysis of archival primary breast tumor tissue and brain metastases (BM)
Authors: Iyengar T. , Tran N. L. , Armstrong B. A. , Berens M. E. 
Published: August 2020

e22203 Background: Patients with metastatic breast cancer are living longer due to advances in therapy. Interestingly, there are times when systemic disease is well controlled but progression continues within the central nervous system (CNS). We report our retrospective analysis of gene expression data from the GEO database. Methods: We interrogated the NCBI/GEO database using the following search terms: breast cancer, gene expression, and brain metastases. We identified a set of tissue samples and compared gene expression arrays from 4 separate BM specimens to 7 primary breast cancer specimens; all specimens were Her-2 neu +/ER - tumors except one (information unavailable). Using a t-test, a two-fold or greater change in gene expression was considered significant if the p-value was <0.05. Results: Analysis of the gene expression profiles revealed several gene candidates over expressed in the BM specimens as compared to primary tumor specimens. Of interest are the motility-associated genes (ICAM1, cortactin, DOCK11, and myosin; p<0.03), pro-survival gene (AKT3; p<0.03), the FGF-growth factor signaling pathway (FGF1; p<0.02), and genes positively regulating the epithelial-to-mesenchymal transformation (EMT) process [TGFB1, SNAI2 (SLUG), NOTCH2; p<0.03]. Notably, the TGFB/Slug pathway is influenced by Sonic hedgehog (SHH). SHH inhibitors are currently being investigated in phase I clinical trials. Conclusions: To the best of our knowledge, this is the first analysis to suggest a role for TGFB and SHH signaling as it relates to the metastatic potential of breast cancer. Our findings argue for gene expression analysis on a larger number of BM specimens for discovery and validation of gene candidates important for this malignant progression. As there are drugs already available to target these pathways, the goal would be to accrue more patients with primary or secondary CNS malignancies to assess response. No significant financial relationships to disclose.