bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Mena (hMena), estrogen receptor-β (ER-β), and epidermal growth factor receptor (EGFR) expression as prognostic factors in node-negative non-small-cell lung cancer (NSCLC)
Authors: Bria E. , Mottolese M. , Sperduti I. , Visca P. , Antoniani B. , Facciolo F. , Terzoli E. , Cognetti F. , Nisticò P. , Milella M. 
Published: August 2020

e22105 Background: hMena is a cytoskeleton regulatory protein involved in adhesion and cell motility, particularly in response to EGFR activation. In addition, a possible correlation between ER-β and EGFR expression has been recently suggested in NSCLC. We therefore investigated the potential relationship and prognostic value of hMena, ER-β, and EGFR expression in node-negative NSCLC patients (pts) who underwent surgery at our institution. Methods: hMena, ER-β (isoforms 1, 2), and EGFR expression, analyzed on Tissue Micro Array, were correlated to disease-free, cancer-specific, and overall survival (DFS/CSS/OS) using a Cox model including sex, stage, age, grading, histology, number of resected nodes (RN). Logistic and generalized linear models were used to evaluate predictors of significant Cox-model variables. Receiver Operative Curve (ROC) analysis identified optimal cutoff values. Internal cross-validation (100 simulations with 80% of the dataset) was accomplished. Results: 248 pts were gathered (median follow-up 26 months, range 1–75; male/female 71/29%; adeno/other 43/57%; grading G1–2/G3 45/55%; Stage I/II 82/8%; RN ≤10/>10 34/66%). Multivariate analysis, highlighting the prognostic role of RN and hMena, is shown in the table . ER-β/2 and EGFR strongly predicted hMena overexpression (p=0.009, p=0.01); indeed, when hMena was removed from the multivariate model, both factors were independent predictors of DFS/CSS. Cross-validation analysis confirmed the prognostic role of hMena with a replication rate of 43/66% for DFS/CSS. Conclusions: hMena expression is prognostic in early NSCLC undergoing curative surgery. ER-β/2 and EGFR strongly correlate with hMena status and their prognostic role deserves further investigation. [Table: see text] No significant financial relationships to disclose.
Circulating tumor cells (CTCs) and endothelial cells (CECs) in the diagnosis of malignant pleural mesothelioma (MPM): A single institutional prospective study
Authors: Yoneda K. , Tanaka F. , Hashimoto M. , Takuwa T. , Matsumoto S. , Okumura Y. , Kondo N. , Hasegawa S. , Tsujimura T. , Fukuoka K. , Nakano T. 
Published: August 2020

e22107 Background: Circulating tumor cell (CTC), a surrogate of distant metastasis, and circulating endothelia cell (CEC), a surrogate of angiogenesis, are potentially useful in the diagnosis of malignant tumors. Following a promising result of our preliminary study showing the diagnostic value of CTC/CEC in malignant pleural mesothelioma (MPM)(Tanaka F, et al. ASCO 2008), we conducted a prospective study. Methods: Patients (pts), who presented at our institute with suspicion or diagnosis of MPM, were eligible in the study. CTCs and CECs in peripheral blood (7.5mL and 4.0mL, respectively) were captured and quantitatively evaluated with the “CellSearch” system without knowledge of clinical characteristics of patients. Results: A total of 92 pts were enrolled into the study, and the final diagnosis was MPM in 68, other malignant tumors in 7, and non-malignant diseases in 17 pts ( Table ). CTC was positive (CTC-count, 1 or more per 7.5mL of the peripheral blood) in 35%(24/68) of MPM pts (range of CTC-count, 0–27 cells/7.5 mL). Among non-malignant pts, 3 pts (18%) showed a positive-CTC, but no patient showed 2 or more CTCs in 7.5mL of the peripheral blood. The mean CEC-count (/4.0mL) was significantly higher in MPM pts than in non-malignant pts (105.1 versus 40.2; p=0.047). When the cut-off value of CEC-count for the diagnosis of MPM was defined as 50(cells/4.0mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of malignant diseases were 66%, 70%, 93%, and 26%, respectively. There was no correlation between CTC-positivity and clinical stage of MPM pts, but was a trend of increase in the mean CEC-count along with tumor progression (mean CEC-count for stage I, II, III, and IV pts: 63.0, 82.4, 95.6, and 116.7, respectively). Conclusions: CTC and CEC are useful clinical markers in the diagnosis of MPM. [Table: see text] No significant financial relationships to disclose.
Effect of caffeine treatment on low-dose γ- irradiation-induced chromatid-type aberrations in human leukemia cells and human normal fibroblast cells in culture
Authors: Jha M. N. , Bedford J. S. , Jha S. , Prasad K. 
Published: August 2020

e22113 Background: It is estimated that low dose radiation can increase the risk of cancer as well as mutations. However, the interaction of low dose radiation with caffeine has not been adequately investigated. We investigated the effects of caffeine on low dose- gamma-radiation-induced chromosomal damage in human T leukemia cells (Jurket T-cells) and two normal human fibroblast cell lines (AG1522 and GM 2149). Method: Jurkat cells were maintained in RPMI 1640 medium and fibroblast in alpha-minimal essential medium (MEM) All cells were incubated at 37o C in a humidified atmosphere of 5% CO2 in air. Cells from the exponential phase were treated with 1 mg/ml caffeine ( control cells received same amount of solvent) and irradiated with low doses (3, 5, 10, 20 and 40 cGy,), using a 137 Cs-gamma radiation source. Colcemid at a concentration of 0.1 μg/ml was added to every flask. Cells were fixed in methanol: acetic acid solution and stained with Giemsa. 100 irradiated and un-irradiated metaphase- like cells were scored for chromatid-type aberrations. Results: Low dose gamma-radiation increased the levels of chromatid breaks(dose dependent) in both normal and cancer cells; however, cancer cells appeared to be more sensitive than the normal cells. Caffeine treatment markedly increased chromatid aberrations in Jurkat T-cells at all radiation doses but not in normal cells. Previously, we reported that caffeine eliminates gamma-ray-induced G2 delay in other human tumor cells but not normal cells (Jha, et.al., Radiat. Res. 157, 26–31, 2002). Conclusions: The mechanisms that may underlie this differential effect of caffeine in cancer and normal cells are unknown, but if one result of a G2 delay is to allow more time for chromosome breakage rejoining processes to occur, then elimination of this delay by caffeine in tumor cells but not normal cells might account for the difference. To the extent these observations are generally true for tumor vs normal cells, the differential sensitization could have an impact in improving the efficacy of radiation therapy. No significant financial relationships to disclose.
Evaluation of plectin-1 immunohistochemical staining in human non-small cell lung cancer
Authors: Harris T. J. , Jones D. R. , Brenin C. M. , Kelly K. A. , George K. , Moskaluk C. A. 
Published: August 2020

e22118 Background: Plectin-1 (PLEC1), a known scaffolding protein, impacts signaling pathways and has been found to be up-regulated and redistributed to the cell membrane in tumor cells. The redistribution of PLEC1 has shown promise as a novel molecular imaging biomarker in experimental systems. The purpose of this study was to examine the variation of PLEC1 staining in human non-small cell lung cancer (NSCLC). Methods: 142 NSCLC samples from 2001–2003 were obtained from pathology archives and placed into tissue microarray (TMA) format. TMA sections were stained with anti-PLEC1 antibody. A total PLEC1 immunohistochemical (IHC) staining score was obtained by multiplying the intensity of PLEC1 staining, scored 0 through 3, by the percent of tumor cells showing membrane staining, scored 1 for <25%, 2 for 25%-75% and 3 for >75%. The samples were then grouped into low (0–2), intermediate (3–5) or high (6- 9) membrane expression and analyzed for clinical correlations to tumor type and pathological staging. Results: A total of 125 samples were successfully stained for PLEC1. In all NSCLC subgroups, there was variability of PLEC1 staining. Approximately 50% of cases showed intermediate to high staining. There was a trend of lower PLEC1 staining as the tumor stage advanced (p=0.1). There appeared to be no significant variations of PLEC1 staining when compared to gender of the patients. Conclusions: These findings are the first to show that a significant number of human NSCLC exhibit strong expression of PLEC1 in the cell membrane. As this biomarker is being developed for molecular imaging modalities in other tumor types, it may have potential to be of use in the non-invasive detection of disease or therapeutic efficacy monitoring in NSCLC. [Table: see text] No significant financial relationships to disclose.
MYCN gene amplification and DNA ploidy in peripheral neuroblastic tumors
Authors: Abdalla D. M. , Hamza M. A. , Kandil A. E. , Younes L. K. , Sorrour A. F. 
Published: August 2020

e22123 Background: Neuroblastoma is a neuroblastic tumor of the primordial crest cells which are precursors of the sympathetic nervous system and is the most common extracranial solid tumor of childhood comprising between 8 and 10% of all childhood cancers. Neuroblastoma is characterized by a diverse clinical and biological behavior The spectrum of clinical behavior suggests that genetic, biological and morphological features may be useful markers to stratify children with this disease for the most appropriate management Fluorescence in situ hybridization (FISH) is considered the best approach for detection of MYCN amplification because it can detect small copy number gains and copy number heterogeneity among tumor cells. Also, it can determine the source of amplified MYCN signal, whether extrachromosomal double minutes, expanded intrachromosomal region or chromosome 2 aneuploidy. Methods: 30 cases of peripheral neuroblastic tumors were analysed for MYCN oncogene copy number and DNA ploidy using FISH. The 30 cases were divided into: 25 cases of neuroblastoma, 2 cases of ganglioneuroblastoma intermixed, and 3 cases of ganglioneuroma. Results: MYCN oncogene was amplified in 8 out of 30 cases (27.5%). 3 cases showed double minutes, 3 cases showed homogenously staining regions and 2 cases showed both forms of amplification. As regard DNA ploidy, 18 cases were diploid and 12 cases were hyperdiploid. MYCN oncogene amplification was significantly correlated with unfavorable histology, advanced tumor stage increased recurrence and poor survival. Also ploidy was associated with increased recurrence and reduced survival. And so, MYCN oncogene amplification and DNA ploidy were poor prognostic markers and it is recommended that assessment of these factors should be routine in the management of any case of neuroblastoma. Conclusions: 1) MYCN gene amplificahion and DNA plidy are poor prognostic markers 2) They should be measured in every case of peripheral neuroblastic tumors. 3) FISH should be used in the detechion of MYCN oncogene amplification and DNA ploidy No significant financial relationships to disclose.
Evaluation on the IGF-IR Inhibitor CP-751,871, alone and in combination with paclitaxel in lung and colon cell lines
Authors: Garcia-Carbonero R. , Agullo-Ortuño M. T. , Lopez-Rios F. , Diaz-Garcia C. V. , Cortijo A. , Cortes-Funes H. , Paz- Ares L. 
Published: August 2020

e22125 Background: Signaling through the insulin-like growth factor 1 receptor (IGF-IR) has been implicated in the resistance to a number of clinically relevant anti-cancer agents. The aim of this study was to assess the direct anti-tumour effects of CP-751,871, alone and in combination with paclitaxel in lung and colon cancer cell lines. Methods: Four lung and four colon cancer cell line where treated with the IGF-IR inhibitor CP-751,871 and/or Paclitaxel in simultaneous or sequential treatments. Response to treatments was evaluated by WST-1 cell survival assays. Flow cytometric analysis was used to estimate the effect on the cell cycle and apoptosis. IGF-IR mRNA expression was determined by quantitative real-time PCR and relative gene expression values were calculated by the ΔΔCt method. Results: No correlation between basal IGF-IR mRNA expression and CP-751,871 response was observed in cell lines tested. Flow cytometric analysis demonstrated that CP-751,871 enhanced cell cycle arrest at the G1/G0 checkpoint with minimal effects on apoptosis. Combined simultaneous and, more strongly, sequential treatment with CP- 751,871 and Paclitaxel showed improved response in cell growth inhibition on HCC78, H1299, Colo205 and HT29 cell lines, and was statistically superior to Paclitaxel alone (p< 0.001) and CP-751,871 alone (p< 0.001). In H460, LS180 and DLD-1 cell lines, concomitant, but no sequential treatment resulted in antagonistic interactions. Conclusions: CP-751,871 showed a modest anti-tumour activity, predominantly cytostatic, against lung and colon cancer cell lines, that is not related to the mRNA expression. CP-751,871 tends to enhance the effects of paclitaxel in vitro, depending on sequence of administration and on the model system used. No significant financial relationships to disclose.
ERCC1, VEGF along with clinical variants impact the outcome of advanced non-small cell lung cancer (NSCLC) patients
Authors: Abdel Karim N. F. , Bui H. X. , Patil N. , Pathrose P. , Rao M. , Mostafa A. , Mehta A. , Anderson M. 
Published: August 2020

e22129 Background: ERCC1 is a useful marker of resistance to cisplatin and its analogues. Longer survival was noted in patients with ERCC1 negative expression when treated with platinum. VEGF and its receptor-KDR previously indicated poor prognosis with high tumor cell expression. Methods: From 1998–2008, a retrospective study included 32 patients with advanced NSCLC, where clinical variants as well as the levels of expression of VEGF and VEGFR using rabbit monoclonal Ab (VEGF: A-20, 1:100, SCBT; VEGFR: 55B11, 1:250, cell signaling) and immunohistochemistry for ERCC1 (Mouse monoclonal ab-8F1, Thermo Scientific, 1:200) were measured and co-related to the overall survival of those patients using Cox proportional hazards model. Results: Of the 32 patients, six received non-platinum and twenty six received platinum based regimens either first line or later. Eight patients were females (25%), three were African Americans (9%) and the median age was 62.5 (42–84). Females had a significantly higher overall survival; median survival of 30 months compared to 10.6 months for males (p=0.00089). There was no significant correlation between age and survival (p=0.2). Well differentiated NSCLC of any subtype showed better survival (p=0.04). VEGF low expression correlated with better overall survival (p=0.021). Among the 26 patients who received platinum based regimens, 11 (42%) were ERCC1 negative, 10 had strongly positive ERCC1 expression (39%) and 5 patients had weakly positive ERCC1 expression (19%). ERCC1 negativity was strongly associated with longer survival (p=0.0019) in patients treated with platinum based regimens, where patients treated with the first line platinum had better survival (p=0.034). VEGFR low expression was associated with longer survival in the same group of patients (p=0.013). Caucasians had better overall survival in comparison to African Americans (p=0.007). Higher White blood cell counts and platelet counts were associated with lower survival (p=0.0019 and 0.065 respectively). Conclusion: ERCC1 negativitiy with the first line platinum therapy, VEGF low expression, females, Caucasians as well as the absence of elevation of White blood cells and platelet counts correlate with improved overall survival in advanced NSCLC. No significant financial relationships to disclose.
Targeting ctla-4 directly on melanoma cells: A possible novel perspective in the immunotherapy of cutaneous melanoma
Authors: Queirolo P. , Laurent S. , Boitano M. , Carrega P. , Saverino D. , Alviano F. , Caielli A. , Camoriano M. , Ferlazzo G. , Pistillo M. P. 
Published: August 2020

e22138 Background: CTLA-4 (CD152) is an omodimeric membrane glycoprotein which behaves as the major negative regulator of T cell-mediated immune response. CTLA-4 inhibitory function in T cells mainly occurs upon engagement with the B7 ligands expressed on antigen presenting cells, resulting in inhibition of cytokine production and T cell proliferation. CTLA-4 expression has also been documented in established human melanoma cell lines and primary melanoma tumours. The aim of this study was to investigate the expression and functional role of CTLA-4 in primary melanoma cultures derived from biopsies of metastatic melanoma patients. Methods: Seven primary cultures were derived from melanoma samples by mechanical tissue dissociation, enzymatic digestion and filtration of single cell suspensions. Flow cytometry (FACS) with an anti-melanoma (MCSP) mAb was used to assess the growth of melanoma cells. CTLA-4 expression analysis was performed by FACS and real-time PCR. Cytokine secretion and apoptotic cells were evaluated by Elisa and Annexin V/PI staining after treatment with an agonistic anti-CTLA-4 mAb (3D5). The angiogenic property of melanoma culture supernatants was evaluated on mesenchimal stromal cells (msc) isolated from human thoracic aortas. All the study was approved by our Institutional Ethics Committee and patients gave written informed consent. Results: Constitutive CTLA-4 expression was found on all melanoma cultures with variable intensity at both the protein and transcript levels. CTLA-4 expressed by these cells is functional as its ligation, with an anti-CTLA-4 agonistic mAb, is able to induce inhibition of cell proliferation, due to apoptosis induction, and of IL-8, TNF-alpha and VEGF cytokine secretion. Moreover, CTLA-4 ligation down-modulates the ability of melanoma culture supernatants to induce angiogenic differentiation of msc as detected by the acquisition of their endothelial phenotype. Conclusions: Given the physiologic inhibitory function of CTLA-4, our results suggest its possible role in the functional biology of melanoma and open up the possibility of an anti-melanoma immunotherapy based on targeting CTLA-4 directly on tumour cells as this might allow inhibition of tumour cell growth and angiogenesis. No significant financial relationships to disclose.
The outcome of patients with triple negative breast cancer: Evidence for a favorable ethnic subgroup? The Turkish Oncology Group experience
Authors: Eralp Y. , Basaran G. , Dogan M. , Dincol D. , Demirci S. , Icli F. , Onur H. , Saip P. , Topuz E. , Haydaroglu A. 
Published: August 2020

e22158 Background: Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with a propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients in a National registry setting and identify clinical and pathologic variables associated with survival. Methods: From a retrospective registry cohort of 296 TNBC patients treated and followed between 1993–2007, we identified 248 patients with early stage disease, with follow-up of at least 12 months. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses. Results: Median age was 48. The majority of the patient group had invasive ductal carcinoma (n:204, 82.3%). Distribution by stage was as follows: stage 1: 49 (19.8%), st 2: 125 (50.4%), st 3: 69 (27.8%). Excluding 11 patients, all had received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84±2.7 % and 69±3.3%, respectively. Median survival after initial recurrence was 20 months. Sites of relapse were as follows: lung: 26 (36.1%), liver:8 (11.1%), brain: 8 (11.1%), bone: 14 (19.4%), skin/lymphatic: 7 (9.7%). Univariate analysis revealed locally advanced disease (p:0.0001), larger tumor size (p:0.004), nodal positivity (p<0.00001), and extent of nodal involvement as significant factors for DFS; whereas, locally advanced disease (p:0.0099) and extent of nodal involvement (p:0.018) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed locally advanced disease (HR: 3.3, p:0.02, 95% CI: 0.14–0.64) and extent of nodal involvement (HR:4.3, p:0.033, 95% CI: 0.059–0.88) as significant independent prognostic factors for DFS and OS, respectively. Conclusions: The outcome of patients with TNBC in this National registry cohort is comparable to other subsets with similar prognostic features and do not support the generally accepted notion that TNBC entails poor prognosis. It may be speculated that there may be inherent ethnic differences leading to distinctive tumor behaviour. Further translational research is required to identify molecular prognostic groups within the TN subset. No significant financial relationships to disclose.
Cytoplasmic expression of HuR and cyclooxygenase-2 expression in colon cancer
Authors: Song J. , Choi S. , Lee J. , Lim S. 
Published: August 2020

e22161 Background: HuR, human family embryonic-lethal abnormal vision-like protein, can bind to mRNAs and stabilizes them in the cytoplasm, resulting in more efficient translation. HuR is predominantly present in the nucleus and shuttles between the nucleus and cytoplasm. The mRNA of cyclooxygenase-2 (Cox-2) is stabilized by HuR in several cancers, including breast, stomach, lung and brain. Methods: We investigated the expression and its cellular location of HuR, and Cox-2 expression in 79 colorectal cancer patients with immunohistochemistry, and evaluated the biological implications in colorectal carcinoma. Results: Nuclear HuR expression was observed in 59 (74.7%) and cytoplasmic HuR expression was seen in 25 (31.6%). Cox-2 immunoreactivity was noted in 42 (53%). The expression of cytoplasmic HuR was significantly associated with Cox-2 expression (p=0.004). And cytoplasmic expression of HuR showed correlation with lymphatic invasion (p=0.025) and lymph node metastasis (p=0.027). Nuclear HuR showed no correlation with Cox-2 expression or other clinicopathological parameters examined. Conclusions: These results suggest that cytoplasmic translocation of HuR is associated with Cox-2 expression in some colorectal carcinoma. No significant financial relationships to disclose.