bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of laser capture microdissection to derive poor prognosis gene expression signatures of epithelial abdominal malignant mesothelioma
Authors: Borczuk A. C. , Chen J. , Parikh F. , Powell C. A. , Taub R. N. 
Published: August 2020

e22098 Background: Prior work in abdominal malignant mesothelioma (AMM) has established a poor prognosis profile of biphasic AMM when compared to more favorable prognosis epithelial AMM. It is evident, however, that epithelial AMM shows heterogeneity in biologic behavior and prognosis. Given improvements in therapy and survival in AMM, stratification of patients with epithelial AMM into favorable and poor prognosis subgroups is desirable and gene expression profiles may provide poor prognosis signatures to further guide therapy. Methods: Favorable and poor prognosis subgroups were defined as 1000 days of survival time (based on median survival of 90 patients with AMM at Columbia Presbyterian as of Sept 2007). Fourteen frozen epithelial AMM (7 favorable prognosis, 7 poor prognosis) with high quality RNA were laser capture microdissected using a PALM Zeiss microscope and analyzed using Affymetrix U133 Plus 2 microarrays. Unsupervised hierarchical clustering and supervised subgroup analysis were performed using BRB tools version 3.2. Results: Unsupervised hierarchical clustering revealed 2 main clades that contained 6 of 7 poor prognosis and 6 of 7 favorable prognosis tumors, respectively. Supervised class comparison revealed a 39-gene signature that distinguished the 2 classes (permutation values of p < .001). High expression of Nde1, UHRF1, and EZH2 by qPCR on a set of 32 AMM (using an upper quartile cutoff) was associated with poor survival (Log rank statistic p<.01, p<.003 and p<.03 respectively). Immunohistochemistry performed on tissue microarrays of 122 AMM for p16 loss and increased EZH2, Col3A1 and UHRF1 immunoreactivity was associated with poor survival (Log rank statistic p<.0001, p<.009, p<.0001 and p<.012, respectively). Conclusions: Using a training set of laser captured favorable and poor prognosis epithelial AMM, a 39-gene signature was obtained that is associated with prognosis. Validation of several of the candidate genes by qPCR expression and immunohistochemistry was performed, confirming favorable and poor prognosis strata among the epithelial AMM. Identification of poor prognosis epithelial AMM at the time of initial biopsy/tumor cytoreduction could lead to more aggressive primary therapeutic intervention. No significant financial relationships to disclose.
Apoptotic and immunomodulatory effects of green tea extracts (GTE) on chemoresistant human tumor cells
Authors: Braun D. P. , Johnson D. M. , Katsantonis N. G. , Bhesaniya K. , Staren E. D. 
Published: August 2020

e22101 Background: GTE and Epigallocatechin 3-gallate (EGCG), the most abundant polyphenol in GTE, have been shown to exert inhibitory effects on carcinogenesis; modulatory effects on tumor proliferation and differentiation; and immunomodulatory effects on tumor immunity in different pre-clinical models. These pluripotent effects suggest that GTE may have clinical activity that could be exploited for treatment of chemo-insensitive but immunologically responsive tumors. Thus, the present study investigated the effects of EGCG on the proliferation and immunologic sensitivity of human renal cell cancer (RCC) and malignant melanoma (MM) cell lines. Methods: Human RCC (769-P) and MM (A375) cell lines were tested following incubation in media ± 21.8μM EGCG, a pharmacologically-achievable concentration produced by 8, 200mg capsules GTE daily. Tumor proliferation was assessed by MTS assay; lytic sensitivity to IL2-activated human peripheral blood lymphocytes (IL2PBL) by 51Chromium release assay; and gene expression by quantitative RT-PCR assay. Results: EGCG produced significant inhibition of proliferation of both RCC and MM cells (61.5% and 67.3% of media control values respectively; p<0.01 by 2-tailed, paired t test). EGCG also caused significantly increased expression (≥ 2 times (×) media control values) of pro-apoptotic genes in both RCC: BCL2L1 (5.4×); BCL2L10 (7.9×); BIK (2.9×); Caspase 5 (6.3×); and Caspase 14 (6.3×) and MM cells: Caspase8 (2X) and Card6 (2.5X). Unfortunately, EGCG pre-treatment also decreased the sensitivity of RCC (43% of control) and MM (53% of control) to IL2PBL-mediated lysis (p<0.01 respectively). This occured in association with significant upregulation of Fas ligand mRNA in RCC (6.3×) and TRAF2 mRNA in MM (33 ×). Conclusions: The results of this pre-clinical study demonstrate that EGCG exerts significant antiproliferative effects against human RCC and MM cells in vitro in association with increased expression of different pro-apoptotic genes. Unfortunately, EGCG-treated cells also demonstrated reduced sensitivity to lysis by IL2-activated human lymphocytes. Taken together, the results suggest that GTE may have activity in vivo in patients against chemoresistant RCC or MM but should not be used in conjunction with IL2 therapy. No significant financial relationships to disclose.
Relationship between lymphovascular invasion (LVI) and prognostic markers in different subtypes of breast cancer
Authors: Panopoulos C. G. , Tzavara C. , Papadimitriou K. , Pistalmatzian N. , Lypas G. , Barbounis V. , Demiri S. , Koumakis G. , Apostolikas N. , Efremidis A. 
Published: August 2020

e22109 Background: Prognostic and predictive factors for invasive breast cancer (BC) are well established. LVI was added to the list of prognostic factors for node negative patients (St.Gallen 2006). The aim of this study was to investigate the relationship of LVI with known prognostic markers and its role on different subtypes of breast cancer. Methods: 367 patients with primary BC were evaluated in this study. Tumoral and peritumoral breast tissue was examined for LVI. The patient's age, menopausal status, tumor histology, tumor size, histologic grade, lymph node (LN) involvement, hormone receptor (HR) status and HER-2 status were determined as markers of prognosis. The association of LVI with the aforementioned markers was evaluated using multiple logistic regression analysis. Results: The distribution of the patients was as follows: 40.9% were HR + and HER-2 - (luminal type), (32.4%) were triple negative, 26.7% were HER-2 Positive (9.5% of them were HER-2 + and HR -, while 17.2% were HER-2 + and HR+). Almost half of the patients (48.8%) had one or more positive nodes. Multiple analysis revealed that histologic grade, LN involvement and HER-2 positivity were independently associated with LVI. Patients with histologic grade II and III had 5.31 (95% CI: 1.14–24.75) and 7.03 (95% CI: 1.47- 33.53) times greater odds for LVI respectively compared to those with grade I. Patients with one or more than three nodes involved had 3.95 (95% CI: 2.13–7.33) and 6.29 (95% CI: 3.14–12.63) times greater odds for LVI respectively compared with node negative tumors. Furthermore, HER-2 positive patients had almost twofold likelihood for LVI (OR=1.80, 95% CI: 1.02–3.16). The effect of HER-2 positivity on LVI was independent of HR status. Age, menopausal status, tumor histology, tumor size and HR status were not significantly associated with LVI. Conclusions: LVI shows a close relationship with known markers of poor prognosis as histologic grade, and LN invasion. More aggressive tumors as HER-2 + tumors have a significantly higher probability of LVI, which may be used as an indicator of more aggressive behavior of the primary tumor. No significant financial relationships to disclose.
Correlation of education, age, and health insurance status with attitudes about and preferences for direct-to-consumer BRCA testing
Authors: Gray S. W. , Smith D. , Karp L. , O'Grady C. , Hornik R. , Armstrong K. 
Published: August 2020

e22116 Background: Direct-to-consumer (DTC) cancer genetic testing is increasingly common. However, little is know about peoples' attitudes about or preferences for DTC testing as compared to clinic-based genetic testing. Methods: We surveyed a convenience sample of 257 women without prior BRCA testing/counseling experience about their attitudes about and intentions to get online BRCA testing (90% participation rate). Subjects completed baseline interviews, viewed a modified commercial DTC website and completed an online survey. Results: Sample characteristics: mean age 37 (range 19–71), 80% white, mean education 3 years college, 45% with a household income <$50,000, 3% with a history of breast/ovarian cancer and mean Frank risk 4.7%. 64% of women expressed interest in BRCA testing at baseline and 24% intended to get tested in the next year. After viewing the website, 22% of women said that they would prefer DTC testing, 60% said that they would prefer clinic-based testing and 18% were indifferent. Overall, women believed that DTC testing would be more convenient (p <0.001), offer greater privacy (p <0.01), and be less likely to lead to discrimination (p <0.001) while clinic testing would provide more information (p <0.001) and counseling (p <0.001). After adjusting for confounders, older and less highly educated women had more positive attitudes about DTC BRCA testing (adjusted odds ratio (OR) 4.20, p= 0.02 and OR 10.3, p=0.03 high school (HS) vs. college and OR 16.1, p=0.02 HS vs. graduate school). Women with no health insurance and more positive attitudes about DTC genetic testing were more likely to prefer DTC genetic testing over clinic testing (adjusted OR 3.1, p=0.03 and OR 3.7, p<0.01). There were no associations between race and outcomes. Conclusions: A substantial minority of women expressed a preference for DTC BRCA testing after viewing a modified commercial website. Preferential interest in DTC testing by less educated and uninsured populations makes it especially critical that these sites provide high quality services. Without high quality service, the availability of DTC testing may only exacerbate disparities in genetic services and prevention. No significant financial relationships to disclose.
High expression levels of putative hepatic stem/progenitor cells biomarkers related to tumor angiogenesis and poor prognosis of hepatocellular carcinoma
Authors: Xu Y. , Fan J. , Yang X. , Zhou J. , Qiu S. 
Published: August 2020

e22121 Background: To investigate the prognostic values of putative hepatic stem/progenitor cells (HSCs/HPCs) biomarkers in hepatocellular carcinoma (HCC) patients. Methods: Fourteen biomarkers related with HSCs/HPCs or tumor angiogenesis were assessed by qRT-PCR and then validated by tissue microarrays (TMAs) in three independent cohorts of HCC patients underwent curative resection (n=67, 314 and 73). Results: Most of the biomarkers were found over-expressed in recurrent HCC patients by qRT-PCR. HSCs/HPCs biomarkers cytokeratin 19, ABCG2, CD133, Nestin, CD44 and angiogenesis agents CD34, VEGF and PD-ECGF, were confirmed as significant predictors for overall survival (OS) and/or relapse-free survival (RFS) in TMAs analysis. Compared with the low HSCs/HPCs profile group, patients with high HSCs/HPCs profile had significantly lower OS and RFS (p<0.0001), expressed higher VEGF levels (p = 0.012) and microvessel density (MVD, determined by CD34 immunostaining, p = 0.030). Based on Cox regression, a simplified model including CD133, CD44, Nestin, and MVD was constructed and confirmed as an independent predictor for OS (p<0.0001) and RFS (p<0.0001), regardless of alpha-fetoprotein level, tumor stage and recurrence time (p<0.0001 for all). Conclusions: High expression levels of HSCs/HPCs biomarkers are related to tumor angiogenesis and poor prognosis of HCC. The simplified model based on HSCs/HPCs and tumor angiogenesis profile can be used to classify HCC patients with high risk of tumor recurrence after operation. No significant financial relationships to disclose.
Prevalence of early-stage prostate and estrogen receptor positive (ER+) breast cancer patients receiving primary androgen deprivation therapy (ADT) and aromatase inhibitors (AIs) in the United States (U.S.)
Authors: Barlev A. , Yong M. , Cherkowski G. , Cetin K. , Fryzek J. 
Published: August 2020

e22126 Background: AIs and ADT are used to prevent recurrence of breast and prostate cancers but have been shown to accelerate bone loss. We estimated the prevalence of early-stage ER+ breast and prostate cancer patients on hormone therapy in the U.S., as this is not well-described in the literature. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program, published literature, clinical practice, and a large claims database were used. We began with the American Cancer Society's estimated number of new breast and prostate cancer cases for the year 2008. We then assessed the number of patients with localized/regional disease and ER+ tumors and those receiving primary ADT (both chemical and surgical) or AI therapy by applying proportions from SEER, published literature, clinical practice, and the claims database. Using these incident case counts, we calculated the 5-year prevalence using appropriate cohort-specific survival rates to sum the number of new and surviving cases over a 5-year period. Results: The estimated 5-year prevalence of early-stage ER+ breast cancer for women aged ≥50 years in the U.S. was 607,411, of which 293,904 (48.4%) were on AI therapy based on the claims database. However, because this data source was limited to women aged <65 years, we also used estimates from clinical practice to capture AI use for women of all ages. Based on clinical practice, 402,637 (66.3%) to 460,156 (75.8%) of early-stage ER+ breast cancer patients were on AI therapy. For early-stage prostate cancer, the estimated 5-year prevalence for all ages was 1,024,238, of which 141,451 (13.8%) were on primary ADT. However, these figures may underestimate current usage of hormone therapies, as our data and the literature show increasing trends in ADT and AI use for early-stage disease. Conclusions: Based on a combination of population-based data and the published literature, approximately half of all early-stage ER+ breast cancer patients and a modest proportion of early-stage prostate cancer patients are on hormone therapy in the U.S. [Table: see text]
Regulatory role of p53 in cancer metabolism through SCO2 and TIGAR in human breast cancer
Authors: Choi S. , Song J. , Lim S. , Lee J. 
Published: August 2020

e22128 Background: Cancer cells showed higher rate of anaerobic respiration than normal cells. The exact mechanisms for this higher rate of glycolysis in cancer cells remain to be elucidated. Recent researches suggest that p53, the most commonly mutated tumor suppressor gene, might play an important roles in the regulation of energy generating metabolic pathways that switch from oxidative phosphorylation to glycolysis through synthesis of cytochrome C oxidase 2 (SCO2) and TP53-induced glycolysis and apoptotic regulator (TIGAR). Methods: We investigated the expression of p53, SCO2, TIGAR and cytochrome C oxidase (COX) in 95 cases of invasive ductal carcinoma using immunohistochemistry. Results: Overexpression of p53, SCO2, TIGAR and COX was observed in 27.4% (26 cases), 82.1% (78 cases), 76.8% (73 cases), and 77.9% (74 cases) respectively. Overexpression of p53 was significantly associated with decreased expression of SCO2 (p=0.009), COX (p=0.001) and TIGAR (p=0.03). Conclusions: These results suggest that p53 can modulate the metabolic pathways via SCO2 and TIGAR in human breast cancer. No significant financial relationships to disclose.
Quantitative estimates of the effects of concomitant chemotherapy on acute dysphagia in patients receiving radical treatment for head and neck cancer
Authors: Bhide S. , Gulliford S. , A'Hern R. , Hall E. , Newbold K. , Harrington K. , Nutting C. 
Published: August 2020

e22134 Purpose: To generate quantitative parameters describing the effect of concomitant chemotherapy on incidence of grade 3 dysphagia (CTCAE v3.0, assisted feeding) using dose response curves in patients receiving radical treatment for head and neck cancer. Methods: Patients treated at a single centre in prospective phase I and II trials of concomitant chemo-IMRT (CRT) (n=85) and the phase III trial of IMRT vs. conventional radiotherapy (PARSPORT) (n=82) formed the basis of this non-randomized comparison. Patients in the PARSPORT trial received radiation alone (RT). Radiation dose for all patients was radiobiologically equivalent to at least 70Gy in 35 fractions. Concomitant chemotherapy was cisplatin (100 mg/m2) on days 1 and 29. G3 dysphagia was recorded prospectively. Dose volume histograms (DVH) were generated for the pharyngeal mucosa. The mean dose (converted to equivalent dose in 2Gy/fraction, MD2) was used as a univariate descriptor of the DVH, for the generation of the dose response curves. A logistic function of the form p=1/[1+(MD50/D)k] was fitted where, p is the probability of the incidence of toxicity, D is the mean dose, MD50 is the mean dose at which 50% of patients experience toxicity and k describes the increase in incidence with increasing dose. The dose response curves were fitted using non-linear logistic regression. Results: The mean MD2 to the pharyngeal mucosa were 56Gy and 55.8Gy respectively, in the CRT and RT groups. There was a statistically significant difference of 25% (95% CI: 10–38, p=0.002) in the incidence of G3 dysphagia between the CRT (68%) and RT (43%) groups. Fitting dose response curves to the clinical data yielded parameter values (95% CIs) of MD50=46 Gy (42–49), k=4.8 (2.3–7.2) for the CRT group and MD50= 58 Gy (55–61), k=3 (1.6-.45) for RT group. Dose response gradients for CRT and RT showed approximately 1.95% and 1.3% increase (respectively) in probability of G3 dysphagia resulting from an increase in mean dose of 1Gy between doses of 30Gy to 70Gy. Conclusions: Addition of concomitant chemotherapy increases the incidence of G3 dysphagia by 0.65% for every 1 Gy increase in radiation dose. The observed MD50 for G3 dysphagia is lower for RT alone (46 Gy vs. 58 Gy). No significant financial relationships to disclose.
Novel genes mediating cisplatin resistance in head and neck cancer
Authors: Gasco M. , Syed N. , Coley H. , Colantonio I. , Merlano M. , Crook T. , Crook T. 
Published: August 2020

e22135 Background: Chemo-radiotherapy with cisplatin-based regimens offers the possibility of cure to a subset of patients with surgically non-resectable squamous carcinomas of the head and neck (HNSCC), but outcome is frequently limited by acquired drug resistance. We have sought novel genes mediating cisplatin resistance in HNSCC. Methods: We derived in vitro cisplatin resistant variants of the HN5 HNSCC cell line and performed micro-array anaylsis to identify differentially expressed genes. Differences in gene expression were confirmed by qPCR and /or western blotting. Methylation-dependent transcriptional silencing of down-regulated genes was studied by bisulphate sequencing and methylation specific PCR. Selected genes were further analysed in a cohort of stage III and IV HNSCC patients treated with cisplatin-based chemo-radiotherapy. Results: We have identified a panel of genes in which changes in expression occur with acquisition of cisplatin resistance both in vitro and, some cases, in vivo. Up-regulated genes include TAOK1, BZW1 and RECQL, whereas down-regulated genes include FAM83D, PAFAH1B2, DLL1, ABPA1 and FH. Conclusions: We report the identification of a novel panel of genes which function as determinants of cisplatin sensitivity. Analysis of expression and/or epigenetic regulation of these genes may have clinical utility in prediction of patients likely to respond to highly toxic combined modality chemo-radiotherapy. No significant financial relationships to disclose.
Serial pro-gastrin-releasing peptide and neuron specific enolase in predicting radiological response and overall survival of patients with small-cell lung cancer
Authors: Ono A. , Naito T. , Tsuya A. , Nakamura Y. , Murakami H. , Kaira K. , Takahashi T. , Endo M. , Yamamoto N. 
Published: August 2020

e22144 Background: Pro-gastrin-releasing peptide (ProGRP: P) and Neuron specific enolase (NSE: N) are specific serological markers in patients (pts) with small-cell lung cancer (SCLC). The aim of this study was to investigate whether decreasing of these tumor markers correlate with radiological response and prognosis in pts with SCLC. Methods: Out of 194 newly diagnosed SCLC pts from September 2002- April 2008 at our institution, we retrospectively reviewed consecutive 118 pts who had measurable lesions and elevated baseline levels of P and N before initial therapy (IT) including chemotherapy or chemoradiotherapy, and survived more than one month. P and N were measured on the first day of the every treatment course and after the final course of IT. Computed tomography (CT) was documented on baseline and every 2 courses of IT. Results: Forty-six (38.9%) pts had limited stage disease (LD) and 72 (61.0%) pts had extensive stage disease (ED). Both P and N levels at baseline were significantly correlated with the sum of longest diameter (SLD) in baseline CT; Spearman's ρ was 0.34 (P=0.001) and 0.44 (p<0.0001), respectively. Also, the decreasing rate of P and N correlated with the decreasing rate of SLD, ρ= 0.45 (p<0.0001) and 0.21 (p=0.03), respectively. Furthermore, the normalization of both P (<46pg/ml) and N (<10ng/ml) levels after 3 courses of IT was significantly associated with radiological response (p=0.015) including partial and complete response assessed by the Response Evaluation Criteria in Solid Tumors. In Cox's multivariate analysis, the normalization of both P and N levels after 3 courses of the IT (p=0.03, hazard ratio: 0.47, 95% CI 0.23–0.93) was significantly associated with prolonged survival, when adjusted by age, PS, and disease extent (LD or ED). Conclusion: Levels of P and N at baseline, and decreasing rate of P and N in IT were both associated with radiological response. In addition, the normalization of both P and N levels might be meaningful in predicting prognosis of SCLC pts. No significant financial relationships to disclose.