bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FOXC1/FBP1 signaling axispromotes tumorigenicity by enhancing the Warburg effect in colorectal cancer.
Authors: Li Dawei , Li Qingguo , Cai Sanjun , Xie Keping 
Published: September 2018

e15123 Background: Aberrant expression of Forkhead Box transcription factors plays vital roles in the oncogenesis and metastasis of many types of cancer. The purpose of this study is to elucidate the function of Forkhead Box C1(FOXC1) in colorectal cancer (CRC)malignancy maintenance. Methods: FOXC1 expression in CRC specimens was analyzed in the TCGA database and validated by immunohistochemistry using a tissue microarray (TMA). The effect of FOXC1 expression on cancer proliferation and glycolysis was assessed in cells by altering the expression of FOXC1 in vitro and in vivo. Mechanistic investigation was carried out by using cell and molecular biology approaches. Results: FOXC1 was found to be overexpressed in CRC specimens compared with that in the adjacent benign tissues. Univariate survival analyses of the TCGA and validated cohorts showed that high expression of FOXC1 was significantly correlated with shortened patient survival ( P< 0.05). Attenuation of FOXC1 expression inhibited proliferation, clone formation and decreased glucose consumption and lactate production. By contrast, overexpression of FOXC1 had the opposite effect. Furthermore, increased FOXC1 expression downregulated the expression of a key glycolytic enzyme,fructose-1, 6-Bisphosphatase 1 (FBP1). Mechanistically, FOXC1 bound directly to the promoter regions of the FBP1 gene and negatively regulated its transcriptional activity. Aberrant FBP1 expression contributes to CRC tumorigenicity, and decreased FBP1 coupled with increased FOXC1 provided better prognostic information than FOXC1 did alone. Conclusions: The FOXC1/FBP1 axis induces cell proliferation, reprograms the metabolic process in CRC and provides potential prognostic predictors and therapeutic targets for patients with CRC.
Prognostic significance of VEGF-A/VEGF-R and EGF in liver metastasis from colorectal cancer.
Authors: Nikipelova Elena Alekseevna , Kit Oleg I. , Frantsiyants Elena Mikhaylovna , Bandovkina Valeria , Kaplieva Irina V. , Trepitaki Lidia K. , Tkalya Lyudmila Dmitriyevna , Kolesnikov Evgeniy N. , Snezhko Alexander V. , Averkin Michail , Kozhushko Mikhail Anatolievich , Sanamyanc Sergey Vladimirovich , Myagkov Roman E. , Kharin Leonid , Trifanov Vladimir 
Published: September 2018

e15128 Background: Liver metastasis from colorectal cancer dramatically reduces the treatment effectiveness and affects survival. Early detection of metastasis allows increasing the median survival and improving the quality of life of patients. The purpose of the study was to reveal factors significant for the prognosis of liver metastasis from colorectal cancer. Methods: Levels of VEGF-A, VEGF-R and EGF were studied by ELISA in tumors and resection line tissues of 113 patients with colorectal cancer (rectal cancer n = 43, colon cancer n = 70). Results: VEGF-A and VEGF-R levels in all tumors were increased compared to the resection line. VEGF-A levels in 46.5% patients with rectal tumors and in 29% patients with colon tumors were 2.5 times higher than in other patients; the VEGF-A/VEGF-R ratio was 2.9 times higher as well. Besides, these patients showed an increase in EGF levels in tumors by 3.9 times (rectal cancer) and 4.2 times (colon cancer), compared to the resection line. The follow-up demonstrated that the patient cohort developed liver metastases during next 3 months. Conclusions: Neoangiogenesis is activated in rectal and sigmoid tumors, and increasing VEGF-А and EGF contribute to tumor progression and metastasis. The VEGF-A/VEGF-R ratio in tumor tissues in comparison with the resection line value can be a reliable factor for the prognosis of liver metastasis.
Complex carbohydrates as a predictive marker in metastatic colorectal cancer (mCRC) cancer patients treated with a vascular endothelial growth factor (VEGF) inhibitor and chemotherapy.
Authors: Martin Petra , Fennelly David William , Rudd Pauline , O'Donoghue Diarmuid , Sheahan Kieran , Nolan Blathnaid , O'Sullivan Jacintha , Stockmann Henning 
Published: September 2018

e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as a key driver in oncopathology. Elevated levels of sialic acid sugars affect tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Changes in sialylation can be associated with malignant transformation and with progression and poor prognosis of carcinomas, which can be explained by the recognition of malignant cells by selectins, causing interactions of tumor cells with platelets, leukocytes and endothelium facilitating metastasis. Secreted or proteolytically released carcinoma mucins bearing unusual forms of sialylation can be detected in the bloodstream and are used as diagnostic and prognostic aids. Bevacizumab directly binds VEGF (a glycoprotein) to inhibit angiogenesis. The aim of this study was to analyze the pool of asparagine-linked complex carbohydrates (i.e. the N-glycome), of whole serum to identify sugars that are associated with survival in mCRC patients treated with a VEGF and chemotherapy. Methods: We used our recently developed high-throughput automated platform to precisely measure the levels of complex serum carbohydrates in patients (n = 68) with metastatic colorectal cancer samples of patients who went on to receive bevacizumab and chemotherapy. Survival analysis was performed using the R package ‘survival’. Results: We observed several sialic-acid bearing glycans that correlated with overall survival and progression free survival. A complex tetra-antennary, highly sialylated glycan, known as A4G4S4, correlated with reduced overall survival probability (p = 0.0007, hazard ratio = 1.86). High levels of a sialylated tri-antennary glycan, called A3G3S3 demonstrated significantly reduced progression-free survival (p = 0.002). Conclusions: We believe that sialylated glycans could be excellent predictive markers of response to therapy and warrant further evaluation in clinical trials. Tri and tetra-antennary sialyated glycoproteins were associated with poorer survival in our patient cohort, suggesting that glycans could be key drivers of pathobiology.
Phosphorylated signal transducer and activator of transcription–3 (p-STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC): Updated analysis.
Authors: Yokom Daniel , Marginean E. Celia , Jonker Derek J. , Gown Allen M. , Sud Shelly , Asmis Timothy R. , Daneshmand Manijeh , Marginean Horia , Goodwin Rachel Anne 
Published: September 2018

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.
Molecular characterization of TP53 mutations and copy number change in colorectal cancers.
Authors: Nusrat Maliha , Manyam Ganiraju C. , Loree Jonathan M. , Lam Michael , Overman Michael J. , Maru Dipen M. , Routbort Mark , Morris Jeffrey , Kopetz Scott 
Published: September 2018

e15143 Background: TP53 mutations (mut) are prevalent in colorectal cancer (CRC) patients (pts) and can result in oncogenic gain of function effect as well as loss of tumor suppressor function depending on the mut. Methods: The Cancer Genome Atlas (TCGA) data of 220 CRC pts with tumors sequenced and gene copy numbers (CN) annotated was obtained. Pts with CMS subtype data also available were included (n = 167). Chi square test was used to compare frequency of TP53 mut and CN change among CMS subtypes. TP53 mRNA and protein levels were compared by TP53 mut and CN change using independent sample t test. Results: 86 (51.5%) pts were TP53 mutant, with 35.3% missense and 16.2% loss of function (LOF) mut. LOF mut included 14 non-sense and 13 frameshift mut, and occurred mostly in codons 213 and 306. Missense mut mostly affected codons 175, 248 and 273 in 10, 9 and 8 pts respectively. TP53 mut were most frequent in CMS2 and CMS4 subtypes (62.7 and 62.5% respectively). TP53 mut in CMS2 were mostly missense and CMS 4 pts mostly had LOF mut. TP53 CN loss was seen in 74.7% CMS 2, 68.8% CMS 4, 43.5% CMS 3 and 6.9% CMS1 pts. 84.9% pts with TP53 mut had CN loss vs 28.4% of wild type pts (p < 0.001). Frequency of TP53 CN loss did not vary significantly by type of TP53 mut. Pts with TP53 missense mut had higher p53 mRNA and protein levels than those with LOF mut. Pts with TP53 CN loss had lower mRNA levels but no change in protein levels than those with normal CN. Conclusions: The higher TP53 mRNA and protein levels with missense mut suggest possible gain of function. Research on interactions of TP53 change with wnt, myc, and TGF beta pathway genes may reveal synthetic lethal treatment combinations. [Table: see text]
Prognostic impact of tumour laterality in early-stage colon cancer: A population-based study.
Authors: Karim Safiya , Brennan Kelly , Nanji Sulaiman , Berry Scott R. , Booth Christopher M. 
Published: September 2018

e15148 Background: Recent data has suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumours. Here we explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer. Methods: Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer in 2002-2008. The study population included a 25% random sample of all patients with resected stage 0-III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure or transverse colon. Left-sided colon cancer was defined as any tumor arising from the splenic flexure, descending colon, sigmoid colon or rectosigmoid colon. Log binomial regression was used to identify factors associated with laterality. Cox models were used to explore the association between laterality and overall (OS) and cancer-specific (CSS) survival. Results: Among the study cohort (n = 6391) median age was 72 and 52% (3307/6391) had right-sided disease. Stage distribution was 2% (98/6391) stage 0, 17% (1091/6391) stage I, 38% (2446/6391) stage II, and 43% (2756/6391) stage III. Patients with right-sided colon cancer were more likely to be older (p < 0.001), female (p < 0.001) and have greater co-morbidity (p = 0.001). Right-sided cancer was more likely to be T4 (19% vs 16%, p = 0.001) and poorly differentiated (21% vs 10%, p < 0.001) but less likely to be node positive (42% vs 45%, p = 0.029) compared to left-sided disease. In adjusted analyses there was no difference in long-term survival for right-sided compared to left-sided colon cancer: OS HR 1.00 (95%CI, 0.92-1.08); CSS HR 1.00 (0.91-1.10). These results were consistent when the survival analyses were restricted to stage III disease: OS HR 1.03 (95%CI 0.93-1.14); CSS HR 1.10 (0.97-1.24). Conclusions: In this population-based cohort of early-stage resected colon cancer disease laterality was not associated with long-term survival.
Initial safety results from a randomized, phase II study of high-risk colorectal cancer patients (stage IIIC) treated with either regorafenib or standard of care (no treatment) after adjuvant FOLFOX.
Authors: Cartwright Thomas H. , Nguyen Thu-Cuc , Cohn Allen Lee , Richards Donald A. 
Published: September 2018

e15152 Background: Standard adjuvant therapy for colorectal cancer (CRC) is fluoropyrimidine or FOLFOX. The stage IIIC relapse rate is high with a median 5 year survival of only 28%. The multi-kinase inhibitor regorafenib has shown significantly improved overall survival (OS) versus placebo in 3rd-line+ metastatic CRC patients (pts) in 2 phase III trials. We explore whether adding regorafenib to standard adjuvant therapy is able to reduce the high relapse rates in stage IIIC CRC pts. Methods: This study compares efficacy and safety of adjuvant FOLFOX +/- 6 cycles of regorafenib in IIIC CRC pts. Study endpoints include: finding the starting dose of regorafenib that allows ≥75% pts to complete therapy after adjuvant FOLFOX. The first 50 pts are being randomly assigned to either 120 or 160 mg of regorafenib daily for 3 weeks followed by 1 week of rest for a total of 6 cycles. We report the initial safety results on the first 24 pts treated. 6 pts discontinued treatment; 2 received 120 mg and 4 received 160 mg Results: Of the pts completing 6 cycles of regorafenib 120 mg vs 160 mg, the most common grade 3 toxicities were hypertension (0 vs. 30%), rash (10 vs.30%), and lipase elevation (0 vs 10%). No grade 4 or 5 toxicities were observed. Conclusions: The interim analysis reveals no increased toxicities from the addition of regorafenib at either 120 mg or the approved dose (160 mg), to adjuvant FOLFOX. Toxicities observed were mostly grade 1 or 2 and medically manageable. No safety signals have been identified. This study continues to enroll pts. Clinical trial information: NCT02425683.
Early postoperative PET-CT in patients with pathological stage III colon cancer may change their outcome: Results from a large single-institution study.
Authors: Moore Assaf , Ben-Aharon Irit , Purim Ofer , Perl Gali , Ulitsky Olga , Amit Limor , Kundel Yulia , Lewin Ron , Wasserberg Nir , Kashtan Hanoch , Brenner Baruch 
Published: September 2018

e15163 Background: Staging of patients (pts) with pathological stage III colon cancer (CC) is currently suboptimal; many pts still recur despite an unremarkable preoperative staging. We previously reported that early postoperative PET-CT can alter the stage and management of up to 15% of pts with high risk stage III CC and later reported also encouraging preliminary results in a larger cohort of consecutive pts with stage III CC, in which staging and management were altered in 14.5%. The aim of the current study was to expand the previous one to a larger cohort and to evaluate the actual impact of early postoperative PET-CT on pts outcome. Methods: A Retrospective study of all consecutive pts with stage III CC who were treated at our institution and underwent early postoperative PET-CT between 2007-2016. Demographic and clinicopathological data were retrieved. Statistical analyses were done using standard methods. Results: 348 pts, 166 (47.7%) males, with a median age of 66 years (range, 29-92), were included. Pathological stage was IIIA, IIIB and IIIC in 21(6%), 254 (73%) and 73 (21%) pts, respectively. The median number of lymph nodes examined and of positive ones were 14 (range, 3-54) and 2 (range, 0-32), respectively. High FDG-uptake was noted in 95 (27.3%) pts, including 23 (6.6%) with clear postoperative changes and 18 (5.2%) with a false positive uptake, of whom 6 underwent invasive diagnostic procedures. PET-CT results modified the management of 52 pts (14.9%) who were found to have true positive findings: 44 (12.6%) with overt metastatic disease and 8 (2.3%) with a second primary tumor. At a median follow-up of 45.6 months, the estimated 5y disease-free survival for true stage III pts was 81.9% and the 6y overall survival of the entire cohort was 76.4%. Interestingly, of the 44 pts found to be metastatic, 12 (27.3%) underwent curative treatments and 8 (66.7%) of those remain free of disease, with a median follow-up of 64.7 months. Conclusions: In this large cohort, early postoperative PET-CT changed the staging and management of 14.9% of pts with resected stage III CC, with encouraging outcome results. We are conducting a prospective trial to further evaluate this strategy.
Utilization of KRAS mutation status testing in stage IV colorectal cancer (CRC) patients in the United States: National Cancer Data Base (NCDB) analysis.
Authors: Orucevic Amila , Bennett Natalie , Gray Keith D , Bell John Lawrence , Robert Heidel 
Published: September 2018

e15172 Background: KRAS mutation status is considered a predictive biomarker of personalized treatment in advanced stage CRC. Its testing is recommended by the National Comprehensive Cancer Network guidelines for stage IV CRC, since it determines the benefit of addition of anti-epidermal growth factor receptor therapy in wild-type KRAS CRC. Data on utilization of the test in the clinical practice across the US are lacking. Methods: Utilization of KRAS testing across the US is presented in a retrospective observational study of NCDB patients (pts) from 2010-2014. Demographics of stage IV CRC pts with recorded KRAS results were analyzed using frequency statistics and logistic regression analysis. Results: 479399 pts had CRC, 93514 (19.5%) were stage IV. 57208/93514 pts with known KRAS testing status entered our study. Mean age was 63.3 years; 51.2% were males. Only 33% (18867/57208) of stage IV CRC pts underwent KRAS testing. Testing was significantly ( p<.001) influenced by pts age and socioeconomic status but not by race or facility type in which pts were treated (Table 1 - see adjusted odds ratio [AOR] and 95% CI). Conclusions: KRAS testing of stage IV CRC pts is underutilized in the US. Impact of its underutilization on outcomes of these pts requires further study. [Table: see text]
An observational study of patients with HER2-positive metastatic gastric cancer treated with trastuzumab: Single center experience.
Authors: Basal Fatma Bugdaycı , Demirci Umut , Aslan Ferit , Yazici Ozan , Oksuzoglu Berna 
Published: September 2018

e15500 Background: In this study, during a 54-month follow-up period, we presented clinicopathological features and survival results of patients treated with trastuzumab. Methods: We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in 21 patients with HER2-positive gastric cancer between January 2012 and July 2016. Results: Eighteen (86%) patients were male with a median age of 61 (34-80) years. One of the patients was stage 2, 2 were stage 3 and 18 were stage 4, at the time of diagnosis. From 21 tumours, 11 (52%) were located in the cardia, 5 (23%) in the antrum and 5 (23%) in the corpus. In the histopathological examination, 18 (86%) cases were adenocarcinoma and 3 (14%) were signet-ring cell. Seven of the patients with metastatic disease were operated (total/subtotal gastrectomi). The most common metastatic sites were liver (%86), lung(%33), distant lymph node(%23), and periton(%14). Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a secondline, and third-line treatment in 18, 2, and 1 patients, respectively. When tumour response was assessed after three cycles of chemotherapy, one complete response (5%),4 partial response (19%),12 stabil disease (57%) were observed, and 4 (19%) patients had progressive disease. Clinical benefit rate was 81%. The maintenance treatment of trastuzumab was applied to 10 patients (47%). At a median follow-up of 17.8 (5-38) months, median progression-free survival was 12.8 months (3-31) and overall survival 18.6 months (3-91). Conclusions: Proximal gastric carcinomas with intestinal phenotype are found to have a higher expression of HER2-gene (range 8-34%) than distal diffuse gastric carcinomas (range 1-7%). The present results are similar to those of the ToGA study in terms of overall survival and response rate.
Nutritional status and quality of life in patients with gastric cancer in China.
Authors: Li Hongli , Ge Shaohua , Ba Yi 
Published: September 2018

e15508 Background: The incidence of gastric cancer is much higher in China than in any other country. Although the overall survival rate of patients with gastric cancer has increased due to the advancements in multimodality management. However, significant morbidity, including loss of appetite, dysphagia, nausea, and vomiting is still associated with gastric cancer patients. These symptoms have a profound impact on nutritional status and quality of life in these patients. The primary objective of the present study was to assess the nutritional status and quality of life in gastric cancer patients. Methods: A preliminary assessment of patients’ nutritional status, quality of life, and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. The nutritional status of the patients fell into three groups by a score of PG-SGA-A, -B, and C. Results: A preliminary assessment of patients’ nutritional status, quality of life, and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. The nutritional status of the patients fell into three groups by a score of PG-SGA-A, -B, and C. Conclusions: These results suggest that the nutritional status of the patients with stomach cancer may impact on their QoL. It is necessary to develop nutritional intervention to improve QoL in gastric cancer patients.