bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary study of three tumor markers for hepatocellular carcinoma: AFP, AFP-L3, and Glypican-3
Authors: Li H. , Qu K. Z. , Ner R. M. , Sferruzza A. D. , Bender R. A. 
Published: March 2020

15014 Background: a-Fetoprotein (AFP) is the most widely used biochemical marker for detection of hepatocellular cancer (HCC). AFP is also elevated in acute and chronic liver disease, limiting its utility as an early indicator of HCC. Recently, AFP-L3 and glypican 3 (GPC3) have been reported for early detection of HCC. AFP-L3 is a glycoform of AFP produced by malignant liver cells. Measurement of AFP-L3 as a percentage of total AFP helps distinguish non-malignant hepatic disease from HCC. GPC3 is a heparin sulfate proteoglycan anchored to the plasma membrane. The level of GPC3 in the serum of HCC patients is higher than in the serum of healthy adults or patients with non-malignant hepatopathy. We tested the concordance of AFP, AFP, AFP-L3%, and GPC3and GPC3 to determine if their simultaneous measurement may increase the sensitivity of identifying individuals at risk for HCC. Method: De-identified clinical samples (n = 176) submitted for AFP-L3% measurement were tested. AFP and AFP-L3 levels were measured using the LiBASys automated analyzer (Wako Chemicals USA Inc, Richmond, VA). GPC3 levels were measured with a commercial ELISA kit (BioMosaics, Inc, Burlington, VT). To assess concordance we categorized results according to accepted cut-off values for AFP and AFP-L3, and a clinically established reference range for GPC3. Results: Fourteen of the 176 samples had elevated GPC3 (=180pg/mL), 6 (43%) of which had normal AFP values (<20ng/mL). Forty- seven of the 176 samples had elevated AFP-L3% (L3 =10%), 6 (12.8%) of which had normal AFP levels. Conclusion: These data suggest that GPC3 and AFP-L3% may be used as supplemental markers, and the simultaneous determination of AFP, AFP-L3, and GPC3 may provide a higher sensitivity for identifying individuals with increased risk of HCC. [Table: see text] No significant financial relationships to disclose.
Gemcitabine (G) combined with gefitinib in patients with inoperable or metastatic pancreatic cancer. A phase II trial
Authors: Fountzilas G. , Murray S. , Xiros N. , Karayannopoulou G. , Dafni U. , Linardou H. , Kalogera-Fountzila A. , Bobos M. , Koumarianou A. , Kosmidis P. 
Published: March 2020

15016 Introduction: Pancreatic cancer is one of the most lethal cancers, with a high incidence of overexpression of EGFR and its ligands. Gemcitabine (G) is the treatment of choice in this tumor. Patients and Methods: From June 2004 to May 2006, 54 patients were registered in the study. Median age was 65 years (range 44–80) and median Karnofsky performance status was 80%. G (1000 mg/m2) was administered weekly for 7 cycles. Gefitinib (250 mg) was given orally. EGFR, HER-2 and PTEN were assessed by IHC and FISH. Biopsies containing =70% tumor were evaluated for the presence of somatic mutations in exons 18–21 of EGFR and exon 2 of RAS by bi-directional sequencing. Results: Ten patients (19%) completed treatment, while 36 patients (67%) progressed before the completion of the treatment. Three patients (6%) had a partial response and 11 patients (20%) had stable disease. After a median follow-up of 9 months, median survival time was 7.4 months, while median time to disease progression (TTP) was 3.9 months. The one-year survival rate was 23%. Rash of any grade was reported in 28 patients (52%). Most common severe toxicities were neutropenia (13%) and leucopenia (6%). RAS mutations were identified in 18/34 patients (53%). Two additional patients had an EGFR point mutation in exon 20. EGFR expression was found in 23/30 patients (77%), while EGFR amplification was not observed. HER-2 gain was detected in 4/20 patients and PTEN deletion in 14/20 patients. PTEN expression was noticed in 7/30 patients and was the only marker associated with significantly increased TTP (p=0.008). Conclusions: The results from this small single arm study were similar to those seen with G plus erlotinib with respect to median and one-year survival. These findings, and the selection of patients with better prognosis based on molecular markers, need to be confirmed in a larger study. No significant financial relationships to disclose.
Optimized preclinical models for human pancreatic adenocarcinoma therapy research
Authors: Carbó N. , Pérez-Torras S. , Vidal-Pla A. , Miquel R. , Almendro V. , Fernández-Cruz L. , Maurel J. , Navarro S. , Gascón P. , Mazo A. 
Published: March 2020

15019 Background: Efforts to find new therapies for human pancreatic ductal adenocarcinoma (PDAC) have not resulted in clear improvements on patient survival. Better knowledge of resistance mechanisms and redefiniton of molecular targets is essential to design more efficient therapies. The multifactorial origin of PDAC points to combined strategies as the therapy of choice, though the effective development of such strategies is hampered by the lack of optimal preclinical models. We have generated and validated optimized human PDAC models by direct implantation of fresh tumoral tissue into the pancreas of athymic mice. Methods: Thirteen pancreatic adenocarcinoma specimens from PDAC patients were obtained by surgical resection. From each specimen, several 10 mg-fragments were used to generate the corresponding intrapancreatic xenografted tumours. Eleven human PDAC orthotopic models have been successfully generated and perpetuated by succesive passages (up to 4). Histological and molecular analyses of both primary and xenografted tumors have been performed by tissue- array, western-blot and DNA sequentiation. Results: Initial engraftment rate ranged from 20 to 100% (mean 59%) and it improved with succesive passages (mean 76% at second and 90% at third generation). Ki67 expression and degree of differentiation in primary tumors correlated with xenograft growth kinetics. Furthermore, their spontaneous metastatic behaviour fairly reproduced the original patient dissemination patterns. Xenografted tumors kept the original architecture and expression patterns of common PDAC markers. Efficacy of several agents was tested on different xenografted tumors, validating this model and underlining its utility to define future therapeutic strategies for drug development and clinical trials. Conclusions: The orthotopic models described here are, probably, the closest resemblance to a patient clinical setting since they preserve human pancreatic structures, genotypic features and biological behaviour. From their use, biological relevant data could be drawn for future clinical trials and for testing new agents and new drug combinations since they represent, very likely, the most reliable animal models at present. No significant financial relationships to disclose.
Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer
Authors: Kim J. , Song H. , Do Y. , Lee K. , Kim M. , Ryu H. , Bae S. , Park G. , Baek J. , Lee W. 
Published: March 2020

15026 Background: The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Methods: Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg/m2 plus oxaliplatin (Oxalpla®, Yuhan.Co. Seoul, Korea) 120 mg/m2 on days 1 in a 3-week cycle. Treatment was continued until disease progression, patient refusal, or an unacceptable toxicity up to 9 cycles. Results: Forty-two patients were enrolled in the current study. Of these, 39 were assessable for efficacy and 41 assessable for toxicity. Seventeen partial responses were confirmed, giving an overall response rate of 40.5% (95% CI: 26.0% to 54.1%, intention-to-treat analysis). At a median follow-up of 160.5 days, the median time to progression was 6.1 months, whereas median overall survival was not reached yet. Grade 3/4 neutropenia occurred in 10 patients, plus febrile neutropenia was observed in 3 patients. Most common non-hamatologic toxicity was nausea (grade 1/2 56.9%). There were two treatment-related deaths. Conclusions: Docetaxel and oxaliplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer. No significant financial relationships to disclose.
A phase I/II study of induction oxaliplatin, 5FU chemoradiation in patients with locally advanced, unresectable pancreatic cancer
Authors: Leung R. C. , Ryan T. , Hochster H. , Newman E. , Chandra A. 
Published: March 2020

15027 Background: Newly diagnosed locally advanced and unresectable pancreatic cancer has a 5 yr survival rate of less than 5%. Aggressive local therapy may provide the best means of achieving local control and prolonging survival. We administered concomitant chemoRT with Oxaliplatin and continuous infusional (CIV) 5FU to determine the maximum tolerated dose (MTD) in the phase I portion. Methods: Pts with histologically proven locally advanced pancreatic cancer were enrolled in standard Phase I 3+3 fashion to determine MTD. ChemoRT included 5FU 200mg/m2 CIV and Oxaliplatin wkly X5 wks. Radiation dose was 4500cGy in 25 fractions (180cGy/fx/d) over 5 wks followed by a conedown to the tumor and margin for an additional 540cGy x3 (total dose 5040 cGy in 28 fractions) Oxaliplatin was escalated from 30mg/m2 in 10mg intervals up to 60mg/m2. Following chemoRT, unresectable pts were treated with mFOLFOX6 x 6. Results: 15 pts enrolled in the phase I portion, all completed neoadjuvant therapy. Most hematologic toxicities were gr 1 and 2. There was 1episode of gr 4 lymphopenia. The most common non-hematologic toxicities were gr1–2 fatigue, anorexia, nausea and vomiting. Gr 3 non-hematologic toxicities included 4 episodes hyperglycemia, 1 diarrhea, 1 anorexia, 3 nausea/vomiting and 2 hypokalemia. The highest planned dose level for weekly Oxaliplatin was tolerable and the RPTD is 60mg/m2/wk. Of the 15 pts: 2 progressed, 2 were explored but were unresectable, 2 await exploration and 9 were deemed still unresectable and proceeded to consolidation. 7/9 completed the planned 6 cycles. 1 pt was removed from protocol due to extended delay of treatment due to gr 3 neuropathy. 1 pt died due to progressive disease. 21% of planned cycles were delayed due to gr2 or 3 myelosuppression. 1 pt required dose reduction due to fever in setting of gr4 neutropenia but was able to complete treatment at the reduced dose. Conclusions: Combined modality treatment for locally advanced pancreatic cancer with Oxaliplatin, CIV 5FU and radiation is well tolerated at full doses of Oxaliplatin (60mg/m2/wk) and does not produce substantially more toxicity than standard chemoRT to the pancreatic bed. The phase II portion of the trial is ongoing. [Table: see text]
Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and down-regulates survivin/BIRC5 gene expression
Authors: Glienke W. , Maute L. , Milz E. , Bauer N. , Bergmann L. 
Published: March 2020

15030 The anti-apoptotic gene survivin/BIRC5 plays an important role in cellular proliferation and survival of cancer cells. Regulated by constitutively activated STAT3, Survivin/BIRC5 may be a target for inhibiting cellular proliferation in pancreatic cancer cell lines. The purpose of this study was (a) to determine the effect of curcumin (diferuloylmethane) on survivin/BIRC5 expression and (b) a possible role of STAT3 activation in Survivin/BIRC5 expression in pancreatic cancer cell lines. We have incubated four pancreatic cancer cell lines with different amounts of curcumin. The expression of Survivin/BIRC5 on mRNA and protein level was measured with RT-PCR and western blot analysis. The activation of STAT3 through phosphorylation, contributing to the regulation of survivin was analyzed with western blot analysis. The incubation of the pancreatic cancer cell lines with curcumin resulted in a down-regulation of cellular proliferation in all cell lines tested but with different rates of inhibition. The expression of survivin/BIRC5 on mRNA and protein level was significantly down-regulated after treatment with 30 μM. Curcumin blocked the phosphorylation of STAT3 in a concentration-dependent manner. Treatment of pancreatic cancer cell lines with curcumin resulted in an induction of apoptosis as measured with FacScan analysis. We conclude that curcumin inhibits several key factors in cancer cellular pathways and may have the potential to be investigated in pancreatic cancer. No significant financial relationships to disclose.
First clinical experience with 90Y-radiolabeled humanized anti-MUC1 antibody (hPAM4) in patients with advanced pancreatic cancer: A phase I study
Authors: Gulec S. A. , Cohen S. J. , Zuckier L. S. , Horne H. , Teoh N. , Wegener W. A. , Gold D. V. , Goldenberg D. M. 
Published: March 2020

15034 Background: The humanized antibody, hPAM4, specifically targets an epitope in the mucin glycoprotein MUC1 expressed in most pancreatic cancers, but not normal pancreas or most other normal tissues. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics (PK), dosimetry and preliminary efficacy of 90Y-DOTA-hPAM4 administered as a single dose to patients (pts) with pancreatic adenocarcinoma. Methods: Pts with locally advanced disease and progression on 1 prior therapy (TX) or metastatic disease with 0–1 prior TX’s were eligible if they were ≥ 4 wks beyond prior TX, had adequate hematology/chemistries, with measurable disease, but no lesion >10 cm. Pts initially received 111In-hPAM4 followed by 7 days of serum samples and imaging for PK, biodistribution and organ radiation dose analysis. Pts then received a single infusion of 90Y-hPAM4 with the 90Y dose escalated in cohorts of 3–6 pts (5-mCi/m2 increments) until 2 evaluable pts/cohort encountered DLT. Treatment toxicity was evaluated by NCI CTC v. 3 criteria and tumor response by CT-based RECIST criteria. Results: Fifteen pts (8F/7M; median age 60; 11 metastatic/4 locally advanced;13 with, 2 without prior TX) received 90Y-hPAM4 at a dose level of 15 mCi/m2 (n=4), 20 mCi/m2 (n=7), and 25 mCi/m2 (n=4). Pre-therapy 111In-hPAM imaging showed acceptable biodistribution and organ radiation dosimetry in all pts. Four wks after treatment, 1 pt at 15 mCi/m2 and 2 pts at 20 mCi/m2 had CT responses, with 32–51% shrinkage of their pancreatic mass, while 3 other pts at various dose levels had stable target lesions by CT. All pts showed disease progression at or after wk 8. The only significant drug-related toxicity was hematologic, with >1 DLT (>7 day grade 4 thrombocytopenia and/or neutropenia) encountered at the 25 mCi/m2 level. Conclusions: For 90Y-hPAM administered once as a single agent, hematologic toxicity was dose-limiting, the MTD was established at 20 mCi/m2, and CT demonstrated several transient reductions or stabilization of index lesions. Based on this Phase I experience, combined/sequential treatment with chemotherapy and fractionated radioimmunotherapy is being considered for future trials. No significant financial relationships to disclose.
Barriers to breast cancer risk screening
Authors: Zwaagstra A. , Hoskins K. 
Published: March 2020

1505 Background: The U. S. Preventive Services Task Force has recommended that physicians assess and discuss breast cancer risk with their female patients. With this recommendation comes the need to develop strategies for providing breast cancer risk-screening and a need to identify potential barriers to the successful implementation of a risk-screening strategy. Methods: A personalized breast cancer risk profile was offered to all women presenting for a screening mammogram at a community hospital. The profile included a Gail model estimate and analysis of family cancer history to detect hereditary breast cancer syndromes utilizing a pedigree assessment tool developed by the authors. Women with 5 year Gail estimates ≥ 1.66%, lifetime Gail estimate ≥ 15% or increased score with the pedigree assessment tool were considered at increased breast cancer risk. Women in the increased risk cohort received written notification of their risk status and were advised to undergo formal risk assessment either through a free consultation with an advanced practice nurse with expertise in cancer risk assessment or with their primary physician. We analyzed compliance with this recommendation over the 6 month period of time after subjects received the risk notification letter. Results: For the three month study period, 242 women met criteria for the increased risk cohort. Of these, 201 (83%) failed to follow through with the advanced practice nurse for formal risk assessment. Surveys were mailed to all 201 non-compliant subjects to identify reasons for non-compliance and 80 surveys were returned (40%). Reasons given for failure to follow- through with formal risk assessment included: self-perception of “average” breast cancer risk (75%), recent normal screening mammogram (55%), primary care physician had not referred them (18%), absence of breast symptoms (15%), and time constraints (15%). Only 11 subjects (14%) indicated that they had discussed risk results with their physician. Conclusions: The majority of women in our study who requested breast cancer risk estimates failed to act on that information. These results could have implications for design and implementation of a successful breast cancer risk-screening program, and point to the need for better patient education and involvement of primary care physicians in the risk assessment process. No significant financial relationships to disclose.
A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial
Authors: Yoshino S. , Nishimura T. , Hazama S. , Oka M. , Ozasa H. , Shimizu R. , Furuya T. , Fukuda S. , Satoh T. , Hara T. 
Published: March 2020

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.
Phase II clinical trial of XELOX as first line treatment for patients with unresectable or metastatic gastric cancer
Authors: Xu R. , Han B. , Shi Y. , Xiong J. , Li Y. , Wang F. , Qiu M. , Jiang W. , Lin T. , Zhang L. , He Y. 
Published: March 2020

15062 Background: The survival of advanced gastric cancer remains poor, while no chemotherapy regimen was recognized standard. Oxaliplatin and Capecitabine (Xeloda) have demonstrated promising antitumor efficacy in advanced colorectal cancer. The present study was conducted to further evaluate the efficacy and safety of XELOX (Oxaliplatin and Xeloda) regimen in gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer were enrolled into this study. They all receive the XELOX regimens (Oxaliplatin 130mg/ m2 intravenously in 2 hours on day 1 followed by oral capecitabine 1000mg/ m2 twice daily for 14 days every 3 weeks).We evaluated the response every 2 cycles. Results: The median age of the total enrolled 45 patients was 55 years (range, 22–82 years), including 32 male and 13 female. They received a median of 5 cycles (range, 2–8 cycles) of XELOX. 21 of 45 patients (46.7%) achieved an objective response, 1 patient (2.2%) had completed response. 17 patients (37.8%) experienced stable disease. Median time to tumor progression (TTP) and median overall survival were not available yet due to the further follow-up needed. Most toxicity events were mild to moderate in XELOX regimen, with grade 3/4 neutropenia of 8.9 %, thrombocytopenia of 6.7%, anemia of 11.1%, hand-foot syndrome of 6.7 % and diarrhea of 6.7 %. Grade 3 neuropathy was 4.4%. The patients with advanced gastric cancer had a good tolerance to this chemotherapy. Conclusions: XELOX is a highly effective first-line treatment for unrsectable and metastatic gastric cancer. The response rates in this trial seems to be similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX is tolerable well in the treatment of advanced gastric cancer. No significant financial relationships to disclose.