Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1

Oncology ◽  
2019 ◽  
Vol 97 (3) ◽  
pp. 135-148 ◽  
Author(s):  
Zensho Ito ◽  
Shin Kan ◽  
Tsuuse Bito ◽  
Sankichi Horiuchi ◽  
Takafumi Akasu ◽  
...  
2020 ◽  
Author(s):  
Kathrin Wode ◽  
Johanna Hök Nordberg ◽  
Gunver Sophia Kienle ◽  
Nils Elander ◽  
Britt-Marie Bernhardson ◽  
...  

Abstract Background Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard 18 treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with 19 regard to overall survival and health-related quality of life. Methods The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01mg to 20mg three times per week for nine months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status zero to two; main exclusion criteria are life expectancy less than four weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews. Discussion To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer. Trial registration EU Clinical Trial Register, EudraCT Number 2014-004552-64. Registered 19 January 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004552-64/SE


2020 ◽  
Vol 125 (5) ◽  
pp. S39
Author(s):  
A. Hancharou ◽  
O. Timohina ◽  
A. Prokhorov ◽  
S. Romanovskaya ◽  
N. Antonevich ◽  
...  

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
Matthew R Farren ◽  
Thomas Mace ◽  
Susan Geyer ◽  
Sameh Mikhail ◽  
Christina Wu ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaomeng Zhang ◽  
Ningyi Ma ◽  
Weiqiang Yao ◽  
Shuo Li ◽  
Zhigang Ren

Abstract Background The DNA damage and repair pathway is considered a promising target for developing strategies against cancer. RAD51, also known as RECA, is a recombinase that performs the critical step in homologous recombination. RAD51 has recently received considerable attention due to its function in tumor progression and its decisive role in tumor resistance to chemotherapy. However, its role in pancreatic cancer has seldom been investigated. In this report, we provide evidence that RAD51, regulated by KRAS, promotes pancreatic cancer cell proliferation. Furthermore, RAD51 regulated aerobic glycolysis by targeting hypoxia inducible factor 1α (HIF1α). Methods TCGA (The Cancer Genome Atlas) dataset analysis was used to examine the impact of RAD51 expression on overall survival of pancreatic cancer patients. Lentivirus-mediated transduction was used to silence RAD51 and KRAS expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown effect. Analysis of the glycolysis process in pancreatic cancer cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Results Pancreatic cancer patients with higher levels of RAD51 exhibited worse survival. In pancreatic cancer cells, RAD51 positively regulated cell proliferation, decreased intracellular reactive oxygen species (ROS) production and increased the HIF1α protein level. KRAS/MEK/ERK activation increased RAD51 expression. In addition, RAD51 was a positive regulator of aerobic glycolysis. Conclusion The present study reveals novel roles for RAD51 in pancreatic cancer that are associated with overall survival prediction, possibly through a mechanism involving regulation of aerobic glycolysis. These findings may provide new predictive and treatment targets for pancreatic cancer.


2018 ◽  
Vol 15 (2) ◽  
pp. 397-406 ◽  
Author(s):  
Shuichi Hanada ◽  
Tomoko Tsuruta ◽  
Kouichi Haraguchi ◽  
Masato Okamoto ◽  
Haruo Sugiyama ◽  
...  

2019 ◽  
Vol 18 ◽  
pp. 153473541982883 ◽  
Author(s):  
Wendy Wong ◽  
Bing Zhong Chen ◽  
Allyson Kin Yan Lee ◽  
Adrian Ho Cheung Chan ◽  
Justin Che Yuen Wu ◽  
...  

Background and Aims: Pancreatic cancer has the lowest survival rate of all cancers (4%), and it accounts for 1.9% of new cancer cases in Hong Kong. Combined treatment with Chinese herbal medicine (CHM) and Western medicine has yielded promising results, leading to improved prognosis and overall survival. This retrospective case series aimed to illustrate the improved survival and quality of life outcomes of pancreatic cancer patients administered CHM based on traditional Chinese medicine theory. Methods: To investigate the effectiveness of CHM in prolonging overall survival, 182 patients diagnosed with pancreatic cancer who received CHM treatment were observed from 2005 to 2015. Results: One hundred eighty-two pancreatic cancer patients were treated with CHM; 21 patients died. The mean and median survival of these patients were 29.6 and 15.2 months, respectively; the 1-year survival rate was 76% (range = 4 months to 9 years). These results are better than those reported in patients treated with Western medicine, suggesting the need for further study of CHM. Conclusion: A superior clinical outcome may be obtained with CHM treatment. The case series illustrates the potential benefits and safety issues of CHM in pancreatic cancer patients that could be relevant for developing strategies to increase individualization of pancreatic cancer treatment and improve survival. This study may facilitate interprofessional communication and improved clinical management of pancreatic cancer patients.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 315-315 ◽  
Author(s):  
R. S. McDermott ◽  
P. Calvert ◽  
M. Parker ◽  
G. Webb ◽  
B. Moulton ◽  
...  

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 314-314
Author(s):  
Tobin Joel Crill Strom ◽  
Sarah E. Hoffe ◽  
Shivakumar Vignesh ◽  
Jason Klapman ◽  
Cynthia L. Harris ◽  
...  

314 Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 >90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.


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