scholarly journals Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers

2012 ◽  
Vol 50 (4) ◽  
Author(s):  
Elad Sharon ◽  
Jingli Zhang ◽  
Kevin Hollevoet ◽  
Seth M. Steinberg ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Pancreatic Disease ◽  
Ductal Adenocarcinoma ◽  
Biliary Carcinoma ◽  
Healthy Donors ◽  
Significant Difference ◽  
Individual Participant ◽  
Pair Wise Comparison

AbstractTumor mesothelin overexpression is present in different malignancies, including the majority of patients with pancreatic or biliary cancers. The objective of this study was to evaluate the use of shed serum mesothelin and megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these cancers.A total of 151 individuals, divided into five groups, were retrospectively analyzed: healthy donors (n=15), patients with benign non-pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF concentrations were measured in serum with the Mesomark™ and Human MPF ELISA, respectively.Mesothelin and MPF concentrations did not significantly differ among the five individual participant groups (p=0.34, p=0.33, respectively), nor did any other combination and pair-wise comparison of the participant groups demonstrated a significant difference in biomarker concentrations. In patients with pancreatic cancer, mesothelin or MPF concentrations were not associated with tumor stage (p=0.87, p=0.48, respectively) or differentiation grade (p=0.73, p=0.52, respectively).Serum mesothelin and MPF concentrations, measured with standard available ELISAs, were not specific for benign or pancreatic disease. Both biomarkers were not elevated in patients with pancreatic or biliary cancers, and consequently do not appear to be useful biomarkers for these malignancies.

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

2014 ◽  
Vol 80 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Clancy J. Clark ◽  
Janani S. Arun ◽  
Rondell P. Graham ◽  
Lizhi Zhang ◽  
Michael Farnell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Perioperative Morbidity ◽  
Log Rank Test ◽  
Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

scholarly journals Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival

2020 ◽  
Vol 29 (3) ◽  
pp. 391-398
Author(s):  
Livia Petrusel ◽  
Maria Bilibou ◽  
Vasile Drug ◽  
Daniel Corneliu Leucuta ◽  
Radu Seicean ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Pancreatic Adenocarcinoma ◽  
Neuroendocrine Tumors ◽  
Tumor Stage ◽  
Ductal Adenocarcinoma ◽  
History Of ◽  
Predictive Role ◽  
New Onset

Background and Aims: Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival. Methods: We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival. Results: 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001). Conclusion: Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

scholarly journals The impact of SPARC expression in survival of pancreatic ductal adenocarcinoma patients after curative resection.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 321-321
Author(s):  
Masaaki Murakawa ◽  
Toru Aoyama ◽  
Yohei Miyagi ◽  
Yousuke Atsumi ◽  
Keisuke Kazama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Curative Resection ◽  
Residual Tumor ◽  
Ductal Adenocarcinoma ◽  
Node Metastasis ◽  
Significant Difference ◽  
Sparc Expression

321 Background: The predictive roles of secreted protein acidic and rich in cysteine (SPARC) in resected pancreatic ductal adenocarcinoma (PDAC) patients have not been clarified. We investigated the correlations between the SPARC expression and the postoperative prognosis. Methods: We retrospectively analyzed the clinical data from consecutive patients who underwent curative resection for pancreatic cancer in our institution from 2005 to 2014. Stromal SPARC expression was analyzed by immunohistochemistry on tumor tissue microarrays (TMAs) from the patients. Results: 179 patients were enrolled to this study. The median follow-up period of the present study was 62.1 months. 70 patients had positive SPARC expression (39.1%). There were no significant difference between the positive SPARC expression group and negative group. In survival analysis, there was significant difference in the 5-year overall survival (OS) rates after surgery, which were 8.1% and 19.8% between the SPARC positive and negative groups, respectively (p = 0.0316). Univariate analysis showed SPARC expression, size of tumor, lymph node metastasis, and residual tumor as the possible prognostic factors. Multivariate analysis revealed SPARC expression (hazard ratio (HR) = 1.44 95%CI; 1.017-2.051), lymph node metastasis (HR = 2.019 95%CI; 1.318-3.091), and residual tumor (HR = 1.648 95%CI; 1.132-2.401)as the independent prognostic factor. Conclusions: Stromal SPARC expression in resectable pancreatic cancer patients might be useful as the predictive survival marker. The prognostic value of SPARC expression should be confirmed in another cohort or in a prospective multicenter-study.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges

2017 ◽  
Vol 313 (5) ◽  
pp. G524-G536 ◽  
Author(s):  
Sandrina Maertin ◽  
Jason M. Elperin ◽  
Ethan Lotshaw ◽  
Matthias Sendler ◽  
Steven D. Speakman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Oxidative Phosphorylation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Environmental Stresses ◽  
Ductal Adenocarcinoma ◽  
Cell Adaptation ◽  
Autophagy Inhibition ◽  
Dependent Mechanism

Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells, basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mechanistic target of rapamycin. Basal, but not stress-induced, autophagy is necessary for PaCa cell proliferation, and AA supply is even more critical to maintain PaCa cell growth. To gain insight into the underlying mechanisms, we analyzed the effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa cells display mixed oxidative/glycolytic metabolism, with oxidative phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS suppressed PaCa cell proliferation. The data indicate that the maintenance of OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell growth. We find that the expression of oncogenic activation mutation in GTPase Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy-dependent mechanism. The results suggest that approaches aimed to suppress OXPHOS, particularly through limiting AA supply, could be beneficial in treating PDAC. NEW & NOTEWORTHY Cancer cells in the highly desmoplastic pancreatic ductal adenocarcinoma confront nutrient [i.e., amino acids (AA)] deprivation and hypoxia, but how pancreatic cancer (PaCa) cells adapt to these conditions is poorly understood. This study provides evidence that the maintenance of mitochondrial function, in particular, oxidative phosphorylation (OXPHOS), is a key mechanism that supports PaCa cell growth, both in normal conditions and under the environmental stresses. OXPHOS in PaCa cells critically depends on autophagy and AA supply. Furthermore, the oncogenic activation mutation in GTPase Kras upregulates OXPHOS through an autophagy-dependent mechanism.

41 Cathepsin D Expression in Pancreatic Ductal Adenocarcinoma (PDAC) Cells Increases Proliferation and Reduces Survival of Pancreatic Cancer Patients

2015 ◽  
Vol 148 (4) ◽  
pp. S-13
Author(s):  
Ujjwal M. Mahajan ◽  
Enno Langhoff ◽  
Eithne Costello ◽  
William Greenhalf ◽  
Christopher Halloran ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Cathepsin D ◽  
Ductal Adenocarcinoma

Precursors of pancreatic cancer in background of chronic opisthorchiasis

2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Morphological Data ◽  
Small Samples ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Opisthorchis Felineus ◽  
Disease Free

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.

scholarly journals Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ewelina Barcińska ◽  
Justyna Wierzbicka ◽  
Agata Zauszkiewicz-Pawlak ◽  
Dagmara Jacewicz ◽  
Aleksandra Dabrowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Pancreatic Cancer ◽  
Silver Nanoparticles ◽  
Oxidative Damage ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cytotoxic Effect ◽  
Mrna Level ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, where the 5-year survival rate is less than 4% worldwide. Successful treatment of pancreatic cancer is a challenge for today’s oncology. Several studies showed that increased levels of oxidative stress may cause cancer cells damage and death. Therefore, we hypothesized that oxidative as well as nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18 nm) as a key factor triggering the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1). Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy. Then, the aim of our study was to evaluate the implication of oxidative and nitro-oxidative stress in this cytotoxic effect of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison purposes. We found that the increase was lower in noncancer cells. Reduction of mitochondrial membrane potential and changes in the cell cycle were also observed. Additionally, we determined the increase in RNS level: nitric oxide (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level. Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3), glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA level. Moreover, we showed cells ultrastructural changes, characteristic for oxidative damage. Summarizing, oxidative and nitro-oxidative stress and mitochondrial disruption are implicated in AgNPs-mediated death in human pancreatic ductal adenocarcinoma cells.

scholarly journals Preoperative Score to Stratify Recurrence Risk After Curative Resection of Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Yu Jiang ◽  
SIYI Zou ◽  
Weishen Wang ◽  
Haoda Chen ◽  
Qian Zhan ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Score ◽  
Multidisciplinary Treatment ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Final Model ◽  
Significant Difference ◽  
Risk Patients

Abstract Background: Oncological survival after operation of resectable pancreatic ductal adenocarcinoma (R-PDAC) is variable depending on various factors. Preoperative risk stratification could guide decision-making in multidisciplinary treatment concepts. We develop and validate a prognostic score for disease-free survival (DFS) in R-PDAC to solve this issue.Methods: 421 R-PDAC patients between January 2012 and December 2015 were enrolled. Performance of the final model was evaluated with respect to discrimination, calibration and clinical usefulness. A prognostic score based on the final model was developed, and external validated in 290 patients.Results: On multivariable analysis, age, tumor size, carbohydrate antigen (CA)19-9, CA125, lymphocyte-monocyte ratio, and systemic-immune-inflammation index were independently associated with DFS. Final model had acceptable calibration, discrimination and internal validity. The prognostic score could delineate low- and high-risk groups with median DFS of 19.6 and 10.1 months (P<0.0001). Tumors in high-risk group exhibited more aggressive pathobiological behaviors. Additionally, at 1-year follow-up, the restricted mean survival time was longer with adjuvant chemotherapy than those without in low-risk patients. However, no significant difference was detected in high-risk patients.Discussion: The prognostic score could accurately predict DFS preoperatively in R-PDAC patients and provide reference for risk-adapted strategies formulation for R-PDAC management in the future.

scholarly journals PancREatic Cancer and Individualised Supervised Exercise (PRECISE): a feasibility trial protocol for patients with resectable pancreatic ductal adenocarcinoma

2020 ◽  
Vol 2 ◽  
pp. 22
Author(s):  
Dominic O'Connor ◽  
Malcolm Brown ◽  
Roy Bowdery ◽  
Martin Eatock ◽  
Claire Hulme ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Exercise Intervention ◽  
Feasibility Trial ◽  
Ductal Adenocarcinoma ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Supervised Exercise ◽  
Health And Social Care

Background: Patients with resectable pancreatic ductal adenocarcinoma (PDAC), undergoing adjuvant chemotherapy can experience an array of complications including fatigue, pain and the loss of physical function. Accumulating evidence from largely early stage breast cancer studies supports exercise as an adjunct therapy to help mitigate treatment complications. However, there is a lack of evidence of its feasibility in pancreatic cancer. The purpose of this study is to explore the initial feasibility of delivering a supervised, individualized, and progressive concurrent exercise intervention to individuals with resectable PDAC who are undergoing adjuvant therapy. Methodology: Ten patients with resectable PDAC undergoing adjuvant chemotherapy will be recruited. Clinical care teams will screen patients against inclusion criteria to determine eligibility. All enrolled participants will complete a 16-week, supervised, tailored, moderate intensity exercise intervention consisting of aerobic and muscle strengthening activities. The primary outcome will be feasibility of delivering a supervised exercise intervention. Secondary outcomes will include measures of physical fitness, fatigue, and quality of life. Outcomes will be measured at baseline (T1), 16 weeks (T2) and 3 months (T3). The feasibility, acceptability and potential utility of the supervised exercise intervention will be explored qualitatively through semi-structured interviews with key stakeholders (e.g. active participants, eligible participants that declined participation and the research staff including exercise physiologists and recruiting clinicians).  The use of health and social care services, medications and personal expenses incurred during the trial will also be used to determine cost-effectiveness of this intervention and a potential further RCT in PDAC. Discussion: The overall aim of this study is to determine the utility of a supervised, tailored, moderate intensity exercise intervention in PDAC patients undergoing adjuvant chemotherapy.  This feasibility study will help inform the design of future randomised controlled trials to determine the efficacy of the exercise intervention in PDAC.

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