scholarly journals Efficacy of primary tumour volume as a predictor of survival compared with size alone in pancreatic ductal adenocarcinoma

2015 ◽  
Vol 10 (2) ◽  
pp. 744-748 ◽  
Author(s):  
JUSTIN S. GUNDARA ◽  
ANTHONY J. GILL ◽  
JASWINDER S. SAMRA
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Primary Tumour ◽  
Tumour Volume ◽  
Ductal Adenocarcinoma

scholarly journals Genexol inhibits primary tumour growth and metastases in gemcitabine-resistant pancreatic ductal adenocarcinoma

HPB ◽  
2011 ◽  
Vol 13 (3) ◽  
pp. 153-157 ◽  
Author(s):  
Jill E. Shea ◽  
Kweon-Ho Nam ◽  
Natalya Rapoport ◽  
Courtney L. Scaife
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumour Growth ◽  
Primary Tumour ◽  
Ductal Adenocarcinoma ◽  
Primary Tumour Growth

scholarly journals Pancreatic Cancer Intrinsic PI3Kα Activity accelerates Metastasis and rewires Macrophage Component

2020 ◽  
Author(s):  
B. Thibault ◽  
F. Ramos Delgado ◽  
E. Pons-Tostivint ◽  
N. Therville ◽  
C. Cintas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Tumour Cell ◽  
Primary Tumour ◽  
Pi3k Pathway ◽  
Ductal Adenocarcinoma ◽  
Preclinical Models ◽  
Micrometastatic Disease

AbstractPancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micrometastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas.We researched a gene signature that could discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events.Amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature predict PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by inhibiting tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the lipid second messenger PIP3 produced, with selective reduction of C36:2 PI-3,4,5-P3. PI3Kα inactivation prevented the accumulation of protumoural CD206-positive macrophages in the tumour-adjacent tissue.Tumour-cell intrinsic PI3Kα therefore promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution.The paper explainedPROBLEM Pancreatic cancer is one of the most lethal solid cancers characterised by rapid progression after primary tumour detection by imaging. Key signalling events that specifically drives this rapid evolution into macro-metastatic disease are so far poorly understood.RESULT With two unbiased approaches to patient data analysis, higher PI3K pathway and more specifically higher PI3Kα activation signature can now be identified in the most aggressive pancreatic cancer primary tumours, that lead to earlier patient death. Our in vitro data showed that PI3Kα is a major positive regulator of tumour cell escape from the primary tumour: tumour-intrinsic PI3Kα activity enables actin cytoskeleton remodelling to escape the pancreatic tumour. We chose to use two preclinical models of pancreatic cancer to validate that PI3Kα is a target for delaying evolution of PDAC. The first one mimicked pancreatic patient micrometastatic disease that is undetected by echography and consisted in treating mice presenting echography detected primary tumours combined with increased circulating DNA as a blood biomarker of the most aggressive tumours. The second model consisted in studying the tumour cell implantation and their early proliferation in metastatic organ after injection in blood. We treated both preclinical models with a clinically relevant PI3K α-selective inhibitor (BYL-719/Alpelisib), that is currently being tested in pancreatic cancer patients (without any patient selection). We found that PI3Kα activity drives evolution of micrometastatic disease towards macro-metastatic stage in both models: inhibition of PI3Kα delayed primary tumour and micro-metastasis evolution. Finally, PI3Kα activity increases protumoural characteristics in peritumoural immune cells via tumour cell-intrinsic cytokine production that could facilitate metastatic evolution.IMPACT Circulating tumour DNA represents a strong independent biomarker linked to relapse and poor survival in solid cancer patients. A clinical study in resected PDAC patients with micrometastatic disease characterised by high circulating tumoural DNA levels is needed to assess if PI3Kα-selective inhibitors significantly delay metastatic progression and death.Graphical AbstractPancreatic ductal adenocarcinoma requires tumour-intrinsic PI3Kα activity to accelerate inflammatory metastatic disease.Biorender illustration.

scholarly journals Mast Cells Density Positive to Tryptase Correlates with Angiogenesis in Pancreatic Ductal Adenocarcinoma Patients Having Undergone Surgery

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Michele Ammendola ◽  
Rosario Sacco ◽  
Giuseppe Sammarco ◽  
Giuseppe Donato ◽  
Valeria Zuccalà ◽  
...  
Keyword(s):  
Mast Cells ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Primary Tumour ◽  
Antiangiogenic Therapy ◽  
Cancer Staging ◽  
Tumour Tissue ◽  
Ductal Adenocarcinoma ◽  
Tissue Samples

Background. Literature data suggest that cells such as mast cells (MCs), are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potentin vivoandin vitroproangiogenic factor. Nevertheless few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed MCs and angiogenesis in primary tumour tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC).Method. A series of 31 PDAC patients with stageT2-3N0-1M0(by AJCC for Pancreas Cancer Staging 7th Edition) was selected and then underwent surgery. Tumour tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCs positive to tryptase (MCDPT), area occupied by MCs positive to tryptase (MCAPT), microvascular density (MVD), and endothelial area (EA). The above parameters were related to each other and to the main clinicopathological features.Results. A significant correlation between MCDPT, MCAPT, MVD, and EA group was found by Pearson’st-test analysis (rranged from 0.69 to 0.81;Pvalue ranged from 0.001 to 0.003). No other significant correlation was found.Conclusion. Our pilot data suggest that MCs positive to tryptase may play a role in PDAC angiogenesis and they could be further evaluated as a novel tumour biomarker and as a target of antiangiogenic therapy.

scholarly journals Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4834
Author(s):  
Hannah Pook ◽  
Siim Pauklin
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Targets ◽  
Primary Tumour ◽  
Standard Of Care ◽  
Tumour Microenvironment ◽  
Late Presentation ◽  
Ductal Adenocarcinoma ◽  
Survival Times ◽  
Therapeutic Implications ◽  
Cancer Cell Death

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that is strongly associated with poor prognosis and short median survival times. In stark contrast to the progress seen in other cancer types in recent decades, discoveries of new treatments in PDAC have been few and far between and there has been little improvement in overall survival (OS). The difficulty in treating this disease is multifactorial, contributed to by late presentation, difficult access to primary tumour sites, an ‘immunologically cold’ phenotype, and a strong tendency of recurrence likely driven by cancer stem cell (CSC) populations. Furthermore, apparently contrasting roles of tumour components (such as fibrotic stroma) and intracellular pathways (such as autophagy and TGFβ) have made it difficult to distinguish beneficial from detrimental drug targets. Despite this, progress has been made in the field, including the determination of mFOLFIRINOX as the standard-of-care adjuvant therapy and the discovery of KRASG12C mutant inhibitors. Moreover, new research, as outlined in this review, has highlighted promising new approaches including the targeting of the tumour microenvironment, enhancement of immunotherapies, epigenetic modulation, and destruction of CSCs.

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma

2000 ◽  
Vol 15 (11) ◽  
pp. 1333-1338 ◽  
Author(s):  
Koji Uno ◽  
Takeshi Azuma ◽  
Masatsugu Nakajima ◽  
Kenjiro Yasuda ◽  
Takanobu Hayakumo ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Significance ◽  
Pancreatic Juice ◽  
Ductal Adenocarcinoma ◽  
Cathepsin E
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