scholarly journals Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

2020 ◽  
Vol 21 (13) ◽  
pp. 4767 ◽  
Author(s):  
Camille Huart ◽  
Jia-Wei Chen ◽  
Benjamin Le Calvé ◽  
Carine Michiels ◽  
Anne-Catherine Wéra
Keyword(s):  
Pancreatic Cancer ◽  
Charged Particles ◽  
Tumour Microenvironment ◽  
Resistance Mechanisms ◽  
Biological Properties ◽  
Cancer Type ◽  
Carbon Ions ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Therapy ◽  
The Impact

Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.

scholarly journals Stromal protein βig-h3 reprogrammes tumour microenvironment in pancreatic cancer

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 693-707 ◽  
Author(s):  
Delphine Goehrig ◽  
Jérémy Nigri ◽  
Rémi Samain ◽  
Zhichong Wu ◽  
Paola Cappello ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumour Growth ◽  
Matrix Protein ◽  
Immune Escape ◽  
Interaction Mechanism ◽  
Tumour Microenvironment ◽  
Extracellular Matrix Protein ◽  
Ductal Adenocarcinoma ◽  
The Impact

ObjectivePancreatic cancer is associated with an abundant stromal reaction leading to immune escape and tumour growth. This massive stroma drives the immune escape in the tumour. We aimed to study the impact of βig-h3 stromal protein in the modulation of the antitumoural immune response in pancreatic cancer.DesignWe performed studies with p48-Cre;KrasG12D, pdx1-Cre;KrasG12D;Ink4a/Arffl/fl, pdx1-Cre;KrasG12D; p53R172H mice and tumour tissues from patients with pancreatic ductal adenocarcinoma (PDA). Some transgenic mice were given injections of anti-βig-h3, anti-CD8, anti-PD1 depleting antibodies. Tumour growth as well as modifications in the activation of local immune cells were analysed by flow cytometry, immunohistochemistry and immunofluorescence. Tissue stiffness was measured by atomic force microscopy.ResultsWe identified βig-h3 stromal-derived protein as a key actor of the immune paracrine interaction mechanism that drives pancreatic cancer. We found that βig-h3 is highly produced by cancer-associated fibroblasts in the stroma of human and mouse. This protein acts directly on tumour-specific CD8+ T cells and F4/80 macrophages. Depleting βig-h3 in vivo reduced tumour growth by enhancing the number of activated CD8+ T cell within the tumour and subsequent apoptotic tumour cells. Furthermore, we found that targeting βig-h3 in established lesions released the tissue tension and functionally reprogrammed F4/80 macrophages in the tumour microenvironment.ConclusionsOur data indicate that targeting stromal extracellular matrix protein βig-h3 improves the antitumoural response and consequently reduces tumour weight. Our findings present βig-h3 as a novel immunological target in pancreatic cancer.

scholarly journals Extracellular vesicles in pancreatic cancer progression and therapies

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Chao-Hui Chang ◽  
Siim Pauklin
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Delayed Diagnosis ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Cancer Hallmarks ◽  
Pancreatic Cancers

AbstractPancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide due to delayed diagnosis and limited treatments. More than 90% of all pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC). Extensive communication between tumour cells and other cell types in the tumour microenvironment have been identified which regulate cancer hallmarks during pancreatic tumorigenesis via secretory factors and extracellular vesicles (EVs). The EV-capsuled factors not only facilitate tumour growth locally, but also enter circulation and reach distant organs to construct a pre-metastatic niche. In this review, we delineate the key factors in pancreatic ductal adenocarcinoma derived EVs that mediate different tumour processes. Also, we highlight the factors that are related to the crosstalk with cancer stem cells/cancer-initiating cells (CSC/CIC), the subpopulation of cancer cells that can efficiently metastasize and resist currently used chemotherapies. Lastly, we discuss the potential of EV-capsuled factors in early diagnosis and antitumour therapeutic strategies.

scholarly journals Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2058
Author(s):  
Raúl Ortíz ◽  
Francisco Quiñonero ◽  
Beatriz García-Pinel ◽  
Marco Fuel ◽  
Cristina Mesas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Treatment ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
New Horizons ◽  
Dna Repair Mechanisms ◽  
Pancreatic Cancers ◽  
Different Types ◽  
Repair Mechanisms

The development of drug resistance is one of the main causes of cancer treatment failure. This phenomenon occurs very frequently in different types of cancer, including colon and pancreatic cancers. However, the underlying molecular mechanisms are not fully understood. In recent years, nanomedicine has improved the delivery and efficacy of drugs, and has decreased their side effects. In addition, it has allowed to design drugs capable of avoiding certain resistance mechanisms of tumors. In this article, we review the main resistance mechanisms in colon and pancreatic cancers, along with the most relevant strategies offered by nanodrugs to overcome this obstacle. These strategies include the inhibition of efflux pumps, the use of specific targets, the development of nanomedicines affecting the environment of cancer-specific tissues, the modulation of DNA repair mechanisms or RNA (miRNA), and specific approaches to damage cancer stem cells, among others. This review aims to illustrate how advanced nanoformulations, including polymeric conjugates, micelles, dendrimers, liposomes, metallic and carbon-based nanoparticles, are allowing to overcome one of the main limitations in the treatment of colon and pancreatic cancers. The future development of nanomedicine opens new horizons for cancer treatment.

Early detection of pancreatic cancers by novel nanobiosensor-based protease biomarkers using hierarchical decision structure.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16273-e16273
Author(s):  
Anup Kasi ◽  
Weijing Sun ◽  
Sumia Ehsan ◽  
Jose Covarrubias ◽  
Kayla Eschliman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Early Stage ◽  
Medical Center ◽  
Cancer Center ◽  
Cancer Society ◽  
Pancreatic Cancers ◽  
Hierarchical Decision ◽  
Decision Structure ◽  
The Impact

e16273 Background: There is a critical need to develop fast, reliable, and cost-effective methods for the detection of pancreatic cancer (PC) at the earliest stage to maximize the impact of treatment. To-date, early detection of PC is close to impossible due to the location of the pancreas and the absence of characteristic symptoms in early cancer stages. Methods: Our team of clinicians and scientists has established a fast and reliable nanobiosensor technology that comprises iron/iron oxide nanoparticles attached to a protease or arginase activatable FRET pair (tetrakis (4- carboxyphenyl) porphyrin (TCPP) /cyanine 5.5). Arginase and seven proteases (MMP1, 3, and 9, cathepsin B, and E, urokinase plasminogen activator, and neutrophil elastase) were identified using the Gene Expression Omnibus (GEO) web tool based on their different expression pattern in pancreatic cancer patients, pancreatitis and healthy control subjects. Protease/arginase activities were measured in serum after 1h of incubation. Based on this data, a novel engineering approach to improved early stage detection of pancreatic cancer is reported here. This study was funded by American Cancer Society Institutional Research Grant (IRG‐16‐194‐07), awarded to the University of Kansas Medical Center. Results: In our study, 159 patients were enrolled at KU Cancer Center from 2000-2019, 47 with metastatic PC, 36 with localized PC, 26 pancreatitis and 50 healthy controls using KUCC Biospecimen Repository. The problem of early stage detection of pancreatic cancer can be modeled as a multi-class classification problem. Conventional classification approaches provide at most 77% accuracy for the dataset under consideration. A new hierarchical decision structure with specific feature engineering at each step is introduced here to improve the performance of the classifier. The fundamental premise of this information fusion-based framework involves tailoring the statistically most significant features with appropriate weights to execute an efficient binary classification task at each hierarchical step. An overall accuracy of 95% was achieved for the detection of patients with early pancreatic cancer (see table). Conclusions: Because of the dire survival statistics of pancreatic cancer, detection at the earliest possible time by means of a liquid biopsy will offer the greatest benefit. Novel nanobiosensor based protease biomarkers achieved high accuracy in early detection of pancreatic cancers by applying hierarchical decision structure. Our results need validation in a larger cohort. Predicted true class considering the following combination of classification methods: Step1 – kNN*, step2 – kNN*, step3 – RFC* (Accuracy = 94.97%).[Table: see text]

The impact of nutritional status on pancreatic cancer therapy

2022 ◽  
Author(s):  
Gabriele Capurso ◽  
Nicolò Pecorelli ◽  
Alice Burini ◽  
Giulia Orsi ◽  
Diego Palumbo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Therapy ◽  
Nutritional Status ◽  
Pancreatic Cancer Therapy ◽  
The Impact

Vitamin D deficiency in patients with newly diagnosed cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13117-e13117
Author(s):  
Hira Shaikh ◽  
Veli Bakalov ◽  
Shifeng Mao
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Tertiary Care ◽  
Multivariate Logistic Regression Analysis ◽  
Cancer Type ◽  
Care Hospital ◽  
Newly Diagnosed ◽  
The Impact

e13117 Background: Vitamin D deficiency (VDD) is pandemic in modern society. There has been increasing interest in vitamin D and its impact on cancer. A number of studies have been published on a possible link between VDD and cancer. However, because of inconsistent results, controversy remains in various aspects of vitamin D. In this study, we assessed the association of VDD with various cancers. Methods: A retrospective study was conducted in a tertiary care hospital network in western Pennsylvania. Electronic health record database was used to extract the data from patients seen in outpatient office with newly diagnosed cancer who had a measured 25-hydroxy vitamin D level at diagnosis between 02/2016 and 02/2018. VDD was defined as level less than 30 ng/dl. Patient demographics, smoking, and vitamin D status were used for multivariate logistic regression analysis in order to determine odds ratio (OR) of certain cancer type in our cohort. We used SPSS version 23 for statistical analysis. Results: A total of 934 patients (59.2% female) with cancer were included. Most patients, 86.4%, were Caucasian, and 10.8% African American (AA). VDD was found in 433 patients (46.4%) and more prevalent in men (n = 203, 53.3%), and AA (n = 65, 64.4%) in our cohort. The most common cancer type was breast cancer (30.9%), followed by prostate cancer (11.3%), lymphoma (11.1%), and lung cancer (7.8%). After adjusting to demographic characteristics and smoking status, VDD was significantly associated with pancreatic cancer (OR = 2.28, p = 0.02), and reversely associated with breast cancer (OR = 0.56, p = 0.001). VDD was also prevalent in colorectal cancer, but not statistically significant, (OR = 1.71, p = 0.064). Conclusions: Our study demonstrated that VDD is prevalent among cancer patients, especially in men and AA patients. There is a strong association between VDD and the malignancies of digestive system, particularly pancreatic cancer. Further studies are needed to assess the effect of VDD on disease-specific risk and cancer mortality as well as the impact of vitamin D supplement.

scholarly journals Evaluation of 64Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates

2021 ◽  
Vol 14 (10) ◽  
pp. 950
Author(s):  
Hiroki Matsumoto ◽  
Tadashi Watabe ◽  
Chika Igarashi ◽  
Tomoko Tachibana ◽  
Fukiko Hihara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Biological Properties ◽  
Binding Assays ◽  
Clinical Issue ◽  
Small Tumor ◽  
Promising Tool ◽  
Pancreatic Cancers ◽  
Positron Emission ◽  
Egfr Antibody

Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered 64Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Methods: NCAB001 was manufactured under cGMP conditions and labeled with 64Cu. The radiochemical and biological properties of 64Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered 64Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of 64Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell-binding assays, and biodistribution of 64Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by 64Cu-NCAB001 ipPET. The ip administration of 64Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered 64Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. Conclusion: Our data support the initiation of clinical trials of 64Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers.

MDM2 Inhibitors for Pancreatic Cancer Therapy

2010 ◽  
Vol 999 (999) ◽  
pp. 1-9
Author(s):  
A. S. Azmi ◽  
P. A. Philip ◽  
K. Almhanna ◽  
F. W. Beck ◽  
Z. K. Kafri ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Therapy ◽  
Pancreatic Cancer Therapy
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