The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of ...different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20–30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers.
Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally ...advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of “biological resectability”. In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer. Methods: A PubMed database search of articles published up to December 2021 has been carried out. Results: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management. Conclusion: The potential of CA 19.9 must be fully explored in order to standardize its role in the “biological staging” of patients with resectable pancreatic cancer.
Pancreatic Ductal Adeno Carcinoma (PDAC) is one of the most lethal malignancies worldwide, and the development of sensitive and specific technologies for its early diagnosis is vital to reduce ...morbidity and mortality rates. In this proof-of-concept study, we demonstrate the diagnostic ability of magnetic levitation (MagLev) to detect PDAC by using levitation of graphene oxide (GO) nanoparticles (NPs) decorated by a biomolecular corona of human plasma proteins collected from PDAC and non-oncological patients (NOP). Levitation profiles of corona-coated GO NPs injected in a MagLev device filled with a paramagnetic solution of dysprosium(III) nitrate hydrate in water enables to distinguish PDAC patients from NOP with 80% specificity, 100% sensitivity, and global classification accuracy of 90%. Our findings indicate that Maglev could be a robust and instrumental tool for the early detection of PDAC and other cancers.
Although the mortality at 90 days has declined, pancreaticoduodenectomy (PD) is an extremely complex surgical procedure, with a non-negligible rate of major postoperative complications ...
Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed the expression and prognostic role of several proteins related to ...angiogenesis. Methods: A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapy was accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to bevacizumab, and follow-up. Results: (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, β1-integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α maintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor for PFS independently on KRAS status. Conclusions: hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.
Hot topics in pancreatic cancer management Caputo, Damiano
World journal of gastrointestinal surgery,
2023-Feb-27, 2023-2-27, 20230227, Letnik:
15, Številka:
2
Journal Article
Odprti dostop
Pancreatic ductal adenocarcinoma (PDAC) is a sneaky and lethal disease burdened by poor prognosis. PDAC is often detected too late to be successfully cured, and it has been estimated that it will be ...a leading cause of cancer-related deaths in the near future. During the last decade, multimodal treatments involving surgery, chemotherapy and radiotherapy have contributed to improving the prognosis of this disease; however, long-term results are still not satisfactory. Postoperative morbidity and mortality rates remain high, and systemic treatments are burdened by toxicity in both neoadjuvant and adjuvant settings. Advancements in technologies, targeted therapies, immunotherapy and PDAC microenvironment modulation strategies may represent useful potential weapons in the future. Nevertheless, in the fight against this dreadful disease, there is an urgent need for new, cheap and user-friendly tools for early detection. In this field, promising results have been found in nanotechnologies and "omics" analyses that search for new biomarkers to be used in primary and secondary prevention. However, there are many issues that need to be solved before considering these tools in daily clinical practice. This editorial reported the state of the art of pancreatic cancer management.
Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the ...gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC.
A PubMed database search of articles published up to September 2022 was carried out.
Many studies showed that FOLFIRINOX or Gemcitabine-nab-paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro-metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process.
The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery.
Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence ...of bacteria species isolated from intraoperative biliary cultures, and related complications after PD. Methods: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF). Results: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli, Klebsiella pneumoniæ and Enterococcus fæcalis (p < 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli, Klebsiella pneumoniæ, Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF (p < 0.001). Biliary culture positive for Escherichia coli, Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE (p < 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30–6.70); p < 0.01). Conclusions: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.
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