Diagnostic strategies for early pancreatic cancer

Hanada, Keiji; Okazaki, Akihito; Hirano, Naomichi; Izumi, Yuichi; Teraoka, Yuji; Ikemoto, Juri; Kanemitsu, Kozue; Hino, Fumiaki; Fukuda, Toshikatsu; Yonehara, Shuji

doi:10.1007/s00535-014-1026-z

Cited by 106 publications

(97 citation statements)

References 56 publications

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“…Although earlier cases in our cohort did not have a cytological diagnosis before surgery, pancreatic juice cytology appeared to be useful for confirming the neoplastic nature of duct stricture. Multiple cytology examinations of pancreatic juice obtained by nasopancreatic drainage also increase diagnostic accuracy . Even if the diagnosis of malignancy is not confirmed, close follow‐up with repeat imaging and/or cytology examinations will be in order for those patients.…”

Section: Discussionmentioning

confidence: 99%

High‐grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer

et al. 2018

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Section: Discussionmentioning

confidence: 99%

High‐grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer

et al. 2018

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“…Pancreatic ductal adenocarcinoma (PDAC), which constitutes over 90% of pancreatic cancers in humans, is a devastating and virtually unexceptionally lethal malignancy [2]. Due to a lack of symptoms in early stages of the disease, PDAC is typically not diagnosed until the disease has progressed to a more advanced state [3, 4]. As a result, despite advances in the field of surgery, chemotherapy, and radiation therapy, the prognosis of PDAC remains extremely poor with a five-year survival rate of less than 5% [5, 6], which is the lowest among common malignancies.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin S-cleavable, multi-block HPMA copolymers for improved SPECT/CT imaging of pancreatic cancer

et al. 2016

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This work continues our efforts to improve the diagnostic and radiotherapeutic effectiveness of nanomedicine platforms by developing approaches to reduce the non-target accumulation of these agents. Herein, we developed multi-block HPMA copolymers with backbones that are susceptible to cleavage by cathepsin S, a protease that is abundantly expressed in tissues of the mononuclear phagocyte system (MPS). Specifically, a bis-thiol terminated HPMA telechelic copolymer containing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was synthesized by reversible addition−fragmentation chain transfer (RAFT) polymerization. Three maleimide modified linkers with different sequences, including cathepsin S degradable oligopeptide, scramble oligopeptide and oligo ethylene glycol, were subsequently synthesized and used for the extension of the HPMA copolymers by thiol–maleimide click chemistry. All multi-block HPMA copolymers could be labeled by 177Lu with high labeling efficiency and exhibited high serum stability. In vitro cleavage studies demonstrated highly selective and efficient cathepsin S mediated cleavage of the cathepsin S-susceptible multi-block HPMA copolymer. A modified multi-block HPMA copolymer series capable of Förster Resonance Energy Transfer (FRET) was utilized to investigate the rate of cleavage of the multi-block HPMA copolymers in monocyte-derived macrophages. Confocal imaging and flow cytometry studies revealed substantially higher rates of cleavage for the multi-block HPMA copolymers containing the cathepsin S-susceptible linker. The efficacy of the cathepsin S-cleavable multi-block HPMA copolymer was further examined using an in vivo model of pancreatic ductal adenocarcinoma. Based on the biodistribution and SPECT/CT studies, the copolymer extended with the cathepsin S susceptible linker exhibited significantly faster clearance and lower non-target retention without compromising tumor targeting. Overall, these results indicate that exploitation of the cathepsin S activity in MPS tissues can be utilized to substantially lower non-target accumulation, suggesting this is a promising approach for the development of diagnostic and radiotherapeutic nanomedicine platforms.

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“…According to the American Cancer Society, about 53,000 people will be diagnosed with pancreatic cancer in 2016 in the United States alone. It is also estimated that 41,750 deaths will occur due to pancreatic cancer in the US each year [2]. On average, the management of one pancreatic cancer patient in the U.S. will cost a total of $65,000 [3].…”

Section: Introductionmentioning

confidence: 99%

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression

et al. 2016

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Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (∼150-1000 nm) and exosomes (∼40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a fingerprint of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

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Diagnostic strategies for early pancreatic cancer

Cited by 106 publications

References 56 publications

High‐grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer

High‐grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer

Cathepsin S-cleavable, multi-block HPMA copolymers for improved SPECT/CT imaging of pancreatic cancer

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression

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