Accumulating evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth. Recently, there have been efforts to explain drug resistance of cancer cells based on the concept of CSCs having an intrinsic detoxifying mechanism. In the present study, to investigate the role of CSCs in acquiring chemoresistance in pancreatic cancer, gemcitabine‐resistant cells were established by exposure to serially escalated doses of gemcitabine in HPAC and CFPAC‐1 cells. Gemcitabine‐resistant cells were more tumorigenic in vitro and in vivo, and had greater sphere‐forming activity than parental cells. After high‐dose gemcitabine treatment to eliminate most of the cells, CD44⁺ cells proliferated and reconstituted the population of resistant cells. CD44⁺CD24⁺ESA⁺ cells remained as a small subset in the resistant cell population. Among ATP‐binding cassette (ABC) transporters, which are known as the mechanism of drug resistance in CSCs, ABCB1 (MDR1) was significantly augmented during the acquisition of drug resistance. ABC transporter inhibitor verapamil resensitized the resistant cells to gemcitabine in a dose‐dependent manner and RNA interference of CD44 inhibited the clonogenic activity of resistant cells. In human pancreatic cancer samples, CD44 expression was correlated with histologic grade and the patients with CD44‐positive tumors showed poor prognosis. These data indicate that cancer stem‐like cells were expanded during the acquisition of gemcitabine resistance and in therapeutic application, targeted therapy against the CD44 or ABC transporter inhibitors could be applied to overcome drug resistance in the treatment of pancreatic cancer. © 2009 UICC

Microrobots that can be precisely guided to target lesions have been studied for in vivo medical applications. However, existing microrobots have challenges in vivo such as biocompatibility, biodegradability, actuation module, and intra- and postoperative imaging. This study reports microrobots visualized with real-time x-ray and magnetic resonance imaging (MRI) that can be magnetically guided to tumor feeding vessels for transcatheter liver chemoembolization in vivo. The microrobots, composed of a hydrogel-enveloped porous structure and magnetic nanoparticles, enable targeted delivery of therapeutic and imaging agents via magnetic guidance from the actuation module under real-time x-ray imaging. In addition, the microrobots can be tracked using MRI as postoperative imaging and then slowly degrade over time. The in vivo validation of microrobot system–mediated chemoembolization was demonstrated in a rat liver with a tumor model. The proposed microrobot provides an advanced medical robotic platform that can overcome the limitations of existing microrobots and current liver chemoembolization.

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. Graphical

Goals The aims of this study were to determine the clinical use of 18-fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET) in the differential diagnosis of patients with suspected pancreatic cancer and in the determination of tumor response after concurrent chemoradiotherapy for pancreatic cancer. Background Despite advances in diagnostic tools for pancreatic cancer, it is difficult to differentiate pancreatic cancer from mass-forming pancreatitis. Even with current imaging modalities, it is also difficult to assess tumor response to therapeutic intervention. Study One hundred two patients with suspected pancreatic cancer were selected for this study. Dynamic computerized tomography (CT) scan and ¹⁸FDG-PET were used sequentially to diagnose pancreatic cancer. After diagnostic confirmation their diagnostic yields were compared. We also evaluated the treatment response in 15 patients who underwent chemoradiation therapy with dynamic CT scan and ¹⁸FDG-PET and compared their results. Results In 93 out of 102 patients, pancreatic cancer was confirmed. ¹⁸FDG-PET showed higher diagnostic accuracy than CT scan (95.1% vs. 76.5%). ¹⁸FDG-PET was also superior to CT in the detection of liver metastasis. ¹⁸FDG-PET detected treatment response in 5 out of 15 cases after chemoradiation therapy, whereas CT could not detect any treatment response. Comparing responder and nonresponder, ¹⁸FDG-PET was able to predict significantly different prognosis (399 vs. 233 d, P<0.05). Conclusions ¹⁸FDG-PET is a very useful tool in diagnosing pancreatic cancer. ¹⁸FDG-PET may be also used as an adjunct for determining the treatment modality of pancreatic cancer and evaluating tumor response to chemoradiation therapy.