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Pancreatic cancer - Top 30 Publications

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model.

Metastatic cancer accounts for 90% of deaths in patients with solid tumors. There is an urgent need to better understand the drivers of cancer metastasis and to identify novel therapeutic targets. To investigate molecular events that drive the progression from primary cancer to metastasis, we have developed a bitransgenic mouse model, RIP-Tag; RIP-tva. In this mouse model, the rat insulin promoter (RIP) drives the expression of the SV40 T antigen (Tag) and the receptor for subgroup A avian leukosis virus (tva) in pancreatic β cells. The mice develop pancreatic neuroendocrine tumors with 100% penetrance through well-defined stages that are similar to human tumorigenesis, with stages including hyperplasia, angiogenesis, adenoma, and invasive carcinoma. Because RIP-Tag; RIP-tva mice do not develop metastatic disease, genetic alterations that promote metastasis can be identified easily. Somatic gene transfer into tva-expressing, proliferating pancreatic β premalignant lesions is achieved through intracardiac injection of avian retroviruses harboring the desired genetic alteration. A titer of >1 x 10(8) infectious units per ml is considered appropriate for in vivo infection. In addition, avian retroviruses can infect cell lines derived from tumors in RIP-Tag; RIP-tva mice with high efficiency. The cell lines can also be used to characterize the metastatic factors. Here we demonstrate how to utilize this mouse model and cell lines to assess the functions of candidate genes in tumor metastasis.

Health Reform and Utilization of High-Volume Hospitals for Complex Cancer Operations.

Underinsured patients are less likely to receive complex cancer operations at hospitals with high surgical volumes (high-volume hospitals, or HVHs), which contributes to disparities in care. To date, the impact of insurance coverage expansion on site of complex cancer surgery remains unknown.

Experimental models of pancreatic cancer desmoplasia.

Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer. Here, we review various in vitro and in vivo models that are being used or have the potential to be used to study desmoplasia in pancreatic cancer.Laboratory Investigation advance online publication, 20 November 2017; doi:10.1038/labinvest.2017.127.

Prognostic Utility of Total (68)Ga-DOTATATE-Avid Tumor Volume in Patients with Neuroendocrine Tumors.

Survival times vary among patients with neuroendocrine tumors (NETs)-even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs, because some patients can survive decades without treatment. (68)Gallium-DOTATATE positron emission tomography with computed tomography ((68)Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of (68)Ga-DOTATATE PET/CT analysis of tumor volume in patients with NETs.

Matrine inhibiting pancreatic cells epithelial-mesenchymal transition and invasion through ROS/NF-κB/MMPs pathway.

Matrine has demonstrated an exclusive anti-tumor effect, including inhibiting cancer cells proliferation and inducing cancer cells apoptosis and autophagy. Whether it can inhibit cancer cells invasion is remain obscure.

Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation.

Although gemcitabine is an effective chemotherapeutic for pancreatic cancer, severe side effects often accompany its use. Since we have discovered that locally administered C1B domain peptides effectively control tumor growth without any side effects, the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer was examined. Two- and three-dimensional cell culture studies clarified that a co-treatment with C1B5 peptide and gemcitabine significantly attenuated growth of PAN02 mouse and PANC-1 human pancreatic cancer cells in 2D and 3D cultures. Although treatment with the low dose of gemcitabine alone (76%) or the C1B5 peptide alone (39%) inhibited tumor growth moderately, a co-treatment with C1B5 peptide and a low dose of gemcitabine markedly inhibited the growth of PAN02 autografts in the mouse peritoneal cavity (94% inhibition) without any noticeable adverse effect. The number of peritoneal cavity-infiltrating neutrophils and granzyme B(+) lymphocytes was significantly higher in the co-treatment group than in the control group. A significant increase of granzyme B mRNA expression was also detected in human T cells by the co-treatment. Taken together, the current study suggests that C1B5 peptide offers a remarkably effective combination treatment strategy to reduce side effects associated with gemcitabine, without losing its tumoricidal effect.

Telomere Diagnostics for Pancreatic Neoplasms and Cysts.

This commentary highlights the article by Hata et al that examines markers for assessing neoplastic progression.

Cardiac muscle wasting in individuals with cancer cachexia.

Cachexia is a severe complication of cancer that adversely affects the course of the disease and is associated with high rates of mortality. Patients with cancer manifest symptoms, such as fatigue, shortness of breath, and impaired exercise tolerance, which are clinical signs of chronic heart failure. The aim of this study was to evaluate cardiac muscle wasting in cancer individuals.

CTRC gene polymorphism may increase pancreatic cancer risk - preliminary study.

Pancreatic cancer is often fatal due to delayed diagnosis and treatment difficulties.

Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas.

Despite expression of oncogenic KRAS, premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras(G12D) acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice. p62 accumulation promotes neoplastic progression by controlling the NRF2-mediated induction of MDM2, which acts through p53-dependent and -independent mechanisms to abrogate checkpoints that prevent conversion of differentiated acinar cells to proliferative ductal progenitors. MDM2 targeting may be useful for preventing PDAC development in high-risk individuals.

Polyphosphonate ligands: From synthesis to design of hybrid PEGylated nanoparticles toward phototherapy studies.

The use of phosphonate ligands to modify the nanoparticle (NPs) surface has attracted a strong interest in the last years for the design of highly functional hybrid materials. Here, we applied a methodology to synthesize bisphosphonates having functionalized PEG side chains with a specific length in order to design a novel class of hybrid nanomaterials composed by tetraphosphonate-complex-gold COOH-terminated PEG-coated NPs (Bis-PO-PEG-AuNPs). The synthetic approach consist in three steps: (1) Complexation between new phosphonate ligands (Bis PO) and tetrachloroauric acid (HAuCl4) to form gold clusters; (2) adsorption of COOH-terminated PEG molecules (PEG) onto Bis PO-Au complex; (3) reduction of metal ions in that vicinity, growth of gold particles and colloidal stabilization. The obtained snow-shape-like hybrid nanoparticles, have been characterized by ultra-violet/visible, Raman spectroscopies, and electron microscopy imaging, involving their optical properties and photothermal activity in pancreatic adenocarcinoma cancer cells (PDAC).

Is distal pancreatectomy with en-bloc celiac axis resection effective for patients with locally advanced pancreatic ductal adenocarcinoma? -Multicenter surgical group study.

We retrospectively investigated the operative outcomes of patients who underwent distal pancreatectomy (DP) for invasive pancreatic ductal adenocarcinoma (PDAC) located at the body and tail.

Heparanase expression in blood is sensitive to monitor response to anticancer treatment in pancreatic cancer, a pilot study.

/Objectives: High heparanase level was shown in maliganant tumor; however, whether or not heparanase may serve as a sensitive marker to monitor response to anticancer treatment is still unknown.

Locally advanced pancreatic cancer: An emerging entity.

Pancreatic adenocarcinoma (PDAC) remains a highly fatal disease that is increasing in incidence. PDAC can be classified according to resectability status with 3 nonmetastatic groups defined: resectable, borderline resectable, and locally advanced PDAC (LAPC). Delineating these subtypes is important with the optimal treatment approach dictated by high-quality CT imaging and multidisciplinary team discussion. Patients with LAPC are thought unresectable and are therefore rarely cured. In these patients, chemotherapy remains the mainstay of treatment. Aggressive approaches in this cohort are increasingly employed. Local therapies after induction chemotherapy including standard fractionation radiation, stereotactic body radiotherapy (SBRT), and irreversible electroporation (IRE) are being investigated in an attempt to improve long-term control. In some cases, responses to neoadjuvant therapy may facilitate surgical resection. Biomarkers that can select patients most likely to benefit from these options are urgently needed. This review aims to highlight the emerging treatment of patients with LAPC and to discuss current trials.

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer.

Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA while 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer.

Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential.

Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an "immune evasion" milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-κB. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.

Emodin and rhein decrease levels of hypoxia-inducible factor-1α in human pancreatic cancer cells and attenuate cancer cachexia in athymic mice carrying these cells.

The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of oxygen-sensitive HIF-1α and constitutive HIF-1β. HIF-1α is undetectable in normal cells, but cancer cells frequently express HIF-1α to support their growth, angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg effect in cancer cells increases energy expenditure and thus participates in cancer-induced metabolic disorder, cancer cachexia. In the present study, we investigated whether two components of Rheum palmatum, emodin and rhein, inhibited HIF-1α expression in human pancreatic cancer cells and whether the inhibiting effect, if any, attenuated cancer cachexia. Using Western blotting, we demonstrated that emodin and rhein decreased HIF-1α expression in MiaPaCa2 and four other human pancreatic cancer cell lines. We also examined HIF-1α expression when MiaPaCa2 cells were exposed to PX-478, noscapine, and phenethyl isothiocyanate, as these compounds were known to inhibit HIF-1α expression in different cancer cells. PX-478 and noscapine inhibited HIF-1α expression to a less extent than emodin and rhein, and phenethyl isothiocyanate did not inhibit HIF-1α expression in tested concentrations. We obtained evidence that emodin and rhein decreased HIF-1α by decreasing its biosynthesis but not gene transcription or protein stability. When MiaPaCa2 cells were implanted in athymic mice, emodin and rhein inhibited cancer-cell growth and HIF-1α expression. In these athymic mice, emodin and rhein also attenuated two pathological constituents of cancer cachexia, namely high hepatic gluconeogenesis and skeletal-muscle proteolysis. In conclusion, emodin and rhein decrease pancreatic cancer cell's growth and HIF-1α expression and attenuate cancer cachexia in the athymic mice carrying the cancer cells.

Identifying and analyzing different cancer subtypes using RNA-seq data of blood platelets.

Detection and diagnosis of cancer are especially important for early prevention and effective treatments. Traditional methods of cancer detection are usually time-consuming and expensive. Liquid biopsy, a newly proposed noninvasive detection approach, can promote the accuracy and decrease the cost of detection according to a personalized expression profile. However, few studies have been performed to analyze this type of data, which can promote more effective methods for detection of different cancer subtypes. In this study, we applied some reliable machine learning algorithms to analyze data retrieved from patients who had one of six cancer subtypes (breast cancer, colorectal cancer, glioblastoma, hepatobiliary cancer, lung cancer and pancreatic cancer) as well as healthy persons. Quantitative gene expression profiles were used to encode each sample. Then, they were analyzed by the maximum relevance minimum redundancy method. Two feature lists were obtained in which genes were ranked rigorously. The incremental feature selection method was applied to the mRMR feature list to extract the optimal feature subset, which can be used in the support vector machine algorithm to determine the best performance for the detection of cancer subtypes and healthy controls. The ten-fold cross-validation for the constructed optimal classification model yielded an overall accuracy of 0.751. On the other hand, we extracted the top eighteen features (genes), including TTN, RHOH, RPS20, TRBC2, in another feature list, the MaxRel feature list, and performed a detailed analysis of them. The results indicated that these genes could be important biomarkers for discriminating different cancer subtypes and healthy controls.

Panbinostat decreases cFLIP and enhances killing of cancer cells by immunotoxin LMB-100 by stimulating the extrinsic apoptotic pathway.

LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death. We found that panbinostat and the combination increased levels of mRNAs encoding TNF/TNFR family members, as well as BNIP3L and CASP-9, and markedly decreased mRNA levels for c-FLIP and BID. Western blots confirmed a fall in levels of cFLIP protein and a rise in BNIP3L and caspase-9. The combination also increased levels of cleaved BID (t-BID), cleaved-capsase-3 and -8 and PARP. To assess the importance of the fall in cFLIP levels, we treated cells with the cFLIP inhibitor, Rocaglamide, and found it also enhanced killing of tumor cells by LMB-100. LMB-100, which activates the intrinsic pathway of apoptosis, and panbinostat, which activates the extrinsic pathway, work in a synergistic manner to kill cancer cell lines.

Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer.

The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed late so that surgery is rarely curative. Earlier detection could significantly increase the likelihood of successful treatment and improve survival. The aim of the study was to provide proof of principle that point mutations in key cancer genes can be identified by sequencing circulating free DNA (cfDNA) and that this could be used to detect early PDACs and potentially, premalignant lesions, to help target early effective treatment. Targeted next generation sequencing (tNGS) analysis of mutation hotspots in 50 cancer genes was conducted in 26 patients with PDAC, 14 patients with chronic pancreatitis (CP) and 12 healthy controls with KRAS status validated by digital droplet PCR. A higher median level of total cfDNA was observed in patients with PDAC (585 ng/ml) compared to either patients with CP (300 ng/ml) or healthy controls (175 ng/ml). PDAC tissue showed wide mutational heterogeneity, whereas KRAS was the most commonly mutated gene in cfDNA of patients with PDAC and was significantly associated with a poor disease specific survival (p=0.018). This study demonstrates that tNGS of cfDNA is feasible to characterise the circulating genomic profile in PDAC and that driver mutations in KRAS have prognostic value but cannot currently be used to detect early emergence of disease. Importantly, monitoring total cfDNA levels may have utility in individuals "at risk" and warrants further investigation.

Outcomes of phase I clinical trials for patients with advanced pancreatic cancer: update of the MD Anderson Cancer Center experience.

In 2011, we reported the outcomes of pancreatic cancer (PC) patients enrolled in phase I trials at our institution from 2004 through 2009. At the time, gemcitabine and erlotinib were the only Food and Drug Administration-approved drugs for PC and median overall survival (OS) from consultation in the phase I clinic was 5 months. We sought to determine the impact of novel therapeutics on PC patients in phase I trials.

Pancreatic Cancer in Lynch Syndrome Patients.

Although colorectal cancer (CRC) is the most common cancer type in Lynch syndrome (LS) families, patients have also increased lifetime risk of other types of tumors. The accumulated risk of pancreatic cancer (PC) in LS patients is around 3.7% and developed tumors often present a characteristically medullary appearance with prominent lymphocytic infiltration. LS patients are considered in high risk for PC development as they present 8.6-fold increase compared with the general population. Here we review PC cases reported in LS patients and current management guidelines. Literature data show that LS is clearly associated with PC and recent publications also demonstrated a connection with pancreatic neoplasic precursor lesions such as intraductal papillary mucinous neoplasms (IPMN) in these patients. While screening techniques are well established for CRC detection, clear strategies are not yet uniform for PC. Magnetic resonance imaging (MRI) and/or endoscopic ultrasound every 1-2 years in MMR mutation carriers with PC in a first or second-degree relative is recommended. Better pancreatic cancer detection strategies should be urgently defined due to the importance of early diagnosis in this disease.

Diagnostic Accuracy of a CA125-Based Biomarker Panel in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Background: Increasing evidence from recent studies has revealed the association of CA125 with the diagnosis of pancreatic cancer, but inconsistent findings have been reported. We aimed to evaluate the diagnostic value of a serum CA125-based diagnostic panel in predicting malignant pancreatic cancer. Materials and Methods: We searched EMBASE, MEDLINE and Web of Science for relevant articles from inception to October 2016. Methodological quality was evaluated using the Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist. The performance characteristics were pooled using random-effects models. The statistical analysis was performed using Meta-Disc 1.4 and Stata Version 12.0 software. Results: A total of 1235 participants pooled from 8 eligible studies were included in the meta-analysis to evaluate the accuracy of tumor predictors for the diagnosis of pancreatic cancer. The pooling accuracy analysis of CA125 alone indicated that the pooled sensitivity was 0.59 (95% CI: 0.54-0.62) and the specificity was 0.78 (95% CI: 0.75-0.82), whereas the serum CA125-based diagnostic panel had a pooled sensitivity of 0.47 (95% CI 0.47-0.51) and a specificity of 0.88 (95% CI 0.86-0.90). Furthermore, the AUC and Q-value of the CA125-based diagnostic panel were 0.89 and 0.82, respectively, which indicated that the CA125-based panel is superior to CA125 or CA19-9 alone in diagnosing pancreatic cancer. No obvious publication bias was found. Conclusions: In summary, a CA125-based diagnostic panel is better at diagnosing pancreatic cancer than a test using CA125 or CA19-9 alone. Further studies should be performed to confirm our conclusion.

Total mesopancreas excision for the treatment of pancreatic head cancer.

Mesopancreas is a controversial structure. This study aimed to explore the anatomical characteristics of the mesopancreas, define the range of the total mesopancreas excision (TMpE), and evaluate the feasibility, safety and effectivity of TMpE in the treatment of pancreatic head cancer. The clinical and pathological data of 58 consecutive patients undergoing TMpE for pancreatic head carcinoma from January 2013 to December 2015 were analyzed prospectively. The perioperative morbidity, mortality and clinical outcomes of patients undergoing TMpE were compared with the patients undergoing conventional pancreaticoduodenectomy. The mesopancreas was located in the retropancreatic area, extending from the head, neck, and uncinated process of pancreas to the aorto-caval groove, in which there were loose areolar tissue, adipose tissue, nerve plexus, lymphatic and capillaries. We observed significantly higher R0 rate (94.8% vs. 81.4%, P=0.035), more lymph nodes (16.2 vs. 11.4, P=0.000), lower total and local recurrence rate (half-year local recurrence rate 7.8% vs. 23.7%, P=0.036, one-year 18.2% vs. 39.5%, P=0.018) and longer disease-free survival (16.9 vs. 13.4 months, P=0.044) in TMpE group than in control group. In conclusion, mesopancreas is different from mesorectum because there is no fascial envelop or anatomical boundary in this area. TMpE could be safely and feasibly performed for the treatment of pancreatic head cancer to increase the R0 resection rate and improve the clinical outcomes.

Fusobacterium nucleatum in gastroenterological cancer: Evaluation of measurement methods using quantitative polymerase chain reaction and a literature review.

The human microbiome Fusobacterium nucleatum, which primarily inhabits the oral cavity, causes periodontal disease and has also been implicated in the development of colorectal cancer. However, whether F. nucleatum is present in other gastroenterological cancer tissues remains to be elucidated. The present study evaluated whether quantitative polymerase chain reaction (qPCR) assays were able to detect F. nucleatum DNA and measure the quantity of F. nucleatum DNA in esophageal, gastric, pancreatic and liver cancer tissues. The accuracy of the qPCR assay was determined from a calibration curve using DNA extracted from cells from the oral cavity. Formalin-fixed paraffin-embedded (FFPE) tumor tissues from 20 patients with gastroenterological [esophageal (squamous cell carcinoma), gastric, colorectal, pancreatic and liver] cancer and 20 matched normal tissues were evaluated for F. nucleatum DNA content. The cycle threshold values in the qPCR assay for F. nucleatum and solute carrier organic anion transporter family member 2A1 (reference sample) decreased linearly with the quantity of input DNA (r(2)>0.99). The F. nucleatum detection rate in esophageal, gastric and colorectal cancer tissues were 20% (4/20), 10% (2/20) and 45% (9/20), respectively. F. nucleatum was not detected in liver and pancreatic cancer tissues. The qPCR results from the frozen and FFPE tissues were consistent. Notably, F. nucleatum was detected at a higher level in superficial areas compared with the invasive areas. F. nucleatum in esophageal, gastric and colorectal cancer tissues was evaluated by qPCR using FFPE tissues. F. nucleatum may be involved in the development of esophageal, gastric and colorectal cancer.

Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy: A case report and literature review.

Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer (PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage IV, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.

Adipocytes sustain pancreatic cancer progression through a non-canonical WNT paracrine network inducing ROR2 nuclear shuttling.

Solid epidemiological evidences connect obesity with incidence, stage, and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions.

An Intrapancreatic Accessory Spleen that Was Difficult to Diagnose Due to Temporal Changes after Splenectomy.

Accessory spleen (AS) is common anomaly, and 20% of AS cases occur in the pancreatic tail(1). An intrapancreatic AS can be difficult to distinguish from pancreatic neoplasms. In most cases, an AS is described as a hypervascular and solitary tumor, but an AS sometimes takes other forms. We herein report a rare case of an intrapancreatic AS with temporal changes in its appearance after splenectomy, which mimicked aspects of pancreatic cancer. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and Tc-99m sulfur colloid scintigraphy were useful for the diagnosis.

The 150 most important questions in cancer research and clinical oncology series: questions 76-85 : Edited by Chinese Journal of Cancer.

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77. How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?

The lactate receptor (HCAR1/GPR81) contributes to doxorubicin chemoresistance via ABCB1 transporter up-regulation in human cervical cancer HeLa cells.

The lactate receptor, also known as hydroxycarboxylic acid receptor 1 (HCAR1/GPR81), plays a vital role in cancer biology. Recently, HCAR1 was reported to enhance metastasis, cell growth, and survival of pancreatic, breast, and cervical cancer cells. This study showed, for the first time, the mechanism of HCAR1-mediated chemoresistance to doxorubicin through regulation of ABCB1 transporter. We observed the HCAR1 agonists L-lactate, D-lactate and 3,5-dihydroxybenzoic acid (DHBA) induced up-regulation of ABCB1. HCAR1 silencing decreased ABCB1 mRNA and protein by 80% and 40%, respectively. Moreover, cellular doxorubicin accumulation decreased by 30% after DHBA treatment, while HCAR1 silencing increased accumulation of ABCB1 substrates by nearly 2-fold. Based on growth inhibition assays, cell cycle analysis, and annexin V staining assays, we demonstrated that HCAR1 enhances cell survival and doxorubicin resistance. Finally, DHBA-stimulated up-regulation of ABCB1 functionality was suppressed by pharmacological inhibition of the PKC pathway. Taken together, our study shows the novel role of HCAR1 in development of chemoresistance in cervical carcinoma HeLa cells via ABCB1 transporter up-regulation.