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pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging

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World Journal of Gastroenterology 2007年第6期13卷 858-865页

作者： Yoshitsugu Tajima Tamotsu Kuroki Ryuji Tsutsumi Ichiro Isomoto Masataka Uetani Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Japan Department of Radiology and Radiation Biology Nagasaki University Graduate School of Biomedical Sciences Japan

AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic ***: pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.

关键词： pancreatic carcinoma Chronic pancreatitis Focal pancreatic mass Tumor-forming pancreatitis Differential diagnosis, Dynamic magnetic resonance imaging Time-signal intensity curve

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Apoptosis-enhanced ferroptosis therapy of pancreatic carcinoma through PAMAM dendrimer-iron(Ⅲ)complex-based plasmid delivery

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Science China Chemistry 2022年第4期65卷 778-788页

作者： Wenjing Ma Yue Gao Zhijun Ouyang Yu Fan Hongwei Yu Mengsi Zhan Han Wang Xiangyang Shi Mingwu Shen State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineCollege of ChemistryChemical Engineering and BiotechnologyDonghua UniversityShanghai 201620China Department of Radiology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

The development of promising strategies to improve the treatment efficacy of pancreatic carcinoma still remains to be a challenging *** report here the development of a new dendrimer-based nanomedicine formulation to tackle pancreatic carcinoma through apoptosis-enhanced ferroptosis *** this article,G5 dendrimers were partially modified with a Fe(Ⅲ)chelator hydroxyquinoline-2-carboxylic acid(8-HQC)on their periphery,entrapped with gold nanoparticles(Au NPs)within their internal cavities,and chelated with Fe(Ⅲ).The thus created dendrimer-entrapped Au NPs(Fe-Au DENP-HQC)with an Au core size of 1.9 nm and 20.0 Fe(Ⅲ)ions complexed per dendrimer are stable,have a pH-dependent Fe(Ⅲ)release profile,and can generate reactive oxygen species under the tumor microenvironment(TME)and effectively compact plasmid DNA encoding p53 protein to form polyplexes with a hydrodynamic size of 143.9 nm and a surface potential of 33.6 *** show that cancer cells treated with the created Fe-Au DENP-HQC/p53 polyplexes can be more significantly inhibited through vector-mediated chemodynamic therapy(CDT)effect via Fe(Ⅲ)-induced Fenton reaction and the p53 gene delivery-boosted cell apoptosis and oxidative stress in the TME than single-mode CDT and gene *** investigations using a xenografted tumor model validated the effectiveness of apoptosis-enhanced ferropotosis therapy through the downregulation of GPX-4 and SLC7A11proteins,upregulation of p53 and PTEN proteins,as well as histological ***,the dendrimer nanoplatform enabled tumor fluorescence imaging through gene delivery-mediated enhanced green fluorescent protein *** Fe(Ⅲ)-complexed dendrimer vector system may be developed as a promising theranostic nanoplatform for ferroptosis or ferroptosis-based combination therapy of other cancer types.

关键词： dendrimers ferroptosis gene delivery pancreatic carcinoma fluorescence imaging

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Value of three-dimensional reconstructions in pancreatic carcinoma using multidetector CT:Initial results

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World Journal of Gastroenterology 2009年第46期15卷 5827-5832页

作者： Miriam Klauβ Max Schbinger Ivo Wolf Jens Werner Hans-Peter Meinzer Hans-Ulrich Kauczor Lars Grenacher Department of Diagnostic and Interventional Radiology University of Heidelberg Department of Medical and Biological Informatics German Cancer Research Center(DKFZ) Surgical Clinic University of Heidelberg

AIM:To evaluate the use of three-dimensional imaging of pancreatic carcinoma using multidetector computed tomography(CT)in a prospective ***:Ten patients with suspected pancreatic tumors were examined prospectively using multidetec-tor CT(Somatom Sensation 16,Siemens,Erlangen,Germany).The images were evaluated for the pres-ence of a pancreatic carcinoma and invasion of the peripancreatic vessels and surrounding *** the isotropic CT data sets,a three-dimensional image was created with automatic vascular analysis and semi-automatic segmentation of the organs and pancreatic tumor by a *** CT examinations and the three-dimensional images were presented to the sur-geon directly before and during the patient's operation using the Medical Imaging Interaction Toolkit-based software "ReLiver".Immediately after surgery,the value of the two images was judged by the *** operation and the histological results served as the gold ***:Nine patients had a pancreatic carcinoma(all pT3),and one patient had a serous *** tumor inf iltrated the superior mesenteric *** inf iltration was correctly *** carcinomas were *** comparison to the CT image with axial and coronal reconstructions,the three-dimensional image was judged by the surgeons as better for operation planning and consistently described as ***:A 3D-image of the pancreas repre-sents an invaluable aid to the ***,the 3D-software must be further developed in order to be integrated into daily clinical routine.

关键词： pancreatic carcinoma 3D-reconstruction Multidetector computed tomography pancreatic carcinomainvasion Segmentation

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Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice

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World Journal of Gastroenterology 2005年第3期11卷 447-450页

作者： LinJia Mei-HuaZhang Shi-ZhenYuan Wen-GeHuang DepartmentofDigestiveDiseases FirstAffiliatedPeople'sHospitalGuangzhouMedicalCollegeGuangzhou510180GuangdongProvinceChina DepartmentofDigestiveDiseases SecondAffiliatedHospitalSunYat-SenUniversityGuangzhou510120GuangdongProvinceChina Animalcenter SunYat-SenUniversityGuangzhou510089GuangdongProvinceChina DepartmentofDigestiveDiseases FirstAffiliatedPeople'sHospitalGuangzhouMedicalCollegeGuangzhou510180GuangdongProvinceChina

AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism. METHODS: A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990 pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d O, 3, 6 and 9 after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group, T15 group, G50 group and combination group (TNP-470 30 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver, lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group. PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor VIII, respectively. RESULTS: There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100 group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100 group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group. However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combin

关键词： pancreatic carcinoma TNP-470 Angiogenesis Inhibitors Xenografts

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Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

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World Journal of Gastroenterology 2008年第27期14卷 4377-4382页

作者： Lin Jia Yuan-Yuan Shang Yu-Yuan Li Department of Digestive Diseases Guangzhou Municipal First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was n

关键词： pancreatic carcinoma Mirtazapine Fluoxetine Body weight Nude mice Locomotor activity Ethology

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Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma

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Acta Pharmaceutica Sinica B 2019年第3期9卷 575-589页

作者： Xi Cao Ying Hu Shi Luo Yuejing Wang Tao Gong Xun Sun Yao Fun Zhirong Zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan University

Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma via na?ve neutrophil membrane-coated poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid)(PEG-PLGA) nanoparticles. Neutrophil membranecoated nanoparticles(NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery in vivo. Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models,celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.

关键词： Na■ve neutrophils membrane Celastrol PEG-PLGA nanoparticle pancreatic carcinoma Inflammation

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Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition

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World Journal of Gastroenterology 2009年第4期15卷 441-448页

作者： Yu-Wei Dong Xing-Peng Wang Kai Wu Department of Gastroenterology Shanghai First-People's Hospital Shanghai Jiaotong UniversityShanghai 200080 China Department of Gastroenterology The Tenth People's Hospital of Tongji University Yanchang Road (M)Shanghai 200072 China

AIM： TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ （PPARγ）, a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METHODS： Expressions of PPARy and retinoid acid receptor （RXRα） were examined by reverse-transcription polymerase chain reaction （RT-PCR） with immunocyto- chemical staining. pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy-△12,14 prostaglandin J2 （15d-PGJ2）, a ligand of PPART, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium （MTT） assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARy, was administered via water drinking in experimental group of nude mice. After 75 d, all mice were sacrificed. Expression of proliferating cell nuclear antigen （PCNA） in tumor tissue was examined with immunohistochemical staining. Expression of vascular endothelial growth factor （VEGF） mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosi- glitazone on changes of microvascular density （MVD） and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immu- nohistochemistry staining labeled with anti-Ⅳ collagen antibody, and indicated by MVD. RESULTS： RT-PCR and immunocytochemical stain- ing showed that PPARγ and RXRα were expressed in PANC-1 cells at both transcription level and translation level. MTT assay demonstrated that 15d-PGJ2, 9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a com- bined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carci

关键词： pancreatic carcinoma Peroxisome prolifer-ator-activated receptor γ Angiogenesis Vascular en-dothelial growth factor

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Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: Mechanism involved

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World Journal of Gastroenterology 2005年第14期11卷 2101-2108页

作者： LuLiu Guo-ShengFeng HongGao Guan-ShengTong YuWang WenGao YingHuang ChengLi InstituteofNuclearMedicineTechnologyofSoutheastUniversity Nanjing210009JiangsuProvinceChina BeijingRailwayGeneralHospital Beijing100038China

AIM: To study the effects of chromic-P32 phosphate (32p colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer ***: Ninety-eight tumor bearing nude mice werekilled at different time points after the injection of 32Pcolloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32p colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Baxrelated gene expression were observed ***: The half-life of effective medication is 13 dafter injection of 32P colloids to the tumor stroma, in 1-6groups, the tumor cell necrosis rates were 20%, 45%,65%, 70%, 95% and 4%, respectively (F= 4.14-105.36, P＜0.01). MVD were 38.5±4.0, 28.0±2.9, 17.0±2.9, 8.8±1.5,5.7±2.3 and 65.0±5.2 (t= 11.9-26.1, P＜0.01), *** TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM inanimals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiationinduced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32

关键词： Chromic-P32 phosphate pancreatic carcinoma

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Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable pancreatic carcinoma

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Chinese Journal of Cancer Research 2011年第3期23卷 194-200页

作者： Jin-luan Li Yong Cai Shan-wen Zhang Shao-wen Xiao Xiao-fan Li You-jia Duan Yong-heng Li Bo Xu Kun Yan Key Laboratory of Carcinogenesis and Translational Research （Ministry of Education） 1Department of Radiotherapy2Department of UltrasonographyPeking University School of OncologyBeijing Cancer Hospital ＆ InstituteBeijing 100142China

Objective：To assess the safety and efficacy of the combination of recombinant adenovirus-p53 （rAd-p53） with radiochemotherapy for treating unresectable pancreatic ***：The eligible patients received concurrent rAd-p53 intratumoral injection and *** injection of rAd-p53 was guided by B *** consisted of intensity-modulated radiotherapy （IMRT） at two dose levels and intravenous gemcitabine （Gem）.For radiotherapy,gross target volume （GTV） and clinical target volume （CTV） were 55-60 Gy and 45-55 Gy in 25-30 fractions,*** intravenous gemcitabine was administered at 350 mg/m2,weekly,for 6 *** primary end points included toxicity,clinical benefit response （CBR） and disease control rate （DCR）.The secondary end points included progression-free survival （PFS） and overall survival （OS）.Results：Fifteen eligible patients were *** patients （53.3%） were evaluated as CBR and 12 （80%） achieved *** median PFS and OS were 6.7 and 13.8 months,***-year PFS and OS were 40.0% and 51.1%,*** were 8 （53.3%） patients reported grade 3 toxicities including neutropenia （6 patients,40%）,fever （1 patient,6.7%） and fatigue （1 patient,6.7%）.There was no grade 4 toxicity ***：Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well ***-term follow-up is needed to confirm the improvement of PFS and OS.

关键词： Recombinant adenovirus-p53 Radiochemotherapy pancreatic carcinoma

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Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3410-3426页

作者： Honglin Tang Yanan Xue Bowen Li Xiaojie Xu Fu Zhang Jiajing Guo Qijun Li Tingting Yuan Yuan Chen Yubin Pan Yuan Ping Da Li Department of Medical Oncology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Department of Hepatobiliary and pancreatic Surgery the First Affiliated HospitalZhejiang UniversityHangzhou 310003China

pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine(GEM) with the molecular-targeted drug erlotinib(Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuliresponsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA(siRNA) for synergistic pancreatic cancer treatment. This “all-in-one”delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor(PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

关键词： Chemotherapy Target therapy siRNA Nanomedicine Hybrid membrane Drug antagonism pancreatic carcinoma Patient-derived tumor

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