keyword
https://read.qxmd.com/read/37376034/improved-therapeutic-delivery-targeting-clinically-relevant-orthotopic-human-pancreatic-tumors-engrafted-in-immunocompromised-pigs-using-ultrasound-induced-cavitation-a-pilot-study
#21
JOURNAL ARTICLE
Khan Mohammad Imran, Benjamin Tintera, Holly A Morrison, Juselyn D Tupik, Margaret A Nagai-Singer, Hannah Ivester, McAlister Council-Troche, Michael Edwards, Sheryl Coutermarsh-Ott, Christopher Byron, Sherrie Clark-Deener, Kyungjun Uh, Kiho Lee, Paul Boulos, Cliff Rowe, Christian Coviello, Irving C Allen
Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients...
May 24, 2023: Pharmaceutics
https://read.qxmd.com/read/37268393/notch-signaling-pathway-in-pancreatic-tumorigenesis
#22
REVIEW
Wen-Cheng Chung, Keli Xu
The Notch signaling pathway is an evolutionary conserved signal transduction cascade that is critical to embryonic and postnatal development, but aberrant Notch signaling is also implicated in tumorigenesis of many organs including the pancreas. Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy in the pancreas, with a dismally low survival rate due to the late-stage diagnosis and peculiar therapeutic resistance. Upregulation of the Notch signaling pathway has been found in preneoplastic lesions as well as PDACs in genetically engineered mouse models and human patients, and inhibition of the Notch signaling suppresses tumor development and progression in mice as well as patient-derived xenograft tumor growth, suggesting a critical role for Notch in PDAC...
2023: Advances in Cancer Research
https://read.qxmd.com/read/37266596/noninvasive-imaging-of-fap-expression-using-positron-emission-tomography-a-comparative-evaluation-of-a-18-f-labeled-glycopeptide-containing-fapi-with-18-f-fapi-42
#23
JOURNAL ARTICLE
Jiawen Huang, LiLan Fu, XiaoJun Zhang, Shun Huang, Ye Dong, Kongzhen Hu, YanJiang Han, Kemin Zhou, Cao Min, YanChao Huang, Ganghua Tang
PURPOSE: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68  Ga]FAPI-04 and [18 F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18 F]-labeled glycopeptide-containing FAPI tracer (named [18 F]FAPT) for PET imaging of FAP in cancers...
June 2, 2023: European Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/37246998/preclinical-and-pilot-clinical-evaluation-of-a-small-molecule-carbonic-anhydrase-ix-targeting-pet-tracer-in-clear-cell-renal-cell-carcinoma
#24
JOURNAL ARTICLE
Wenjia Zhu, Xiaoyuan Li, Guoyang Zheng, Chunmei Bai, Zhigang Ji, Haiqiong Zhang, Haiqun Xing, Yushi Zhang, Li Huo
PURPOSE: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68 Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. METHODS: The in vivo and ex vivo biodistribution of 68 Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples...
May 29, 2023: European Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/37241027/highly-selective-targeting-of-pancreatic-cancer-in-the-liver-with-a-near-infrared-anti-muc5ac-probe-in-a-pdox-mouse-model-a-proof-of-concept-study
#25
JOURNAL ARTICLE
Michael A Turner, Kristin E Cox, Nicholas Neel, Siamak Amirfakhri, Hiroto Nishino, Bryan M Clary, Mojgan Hosseini, Gopalakrishnan Natarajan, Kavita Mallya, Aaron M Mohs, Robert M Hoffman, Surinder K Batra, Michael Bouvet
Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer ( Panc Met ) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1...
May 20, 2023: Journal of Personalized Medicine
https://read.qxmd.com/read/37144505/current-state-of-clinical-trials-on-xenograft
#26
JOURNAL ARTICLE
Jad El Masri, Ahmad Afyouni, Maya Ghazi, Tarek Baroud, Doha Al Majdalany, Aalaa Saleh, Hadi El Assaad, Pascale Salameh
BACKGROUND: Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field...
May 5, 2023: Xenotransplantation
https://read.qxmd.com/read/37097516/identification-of-a-novel-immune-checkpoint-molecule-v-set-immunoglobulin-domain-containing-4-that-leads-to-impaired-immunity-infiltration-in-pancreatic-ductal-adenocarcinoma
#27
JOURNAL ARTICLE
Yongsheng Jiang, Lijie Han, Jian Yang, Minwei Yang, Jian Zhang, Meilin Xue, Youwei Zhu, Cheng Xiong, Minmin Shi, Shiwei Zhao, Baiyong Shen, Zhiwei Xu, Lingxi Jiang, Hao Chen
BACKGROUND: Checkpoint-based immunotherapy has failed to elicit responses in the majority of patients with pancreatic cancer. In our study, we aimed to identify the role of a novel immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) in pancreatic ductal adenocarcinoma (PDAC). METHODS: Online datasets and tissue microarray (TMA) were utilized to analyze the expression level of VSIG4 and its correlation with clinical parameters in PDAC. CCK8, transwell assay and wound healing assay were applied to explore the function of VSIG4 in vitro...
April 25, 2023: Cancer Immunology, Immunotherapy: CII
https://read.qxmd.com/read/37078953/cytokine-induced-killer-cell-immunotherapy-combined-with-gemcitabine-reduces-systemic-metastasis-in-pancreatic-cancer-an-analysis-using-preclinical-adjuvant-therapy-mimicking-pancreatic-cancer-xenograft-model
#28
JOURNAL ARTICLE
Jin Ho Choi, Gun He Nam, Jun-Man Hong, In Rae Cho, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim, Sang Hyub Lee
OBJECTIVES: To evaluate the efficacy and safety of cytokine-induced killer (CIK) cell therapy in pancreatic cancer. METHODS: An orthotopic murine model of pancreatic cancer and adjuvant therapy-mimicking xenograft murine model that underwent splenectomy was created. Eighty mice were randomized into four groups: the control, gemcitabine alone, CIK alone, and CIK with gemcitabine groups. The tumor growth was monitored using bioluminescence imaging once weekly. RESULTS: In the orthotopic murine model, the treatment groups showed a significantly longer survival than the control group (median: not reached vs 125...
October 1, 2022: Pancreas
https://read.qxmd.com/read/37054529/design-of-orally-bioavailable-tetra-cyclic-phthalazine-sos1-inhibitors-with-high-selectivity-against-egfr
#29
JOURNAL ARTICLE
Huan He, Ruiqi Chen, Ziwei Wang, Luolong Qing, Yu Zhang, Yi Liu, Weidong Pan, Huaxiang Fang, Silong Zhang
KRAS mutations (G12C, G12D, etc.) are implicated in the oncogenesis and progression of many deadliest cancers. Son of sevenless homolog 1 (SOS1) is a crucial regulator of KRAS to modulate KRAS from inactive to active states. We previously discovered tetra-cyclic quinazolines as an improved scaffold for inhibiting SOS1-KRAS interaction. In this work, we report the design of tetra-cyclic phthalazine derivatives for selectively inhibiting SOS1 against EGFR. The lead compound 6c displayed remarkable activity to inhibit the proliferation of KRAS(G12C)-mutant pancreas cells...
April 10, 2023: Bioorganic Chemistry
https://read.qxmd.com/read/37034710/implantation-of-engineered-adipocytes-that-outcompete-tumors-for-resources-suppresses-cancer-progression
#30
Hai P Nguyen, Rory Sheng, Elizabeth Murray, Yusuke Ito, Michael Bruck, Cassidy Biellak, Kelly An, Filipa Lynce, Deborah A Dillon, Mark Jesus M Magbanua, Laura A Huppert, Heinz Hammerlindl, Laura Esserman, Jennifer M Rosenbluth, Nadav Ahituv
Tumors acquire an increased ability to obtain and metabolize nutrients. Here, we engineered and implanted adipocytes to outcompete tumors for nutrients and show that they can substantially reduce cancer progression. Growing cells or xenografts from several cancers (breast, colon, pancreas, prostate) alongside engineered human adipocytes or adipose organoids significantly suppresses cancer progression and reduces hypoxia and angiogenesis. Transplanting modulated adipocyte organoids in pancreatic or breast cancer mouse models nearby or distal from the tumor significantly suppresses its growth...
March 29, 2023: bioRxiv
https://read.qxmd.com/read/36985425/the-potent-g-quadruplex-binding-compound-qn-302-downregulates-s100p-gene-expression-in-cells-and-in-an-in-vivo-model-of-pancreatic-cancer
#31
JOURNAL ARTICLE
Ahmed A Ahmed, William Greenhalf, Daniel H Palmer, Nicole Williams, Jenny Worthington, Tariq Arshad, Shozeb Haider, Effrosyni Alexandrou, Dilek Guneri, Zoe A E Waller, Stephen Neidle
The naphthalene diimide compound QN-302, designed to bind to G-quadruplex DNA sequences within the promoter regions of cancer-related genes, has high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. We show here that QN-302 also causes downregulation of the expression of the S100P gene and the S100P protein in cells and in vivo. This protein is well established as being involved in key proliferation and motility pathways in several human cancers and has been identified as a potential biomarker in pancreatic cancer...
March 7, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/36970055/a-preclinical-and-phase-ib-study-of-palbociclib-plus-nab-paclitaxel-in-patients-with-metastatic-adenocarcinoma-of-the-pancreas
#32
JOURNAL ARTICLE
Manuel Hidalgo, Rocio Garcia-Carbonero, Kian-Huat Lim, Wells A Messersmith, Ignacio Garrido-Laguna, Erkut Borazanci, Andrew M Lowy, Laura Medina Rodriguez, Daniel Laheru, Beatriz Salvador-Barbero, Marcos Malumbres, David J Shields, Joseph E Grossman, Xin Huang, Meggan Tammaro, Jean-François Martini, Yanke Yu, Kenneth Kern, Teresa Macarulla
PURPOSE: To assess the preclinical efficacy, clinical safety and efficacy, and MTD of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma (PDAC). EXPERIMENTAL DESIGN: Preclinical activity was tested in patient-derived xenograft (PDX) models of PDAC. In the open-label, phase I clinical study, the dose-escalation cohort received oral palbociclib initially at 75 mg/day (range, 50‒125 mg/day; modified 3+3 design; 3/1 schedule); intravenous nab-paclitaxel was administered weekly for 3 weeks/28-day cycle at 100‒125 mg/m2 ...
November 2022: Cancer Res Commun
https://read.qxmd.com/read/36961421/combating-pancreatic-cancer-with-ovarian-cancer-cells
#33
JOURNAL ARTICLE
Xiao Lin, Chunmei Cui, Qinghua Cui
With overall five-year survival rate less than 10%, pancreatic cancer (PC) represents the most lethal one in all human cancers. Given that the incidence of PC is still increasing and current cancer treatment strategies are often inefficacious, its therapy is still a huge challenge. Here, we first revealed ovarian serous carcinoma is mostly anti-correlated with pancreatic cancer in gene expression signatures. Based on this observation, we proposed that ovarian cancer cells could defend PC. To confirm this strategy, we first showed that ovarian cancer cell SKOV3 can significantly inhibit the proliferation of pancreatic cancer cell SW1990 when they were co-cultured...
March 23, 2023: Aging
https://read.qxmd.com/read/36923555/proteome-analysis-of-pancreatic-tumors-implicates-extracellular-matrix-in-patient-outcome
#34
JOURNAL ARTICLE
Laxmi Silwal-Pandit, Stina M Stålberg, Henrik J Johansson, Georgios Mermelekas, Inger Marie B Lothe, Martina L Skrede, Astrid Marie Dalsgaard, Daniel J H Nebdal, Åslaug Helland, Ole Christian Lingjærde, Knut Jørgen Labori, Bjørn S Skålhegg, Janne Lehtiö, Elin H Kure
UNLABELLED: Pancreatic cancer remains a disease with unmet clinical needs and inadequate diagnostic, prognostic, and predictive biomarkers. In-depth characterization of the disease proteome is limited. This study thus aims to define and describe protein networks underlying pancreatic cancer and identify protein centric subtypes with clinical relevance. Mass spectrometry-based proteomics was used to identify and quantify the proteome in tumor tissue, tumor-adjacent tissue, and patient-derived xenografts (PDX)-derived cell lines from patients with pancreatic cancer, and tissues from patients with chronic pancreatitis...
June 2022: Cancer Res Commun
https://read.qxmd.com/read/36854520/cyclodextrin-conjugated-%C3%AE-bisabolol-suppresses-fak-phosphorylation-and-induces-apoptosis-in-pancreatic-cancer
#35
JOURNAL ARTICLE
Mikiko Takebayashi Kano, Toshio Kokuryo, Taisuke Baba, Kimitoshi Yamazaki, Junpei Yamaguchi, Masaki Sunagawa, Atsushi Ogura, Nobuyuki Watanabe, Shunsuke Onoe, Kazushi Miyata, Takashi Mizuno, Kay Uehara, Tsuyoshi Igami, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino
BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer...
March 2023: Anticancer Research
https://read.qxmd.com/read/36844603/design-synthesis-and-biological-evaluation-of-the-first-radio-metalated-neurotensin-analogue-targeting-neurotensin-receptor-2
#36
JOURNAL ARTICLE
Sacha Bodin, Santo Previti, Emmanuelle Jestin, Delphine Vimont, Imade Ait-Arsa, Frédéric Lamare, Emmanuelle Rémond, Elif Hindié, Florine Cavelier, Clément Morgat
Neurotensin receptor 2 (NTS2 ) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS2 overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS2 . JMV 7488 (DOTA-(βAla)2 -Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with 68 Ga and 111 In, and investigated in vitro on HT-29 cells and MCF-7 cells, respectively, and in vivo on HT-29 xenografts...
February 21, 2023: ACS Omega
https://read.qxmd.com/read/36838968/-68-ga-labeled-thz-14-bombesin-7-14-analogs-promising-grpr-targeting-agonist-pet-tracers-with-low-pancreas-uptake
#37
JOURNAL ARTICLE
Lei Wang, Ivica Jerolim Bratanovic, Zhengxing Zhang, Hsiou-Ting Kuo, Helen Merkens, Jutta Zeisler, Chengcheng Zhang, Ruiyan Tan, François Bénard, Kuo-Shyan Lin
With overexpression in various cancers, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer imaging and therapy. However, the high pancreas uptake of reported GRPR-targeting radioligands limits their clinical application. Our goal was to develop 68 Ga-labeled agonist tracers for detecting GRPR-expressing tumors with positron emission tomography (PET), and compare them with the clinically validated agonist PET tracer, [68 Ga]Ga-AMBA. Ga-TacBOMB2, TacBOMB3, and TacBOMB4, derived from [Thz14 ]Bombesin(7-14), were confirmed to be GRPR agonists by a calcium mobilization study, and their binding affinities (Ki (GRPR)) were determined to be 7...
February 20, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/36748727/heterogenous-expression-of-endocrine-and-progenitor-cells-within-the-neonatal-porcine-pancreatic-lobes-implications-for-neonatal-porcine-islet-xenotransplantation
#38
JOURNAL ARTICLE
Karen L Seeberger, Bassem F Salama, Sandra Kelly, Mandy Rosko, Chelsea Castro, Jessica DesAulniers, Gregory S Korbutt
Neonatal porcine islets (NPIs) are a source of islets for xenotransplantation. In the pig, the pancreatic lobes remain separate, thus, when optimizing NPI isolation, the pancreatic lobes included in the pancreatic digest should be specified. These lobes are the duodenal (DL), splenic (SL) and connecting (CL) lobe that correspond to the head, body-tail, and uncinate process of the human pancreas. In this study we are the first to evaluate all three neonatal porcine pancreatic lobes and NPIs isolated from these lobes...
February 7, 2023: Xenotransplantation
https://read.qxmd.com/read/36725963/tumor-organoid-biobank-new-platform-for-medical-research
#39
JOURNAL ARTICLE
Xuexue Xie, Xinyu Li, Wei Song
Organoids are a new type of 3D model for tumor research, which makes up for the shortcomings of cell lines and xenograft models, and promotes the development of personalized precision medicine. Long-term culture, expansion and storage of organoids provide the necessary conditions for the establishment of biobanks. Biobanks standardize the collection and preservation of normal or pathological specimens, as well as related clinical information. The tumor organoid biobank has a good quality control system, which is conducive to the clinical transformation and large-scale application of tumor organoids, such as disease modeling, new drug development and high-throughput drug screening...
February 1, 2023: Scientific Reports
https://read.qxmd.com/read/36672390/preclinical-characterisation-of-psma-grpr-targeting-heterodimer-68-ga-ga-bq7812-for-pet-diagnostic-imaging-of-prostate-cancer-a-step-towards-clinical-translation
#40
JOURNAL ARTICLE
Fanny Lundmark, Ayman Abouzayed, Sara S Rinne, Vasiliy Timofeev, Nadezhda Sipkina, Maria Naan, Anastasia Kirichenko, Maria Vasyutina, Daria Ryzhkova, Vladimir Tolmachev, Ulrika Rosenström, Anna Orlova
The development of radioligands targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) has shown promising results for the imaging and therapy of prostate cancer. However, studies have shown that tumors and metastases can express such targets heterogeneously. To overcome this issue and to improve protein binding, radioligands with the ability to bind both PSMA and GRPR have been developed. Herein, we present the preclinical characterization of [68 Ga]Ga-BQ7812; a PSMA/GRPR-targeting radioligand for the diagnostic PET imaging of prostate cancer...
January 10, 2023: Cancers
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