Human pancreatic cancer cells (MPANC-96) recognized by autologous tumor-infiltrating lymphocytes afterin vitro as well asin vivo tumor expansion

Peiper, Matthias; Nagoshi, Makoto; Patel, Dipak R.; Fletcher, Jonathan A.; Goegebuure, Peter S.; Eberlein, Timothy J.

doi:10.1002/(sici)1097-0215(19970611)71:6<993::aid-ijc15>3.0.co;2-7

Cited by 23 publications

(19 citation statements)

References 15 publications

(15 reference statements)

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“…We used 37 human paraffin samples (10 of normal pancreas, 12 with PanIN1, 22 with PanIN2, 9 with PanIN3 and 13 with invasive carcinoma). A cell line derived from primary tumour grafts, MD Anderson pancreatic adenocarcinoma tumour cells 3 (MDA PATC-3) and an establish pancreatic cancer cell line (Mpanc96)20 (kindly provided by Dr Timothy J Eberlein, St Louis, Missouri, USA) were used and grown in RPMI-1640 supplemented with 10% fetal bovine serum, 1 mM sodium pyruvate, 2 mM l -glutamine, 1X non-essential amino acids (Gibco, Carlsbad, California, USA), and 1X Pen/Strep (100 U/ml penicillin, 100 ug/ml streptomycin).…”

Section: Methodsmentioning

confidence: 99%

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models

Cruz‐Monserrate

Abd-Elgaliel

Grote

et al. 2011

Gut

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Background and Aims Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. Surgical resection is the only effective treatment; however, only 20% of patients are candidates for surgery. The ability to detect early PDAC would increase the availability of surgery and improve patient survival. This study assessed the feasibility of using the enzymatic activity of cathepsin E (Cath E), a protease highly and specifically expressed in PDAC, as a novel biomarker for the detection of pancreas-bearing pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC. Methods Pancreas from normal, chronic pancreatitis and PDAC patients was assessed for Cath E expression by quantitative real-time PCR and immunohistochemistry. Human PDAC xenografts and genetically engineered mouse models (GEMM) of PDAC were injected with a Cath E activity selective fluorescent probe and imaged using an optical imaging system. Results The specificity of Cath E expression in PDAC patients and GEMM of pancreatic cancer was confirmed by quantitative real-time PCR and immunohistochemistry. The novel probe for Cath E activity specifically detected PDAC in both human xenografts and GEMM in vivo. The Cath E sensitive probe was also able to detect pancreas with PanIN lesions in GEMM before tumour formation. Conclusions The elevated Cath E expression in PanIN and pancreatic tumours allowed in-vivo detection of human PDAC xenografts and imaging of pancreas with PanIN and PDAC tumours in GEMM. Our results support the usefulness of Cath E activity as a potential molecular target for PDAC and early detection imaging.

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Section: Methodsmentioning

confidence: 99%

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models

Cruz‐Monserrate

Abd-Elgaliel

Grote

et al. 2011

Gut

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“…Pancreatic cancer cell lines BxPC3, MiaPaCa-2, CFPAC-1, HPAC, Panc-1, Aspc-1, and SU.86.86 were obtained from the American Type Culture Collection. MPanc-96 pancreatic adenocarcinoma cell lines were originally established by Dr. Timothy J. Eberlein (20). BxPC3 and SU.86.86 cells were cultured in RPMI 1640 with 10% fetal bovine serum (FBS).…”

Section: Methodsmentioning

confidence: 99%

Anterior Gradient 2 Is Expressed and Secreted during the Development of Pancreatic Cancer and Promotes Cancer Cell Survival

Ramachandran¹,

Arumugam²,

et al. 2008

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Pancreatic cancer is a major oncological challenge due to its aggressive growth and metastasis. In the current study, we investigated the role of anterior gradient 2 (AGR2) in these processes. AGR2 mRNA, as assessed by quantitative real-time reverse transcription–PCR (Q-RT-PCR), was 14-fold higher in pancreatic cancer compared with normal and pancreatitis tissues. Immunohistochemistry revealed high expression of AGR2 in neoplastic cells with 98% (56 of 57) positivity on pancreatic cancer and minimal staining in normal and pancreatitis tissues. AGR2 was also expressed in early pancreatic intraepithelial neoplastic lesions. RT-PCR and Western blotting showed elevated AGR2 expression in seven of nine pancreatic cancer cell lines. AGR2, as detected in conditioned media from cancer cells, indicated that it was secreted. The influence of AGR2 on pancreatic cancer cells was evaluated by silencing with small interfering RNA and short hairpin RNA. Silencing of AGR2 significantly reduced cell proliferation (MTS assay) and invasion (Boyden chamber assay) and improved gemcitabine sensitivity (fluorescence-activated cell sorting analysis). Conditioned media from cells in which AGR2 was silenced had a reduced ability to stimulate proliferation of pancreatic cancer cells, suggesting that secreted AGR2 was active. In vivo, silencing of AGR2 in MPanc-96 cells led to a significant reduction of tumor growth and increased the effectiveness of gemcitabine treatments in orthotopic tumor models evaluated by noninvasive bioluminescence imaging. In summary, AGR2 is expressed and secreted during pancreatic cancer development and plays an important role in cancer cell growth and survival. These observations suggest that AGR2 may be a useful molecular target in pancreatic cancer.

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“…MPanc-96 cells were a kind gift from Dr. Craig Logsdon, University of Texas, M.D. Anderson Cancer Center (19). This human pancreatic cell line has been found to harbor a mutation in exon 1 of K-ras and a frameshift in exons 5 to 8 of p53 (20).…”

Section: Cell Lines and Virusesmentioning

confidence: 99%

Effective Treatment of Pancreatic Cancer Xenografts with a Conditionally Replicating Virus Derived from Type 2 Herpes Simplex Virus

Tao

et al. 2006

Clinical Cancer Research

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Purpose: Pancreatic cancer is a devastating disease that is almost universally fatal because of the lack of effective treatments.We recently constructed a novel oncolytic virus (FusOn-H2) from the type 2 herpes simplex virus. Because the replication potential of FusOn-H2 depends on the activation of the Ras signaling pathway, we evaluated its antitumor effect against pancreatic cancer, which often harbors K-ras gene mutations. Experimental Design: Human pancreatic cancer xenografts were established in nude mice either s.c. or orthotopically (n = 8/group). FusOn-H2 was injected either directly (s.c. tumors) or by the i.v. or i.p. route (orthotopic tumors).Tumor volume, weight, and survival time were recorded for each animal. Statistical analyses were done by Student's t test. Results: A single intratumor injection of FusOn-H2 completely eradicated s.c. pancreatic cancers in all animals. Systemic injection of the oncolytic virus produced clear antitumor effects but did not abolish tumors in any animal. The most striking antitumor effect was seen when the virus was given i.p. Delivery of FusOn-H2 by this route completely eradicated established orthotopic tumors in 75% of the animals and completely prevented local metastases. Conclusions: FusOn-H2 has potent activity against human pancreatic cancer xenografts and may be a promising candidate for investigative virotherapy of this malignancy.Pancreatic cancer, which is usually diagnosed at an advanced stage, carries the highest fatality rate among all human cancers and accounts for the fourth highest number of cancer deaths in the U.S. (1). The dismal prognosis associated with this tumor has not improved over the past three decades, largely because effective treatments for metastatic disease have not been developed. This outlook may be changing due to the recently acquired ability to isolate or to genetically engineer viruses that could act as oncolytic agents in the treatment of solid tumors such as pancreatic cancer.Oncolytic viruses infect, replicate in, and destroy cancer cells without harming normal cells. Nonengineered oncolytic viruses are naturally occurring viruses that preferentially target tumor cells (2), but they are limited in number and are not available for all types of cancers. This disadvantage can be overcome with ''engineered'' oncolytic viruses that have been genetically modified to target cancer cells. In general, there are three ways to engineer viruses to target malignant cells. One approach is to alter surface viral proteins involved in the entry of viruses into cells, so that the virus is specifically targeted to tumor cells (3, 4). Another approach is to modify the virus to replicate only in the absence of a functional tumor suppressor gene, such as p53, which is mutated in many cancer cells (5). In the third approach, the virus is altered so that it will replicate only in dividing cells (6). Several viruses modified for oncolytic purposes are currently in clinical trials for a variety of solid tumors of different tissue origins. On...

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Human pancreatic cancer cells (MPANC-96) recognized by autologous tumor-infiltrating lymphocytes afterin vitro as well asin vivo tumor expansion

Cited by 23 publications

References 15 publications

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models

Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models

Anterior Gradient 2 Is Expressed and Secreted during the Development of Pancreatic Cancer and Promotes Cancer Cell Survival

Effective Treatment of Pancreatic Cancer Xenografts with a Conditionally Replicating Virus Derived from Type 2 Herpes Simplex Virus

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