Human pancreatic adenocarcinoma: In vitro and in vivo morphology of a new tumor line established from ascites

In Vitro ◽  
1982 ◽  
Vol 18 (1) ◽  
pp. 24-34 ◽  
Author(s):  
W. H. Chen ◽  
J. S. Horoszewicz ◽  
S. S. Leong ◽  
T. Shimano ◽  
R. Penetrante ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Tumor Line ◽  
Human Pancreatic Adenocarcinoma

Effect of raloxifene on human pancreatic adenocarcinoma growth in vitro and in vivo.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 207-207
Author(s):  
H. Seeliger ◽  
N. Seel ◽  
P. Camaj ◽  
I. Ischenko ◽  
K. Jauch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Estrogen Receptor ◽  
Tumor Growth ◽  
Pancreatic Adenocarcinoma ◽  
Ki 67 ◽  
Orthotopic Tumor ◽  
Human Pancreatic Adenocarcinoma ◽  
Er Alpha

207 Background: The role of estrogen receptor (ER) signaling in pancreatic cancer is unknown. Recently, we demonstated that expression of the isoform ER beta correlates with an adverse prognosis in patients with pancreatic cancer. Here, we show that raloxifene, a specific estrogen receptor modulator (SERM), suppresses in vitro and in vivo tumor growth by interfering with ER beta signaling in human pancreatic adenocarcinoma. Methods: The human pancreatic adenocarcinoma cell line L3.6pl was cultured and exposed to raloxifene in vitro, and cell proliferation was determined by the BrdU assay. To analyze the specificity of raloxifene induced effects, ER knockdown was performed using siRNA specific for ER alpha and ER beta. In an in vivo model of orthotopic tumor xenografts in nude mice, raloxifene was administered daily, and tumor growth was monitored. Expression of ER beta and the proliferation marker Ki-67 were determined by immunohistochemistry. Results: Raloxifene treatment resulted in a potent, dose dependent reduction of proliferation in vitro over a nanomolar dose range. This effect was completely reversed by siRNA knockdown of ER beta, but not ER alpha, indicating an ER isotype specific signaling. In vivo, orthotopic tumor growth, as well as lymph node and liver metastases, was significantly suppressed in raloxifene treated mice. Analogous to the in vitro data, Ki-67 expression in vivo was significantly reduced in raloxifene treated mice, while ER beta expression was not changed in vivo. Conclusions: Inhibition of ER beta signaling by raloxifene results in a potent reduction of human pancreatic adenocarcinoma growth in vitro and in vivo. Treatment with SERMs may be an attractive therapeutic option in subjects expressing the ER beta isotype. No significant financial relationships to disclose.

scholarly journals EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

2009 ◽  
Vol 7 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Hendrik Seeliger ◽  
Peter Camaj ◽  
Ivan Ischenko ◽  
Axel Kleespies ◽  
Enrico N. De Toni ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pancreatic Adenocarcinoma ◽  
Human Pancreatic Adenocarcinoma

General and efficient synthesis of benzoxazol-2(3H)-ones: evolution of their anti-cancer and anti-mycobacterial activities

RSC Advances ◽  
2014 ◽  
Vol 4 (103) ◽  
pp. 59594-59602 ◽  
Author(s):  
K. Indrasena Reddy ◽  
C. Aruna ◽  
K. Sudhakar Babu ◽  
V. Vijayakumar ◽  
M. Manisha ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Efficient Synthesis ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Human Pancreatic Adenocarcinoma ◽  
Anti Cancer

A novel class of benzo[d]oxazol-2(3H)-one derivatives has been synthesized and their in vitro cytotoxicity against human pancreatic adenocarcinoma and human non-small cell lung carcinoma cancer cell lines was evaluated.

scholarly journals Antagonistic Roles of the Tumor Suppressor miR-210-3p and Oncomucin MUC4 Forming a Negative Feedback Loop in Pancreatic Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6197
Author(s):  
Nihad Boukrout ◽  
Mouloud Souidi ◽  
Fatima Lahdaoui ◽  
Belinda Duchêne ◽  
Bernadette Neve ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Chromatin Immunoprecipitation ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Cell Proliferation And Migration ◽  
Muc4 Expression ◽  
And Migration ◽  
Proliferation And Migration

Background: Pancreatic adenocarcinoma (PDAC) is a deadly cancer with an extremely poor prognosis. MUC4 membrane-bound mucin is neoexpressed in early pancreatic neoplastic lesions and is associated with PDAC progression and chemoresistance. In cancers, microRNAs (miRNAs, small noncoding RNAs) are crucial regulators of carcinogenesis, chemotherapy response and even metastatic processes. In this study, we aimed at identifying and characterizing miRNAs activated downstream of MUC4-associated signaling in pancreatic adenocarcinoma. MiRnome analysis comparing MUC4-KD versus Mock cancer cells showed that MUC4 inhibition impaired miR-210-3p expression. Therefore, we aimed to better understand the miR-210-3p biological roles. Methods: miR-210-3p expression level was analyzed by RT-qPCR in PDAC-derived cell lines (PANC89 Mock and MUC4-KD, PANC-1 and MiaPACA-2), as well as in mice and patients tissues. The MUC4-miR-210-3p regulation was investigated using luciferase reporter construct and chromatin immunoprecipitation experiments. Stable cell lines expressing miR-210-3p or anti-miR-210-3p were established using CRISPR/Cas9 technology or lentiviral transduction. We evaluated the biological activity of miR-210-3p in vitro by measuring cell proliferation and migration and in vivo using a model of subcutaneous xenograft. Results: miR-210-3p expression is correlated with MUC4 expression in PDAC-derived cells and human samples, and in pancreatic PanIN lesions of Pdx1-Cre; LstopL-KrasG12D mice. MUC4 enhances miR-210-3p expression levels via alteration of the NF-κB signaling pathway. Chromatin immunoprecipitation experiments showed p50 NF-κB subunit binding on miR-210-3p promoter regions. We established a reciprocal regulation since miR-210-3p repressed MUC4 expression via its 3′-UTR. MiR-210-3p transient transfection of PANC89, PANC-1 and MiaPACA-2 cells led to a decrease in cell proliferation and migration. These biological effects were validated in cells overexpressing or knocked-down for miR-210-3p. Finally, we showed that miR-210-3p inhibits pancreatic tumor growth and proliferation in vivo. Conclusion: We identified a MUC4-miR-210-3p negative feedback loop in early-onset PDAC, but also revealed new functions of miR-210-3p in both in vitro and in vivo proliferation and migration of pancreatic cancer cells, suggesting a complex balance between MUC4 pro-oncogenic roles and miR-210-3p anti-tumoral effects.

Effect of MM-141 on gemcitabine and nab-paclitaxel potentiation in preclinical models of pancreatic cancer through induction of IGF-1R and ErbB3 degradation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 289-289 ◽  
Author(s):  
Emily Pace ◽  
Sharlene Adams ◽  
Adam Camblin ◽  
Michael Curley ◽  
Victoria Rimkunas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Stage Iv ◽  
Akt Signaling ◽  
Preclinical Models ◽  
Patient Response ◽  
Receptor Complexes

289 Background: Gemcitabine, the first-line treatment for pancreatic cancer, has been improved by addition of nab-paclitaxel. However, patient response to this regimen is limited. Oncogenic insulin-like growth factor 1 (IGF-1) and heregulin (HRG) signaling are associated with increased cancer risk and decreased response to anti-metabolites and taxanes. Therefore, we explored MM-141, a novel bispecific antibody that blocks ErbB3 and IGF-1 receptor (IGF-1R) signaling, in combination with nab-paclitaxel and gemcitabine in preclinical models of pancreatic cancer. Methods: Combinations with MM-141, gemcitabine, and nab-paclitaxel were investigated in pancreatic cancer cell lines, in vitro and in vivo. The effects of MM-141, gemcitabine, and nab-paclitaxel on tumor growth and signaling were measured by 3D spheroid growth, ELISA, Western, and mouse xenograft experiments. Results: In vitro studies show that IGF-1 and HRG are potent activators of AKT signaling, leading to increased pancreatic tumor cell proliferation and decreased sensitivity to gemcitabine and nab-paclitaxel. MM-141 inhibits ligand-induced AKT activation, induces IGF-1R and ErbB3 degradation better than a mixture of IGF-1R and ErbB3 antibodies, and sensitizes cells to gemcitabine and nab-paclitaxel, in vitro. In vivo, MM-141 combines favorably with a nab-paclitaxel/gemcitabine regimen, leading to curative outcomes in a subset of treated mice. Conclusions: ErbB3 and IGF-1R co-inhibition is required to inhibit AKT signaling in pancreatic adenocarcinoma cell lines. These receptors are associated with chemoresistance to gemcitabine and nab-paclitaxel, which is abrogated by co-administration with MM-141. MM-141-induced degradation of oncogenic receptor complexes is likely essential to reverse chemoresistance and enhance effects of the nab-paclitaxel/gemcitabine regimen. These data, taken together with wide-spread expression of IGF-1R and ErbB3 in Stage IV pancreatic adenocarcinoma tissue, support clinical exploration of a MM-141/nab-paclitaxel/gemcitabine regimen in frontline metastatic pancreatic cancer. Preparations for a randomized Phase 2 study are underway.

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