Ensituximab (E) in patients (pts) with refractory metastatic colorectal cancer (mCRC): Results of a phase I/II clinical trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3081-3081 ◽  
Author(s):  
Richard D. Kim ◽  
Philip M. Arlen ◽  
Kwong Y. Tsang ◽  
Sharon Mavroukakis ◽  
Anjum Zaki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase 1 ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Serum Cytokine ◽  
Open Label ◽  
Related Factors

3081 Background: E is an investigational, novel, chimeric monoclonal IgG1 antibody derived from an immunogenic neoantigen with sequence homology to MUC5AC that is preferentially expressed with exquisite specificity to pancreatic cancer and CRC. Its mechanism of action is via antibody-dependent cellular cytotoxicity (ADCC). The efficacy and safety of E was evaluated in a single-arm, open-label, phase 1/2 clinical trial of adult pts with refractory mCRC. Methods: Pts were selected based on > 20% expression of tumor antigen, as measured by immunohistochemistry. Based on phase 1 results, E was administered 3 mg/kg IV every 2 weeks until unacceptable toxicity or disease progression. Primary endpoint was overall survival (OS). Serum cytokine levels were analyzed at baseline, day 4, and day 15. E-mediated ADCC of CD16 genotype V/V, V/F, and F/F pt PBMCs was measured with an IN-111 release assay using the E target-expressing ASPC-1 pancreatic cancer cell line. Results: Fifty-seven and 63 pts were evaluable for OS and safety, respectively. Median OS was significantly longer than historical control: 6.8 vs 5.0 months (mo); p = 0.007; 95% CI: 5.39,8.02. Three pts were alive at end of study (21, 21, and 24 mo); 21 pts survived ≥ 12 mo. Pts had a median of 4 prior therapies (range 2-9); 25% had received regorafenib. Forty-seven pts were evaluable by RECIST, and 20 (43%) had stable disease of target lesions at end of first course (day 57). E was well tolerated, with < 2% grade 3 and no grade 4 toxicities. There were no trends in serum cytokine and chemokine levels. Analysis of 56 samples (8 V/V, 26 V/F, 17 F/F, and 5 undetermined) showed that V/V PBMCs had significantly higher E-mediated ADCC than PBMCs harboring other genotypes. No correlation between CD16 polymorphism and pt outcome was observed. Conclusions: E demonstrated excellent tolerability and encouraging OS in this heavily pretreated population. Correlative in vitro data suggest that E can mediate higher levels of ADCC activity in individuals with a V/V versus other genotypes. The lack of correlation between CD16 polymorphism and pt outcomes in this study suggests that other immune-related factors (under investigation) may impact the efficacy of E in vivo. Clinical trial information: NCT01040000.

scholarly journals Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2017
Author(s):  
Lital Sharvit ◽  
Rinat Bar-Shalom ◽  
Naiel Azzam ◽  
Yaniv Yechiel ◽  
Solomon Wasser ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Culture Liquid ◽  
Human Pancreatic Cancer ◽  
P53 Signaling ◽  
Pancreatic Cancer Cells

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.

scholarly journals Attenuation of Pancreatic Cancer In Vitro and In Vivo via Modulation of Nrf2 and NF-κB Signaling Pathways by Natural Compounds

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3556
Author(s):  
Marta Cykowiak ◽  
Robert Kleszcz ◽  
Małgorzata Kucińska ◽  
Jarosław Paluszczak ◽  
Hanna Szaefer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Cell Line ◽  
Target Genes ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
In Vivo Studies ◽  
Phenethyl Isothiocyanate

Pancreatic cancer is a disease in which deregulation of signaling pathways plays a key role, thus searching for their novel modulators is a promising therapeutic strategy. Hence, in this study, the effect of phytochemical combinations on the canonical and non-canonical activation of Nrf2 and its interaction with the NF-κB pathway was evaluated in extensively proliferating pancreatic cancer cell line, PSN-1, in comparison to non-cancerous MS1 cells. The activation of Nrf2 and NF-κB, expression of their target genes, and effect on cell survival were assessed in PSN-1 cells. The tumor burden was evaluated in mice carrying xenografts. PSN-1 cells were more sensitive to the tested compounds as compared to the MS1 cell line. Combination of xanthohumol and phenethyl isothiocyanate was more effective than single compounds at decreasing the canonical and non-canonical activation of Nrf2 in PSN-1 cancer cells. Decreased activation of NF-κB, and subsequent reduced cytosolic COX-2 and nuclear STAT3 level indicated their anti-inflammatory and pro-apoptotic activities. In vivo studies showed the partial response in groups treated with xanthohumol or the combination of xanthohumol and phenethyl isothiocyanate. Overall, these results suggest that the combination of xanthohumol and phenethyl isothiocyanate may be a promising therapeutic candidate against pancreatic cancer.

scholarly journals Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo

2020 ◽  
Vol Volume 12 ◽  
pp. 4645-4665 ◽  
Author(s):  
Ya-Hui Chen ◽  
Yi-Chun Chen ◽  
Chi-Chen Lin ◽  
Yao-Peng Hsieh ◽  
Chien-Sheng Hsu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Anticancer Effects

scholarly journals Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells

2020 ◽  
Vol 64 (2) ◽  
pp. 103-113
Author(s):  
He-jun Zhao ◽  
Xia Jiang ◽  
Li-juan Hu ◽  
Lei Yang ◽  
Lian-dong Deng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

scholarly journals Human Mesenchymal Stem Cell-Derived Exosomal microRNA-143 Promotes Apoptosis and Suppresses Cell Growth in Pancreatic Cancer via Target Gene Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Bingyi Wang ◽  
Yan Xu ◽  
Yuhua Wei ◽  
Lixin Lv ◽  
Nanbin Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Human Mesenchymal Stem Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Luciferase Assay ◽  
Human Pancreatic Cancer

BackgroundThis study aimed to explore the regulatory mechanism of hsa-miR-143-3p and lncRNA RP11-363N22.3–functioning upstream of KRAS–in exosomes derived from human mesenchymal stem cells (hMSCs) in pancreatic cancer.MethodsWestern blotting and quantitative PCR were used to determine gene expression. In vitro, cell proliferation, apoptosis, and cell cycle and invasion were evaluated using CCK-8 assay, flow cytometry, and transwell assays, respectively. In vivo, the effect of hsa-miR143-3p was investigated using a tumorigenesis test in nude mice. The association between hsa-miR-143-3p and lncRNA RP11-363N22.3 was investigated using the dual-luciferase assay.Resultshsa-miR-143-3p expression significantly increased in hMSC exosomes than in those in human pancreatic cancer cell line (CFPAC-1) exosomes. In vitro, compared to the MOCK (CFPAC-1 only) group, cell proliferation and invasion were inhibited and apoptosis was induced in the inhibitor NC (CFPAC-1 + MSC-hsa-miR-3p inhibitor NC) group, while these changes were reversed in the inhibitor (CFPAC-1 + MSC-hsa-miR-3p inhibitor) group. The expression of lncRNA RP11-363N22.3 and genes related to miR-143 significantly decreased in the inhibitor NC group compared to the MOCK group, and increased in the inhibitor group compared to inhibitor NC group. A targeted combinatorial effect was observed between lncRNA RP11-363N22.3 and hsa-miR-143-3p. In vivo, the tumor volume of the mimics (CFPAC-1 + MSC-hsa-miR-143-3p mimics) group was smaller than that of the mimics NC (CFPAC-1 + MSC-hsa-miR-143-3p mimics NC) and MOCK groups. H&amp;E staining showed that there were no obvious pathological changes in MOCK and mimic NC groups, while cell necrosis was seen in some regions in mimic groups.Conclusionhsa-miR-143-3p may promote apoptosis and suppress cell growth and invasion in pancreatic cancer.

scholarly journals Forkhead box B2 inhibits the malignant characteristics of the pancreatic cancer cell line Panc‐1 in vitro

2019 ◽  
Vol 24 (10) ◽  
pp. 674-681
Author(s):  
Hiroki Fukuchi ◽  
Yukinobu Hayashida ◽  
Kunio Inoue ◽  
Yoshifusa Sadamura
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Forkhead Box
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