scholarly journals Charged Particle Irradiation for Pancreatic Cancer: A Systematic Review of In Vitro Studies

2022 ◽  
Vol 11 ◽  
Author(s):  
Dandan Wang ◽  
Ruifeng Liu ◽  
Qiuning Zhang ◽  
Hongtao Luo ◽  
Junru Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Charged Particle ◽  
Cell Lines ◽  
Proton Irradiation ◽  
Ion Irradiation ◽  
Carbon Ion ◽  
Photon Irradiation ◽  
Particle Irradiation ◽  
Radiobiological Effects

PurposeGiven the higher precision accompanied by optimized sparing of normal tissue, charged particle therapy was thought of as a promising treatment for pancreatic cancer. However, systematic preclinical studies were scarce. We aimed to investigate the radiobiological effects of charged particle irradiation on pancreatic cancer cell lines.MethodsA systematic literature search was performed in EMBASE (OVID), Medline (OVID), and Web of Science databases. Included studies were in vitro English publications that reported the radiobiological effects of charged particle irradiation on pancreatic cancer cells.ResultsThirteen carbon ion irradiation and seven proton irradiation in vitro studies were included finally. Relative biological effectiveness (RBE) values of carbon ion irradiation and proton irradiation in different human pancreatic cancer cell lines ranged from 1.29 to 4.5, and 0.6 to 2.1, respectively. The mean of the surviving fraction of 2 Gy (SF2) of carbon ion, proton, and photon irradiation was 0.18 ± 0.11, 0.48 ± 0.11, and 0.57 ± 0.13, respectively. Carbon ion irradiation induced more G2/M arrest and a longer-lasting expression of γH2AX than photon irradiation. Combination therapies enhanced the therapeutic effects of pancreatic cell lines with a mean standard enhancement ratio (SER) of 1.66 ± 0.63 for carbon ion irradiation, 1.55 ± 0.27 for proton irradiation, and 1.52 ± 0.30 for photon irradiation. Carbon ion irradiation was more effective in suppressing the migration and invasion than photon irradiation, except for the PANC-1 cells.ConclusionsCurrent in vitro evidence demonstrates that, compared with photon irradiation, carbon ion irradiation offers superior radiobiological effects in the treatment of pancreatic cancer. Mechanistically, high-LET irradiation may induce complex DNA damage and ultimately promote genomic instability and cell death. Both carbon ion irradiation and proton irradiation confer similar sensitization effects in comparison with photon irradiation when combined with chemotherapy or targeted therapy.

scholarly journals In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

2013 ◽  
Vol 54 (suppl 1) ◽  
pp. i113-i119 ◽  
Author(s):  
R. A. El Shafie ◽  
D. Habermehl ◽  
S. Rieken ◽  
A. Mairani ◽  
L. Orschiedt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Carbon Ion Radiotherapy ◽  
In Vitro Evaluation ◽  
Carbon Ion

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

Biologically optimized schedule of gemcitabine and nab-paclitaxel regimen in metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4168-TPS4168
Author(s):  
Laith I. Abushahin ◽  
Anne M. Noonan ◽  
John L. Hays ◽  
Pannaga G. Malalur ◽  
Ashish Manne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Dose Intensity ◽  
Standard Of Care ◽  
Significance Level ◽  
Pancreatic Cancer Cells ◽  
Metastatic Pancreatic Adenocarcinoma

TPS4168 Background: Metastatic pancreatic adenocarcinoma has a poor prognosis, and improvements in therapy have been challenging. Alongside efforts in developing novel agents, there is a need to optimize and maximize the benefit of currently approved drugs. Gemcitabine + nab-paclitaxel is a frequently used regimen for pancreatic adenocarcinoma. Nab-paclitaxel is albumin–bound chemotherapy; hence the role of albumin uptake is critical for its effect. Caveolae are small membrane invaginations essential for transendothelial albumin uptake. Cav-1 is the principal structural component of caveolae. Williams and colleagues have published a series of preclinical studies demonstrating that tumor cell-specific Cav-1 expression directly correlates with albumin and albumin-bound chemotherapy uptake and subsequent apoptotic response in tumor cells. In vitro studies showed that exposure of pancreatic cancer cells to Gemcitabine resulted in up-regulation of Cav-1 peaking 48 hours after gemcitabine exposure. This Cav-1 up-regulation correlated with increased temporal albumin cellular uptake. In addition, Williams and colleagues noted that exposure of pancreatic cancer cell lines to Gemcitabine resulted in a time–specific re-entry of cells into the G2/M phase (nab-paclitaxel cytotoxicity phase) between 48-60 hours after gemcitabine treatment. Collectively this data suggest that infusing nab-paclitaxel after 48 hours of gemcitabine infusion would be optimal for both increased uptake as well as increased susceptible tumor cells. We had previously shown this effect on multiple cell lines as well as mouse models. Methods: This is a phase II trial; patients will receive a standard of care chemotherapy regimen consisting of FDA-approved Gemcitabine + nab-paclitaxel with modification of the schedule to deliver nab-paclitaxel 48 hours (2 days) after gemcitabine infusions. The primary endpoint is ORR, with a null hypothesis of 20% vs. a target of 35%. Employing a 2-stage design (minimax) and assuming 80% power and a 0.05 significance level, a total of 53 patients will be required. In the first stage, if at least 7/31 patients respond to therapy, an additional 22 patients will be added for a total of 53 patients. The study will be terminated early if ≤ six patients respond in the first stage. Observation of response in at least 16/53 patients would be required to warrant further investigation of this infusion schedule of combination therapy. The secondary endpoints include the safety of the regimen schedule, Relative dose intensity, disease control rate, PFS, and OS. The trial opened to enrollment in June 2020 and is accepting patients. Clinical trial information: NCT04115163.

scholarly journals Selenium Induces Pancreatic Cancer Cell Death Alone and in Combination with Gemcitabine

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 149
Author(s):  
David J. Wooten ◽  
Indu Sinha ◽  
Raghu Sinha
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Single Agent ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Death ◽  
Pancreatic Cancer Cells

Survival rate for pancreatic cancer remains poor and newer treatments are urgently required. Selenium, an essential trace element, offers protection against several cancer types and has not been explored much against pancreatic cancer specifically in combination with known chemotherapeutic agents. The present study was designed to investigate selenium and Gemcitabine at varying doses alone and in combination in established pancreatic cancer cell lines growing in 2D as well as 3D platforms. Comparison of multi-dimensional synergy of combinations’ (MuSyc) model and highest single agent (HSA) model provided quantitative insights into how much better the combination performed than either compound tested alone in a 2D versus 3D growth of pancreatic cancer cell lines. The outcomes of the study further showed promise in combining selenium and Gemcitabine when evaluated for apoptosis, proliferation, and ENT1 protein expression, specifically in BxPC-3 pancreatic cancer cells in vitro.

scholarly journals Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Hartmann ◽  
Philipp Schröter ◽  
Wolfram Osen ◽  
Daniel Baumann ◽  
Rienk Offringa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Ion Irradiation ◽  
Dose Range ◽  
Cancer Cell Line ◽  
Surface Expression ◽  
Photon Radiation ◽  
Immunomodulatory Effects ◽  
Carbon Ion ◽  
Dose Dependent

AbstractWhile for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-Db and H2-Kb was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.

Identification and characterization of CCK-B/gastrin receptors in human pancreatic cancer cell lines

1994 ◽  
Vol 266 (1) ◽  
pp. R277-R283 ◽  
Author(s):  
J. P. Smith ◽  
G. Liu ◽  
V. Soundararajan ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cells

The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth of human pancreatic cancer in a receptor-mediated fashion. The purpose of this study was to characterize the receptor responsible for the trophic effects of CCK in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer cells grown in vitro, the binding characteristics and optimal conditions of radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718) were examined. Specific and saturable binding was detected with [3H]L-365,260, and Scatchard analysis revealed that the data were consistent for a single site of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on protein concentration, time, temperature, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and postconfluent cultures, respectively. Subcellular fractionation studies revealed that binding was in the membrane fraction. Competition experiments indicated that L-365,260 and gastrin were more effective at displacing the radiolabeled L-365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L-364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic cancer cell lines in vitro and tumor tissue from xenografts in nude mice also revealed specific and saturable binding. These results provide the first identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and tumors and explain the effects of CCK on the growth of this malignancy.

Proteomic Analysis of Cell Lines and Primary Tumors in Pancreatic Cancer Identifies Proteins Expressed Only In Vitro and Only In Vivo

Pancreas ◽  
2020 ◽  
Vol 49 (8) ◽  
pp. 1109-1116
Author(s):  
Orla Coleman ◽  
Michael Henry ◽  
Fiona O'Neill ◽  
Sandra Roche ◽  
Niall Swan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Proteomic Analysis ◽  
Primary Tumors

scholarly journals Evaluation of the In Vitro Cytotoxic Activity of Caffeic Acid Derivatives and Liposomal Formulation against Pancreatic Cancer Cell Lines

Materials ◽  
2020 ◽  
Vol 13 (24) ◽  
pp. 5813
Author(s):  
Magdalena Zaremba-Czogalla ◽  
Anna Jaromin ◽  
Katarzyna Sidoryk ◽  
Agnieszka Zagórska ◽  
Marcin Cybulski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cytotoxic Activity ◽  
Caffeic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Liposomal Formulation ◽  
Caffeic Acid Derivatives

Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives. For this purpose, we analyzed twelve compounds and evaluated their in vitro cytotoxic activity against two human pancreatic cancer cell lines, along with a control, normal fibroblast cell line, by the classic MTT assay. Six out of twelve tested caffeic acid derivatives showed a desirable effect. To improve the therapeutic efficacy of such active compounds, we developed a formulation where caffeic acid derivative (7) was encapsulated into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000. Subsequently, we analyzed the properties of this formulation in terms of basic physical parameters (such as size, zeta potential, stability at 4 °C and morphology), hemolytic and cytotoxic activity and cellular uptake. Overall, the liposomal formulation was found to be stable, non-hemolytic and had activity against pancreatic cancer cells (IC50 19.44 µM and 24.3 µM, towards AsPC1 and BxPC3 cells, respectively) with less toxicity against normal fibroblasts. This could represent a promising alternative to currently available treatment options.

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