Abstract 3307: Chemopotentiation by low dose fractionated radiation therapy in colon cancer cells

2015 ◽  
Author(s):  
Teresa Smith ◽  
Palak R. Parekh ◽  
Elizabeth T. Chang ◽  
Michael Chuong ◽  
France Carrier
Keyword(s):  
Colon Cancer ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Low Dose ◽  
Colon Cancer Cells ◽  
Fractionated Radiation Therapy ◽  
Fractionated Radiation

Investigating chemopotentiation by low-dose fractionated radiation therapy for disseminated intra-abdominal gastric cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 242-242
Author(s):  
France Carrier ◽  
Palak Parekh ◽  
Eduardo Solano-Gonzalez ◽  
Xinrong Ma ◽  
Kayla Tighe ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Low Dose ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Potential Biomarker ◽  
Fractionated Radiation Therapy ◽  
Fractionated Radiation

242 Background: Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. There is currently no modality that has been shown to prolong survival of this patient sub-population. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, the Dual Oxidase 2 (DUOX2) enzyme. Methods: Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or lower levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; chemotherapy consisting of a modified regimen of docetaxel, cisplatin and 5’-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 15 cGy in three days), 4; mDCF and LD-WART. Blood was harvested at day 14 and 45 and cancer progression was evaluated by fluorescence imaging (Xenogen). Results: The combined regimen was well tolerated in all animals and led to DUOX2 upregulation, increased serum protein oxidation and reduced cancer progression in the DUOX2 positive tumors. Tumors expressing lower DUOX2 levels were more sensitive to chemotherapy but no additional benefit was obtained with LD-WART. The potential clinical significance of these findings is exemplified by a tumor microarray demonstrating that only about 46% of human gastric tumors expressed DUOX2. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-kB upregulation and VEGF down regulation. Moreover, the combined regimen of mDCF and LDFRT was also effective on a Cancer Stem Cell (CSC)-Like subpopulation of mouse gastric cancer cells. Conclusions: Taken together these data suggest that DUOX2 could be used as a potential biomarker for patient stratification for chemopotentiation by LD-WART for positive tumors while chemotherapy alone would be more effective for DUOX2 negative tumors. The absence of added toxicity suggests that these cycles could be repeated.

Increasing the colon cancer cells sensitivity toward radiation therapy via application of Oct4–Sox2 complex decoy oligodeoxynucleotides

2020 ◽  
Vol 47 (9) ◽  
pp. 6793-6805
Author(s):  
Behrooz Johari ◽  
Hamed Rezaeejam ◽  
Mohammad Moradi ◽  
Zahraa Taghipour ◽  
Zohreh Saltanatpour ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Colon Cancer Cells

scholarly journals EFFECT OF ANTITUMOR DRUGS IN LOW CONCENTRATIONS ON THE BIOLOGICAL, IMMUNOPHENOTYPIC AND CYTOGENETIC CHARACTERISTICS OF HUMAN COLON CANCER CELLS in vitro

2017 ◽  
Vol 39 (1) ◽  
pp. 17-24
Author(s):  
N Bezdieniezhnykh ◽  
O Kovalova ◽  
O Lykhova ◽  
R Kocherga ◽  
A Vorontsova ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Low Dose ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Cells With Micronuclei ◽  
Human Colon Cancer Cells ◽  
Ht 29

Objective: To estimate the impact of the low-dose anticancer drugs (ACD) with the different mechanisms of action and human interferon (IFN) alpha 2b on the biological properties, immunophenotypic and cytogenetic characteristics of colon cancer cells in vitro. Materials and Methods: The study was performed on human colon cancer cell lines COLO 205, HT-29 and 3C-P treated with ACD and IFN in subtoxic concentrations. Expression of CD44, N-cadherin, vimentin, β-catenin, ERCC1 and Slug was assessed by immunocytochemical method. Using cytogenetic analysis, the numbers of mitoses, cells with micronuclei, apoptotic cells and cells with nuclear protrusions were studied. Results: The prolonged exposure (up to 30 days) of colon cancer cells to low-dose ACD (0.2–0.5 µg/ml cisplatin and 0.1–0.2 µg/ml irinotecan) in combination with IFN (500–1000 IU/ml) led to 37-fold decreased colony-forming activity of these cell and 10-fold reduction of the number of cells expressing mesenchymal protein markers (N-cadherin, vimentin). Also, in COLO 205 cells treated with ACD and IFN the number of SLUG- and CD44-positive cells decreased by 92 and by 85%, respectively. Long-term cultivation of HT-29 cells in the presence of cisplatin and IFN resulted in 5-fold suppression of ERCC1 expression. The cytogenetic analysis has shown that the ACD, IFN and their combinations in subtoxic concentrations caused significant genotoxic effect, suppression of cell proliferation and accumulation of cells with micronuclei. The sensitivity of colon cancer cells to ACD in standard cytotoxic concentrations did not change after prolonged low-dose exposure. Conclusion: The data showed that the prolonged action of the low doses of ACD on human colon cancer cells resulted in the suppression of cell proliferation, colony-forming activity in soft agar, expression of epithelialmesenchymal transition-associated markers and significant cytogenetic changes.

Sign in / Sign up

Export Citation Format

Share Document