The Irinotecan/5-Fluorouracil Combination Induces Apoptosis and Enhances Manganese Superoxide Dismutase Activity in HT-29 Human Colon Carcinoma Cells

Grivicich, Ivana; Regner, Andréa; Rocha, Adriana Brondani da; Kayser, Guilherme B.; Schunemann, Daniel Pretto; Grass, Luciano B.; Alves, Pedro A. G.; Henriques, João Antônio Pêgas; Schwartsmann, Gilberto

doi:10.1159/000085617

Cited by 28 publications

(19 citation statements)

References 103 publications

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“…With the APH assay, classic drug combinations such as 5-FU and Irinotecan, which already showed increased response rate, time to progression, and survival in patients, 50 can now be more easily monitored in spheroids and compared with monolayer data. 38,[51][52][53] A particular prospective is the potential application of the spheroid-APH assay platform for the testing of single and combined therapeutic strategies with new, target, and/or pathway-specific treatment modalities. Further experiments to evaluate the feasibility of this approach are in progress.…”

Section: Discussionmentioning

confidence: 99%

A Reliable Tool to Determine Cell Viability in Complex 3-D Culture: The Acid Phosphatase Assay

Friedrich¹,

Eder²,

Castaneda³

et al. 2007

SLAS Discovery

184

144

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Cell-based assays are more complex than cell-free test systems but still reflect a highly artificial cellular environment. Incorporation of organotypic 3-dimensional (3-D) culture systems into mainstream drug development processes is increasingly discussed but severely limited by complex methodological requirements. The objective of this study was to explore a panel of standard assays to provide an easy-handling, standardized protocol for rapid routine analysis of cell survival in multicellular tumor spheroid-based antitumor drug testing. Spheroids of 2 colon carcinoma cell lines were characterized for evaluation. One of the assay systems tested could reliably be used to determine cell viability in spheroids. The authors verified that the acid phosphatase assay (APH) is applicable for single spheroids in 96-well plates, does not require spheroid dissociation, and is linear and highly sensitive for HT29 and HCT-116 spheroids up to diameters of 650 µm and 900 µm, consisting of 40,000 and 80,000 cells, respectively. Treatment of HT29 and HCT-116 cells with 5-fluorouracil, Irinotecan, and C-1311 revealed critically reduced drug efficacies in 3-D versus monolayer culture, which is discussed in light of literature data. The experimental protocol presented herein is a small but substantial contribution to the establishment of sophisticated 3-D in vitro systems in the antitumor drug screening scenario. (Journal of Biomolecular Screening 2007:925-937)

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Section: Discussionmentioning

confidence: 99%

A Reliable Tool to Determine Cell Viability in Complex 3-D Culture: The Acid Phosphatase Assay

Friedrich¹,

Eder²,

Castaneda³

et al. 2007

SLAS Discovery

184

144

View full text Add to dashboard Cite

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“…The immunopositivity, however, was found to be rare in normal colorectal epithelium. The higher frequency of LC3 expression in colorectal adenocarcinomas compared with the corresponding normal tissue may indicate that the ex- each pathway may play an important role in cell death, which is associated with chemotherapy regimens (3,5,8,13,16). Further investigation is therefore needed to clarify the contribution of CC8, CC9, AIF, and LC3 in gastrointestinal cancer prognosis or response to treatment.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of cell death pathways in gastrointestinal adenocarcinoma

Shintani

Sangawa

Yamao³

et al. 2011

Biomed. Res.

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Caspase-8 and caspase-9 play crucial roles in the extrinsic and intrinsic apoptotic pathways, respectively. The nuclear translocation of apoptosis-inducing factor (AIF) is involved in caspase-independent apoptosis. Microtubule-associated protein 1 light chain 3 (LC3) plays a pivotal role in autophagy. In the present study, we analyzed the expression of cleaved caspase-8 (CC8), cleaved caspase-9 (CC9), AIF, and LC3 in 160 gastrointestinal adenocarcinomas. The nuclear expression of AIF was rare. The expression of CC8 in gastric and colorectal adenocarcinomas did not differ, whereas the percentage of CC9-positive tumors in gastric adenocarcinomas was significantly higher than in colorectal adenocarcinomas. In contrast, the percentage of LC3-positive tumors in gastric adenocarcinomas was significantly lower than in colorectal adenocarcinomas. CC8 and CC9 occasionally co-existed in the same tumor cells in gastric adenocarcinoma. However, LC3-positive tumor cells in colorectal adenocarcinomas were constantly negative for CC8. No correlation was identified between the expression of any markers and clinicopathological parameters. These results suggest that different cell death pathways are activated in a manner that depends upon the primary site and cell type. The extrinsic and intrinsic apoptotic pathways may be mutually regulated in gastric adenocarcinomas. Also, autophagy may function as a cellular guardian to avoid apoptosis in colorectal adenocarcinomas.

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“…Recently, Grivicich et al [14] reported that CPT-11 and 5-FU combination therapy induces apoptosis. Oxaliplatin, the key drug of FOLFOX, is mainly excreted into urine.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Study of the Saltz Regimen for Metastatic Colorectal Cancer in a Hemodialyzed Patient

Akiyama

Nakayama

Takami³

et al. 2007

Chemotherapy

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Objective: Combination therapy with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin is widely used for the treatment of metastatic colorectal cancer. However, little is known about the safety of chemotherapy of malignancies in hemodialysis (HD) patients. We encountered a patient with colorectal carcinoma on HD. We decided to administer combination chemotherapy while monitoring the pharmacodynamics of the patient. Case Report: A 74-year-old male received regular HD 3 times a week because of type 1 diabetes mellitus. He was diagnosed with stage IV colorectal cancer in November 2004. After sigmoidectomy, the patient received chemotherapy: a weekly schedule of CPT-11 (50 mg/m²) was administered followed by l-leucovorin (10 mg/m²) and 5-FU (400 mg/m²) just after HD. During the course, the plasma concentrations of both SN-38, an active metabolite of CPT-11, and 5-FU were not increased compared with those of patients with normal renal function. Our patient presented with grade III hematological toxicity that was easily recovered by granulocyte colony-stimulating factor. Conclusion: These data suggest that the dose-reduced Saltz regimen can be feasible for colorectal cancer patients receiving dialysis as postoperative adjuvant chemotherapy.

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The Irinotecan/5-Fluorouracil Combination Induces Apoptosis and Enhances Manganese Superoxide Dismutase Activity in HT-29 Human Colon Carcinoma Cells

Cited by 28 publications

References 103 publications

A Reliable Tool to Determine Cell Viability in Complex 3-D Culture: The Acid Phosphatase Assay

A Reliable Tool to Determine Cell Viability in Complex 3-D Culture: The Acid Phosphatase Assay

Immunohistochemical analysis of cell death pathways in gastrointestinal adenocarcinoma

Pharmacodynamic Study of the Saltz Regimen for Metastatic Colorectal Cancer in a Hemodialyzed Patient

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