Clinical effectiveness and toxicity of second-line irinotecan in advanced gastric and gastroesophageal junction adenocarcinoma: a single-center observational study

Ochenduszko, Sebastián; Püsküllüoğlu, Mirosława; Konopka, Kamil; Fijorek, Kamil; Słowik, Agnieszka; Pędziwiatr, Michał; Budzyński, Andrzej

doi:10.1177/1758834016689029

Cited by 6 publications

(7 citation statements)

References 26 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that IRI is an effective therapeutic agent as a second-line treatment of advanced gastric and gastroesophageal adenocarcinomas. 10 Besides, IRI therapy alone is considered a salvage-line treatment of advanced gastric cancer in clinical practice. 24 Even though cytotoxic chemotherapy of gastric cancer patients with IRI is capable of enhancing the antitumor effects of other treatments, acquired chemoresistance remains a serious clinical problem in gastric cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

Zhu¹,

Guo²,

Chen³

et al. 2020

OTT

View full text Add to dashboard Cite

Background: Irinotecan (IRI) is considered an option for second-line treatment of advanced gastric cancer; however, acquired drug resistance currently limits its clinical application. Recently, many researchers have shown that autophagy plays a crucial role in the resistance of tumor cells to chemotherapy and radiotherapy. In this study, we investigated the relationship between autophagy and antitumor activity of IRI in gastric cancer cells. Methods: We used MTT assay, flow cytometry and immunofluorescence staining to detect viability, apoptosis and autophagy in gastric cancer. Western blotting assay was used to determine the expression of LC3, Beclin-1, P62, cleaved PARP and Caspase 3. In vivo animal study was performed finally. Results: We found that IRI treatment dose-and time-dependently inhibited growth and induced apoptosis in gastric cancer cells. Moreover, IRI treatment caused autophagy in these cells, whereas autophagy inhibitors-3-methyladenine (3-MA), chloroquine (CQ), and Beclin-1 small interfering RNA (siRNA)-suppressed cytotoxicity of IRI. A mechanistic analysis showed that IRI-induced autophagy and apoptosis were related to increased reactive oxygen species (ROS) accumulation and activation of the JNK-and p38-MAPK pathways. Further in vivo experiments revealed that IRI suppressed tumor growth, induced autophagy, and stimulated the JNK-and p38-MAPK pathways, whereas 3-MA attenuated these effects. Conclusion: Taken together, these results indicate that IRI stimulates the ROS-related JNKand p38-MAPK pathways to promote autophagy-dependent apoptosis. Thus, a combination of IRI with a pharmacological autophagy enhancer may be a promising therapeutic strategy against gastric cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] It has also been applied to gastric cancer treatment. 9,10 Nonetheless, the therapeutic effect of IRI is still hampered by acquired chemotherapy resistance. 11 Therefore, it is necessary to devise a promising and safe treatment regimen to overcome drug resistance and reduce drug side effects in gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

Zhu¹,

Guo²,

Chen³

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…GC is usually diagnosed in locally advanced stage. Prognosis is poor, with 5-year OS of 5–20% [ 5 ]. Surgery is considered the current standard recommendation.…”

Section: Discussionmentioning

confidence: 99%

The role of different adjuvant therapies in locally advanced gastric adenocarcinoma

et al. 2018

View full text Add to dashboard Cite

Background and PurposeComplete surgical resection remains the only curative treatment option in locally advanced gastric cancer (GC). Several studies were conducted to prevent local recurrence and to increase the chance of cure. The aim of this study was to summarize our experience in locally advanced GC patients treated with adjuvant chemoradiotherapy (CRT) and to evaluate overall survival (OS), disease-free survival (DFS), toxicity rate and compliance to treatment.Materials and MethodsLocally advanced GC stage IB-III were included. Adjuvant CRT consisted of 45–50.4 Gy (1.8 Gy/day, 5 days/week) with concomitant Macdonald regimen (Mcd) or Epirubicin, Cisplatin and 5-Fluorouracil (ECF) scheme. Univariate and multivariate analysis of several prognostic factors for OS was conducted.ResultsFourty-nine GC patients were treated: 24 received Mcd and 25 received ECF. Median follow up was 48 months. Acute grade 3–4 toxicity was observed in 6 patients. The 2-year and 5-year OS rates were 65.3% and 41.5%, respectively. The 2-year and 5-year DFS were 59.2% and 41.2%, respectively. No prognostic factors were significantly associated with OS.ConclusionsAdjuvant CRT is a feasible strategy in locally advanced GC. It has an acceptable toxicity rate and it is able to increase both DFS and OS.

show abstract

“…Since a majority of patients are diagnosed with GC in locally advanced stage. Advanced disease carries a poor prognosis, with 5-year OS of 5-20% [3,4]. Thus despite decreasing incidence, the mortality rate associated with GC remains relatively high.…”

Section: Introductionmentioning

confidence: 99%

A methylation‐based mRNA signature predicts survival in patients with gastric cancer

Sun

Zhang

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC. Methods: Four genomics profiling datasets were used to identify MDEGs. Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis were used to explore the biological roles of MDEGs in GC. Univariate Cox and LASSO analysis were used to identify survival-related MDEGs and to construct a MDEGs-based signature. The prognostic performance was evaluated in two independent cohorts. Results: We identified a total of 255 MDEGs, including 192 hypermethylation-low expression and 63 Hypomethylation-high expression genes. The univariate Cox regression analysis showed that 83 MDEGs were associated with overall survival. Further we constructed an eight-MDEGs signature that was independent predictive of prognosis in the training cohort. By applying the eight-MDEGs signature, patients in the training cohort could be categorized into high-risk or low-risk subgroup with significantly different overall survival (HR = 2.62, 95% CI 1.71-4.02, P < 0.0001). The prognostic value of the eight-MDEGs signature was confirmed in another independent GEO cohort (HR = 1.35, 95% CI 1.03-1.78, P = 0.0302) and TCGA-GC cohort (HR = 1.85, 95% CI 1.16-2.94, P = 0.0084). Multivariate cox regression analysis proved the eight-MDEGs signature was an independent prognostic factor for GC. Conclusion: We have thus established an innovative eight-MDEGs signature that is predictive of overall survival and could be a potentially useful guide for personalized treatment of GC patients.

show abstract

Clinical effectiveness and toxicity of second-line irinotecan in advanced gastric and gastroesophageal junction adenocarcinoma: a single-center observational study

Cited by 6 publications

References 26 publications

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

The role of different adjuvant therapies in locally advanced gastric adenocarcinoma

A methylation‐based mRNA signature predicts survival in patients with gastric cancer

Contact Info

Product

Resources

About