Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

Yang, Dejun; Shi, Jianghong; Fu, Hongbing; Wei, Ziran; Xu, Jiapeng; Hu, Zunqi; Yan, Ran; Cai, Qing-Qing

doi:10.1007/s13277-016-5061-7

Cited by 15 publications

(16 citation statements)

References 39 publications

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“…Interestingly, patients who recurred more than 12 months after initial treatment showed better survival outcomes. This observation may be due to inherent differences in tumor biology across the patient cohort, rendering different grades of tumor aggressiveness and response to treatment, as has been reported in the literature 25, 26, 27, 28…”

Section: Discussionmentioning

confidence: 89%

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

Koong

Toesca

Eyben

et al. 2017

Advances in Radiation Oncology

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PurposeLocally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT).Methods and materialsOutcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions).ResultsMedian follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm3 (range, 14-89 cm3). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen.ConclusionsOur report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.

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Section: Discussionmentioning

confidence: 89%

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

Koong

Toesca

Eyben

et al. 2017

Advances in Radiation Oncology

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“…These prognostic biomarkers associate with tumor clinical stage, overall survival (OS) time, and disease-free survival (DFS) time by regulating tumor biological behavior. For example, integrin β1 modulates tumor resistance to gemcitabine and serves as an independent prognostic factor in PDAC ( 8 ). Regenerating family member proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in PDAC ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-κB axis

Wu³

et al. 2017

International Journal of Oncology

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Stress associated endoplasmic reticulum protein 1 (SERP1), can cause accumulation of unfolded proteins in ER stress. However, studies on the role of SERP1 in pancreatic ductal adenocarcinoma (PDAC) are still incomplete. The present study aimed at identifying whether SERP1 acts as a potential novel prognostic marker of PDAC, and analyzed its possible mechanism. GEO database analysis showed SERP1 was significantly upregulated in PDAC tissues, and strongly associated with advanced clinical stage of PDAC patients from TCGA database. Univariate and multivariate Cox regression analysis further revealed SERP1 high expression was an independent factor for the prognosis of PDAC. Gene set enrichment analysis (GSEA) revealed that SERP1 was mainly involved in regulating cell apoptosis and nuclear factor-κB (NF-κB) signaling pathway, and downregulated SERP1 significantly promoted PANC-1 cell apoptosis. To further explore its possible mechanism, protein-protein interaction (PPI) and gene ontology (GO) analysis showed the functions of proteins interacting with SERP1 were mainly enriched in regulating cell apoptosis, and SRP receptor β subunit (SRPRB) was the core of the whole PPI network. The expression of SERP1 was negatively correlated with SRPRB expression. In vitro, downregulated SERP1 significantly increased SRPRB expression. Furthermore, upregulated SRPRB could increase cell apoptosis rate and decreased the expression level of NF-κB and the phosphorylation NF-κB. The above results indicated that SERP1 as a potential novel prognostic marker of PDAC probably via regulating cell apoptosis and NF-κB activation, which may be associated with SRPRB.

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“…We found that the expression of CD29 was significantly reduced. This integrin has been linked to gemcitabine resistance and a poor outcome in pancreatic cancer [ 35 ]. Moreover, its knockdown has been reported to inhibit cell adhesion, migration, proliferation, and metastasis of pancreatic cancer, unveiling CD29 as a potential therapeutic target [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells

Khalkar

Díaz-Argelich

Palop

et al. 2018

IJMS

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Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds.

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Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

Cited by 15 publications

References 39 publications

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-κB axis

Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells

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