scholarly journals A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma

2014 ◽  
Vol 44 (4) ◽  
pp. 1146-1152 ◽  
Author(s):  
GULBOSTAN YUSUP ◽  
YASUNORI AKUTSU ◽  
MURADIL MUTALLIP ◽  
WEI QIN ◽  
XIN HU ◽  
...  
2019 ◽  
Vol 19 (8) ◽  
pp. 1021-1028 ◽  
Author(s):  
Fanghua Qiu ◽  
Lifang Liu ◽  
Yu Lin ◽  
Zetian Yang ◽  
Feng Qiu

Background:Esophageal squamous cell carcinoma (ESCC), the most prevalent histologic subtype of esophageal cancer, is an aggressive malignancy with poor prognosis and a high incidence in the East. Corilagin, an active component present in Phyllanthus niruri L., has been shown to suppress tumor growth in various cancers. However, the effects of corilagin on ESCC and the mechanisms for its tumor suppressive function remain unknown.Methods:Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assays. Annexin V/PI double-staining was performed to assess cell apoptosis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. A xenograft mice model was used to assess the in vivo antitumor effects of corilagin alone or in combination with cisplatin.Results:We for the first time showed that corilagin was effectively able to inhibit ESCC cell proliferation and induce cell apoptosis. Additionally, our results validated its antitumor effects in vivo using a xenograft mouse model. Mechanistically, we found that corilagin caused significant DNA damage in ESCC cells. We found that corilagin could significantly attenuate the expression of the E3 ubiquitin ligase RING finger protein 8 (RNF8) through ubiquitin-proteasome pathway, leading to the inability of DNA damage repair response and eventually causing cell apoptosis. Furthermore, we also showed that corilagin substantially enhanced the antitumor effects of chemotherapy drug cisplatin both in vitro and in vivo.Conclusion:Our results not only provided novel and previously unrecognized evidences for corilagin-induced tumor suppression through inducing DNA damage and targeting RNF8 in ESCC, but also highlighted that corilagin might serve as an adjunctive treatment to conventional chemotherapeutic drugs in ESCC patients.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4147-TPS4147
Author(s):  
Feng Wang ◽  
Xiangrui Meng ◽  
Qingxia Fan

TPS4147 Background: Approximately 40% of patients (pts) with esophageal cancer are diagnosed with advanced unresectable or metastatic disease; the 5-year survival rate for advanced disease is 5%. No standard therapy is available in China for Advanced Esophageal Squamous Cell Carcinoma(ESCC) patients progressed after first-line chemotherapy.Inhibition of programmed cell death protein-1 (PD-1) has demonstrated promising antitumor activity and manageable safety in pts with advanced unresectable or metastatic ESCC. SHR-1210, a humanized IgG4 monoclonal antibody, has high affinity and specificity for PD-1 molecule. SHR-1210 was generally well tolerated and had preliminary antitumor effects in pts with solid tumors, including ESCC. Nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody h-R3, has been shown to be effective and safe in the treatment of head and neck cancer,non-small cell lung cancer (NSCLC) and esophageal Cancer in several phase II studies.The purpose of this study is to observe and evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210 combined with nimotuzumab as second-line therapy in patients with advanced ESCC. Methods: Patients, age 18-75, with measurable tumor lesion, failed in or progression after 1st line chemotherapy, were enrolled in this study.Patients received SHR-1210 200 mg once every 2 weeks (Q2W) combined nimotuzumab 200 mg weekly until disease progression, death or unacceptable toxicity.Assessments included response by RECIST v1.1 every 6 wks and safety (physical examination, vital signs, ECOG PS, laboratory tests).The primary endpoint is the objective response rate (ORR),and the secondary end points include the diseases control rate (DCR),duration of response (DOR),progression-free survival (PFS),and overall survival(OS). Additionally, we try to identify biomarker to predict efficacy of SHR-1210 and Nimotuzumab with target capture sequencing and gene expression profile as exploratory endpoints. Clinical trial information: NCT03766178.


2013 ◽  
Vol 209 (1) ◽  
pp. 6-9 ◽  
Author(s):  
Thiago Simão Gomes ◽  
Juliana Noguti ◽  
Nora Manoukian Forones ◽  
Flavio Oliveira Lima ◽  
Cristine Dobo ◽  
...  

2005 ◽  
Vol 27 (6) ◽  
pp. 1214-1221 ◽  
Author(s):  
Huiying Zhi ◽  
Lin Wang ◽  
Jian Zhang ◽  
Chuannong Zhou ◽  
Fang Ding ◽  
...  

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