New strategies in esophageal carcinoma: promises and problems

Xiong, Zhaohui; He, Jingxi; Chen, Xiaoxin Luke

doi:10.21037/jtd.2016.11.22

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…Recent studies indicate that various tumorigenic signaling pathways are involved in ESCC, such as tumor growth, cell cycle, angiogenesis, invasion and apoptosis [ 7 – 9 ], so targeting these signaling pathways may be strategies for treating ESCC. Target therapy also showed exciting effect when combined with immunotherapy [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

et al. 2018

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BackgroundSquamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application.MethodsFresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing.ResultsTwenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50–120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results.ConclusionsOur PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1379-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

et al. 2018

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“…1,2 As the main pathological type of esophageal cancer, ESCC accounts for about 90% of cases of esophageal cancer worldwide and distributes a generally poor prognosis due to lack of a singular effective clinical method for early diagnosis. 5,19 The still poor clinical outcome implies an urgent requirement to improve our recognition of the molecular mechanism underlying carcinogenesis of esophageal cancer, which may contribute to the development of novel prognostic methods. Accumulating evidence indicates that dysregulation of specific proteins is crucial for ESCC progression.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Despite considerable advances achieved in diagnosis and multimodality therapies, the overall 5-year survival rate for esophageal cancer remains approximately 17%. 2,5 Previous reports have shown that genetic variations frequently associated with the development of esophageal cancer include the p53 mutation, the inactivation of p16, the amplification of cyclin D1, and the amplification of c-Myc or the epidermal growth factor receptor. 3,6,7 The carcinogenesis and development of esophageal cancer is a complex process that involves cumulative mutations or amplification in multiple genes.…”

Section: Introductionmentioning

confidence: 99%

High expression of IGBP1 correlates with poor prognosis in esophageal squamous cell carcinoma

Jiang

Liang

et al. 2019

Int J Biol Markers

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Background: Immunoglobulin binding protein 1 (IGBP1) is an important signal transduction regulator that mediates various functions. However, its expression profile, role, and clinical significance in cancers are uncertain. The purpose of this study was to determine the expression profile and the prognostic significance of IGBP1 in esophageal squamous cell carcinoma (ESCC). Methods: Polymerase chain reaction assay, western blotting, and immunohistochemistry (IHC) assay were performed to examine IGBP1 expression in ESCC tissues and matched adjacent non-cancerous tissues. Moreover, IHC was used to evaluate IGBP1 expression in archived 190 paraffin-embedded ESCC specimens. Statistical analyses were applied to evaluate the prognostic value and the correlations between IGBP1 expression and the clinical parameters. Results: We found that the messenger RNA and protein levels of IGBP1 were up-regulated in the ESCC tissues compared with their adjacent non-cancerous tissues. High expression of IGBP1 in ESCC patients was positively associated with T classification ( P=0.013) and vital status ( P=0.03). The ESCC patients with higher IGBP1expression had a shorter survival time than those with lower IGBP1 expression. Importantly, multivariate analysis demonstrated that the expression of IGBP1 was an independent prognostic factor for ESCC ( P< 0.05). Conclusions: We provide the first evidence that increased IGBP1 expression correlates with poor prognosis of ESCC, and that IGBP1 may be a tumor promoter of ESCC, which provide a promising prognostic biomarker and therapeutic target for ESCC.

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“…Moreover, due to the dense submucosal lymphovascular network with direct connections to both the regional lymph nodes and the thoracic duct, the esophageal cancer could frequently have lymph node metastases in the early stage [ 6 ]. The targeted therapies, which have been demonstrated effective in other cancers such as lung cancer, breast cancer, showed limited therapeutic effects in the case of esophageal cancer [ 5 ]. Considering the necessity of developing effective therapeutic options, combinational drugs therapy can be a suitable option to treat esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells

et al. 2021

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Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro , to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.

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New strategies in esophageal carcinoma: promises and problems

Cited by 5 publications

References 19 publications

Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

High expression of IGBP1 correlates with poor prognosis in esophageal squamous cell carcinoma

Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells

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