Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer

Sun, Dawei; Chen, Chengyu; Hu, Wensi; Zhong, Caiyun; Fan, Limin; Song, Xiaoming; Gai, Zhibo

doi:10.2147/ott.s178131

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…Sections were treated with the Envision + DAB kit (Dako, Glostrup, Denmark), according to the manufacturer’s instructions. A semi-quantitative blind method previously described was used to measure the staining intensity and the proportion of positive cells ( Sun et al, 2018 ). Ten visual fields were observed at 400X magnification.…”

Section: Methodsmentioning

confidence: 99%

The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin

et al. 2021

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Esophageal cancer is the ninth most common malignancy worldwide, ranking sixth in mortality. Platinum-based chemotherapy is commonly used for treating locally advanced esophageal cancer, yet it is ineffective in a large portion of patients. There is a need for reliable molecular markers with direct clinical application for a prospective selection of patients who can benefit from chemotherapy and patients in whom toxicity is likely to outweigh the benefit. The cytotoxic activity of platinum derivatives largely depends on the uptake and accumulation into cells, primarily by organic cation transporters (OCTs). The aim of the study was to investigate the impact of OCT expression on the clinical outcome of patients with esophageal cancer treated with oxaliplatin. Twenty patients with esophageal squamous cell carcinoma (SCC) were prospectively enrolled and surgical specimens used for screening OCT expression level by western blotting and/or immunostaining, and for culture of cancer cells. Sixty-seven patients with SCC who received oxaliplatin and for whom follow-up was available were retrospectively assessed for organic cation/carnitine transporter 2 (OCTN2) expression by real time RT-PCR and immunostaining. OCTN2 staining was also performed in 22 esophageal adenocarcinomas. OCTN2 function in patient-derived cancer cells was evaluated by assessing L-carnitine uptake and sensitivity to oxaliplatin. The impact of OCTN2 on oxaliplatin activity was also assessed in HEK293 cells overexpressing OCTN2. OCTN2 expression was higher in tumor than in normal tissues. In patient-derived cancer cells and HEK293 cells, the expression of OCTN2 sensitized to oxaliplatin. Patients treated with oxaliplatin who had high OCTN2 level in the tumor tissue had a reduced risk of recurrence and a longer survival time than those with low expression of OCTN2 in tumor tissue. In conclusion, OCTN2 is expressed in esophageal cancer and it is likely to contribute to the accumulation and cytotoxic activity of oxaliplatin in patients with esophageal carcinoma treated with oxaliplatin.

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Section: Methodsmentioning

confidence: 99%

The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin

et al. 2021

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“…VEGF may have an important role in tumor progression and metastatic spreading as well as in cancer angiogenesis [ 4 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. One of the regulators of VEGF-A is the NFE2L3 nuclear transcription factor which is associated with a poor prognosis in pancreatic cancer.…”

Section: Influence Of Vegf On Tumor Growth and Vascularizationmentioning

confidence: 99%

“…None of the patients had distant metastases before surgery, and they did not undergo preoperative chemotherapy or radiotherapy. Patients with a high expression of VEGFR-2 and a high level of tumor vascularization were characterized by a lower five-year survival rate ( p < 0.05) [ 24 ]. About 70% of the 408 examined BC patients had high VEGF-C expression which was strongly associated with severe tumor stages ( p = 0.019), significant Ki67 proliferation index, LN metastases (N3) and lymphatic vascular invasion in univariate analysis [ 4 ].…”

Section: Influence Of Vegf On Tumor Growth and Vascularizationmentioning

confidence: 99%

Cancer Angiogenesis and Opportunity of Influence on Tumor by Changing Vascularization

Maiborodin

Mansurova

Chernyavskiy

et al. 2022

JPM

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Based on the study of recent scientific literature devoted to neovascularization and angiogenesis in malignant neoplasms, it was concluded that there are many publications on each of the problems of tumor angiogenesis and vascularization. The formation of blood vessels in a tumor and certain aspects of the prognostic value of the severity of vascularization in almost all forms of cancer are considered. Special attention is paid to the peculiarities of angiogenesis in tumors of the female reproductive system. A large number of vessels in the tumor often indicates a poor prognosis. The influence of various factors on the initiation of angiogenesis and the process itself, as well as the possibility of suppressing such signals to slow down the formation of blood vessels and thus the development of the tumor are widely studied. The results of pharmacological suppression of tumor vessel formation demonstrate a good clinical outcome but one accompanied by a large number of severe adverse side effects. Such a significant amount of studies on each of the problems of tumor vascularization indicates the increasing importance of this area of oncology. At the same time, only a very small number of works are devoted to the study of the differences in angiogenesis and number of vessels between different parts of the tumor, as well as between the primary tumor node and its metastases. The refinement of the results is still to be done. It was noted that the expression of proangiogenic factors in metastases is usually higher than in the source of metastasis, and the expression in lymphogenous metastases is higher than in hematogenous ones.

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“…Particularly, downregulation of DAB2IP expression was reported to be associated with resistance to chemo or radio therapy and worse outcome in several types of human cancers [ 6 , 11 – 16 ]. Additionally, Sun et al reported that decreased expression of DAB2IP correlated with ESCC progression and poor prognosis in surgically resected samples [ 17 ]. To date, however, the molecular status of the DAB2IP gene in ESCC patients treated with definitive chemoradiotherapy and the relationship between the expression of DAB2IP and chemoradiosensitivity in ESCC has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway

Tong

Fang

et al. 2022

Cancer Cell Int

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Background Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy is rarely reported. Methods We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definitive chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC. Results Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway. Conclusions Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients.

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Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer

Cited by 9 publications

References 39 publications

The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin

The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin

Cancer Angiogenesis and Opportunity of Influence on Tumor by Changing Vascularization

DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway

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