Immunohistochemical detection of high-mobility group box 1 correlates with resistance of preoperative chemoradiotherapy for lower rectal cancer: a retrospective study

Hongo, Kumiko; Kazama, Shinsuke; Tsuno, Nelson H.; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

doi:10.1186/1477-7819-13-7

Cited by 17 publications

(24 citation statements)

References 47 publications

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“…In the present study, it was revealed that a deficiency in HMGB1 suppressed the proliferation of ESCC cells both before and after irradiation in vitro and in vivo, indicating the significant role that HMGB1 played in the growth of esophageal cancer. In clinical studies of HMGB1 detection in nasopharyngeal carcinoma (13), rectal cancer (11), and our own present study of esophageal cancer, comparative studies on metastasis in cancer biopsies revealed that overexpression of HMGB1 may contribute to metastasis. Then, a wound healing and Transwell assays were carried out using 2 esophageal cancer cell lines to confirm the clinical findings aforementioned in vitro.…”

Section: Discussionmentioning

confidence: 48%

“…Therefore, the discovery of effective therapeutic targets to enhance radiosensitivity may improve the survival of ESCC patients. The overexpression of HMGB1 has been implicated in multiple cancers, including breast (18), rectal (11), bladder (19) and gallbladder cancer (20), pleural mesothelioma (21), nasopharyngeal carcinoma (22), and esophageal cancer (23). During tumor development and cancer treatment, diverse roles for HMGB1 have been revealed in previous studies, including roles in inflammation (24), immune responses (25), angiogenesis (26), DNA damage repair (27), autophagy (28), proliferation, apoptosis, invasion and metastasis (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies, HMGB1 was revealed to be strongly associated with the occurrence and progression of tumors, and its expression level has been connected with the radiosensitivity of various types of cancers (8)(9)(10)(11), however, the underlying mechanism is unclear. In the present study, the expression level of HMGB1 was detected in both esophageal cancer tissues and cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression

et al. 2018

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Radiotherapy (RT) is a traditional and important treatment for carcinoma of the esophagus along with surgery and chemotherapy. High mobility group box 1 (HMGB1) plays a crucial part in inhibiting the apoptosis of cancer cells after irradiation treatment. The present study, was designed to analyze the function of HMGB1 in esophageal cancer progression and elucidate the effects of HMGB1 on the radiosensitivity of human esophageal cancer cell lines. In the present study, an immunohistochemical evaluation of HMGB1 was performed on 77 biopsies, and the results revealed that HMGB1 overexpression was positively correlated with gross tumor volume (GTV), tumor-node-metastasis (TNM) stage, T classification, distant metastasis, and relapse and negatively correlated with patient survival rates, suggesting that HMGB1 acts as a key factor in the development of esophageal cancer. An shRNA targeting HMGB1 was designed for the knockdown of HMGB1 in ECA109 and TE13 cells, and the transfection efficiency of the shRNA was assessed using quantitative real-time reverse transcription polymerase chain reaction and western blot analysis. CCK-8 and clonogenic assays were used to analyze the effect of HMGB1 on the proliferation and radiosensitivity, respectively, of esophageal cancer cells in vitro. The influence of HMGB1 on radiation-induced changes in the migration, invasion, and cell cycle as well as apoptosis of tumor cells was examined by wound-healing and Transwell assays and flow cytometry, respectively. In addition, xenograft tumor models were constructed to observe the effect of HMGB1 on tumor growth in vivo. The results of the study in vitro revealed that the proliferation of the HMGB1-shRNA group decreased after irradiation, and the radiation treatment reduced the tumor volume of the xenograft model which was more marked in HMGB1-shRNA group. Moreover, HMGB1 was involved in the phosphorylation of H2AX after irradiation, and HMGB1 knockdown blocked the cell cycle in the G0/G1 phase and increased apoptosis. HMGB1 deficiency was also correlated with the upregulation of p16, Bax and caspase-9 and the downregulation of MMP-2, MMP-9, cyclin D1, CDK4, γH2AX and Bcl-2. These data indicated that the overexpression of HMGB1 prior to treatment was correlated with poor clinical outcome in esophageal carcinoma and that knockdown HMGB1 expression in human esophageal cancer cell lines increased their radiosensitivity by allowing the induction of apoptosis and G0/G1 arrest after exposure to radiation.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression

et al. 2018

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“…Though with a higher rate of microsatellite instability (MSI) in MC, the predictive value of MSI in response to radiotherapy is still controversial272829. Expression of high-mobility group box 1, Paf15 and several microRNAs had been reported to be associated with response to chemoradiotherapy3031323334. Unfortunately, neither lymph node dissemination nor molecular phenotype status had been recorded in our study and these analyses could not be performed.…”

Section: Discussionmentioning

confidence: 79%

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Chen

Wang

et al. 2017

Sci Rep

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As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC.

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“…14,15 Previous study has also found that HMGB1 expression in lower rectal cancer correlates with the resistance of patients treated with preoperative chemoradiotherapy. 16 HMGB1 is reportedly regulated by multiple signaling pathways. 12 However, whether inhibition of HMGB1 expression is involved in OXA-induced cytotoxicity in CRC cells is still unclear.…”

mentioning

confidence: 99%

Metformin increases the cytotoxicity of oxaliplatin in human DLD‐1 colorectal cancer cells through down‐regulating HMGB1 expression

Huang

Lin

Chen

et al. 2018

J of Cellular Biochemistry

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Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent. In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells. The results showed that treatment with OXA increased HMGB1 expression in the ERK1/2- and Akt-dependent manners in DLD-1 cells. HMGB1 gene knockdown enhanced the cytotoxicity and cell growth inhibition of OXA. Moreover, OXA-increased HMGB1 expression was by inducing NF-κB-DNA-binding activity to in DLD-1 cells. Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level. These findings may have implications for the rational design of future drug regimens incorporating OXA and metformin for the treatment of CRC.

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Immunohistochemical detection of high-mobility group box 1 correlates with resistance of preoperative chemoradiotherapy for lower rectal cancer: a retrospective study

Cited by 17 publications

References 47 publications

Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression

Radiosensitization of esophageal carcinoma cells by knockdown of HMGB1 expression

Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

Metformin increases the cytotoxicity of oxaliplatin in human DLD‐1 colorectal cancer cells through down‐regulating HMGB1 expression

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