Evidence map›Paper›PMID 25986235›Full record

ArticleJournal of experimental & clinical cancer research : CR2015

Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.

Zhengxiang Zhang, Min Wang, Ling Zhou, Xiao Feng, Jin Cheng, Yang Yu, Yanping Gong, Ying Zhu, Chuanyuan Li, Ling Tian and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 4 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 4 syntheses or guidelines pooled it, 74 citations in OpenAlex.

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  15. Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Zhengxiang ZhangThe Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. kanardo@163.com.
Min WangThe Department of Surgery, The Branch Hospital of Shanghai General Hospital, Shanghai, 200080, China. minniewang01@163.com.
Ling ZhouThe Department of Surgery, The Branch Hospital of Shanghai General Hospital, Shanghai, 200080, China. zhouling_2005@126.com.
Xiao FengThe Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. fxngtg@163.com.
Jin ChengThe Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. ajinch@163.com.
Yang YuThe Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. yuyang1611@163.com.
Yanping GongExperimental Research Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. yanpinggong2003@aliyun.com.
Ying ZhuThe Department of Surgery, The Branch Hospital of Shanghai General Hospital, Shanghai, 200080, China. rabbityy1975@163.com.
Chuanyuan LiDepartment of Dermatology, Medical Center, Duke University, Durham, NC, 27710, USA. chuan.li@duke.edu.
Ling TianExperimental Research Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. tl09168@hotmail.com.
Qian HuangThe Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. qianh2011@126.com.
Shanghai First People's Hospital · CNShanghai Jiao Tong University · CNDuke University · US

Funding

The "Phoenix Rising" pathway of tumor repopulation during radiotherapyR01CA155270 · NCI · DUKE UNIVERSITY · PI LI, CHUAN-YUAN · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA155270
6 · The paper itself

Abstract

backgroundDying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repopulation. In this study, we investigated whether high mobility group box 1(HMGB1) is also involved in tumor repopulation.

methodsColorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected by Western blot. A large number of irradiated colorectal tumor cells (feeder cells) were then co-cultured with a small number of luciferase-labeled living colorectal tumor cells (reporter cells) and proliferation of reporter cells was measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in colorectal tumor and peritumoral tissues were detected by immunohistochemistry and their correlation with prognosis were analyzed.

resultsThe irradiated colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor cells and HMGB1 in the supernatant of cultured cells. The increased expression of secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen (PCNA) after irradiation in vitro. The irradiated dying cells remarkably stimulated living tumor cell proliferation. Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01). Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

conclusionBoth apoptotic and necrotic cells could stimulate proliferation of living tumor cells, and the increased expression of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in colorectal cancer patients.

Indexed as

AcetyltransferasesAdultAgedAged, 80 and overCell Line, TumorCell ProliferationColorectal NeoplasmsFemaleHMGB1 ProteinHumansKaplan-Meier EstimateKi-67 AntigenMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingAcetyltransferasesHMGB1 ProteinHTATIP2 protein, humanKi-67 AntigenReceptor for Advanced Glycation End ProductsTranscription Factors

Identifiers

PMID25986235
PMCPMC4446854
OpenAlexW1922673049

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.