TO THE EDlTOR

We read with interest the review by Majumder

[1],which is titled “Inflammatory bowel diseaserelated colorectal cancer: Past,present and future perspectives.” The tumor pathogenesis is complex and not yet clear.Recently,inflammation induced and promoted tumor occurrence and deterioration,and the presence of high levels of inflammatory factors in many tumor patients has gradually become clear.The gastrointestinal system is one of the most prone to inflammation.Patients with chronic inflammation are more likely to develop liver cancer,pancreatic cancer,stomach cancer and colon cancer than those without inflammation,.Studies have demonstrated that hepatitis B virus patients were more likely to get cancer of the liver,and prognosis and survival time is far less than the patients without hepatitis B virus[2].Patients with pancreatitis had a 4.8-times significantly higher risk of developing cancer than those without pancreatitis[3].

is one of the important risk factors for gastric cancer patients,and

will induce the occurrence of chronic gastritis[4].In addition,patients with colitis have an increased mortality of colon cancer by 15%[1].Therefore,if the potential biomarkers can be identified by early intervention of the synthesis,secretion and release of inflammatory factors,it may have great clinical significance for gastrointestinal tumors and improve the overall understanding of gastrointestinal tumors.

Jurgen turned these things over in his mind all night. Somethingwas working within him, he hardly knew what it was, but it was evenstronger than his love for Else; and so he went to Martin s, andwhat he said and did there was well considered. He let the house toMartin on most liberal terms, saying that he wished to go to seaagain, because he loved it. And Else kissed him when she heard ofit, for she loved Martin best.

The interleukin (IL) family is the most common biomarker of inflammation.IL-1β,IL-6 and IL-10 are involved in the development and progression of gastrointestinal tumors.On the other hand,external stimuli,such as excessive oxidative stress,promote the secretion and release of the IL family,while the IL family itself has a certain feedback activation effect,thus exacerbating the inflammatory response[5].In colitis-cancer,IL-6 and other factors promote epidermal cell damage,and prolonged inflammatory damage will lead to abnormal proliferation of epidermal cells,which if not controlled will eventually lead to gene epigenetic modification mutation and ultimately induce tumorigenesis[6,7].

Tumor necrosis factor (TNF),another classic inflammatory factor,can promote the activation of neutrophils or macrophages to aggravate tissue damage by regulating monocyte chemotactic protein-1 and other mRNAs[8].Moreover,TNF accelerates the inflammatory process and thus leads to the occurrence of tumors[9].In addition,the role of a c-x-c motif chemokine ligand (CCL) family in gastrointestinal tumors is gradually becoming clear.CCLs infiltrated tissues by recruiting macrophages and releasing IL family members or TNF,further leading to local inflammatory infiltration of tissues,gene mutation and ultimately tumorigenesis[10].

Interestingly,some papers showed that chronic inflammatory responses promoted tumorigenesis and development,while acute inflammation is currently considered to inhibit tumor progression (Figure 1)[11].The new clinical research paper indicated that colon cancer patients with higher IL-6 and TNF(chronic inflammatory factors) developed a cancer recurrence.However,acute inflammatory factors,IL-10 and interferon γ,were lower in expression compared with those who did not recur[7].IL-12 is an acute inflammatory factor that could inhibit tumor progression in gastrointestinal tumors,and its high expression leads to a longer survival time[12].Additionally,the interferon family is a potential therapeutic biomarker,which could inhibit the occurrence and progression of gastrointestinal tumors by regulating cellular immunity,controlling cell cycle or promoting cell apoptosis[13,14].Moreover,the interferon family has been approved by the Food and Drug Administration for the treatment of tumors[15].

In conclusion,inflammation is involved in the entire gastrointestinal tumor process.The worse inflammation is mainly chronic inflammation,which can be induced by many reasons,such as unhealthy high-fat diet,excessive use of antibiotics,imbalance of intestinal flora and so on[16].Majumder

[1] systematically summarized the role of inflammatory factors in colon cancer.However,they failed to study and consider the role of acute inflammation in colon cancer.Therefore,inflammatory factors should be considered as important triggers to optimize current diagnosis and treatment strategies for early tumor diagnosis.

13.Will you give me your youngest daughter?: Here we have one of the first motifs57 which make this tale very similar to Beauty and the Beast. A beast asks for the youngest, beautiful daughter. The implication is that he wants to marry her, although a wedding ceremony is usually not acknowledged or detailed until the end of the tale once the enchantment58 has been broken.Return to place in story.

As I cared for my patients, George was right alongside. I watched him spread holiday cheer as he became a guest to the patients who had no visitors that day. When trays arrived he knew who needed assistance and who needed to be fed. He read letters and cards to those whose eyes could no longer see the letters on a printed page. George’s powerful body and tender hands were always ready to help hold, turn, pull-up or lift a patient. He was a “gopher” who made countless15 trips to the supply room for the “needs of the moment.”

China

Chen HJ and Chen X designed the research; Chen HJ wrote this comment; Liang GY and Du Z reviewed and supervised this manuscript; All authors approved the final version of the article.

All authors have nothing to disclose.

As sometimes happened in those days, long before shared custody1（，） and divorce mediation2, we didn t maintain much contact with our natural father. It was hoped that our new stepfather would grow to be the apple of our eyes.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

the Start-up Fund of Guizhou Medical University,No.J2021032; the Postdoctoral Research Fund of Affiliated Hospital of Guizhou Medical University,No.BSH-Q-2021-10; and the Guizhou Provincial Health Commission,No.gzwkj2022-082.

Hong-Jin Chen 0000-0002-0513-9584; Gui-You Liang 0000-0002-4555-9102; Xiong Chen 0000-0002-1799-2654; Zhou Du 0000-0001-8726-1016.

Wang LL

Filipodia

Wang LL

1 Majumder S,Shivaji UN,Kasturi R,Sigamani A,Ghosh S,Iacucci M.Inflammatory bowel disease-related colorectal cancer: Past,present and future perspectives.

2022; 14: 547-567 [PMID: 35321275 DOI:10.4251/wjgo.v14.i3.547]

2 Zhou Q,Zhang Q,Wang K,Huang T,Deng S,Wang Y,Cheng C.Anti-rheumatic drug-induced hepatitis B virus reactivation and preventive strategies for hepatocellular carcinoma.

2022; 178: 106181 [PMID: 35301112 DOI: 10.1016/j.phrs.2022.106181]

3 Petrov MS.Post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition as harbingers of pancreatic cancer.

2021; 27: 1936-1942 [PMID: 34007131 DOI: 10.3748/wjg.v27.i17.1936]

4 El Hafa F,Wang T,Ndifor VM,Jin G.Association between Helicobacter pylori antibodies determined by multiplex serology and gastric cancer risk: A meta-analysis.

2022; e12881 [DOI: 10.1111/hel.12881]

5 Zhou CB,Fang JY.The role of pyroptosis in gastrointestinal cancer and immune responses to intestinal microbial infection.

2019; 1872: 1-10 [PMID: 31059737 DOI: 10.1016/j.bbcan.2019.05.001]

6 Deng J,Zhao L,Yuan X,Li Y,Shi J,Zhang H,Zhao Y,Han L,Wang H,Yan Y,Zhao H,Zou F.Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice

Modulating Inflammation and Intestinal Microbiota.

2022; 14 [PMID: 35215376 DOI: 10.3390/nu14040726]

7 Fleming CA,O'Connell EP,Kavanagh RG,O'Leary DP,Twomey M,Corrigan MA,Wang JH,Maher MM,O'Connor OJ,Redmond HP.Body Composition,Inflammation,and 5-Year Outcomes in Colon Cancer.

2021; 4:e2115274 [PMID: 34459908 DOI: 10.1001/jamanetworkopen.2021.15274]

8 Chen H,Zhang Y,Zhang W,Liu H,Sun C,Zhang B,Bai B,Wu D,Xiao Z,Lum H,Zhou J,Chen R,Liang G.Inhibition of myeloid differentiation factor 2 by baicalein protects against acute lung injury.

2019; 63: 152997 [PMID:31254764 DOI: 10.1016/j.phymed.2019.152997]

9 Tu M,Klein L,Espinet E,Georgomanolis T,Wegwitz F,Li X,Urbach L,Danieli-Mackay A,Küffer S,Bojarczuk K,Mizi A,Günesdogan U,Chapuy B,Gu Z,Neesse A,Kishore U,Str?bel P,Hessmann E,Hahn SA,Trumpp A,Papantonis A,Ellenrieder V,Singh SK.TNF-α-producing macrophages determine subtype identity and prognosis

AP1 enhancer reprogramming in pancreatic cancer.

2021; 2: 1185-1203 [PMID: 35122059 DOI:10.1038/s43018-021-00258-w]

10 Fogelman DR,Morris J,Xiao L,Hassan M,Vadhan S,Overman M,Javle S,Shroff R,Varadhachary G,Wolff R,Vence L,Maitra A,Cleeland C,Wang XS.A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients.

2017; 25: 1809-1817 [PMID: 28111717 DOI: 10.1007/s00520-016-3553-z]

11 Zhao H,Wu L,Yan G,Chen Y,Zhou M,Wu Y,Li Y.Inflammation and tumor progression: signaling pathways and targeted intervention.

2021; 6: 263 [PMID: 34248142 DOI: 10.1038/s41392-021-00658-5]

12 Hu J,Yang Q,Zhang W,Du H,Chen Y,Zhao Q,Dao L,Xia X,Natalie Wall F,Zhang Z,Mahadeo K,Gorlick R,Kopetz S,Dotti G,Li S.Cell membrane-anchored and tumor-targeted IL-12 (attIL12)-T cell therapy for eliminating large and heterogeneous solid tumors.

2022; 10 [PMID: 35027427 DOI: 10.1136/jitc-2021-003633]

13 Shi XY,Zhang XL,Shi QY,Qiu X,Wu XB,Zheng BL,Jiang HX,Qin SY.IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis

AKT/mTOR signaling pathway.

2022; 24: 1073-1085 [PMID:35037236 DOI: 10.1007/s12094-021-02748-w]

14 Peng Y,Hu Y,Qiu L.Vesicular IFN-γ as a cooperative attacker to enhance anti-cancer effect of 5-fluorouracil

thymidine phosphorylase upregulation and tumor microenvironment normalization.

2022; 40: 102501[PMID: 34843983 DOI: 10.1016/j.nano.2021.102501]

15 Miller CH,Maher SG,Young HA.Clinical Use of Interferon-gamma.

2009; 1182: 69-79 [PMID:20074276 DOI: 10.1111/j.1749-6632.2009.05069.x]

16 Alhobayb T,Peravali R,Ashkar M.The Relationship between Acute and Chronic Pancreatitis with Pancreatic Adenocarcinoma: Review.

2021; 9 [PMID: 34940031 DOI: 10.3390/diseases9040093]