Guanylate binding protein 5 (GBP5) is a member of the interferon (IFN)-inducible large guanosine triphosphate hydrolases (GTPase) family that regulates cell-autonomous immunity and malignant tumor transformation. However, its specific roles and underlying mechanisms GBP5 in gastric cancer (GC) remain unknown. In this study, we aimed to determine the role GBP5 and underlying mechanism of GBP5 in GC cell progression. Potential oncogenic roles of GBP5 in GC as well as its relationship with the tumor immune microenvironment (TIME) were comprehensively evaluated using bioinformatics analysis. Protein expression levels of GBP5 and their correlation with clinicopathological features of patients were assessed using immunohistochemistry. In addition, diverse in vitro functional experiments were performed to identify the functions of GBP5 in GC. Downstream targets of GBP5 were identified using RNA-sequencing analysis and verified using western blotting or quantitative polymerase chain reaction analysis in different cell lines. GBP5 expression is commonly upregulated and promotes the proliferation and migration of GC cells. Mechanistically, GBP5 was regulated by the IFNγ-Janus kinase (JAK1)-signal transducer and activator of transcription 1 (STAT1) axis and induced CXCL8 expression. Interestingly, GBP5-induced CXCL8 regulated the JAK1-STAT1 signaling pathway to form a positive feedback loop. Moreover, GBP5 is closely related to the TIME and may be used as a biomarker for predicting the efficacy of immunotherapy. Our findings revealed a new JAK1-STAT1/GBP5/CXCL8 pathway and highlighted the value of GBP5 as a predictive biomarker and novel target for GC intervention.

BackgroundUrinary and sexual dysfunctions are among the most common complications in rectal cancer surgery. This study aimed to investigate the protective effect of laparoscopic functional total mesorectum excision (TME) on urinary and sexual functions in male patients.MethodsA total of 248 male patients with mid-low rectal cancer were recruited in this study between February 2017 and July 2020. To overcome selection bias, we performed a 1:1 match using six variables, including age, BMI, ASA score, tumor distance, clinical T stage, and tumor size. The urinary function was assessed by the International Prostate Symptom Score (IPSS), sexual function was assessed by a 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading at postoperative 3 and 12 months.Results79 patients received functional TME surgery (FTME group), and 169 patients received routine TME surgery (RTME group). After the propensity score, 79 pairs were balanced and analyzed. Patients in the FTME group showed a lower IPSS score and higher IIEF-5 score than patients in the RTME group at postoperative 3 and 12 months. The incidence of ejaculation dysfunction for patients in the FTME group was lower than patients in the RTME group at postoperative 3 and 12 months.ConclusionLaparoscopic functional total mesorectal excision was beneficial to faster recovery of urinary and sexual function for patients with rectal cancer, and it could be used as a superior surgical technique for pelvic autonomic nerve preservation in mid-low rectal cancer.

全直肠系膜切除术(total mesorectal excision,TME)是中低位直肠癌的标准手术方式,尽管直肠癌病人手术后的生存率得到大幅度提高,然而手术导致的器官功能障碍已成为影响病人术后生活质量的重要问题,主要包括术后排粪、排尿以及性功能障碍,其主要原因为术中盆腔自主神经的损伤.神经层面作为盆腔自主神经保护关系密切的重要解剖结构近年来逐步受到重视.该文拟从胚胎发育解剖理念来重点介绍腹腔镜直肠癌根治术中,如何正确辨识神经层面,实现盆腔自主神经保护,从而阐述神经层面在腹腔镜直肠癌手术中对盆腔自主神经保护的意义及研究前景.

Objective . To study the role of long noncoding RNA HOXA10-AS in gastric cancer (GC) and its underlying mechanism which is one of the most common and fetal malignancies. Long noncoding RNA HOXA10-AS is highly expressed and acts in an oncogenic role in cancers. However, its roles in GC are still unknown. Methods . The expression of HOXA10-AS and HOXA10 in GC tissues from the TCGA database was analyzed. Western blot and qRT-PCR assays were applied to examine the expression of HOXA10-AS and HOXA10. Cell proliferation was evaluated with CCK-8 and EdU incorporation assays. Cell apoptosis was analyzed by flow cytometry. Migratory and invasive capacities were evaluated with wound healing and transwell assays. Results . HOXA10-AS and HOXA10 were upregulated in GC, and their expressions were positively correlated. Knockdown of HOXA10-AS inhibited HOXA10 expression in GC cells. Furthermore, knockdown of HOXA10-AS restrained GC cell proliferation, migration, and invasion but promoted apoptosis. In addition, overexpression of HOXA10-AS promoted malignant phenotypes of GC cells, but all these effects could be reversed by knockdown of HOXA10. Conclusion . HOXA10-AS promoted GC cell proliferation, migration and invasion and enhanced apoptosis via upregulating HOXA10. Our study implies a novel regulatory mechanism of malignant phenotypes and provides potential therapeutic targets for GC.

比较接受发育解剖应用于腹腔镜右半结肠癌全系膜切除和全结肠系膜切除患者的短期疗效。两组手术时间、术中出血、清扫淋巴结个数和系膜完整度及围手术期并发症（乳糜漏和肠梗阻）发生率差异均有统计学意义（均 P<0.05）。发育解剖应用于右半结肠癌腹腔镜完整系膜切除具有较好的手术安全性，在功能保护上具有一定优势。

BackgroundStation 253 node dissection with high ligation of the inferior mesenteric artery (IMA) is difficult to perform without damage to the surrounding autonomic nerve plexuses. This study aimed to investigate the significance of the nerve plane for inferior mesenteric plexus (IMP) preservation in laparoscopic rectal cancer surgery.MethodsA total of 56 consecutive rectal patients underwent laparoscopic en bloc station 253 node dissection with high ligation of the IMA. Station 253 nodes were divided into the extra- and intra-nerve plane station 253 nodes for further H&E staining and immunohistochemical analysis. Based on IMP nerve plane-based evidence and histopathological results, a novel nerve-sparing technique, IMP nerve plane orientation, was proposed and performed on 68 rectal cancer patients. Urinary and sexual functions in all patients were evaluated at 6 months postoperatively.ResultsLymph node metastasis was not found, but abundant nerve bundles containing gangliocytes were observed in extra-nerve plane station 253 nodes. The nerve plane was identified intraoperatively and then confirmed by both postoperative gross specimen evaluation and histopathological analysis. The novel nerve-sparing technique (IMP nerve plane orientation) was successfully performed with no postoperative complications, and the operated patients had improved postoperative urinary and sexual functions.ConclusionThe nerve plane is helpful for IMP preservation and station 253 node dissection. This novel nerve-sparing technique of nerve plane orientation is technically feasible and safe, which could result in faster recovery of urinary and sexual functions.

Objective To study the role of long noncoding RNA HOXA10-AS in gastric cancer (GC) and its underlying mechanism which is one of the most common and fetal malignancies. Long noncoding RNA HOXA10-AS is highly expressed and acts in an oncogenic role in cancers. However, its roles in GC are still unknown. Methods The expression of HOXA10-AS and HOXA10 in GC tissues from the TCGA database was analyzed. Western blot and qRT-PCR assays were applied to examine the expression of HOXA10-AS and HOXA10. Cell proliferation was evaluated with CCK-8 and EdU incorporation assays. Cell apoptosis was analyzed by flow cytometry. Migratory and invasive capacities were evaluated with wound healing and transwell assays. Results HOXA10-AS and HOXA10 were upregulated in GC, and their expressions were positively correlated. Knockdown of HOXA10-AS inhibited HOXA10 expression in GC cells. Furthermore, knockdown of HOXA10-AS restrained GC cell proliferation, migration, and invasion but promoted apoptosis. In addition, overexpression of HOXA10-AS promoted malignant phenotypes of GC cells, but all these effects could be reversed by knockdown of HOXA10. Conclusion HOXA10-AS promoted GC cell proliferation, migration and invasion and enhanced apoptosis via upregulating HOXA10. Our study implies a novel regulatory mechanism of malignant phenotypes and provides potential therapeutic targets for GC.

BACKGROUND:Sexual dysfunctions seriously affect the quality of life of patients. The aim of this study was to identify the risk factors for sexual dysfunction after rectal cancer surgery. METHODS:A total of 948 consecutive patients undergoing rectal cancer radical resection were included between January 2012 and August 2019. The sexual functions were evaluated by the 5-item version of the International Index of Erectile Function (IIEF-5) in men and Index of Female Sexual Function (IFSF) in women at 12 months postoperatively. RESULTS:Postoperative sexual dysfunction was observed in 228 patients with rectal cancer (24.05%), which included 150 cases in male patients (25.0%) and 78 cases in female patients (22.5%). A multivariate logistic regression analysis results showed that age ≥45 years old (OR = 1.72, p = 0.001), tumor below the peritoneal reflection (OR = 1.64, p = 0.005), receiving preoperative radiotherapy (OR = 4.12, p < 0.001) and undergoing abdominoperineal resection (APR), intersphincteric resection (ISR) and Hartmann surgery (OR = 2.43, p < 0.001) were the independent risk factors of sexual dysfunction for patients with rectal cancer. CONCLUSION:Age ≥45 years old, tumors below the peritoneal reflection, receiving preoperative radiotherapy, and undergoing APR, ISR and Hartmann surgery were the independent risk factors of sexual dysfunction. Patients should be informed about the sexual dysfunctions in the pre-operative consultations. More attention should be paid to intraoperative pelvic autonomic nerve preservation on rectal cancer patients with these risk factors for clinic surgeons.

目的 探讨以问题为导向的教学方法(PBL)联合以案例为基础的教学方法(CBL)在胃肠外科规培生教学中的应用价值.方法 将2018年在武汉大学人民医院胃肠外科进行住院医师规范化培训的学员作为对照组(n=50),采用传统教学方法,2019年的学员采用PBL+CBL教学方法作为实验组(n=54).比较两组学员的基础理论,操作技能,病例分析能力等出科考试成绩.同时进行问卷调查,比较两组学员的学习积极性,自主学习能力,团队合作能力,语音表达能力,文献查找能力.结果 PBL+CBL教学方法组学员基础理论,操作技能,病例分析得分均较传统教学方法组高(P<0.05).同时,PBL+CBL组学员的学习积极性、自主学习能力、团队合作能力、语音表达能力、文献查找能力也较传统教学方法组高,差异有统计学意义(P<0.05).结论 PBL+CBL教学法能够提高胃肠外科规培生的教学效果,同时能激发学员的主动性和积极性,具有较好的应用价值.

目的 调查分析湖北省胃肠道肿瘤病人围手术期静脉血栓栓塞症(VTE)防治现状.方法 回顾性分析2019-01-01至2019-12-31湖北省胃肠外科联盟成员医院收治的行手术治疗的胃肠道肿瘤病人VTE防治相关临床资料.结果 收集62家医院调查问卷7751份,其中有效问卷共计7474份,有效率96.4％.所有病人中,术前736例(9.8％)接受恰当预防措施,7012例(93.8％)术前行D-二聚体检查,2301例(30.7％)术前行下肢静脉超声检查.术后451例(6.0％)病人接受恰当预防措施.术后6434例(86.1％)病人行D-二聚体检查;1675例(22.2％)行下肢静脉超声检查,其中164例发生下肢深静脉血栓(DVT),20例病人发生肺动脉栓塞(PE),有5例PE病人住院期间死亡.结论 当前湖北省胃肠道肿瘤病人围手术期下肢静脉超声检查及恰当预防比例偏低,围手术期VTE规范化防治水平有待提高.

Objective:To construct a small molecular gated chimeric antigen receptor T (smgCAR-T) cell system targeting vascular endothelial growth factor receptor 2 (VEGFR2) and to verify its antitumor and regulatory activity in vitro. Methods:After verifying and screening the successfully constructed cells, the targeting binding ability of CAR-T cells was verified in vitro. The concentrations of interleukin-2 and interferon-γ secretion from CAR-T cells were detect by kits in vitro, and antitumor activity of CAR-T cells was evaluated by lactate dehydrogenase kit. Continuous variables were expressed as mean±SD, and comparison between groups were performed by t test or analysis of variance. Results:Compared with the control groups, the CAR + -T cell+ MCA38 VEGFR2+ group had the strongest target cell killing ability. In the smgCAR-T cell+ MCA38 VEGFR2+ group, the target cell killing rate gradually increased with the increase of Rapalog. The maximum killing rate was (66.25±13.20)% when Rapalog was 40 nmol/L. At 24 h, the killing rate of the two groups increased simultaneously with not statistically significant after Rapalog was added to the smgCAR-T+ MCA38 VEGFR2+ groups [(44.25±6.24)% vs. (49.25±5.56)%, t=1.197, P>0.05]. At 36 h, the killing rate of group A (adding Rapalog again) and B (without adding Rapalog again) was statistically significant [(89.00±3.16)% vs. (56.50±6.61)%, t=8.873, P<0.01]. Conclusion:The smgCAR-T cells exhibited certain antitumor activity in vitro, and its activity was regulated by the small molecule compound Rapalog.

Radical resection for rectal cancer with total mesorectal excision has been widely recognized in mid-low rectal cancer. Although such surgery reduced the tumor recurrence rate and improved the survival rate of patients, the rate of urinary and sexual dysfunction was high after rectal cancer surgery, which might be attributed to pelvic autonomic nerve injury. The present study found that the pelvic autonomic nerves never exist alone. These are always surrounded by tiny capillaries and adipose tissue and covered by a thin layer of membranous tissue, leading to a continuous plane that should be preserved pelvic autonomic nerve from thermal damage, ischemic injury, nerve stretching, and chemical factors produced by local inflammatory effects. However, the completeness of the continuous plane is easily damaged intraoperatively in routine total mesorectal excision in rectal cancer. Postoperative urinary and sexual dysfunction might be closely associated with the injury of continuous plane. Therefore, the continuous plane should be protected and considered as the optimal surgical plane for rectal cancer surgery.

Accumulating studies have shown that the dysregulation of microRNAs is related to the carcinogenesis and development of gastric cancer (GC), and the role of miR-635 in GC remains largely unknown. miR-635 and Kinesin Family Member C1 (KIFC1) mRNA expression in GC tissues and paracancerous tissues and cells were detected by quantitative real-time PCR. KIFC1 protein expression in GC tissues and paracancerous normal tissues and cells was detected by immunohistochemistry and western blot. Cell proliferation was monitored by Cell Counting Kit-8 assay and 5-bromo-2′-deoxyuridine assay. Transwell assay was employed to detect the migration and invasion of GC cells. The dual-luciferase reporter gene assay was adopted to detect the targeting relationship between miR-635 and KIFC1. Compared with paracancerous tissues, miR-635 expression was remarkably decreased in GC tissues; conversely, KIFC1 expression was significantly increased. Compared with human normal gastric epithelial cell GSE-1, miR-635 expression was markedly decreased in GC cell lines. Meanwhile, KIFC1 expression was significantly increased, and the Kaplan-Meier Plotter database showed that its high expression was remarkably associated with poor prognosis. Additionally, miR-635 can negatively regulate KIFC1. miR-635 can target KIFC1 to inhibit proliferation, migration and invasion of GC cells. Collectively, miR-635 is lowly expressed in GC, and it inhibits proliferation, migration and invasion of GC cells via regulating KIFC1.

[目的]观察抗氧化物MnTE-2-PyP对大鼠新辅助放化疗肠切除-吻合术(以下简称"手术")后直肠吻合口愈合的影响.[方法]75只大鼠随机分为5组:对照组、模拟放化疗组、模拟放化疗+MnTE-2-PyP组、放化疗组及放化疗+MnTE-2-PyP组,每组15只.对照组:标准手术;模拟放化疗组:模拟放化疗+手术+腹腔注射磷酸盐缓冲液;模拟放化疗+MnTE-2-PyP组:模拟放化疗+手术+腹腔注射MnTE-2-PyP;放化疗组:放化疗+手术+腹腔注射磷酸盐缓冲液;放化疗+MnTE-2-PyP组:放化疗+手术+腹腔注射MnTE-2-PyP.各组术后第7天测量吻合口破裂压力,免疫组织化学染色观察微血管密度,天狼星红染色检测吻合口处胶原沉积.[结果]与对照组相比,新辅助放化疗降低大鼠术后直肠吻合口破裂压力(P＜0.05)及羟脯氨酸水平(P＜0.01).经过MnTE-2-PyP处理后,肠吻合口的破裂压力(P＜0.05)和羟脯氨酸水平(P＜0.01)均显著增加.此外,吻合口组织CD34免疫组织化学染色结果表明MnTE-2-PyP促进吻合口处微血管新生(P＜0.05),天狼星红染色提示MnTE-2-PyP增加吻合口处胶原沉积(P＜0.05),有利于吻合口愈合.[结论]MnTE-2-PyP通过促进微血管形成及胶原合成,增强大鼠新辅助放化疗术后肠吻合口强度,减少吻合口漏的发生.

Background. Rectal cancer is one of the malignant diseases with high morbidity and mortality in the world. Currently, surgical resection is the main treatment method, and preoperative chemoradiotherapy (CRT) is widely used in clinical application to increase resectability and decrease the local recurrence rate. However, CRT increases the risk of colon anastomotic leak, and currently, there are no FDA approved treatments against this side effect. It is essential to develop new drugs to reduce postoperative anastomotic leak after preoperative CRT. Methods. 90 rats underwent standard resection and intestine anastomosis treatment and were divided into six groups for different treatments. During the relaparotomy, bursting pressure of anastomosis was measured and intestinal segments were taken for histopathologic examination and biochemical analyses. RT-PCR and ELISA were applied to measure matrix metalloproteinase (MMP) mRNA and protein levels. Blood vessels were observed by immunohistochemistry, and collagen deposition was observed by Picrosirius Red staining. Results. Preoperative CRT reduced the postoperative anastomotic strength. MnTE-2-PyP increased the bursting pressure and hydroxyproline levels of intestine anastomosis after CRT treatment. Mechanically, MnTE-2-PyP decreased the MMP levels and increased microvessel density (MVD) and collagen deposition. The MMP inhibitor doxycycline had a positive effect on anastomosis healing, but was inferior to MnTE-2-PyP. Conclusions. MnTE-2-PyP enhanced intestine anastomotic strength in rats with preoperative CRT. Specifically, MnTE-2-PyP decreased MMP levels and increased MVD in anastomosis. Therefore, MnTE-2-PyP may be helpful in the prevention of anastomotic leak after preoperative CRT.

Objective:To explore the protective effect of nerve plane-oriented laparoscopic total mesorectal excision (NPO+ LTME) for postoperative urinary and sexual function in patients with rectal cancer.Methods:Retrospective analysis was performed on rectal cancer patients who received surgical treatment at Renmin Hospital of Wuhan University from Jan 2016 to Dec 2018, including 114 patients in the NPO+ LTME group and 92 patients in the laparoscopic TME combined with pelvic autonomic nerve preservation (LTME+ PANP) group. Surgical and tumor-related indicators were recorded and compared between the two groups, and postoperative urination and sexual function were followed up.Results:There was no significant difference in baseline indicators between the two groups ( P>0.05). The operative time of the two groups was (150±7) min and (154±7) min, respectively ( t=3.585, P<0.05). Intraoperative bleeding was (9±3) ml and (15±6) ml ( t=7.654, P<0.05), respectively.Three months after surgery, the rate of urinary dysfunction in the NPO+ LTME group was lower than that in the LTME+ PANP group ( Z=2.549, P<0.05), but there was no difference between the two groups 6 and 12 months after surgery ( Z=0.814, P>0.05 and Z=1.275, P>0.05). At 3, 6 and 12 months after surgery, the erectile function in NPO+ LTME group was better than that in LTME+ PANP group ( Z=4.917, P<0.05; Z=4.947, P<0.05 and Z=4.081, P<0.05); The rate of ejaculation dysfunction was also lower than that of the LTME+ PANP group ( Z=4.464, P<0.05; Z=4.948, P<0.05 and Z=4.434, P<0.05); In addition, postoperative female sexual function was superior to LTME+ PANP group ( Z=2.532, P<0.05; Z=2.364, P<0.05; Z=2.076, P<0.05). Conclusion:NPO+ LTME has good surgical safety and also has certain advantages for patient sexual function and early urinary function protection.

Background. In patients with gastric cancer (GC), peritoneal metastasis is an indication of the end stage and often indicates a poor outcome. The diagnosis of peritoneal metastasis, especially occult peritoneal metastasis (OPM), remains a challenge for surgeons. This study was designed to explore the relationship between OPM and clinicopathological characteristics and preoperative hematological parameters in patients with GC and to develop a nomogram to predict the probability of OPM before surgery. Methods. A total of 672 patients with GC from our center were included, including 583 OPM-negative and 89 OPM-positive patients. These patients were divided into training and validation groups based on when they received treatment. OPM was diagnosed during surgery in patients without any signs of metastasis through imaging examination. Predictive factors were screened by least absolute shrinkage and selection operator logistic regression of all 18 characteristics. The nomogram of OPM was constructed based on these filtered variables. The discriminative and calibration performance of the model were simultaneously evaluated. Results. A total of six variables, including tumor size, degree of differentiation, depth of invasion, Glasgow prognosis score, and plasma levels of CA125 and fibrinogen, were selected for integration into the final predictive nomogram. The area under curve (AUC) of the nomogram with six factors was 0.906 (95% confidence interval (CI): 0.872-0.941) and 0.889 (95% CI: 0.795-0.984) in the training and validation groups, respectively. Calibration plots of the nomogram in the two sets revealed a good consistency between predicted and actual probabilities. Decision curve analysis showed that the nomogram had a positive net benefit among all threshold probabilities between 0% and 82%. This nomogram was superior to models incorporating only clinicopathologic or hematologic features. Conclusion. Both clinicopathological and preoperative hematological parameters are significantly associated with OPM. The nomogram constructed with six factors could be used to calculate the probability of OPM and identify the high-risk population in GC. This may be helpful for early detection of OPM in patients with GC.

BACKGROUND:Metastasis and invasion are the main causes of mortality in gastric cancer. To improve the treatment of gastric cancer, the development of effective and innovative antitumor agents toward invasion and proliferation is needed. Alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, showed antiproliferative and cytotoxic effects on several cancers. So it is feasible to explore whether ALA can be used to inhibit proliferation and invasion in human gastric cancer.METHODS:The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performed in vitro cell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3.RESULTS:We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region.CONCLUSION:ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

Background. As a key step in enhancing cancer cell invasion and metastasis, epithelial-mesenchymal transition (EMT) plays an important role in colorectal cancer progression. EMT is triggered by a variety of signaling pathways, among which the transforming growth factor β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β in the presence or absence of MnTE-2-PyP. Cells were analyzed by several techniques including western blotting, real-time quantitative PCR, transwell assay, and wound healing assay. Results. MnTE-2-PyP reverses cell phenotypes induced by TGF-β in colon cancer cells. MnTE-2-PyP treatment significantly reduced the expression of mesenchymal markers but maintained epithelial marker expression. Mechanistically, MnTE-2-PyP suppressed the phosphorylated Smad2/3 protein levels induced by TGF-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-mediated cell migration and invasion and the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in colorectal cells. Conclusion. Taken together, we provide an in-depth mechanism by which MnTE-2-PyP inhibits colorectal cancer progression, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in colorectal cancer.