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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG YICHUN TANG FENG MA YUCHUN NIU LEI SUN department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China department of Pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China department of Radiation oncology The First People’s Hospital of FoshanFoshan528000China department of oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China department of oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

Assessment of new pathological markers in early stage colon cancer:Insights and limitations

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World Journal of Gastrointestinal oncology 2025年第3期17卷 113-121页

作者： Bulent Erdogan Fatma Elif UsturalıKeskin ErkanÖzcan Ahmet Küçükarda Ali Kaan Güren Osman Köstek Bekir Muhammet Hacioglu Hilmi Kodaz department of Medical oncology Division of Medical OncologyDepartment of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye department of Pathology Trakya University School of MedicineTrakya UniversityEdirne 22000Türkiye Division of Medical oncology Trakya University School of MedicineEdirne 22000Türkiye Division of Medical oncology Department of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye Division of Medical oncology Department of Internal MedicineMarmara University School of MedicineMarmara UniversityIstanbul 34000Türkiye Division of Medical oncology Department of Internal MedicineMarmara University School of MedicineIstanbul 34000Türkiye department of Medical oncology Acibadem Eskisehir HospitalEskisehir 26130Türkiye

BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or ***-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being *** To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,department of Medical *** divided those with and without high-risk factors into two *** examined the relationship of new pathological markers with these groups and with pathological markers in risk *** There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T *** No relationship was found between the presence of new pathological markers and high-low risk *** we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.

关键词： Colon cancer Early stage Risk factors New pathological markers Tumor-stroma ratio Tumor infiltrating lymphocytes Crohn-like reaction Desmoid reaction Poorly differentiated clusters

Combination therapy strategy based on selective internal radiation therapy as conversion therapy for inoperable giant hepatocellular carcinoma:A case report

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World Journal of Gastrointestinal oncology 2025年第3期17卷 410-417页

作者： Ming-Zhi Hao Hai-Lan Lin Yu-Bin Hu Qi-Zhong Chen Zhang-Xian Chen Lin-Bin Qiu Duan-Yu Lin Hui Zhang De-Chun Zheng Zhu-Ting Fang Jing-Feng Liu department of Tumor Interventional Radiology Clinical Ocology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of oncology and Vascular Interventional Radiology Clinical Oncology School of Fujian Medical UniversityFuzhou 350014Fujian ProvinceChina department of Nuclear Medicine Clinical Oncology School of Fujian Medical UniversityFuzhou 350014Fujian ProvinceChina department of Hepatopancreatobiliary Surgical oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of Radiology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of oncology and Vascular Interventional Radiology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina department of Hepatobiliary Surgery Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014Fujian ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)has become a growing health concern *** invasion and high tumor burden are key factors limiting the curative effect of selective internal radiation therapy(SIRT).CASE SUMMARY This case study reports a 49-year-old woman who was diagnosed with China Liver Cancer Staging(CNLC)IIIa HCC and>15 cm tumor ***,due to insufficient future liver remnant and vascular invasion,the tumor was unresectable;however,radical hepatectomy was performed after successful conversion therapy with SIRT using yttrium-90(90Y)resin microspheres followed by hepatic arterial infusion chemotherapy(HAIC)with tyrosine kinase inhibitor(TKI)and anti-programmed death-1(PD-1)*** using 90Y resin microspheres was given by the right hepatic artery and chemoembolization was simultaneously performed in the tumor’s feeding vessels from the right diaphragmatic *** was followed every three weeks with lenvatinib and *** 4 months post-SIRT,the tumor was downstaged to CNLC Ib and the patient successfully underwent *** histopathological examination of the resected specimen showed extensive *** This case study provides evidence for an integrated treatment strategy combining SIRT and HAIC with TKI and anti-PD-1 antibodies for patients with large HCC and microvascular *** confirmatory trials are required in the future.

关键词： Selective internal radiation therapy Hepatic arterial infusion chemotherapy Yttrium-90 resin microspheres Hepatocellular carcinoma Conversion therapy Case report

Improved treatment of colorectal liver metastases by early response evaluation and regimen adjustment: a prospective study of clinical functional MR-based modeling

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Cancer Biology & Medicine 2025年第02期 166-176页

作者： Wenhua Li Huan Zhang Zhe Gong Yue Li Zhiyu Chen Xiaodong Zhu Mingzhu Huang Zhe Zhang Chenchen Wang Lixin Qiu Qirong Geng Jinjia Chang Xiaoying Zhao Xuedan Sheng Wen Zhang Tong Tong Weijian Guo department of Medical oncology Fudan University Shanghai Cancer Center department of oncology Shanghai Medical College Fudan University department of Radiology Fudan University Shanghai Cancer Center department of Radiation oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences

Objective: The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods: A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023. Functional MR was performed at baseline and after one cycle of chemotherapy. The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package. The initial 100 cases were designated as the training set, the following 48 cases were designated as the validation set, and the final 48 cases were designated as the intervention validation ***: Good performance for the response prediction(AUC = 0.818 in the training set and 0.755 in the validation set) was demonstrated. The objective response rates(ORRs) in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets. Worse progression-free survival and overall survival rates were noted in the high-risk population. In the intervention set 22.9%(11/48) of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1%(37/48), which was significantly higher than the training and validation sets [47.97%(71/148); P = 0.000].Conclusions: A functional MR signature effectively predicted the chemotherapy response and long-term survival. The adjustment of the regimen guided by the model significantly improved the ORR.

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Identification of common genetic variants in KCNQ family genes associated with gastric cancer survival in a Chinese population

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Journal of Biomedical Research 2025年第1期39卷 76-86页

作者： Yuetong Chen Chen Li Yi Shi Jiali Dai Yixuan Meng Shuwei Li Cuiju Tang Dongying Gu Jinfei Chen department of Radiation oncology the Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215008China department of oncology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China department of oncology the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325015China department of oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China department of Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China

The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in ***,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain *** this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic *** both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 *** rs10832417 T allele was predicted to increase the minimum free energy of the secondary ***,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public *** findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.

关键词： gastric cancer survival genetic variants ionic channels

Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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oncology Research 2025年第1期33卷 225-234页

作者： WEI ZHANG WEICHENG WANG RUI WANG XIAO HAN LIJUN ZHU WENJIE GUO YANHONG GU department of oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China department of oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric

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World Journal of Gastrointestinal oncology 2025年第2期17卷 198-210页

作者： Long Wang Qi Wu Zong-Wen Zhang Hui Zhang Hui Jin Xin-Liang Zhou Jia-Yin Liu Dan Li Yan Liu Zhi-Song Fan department of oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and ***,their effects on the immune microenvironment remain *** analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in *** hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to *** To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in *** Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R *** expressed genes and immune checkpoints were ***(IHC)was performed on GC *** analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC *** cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western *** Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant *** results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC *** positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC *** nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory *** The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.

关键词： Gastric cancer Immunosuppressive receptor Colony-stimulating factor 3 Colony-stimulating factor 3 receptor Leukocyte immunoglobulin-like receptor B2 Angiopoietin-like protein 2 Human leukocyte antigen-G Heterogeneous nuclear ribonucleoprotein H1

Effects of Shenqi Xiangyi granules in advanced gastric cancer chemotherapy

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World Journal of Gastrointestinal oncology 2025年第1期17卷 169-175页

作者： Xiao-Jing Shi Yu Song Xue-Xue Liang Ting Chen Huang-Yu Hao Xue Han Ya-Nan Chen department of oncology Zhangjiagang First People's HospitalSuzhou 215600Jiangsu ProvinceChina

BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced *** a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table *** control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous *** observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei *** groups underwent treatment cycles of 3 weeks,with a minimum of two *** therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the *** objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.

关键词： Sindilizumab FOLFOX4 chemotherapy Advanced gastric cancer Ginseng Qi Xiangyi granule Clinic treatment

Advanced pancreatic cancer treated with camrelizumab combined with apatinib:A case report

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World Journal of Gastrointestinal oncology 2025年第2期17卷 284-290页

作者： Yun-Hao Luo Ting He Lu Lin Rong-Qiu Wang Hong-Xia Cai Wen Hu department of Critical Care Medicine Chengdu First People's HospitalChengdu 610000Sichuan ProvinceChina department of Radiology Sichuan Second Hospital of Traditional Chinese MedicineChengdu 610000Sichuan ProvinceChina department of oncology Chengdu Seventh People's HospitalChengdu 610000Sichuan ProvinceChina department of oncology West China Tianfu HospitalSichuan UniversityChengdu 610000Sichuan ProvinceChina

BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for *** is prone to recurrence and metastasis,and the antitumor effect of chemotherapy is notably *** SUMMARY Histopathological analysis of a 53-year-old female PC patient who underwent Whipple surgery revealed poorly differentiated tumor cells infiltrating nerves,lymphatics,and blood *** patient received two different first-line chemotherapy regimens consecutively;however,both regimens struggled to control disease *** this period,the patient underwent liver metastasis ablation surgery,Candida albicans liver abscess,and stereotactic body *** the addition of camrelizumab to the modified FOLFIRINOX regimen,tumor control was *** patient subsequently refused to continue chemotherapy,and the antitumor regimen was changed to a combination of camrelizumab and *** patients received a combination of immunotherapy and targeted therapy,the length of hospital stay was significantly ***,all side effects were within acceptable limits,leading to an improved quality of life and prolonged progression-free ***,the pain associated with cancer,coupled with the side effects of opioid analgesics,has led the patient to reject all available anticancer treatment *** one month after camrelizumab and apatinib were discontinued without medical authorization,the PC recurred and rapidly progressed to widespread metastasis,ultimately leading to the patient's death approximately one month *** overall survival was 2 *** Immunotherapy and targeted therapy have the potential to increase both the quality of life and survival time of PC patients,particularly those whose tumor progression is not effectively controlled by chemotherapy ***,further clinical trials a

关键词： Advanced pancreatic cancer Immunotherapy Camrelizumab Targeted therapy Apatinib Case report