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CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Oncology research 2024年第2期32卷 261-272页

作者： SHUANGSHUANG ZENG XI CHEN QIAOLI YI ABHIMANYU THAKUR HUI YANG YUANLIANG YAN SHAO LIU department of Pharmacy Xiangya HospitalCentral South UniversityChangsha410008China National Clinical research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha410008China Pritzker School of Molecular Engineering Ben May Department for Cancer ResearchUniversity of ChicagoChicagoILUSA department of Pathology The Second Affiliated Hospital of Shandong First Medical UniversityTaian271000China

Finding biomarkers for immunotherapy is an urgent issue in cancer *** retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human ***,there is limited research on the relationship between CRABP2 and immunotherapy *** study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor ***,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell *** expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in *** validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been *** models showed an increase in tumor weight and *** analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of *** conclusion,this study provides new insights into the role of CRABP2 in immunotherapy *** findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM *** research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

关键词： CRABP2 Melanoma PD-1 cancer-associated fibroblasts Immune infiltration

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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong department of Colorectal cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao department of Pancreatic cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China department of Gastrointestinal Pancreatic Surgery Shanxi Provincial People’s HospitalTaiyuan 030012China

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell ***-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine ***,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains ***:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were *** of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was ***:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and *** GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic *** tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and ***:Ki-67 is a valuable prognostic indicator for *** of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Pancreatic ductal adenocarcinoma prognosis Ki-67 differentiation TNM stage

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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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Categorizing methods for integrating machine learning with executable specifications

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Science China(Information Sciences) 2024年第1期67卷 5-19页

作者： David HAREL Raz YERUSHALMI Assaf MARRON Achiya ELYASAF department of Computer Science and Applied Mathematics Weizmann Institute of Science department of Software and Information Systems Engineering Ben-Gurion University of the Negev

Deep learning(DL),which includes deep reinforcement learning(DRL),holds great promise for carrying out real-world tasks that human minds seem to cope with quite *** promise is already delivering extremely impressive results in a variety of ***,while DL-enabled systems achieve excellent performance,they are far from *** has been demonstrated,in several domains,that DL systems can err when they encounter cases they had not hitherto ***,the opacity of the produced agents makes it difficult to explain their behavior and ensure that they adhere to various requirements posed by human *** the other end of the software development spectrum of methods,behavioral programming(BP) facilitates orderly system development using self-standing executable modules aligned with how humans intuitively describe desired system *** this paper,we elaborate on different approaches for combining DRL with BP and,more generally,machine learning(ML) with executable specifications(ES).We begin by defining a framework for studying the various approaches,which can also be used to study new emerging approaches not covered *** then briefly review state-of-the-art approaches to integrating ML with ES,continue with a focus on DRL,and then present the merits of integrating ML with *** conclude with guidelines on how this categorization can be used in decision making in system development,and outline future research challenges.

关键词： machine learning artificial intelligence grey box learning domain knowledge rules behavioral programming deep reinforcement learning survey

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Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

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Chinese Journal of cancer research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei department of Epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of ***: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by ***: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity ***: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study

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Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children:analysis of 571 patients

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World Journal of Pediatrics 2024年第3期20卷 250-258页

作者： Min He Jia-Bin Cai Xuan Wu Yin-Bing Tang Jin-Yan Wang Jun-Qin Mao Ji-Jun Chen Li-Feng Zhang Zhong-Hai Guan Jie-Ni Xiong Wan-Xin Peng Jin-Hu Wang Ting Tao Pediatric cancer research Center National Clinical Research Center for Child HealthHangzhouChina department of Surgical Oncology Children's HospitalZhejiang University School of MedicineHangzhouChina cancer Center Zhejiang UniversityNo.3333 Binsheng RodeHangzhouChina

Background Surgery plays an important role in the treatment of *** complications may impact the course of neuroblastoma *** date,comprehensive analyses of complications and risk factors have been *** Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and *** data collected included clinical characteristics,operative details,operative complications and postopera-tive *** factors for perioperative complications of retroperitoneal neuroblastoma were *** A total of 571 patients were enrolled in this *** complications were observed in 255(44.7%)*** leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent *** were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative *** Despite the high incidence of perioperative complications,the associated mortality rate was quite ***-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular *** with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.

关键词： Complication Neuroblastoma Risk factors Surgery

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Tau's function and dysfunction in the brain:when small changes have big consequences

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Neural Regeneration research 2024年第1期19卷 152-153页

作者： Miguel Portillo Debra Toiber department of Life Sciences Ben-Gurion University of the NegevBeer ShevaIsraelThe Zlotowski Center for NeuroscienceBen-Gurion University of the NegevBeer ShevaIsrael

With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by *** diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of *** the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.

关键词： diseases consequences function

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China department of Clinical Laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1395-1406页

作者： Qiu-Xiao Yu Ping-Ying Fu Chi Zhang Li Li Wen-Ting Huang department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality ***-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor *** amplification has been reported in CRC,but data are very *** pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical *** To determine the pathological significance of MET amplification in CRC and to propose a feasible screening *** A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen cancer Hospital of Chinese Academy of Medical Sciences were *** patients were without RAS/RAF mutation or microsatellite *** amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),*** between MET aberration and pathological features were detected using the chi-squared *** free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank *** results of MET FISH and IHC were com pared using one-way *** Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not ***-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(P<0.001)and higher tumor budding grade(P=0.02).In the survival analysis,significant difference was detected between patients with amplified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was dete

关键词： Colorectal cancer MET Amplification Pathological features Prognosis Fluorescence in situ hybridization

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