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Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology Research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth clinical Medical College of Yangzhou university Nantong Rich HospitalNantongChina Molecular and Experimental surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany Department of Pathology and Experimental Cancer Research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and *** study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient ***-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,***,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional *** support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy *** findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD *** of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk ***-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression ***,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of ***,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data a

关键词： Colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： LISANNE K.A.NEIJENHUIS LEUTA L.NAUMANN SONIA A.M.FERKEL SAMUEL J.S.RUBIN STEPHAN ROGALLA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA Department of surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands Centre for Human Drug Research Leiden2333 CLThe Netherlands Department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone *** prognosis for patients with disseminated disease remains very poor despite recent advancements in ***,current treatment regimens bear a signiﬁcant risk of serious side ***,there is an unmet clinical need for effective therapies with improved safety proﬁ*** is an antibacterial agent that has been shown to induce cell death in different types of cancer cell ***:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day *** were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal ***:After 35 days,mice were euthanized,and the tumors were harvested for *** mice were excluded from the analysis due to *** weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this *** tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the *** antineoplastic effects were observed on intramuscular tumors or for intravenous administration of *** were no signiﬁcant differences in microvessel density or mitotic rate between treatment *** body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is ***:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are ***,its toxic proﬁle grants further *** these observations,further research is necessary to

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano Department of Orthopedic surgery Keio University School of Medicine Department of Physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

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Chinese Journal of Cancer Research 2024年第4期36卷 368-378页

作者： Ji Yeong An Sung Eun Oh Soomin Ahn Hyoung-II Kim Yoo Min Kim Minah Cho Keun Won Ryu Hong Man Yoon Young Kyu Park In Gyu Kwon Sung Hoon Noh Kyung Hee Lee In Cho Myoung Won Son Jong Won Kim Young-Woo Kim Department of surgery Samsung Medical Center Sungkyunkwan University School of Medicine Department of Pathology and Translational Genomics Samsung Medical Center Sungkyunkwan University School of Medicine Department of surgery Yonsei University College of Medicine Gastric Cancer Center Yonsei Cancer CenterYonsei University Health System Center for Gastric Cancer National Cancer Center Department of surgery Chonnam National University Hwasun Hospital Chonnam National University College of Medicine Department of surgery Gangnam Severance Hospital Yonsei University College of Medicine Department of Hematology-Oncology Yeungnam University Medical Center Department of surgery Soonchunhyang University College of Medicine Department of surgery Soonchunhyang University Cheonan Hospital Soonchunhyang University College of Medicine Department of surgery Chung-Ang University Hospital Chung-Ang University College of Medicine

Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier(SPC) test, a new clinical-grade prognostic assay, in stage Ⅱ-Ⅲ gastric cancer ***: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were ***: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC ***: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

关键词： Prognostic test adjuvant chemotherapy advanced gastric cancer feasibility gastrectomy

Sarcopenia in cirrhotic patients: Does frailty matter while waiting for a liver transplant?

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World Journal of Gastrointestinal surgery 2024年第1期16卷 257-259页

作者： Xing-Jie Li Kang He Division of Transplant surgery Mayo Clinic ArizonaPhoenixAZ 85054United States Department of Liver surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

Sarcopenia reflects patient frailty and should be routinely assessed due to its high prevalence in cirrhotic patients awaiting liver ***-transplant nutritional optimization should be tailored for patients with a definitive diagnosis of sarcopenia,therefore improving functional status at transplant and reducing posttransplant *** and transplant surgeons should have raised awareness regarding sarcopenia and the reflected frailty that hinder posttransplant *** policymakers should also take into account when modifying the organ allocation model that sarcopenia or frailty might become a decisive factor in allocating organs for cirrhotic patients,in order to ensure post-transplant survival and quality of life.

关键词： Sarcopenia Liver transplant Organ allocation policy Cirrhosis Frailty

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of Stem Cells 2024年第3期16卷 257-266页

作者： Min Young Park Yong Sik Yoon Jae Ha Park Jong Lyul Lee Chang Sik Yu Division of Colon and Rectal surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as ***,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula *** This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and *** The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were *** data were compared according to anti-TNF therapy and CPF *** A total of 65 patients were *** median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)*** closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for *** cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,*** Anti-TNF therapy does not increase CPF closure rates in patients with stem cell ***,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF *** tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula Stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab

Boosting liver regeneration: kinase inhibitor as a new tool to prevent liver failure

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3145-3146页

作者： Anna Sichler Norbert Huser Klaus-Peter Janssen Department of surgery School of Medicine and HealthTechnical University of MunichMunichGermany

In a recent manuscript in Cell,a first-in-class small molecule inhibitor of the kinase MKK4(mitogen-activated protein kinase kinase 4)was described that greatly enhances liver regeneration after partial hepatectomy in animal models,with an excellent safety profile in humans.1 The findings of Zwirner et *** promise to alter the clinical management of liver failure in critically ill patients.

关键词： liver al. clinical

Retroaortic left renal vein associated to variations of liver vasculature and biliary system in a patient submitted to total pancreatectomy

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 526-529页

作者： Alessandro Fancellu Mario Maiore Lavinia Grasso Miriam Ferrara Alberto Porcu Department of medicine Surgery and PharmacyUnit of General Surgery 2-Clinica ChirurgicaUniversity of SassariSassari 07100Italy Department of medicine Surgery and PharmacyUnit of RadiologyUniversity of SassariSassari 07100Italy

Total pancreatectomy(TP) is a surgical procedure which includes the complete removal of the pancreatic gland, the spleen, the duodenum, the gallbladder, and the distal part of the stomach. TP represents the curative treatment of pancreatic cancer which simultaneously involves the head and the body/tail of the pancreas. Other possible indications for TP comprise multifocal parenchymal diseases, such as intraductal papillary mucinous neoplasms, pancreatic neuroendocrine tumors, multiple endocrine neoplasms, and chronic pancreatitis. Sometimes, TP is carried out in patients scheduled for pancreaticoduodenectomy(where only the head of the pancreas is removed) when a cancer located in the pancreatic head is intraoperatively found to also extend to the pancreatic body [1].

关键词： neoplasms stomach spleen

Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang Department of Thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina Department of Thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina Department of Thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment