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Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative Tumor recurrence and metastasis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3383-3397页

作者： Minglu Zhou Qingting Zuo Yuan Huang Lian Li Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and oncefor-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition,immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell “seeds” but also resulted in abscopal effect on disturbing pre-metastatic “soil”. Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.

关键词： Hydrogel Postoperative treatment Tumor recurrence Pre-metastatic niche CXCR4 inhibition Immunotherapy Local therapy Immunogenic cell death

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Anti-inflammatory catecholic chitosan hydrogel for rapid surgical trauma healing and subsequent prevention of Tumor recurrence

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Chinese Chemical Letters 2020年第7期31卷 1807-1811页

作者： Gang He Xu Yan Zhaohua Miao Haisheng Qian Yan Ma Yan Xu Li Gao Yang Lu Zhengbao Zha School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Hefei University of TechnologyHefei 230009China School of Biomedical Engineering Research and Engineering Center of Biomedical MaterialsAnhui Medical UniversityHefei 230032China

Although occupying pillar position in clinical cancer treatments,surgery itself and surgical trauma would elicit series of local/systemic inflammation-related responses that resulted in high rate of Tumor recurrence.Herein,chitosan with conjugated gallic acid(CSG)molecules were coordinated with Fe3+to form CSG/Fe3+hydrogel for filling the tumo r-resected cavity with considerable wet-adhesion ability and anti-inflammatory performance.With the assistance of doxorubicin hydrochloride(DOX·HCl),CSG/Fe3+/DOX hydrogel exhibited syne rgistic photothermal-chemo tumo r-inhibited performance under near-infrared(NIR)light irradiation for eradicating residual and/or surgical trauma-recruited cancer cells.Thus,our study attempts to show a paradigm that realizes quick surgical trauma healing,inflammation inhibition and prevention of postsurgical Tumor recurrence.

关键词： Surgery Anti-inflammation Bactericidal capacity Trauma healing Tumor recurrence

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High Expression of p300 in Human Breast Cancer Correlates with Tumor recurrence and Predicts Adverse Prognosis

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Chinese Journal of Cancer Research 2011年第3期23卷 201-207页

作者： Xiang-sheng Xiao Mu-yan Cai Jie-wei Chen Xin-yuan Guan Hsiang-fu Kung Yi-xin Zeng Dan Xie State Key Laboratory of Oncology in South China Guangzhou 510060China Department of Breast Oncology Guangzhou 510060China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China The Chinese University of Hong Kong Hong KongChina

Objective：Transcriptional coactivator p300 has been shown to play a variety of roles in the transcription process and mutation of p300 has been found in certain types of human cancers.However,the expression dynamics of p300 in breast cancer （BC） and its effect on BC patients＇ prognosis are poorly understood.Methods：In the present study,the methods of tissue microarray and immunohistochemistry （IHC） were used to investigate the protein expression of p300 in BCs.Receiver operating characteristic （ROC） curve analysis,Spearman＇s rank correlation,Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data.Results：Based on the ROC curve analysis,the cutoff value for p300 high expression was defined when the H score for p300 was more than 105.High expression of p300 could be observed in 105/193 （54.4%） of BCs,in 6/25 （24.0%） of non-malignant breast tissues,respectively （P=0.004）.Further correlation analysis showed that high expression of p300 was positively correlated with higher histological grade,advanced clinical stage and Tumor recurrence （P0.05）.In univariate survival analysis,a significant association between high expression of p300 and shortened patients＇ survival and poor progression-free survival was found （P0.05）.Importantly,p300 expression was evaluated as an independent prognostic factor in multivariate analysis （P0.05）.Conclusion：Our findings provide a basis for the concept that high expression of p300 in BC may be important in the acquisition of a recurrence phenotype,suggesting that p300 high expression,as examined by IHC,is an independent biomarker for poor prognosis of patients with BC.

关键词： Breast cancer p300 Tumor recurrence Prognosis

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tumor Interstitial Fluid and Postoperative recurrence of tumors: an Experimental Study for Verifying Hypothesis of "tumor-phlegm Microenvironment"

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Chinese Journal of Integrative Medicine 2010年第5期16卷 435-441页

作者：孙大志巨大维何金陆烨武峰李畅魏品康 Department of Traditional Chinese Medicine Shanghai Changzheng Hospital the Second Military Medical University Department of Laboratory Digniostics Shanghai Changzheng Hospital the Second Military Medical University Department of Pathology Shanghai Changzheng Hospital the Second Military Medical University

Objective： To explore a method of extracting tumor interstitial fluid （TIF） which is similar to muddy phlegm in Chinese medicine （CM）, interleukin-8 （IL-8） in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on Tumor recurrence. Methods： tumor tissue was ground, centrifuged, and filtered for intercellular substances. tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline （NS） and a blank control on Tumor recurrence. Results： The content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different （P0.05）. Postoperative Tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups （60%, 12/20 vs. 20%, 4/20 vs. 15%, 3/20, χ2=11.058, P0.01）. tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group. Conclusions： TIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative Tumor recurrence, which provided preliminary experimental basis for hypothesis of ＂tumor-phlegm microenvironment＂.

关键词： tumor interstitial fluid muddy phlegm interleukin-8 Tumor recurrence

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Survival Reassessment at Tumor recurrence in Soft Matter

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Open Journal of Modelling and Simulation 2022年第1期10卷 58-69页

作者： Irina Trifonova Stefan Z. Stefanov Specialized Hospital for Active Treatment in Oncology Sofia Bulgaria Electricity System Operator (ESO EAD) Sofia Bulgaria

The paper reassesses a survival at Tumor recurrence in soft matter. First, the stability of structural motifs under shear in clusters of dipolar spheres is characterized. Next, there are introduced transitions between... 详细信息

The paper reassesses a survival at tumor recurrence in soft matter. First, the stability of structural motifs under shear in clusters of dipolar spheres is characterized. Next, there are introduced transitions between polymer knots and rhythms of these transitions are obtained. The sensor is built for these rhythms. Treatment, with a tensile force protocol, is modeled, when the tumor in soft matter is observed by the above sensor. Survival probability, at

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Survival at Tumor recurrence in Soft Matter

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Open Journal of Biophysics 2021年第2期11卷 147-158页

作者： Irina Trifonova Galina Kurteva Stefan Z. Stefanov Specialized Hospital for Active Treatment in Oncology Sofia Bulgaria ESO EAD Sofia Bulgaria

Survival at Tumor recurrence in soft matter, after chemotherapy, is assessed by RNA folding. It is shown that this recurrence is starting with development of a fluidlike globule;it changes the energy of soft matter;it proceeds as a resonant mixing;and at the end it causes diffusion. This diffusion is interpreted as metastasis in soft matter. A tumor memory is designed for its recurrence oscillations. These oscillations are marked as positive or negative according to their influence on life stabilization or destabilization. It is demonstrated that a tumor memorizes two types of recurrences. The intensity of chemotherapy in soft matter for a tumor with such memory is obtained. Survival at Tumor recurrence in soft matter, after chemotherapy, is assigned to one of the five regions of the phase diagram of the “thermalized” tumor by microenvironment. To each of these regions is collated a breast cancer survival class. It is found that the survival at Tumor recurrence in soft matter, after chemotherapy, well represents actual survival of 32 patients with breast cancer.

关键词： Survival Tumor recurrence Life Stabilization Chemotherapy Soft Matter

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A mixed blessing for liver transplantation patients—Rapamycin

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 14-21页

作者： Guang-Han Fan Chen-Zhi Zhang Feng-Qiang Gao Xu-Yong Wei Sun-Bin Ling Kai Wang Jian-Guo Wang Shu-Sen Zheng Mehrdad Nikfarjam Xiao Xu Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University CancerGuangzhou 510060China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou 310024China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310000China NHC Key Laboratory of Combined Multi-Organ Transplantation Hangzhou 310003China Department of Surgery University of MelbourneAustin HealthHeidelbergVIC 3084Australia

Background:Liver transplantation(LT)is an effective treatment option for end-stage liver disease.Mammalian target of rapamycin(m TOR)inhibitors,such as rapamycin,are widely used post LT.Data sources:In this review,we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT.The literature available on Pub Med for the period of January 1999-September 2022 was reviewed.The key words were rapamycin,sirolimus,liver transplantation,hepatocellular carcinoma,diabetes,and lipid metabolism disorder.Results:Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens.It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma(HCC)recurrence post LT.Rapamycin is closely related to two long-term complications after LT,diabetes and lipid metabolism disorders.Conclusions:Rapamycin prevents HCC recurrence post LT in some patients,but it also induces metabolic disorders.Reasonable use of rapamycin benefits the liver recipients.

关键词： Liver transplantation Rapamycin Metabolic disease Hepatocellular carcinoma Tumor recurrence

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Sirolimus improves the prognosis of liver recipients with hepatocellular carcinoma:A single-center experience

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Hepatobiliary & Pancreatic Diseases International 2023年第1期22卷 34-40页

作者： Peng Liu Xin Wang Huan Liu Shu-Xian Wang Qing-Guo Xu Lin Wang Xiao Xu Jin-Zhen Cai Organ Transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266100China Institute of Organ Donation and Transplantation Department of MedicineQingdao UniversityQingdao 266100China Department of Hepatobiliary and Pancreatic Surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China National Health Commission(NHC)Key Laboratory of Combined Multi-Organ Transplantation Hangzhou 310003China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China

Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients.The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.Methods:The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed.These patients were divided into the sirolimus group[patients took sirolimus combined with calcineurin inhibitors(CNIs)(n=125)]and non-sirolimus group[patients took CNI-based therapy without sirolimus(n=68)].recurrence-free survival(RFS)and overall survival(OS)were compared between the two groups.The prognostic factors and independent risk factors for RFS and OS were further evaluated.Results:Non-sirolimus was an independent risk factor for RFS(HR=2.990;95%CI:1.050-8.470;P=0.040)and OS(HR=3.100;95%CI:1.190-8.000;P=0.020).A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group(69.6%vs.80.9%,P=0.030).Compared with the non-sirolimus group,the sirolimus group had significantly better RFS(Precurrence and prolonged RFS and OS in LT patients with different stage of HCC.

关键词： Hepatocellular carcinoma Liver transplantation Sirolimus Tumor recurrence recurrence-free survival Overall survival

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Astragaloside in cancer chemoprevention and therapy

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Chinese Medical Journal 2023年第10期136卷 1144-1154页

作者： Yaning Wang Zhuo Zhang Zhaohua Cheng Wei Xie Hanjiao Qin Jiyao Sheng Department of Hepatobiliary and Pancreatic Surgery Second Hospital of Jilin UniversityChangchunJilin 130041China Department of Orthopedics China-Japan Union Hospital of Jilin UniversityChangchunJilin 13033China Department of Ophthalmology Second Hospital of Jilin UniversityChangchunJilin 130041China Department of Radiotherapy Second Hospital of Jilin UniversityChangchunJilin 130041China

tumor chemoprevention and treatment are two approaches aimed at improving the survival of patients with cancers.An ideal anti-tumor drug is that which not only kills tumor cells but also alleviates tumor-causing risk factors,such as precancerous lesions,and prevents Tumor recurrence.Chinese herbal monomers are considered to be ideal treatment agents due to their multi-target effects.Astragaloside has been shown to possess tumor chemoprevention,direct anti-tumor,and chemotherapeutic drug sensitization effects.In this paper,we review the effects of astragaloside on tumor prevention and treatment and provide directions for further research.

关键词： Astragaloside Carcinoma Chemoprevention Anti-tumor Tumor recurrence

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Fluctuations induced the competition between extinction and recurrence in a model of tumor growth

Fluctuations induced the competition between extinction and ...

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第九届全国动力学与控制学术会议

作者： LI Dong-Xi Xu Wei Department of Applied Mathematics Northwestern Polytechnical University

In this paper we mainly investigate the effects of the fluctuations on the competition between tumor extinction and recurrence in the model of tumor growth derived from the catalytic Michaelis-Menten reaction.Firstly,the stochastic model of tumor growth and the statistical properties of the different fluctuations are given.Then, for taking into account the influences of the fluctuations on the transition between two stable states:the state of extinction and the state of stable tumor,the Mean First

关键词： fluctuations model of tumor growth tumor extinction Tumor recurrence

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