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Chinese Journal of Chemistry 2024年第10期42卷 1175-1189页

作者： Guo-Feng Luo Wei-Hai Chen Xian-Zheng Zhang state Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei KeyLaboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanHubei 430079China Key Laboratoryof Biomedical Polymers of Ministry of Education&Departmentof Chemistry Wuhan UniversityWuhanHubei 430072China

tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of *** barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration *** achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing *** these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were *** the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

关键词： Nanomedicine tumor stroma Deep penetration Enhanced drug perfusion Cancer therapy Drug carriers Biomaterials Nanotechnology

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 103-118页

作者： Chenglin Liang Ge Zhang Linlin Guo Xinyi Ding Heng Yang Hongling Zhang Zhenzhong Zhang Lin Hou School of Pharmaceutical Sciences Key Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou UniversityZhengzhou 450001China

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells ***,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific *** detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive *** arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide *** can degrade the extracellularmatrix,leading to the enhanced penetration of *** targets tumor cells,releases DOX to induce senescence,and recruits effector immune ***,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor *** vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice *** work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

关键词： Cells senescence tumor stroma Structure transformable Programmed delivery Anti-tumor immunotherapy

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1878-1889页

作者： Fouzia Fazal Muhammad Arsalan Khan Sumayya Shawana Rahma Rashid Muhammed Mubarak Department of Pathology Jinnah Medical and Dental CollegeKarachi 74800SindhPakistan Department of General Surgery Sindh Institute of Urology&Transplantation(SIUT)Karachi 74200SindhPakistan Department of Pathology Bahria University of Health SciencesKarachi 74400SindhPakistan Department of Pathology SIUTKarachi 74200SindhPakistan

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic ***-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 *** We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological *** A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC *** CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 ***,histopathological,and clinical parameters were *** TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both *** tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological *** Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue *** demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and *** suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

关键词： Colorectal cancer Macrophages tumor stroma M2 subset tumor front tumor stage Lymphovascular invasion Prognosis tumor-associated macrophages Immunohistochemistry

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

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World Journal of Clinical Oncology 2024年第5期15卷 614-634页

作者： Marina A Senchukova Evgeniy A Kalinin Nadezhda N Volchenko Department of Oncology Orenburg State Medical UniversityOrenburg 460000Russia Department of Thoracic Surgery Orenburg Regional Cancer ClinicOrenburg 460021Russia Department of Pathology PA Hertzen Moscow Oncology Research CentreBranch of National Medical Research Radiological CenterMoscow 125284Russia

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant *** the diagnosis and treatment of LC remains an urgent task of modern ***,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic *** connection between different types of tumor MVs and the progression of LC is not well *** To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,*** patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/*** sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were *** morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC *** analysis was performed using Statistica 10.0 *** and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease *** operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease *** effectiveness of the predictive models was assessed by the area under the *** was analyzed using the Kaplan-Meier *** log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical *** Depending

关键词： Lung cancer Lung squamous cell carcinoma tumor microvessels tumor stroma Regional lymph node metastases Disease recurrence Disease prognosis

How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

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World Journal of Stem Cells 2023年第5期15卷 281-301页

作者： María Belén Novoa Díaz Pedro Carriere Claudia Gentili Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del SurBahía Blanca 8000Buenos AiresArgentina Instituto de Ciencias Biológicas y Biomédicas del Sur Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)-Universidad Nacional del Sur(UNS)Bahía Blanca 8000Buenos AiresArgentina

Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant *** is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment ***,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug *** data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic *** alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine *** is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and ***,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on *** TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of *** in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

关键词： Colorectal cancer Colorectal cancer stem cells tumor microenvironment factors tumor stroma Gut microbiota Cancer progression

tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway:Providing understanding of the complex mechanisms of chemoresistance

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World Journal of Gastroenterology 2022年第26期28卷 3027-3046页

作者： María Belén Novoa Díaz María Julia Martín Claudia Gentili Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Argentina Departamento de Química Universidad Nacional del Sur(UNS)-INQUISUR(CONICET-UNS)Bahía Blanca 8000Argentina

Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current *** of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including *** many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli ***,it can also be associated with other *** recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of *** this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the ***-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling *** advances in the field of oncology have been made in the last *** Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness,focusing on crosscommunication between CRC cells and the *** this analysis,our main objective was to increase the understanding of this complex disease considering a more global *** many treatments for advanced CRC fail due to mechanisms involving chemoresistance,the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

关键词： Colorectal cancer β-catenin pathway tumor stroma tumor microenvironment factors Cancer progression Drug resistance

NON-LINEAR OPTICAL IMAGING OF OBESITY-RELATED HEALTH RISKS:REVIEW

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Journal of Innovative Optical Health Sciences 2009年第1期2卷 9-25页

作者： THUC T.LE JI-XIN CHENG Weldon School of Biomedical Engineering Purdue University West Lafayette Indiana 47907USA Department of Chemistry and Weldon School of Biomedical Engineering Purdue University West Lafayette Indiana 47907USA

This review highlights the recent applications of non-linear optical(NLO)microscopy to study obesity-related health risks.A strong emphasis is given to the applications of coherent anti-Stokes Raman scattering(CARS)microscopy where multiple non-linear optical imaging modalities including CARS,sum-frequency generation(SFG),and two-photon fluorescence are employed simultaneously on a single microscope *** examples on applications of NLO microscopy to study lipid-droplet biology,obesity-cancer relationship,atherosclerosis,and lipidrich biological structures are discussed.

关键词： Atherosclerosis coherent anti-Stokes Raman scattering lipid droplet mammary cancer non-linear optics obesity second harmonic generation sum-frequency generation twophoton fluorescence tumor stroma

Influencing factors and strategies of enhancing nanoparticles into tumors in vivo

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2265-2285页

作者： Mingming Zhang Shan Gao Dongjuan Yang Yan Fang Xiaojie Lin Xuechao Jin Yuli Liu Xiu Liu Kexin Su Kai Shi Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical UniversityShenyang 117004China

The administration of nanoparticles(NPs)first faces the challenges of evading renal filtration and clearance of reticuloendothelial system(RES).After that,NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor *** long as possible to prolong the time of NPs remaining in tumor tissue,NPs release active agent and induce pharmacological *** review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment,and discusses how to improve the final efficacy through adjusting the characteristics and structure of *** and future directions are also provided.

关键词： Nanoparticles Drug delivery Reticuloendothelial system tumor microenvironment tumor stroma Cancer-associated fibroblasts Extracellular matrix tumor vascular endothelial cells