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Nestin:A novel angiogenesis marker and possible target for tumor angiogenesis

World Journal of Gastroenterology 2013年第1期19卷 42-48页

作者： Yoko Matsuda Masahito Hagio Toshiyuki Ishiwata departments of pathology and integrative oncological pathology Nippon Medical SchoolTokyo 113-8602Japan

Abnormal vasculature,termed tumor vessels,is a hallmark of solid *** degree of angiogenesis is associated with tumor aggressiveness and clinical ***,exact quantification of tumor vessels is useful to evaluate ***,selective detection of newly formed tumor vessels within cancer tissues using specific markers raises the possibility of molecular targeted therapy via the inhibition of tumor ***,an intermediate filament protein,is reportedly expressed in repair processes,various neoplasms,and proliferating vascular endothelial *** expression is detected in endothelial cells of embryonic capillaries,capillaries of the corpus luteum,which replenishes itself by angiogenesis,and proliferating endothelial progenitor cells,but not in mature endothelial ***,expression of nestin is relatively limited to proliferating vascular endothelial cells and endothelial progenitor *** expression is also reported in blood vessels within glioblastoma,prostate cancer,colorectal cancer,and pancreatic cancer,and its expression is more specific for newly formed blood vessels than other endothelial cell ***-positive blood vessels form smaller vessels with high proliferation activity in *** of nestin in vascular endothelial cells suppresses endothelial cell growth and tumor formation ability of pancreatic cancers in *** nestin to more accurately evaluate microvessel density in cancer specimens may be a novel prognostic ***,nestin-targeted therapy may suppress tumor proliferation via inhibition of angiogenesis in numerous malignancies,including pancreatic *** this review article,we focus on nestin as a novel angiogenesis marker and possible therapeutic target via inhibition of tumor angiogenesis.

关键词： Nestin Angiogenesis Molecular targeting therapy Gastrointestinal cancer Pancreatic cancer Microvessel density CD34 CD31 Factor VIII

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Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

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World Journal of Gastroenterology 2011年第4期17卷 409-418页

作者： Toshiyuki Ishiwata Yoko Matsuda Zenya Naito Department of pathology Integrative Oncological Pathology Nippon Medical School

Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

关键词： Cancer growth Intermediate filament protein Cancer invasion Tumor migration Nestin Stem cell marker Tumor angiogenesis

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Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

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Oncology Research 2024年第4期32卷 769-784页

作者： HUAN GAO JIE ZHANG TONY GKLEIJN ZHAOYONG WU BING LIU YUJIN MA BAOYUE DING DONGFENG YIN Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics Department of PharmaceuticsCollege of MedicineJiaxing UniversityJiaxing314001China Department of Pharmacy The General Hospital of Xinjiang Military RegionUrumqi830000China Department of pathology and Medical Biology University Medical Center GroningenUniversity of GroningenGroningen9713 GZThe Netherlands Department of pathology Laboratory of Experimental OncologyErasmus MCRotterdam3015 GDThe Netherlands Department of Pharmacy Jiaxing Maternal and Child Health Care HospitalAffiliated Hospital of Jiaxing UniversityJiaxing314001China Qinghai Enlu Biotechnology Co. Ltd.Haidong810700China

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and *** treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic *** improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone ***(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size *** in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX *** micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated *** binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis *** vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic *** conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

关键词： Pluronic micelles Targeted nanotherapeutics Nanoparticulate drug delivery system Breast cancer with bone metastasis Therapeutic efficacy

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Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

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World Journal of Gastroenterology 2024年第40期30卷 4399-4403页

作者： Vladislav V Tsukanov Julia L Tonkikh Edward V Kasparov Alexander V Vasyutin Clinical Department of the Digestive System pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol *** deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver *** et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin *** interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular *** is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of *** is assumed that M2 TAM promote proliferation and migration of tumor *** to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological ***,the work of the Chinese authors deserves attention and further development.

关键词： Liver cancer Treatment Calculus bovis Tumor-associated macrophages M2 tumor Macrophage polarization Wnt/β-catenin pathway

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Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

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Oncology Research 2024年第3期32卷 503-515页

作者： XING YE ZHOUTING TUO KAI CHEN RUICHENG WU JIE WANG QINGXIN YU LUXIA YE AKIRA MIYAMOTO KOO HAN YOO CHI ZHANG WURAN WEI DENGXIONG LI DECHAO FENG Samuel Oschin Comprehensive Cancer Institute Department of MedicineDepartment of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesCA90048USA Department of Urology The Second Afiliated Hospital of Anhui Medical UniversityHefei230601China Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu610041China Department of pathology Ningbo Diagnostic pathology Center Ningbo315021China Department of Public Research Platfom Taizhou Hospital of Zhejiang Province Afliated to Wenzhou Medical UniversityLinhai317000China Department of Rehabilitation West Kyushu UniversityKanzaki shi842-8585Japan Department of Urology Kyung Hee UniversitySeoul446701South Korea Department of Rehabilitation The Afliated Hospital of Southwest Medical UniversityLuwzhou646000China

The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic *** study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in *** observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these *** conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.

关键词： Pan-cancer RNA 5-methylcytosine ALYREF Immwno-oncological efects

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Low-grade myofibrosarcoma of the maxillary sinus:Two case reports

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World Journal of Clinical Oncology 2024年第4期15卷 566-575页

作者： Anna Mydlak ŁukaszŚcibik Monika Durzynska Jakub Zwoliński Karolina Buchajska Olga Lenartowicz Jakub Kucharz Department of Head and Neck Cancer Maria Sklodowska-Curie National Research Institute of OncologyWarsaw 02-781Poland Department of Otolaryngology and Head and Neck oncological Surgery The 5th Military Clinical Hospital with PolyclinicKrakow 30-901Poland Department of pathology Maria Sklodowska-Curie National Research Institute of OncologyWarsaw 02-781Poland Department of Genitourinary Oncology Maria Sklodowska-Curie National Research Institute of OncologyWarsaw 02-781Poland

BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is an extremely rare tumor characterized by the malignant proliferation of *** most commonly develops in adults,predominantly in males,in the head and neck region,oral cavity,especially on the tongue,mandible,and *** article presents 2 cases of LGMS localized to the maxillary sinus and provides an overview of the available *** SUMMARY Two patients with LGMS located in the maxillary sinus underwent surgery at the Department of Head and Neck *** 1:A 46-year-old patient was admitted to the clinic with suspected LGMS recurrence in the right maxillary sinus(rT4aN0M0),with symptoms of pain in the suborbital area,watering of the right eye,thick discharge from the right nostril,and augmented facial *** open biopsy-confirmed LGMS,the patient underwent expanded maxillectomy of the right side with immediate palate reconstruction using a microvascular skin flap harvested surgically from the middle *** patient qualified for adjuvant radiotherapy for the postoperative bed,with an additional ***,the patient is under 1.5 years of observation with no evidence of *** 2:A 45-year-old man was admitted to our clinic with facial asymmetry,strabismus,exophthalmos,and visual impairment in the right *** months earlier,the patient had undergone partial jaw resection at another hospital for fibromatosis.A contrast-enhanced computed tomography scan revealed a tumor mass in the postoperative log after an earlier *** open biopsy confirmed lowgrade fibrosarcoma(rT4aN0M0).The patient qualified for an extended total right maxillectomy with orbital excision and right hemimandibulectomy with immediate microvascular reconstruction using an anterolateral thigh *** patient subsequently underwent adjuvant radiotherapy to the postoperative *** 9 months,recurrence occurred in the right mandibular arch below the irradiated *** lesion infiltrated t

关键词： Head and neck cancer Paranasal sinuses Maxillary sinus Sarcoma Low-grade myofibroblastic sarcoma Case report

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A review on Eph/ephrin,angiogenesis and lymphangiogenesis in gastric,colorectal and pancreatic cancers

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Chinese Journal of Cancer Research 2017年第4期29卷 303-312页

作者： Julia Rudno-Rudzifiskal Wojciech Kielan Ewelina Frejlichl Krzysztof Kotulski Wojciech Hap Krzysztof Kurnoll Przemystaw Dzierzek Marcin Zawadzkil, Agnieszka Haton -nd Department of General and oncological Surgery pathology Department Wrodaw Medical University Borowska 213 50-556 Wrochw Poland

Erythroprotein-producing human hepatocellular carcinoma receptors （Eph receptors） compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins （Ephrins） are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes. Moreover Eph/ephrin system is one of the crucial ones in angiogenesis and lymphangJogenesis. With such a wide range of impact it is clear that disturbed function of this system leads to pathology. Eph/ephrin system is involved in carcinogenesis and cancer progression. Although the idea of participation of ephrin in carcinogenesis is obvious, the exact way remains unclear because of complex bi-directional signaling and cross-talks with other pathways. Further studies are necessary to find a new target for treatment.

关键词： Epldephrin system lymphangiogenesis angiogenesis gastric cancer colon cancer pancreatic cancer

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Assessing risks for gastric cancer: New tools for pathologists

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World Journal of Gastroenterology 2006年第35期12卷 5622-5627页

作者： Robert M Genta Massimo Rugge Department of pathology University of Texas Southwestern Medical Center at Dallas Texas United states Department of oncological and Surgical Sciences University of Padova Italy

Although the Sydney Systems (original and updated) for the classification of gastritis have contributed substantially to the uniformity of the reporting of gastric conditions, they lack immediacy in conveying to the user information about gastric cancer risk. In this review, we summarize the current understanding of the gastric lesions associated with an increased risk for cancer, and present the rationale for a proposal for new ways of reporting gastritis. In addition to the traditional histopathological data gathered and evaluated according to the Sydney System rules, pathologists could add an assessment expressed as grading and staging of the gastric inflammatory and atrophic lesions and integrate these findings with pertinent laboratory information on pepsinogens and gastrin levels. Such an integrated report could facilitate clinicians’ approach to the management of patients with gastric conditions.

关键词： Gastritis Staging and grading Gastritis Histology

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Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

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World Journal of Gastroenterology 2008年第5期14卷 800-802页

作者： Carlos Eduardo Paiva Francisco Alves Moraes Neto Abbas Agaimy Maria Aparecida Custódio Domingues Silvia Regina Rogatto oncological and Hemato-oncological Center So Paulo State University Botucatu So Paulo 18610-170 Brazil Department of pathology Amaral Carvalho Hospital Jaú So Paulo Brazil Institute of pathology Nuremberg Clinic Center Nuremberg Germany Department of pathology So Paulo State University Botucatu So Paulo 18610-170 Brazil Department of Urology So Paulo State University Botucatu So Paulo 18610-170 Brazil

Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.

关键词： Gastrointestinal stromal tumors PEComa Coexistence Liver Synchronous

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Solid pseudopapillary tumor of the pancreas:A systematic review of clinical,surgical and oncological characteristics of 1384 patients underwent pancreatic surgery

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 331-338页

作者： Gennaro Mazzarella Edoardo Maria Muttillo Diego Coletta Biagio Picardi Stefano Rossi Simone Rossi Del Monte Vito Gomes Irnerio Angelo Muttillo Division of General and Emergency Surgery San Filippo Neri Hospital00136 RomeItaly Department of Surgery“Pietro Valdoni” Sapienza University of RomeViale del Policlinico 15500161 RomeItaly Surgical and Medical Department of Translational Medicine Sant’Andrea HospitalSapienza University of Rome00185 RomeItaly Department of Surgical Sciences Umberto I University HospitalSapienza University of Rome00136 RomeItaly Department of General Surgery Ospedali Riuniti Marche Nord61121 PesaroItaly Department of pathology San Filippo Neri Hospital00136 RomeItaly

Background:Pancreatic solid pseudopapillary tumors(SPTs)are rare clinical entity,with low malignancy and still unclear *** account for less than 2%of exocrine pancreatic *** study aimed to perform a systematic review of the main clinical,surgical and oncological characteristics of pancreatic *** sources:MEDLINE/PubMed,Web of Science and Scopus databases were systematically searched for the main clinical,surgical and oncological characteristics of pancreatic SPTs up to April 2021,in accordance with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)*** endpoints were to analyze treatments and oncological ***:A total of 823 studies were recorded,86 studies underwent full-text reviews and 28 met inclusion ***,1384 patients underwent pancreatic *** age was 30 years and 1181 patients(85.3%)were *** most common clinical presentation was non-specific abdominal pain(52.6%of cases).Mean overall survival was 98.1%.Mean recurrence rate was 2.8%.Mean follow-up was 4.2 ***:Pancreatic SPTs are rare,and predominantly affect young women with unclear *** resection is the gold standard of treatment achieving good oncological impact and a favorable prognosis in a yearly life-long follow-up.

关键词： Frantz’s tumor Pancreas Pancreatic neoplasms Pancreatic surgery Solid pseudopapillary tumor

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