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Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen Wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He Yulong Fan Xuan Li Makoto Kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao Cheng Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin Institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of Cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

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Effect of oral Lactococcus lactis containing endostatin on 1, 2-dimethylhydrazine-induced colon tumor in rats

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World Journal of Gastroenterology 2005年第46期11卷 7242-7247页

作者： Wei Li Chong-Bi Li Department of Obstetrics and Gynecology First People's Hospital of Hangzhou Hangzhou 310006 Zhejiang ProvinceChina Department of biology Zhaoqing CollegeZhaoqing 526000 Guangdong Province China

AIM： To investigate the effects of oral Lactococcus lactis （L lactis） containing endostatin on 1, 2-dimethylhydrazine （DMH）-induced rat colorectal cancer. METHODS： Recombinant endostatin was produced by the expression of L lactis NZ9000. Sixty male Wistar rats were injected with DMH （40 mg/kg body weight） subcutaneously once a week for 10 wk to induce colorectal cancer. The rats were gavaged with 1 mL of endostatin at a dose of 1×10^8/d and fed with the basal diet. The animals were killed after 22 wk for histopathological examination. The total time of experimental observation was 58 wk. RESULTS： Rat endostatin protein was expressed in L lactis. Recombinant endostatin exhibited a significant effect on colorectal cancer （P〈0.05）. Furthermore, the mean survival time of the rats treated with endostatin was longer than that of the animals treated with DMH. There was no statistically significant difference between the rats treated with endostatin and those treated with DMH. The results showed that endostatin could not result in complete cure. CONCLUSION： Oral endostatin exerts an influence on the progression of chemically induced colon tumors.

关键词： Endostatin DMH tumors

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MicroRNAs as Targets and Tools in B-Cell Lymphoma therapy

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Journal of Cancer therapy 2013年第3期4卷 466-474页

作者： Kalman Szenthe Katalin Nagy Krisztina Buzas Hans Helmut Niller Janos Minarovits Department of Medical Microbiology and Hygiene University of Regensburg Regensburg Germany Department of Oral biology and experimental Dental Research Faculty of Dentistry University of Szeged Szeged Hungary Department of Oral Surgery Faculty of Dentistry University of Szeged Szeged Hungary RT-Europe Nonprofit Research Center Mosonmagyarovar Hungary

MicroRNAs (miRNAs) are posttranscriptional regulators fine-tuning the level of most messenger RNAs (mRNAs) and proteins in mammalian cells. Their expression is dysregulated in neoplastic cells and upregulated or downregulated miRNAs play an important role in tumorigenesis. Changes in the miRNA transcriptome appear to be suitable markers for the differential diagnosis of various B-cell lymphoma types and there are therapeutic attempts to normalize the expression level of key cellular miRNAs involved in lymphomagenesis. In this review we wish to outline the most recent developments in the application of sophisticated, chemically modified antisense oligonucleotides and their nanoparticle complexes to suppress oncogenic miRNAs. These advances form the basis of a new therapeutic approach that may complement current protocols for B-cell lymphoma therapy. Anti-cytokine therapy aiming at the removal of cytokines that activate key oncomirs, and switching on silenced tumor suppressor miRNAs by epigenetic drugs might also be considered, on the long run, in the treatment of well defined B-cell lymphoma types.

关键词： MicroRNAs B-Cell Lymphoma therapy Antisense Oligonucleotides Anti-Cytokine therapy Epigenetic Drugs

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A melatonin-based targetable fluorescent probe for screening of tumor cells and real-time imaging of glutathione fluctuations in tumor cells

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Chinese Chemical Letters 2022年第5期33卷 2527-2531页

作者： Xiwei Li Caiyun Liu Na Gao Wenlong Sheng Baocun Zhu School of Water Conservancy and Environment University of JinanJi’nan 250022China biology Institute Qilu University of Technology(Shandong Academy of Sciences)Ji’nan 250103China

Glutathione(GSH)is a key maintainer of cellular redox balance and plays an important role in many physiological *** example,GSH has been widely implicated in cancer initiation,progression and ***,the concentrations of GSH in tumor cells can influence drug *** the serious harmfulness of cancer and the important roles of GSH in cancer,it has great significance to devel-opment probes for screening of tumor cells and real-time monitoring of GSH fluctuations in tumor ***,no targetable probe for reversible imaging of GSH in tumor cells has been ***,we constructed a melatonin-based targetable and reversible fluorescent probe(GR-MT)for screening of tumor cells and real-time imaging of GSH fluctuations in tumor *** probe uses coumarin as the skeleton,Michael addition reaction as the reaction mechanism,and melatonin as the targeted groups of tumor *** experimental results demonstrate this probe has many advantages including high selec-tivity,satisfactory sensitivity,excellent reversible ability,rapid reaction speed,and outstanding targetabil-ity of tumor ***,this study provides a promising tool for tumor cells screening and real-time detection of GSH fluctuations in specific tumor cells.

关键词： Glutathione Reversible detection Fluorescent probe tumor cells screening Melatonin

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Application of Proteomics in the Study of tumor Metastasis

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Genomics, Proteomics & Bioinformatics 2004年第3期2卷 152-166页

作者： Zhen Cai Jen-Fu Chiu Qing-Yu He Department of Surgery The University of Hong KongHong KongChina Open Laboratory of Chemical biology of the Institute of Molecular Technology for Drug Discovery and Synthesis The University of Hong KongHong KongChina Institute of Molecular biology The University of Hong KongHong KongChina Department of Chemistry The University of Hong KongHong KongChina

tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.

关键词： proteomics metastasis tumor mechanism protein identification MALDI-TOF SELDI-ProteinChip

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experimental RESEARCH ON THE ANTI-CANCER IMMUNOMODULA-TIVE EFFECT OF THE POLYSOCOHARIBE-PEPTIDE OF CORIOLUS VERSICOLOR

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Chinese Journal of Cancer Research 1989年第2期1卷 10-15页

作者：许良中杨庆尧周金煦陈瑞婷李晓玉胡玉娟王筠默 Laboratory of Pathology Cancer Institute Shanghai Medical University Mushroom Research Laboratory Department of Biology Shanghai Teachers' University Department of Pharmacology Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai Institute of Traditional Chinese Medicine Shanghai Second Pharmaceutical Factoryolysocoharibe-peptide of Coriolus Versicolor (PSP) is a new anti-cancer immunomodulative drug. The present paper reports on the experimental research done with this drug. It was found that PSP had the ability to recover hemolysin HC50 to increase the weight of the thymus and increase the alexin of serum C3 and the IgG content of tumor bearing mice. FSP also significantly raised the pha-gocytic activity of macrophages in normal mice. PSP had a significant inhibitory effect on P38S and S180 cells. At the concentration of 1 mg/ml PSP inhibited the proliferating activity of some human tumor call lines such as SGC 7901 SPC SLY and Mei. It had a direct toxic effect on SPC cells. PSP significantly inhibited the synthesis of nucleic acids of Ehrlich ascites carcinoma cells. In addition PSP was antagonistic to the side effects of chemotherapy and radiotherapy.

Polysocoharibe-peptide of Coriolus Versicolor (PSP) is a new anti-cancer immunomodulative drug. The present paper reports on the experimental research done with this drug. It was found that PSP had the ability to recover hemolysin HC50, to increase the weight of the thymus, and increase the alexin of serum C3 and the IgG content of tumor bearing mice. FSP also significantly raised the pha-gocytic activity of macrophages in normal mice. PSP had a significant inhibitory effect on P38S and S180 cells. At the concentration of 1 mg/ml, PSP inhibited the proliferating activity of some human tumor call lines, such as SGC 7901, SPC, SLY and Mei. It had a direct toxic effect on SPC cells. PSP significantly inhibited the synthesis of nucleic acids of Ehrlich ascites carcinoma cells. In addition, PSP was antagonistic to the side effects of chemotherapy and radiotherapy.

关键词： PSP experimental RESEARCH ON THE ANTI-CANCER IMMUNOMODULA-TIVE EFFECT OF THE POLYSOCOHARIBE-PEPTIDE OF CORIOLUS VERSICOLOR SPC

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Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 199-210页

作者： Eckhard Klieser Stefan Swierczynski Christian Mayr Tarkan Jager Johanna Schmidt Daniel Neureiter Tobias Kiesslich Romana Illig Institute of Pathology Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Surgery Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Internal Medicine I Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Laboratory for Tumour biology and experimental Therapies(TREAT) Institute of Physiology and PathophysiologyParacelsus Medical University

Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last *** is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until *** general,Hh signaling is essential for pancreatic organogenesis,development,and tissue *** the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating *** vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor *** application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic *** this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

关键词： Pancreatic cancer Hedgehog Pancreatitis Pancreas Development

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Mitochondrial fission promotes cell migration by Ca2+/CaMKII/ERK/FAK pathway in hepatocellular carcinoma

Mitochondrial fission promotes cell migration by Ca2+/CaMKII...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Xiacheng Sun Haiyan Cao Lei Zhan Gang Wang Jibin Li Zhe Wang Bingrong Liu Qichao Huang Jinliang Xing State Key Laboratory of Cancer biology and experimental Teaching Center of Basic Medicine Fourth Military Medical University Department of Gastroenterology Second Affiliated Hospital of Harbin Medical University Department of General Surgery Tangdu HospitalFourth Military Medical University

Background and Aims: Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma(HCC) cells. However, how they influence the migration of tumor cells remained largely unknown. Methods: In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of HCC cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Results: Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of HCC when compared to primary HCC. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of HCC patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal adhesion dynamics and lamellipodia formation in HCC cells mainly by activating typical Ca2+/CaMKⅡ/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signaling in HCC cells and had a potential treatment effect for HCC metastasis in vivo. Conclusions: Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of HCC cell migration, which provides strong evidence for this process as a drug target in HCC metastasis treatment.

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Kinase inhibitors:look beyond the label on the bottle

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Cancer Drug Resistance 2019年第4期2卷 1032-1043页

作者： Paul Dent Andrew Poklepovic Laurence Booth John F.Hancock Department of Biochemistry and Molecular biology1 Virginia Commonwealth UniversityRichmondVA 23298-0035USA Department of Medicine Virginia Commonwealth UniversityRichmondVA 23298-0035USA Department of Integrative biology and Pharmacology University of Texas Health Science CenterHoustonTX 77030USA

The majority of scientists working in the field of cancer experimental therapeutics recognize that many drugs that claim to be“specific”for one target enzyme in fact regulate to varying degrees the activities of other additional protein *** of these targets are known and are recognized as being an essential component of a drug’s ***,many other targets fall into the category of“unknown unknowns”.Thus,the collective therapeutic outcome for almost all clinically relevant drugs is reliant on both the claimed primary and secondary“on”targets as well as some of the unexpected unknown“off”*** review discusses the biology of several FDA approved cancer therapeutic drugs whose initial reported targets only represented the tip-of-the-iceberg in terms of how each agent acted as an anti-tumor *** review also discusses a putative thorough pre-visualization methodology for drug-based research,prior to executing any wet *** approaches should be performed in an agnostic fashion and be based in part on the clinically safe drug’s C max and its area under the curve in a *** on tumor heterogeneity,considerations of how to approach developmental therapeutics in the age of“personalized medicine”are also discussed.

关键词： Autophagy histone deacetylase chaperone cancer

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P2X receptors: New players in cancer pain

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World Journal of Biological Chemistry 2014年第4期5卷 429-436页

作者： Alessia Franceschini Elena Adinolfi Department of Morphology Surgery and Experimental Medicine Section of Experimental Pathology Oncology and Biology University of Ferrara 44121 Ferrara Italy

Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2 X receptor are adenosine triphosphate(ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2 X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2 X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2 X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesisof cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2 X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.

关键词： Cancer Pain Adenosine triphosphate P2X2 P2X3 P2X2/3 P2X4 P2X7

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