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Efficacy of Detoxsan~? powder on diarrhea caused by gastrointestinal neuroendocrine tumors

World Journal of Gastroenterology 2019年第17期25卷 2133-2143页

作者： Thomas Langbein Wilfried Dathe Anika Deuerling Richard P Baum theranostics Center for molecular Radiotherapy and molecular imaging Zentralklinik Bad Berka Scientific Managment Heck Bio-Pharma GmbH

BACKGROUND Patients with neuroendocrine tumors(NETs) of the gastrointestinal tract suffer frequently from chronic diarrhea. A well characterized medical advice containing zeolite(Detoxsan~? powder) was applied to patients suffered from therapyrefractory diarrhea either by its frequency or by watery stool, despite receiving standard pharmacotherapy according to the guidelines for carcinoid syndrome and comorbidities. Detoxsan~? powder acts as an adsorbent and might reduce significantly symptoms of diarrhea in patients suffering from *** To overcome the therapy-refractory diarrhea of patients with NETs by the zeolite containing medical advice Detoxsan~? *** A total of 20 patients(12 female and 8 male) suffering from diarrhea either by its frequency or from watery stool caused by NETs were included. In each patient,the diagnosis had been confirmed by histology and somatostatin receptors expression proven by positron emission tomography/computed tomography using Ga-68-labeled somatostatin analogs. All patients received standard-of-care pharmacotherapy and were additionally given Detoxsan~? powder as an extemporaneous drug containing 90% natural Cuban zeolite and 10% magnesium aspartate. Recommended daily dosage ranges between 3 g once to three times per day. Each day dose and bowel movements were documented by the patients themselves in a pre-defined table. Additionally to the bowel movements quantitative determinations of serotonin, urea, creatinine and single ions were performed within the serum of the patients by commercially available equipment used as a matter of routine in the *** All patients enrolled in this pilot study did not only suffer from NETs, but also from comorbidities and treatment-resistant diarrhea. There was insufficient control of diarrhea, most probably due to the secretion of hormones like serotonin produced by the slowly growing and highly differentiated NETs. All patients only took Detoxsan~? powder as an antidiarrhea

关键词： Neuroendocrine tumor Diarrhea Carcinoid syndrome Treatment Clinoptilolite Mordenite Zeolite

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Overproduction of reactive oxygen species–obligatory or not for induction of apoptosis by anticancer drugs

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Chinese Journal of Cancer Research 2016年第4期28卷 383-396页

作者： Donika Ivanova Zhivko Zhelev Ichio Aoki Rumiana Bakalova Tatsuya Higashi Medical Faculty Trakia University Institute of Biophysics & Biomedical Engineering Bulgarian Academy of Sciences Department of molecular imaging and theranostics National Institute of Radiological SciencesNational Institute for Quantum and Radiological Science and Technology Medical Faculty Sofia University

Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species （ROS） and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS^independent pathways. We try to answer the question：＂Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues？＂ The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.

关键词： Cancer reactive oxygen species chemotherapy ROS-independent apoptosis ROS-dependent apoptosis

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Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

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World Journal of Gastroenterology 2018年第48期24卷 5491-5504页

作者： Winn Aung Atsushi B Tsuji Aya Sugyo Hiroki Takashima Masahiro Yasunaga Yasuhiro Matsumura Tatsuya Higashi Department of molecular imaging and theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology (QST-NIRS) Division of Developmental Therapeutics Exploratory Oncology Research and Clinical Trial CenterNational Cancer Center

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer *** Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for

关键词： Pancreatic cancer Anti-tissue factor antibody Indocyanine green Photoimmunotherapy Near-infrared

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Beyond Antibiotics:Photo/Sonodynamic Approaches for Bacterial theranostics

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Nano-Micro Letters 2020年第10期12卷 313-335页

作者： Xin Pang Dengfeng Li Jing Zhu Jingliang Cheng Gang Liu Henan Key Laboratory of Functional Magnetic Resonance imaging and molecular imaging Department of Magnetic Resonance ImagingThe First Affiliated Hospital of Zhengzhou University450052 ZhengzhouPeople’s Republic of China State Key Laboratory of molecular Vaccinology and molecular Diagnostics and Center for molecular imaging and Translational Medicine School of Public HealthXiamen University361102 XiamenPeople’s Republic of China Amoy Hopeful Biotechnology Co. Ltd361027 XiamenPeople’s Republic of China

Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent *** treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance *** replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for *** this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic ***,potential limitations and future perspectives are also highlighted.

关键词： Photodynamic therapy Sonodynamic therapy theranostics Multidrug resistant Reactive oxygen species

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Terpyridine-Grafted Nitrogen-Terminal Endowing Cyanine with Metal-Ion-Regulated Photophysical Properties for Cancer theranostics

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Research 2023年第4期2023卷 117-130页

作者： Junfei Zhu Gang He Peng-Hang Chen Yajie Zhang Yafei Zhang Shan Lei Yu Zhang Meng Li Peng Huang Jing Lin Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)Guangdong Key Laboratory for Biomedical Measurements and Ultrasound ImagingSchool of Biomedical EngineeringShenzhen University Medical SchoolShenzhen 518060China

Heptamethine cyanines(Cy7)are one of the most important dyes in bioimaging and phototherapy,but they often suffer from poor photostability or limited photothermal conversion ***,a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is *** innovatively modifying the nitrogen with functional groups,a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold(denoted as CydtPy)was synthesized and exhibited tunable photophysical properties when chelating with various metal ions(Mn^(2+),Fe^(2+),etc.).In comparison with metal-ion-free PEGylated CydtPy(LET-11),Mn^(2+)-chelated LET-11(namely,LET-11-Mn)exhibited the increased fluorescence emission intensity,and Fe^(2+)-chelated LET-11(namely,LET-11-Fe)showed the enhanced photostability with~2-fold increase in photothermal conversion *** simply switching the chelated metal ion species,LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging,magnetic resonance imaging,or photoacoustic ***,LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in *** work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.

关键词： versatile terminated cyanine

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Cell-surface cascaded landing location for nanotheranostics

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Chinese Chemical Letters 2017年第9期28卷 1799-1800页

作者： En Ren Junqing Wang Gang Liu State Key Laboratory of molecular Vaccinology molecular Diagnostics Center for Molecular Imaging Translational MedicineSchool of Public Health Xiamen UniversityXiamen 361005 China

theranostics is an appealing approach in precision medicine and it is still a critical challenge to design smart strategies which can precisely accumulate the functional probes/drugs into targeted disease ***-surface cascaded landing location is an effective strategy to develop functional drug-loading platforms to explore basic physiological processes at the cellular level and to facilitate the development of nanotheranostics for disease treatment.

关键词： theranostics molecular imaging Nanomedicine Cell-surface engineering Self-assembliag

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Traceable Lactate-Fueled Self-Acting Photodynamic Therapy against Triple-Negative Breast Cancer

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Research 2024年第3期2024卷 723-733页

作者： Yifan Zhang Guangle Feng Ting He Min Yang Jing Lin Peng Huang Marshall Laboratory of Biomedical Engineering International Cancer CenterShenzhen Key Laboratory of Tumor Visualization Molecular MedicineLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen UniversityShenzhen518055China.

The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy(PDT)in triple-negative breast cancer(TNBC),while the overproduction of lactate(LA)facilitates the development,aggressiveness,and therapy resistance of *** address these issues,a self-acting PDT nanosystem(HL@hMnO_(2)-LO_(x)@HA)is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha(HPPH),luminol,and LA oxidase(LO_(x))in a hyaluronic acid(HA)-coated hollow manganese dioxide(hMnO_(2))***_(x) catalyzes the oxidation of LA into pyruvate and hydrogen peroxide(H_(2)O_(2)),thus depleting the overproduced intratumoral *** the acidic tumor microenvironment,H_(2)O_(2) reacts with luminol and hMnO_(2) to yield blue luminescence as well as O_(2) and Mn^(2+),***^(2+)could further enhance this *** is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated *** generated O_(2) alleviates the hypoxia state of the TNBC tumor to produce sufficient 1O_(2) for self-oxygenation *** Mn^(2+)performs T1 magnetic resonance imaging to trace the self-acting PDT *** work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.

关键词： Breast Therapy manganese

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Boron difluoride formazanate dye for high-efficiency NIR-Ⅱ fluorescence imaging-guided cancer photothermal therapy

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Chinese Chemical Letters 2022年第5期33卷 2501-2506页

作者： Hanming Dai Zijin Cheng Tian Zhang Weili Wang Jinjun Shao Wenjun Wang Yongxiang Zhao Xiaochen Dong Liping Zhong Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Nanjing Tech University(NanjingTech)Nanjing 211800China School of Physical Science and Information Technology Liaocheng UniversityLiaocheng 252059China National Center for International Biotargeting theranostics Guangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor TheranosticsGuangxi Medical UniversityNanning 530021China

The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic ***, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.

关键词： NIR-II nanotheranostics Boron difluoride formazanate Fluorescence imaging Photothermal therapy Phototheranostics

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Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/m TOR inhibitor

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World Journal of Gastroenterology 2017年第42期23卷 7551-7562页

作者： Winn Aung Atsushi B Tsuji Hitomi Sudo Aya Sugyo Yoshinori Ukai Katsushi Kouda Yoshikazu Kurosawa Takako Furukawa Tsuneo Saga Tatsuya Higashi Department of molecular imaging and theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology(QST-NIRS) Perseus Proteomics Inc. Innovation Center for Advanced Medicine Fujita Health University Department of Radiological and Medical Laboratory Sciences Nagoya University Graduate School of Medicine Department of Diagnostic Radiology Kyoto University Hospital

AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer *** Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm *** We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, dec

关键词： Radioimmunotherapy Pancreatic cancer Anti-integrin α6β4 antibody Yttrium-90 NVP-BEZ235

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Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Center for molecular imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

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