A5048749176- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Esophageal Cancer Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Pancreatic and Hepatic Oncology Research
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Gastric Cancer Management and Outcomes
- Ubiquitin and proteasome pathways
- Retinoids in leukemia and cellular processes
- Advanced Proteomics Techniques and Applications
- Pancreatitis Pathology and Treatment
- Supramolecular Self-Assembly in Materials
- Gallbladder and Bile Duct Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Biotin and Related Studies
- Photodynamic Therapy Research Studies
- Chronic Kidney Disease and Diabetes
- Biochemical and Molecular Research
- Advancements in Photolithography Techniques
- Porphyrin and Phthalocyanine Chemistry
- Advanced Fluorescence Microscopy Techniques
- Nanofabrication and Lithography Techniques
- Cholinesterase and Neurodegenerative Diseases
The University of Tokyo
2016-2023
University of Tokyo Hospital
2021
Bunkyo University
2018
Abstract Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization considered a promising approach, we aimed develop activatable fluorescence probe visualize ESCCs. First, based on the fact that aminopeptidase...
Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal peptides proteins. However, methodology to monitor activities CPs is poorly developed. Here, we present first versatile design strategy obtain activatable fluorescent probes for by utilizing intramolecular spirocyclization rhodamine translate "aliphatic carboxamide aliphatic carboxylate" structural conversion catalyzed into dynamic fluorescence activation. Based on this novel strategy,...
Fluorescent probes that can selectively detect tumour lesions have great potential for fluorescence imaging-guided surgery. Here, we established a library-based approach efficient screening of tumour-selective imaging based on discovery biomarker enzymes. We constructed combinatorial fluorescent probe library aminopeptidases and proteases, which is composed 380 with various substrate moieties. Using this library, performed lysate-based in vitro and/or direct imaging-based ex vivo freshly...
Si-Rhodamines are bright fluorophores with red to near-infrared (NIR) emission, and widely used for fluorescence imaging of biological phenomena. Here, in order extend the scope Si-rhodamine fluorophores, we established a versatile synthesis unsymmetrical Si-rhodamines. To illustrate its value, one these new synthesize far-red NIR probe hypoxia, showed that it can visualize hepatic ischemia mice vivo.
Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival patients. However, there exist some cases where 5-ALA fails to fluoresce. In other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed develop a novel hydroxymethyl rhodamine green (HMRG)-based labeling system that can repeatedly administered topical...
Postoperative pancreatic fistula is a serious and fatal complication of gastrectomy for gastric cancer. Blunt trauma to the parenchyma pancreas can result from an assistant's forceps compressing retracting pancreas, which in turn may juice leakage. However, no published studies have focused on blunt during laparoscopic surgery. Our aim was investigate relationship between compression leakage swine model.Three female pigs were used this study. The gently compressed dorsally 15 minutes...
We have developed an activatable red fluorescence probe for dipeptidylpeptidase-IV (DPP-IV) by precisely controlling the photoinduced electron transfer (PeT) process of a fluorescent scaffold, SiR600. The exhibited extremely low background signal and showed significant activation upon reaction with DPP-IV, enabling sensitive detection esophageal cancer in clinical specimens from patients.
Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal peptides proteins and play indispensable roles in various physiological pathological processes. However, only few highly activatable fluorescence probes for CPs have been reported, there is need flexibly tunable molecular design platform to afford range biological medical research. Here, we focused on unique activation mechanism ProTide-based prodrugs established modular CP-targeting...
Tissue-restricted bioreactions can be utilized to design chemical-biological tools and prodrugs. We have developed a fluorescent-substrate-library-based enzyme discovery approach screen tissue extracts for enzymatic activities of interest. Assay-positive candidate proteins were identified by diced electrophoresis gel assay followed peptide mass fingerprinting. discovered that pyruvyl anilide is specifically hydrolyzed carboxylesterase 2 (CES2), which predominantly localized in the liver...
Abstract Rapid diagnosis of metastatic lymph nodes (mLNs) colorectal cancer (CRC) is desirable either intraoperatively or in resected fresh specimens. We have developed a series activatable fluorescence probes for peptidase activities that are specifically upregulated various tumors. aimed to discover target enzyme detecting mLNs CRC. Among our probes, we found gGlu-HMRG, gamma-glutamyl transpeptidase (GGT)-activatable probe, could detect mLNs. This was unexpected, because previously...
Cellular homeostasis is maintained by a complex network of reactions catalyzed enormous numbers enzymatic activities (the enzymome), which serve to determine the phenotypes cells. Here, we focused on enzymomics proteases and peptidases because these enzymes are an important class disease-related proteins. We describe system that (A) simultaneously evaluates metabolic peptides using series exogenous peptide substrates (B) identifies metabolize specified substrate with high throughput....
Abstract Background A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP‐HMRG), which becomes after cleavage by dipeptidyl peptidase‐IV (DPP‐IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can detected spraying EP‐HMRG. Methods Fluorescence imaging 17 cases HNSCCs resected using endoscopic or surgical resection was performed ex vivo EP‐HMRG, then fluorescence intensity...
It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated become after cleavage a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed reported useful for detection squamous cell carcinoma head neck, esophagus; however, there lack studies focuses on detecting EGJ by...
Complete resection is the only possible treatment for cholangiocarcinoma in extrahepatic biliary tree (eCCA), although current imaging modalities are limited their ability to accurately diagnose longitudinal spread. We aimed develop fluorescence techniques real-time identification of eCCA using an enzyme-activatable probe, which emits immediately after activation by a cancer-specific enzyme.Using lysates and small tissue fragments collected from surgically resected specimens, we selected...
OPINION article Front. Oncol., 06 August 2019Sec. Cancer Imaging and Image-directed Interventions Volume 9 - 2019 | https://doi.org/10.3389/fonc.2019.00727
Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme fluorescence imaging for GC.GC and normal (NP) tissues from 96 20 patients, respectively were evaluated MMP-14 expression. Live cell GC lines (NUGC4, MKN45, MKN74, HGC-27, Kato-III) performed using MMP-14-activatable probe; BODIPY-MMP. Furthermore, overall survival (OS) calculated all...
Radical resection is the only curative treatment for pancreatic cancer, which a life-threatening disease. However, it often not easy to accurately identify extent of tumor before and during surgery. Here we describe development novel method detect tumors using tumor-specific enzyme-activatable fluorescence probe.Tumor non-tumor lysate or small specimen collected from resected were selected serve as most appropriate probe distinguish cancer tissues noncancerous tissues. The was sprayed onto...
Since gamma-glutamyl transpeptidase (GGT) is highly and locally expressed in human breast cancer, a GGT-enzymatically activatable fluorescent probe, hydroxymethyl rhodamine green (gGlu-HMRG), has been developed to detect the cancer area with high performance. In this study, GGT expression efficacy of gGlu-HMRG on visualization were investigated canine mammary gland tumors (MGT). Seventeen non-fixed fresh-frozen MGT specimens each peritumoral control tissue utilized. The mRNA levels observed...
Objective: To assess the predictive value of chymotrypsin activity in pancreatic juice on clinically relevant postoperative fistula (CR-POPF) after resection, since peptidases rather than glycolytic enzymes play a pivotal role causing tissue damage due to leakage. Background: The risk CR-POPF has been estimated based amylase level abdominal drainage fluid. Methods: Eighty-one consecutive patients underwent pancreatoduodenectomy, and fluids were collected for 14 days. fluid these measured,...
Abstract Background Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative bile had not been established. Method Bilirubin levels in drained abdominal fluids collected from 23 patients who undergone hepatectomy ( n = 22) or liver transplantation 1) were measured using microplate reader excitation/emission wavelengths of 497/527 nm after applying 5 µM...
Irritable bowel syndrome (IBS) has no clinically accepted biomarkers even though it affects a large number of individuals worldwide. To address this lack understanding, we evaluated peptidase activity in fecal samples from 35 patients with diarrheal IBS without symptom exacerbation (IBS-n) and healthy subjects using library 384 fluorescent enzymatic substrate probes. IBS-n had high trypsin-like for cleavage C-terminal lysine arginine residues low elastase-like serine glycine residues. These...
ADVERTISEMENT RETURN TO ISSUEIn FocusNEXTMeeting Proceedings ICBS2016—Translating the Power of Chemical Biology to Clinical AdvancesYugo Kuriki†, Toru Komatsu*†‡, Peter D. Ycas§, Sara K. Coulup∥, Erick J. Carlson∥, and William C. Pomerantz*§∥View Author Information† Graduate School Pharmaceutical Sciences, University Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan‡ Japan Science Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan§ Department Chemistry, Minnesota,...
Abstract PURPOSE: ALA is commonly used as an intraoperative tool in malignant glioma surgery, which has been proven effective for radical tumor resection and extended progression-free survival. However, there are some limitations its use, such false positivity, negativity, inability of re-administration. We aim to develop a novel fluorescent labeling system can be repeatedly administered by spray during using hydroxymethyl rhodamine green (HMRG) scaffold originally designed at our university...
<title>Abstract</title> Background: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated become after cleavage a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed reported useful for detection squamous cell carcinoma head neck, esophagus; however, there lack...