A5025820520- PARP inhibition in cancer therapy
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- DNA Repair Mechanisms
- Click Chemistry and Applications
- Histone Deacetylase Inhibitors Research
- Microscopic Colitis
- Colorectal Cancer Screening and Detection
- Inflammasome and immune disorders
- Autoimmune and Inflammatory Disorders Research
- Biotin and Related Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Clinical Nutrition and Gastroenterology
- interferon and immune responses
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- Gastrointestinal disorders and treatments
- DNA and Nucleic Acid Chemistry
- Inflammatory Bowel Disease
National Cancer Institute
2020-2024
Center for Cancer Research
2021-2024
Hirosaki University
2019-2024
Kamituga General Hospital
2024
National Institutes of Health
2022-2024
Government of the United States of America
2022
Saitama University
1953
Abstract Although several ATR inhibitors are in development, there unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy the newly developed inhibitor, M4344 using vitro vivo models. The potency was compared clinically BAY1895344, berzosertib, ceralasertib. anticancer activity investigated as monotherapy combination...
Significance Schlafen-11 (SLFN11) inactivation leads to chemoresistance of a broad range DNA-damaging agents. We uncover an expanded Ataxia Telangiectasia- and Rad3-related (ATR)-mediated signaling network that overcomes by unbiased genome-wide RNAi screen in SLFN11 -knockout cells is validated with clinically developing ATR/CHK1 inhibitors. ATR inhibition induces CDT1 phosphorylation, leading mitotic catastrophe cell death SLFN11-deficient cells. identify key role for degradation binding...
Abstract Exatecan and deruxtecan are antineoplastic camptothecin derivatives in development as tumor-targeted-delivery warheads various formulations including peptides, liposomes, polyethylene glycol nanoparticles, antibody–drug conjugates. Here, we report the molecular pharmacology of exatecan compared with clinically approved topoisomerase I (TOP1) inhibitors preclinical models for validating biomarkers combination ataxia telangiectasia Rad3-related kinase (ATR) inhibitors. Modeling...
Abstract Small‐cell lung cancer (SCLC) is the most lethal type of cancer. Specifically, MYC‐driven non‐neuroendocrine SCLC particularly resistant to standard therapies. Lurbinectedin was recently approved for treatment relapsed SCLC, but combinatorial approaches are needed increase depth and duration responses lurbinectedin. Using high‐throughput screens, we found inhibitors ataxia telangiectasia mutated rad3 related (ATR) as effective agents augmenting lurbinectedin efficacy. First‐in‐class...
Abstract Schlafen11 (SLFN11) inactivation occurs in approximately 50% of cancer cell lines and a large fraction patient tumor samples, which leads to chemoresistance. Therefore, new therapeutic approaches are needed target SLFN11-deficient cancers. To that effect, we conducted drug screen with the NCATS mechanistic library 1,978 compounds isogenic SLFN11-knockout (KO) wild-type (WT) leukemia lines. Here report TAK-243, first-in-class ubiquitin activating enzyme UBA1 inhibitor clinical...
Abstract Plasmablastic lymphoma (PBL) is a rare B-cell lymphoma. Reports on primary gastric PBL are limited, and its endoscopic features remain poorly understood. We report case of with multiple polypoid lesions in an immunocompetent individual. A 72-year-old man presented upper abdominal discomfort. Esophagogastroduodenoscopy (EGD) revealed raised variable sizes the stomach, prompting tumor biopsy. Based histopathological findings, diffuse large was suspected. Rituximab, cyclophosphamide,...
Abstract The antitumor activity of poly(ADP-ribose) polymerase inhibitors (PARPis) has been ascribed to PARP trapping, which consists in tight DNA–protein complexes. Here we demonstrate that the cytotoxicity talazoparib and olaparib results from DNA replication. To elucidate repair PARP1–DNA complexes associated with replication human TK6 chicken DT40 lymphoblastoid cells, explored role Spartan (SPRTN), a metalloprotease replication, removes proteins forming DPCs. We find SPRTN-deficient...
Capsule endoscopy has been widely used as a non-invasive diagnostic tool for small or large intestinal lesions. In recent years, automated lesion detection systems using machine learning have devised. This study aimed to develop an system capsule endoscopic severity in patients with ulcerative colitis along the entire length of colon ResNet50. videos from were collected prospectively. Each single examination video file was partitioned into four segments: cecum and ascending colon, transverse...
Currently, the number of patients treated with immune-checkpoint inhibitor involving nivolumab is increasing. Nevertheless, it causes various immune-related adverse events (irAEs). Here, we report case a patient who underwent long-term follow-up after suffering from nivolumab-associated colitis. The was 57-year-old man resection bladder tumor. Following surgery, lymph node metastasis detected, and he by nivolumab. Two months treatment nivolumab, complained bloody diarrhea. Colonoscopy...
Abstract Schlafen 11 (SLFN11) is an increasingly prominent predictive biomarker and a molecular sensor for wide range of clinical drugs: topoisomerases, PARP replication inhibitors, platinum derivatives. To expand the spectrum drugs pathways targeting SLFN11, we ran high-throughput screen with 1,978 mechanistically annotated, oncology-focused compounds in two isogenic pairs SLFN11-proficient -deficient cells (CCRF-CEM K562). We identified 29 hit that selectively kill cells, including not...
Schlafen11 (SLFN11) is referred to as interferon (IFN)-inducible. Based on cancer genomic databases, we identified human acute myeloid and lymphoblastic leukemia cells with gain-of-function mutations in the Janus kinase (JAK) family exhibiting high SLFN11 expression. In these cells, clinical JAK inhibitors cerdulatinib, ruxolitinib, tofacitinib reduced expression, but IFN did not further induce despite phosphorylated STAT1. We provide evidence that suppression of by caused inactivation...
The possible irreducible representations of Lie algebra the transformation group which leaves fundamental quadratic form, invariant, are investigated. Three invariants commute with all elements given and every representation is characterized by values these invariants.
Recently, the importance of achieving clinical and deep remissions with mucosal healing (MH) has been demonstrated as a therapeutic goal to avoid Crohn's disease (CD) surgical operations. Although ileocolonoscopy (CS) is considered gold standard, there are increasing reports on benefits capsule endoscopy (CE) serum leucine-rich α2-glycoprotein (LRG) for evaluating small-bowel lesions in CD. We evaluated data 20 patients CD who underwent CE our department between July 2020 June 2021 whose LRG...
Indigo naturalis, a herbal medicine purified from indigo-containing plants, such as Strobilanthes cusia, Isatis tinctoria, and Polygonum tinctorium, has been reported to be useful in the treatment of ulcerative colitis by activating aryl hydrocarbon receptor. However, receptor pathway causes crucial side effects, pulmonary arterial hypertension. Although P. tinctorium is one plant derivatives indigo it not identical it. To date, pure leaves have ameliorate colitis. Therefore, we investigated...
Myelodysplastic syndromes (MDSs) are a group of myeloid neoplasms characterized by blood cell deformation and dysfunction, MDS with trisomy 8 is closely linked intestinal Behçet's-like diseases. Intestinal disease refractory to conventional therapies, including prednisolone, immunomodulators, anti-tumor necrosis factor α agents. Here, we describe 56-year-old woman ascribed who had multiple intractable ulcers. She presented periodic fever abdominal pain. The genetic analysis showed...
A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine leads to rapid improvement severe ulcerative colitis. We hypothesized that the potent effects of cyclosporine would be exerted through relationships epithelial cells (IECs) host microbiota. The present study was designed elucidate on monocarboxylate transporter 1 (MCT1) regulation butyrate uptake by IECs. Colitis induced C57BL6 mice via...
Vitamin A ensures intestinal homeostasis, impacting acquired immunity and epithelial barrier function; however, its role in innate is mostly unknown. Here, we studied the impact of vitamin different dextran sulfate sodium (DSS)-induced colitis animal models. Interestingly, more severe DSS-induced was observed A-deficient (VAD) mice than A-sufficient (VAS) mice; same VAD combined immunodeficient lacking T/B cells. Remarkably, IL-1β production, LC3B-II expression, inflammasome activity lamina...
Fever of unknown origin (FUO) is caused by various diseases, making differential diagnosis difficult. This study aimed to determine the clinical features patients with FUO for use in daily medical practice. Medical records who first visited our department between January 2008 and December 2017 were reviewed. We classified diagnostic categories as infection, non-infectious inflammation, neoplasm, others, unidentified through definitive compared characteristics fulfilled criteria classical...
Delayed bleeding is the most frequent adverse event associated with endoscopic mucosal resection (EMR) and hot snare polypectomy (HSP) of colorectal polyps. However, whether incidence delayed differs between outpatient inpatient treatment unknown. Therefore, in this study, we aimed to evaluate rates treatments clarify safety treatment.
<p>Figure S4</p>