A5019616999- Neuroblastoma Research and Treatments
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Silicon and Solar Cell Technologies
- Lung Cancer Research Studies
- Synthesis and Biological Evaluation
- PARP inhibition in cancer therapy
- Monoclonal and Polyclonal Antibodies Research
- Genetics and Neurodevelopmental Disorders
- Wireless Power Transfer Systems
- Signaling Pathways in Disease
- Structural Engineering and Vibration Analysis
Chiba Cancer Center
2016-2025
University of California, San Francisco
2022-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2022-2024
Chiba University
2018-2023
Cancer Genetics (United States)
2016-2021
The University of Tokyo
2021
University of the Philippines Los Baños
2021
Nihon University
2012-2019
Nagoya University
1998
Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively killing tumour cells harbouring KRAS mutations have remained unavailable. Here we demonstrate the direct targeting mutant DNA using a synthetic alkylating agent (pyrrole–imidazole polyamide indole-seco-CBI conjugate; KR12) that recognizes oncogenic codon 12 mutations. KR12 alkylates adenine N3 at sequence, causing strand cleavage and growth suppression in human colon cancer with G12D or G12V...
Amplification of MYCN is a major oncogenic driver high-risk neuroblastomas. We previously developed CCC-002, MYCN-selective pyrrole-imidazole polyamide conjugated to DNA alkylating agent. Administration CCC-002 MYCN-amplified (MYCN-amp) neuroblastoma cells triggered the activation damage responses. Here, we demonstrated that among response inhibitors, ataxia telangiectasia and Rad3-related (ATR) inhibitors synergized with suppress repair-related genes induce apoptosis in MYCN-amp cells. A...
Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to formation remains unclear. Here, we used a human stem cell-based model neuroblastoma. Mis-expression ALKF1174L resulted shorter latency compared alone. tumors resembled adrenergic, while ALK/MYCN mesenchymal, Transcriptomic analysis revealed enrichment focal adhesion signaling, particularly extracellular matrix...
We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) normal (human umbilical vein endothelial cells (HUVEC) human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH3) showed especially potent cytotoxic activities compared with cells. In Hoechst 33342 staining experiment, apoptotic...
Abstract Amplification of MYCN plays a pivotal role in multiple types tumors and correlates with poor prognosis high-risk neuroblastoma. Despite recent advances the treatment neuroblastoma, no approaches directly target master oncogene MYCN. Difficulties targeting protein inspired us to develop new gene-level–inhibitory strategy using sequence-specific gene regulator. Here, we generated MYCN-targeting pyrrole-imidazole (PI) polyamide, MYCN-A3, which binds alkylates DNA at homing motifs...
Although runt-related transcription factor 2 (RUNX2) is known to be an essential key for osteoblast differentiation and bone formation, RUNX2 also plays a pivotal role in the regulation of p53-dependent DNA damage response. In present study, we report that, addition p53, downregulates pro-apoptotic TAp73 during damage-dependent cell death. Upon adriamycin (ADR) exposure, human osteosarcoma-derived U2OS cells underwent death association with upregulation various p53/TAp73-target gene products...
Abstract Background Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant EGFR, represent hallmark genetic lesions in glioblastoma. Methods We used phospho-proteomics, RNA-sequencing, TCGA data glioblastoma cell culture mouse models to study the signal transduction mediated by EGFRvIII. Results report that EGFRvIII stimulate innate immune defense receptor Toll-like Receptor 2 (TLR2); knockout TLR2 dramatically improved survival orthotopic xenografts. activated...
Runt-related transcription factor 2 (RUNX2) has been considered to be one of master regulators for osteoblast differentiation and bone formation. Recently, we have described that RUNX2 attenuates p53/TAp73-dependent cell death human osteosarcoma U2OS cells bearing wild-type p53 in response adriamycin. In this study, asked whether silencing could enhance gemcitabine (GEM) sensitivity p53-deficient pancreatic cancer AsPC-1 cells. Under our experimental conditions, GEM treatment increased the...
Pancreatic cancer exhibits the worst prognostic outcome among human cancers. Recently, we have described that depletion of RUNX2 enhances gemcitabine (GEM) sensitivity p53-deficient pancreatic AsPC-1 cells through activation TAp63-mediated cell death pathway. These findings raised a question whether silencing could also improve GEM efficacy on bearing p53 mutation. In present study, extended our study to p53-mutated MiaPaCa-2 cells. Based current results, were much more resistant as compared...
Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation p53 family TAp63-dependent cell death pathway. In this manuscript, extended our study to p53-mutated Panc-1 cells. According present results, knockdown mutant alone had a marginal effect on GEM-mediated We then sought deplete RUNX2 using siRNA in and examined...
Abstract PIK3CA is the most frequently mutated oncogene in cervical cancer, and somatic mutations gene result increased activity of PI3K. In E545K mutation leads to elevated cell proliferation reduced apoptosis. present study, we designed synthesized a novel pyrrole‐imidazole polyamide‐ seco ‐CBI conjugate, P3AE5K, target bearing mutation, rendered possible by nuclear access unique sequence specificity polyamides. P3AE5K interacted with double‐stranded DNA coding region containing mutation....
Receptor-type protein tyrosine phosphatase κ (PTPRK) is considered to be a candidate tumor suppressor. PTPRK dephosphorylates CD133, which stem cell marker; phosphorylated CD133 accelerates xenograft growth of colon cancer cells through the activation AKT, but functional significance this has remained elusive. In study, we have demonstrated that knockdown potentiates pro-oncogenic CD133-AKT pathway in cells. Intriguingly, depletion significantly reduced sensitivity anti-cancer drug...
It has been well-known that human pancreatic cancer represents the fourth and fifth leading causes of cancer-related deaths in United States Japan, respectively.1, 2 Notably, is characterized by high metastatic potential, resistance to chemotherapy thus its prognosis extremely poor with 5-year survival <5%. At diagnosis, more than 80% cases are already advanced non-resectable.3 Therefore, and/or radiotherapy only option. Despite improvements treatments, rate not significantly ameliorated...
Suberoylanilide hydroxamic acid (SAHA) represents one of the new class anti-cancer drugs. However, multiple lines clinical evidence indicate that SAHA might be sometimes ineffective on certain solid tumors including pancreatic cancer. In this study, we have found for first time RUNX2/mutant p53/TAp63-regulatory axis has a pivotal role in determination sensitivity p53-mutated cancer MiaPaCa-2 cells. According to our present results, cells responded poorly SAHA. Forced depletion mutant p53...
During the early phase of tumorigenesis, primary malignant cells survive within a low nutrition environment caused by poorly organized vascular system. Here, we sought to determine functional significance CD133 in survival cancer under nutrient-poor conditions. Knockdown and overexpression experiments demonstrated that suppresses colon cell death induced serum deprivation through activation Akt-mediated anti-apoptosis protein synthesis pathways. Furthermore, increased amount endogenous...
In the search for new pharmaceutical leads, especially with DNA-binding molecules or genome editing methods, issue of side and off-target effects have always been thorny in nature. A particular case is investigation into N-methylpyrrole-N-methylimidazole polyamides, a naturally inspired class DNA binders strong affinity to minor-groove sequence specificity, but at < 20 bases, their relatively short motifs also insinuate possibility non-unique genomic binding. Binding non-intended loci...
Neuroblastoma is a pediatric malignant tumor arising from the sympathetic nervous system. The patients with high-risk neuroblastomas frequently exhibit amplification and high expression of MYCN gene, resulting in worse clinical outcomes. Vitamin K3 (VK3) synthetic VK-like compound that has been known to have antitumor activity against various types cancers. In present study, we asked whether VK3 its derivative, VK3-OH, could neuroblastoma-derived cells. Based on our results, VK3-OH strongly...
Low-noise and low-power cryogenic readout electronics are developed for a focal plane instrument of the IR Imaging Surveyor. We measured static characteristics noise spectra several types silicon MOSFETs at temperature where JFETs do not work well due to carrier freeze-out. The 'kink' behavior n- channel was observed below freeze-out temperature, but it obvious p-channel MOSFET. It demonstrated can be used IRIS's far-IR array with an acceptable performance. amplifier integrated these showed...
Activating mutations of the KRAS occurs in >90% pancreatic ductal adenocarcinoma (PDAC) cases. However, direct pharmacological targeting activated protein has been challenging. We previously reported that KR12, a DNA-alkylating pyrrole-imidazole polyamide designed to recognize G12D/V mutation, showed an anti-tumor effect colorectal cancer. In this study, we evaluated KR12 PDAC.KR12 was synthesized by automated peptide synthesizer PSSM-8 and tested for PDAC mouse models.KR12 inhibited tumor...
Anaplastic lymphoma kinase ( ALK ) aberration is related to high-risk neuroblastomas and an important therapeutic target. As acquired resistance tyrosine inhibitors inevitable, novel anti-ALK drug development necessary in order overcome potential against ATP-competitive inhibitors. In this study, inhibitor resistance, we examined the growth inhibition effects of newly developed -targeting pyrrole-imidazole polyamide CCC-003, which was designed directly bind alkylate DNA within F1174L-mutated...
Novelty detection represents the of anomalous data based on a training set consisting only normal data.In this study, we propose new probabilistic approach for novelty to effectively detect data, particularly case multimodal dataset.Our method is inspired by Least-Squares Probabilistic Classifier (LSPC), which an efficient multi-class classification method.Numerical experimental results datasets show that proposed outperforms related methods.
Propolis is a nature resinous mixture produced by honeybees that exhibit wide range of biological functions.We previously reported the propolis derived from Philippine endemic stingless bees (Tetragonula biroi, Friese) had anti-gastric cancer and hair growth activities in JALAS annual meetings.However, stimulating activity remains poorly understood.In this study, we investigate effects underlying mechanism on using mice.Treatment 99.5% ethanol-crude extract (EEPP) significantly stimulated...
Abstract Cancer may be recognized as non-self by antibiotics such minor groove binders, which show self / recognition partially due to preferential DNA sequence and distinguish from other bacteria. We learned binders produced Streptomyces synthesized Pyrrole-Imidazole polyamide indol-seco CBI conjugate alkylate specific sites in the cancer genome. Although a tremendous amount of studies has been made directly target oncogenic drivers, RAS MYC, yet no drug is clinically available because...
Abstract RAS mutations are found in around 30% of all human cancers, with KRAS being the most frequently activated family oncogenes. Although extensive efforts to develop attractive chemotherapeutic drugs targeting clinical benefit have been made, these experimental trials often resulted unsuccessful. Recently, we successfully produced for first time a novel alkylating agent (termed KR12) conjugated sequence-specific Pyrrole-Imidazole polyamide (PI polyamide), which was expected an ability...