Kazuko Sakai

ORCID: 0000-0003-1822-2720
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About
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Research Areas
  • Lung Cancer Treatments and Mutations
  • HER2/EGFR in Cancer Research
  • Cancer Genomics and Diagnostics
  • Lung Cancer Research Studies
  • Cancer Immunotherapy and Biomarkers
  • Colorectal Cancer Treatments and Studies
  • Cancer Mechanisms and Therapy
  • PI3K/AKT/mTOR signaling in cancer
  • Prostate Cancer Treatment and Research
  • Monoclonal and Polyclonal Antibodies Research
  • MicroRNA in disease regulation
  • Immunotherapy and Immune Responses
  • Genetic factors in colorectal cancer
  • RNA modifications and cancer
  • Gastric Cancer Management and Outcomes
  • Pancreatic and Hepatic Oncology Research
  • Synthesis and biological activity
  • Protein Tyrosine Phosphatases
  • Ferroptosis and cancer prognosis
  • Cancer, Hypoxia, and Metabolism
  • Cancer Diagnosis and Treatment
  • Hepatocellular Carcinoma Treatment and Prognosis
  • Cancer therapeutics and mechanisms
  • Cancer, Lipids, and Metabolism
  • Cancer Cells and Metastasis

Kindai University
2016-2025

Weatherford College
2022

Kansai Medical University
2021

Kindai University Hospital
2021

Saiseikai Fukuoka General Hospital
2020

Kurume University
1988-2017

Kanazawa University Hospital
2006-2017

Yokohama City University
2017

Shikoku Cancer Center
2017

Toranomon Hospital
2017

Cetuximab (Erbitux, IMC‐C225) is a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR). To clarify mode of antitumor action cetuximab, we examined antibody‐dependent cellular cytotoxicity (ADCC) activity against several tumor cell lines expressing wild‐type or mutant EGFR. ADCC and complement‐dependent cytolysis were analyzed using CytoTox 96 assay. activities correlated with EGFR expression value ( R = 0.924). detected all lines, except K562 cells in manner dependent...

10.1111/j.1349-7006.2007.00510.x article EN Cancer Science 2007-05-13

Abstract Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion mucin gene expression mice. However, role FOXQ1 humans especially cancer cells remains unknown. We found that mRNA overexpressed clinical specimens colorectal (CRC; 28-fold/colonic mucosa). A microarray analysis revealed knockdown using small interfering RNA resulted decrease p21CIP1/WAF1 expression, reporter assay chromatin...

10.1158/0008-5472.can-09-2161 article EN Cancer Research 2010-02-10

Although a high level of thymidylate synthase (TS) expression in malignant tumours has been suggested to be related reduced sensitivity the antifolate drug pemetrexed, no direct evidence for such an association demonstrated non-small cell lung cancer (NSCLC). We have now investigated effect TS overexpression on pemetrexed NSCLC cells.We established lines that stably overexpress and examined effects cytotoxicity both vitro xenograft models. further relation between tumour specimens from...

10.1038/bjc.2011.129 article EN cc-by-nc-sa British Journal of Cancer 2011-04-12

Anaplastic lymphoma kinase (ALK) tyrosine inhibitors (TKI) such as crizotinib show marked efficacy in patients with non-small cell lung cancer positive for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion protein. However, acquired resistance to these agents has already been described treated patients, and mechanisms of remain largely unknown.We established lines EML4-ALK-positive H3122 cells that are resistant ALK inhibitor TAE684 (H3122/TR cells) investigated their...

10.1158/1078-0432.ccr-12-0392 article EN Clinical Cancer Research 2012-07-28

Anti‐HER2 therapies are beneficial for patients with HER2‐positive breast or gastric cancer. T‐DM1 is a HER2‐targeting antibody–drug conjugate (ADC) comprising the antibody trastuzumab, linker, and tubulin inhibitor DM1. Although effective in treating advanced cancer, all eventually develop resistance. DS‐8201a new ADC incorporating an anti‐HER2 antibody, newly developed, enzymatically cleavable peptide novel, potent, exatecan‐derivative topoisomerase I (DXd). has drug‐to‐antibody‐ratio...

10.1002/ijc.30870 article EN International Journal of Cancer 2017-07-05

Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared empirical chemotherapy. We therefore performed randomized study assess whether such improves outcome chemotherapy in previously untreated CUP.Comprehensive was microarray analysis, and an established algorithm applied predict tumor origin....

10.1200/jco.18.00771 article EN Journal of Clinical Oncology 2019-01-17

Purpose: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed various malignancies. To our knowledge, this study the first evaluate B7-H3 expression NSCLCs treated with anti-PD-1 therapy and therapeutic potential of a combination targeting.Experimental Design: was evaluated immunohistochemically patients...

10.1158/1078-0432.ccr-17-2852 article EN Clinical Cancer Research 2018-03-12

Abstract The epithelial mesenchymal transition (EMT) has emerged as a pivotal event in the development of invasive and metastatic potentials cancer progression. Sorafenib, VEGFR inhibitor with activity against RAF kinase, is active hepatocellular carcinoma (HCC); however, possible involvement sorafenib EMT remains unclear. Here, we examined effect on EMT. Hepatocyte growth factor (HGF) induced EMT-like morphologic changes upregulation SNAI1 N-cadherin expression. downregulation E-cadherin...

10.1158/1535-7163.mct-10-0544 article EN Molecular Cancer Therapeutics 2011-01-01

MET is a receptor tyrosine kinase (RTK) whose gene amplified in various tumour types. We investigated the roles and mechanisms of RTK heterodimerisation lung cancer with amplification.With use an array, we identified phosphorylated RTKs cells amplification. examined action these immunoprecipitation, annexin V binding, cell migration assays.We epidermal growth factor (EGFR), human EGFR (HER)2, HER3, RET addition to as highly Immunoprecipitation revealed that EGFR, HER2, each formed...

10.1038/bjc.2011.322 article EN cc-by-nc-sa British Journal of Cancer 2011-08-16

Abstract The most common event responsible for resistance to first- and second-generation (1st 2nd) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is acquisition of T790M mutation. We examined whether related clinicopathologic or prognostic factors in patients with relapse EGFR mutant non-small cell lung cancer (NSCLC) after treatment 1st 2nd EGFR-TKIs. retrospectively reviewed the status clinical characteristics 73 advanced recurrent NSCLC who had been treated...

10.1038/srep36458 article EN cc-by Scientific Reports 2016-11-04

Although profiling of gene expression and alterations by next-generation sequencing (NGS) to predict the primary tumor site guide molecularly targeted therapy might be expected improve clinical outcomes for cancer unknown (CUP), our knowledge, no trial has previously evaluated this approach.To assess use site-specific treatment, including based on NGS results, patients with CUP.This phase 2 was conducted at 19 institutions in Japan enrolled 111 untreated unfavorable subset CUP between March...

10.1001/jamaoncol.2020.4643 article EN JAMA Oncology 2020-10-15

Implementation of personalized medicine requires the accessibility tumor molecular profiling in order to allow prioritization appropriate targeted therapies for individual patients. Our aim was study role comprehensive genomic assays that may inform treatment recommendations patients with solid tumors.

10.1002/onco.13639 article EN cc-by-nc-nd The Oncologist 2020-12-16

Abstract Purpose: Treatment with KRASG12C inhibitors such as sotorasib can produce substantial regression of tumors in some patients non–small cell lung cancer (NSCLC). These require alternative treatment after acquiring resistance to the inhibitor. The mechanisms underlying this acquired are unclear. purpose study was identify resistance, and explore potential treatments for rescuing sotorasib-resistant NSCLC cells. Experimental Design: Clones sotorasib-sensitive H23 cells exposed different...

10.1158/1078-0432.ccr-21-0856 article EN Clinical Cancer Research 2021-08-07

<b><i>Introduction:</i></b> Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was low 20%. Identifying subgroups respond well ICIs is clinically important. Here, we studied prognostic factors anti-PD-1 antibody based on molecular and immunological features HCC....

10.1159/000516899 article EN cc-by-nc Liver Cancer 2021-01-01

EGFR-tyrosine kinase inhibitor (TKI) is a standard first-line therapy for activated EGFR-mutated non-small cell lung cancer (NSCLC). Treatment options patients with acquired EGFR-TKI resistance are limited. HER3 mediates resistance. Clinical trials of the HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated its anticancer activity in NSCLC; however, mechanisms that regulate expression unknown. This study was conducted aim to clarify underlying regulation NSCLC...

10.1158/1078-0432.ccr-21-3359 article EN Clinical Cancer Research 2021-12-17

BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma advanced NSCLC before blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated who received nivolumab. retrospective observational study was performed any therapy (cohorts B C), cytotoxic chemotherapy D), or...

10.1172/jci168318 article EN cc-by Journal of Clinical Investigation 2024-03-31

ABSTRACT Background Recognizing rare molecular variants of driver mutations poses a challenge in precision oncology, particularly for treatment non‐small cell lung cancer (NSCLC). In this study, we aimed to determine whether Oncomine Dx Target Test Multi‐CDx System (ODxTT), the most widely used genetic test NSCLC Japan, potentially overlooks druggable EGFR mutations. Materials and Methods Among 418 patients who underwent testing using ODxTT at our hospital, 267 were diagnosed with...

10.1111/1759-7714.70007 article EN cc-by Thoracic Cancer 2025-02-01

Activin A is a multi-functional cytokine belonging to the transforming growth factor-β (TGF-β) superfamily; however, effect of activin on angiogenesis remains largely unclear. We found that inhibin β subunit (INHBA) mRNA overexpressed in gastric cancer (GC) specimens and investigated A, homodimer INHBA, GC.Anti-angiogenic effects via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) vitro stable INHBA-introduced GC cell line vivo.Compared with TGF-β, potently...

10.1038/bjc.2011.348 article EN cc-by-nc-sa British Journal of Cancer 2011-09-06

Therapeutic strategies that target the tyrosine kinase MET hold promise for gastric cancer, but mechanism underlying antitumor activity of such remains unclear. We examined action inhibitor crizotinib (PF-02341066) in cancer cells positive or negative amplification. Inhibition signaling by RNA interference-mediated depletion resulted induction apoptosis accompanied inhibition AKT and extracellular signal-regulated phosphorylation with amplification not those without it, suggesting is...

10.1158/1535-7163.mct-11-0934 article EN Molecular Cancer Therapeutics 2012-06-23

Most patients with non‐small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor ( EGFR ) mutations, such as deletions in exon 19 or the L858R mutation 21, respond dramatically to tyrosine kinase inhibitors (EGFR‐TKI), and their sensitivities various EGFR‐TKI have been well characterized. Our previous article showed vitro of 18 mutations EGFR‐TKI, but little information regarding other uncommon is available. First, stable transfectant Ba/F3 lines (Ba/F3‐L858R), L861Q...

10.1111/cas.12980 article EN cc-by-nc-nd Cancer Science 2016-05-30
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