Publications by authors named "Motoyasu Kan"

8 Publications

  • Page 1 of 1

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Biochem Biophys Res Commun 2021 Apr 3;549:171-178. Epub 2021 Mar 3.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.097DOI Listing
April 2021

Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study.

Cancer Chemother Pharmacol 2020 08 6;86(2):203-210. Epub 2020 Jul 6.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan.

Objectives: Chemotherapy-induced neutropenia (CIN) is a common adverse event of chemotherapy. Several reports have suggested that CIN could be an important prognostic factor in chemotherapy of various cancers. However, whether CIN is a prognostic factor in unresectable pancreatic cancer (PC) treated with gemcitabine plus nab-paclitaxel (GnP) is unknown. The primary endpoint of this study was to compare overall survival (OS) between patients with severe CIN (grade ≥ 3) and those with absent/mild CIN (grade ≤ 2) in unresectable PC cases treated with GnP as first-line chemotherapy.

Methods: A retrospective, cohort study was conducted using data from a computerized database. A total of 290 patients with pathologically confirmed PC treated with GnP as first-line chemotherapy were analyzed (severe CIN: ≥ grade 3, n = 174; absent/mild CIN: ≤ grade 2, n = 116).

Results: The median OS was longer in the severe CIN group than in the absent/mild CIN group (19.2 months vs 11.3 months, respectively; P < 0.001). After adjustment, severe CIN was an independent predictive factor for OS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < 0.001). After adjustment by time-varying covariates, severe CIN was still a significant prognostic factor for OS (HR, 0.79; 95% CI 0.69-0.91, P = 0.001).

Conclusion: The present results show that severe CIN is an independent and useful prognostic factor in PC patients treated with GnP.
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http://dx.doi.org/10.1007/s00280-020-04110-3DOI Listing
August 2020

Skill-up study of systemic endoscopic examination technique using narrow band imaging of the head and neck region of patients with esophageal squamous cell carcinoma: Prospective multicenter study.

Dig Endosc 2019 Nov 20;31(6):653-661. Epub 2019 Jun 20.

Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.

Objective: To evaluate the usefulness of a training program on endoscopic head and neck surveillance for beginner endoscopists.

Methods: This prospective multicenter study included 13 beginner endoscopists from 10 institutions who received training in systematic observation techniques and diagnostic criteria, and the training involved hands-on learning. Between May 2016 and February 2017, enrolled patients with current or previously diagnosed esophageal squamous cell carcinomas underwent head and neck surveillance using narrow band imaging (NBI) endoscopy, and histologically confirmed head and neck squamous cell carcinoma (HNSCC) detection rates, endoscopic image quality, and examination times were compared before (group A) and after (group B) the training program. Maximum possible score for the endoscopic images was 30 points.

Results: A total of 330 patients, comprising 181 in group A and 149 in group B, were enrolled. Three patients with HNSCC were detected in group A (1.7%) and in group B (2.0%; P = 1.000). Mean ± standard deviation (SD) examination times were 157 ± 71 s and 174 ± 109 s in groups A and B, respectively, (P = 0.073). Mean ± SD scores of the endoscopic images were 25.04 ± 5.47 points and 27.01 ± 4.35 points in groups A and B, respectively, (P < 0.001).

Conclusion: The HNSCC detection rate based on the use of NBI on patients with ESCC did not improve after the training program for beginner endoscopists; however, endoscopic image quality improved significantly after the training program.
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http://dx.doi.org/10.1111/den.13445DOI Listing
November 2019

Endoscopic Ultrasound-Guided Gallbladder Drainage for Aberrant Right Posterior Duct Obstruction Developing after Placement of a Covered Self-Expandable Metallic Stent in a Patient with Distal Biliary Obstruction.

Case Rep Gastroenterol 2018 Sep-Dec;12(3):722-728. Epub 2018 Nov 28.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been utilized as an alternative endoscopic technique for patients with acute cholecystitis. In addition to EUS-guided hepaticogastrostomy and EUS-guided cystogastrostomy, EUS-GBD has been reported as being useful for biliary drainage in cases with distal malignant biliary obstruction instead of conventional endoscopic retrograde cholangiopancreatography. We present a case of successful EUS-GBD for malignant obstruction of an aberrant hepatic duct draining directly into the cystic duct.
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http://dx.doi.org/10.1159/000492215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323387PMC
November 2018

Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy.

J Gastroenterol 2019 Mar 8;54(3):281-290. Epub 2018 Oct 8.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen.

Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy.

Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset.

Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups).

Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups.
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http://dx.doi.org/10.1007/s00535-018-1518-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394712PMC
March 2019

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors.

Oncologist 2019 01 2;24(1):47-53. Epub 2018 Aug 2.

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Background: In phase II trials for neuroendocrine tumors (NETs), the objective response rate (ORR) is traditionally used as a primary endpoint. However, the validity of the ORR as a primary endpoint has never been systematically examined. Therefore, a literature-based analysis of phase II trials for NETs was performed to identify valid alternative endpoints for predicting median progression-free survival (PFS) in clinical trials for NETs.

Materials And Methods: Phase II trials of medical treatment for advanced NETs were identified based on a systematic search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.

Results: A total of 22 trials were identified, and 1,310 patients and 27 treatment arms were included in the analysis. There was no significant relationship between the ORR and median PFS ( = .374; 95% confidence interval [CI], -0.051 to 0.800; = .085). Conversely, 12-month PFS rates showed very strong correlations with median PFS ( = .929; 95% CI, 0.831-1.027; < .001).

Conclusion: The results of the present analysis indicate that the ORR is not significantly correlated with median PFS and suggest that 12-month PFS rates are good alternate endpoints for screening phase II trials for NETs.

Implications For Practice: Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development. Thus, earlier endpoints are preferable, and the objective response rate (ORR) has been traditionally used as a surrogate endpoint in phase II trials for neuroendocrine tumors (NETs). However, the present study showed that the ORR was not significantly correlated with median progression-free survival (PFS). On the other hand, the 12-month PFS rate showed very strong correlation with median PFS and is considered a good alternate endpoint for screening phase II trials for NETs.
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http://dx.doi.org/10.1634/theoncologist.2017-0651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324626PMC
January 2019

Histopathology of immature (ongoing) squamous metaplasia of the stomach.

Pathol Int 2018 05 2;68(5):318-320. Epub 2018 Feb 2.

Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524, Japan.

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http://dx.doi.org/10.1111/pin.12636DOI Listing
May 2018

Metachronous early gastric cancer over a period of 13 years after eradication of Helicobacter pylori.

Clin J Gastroenterol 2014 Dec 4;7(6):490-5. Epub 2014 Nov 4.

Department of Endoscopy, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo, Chiba, 276-8524, Japan,

Stomach cancer can occur during chronic inflammation from Helicobacter pylori (HP) infection, and its occurrence can be suppressed by eradication of HP. However, the effects of suppressing stomach cancer by HP eradication are limited, and the cancer is known to recur even after eradication of this infection. Here, we report the case of a 56-year-old male patient with gastric cancer who, although undergoing HP eradication after treatment of early gastric cancer with endoscopy, experienced five metachronous cancer recurrences over a period of 13 years. Whether observation of patients who undergo eradication of HP due to peptic ulcers or chronic gastritis and patients who undergo eradication after endoscopic treatment for early gastric cancer should be performed at the same interval is an issue that must be addressed in the future. The appropriate observation period for each patient must be established while considering the burdens to the patient and from the medical economic perspective.
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http://dx.doi.org/10.1007/s12328-014-0536-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261136PMC
December 2014