Publications by authors named "Takafumi Sakuma"

6 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.02.097DOI Listing
April 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

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

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Chronic expanding hematoma in the chest: A case report.

Exp Ther Med 2018 Jun 24;15(6):5457-5460. Epub 2018 Apr 24.

Division of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Chronic expanding hematoma (CEH) is a rare disease that is usually present as a large solitary pulmonary nodule. CEHs are slow growing, but processes underlying their development remain unknown. The present study herein reports the case of a 76-year-old male patient with CEH and discusses a number of CEH cases published in the literature. The majority of these previously described patients were Asians. The CEH in the present case was not a successfully resected one, but the patient's clinical course provided information concerning the natural history of the disease. During the clinical course, the patient underwent several chest computed tomography scans. For the present case report, the doubling time and volume change of the mass was calculated, which revealed that the lesion had an inconstant growth rate and that its onset was between 8.2-11.0 years before the patient succumbed to this disease. Accumulation of knowledge about this rare disease will help to elucidate it further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2018.6091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958822PMC
June 2018

Comparison of CatWalk analysis and von Frey testing for pain assessment in a rat model of nerve crush plus inflammation.

Spine (Phila Pa 1976) 2013 Jul;38(15):E919-24

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.

Study Design: Assessment of pain-related behavior and immunohistology of the dorsal root ganglion in a rat model.

Objective: To investigate pain-related behavior in a rat model of nerve crush plus inflammation using the CatWalk system.

Summary Of Background Data: A definitive method for evaluating animal models of lumbar disease has not been established. Von Frey testing has often been used in this type of study, but the reliability remains in question. The CatWalk system is a computer-assisted apparatus for analyzing gait that provides an automated way to assess gait function during pain. However, there have been few reports using this system for models of lumbar disease.

Methods: Fourteen rats were divided into 2 groups: a treatment group and a sham group. For the treatment group, nucleus pulposus was applied to the sciatic nerve and the sciatic nerve was pinched. Two different methods for assessment of pain-related behavior, von Frey testing and CatWalk analysis, were used before surgery and at 4 and 7 days after surgery. Immunohistochemistry was used to examine calcitonin gene-related peptide expression in L4 to L6 dorsal root ganglia.

Results: No significant differences were found between the treatment and sham control groups using von Frey testing. However, significant differences in 4 parameters were found between the 2 groups using the CatWalk system (P < 0.05). The proportion of calcitonin gene-related peptide-immunoreactive neurons was higher in the treatment group than in the control group (P < 0.05).

Conclusion: Our results demonstrate that the CatWalk system is useful for the measurement of pain-related behavioral change in our rat model in which nociception was indicated at a cellular level. Although further studies are needed, we think that this system is a valid alternative method for the evaluation of models of lumbar disease in rodents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0b013e318297bfb6DOI Listing
July 2013

Investigation of dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and intervertebral disc or facet joint or sacroiliac joint in rats.

Spine (Phila Pa 1976) 2012 Apr;37(7):557-62

School of Medicine, Chiba University, Chiba, Japan.

Study Design: Immunohistological analysis of dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and intervertebral disc (IVD), facet joint (FJ), or sacroiliac joint (SIJ) in rats.

Objective: To elucidate dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and to IVDs, FJs, or SIJs.

Summary Of Background Data: Clinically, the origin of low back pain remains unknown. Multiple studies have identified lumbar muscles, IVDs, FJs, and SIJs as sources of low back pain. Pain may originate directly from lumbar muscles or be referred from the spine, or both. Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in several species and are thought to be related to referred pain.

Methods: We used 2 neurotracers, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) and fluorogold (FG), in this double-labeling study involving 30 Sprague Dawley rats. DiI was applied to lumbar multifidus muscles in all rats. Simultaneously, FG was applied to the anterior left portion of L5-L6 IVDs in the IVD group (n = 10), to the left L5-L6 FJs in the FJ group (n = 10), and to the left SIJs in the SIJ group (n = 10). Fourteen days after surgery, left DRGs from L1 to L6 were harvested, sectioned, and observed under a fluorescence microscope.

Results: We verified the existence of double-labeled DRG neurons (i.e., dichotomizing sensory nerve fibers) projecting to lumbar multifidus muscles and to IVDs, FJs, or SIJs, depending on the group. The proportion of double-labeled cells in all DiI-labeled DRG neurons was higher in the FJ group (6.8%) and SIJ group (7.1%) than in the IVD group (3.1%) (P < 0.05).

Conclusion: Our results document the presence of dichotomizing sensory nerve fibers projecting to lumbar multifidus muscles and to IVDs, FJs, and SIJs. Referred low back muscle pain may reflect disorders of lumbar posterior structures, such as FJs and SIJs, rather than disorders of lumbar anterior structures, such as IVDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0b013e3182293178DOI Listing
April 2012