Publications by authors named "Satoshi Tanaka"

627 Publications

The histamine H receptor antagonist hydroxyzine enhances sevoflurane and propofol anesthesia: A quantitative EEG study.

Clin Neurophysiol 2021 Jun 24;132(9):2054-2061. Epub 2021 Jun 24.

Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Japan.

Objective: The aim of this study was to determine the anesthesia-promoting effects of hydroxyzine on electroencephalograms during sevoflurane anesthesia and during propofol anesthesia.

Methods: We analyzed 40 patients scheduled for elective surgery under sevoflurane anesthesia (n = 20) or propofol anesthesia (n = 20). Anesthesia was adjusted at a bispectral index value of 50-60, and then 0.5 mg/kg of hydroxyzine was administered intravenously. We analyzed frontal electroencephalograms before and after hydroxyzine injection with power spectral and bicoherence analyses, which are suitable for assessing the anesthetic depth induced by γ-aminobutyric acid (GABA)ergic anesthetics.

Results: Hydroxyzine increased the α bicoherence peaks in both sevoflurane anesthesia (mean difference, 11.2%; 95% confidence interval (CI), 7.6 to 14.8; P < 0.001) and propofol anesthesia (mean difference, 5.6%; 95% CI, 1.7 to 9.4; P = 0.008). Hydroxyzine increased the averaged δ bicoherence values in both sevoflurane anesthesia (mean difference, 5.5%; 95% CI, 2.1 to 8.8; P = 0.003) and propofol anesthesia (mean difference, 3.9%; 95% CI, 1.0 to 6.8; P = 0.011).

Conclusions: Hydroxyzine enhances both sevoflurane anesthesia and propofol anesthesia probably by facilitation of GABAergic neural circuit mechanisms.

Significance: The findings provide a new insight into the role of histaminergic neurons during general anesthesia in humans.
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http://dx.doi.org/10.1016/j.clinph.2021.05.024DOI Listing
June 2021

Neuroanatomical correlates of the perception of body axis orientation during body tilt: a voxel-based morphometry study.

Sci Rep 2021 Jul 19;11(1):14659. Epub 2021 Jul 19.

Laboratory of Psychology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.

Accurate perception of the orientations of the body axis and gravity is essential for actions. The ability to perceive these orientations during head and body tilt varies across individuals, and its underlying neural basis is unknown. To address this, we investigated the association between inter-individual differences in local gray matter (GM) volume and inter-individual differences in the ability to estimate the directions of body longitudinal axis or gravity during whole-body tilt using voxel-based morphometry (VBM) analysis in 50 healthy adults (20-46 years, 25 men and 25 women). Although no anatomical regions were identified relating to performance requiring estimates of gravitational direction, we found a significant correlation between the GM volume in the right middle occipital gyrus and the ability to estimate the body axis orientation. This finding provides the first evidence on neuroanatomical substrates of the perception of body axis orientation during body tilt.
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http://dx.doi.org/10.1038/s41598-021-93961-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289860PMC
July 2021

Another route of CO gas excretion independent of red blood cells in human lungs.

Pflugers Arch 2021 Jul 12. Epub 2021 Jul 12.

Department of Innovation of Medical and Health Sciences Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

We demonstrated pulmonary arteriolar blood flow-mediated CO gas excretion in rabbit lungs. The shear stress stimulation produced CO gas in cultured human endothelial cells of pulmonary arterioles via the activation of F/F ATP synthase. To confirm the findings in human subjects undergoing the operation with heart-lung machines, we aimed to evaluate the effects of a stepwise switch, from a partial to a complete cardiopulmonary bypass, of the circulatory blood volume (BV, 100% = 2.4 × cardiac index), on the end-expiratory CO pressure (PetCO), maximal flow velocity in the pulmonary artery (Max Vp), the inner diameter (ID) of pulmonary artery, pulmonary arterial CO pressure (P mix v CO), pulmonary arterial O pressure (P mix v O), hematocrit (Hct), pH, the concentration of HCO, and base excess (BE) in mixed venous blood in 9 patients with a mean age of 72.3 ± 3.4 years. In addition, the effects of the decrease in Hct infused with physiological saline solution (PSS) on PetCO were investigated in the human subjects. An approximately linear relationship between the PetCO and Max Vp was observed. The pumping out of 100% BV produced little or no change in the Hct, pH, P mix v CO, and P mix v O, respectively. The hemodilution produced by intravenous infusion of PSS caused a significant decrease in the Hct, but not in the PetCO. In conclusion, another route of CO gas excretion, independent of red blood cells, may be involved in human lungs.
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http://dx.doi.org/10.1007/s00424-021-02586-3DOI Listing
July 2021

Acute Phase Reactions After Intravenous Infusion of Zoledronic Acid in Japanese Patients with Osteoporosis: Sub-analyses of the Phase III ZONE Study.

Calcif Tissue Int 2021 Jul 10. Epub 2021 Jul 10.

Touto Sangenjaya Rehabilitation Hospital, 1-24-3 Sangenjaya Setagaya-ku, Tokyo, 154-0024, Japan.

In a clinical trial involving Japanese patients with osteoporosis, post hoc analyses were performed to evaluate the incidence of acute phase reactions (APRs) after infusion of zoledronic acid (ZOL). The results highlighted differences in baseline factors between patients with vs without APRs. Changes in efficacy indicators such as bone turnover markers (BTMs) also showed significant differences. We, therefore, investigated the factors involved in the development of APRs in Japanese patients treated with a once-yearly intravenous infusion of ZOL 5 mg for 2 years by assessing the relation between APRs and efficacy. APRs reported in patients with primary osteoporosis from the ZONE study were analyzed post hoc. Baseline factors were compared in patients with vs without APRs, and changes in BTMs and bone mineral density (BMD) were also investigated. In the ZOL group, 51.2% (169/330) of patients developed APRs after the first infusion and 12.3% (33/268) after the second infusion. Comparison of baseline factors showed that patients without APRs in the ZOL group had a significantly higher neutrophil/lymphocyte ratio, lower serum levels of procollagen type I N-terminal propeptide, older age, and higher likelihood of prior bisphosphonate use vs patients with APRs. Patients with APRs showed significantly higher increases in total hip BMD at 6 and 12 months and larger reductions in BTMs vs patients without APRs. Patient profiles differed significantly between patients with vs without APRs, with APRs after the first infusion of ZOL being related to increases in total hip BMD and suppression of BTMs.This study is registered with ClinicalTrials.gov (identifier: NCT01522521; January 31, 2012).
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http://dx.doi.org/10.1007/s00223-021-00884-7DOI Listing
July 2021

Corrigendum to "Plantar incision with severe muscle injury can be a cause of long-lasting postsurgical pain in the skin" [Life Sci. 275 (2021) 119389].

Life Sci 2021 Sep 7;281:119809. Epub 2021 Jul 7.

Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan.

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http://dx.doi.org/10.1016/j.lfs.2021.119809DOI Listing
September 2021

Who spent their COVID-19 stimulus payment? Evidence from personal finance software in Japan.

Jpn Econ Rev (Oxf) 2021 Jun 24:1-29. Epub 2021 Jun 24.

School of Economics, University of Queensland, Level 6 Colin Clark Building (39), Blair Dr, Saint Lucia, QLD 4072 Australia.

In response to the COVID-19 crisis, governments worldwide have been formulating and implementing different strategies to mitigate its social and economic impacts. We study the household consumption responses to Japan's COVID-19 unconditional cash transfer program. Owing to frequent delays in local governments' administrative procedures, the timing of the payment to households varied unexpectedly. Using this natural experiment, we analyze households' consumption responses to cash transfers using high-frequency data from personal finance management software that links detailed information on expenditure, income, and wealth. We construct three consumption measures: one captures the baseline marginal propensity to consume (MPC), and the other two are for the lower and the upper bound of MPC. Additionally, we explore heterogeneity in MPCs by household income, wealth, and population characteristics, as well as consumption categories. Our results show that households exhibit immediate and non-negligible positive responses in household expenditure. There is significant heterogeneity depending on various household characteristics, with liquidity constraint status being the most crucial factor, in line with the standard consumption theory. Additionally, this study provides policymakers with insights regarding targeted cash transfer programs, conditioning on labor income, and liquidity constraints.
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http://dx.doi.org/10.1007/s42973-021-00080-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221901PMC
June 2021

Oocyte-specific linker histone H1foo interacts with Esrrb to induce chromatin decondensation at specific gene loci.

Biochem Biophys Res Commun 2021 Jul 21;561:165-171. Epub 2021 May 21.

Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Linker histone H1 is mainly localized in the linker DNA region, between two nucleosome cores, and regulates chromatin structures linking gene expression. Mammalian oocytes contain the histone H1foo, a distinct member with low sequence similarity to other members in the H1 histone family. Although, from various previous studies, evidence related to H1foo function in chromatin structures is being accumulated, the distribution of H1foo at the target gene loci in a genome-wide manner and the molecular mechanism of H1foo-dependent chromatin architecture remain unclear. In this study, we aimed to identify the target loci and the physiological factor bound to H1foo at the loci. Chromatin immunoprecipitation sequencing analysis of H1foo-overexpressing mouse embryonic stem cells showed that H1foo is enriched around the transcriptional start sites of genes such as oocyte-specific genes and that the chromatin structures at these regions were relaxed. We demonstrated that H1foo was physiologically bound to the nuclear receptor estrogen-related receptor beta (Esrrb), and Esrrb was necessary for H1foo activity of chromatin decondensation at the target loci. The specific localization and interaction with Esrrb were validated in endogenous H1foo of oocytes. Overall, H1foo induces chromatin decondensation in a locus-specific manner and this function is achieved by interacting with Esrrb.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.033DOI Listing
July 2021

Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study.

Radiother Oncol 2021 07 21;160:266-272. Epub 2021 May 21.

Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background And Purpose: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab.

Materials And Methods: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis.

Results: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab.

Conclusion: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.
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http://dx.doi.org/10.1016/j.radonc.2021.05.016DOI Listing
July 2021

Pedicle screw placement with use of a navigated surgical drill at subaxial cervical spine.

J Clin Neurosci 2021 Jun 29;88:28-33. Epub 2021 Mar 29.

Department of Orthopedic Surgery, Nagoya University, Nagoya, Japan.

Study Design: Retrospective cohort study.

Objective: This study was performed to evaluate the accuracy of cervical pedicle screw (CPS) placement with use of a navigated surgical drill (ND) and to compare it with navigated manual probe (MP) at C3-C6.

Methods: 47 consecutive patients (27 males and 20 females, 67.2 [33-91] years) underwent a posterior cervical fixation using CPSs under an intraoperative 3D - - CT based navigation system (total 207 CPSs). For initial probing, ND with 2.2-mm steel burr was used since Apr. 2017 (Group ND; 33 patients, 152 CPSs). MP was used earlier (Group MP; 14 patients, 55 CPSs). There were no other different procedures between the two groups. The accuracy of CPS placement was graded with postoperative CT and compared between the two groups.

Results: There were no significant differences in the total perforation rates both in axial and sagittal planes between Groups ND and MP (axial; 7.2% vs. 14.5%, p = 0.25, sagittal; 10.5% vs. 14.5%, p = 0.46). However, the lateral and rostral perforation rates were significantly reduced in Group ND compared to Group MP (lateral: 36.4% vs. 87.5%, p = 0.04; rostral: 6.3% vs. 100%, p = 0.001).

Conclusion: Although ND did not decrease the total perforation rate significantly, it reduced the incidence of lateral and rostral perforation. ND is likely to make initial probing easier without a forcible manipulation which might cause vertebral rotation.
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http://dx.doi.org/10.1016/j.jocn.2021.03.009DOI Listing
June 2021

Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD).

Clin Exp Nephrol 2021 Apr 29. Epub 2021 Apr 29.

Department of Advanced Informatics for Genetic Disease, Juntendo University, Tokyo, Japan.

Background: Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan.

Methods: This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients' data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis.

Results: Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: - 2.7 (- 4.2 to - 1.5) (ml/min/1.73 m/year), - 5.0 (- 9.6 to - 2.3) (%/year), and 4.78 (0.86-8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively).

Conclusions: This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.
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http://dx.doi.org/10.1007/s10157-021-02068-xDOI Listing
April 2021

Bioelectrical Impedance Analysis and Manual Measurements of Neck Circumference Are Interchangeable, and Declining Neck Circumference Is Related to Presarcopenia.

Biomed Res Int 2021 29;2021:6622398. Epub 2021 Mar 29.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Japan.

Purpose: Preventive medicine is important in an aging society. Presarcopenia is the preliminary stage of sarcopenia. Recent advances in bioelectrical impedance analysis (BIA) devices have enabled automatic estimation of neck circumference (NC). However, the agreement between and interchangeability of NC measured manually and that calculated with BIA have not been evaluated. We performed these analyses in the context of health checkups and investigated their associations with presarcopenia.

Methods: We enrolled 318 participants who underwent anthropometric measurements, including NC measured manually and by BIA; assessment of physical function; and blood testing. We used Bland-Altman analysis to calculate the agreement between and interchangeability of NC measurements by BIA and by the manual method. We then statistically compared normal participants and those with presarcopenia. Using multivariable analysis, we subsequently investigated significant risk factors for presarcopenia. We defined presarcopenia according to the appendicular skeletal muscle index (aSMI; the ratio of arm and leg skeletal muscle mass to height).

Results: Bland-Altman analysis showed that bias (BIA-manual) was negative overall (-1.07), for male participants (-1.23), and for female participants (-0.96). This finding suggests that BIA measurement is an underestimate in comparison with manual measurement. NC measurement by BIA was found to be interchangeable with that by manual methods, inasmuch as the percentage error was less than 5% overall (4.38%), for male participants (3.81%), and for female participants (4.58%). Univariable analysis revealed that NC was significantly smaller in the participants with presarcopenia than in those without. Multivariable analysis, adjusted for confounding factors, revealed that a decrease in NC was significantly correlated with presarcopenia.

Conclusions: BIA measurements of NC are interchangeable within about 95% with manual measurements. The decrease in NC measured by BIA was significantly associated with presarcopenia in both genders. NC measurement can be used for early detection of presarcopenia.
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http://dx.doi.org/10.1155/2021/6622398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024069PMC
May 2021

Loss-Modulation-Based Wavelength-Range Shifting of Tunable EDF Ring Laser with Cascaded-Chirped Long-Period Fiber Grating for Temperature Measurement.

Sensors (Basel) 2021 Mar 27;21(7). Epub 2021 Mar 27.

Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-cho, Shimane, Matsue 690-8504, Japan.

A novel tunable Erbium-doped fiber ring laser (EDFRL) with a cascaded-chirped long-period fiber grating (C-CLPG) as a wavelength selection filter is proposed from the viewpoint of the sensor use, in which a variable optical attenuator (VOA) is employed as an intracavity loss modulator to change the oscillation wavelength region so that the resultant tuning wavelength range is widened. In the demonstrative experiment for temperature measurements, oscillation over the wavelength range of 12.85 nm (1557.62~1570.47 nm), which is more than three times range of the previously presented laser and is equivalent to 64 °C in terms of temperature change, was achieved, while a single-wavelength oscillation was maintained. In addition, a practical technique for realizing a temperature measurement by combining with the VOA control is also discussed.
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http://dx.doi.org/10.3390/s21072342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036910PMC
March 2021

Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study.

BMC Cancer 2021 Apr 1;21(1):346. Epub 2021 Apr 1.

Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.

Background: Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.

Methods: We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.

Results: Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.

Conclusions: Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
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http://dx.doi.org/10.1186/s12885-021-08048-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017679PMC
April 2021

Plantar incision with severe muscle injury can be a cause of long-lasting postsurgical pain in the skin.

Life Sci 2021 Jun 24;275:119389. Epub 2021 Mar 24.

Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan.

Aims: Although chronic local inflammation in deeper tissues after skin wound healing might produce chronification of acute postsurgical pain, its mechanisms have not been fully elucidated. We hypothesized that muscle injury and severe inflammation would prolong acute postsurgical pain by its central nervous system mechanisms.

Main Methods: After approval of the Animal Care Committee, experiments were performed in Male Sprague-Dawley rats weighing 250-300 g. Plantar incision and plantar incision combined with cryoinjury of the plantar flexor digitorum brevis muscle were made in the plantar incision group and muscle injury group, respectively. Pain-related behaviors were assessed, and inflammatory cells were isolated from injured muscle and analyzed by flow cytometry. Spinal microglial activation was assessed with Iba-1 staining.

Key Findings: Mechanical hyperalgesia from day 5 to day 8 and spontaneous pain-related behavior from day 3 to day 7 were significantly greater in the muscle injury group than in the plantar incision group (P < 0.05), whereas there was no significant difference between the two groups in thermal hyperalgesia. In the muscle injury group, the number of inflammatory cells on day 4 was significantly larger and spinal Iba-1 expression levels on days 4 and 7 were significantly higher than those in the plantar incision group (P < 0.05).

Significance: Surgical injury in deep tissues accompanying severe muscle inflammation induced prolonged postsurgical pain in the healing wound of the skin not by the persistence of muscle inflammation but by a central mechanism involving microglial activation at the level of the spinal cord.
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http://dx.doi.org/10.1016/j.lfs.2021.119389DOI Listing
June 2021

Maintenance of mouse trophoblast stem cells in KSR-based medium allows conventional 3D culture.

J Reprod Dev 2021 Jun 20;67(3):197-205. Epub 2021 Mar 20.

Department of Animal Resource Sciences/Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

Mouse trophoblast stem cells (TSCs) can differentiate into trophoblast cells, which constitute the placenta. Under conventional culture conditions, in a medium supplemented with 20% fetal bovine serum (FBS), fibroblast growth factor 4 (FGF4), and heparin and in the presence of mouse embryonic fibroblast cells (MEFs) as feeder cells, TSCs maintain their undifferentiated, proliferative status. MEFs can be replaced by a 70% MEF-conditioned medium (MEF-CM) or by TGF-ß/activin A. To find out if KnockOut Serum Replacement (KSR) can replace FBS for TSC maintenance, we cultured mouse TSCs in KSR-based, FBS-free medium and investigated their proliferation capacity, stemness, and differentiation potential. The results indicated that fibronectin, vitronectin, or laminin coating was necessary for adhesion of TSCs under KSR-based conditions but not for their survival or proliferation. While the presence of FGF4, heparin, and activin A was not sufficient to support the proliferation of TSCs, the addition of a pan-retinoic acid receptor inverse agonist and a ROCK-inhibitor yielded a proliferation rate comparable to that obtained under the conventional FBS-based conditions. TSCs cultured under the KSR-based conditions had a gene expression and DNA methylation profile characteristic of TSCs and exhibited a differentiation potential. Moreover, under KSR-based conditions, we could obtain a suspension culture of TSCs using extracellular matrix (ECM) coating-free dishes. Thus, we have established here, KSR-based culture conditions for the maintenance of TSCs, which should be useful for future studies.
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http://dx.doi.org/10.1262/jrd.2020-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238679PMC
June 2021

The dual presence of frailty and locomotive syndrome is associated with a greater decrease in the EQ-5D-5L index.

Nagoya J Med Sci 2021 Feb;83(1):159-167

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Japan's aging society is facing an increase in the prevalence of frailty and locomotive syndrome (LS) among older adults. To evaluate the association of these age-related declines on health-related quality of life (QOL) in Japan, we investigated this relationship among Japanese middle-aged and older adults who underwent general checkups and examined whether LS or frailty has a stronger association with the Japanese version of EuroQol's five-level EQ-5D (EQ-5D-5L) index. Participants were 231 middle-aged and older Japanese adults receiving routine health checkups. The study utilized the 25-item Geriatric Locomotive Function Scale, the Japanese version of the Cardiovascular Health Study, and the Japanese version of the EQ-5D-5L. Univariate and multivariate analyses were performed to examine how frailty and LS are related to the EQ-5D-5L index. Patients with both frailty (p = 0.003) and LS (p < 0.001) had a significantly lower EQ-5D-5L index. After adjusting for age, gender, and body mass index, LS was significantly associated with a decrease in the EQ-5D-5L index (p < 0.001), whereas frailty had no significant association with the EQ-5D-5L index (p = 0.052). Further analysis showed no significant decrease in the EQ-5D-5L index among those with frailty but no LS, and a significant decrease among those with frailty and LS. The results suggest that frailty and LS are associated with a decrease in the EQ-5D-5L index, but LS has a more pronounced effect. In evaluating frailty's effects on health-related QOL, we determined the importance of separately assessing frailty both with and without LS, even within the same frailty group.
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http://dx.doi.org/10.18999/nagjms.83.1.159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938103PMC
February 2021

Differences in the prevalence of locomotive syndrome and osteoporosis in Japanese urban and rural regions: The Kashiwara and Yakumo studies.

Mod Rheumatol 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: To clarify whether the prevalence of locomotive syndrome (LS) and osteoporosis differed according to region, gender, and physical functions in Japan.

Methods: Data were collected in Kashiwara City (urban region) and Yakumo Town (rural region). Totally, 208 participants from the urban region and 782 participants from the rural region were included in this study. LS was assessed using the 25-item Geriatric Locomotive Function Scale and osteoporosis was assessed using a quantitative ultrasound. Physical functions were measured using grip strength and the 3-m timed up-and-go test. Differences between urban and rural regions were investigated using standardized incidence ratio and multivariate analysis.

Results: The prevalence of LS and osteoporosis was 24.5% and 42.8% in the urban region and 10.9% and 28.8% in the rural region, respectively. The standardized incidence ratio of the urban region versus the rural region was 1.80 (95% confidence intervals [CI] = 1.35-2.39) for LS and 1.21 (95% CI = 1.32-2.43) for osteoporosis, showing that the prevalence of LS was significantly higher in the urban region. Multivariate analysis indicated that LS was significantly associated with the urban sample and timed up-and-go was significantly longer in the urban sample.

Conclusion: Regional differences may be considered when evaluating LS in health checkups. Understanding the results of this study may help reduce LS prevalence.
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http://dx.doi.org/10.1080/14397595.2021.1899890DOI Listing
March 2021

Dosimetry Analysis in Non-brain Tissues During TMS Exposure of Broca's and M1 Areas.

Front Neurosci 2021 19;15:644951. Epub 2021 Feb 19.

Department of Electrical and Mechanical Engineering, Nagoya Institute of Technology, Nagoya, Japan.

For human protection, the internal electric field is used as a dosimetric quantity for electromagnetic fields lower than 5-10 MHz. According to international standards, in this frequency range, electrostimulation is the main adverse effect against which protection is needed. One of the topics to be investigated is the quantification of the internal electric field threshold levels of perception and pain. Pain has been reported as a side effect during transcranial magnetic stimulation (TMS), especially during stimulation of the Broca's (speech) area of the brain. In this study, we designed an experiment to conduct a dosimetry analysis to quantify the internal electric field corresponding to perception and pain thresholds when targeting the Broca's and M1 areas from magnetic stimulator exposure. Dosimetry analysis was conducted using a multi-scale analysis in an individualized head model to investigate electrostimulation in an axonal model. The main finding is that the stimulation on the primary motor cortex has higher perception and pain thresholds when compared to Broca's area. Also, TMS-induced electric field applied to Broca's area exhibited dependence on the coil orientation at lower electric field threshold which was found to be related to the location and thickness of pain fibers. The derived dosimetry quantities provide a scientific rationale for the development of human protection guidelines and the estimation of possible side effects of magnetic stimulation in clinical applications.
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http://dx.doi.org/10.3389/fnins.2021.644951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933205PMC
February 2021

Postoperative Syrinx Shrinkage in Spinal Ependymoma of WHO Grade II.

Clin Spine Surg 2021 Mar;34(2):E100-E106

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya.

Study Design: A retrospective study of preoperative and postoperative magnetic resonance imaging (MRI) findings in spinal ependymoma.

Objective: The goal of the study was to examine MRI features, including the syrinx component volume, after surgical resection of spinal ependymoma, and to relate these features to extent of resection and improvement of postoperative neurological status.

Summary Of Background Data: Spinal ependymomas have a variety of MRI findings preoperatively, including a hemorrhage cap sign, gadolinium enhancement, and a spinal tumor cyst. However, little is known about these features on postoperative MRI after tumor resection.

Materials And Methods: The subjects were 38 patients treated for spinal cord ependymoma of World Health Organization grade II at our hospital. All had a spinal tumor cyst on preoperative MRI. All cases were followed with MRI for >1 year after surgery, including imaging at postoperative months (POM) 1 and 12. The maximum diameter of the syrinx was measured on mid-sagittal MRI. The extent of tumor resection was categorized as gross total resection (GTR) and subtotal resection (STR).

Results: The mean age of the 38 patients (22 male and 16 female individuals) was 50.9 years (range, 21-71 y) at the time of surgery. The mean preoperative duration from disease onset was 14.9 months (range, 2-47 mo). GTR was achieved in 28 patients (74%) and STR in 10 (26%). The mean syrinx sizes preoperatively and at POM 1 and POM 12 were 7.5±2.3, 4.1±1.9, and 2.5±1.8 mm, respectively, with significant differences among the time points (P<0.01). The syrinx size shrunk over time after GTR and STR. The shrinkage rate was significantly higher in GTR cases (P<0.05) and in cases with the improvement of McCormick grade for neurological status after both GTR and STR (P<0.05).

Conclusions: These findings suggest that MRI can be used to evaluate the improvement of neurological status after surgery for spinal ependymoma.
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http://dx.doi.org/10.1097/BSD.0000000000001061DOI Listing
March 2021

Persistent hepatocyte apoptosis promotes tumorigenesis from diethylnitrosamine-transformed hepatocytes through increased oxidative stress, independent of compensatory liver regeneration.

Sci Rep 2021 Feb 9;11(1):3363. Epub 2021 Feb 9.

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.

Hepatocellular carcinoma highly occurs in chronic hepatitis livers, where hepatocyte apoptosis is frequently detected. Apoptosis is a mechanism that eliminates mutated cells. Hepatocyte apoptosis induces compensatory liver regeneration, which is believed to contribute to tumor formation. Hepatocyte-specific Mcl-1 knockout mice (Mcl-1 mice) developed persistent hepatocyte apoptosis and compensatory liver regeneration with increased oxidative stress in adulthood but had not yet developed hepatocyte apoptosis at the age of 2 weeks. When diethylnitrosamine (DEN) was administered to 2-week-old Mcl-1 mice, multiple liver tumors were formed at 4 months, while wild-type mice did not develop any tumors. These tumors contained the B-Raf V637E mutation, indicating that DEN-initiated tumorigenesis was promoted by persistent hepatocyte apoptosis. When N-acetyl-L-cysteine was given from 6 weeks of age, DEN-administered Mcl-1 mice had reduced oxidative stress and suppressed tumorigenesis in the liver but showed no changes in hepatocyte apoptosis or proliferation. In conclusion, enhanced tumor formation from DEN-transformed hepatocytes by persistent hepatocyte apoptosis is mediated by increased oxidative stress, independent of compensatory liver regeneration. For patients with livers harboring transformed cells, the control of oxidative stress may suppress hepatocarcinogenesis based on chronic liver injury.
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http://dx.doi.org/10.1038/s41598-021-83082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873060PMC
February 2021

Association between Drinking Habits and Oral Symptoms: A Cross-Sectional Study Based on Japanese National Statistical Data.

Int J Dent 2020 8;2020:8874587. Epub 2020 Dec 8.

Oral Environment and Community Dental Health, The Nippon Dental University Graduate School of Life Dentistry at Niigata, Niigata City 15103/951-8151, Japan.

Aim: The purpose of this study was to investigate the association between drinking habits and subjective symptoms of the oral cavity based on Japanese national statistical data.

Methods: The subjects were 8,698 respondents of the Japan National Livelihood Survey 2013, in their 30s to 60s. The association between drinking habits and each survey item was investigated by contingency table analysis and binary logistic regression analysis.

Results: The proportion of people with drinking habits was 55.3% among men and 20.3% among women, and the proportion of men with drinking habits above the age of 40 years was high. Contingency table analysis indicated an association between drinking habits and the following items in men: subjective symptoms ( < 0.01), chewing difficulty ( < 0.05), subjective impression of health ( < 0.01), smoking habit ( < 0.01), and income level ( < 0.01). Analysis indicated an association between drinking habits and hospital visits ( < 0.01) and smoking habits ( < 0.01) in women. When comparing the response rates of symptoms and presence of disease stratified according to drinking habits, inflammatory and sensory system symptoms were common in those who had drinking habits, as were diabetes and gout. Binomial logistic regression analysis with drinking habit as the objective variable indicated statistically significant odds ratios for smoking habit (2.13; 95% CI: 1.65-2.75), difficulty in chewing (1.63; 95% CI: 1.01-2.62), and working hours (1.50; 95% CI: 1.10-2.04). This study identified a correlation between drinking habits and masticatory disorders, suggesting that the effects of drinking as a risk factor for dental diseases should be examined in greater detail in the future.
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http://dx.doi.org/10.1155/2020/8874587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787800PMC
December 2020

[A Case of Synchronous Triple Cancer of the Stomach, Intrahepatic Bile Duct, and Prostate].

Gan To Kagaku Ryoho 2020 Dec;47(13):2346-2348

Dept. of Gastrointestinal Surgery, Takatsuki General Hospital.

A 73-year-old man presented with the chief complaint of hematemesis(bloody vomiting). Upon examination, he was diagnosed as having gastric cancer with liver metastasis. He consulted our hospital for a second opinion. Gastrointestinal endoscopy showed a 50 mm early stomach cancer. Contrast-enhanced CT showed a progressive contrast-enhanced tumor in the S7 segment of the liver. FDG-PET/CT showed increased FDG uptake in the prostate. High PSA levels were also observed. He was diagnosed as having gastric cancer and prostate carcinoma. Intrahepatic cholangiocarcinoma and metastatic liver cancer were mentioned as differential diagnoses of the liver tumor. Hormonal therapy for prostate carcinoma failed to reduce the size of the liver tumor. PSA staining of the liver biopsy revealed negative results. As gastric cancer rarely metastasizes, metastatic liver cancer was unlikely. The patient was diagnosed as having intrahepatic cholangiocarcinoma. He underwent distal gastrectomy with hepatic posterior sectionectomy. The treatment strategy for multiple cancers depends on the primary lesion and the stage of cancer progression. Therefore, adequate evaluation is necessary before initiating treatment.
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December 2020

[A Case of Pancreatic Body Cancer with Peritoneal Dissemination Followed Up for 15 Months without Recurrence].

Gan To Kagaku Ryoho 2020 Dec;47(13):2248-2250

Dept. of Gastroenterology, Takatsuki General Hospital.

A 72-year-old woman was admitted to the gastroenterology division of our hospital due to abdominal pain and vomiting. Dynamic contrast-enhanced CT showed a tumor at the body of the pancreas and main pancreatic duct dilation. She was diagnosed with carcinoma of the body of the pancreas via EUS-FNA. There was no vascular invasion or distant metastasis on preoperative imaging. She was introduced to the Gastrointestinal Surgery division where a mesenteric nodule was found at the time of the surgery. Intraoperative frozen section confirmed the diagnosis of occult peritoneal metastases. After consulting with her family, we completed the pancreatosplenectomy. On histopathological examination, this case was TS2, tub2, pT3, mpd0, S1, RP1, PV0, A0, PL0, OO0, N0, M1(PER), CY1, PCM0, DPM0, R1, stage Ⅳ. After the operation, we treated the patient with gemcitabine(GEM)plus nab-paclitaxel for 3 months(4 courses). She then developed side effects such as anorexia and tiredness. After discussing with the patient, chemotherapy was discontinued. The patient remains alive without recurrence 19 months after the operation. Patients with metastatic pancreatic adenocarcinoma have poor prognoses because they are no longer candidates for surgical therapy. We encountered a case of pancreatic body cancer with peritoneal dissemination, followed up for 15 months without recurrence.
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December 2020

Occupational Therapy with the Screw Block Kit for Improving Upper Limb Function in Stroke Patients: A Quasi-randomized Controlled Trial.

Prog Rehabil Med 2021 8;6:20210002. Epub 2021 Jan 8.

Department of Innovative Medical Photonics, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Shizuoka, Japan.

Objectives: : A pilot study was conducted primarily to examine the effect of rehabilitation using the Screw Block kit on the upper limb function of hemiplegic stroke patients.

Methods: : In this pilot, single-center, quasi-randomized, controlled trial, 30 stroke patients were randomly allocated to either the experimental group or the control group. They received training with either Screw Block for 20 min in addition to conventional occupational therapy (20-40 min) or conventional occupational therapy, which included upper limb functional training for 40-60 min. In both groups, training was conducted 5 days a week for 3 weeks (15 sessions in total). Upper extremity function on the paralyzed side, which was the primary outcome, was evaluated using the Simple Test for Evaluating Hand Function (STEF) before and after the interventions.

Results: : The study sample included 28 men and 2 women (mean age, 62.5 years). The experimental group showed a significant improvement in mean STEF score compared with the control group (T=2.252, P=0.032, Cohen's d=0.82).

Conclusion: : Occupational therapy using Screw Block was more effective than conventional occupational therapy alone in improving the upper limb function in stroke patients.
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http://dx.doi.org/10.2490/prm.20210002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788085PMC
January 2021

Sacroiliac Joint Degeneration After Lumbopelvic Fixation.

Global Spine J 2020 Dec 30:2192568220978235. Epub 2020 Dec 30.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Shouwa-ku, Nagoya, Aichi, Japan.

Study Design: Retrospective Study.

Objectives: Sacroiliac buttress screws (SBS) and S2 alar iliac screws (SAI) are used as distal screws in cases with long fusion to the pelvis. Distal fixation ends, whether exceeding the sacroiliac joint (SIJ), may affect postoperative degenerative changes in the SIJ. The aim of this study was to investigate SIJ degeneration after lumbosacral and lumbopelvic fixation, using SBS and SAI in degenerative spine diseases, respectively.

Methods: This study included 70 patients aged ≥50 years with lumbosacral fusion (>3 levels). They were divided into 2 groups (SBS 20 and SAI 50 cases) based on the type of distal screws. Radiographical and clinical data were reviewed with a minimum 2-year follow-up. Radiographical SIJ degeneration was analyzed using computed tomography; clinical outcomes were evaluated using visual analog scale (VAS) and Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ).

Results: No significant differences were observed in patients' preoperative characteristics between the 2 groups. The incidence of SIJ degeneration, including osteophyte formation (30.0% and 8.0%, p = 0.03), intraarticular air (75.0% and 16.0%, p < 0.001), and subchondral cyst (20.0% and 2.0%. p = 0.02) in SBS and SAI groups, respectively, at the follow-up, was significantly higher in the SBS group. Although SIJ degenerative changes were significantly different between the SBS and SAI groups, there was no significant difference in VAS and JOABPEQ scores between the groups at 2 years post-surgery.

Conclusions: Lumbosacral fusion can cause SIJ degeneration, which is more frequent when SBS are used in fixation to the sacrum.
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http://dx.doi.org/10.1177/2192568220978235DOI Listing
December 2020

Effects of Continuous In Utero Low- and Medium-Dose-Rate Gamma-Ray Exposure on Fetal Germ Cells.

Radiat Res 2021 03;195(3):235-243

Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho, Kamikita, Aomori, 039-3212, Japan.

The effects of radiation exposure on germ cells and the gonads have been well studied at acute high-dose exposures, but the effects of chronic low-dose-rate (LDR) irradiation, particularly relevant for radiation protection, on germ cells and the gonads are largely unknown. Our previous study revealed that chronic exposure of mice to medium-dose-rate (MDR, 200 or 400 mGy/day) gamma-rays in utero for the entire gestation period (18 days) induced only a mild degree of general growth retardation, but with very drastic effects on the gonads and germ cells. In the current study, we further investigated the histomorphological changes in the gonads and the number of germ cells from gestation day (GD) 18 fetuses irradiated with MDR throughout the entire gestation period. The germ cells in the testes and ovaries of the MDR-irradiated fetuses were almost obliterated. Gestation day 18 fetuses exposed to LDR (20 mGy/day) radiation for the entire gestation period showed decreases in the number of the germ cells, which were not statistically significant or only marginally significant at most. Further investigations on the effects of LDR irradiation in utero using more sensitive methods are necessary.
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http://dx.doi.org/10.1667/RADE-20-00093.1DOI Listing
March 2021

Phospholipase Cβ3 Expressed in Mouse DRGs is Involved in Inflammatory and Postoperative Pain.

J Pain Res 2020 10;13:3371-3384. Epub 2020 Dec 10.

Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

Background: Previous studies suggested that phospholipase Cβ3 (PLCβ3), which is a common downstream component in the signaling cascade, plays an important role in peripheral mechanisms of perception including nociception. However, detailed profiles of PLCβ3-expressing dorsal root ganglion (DRG) neurons and involvement of PLCβ3 in inflammatory and postoperative pain have not been fully investigated.

Purpose: We evaluated neurochemical char0acteristics of PLCβ3-expressing DRG neurons in mice and then we examined the effects of selective knockdown of PLCβ3 expression in DRGs on inflammatory and postoperative pain.

Methods: Male C57BL/6-strain mice were used. For the inflammatory model, each mouse received subcutaneous injection of complete Freund's adjuvant (CFA) in the left hindpaw. For the postoperative pain model, a plantar incision was made in the left hindpaw. PLCβ3 antisense oligodeoxynucleotide or PLCβ3 mismatch oligodeoxynucleotide was intrathecally administered once a day for three consecutive days in each model. The time courses of thermal hyperalgesia and mechanical hyperalgesia were investigated. Changes in PLCβ3 protein levels in DRGs were evaluated by Western blotting.

Results: Immunohistochemical analysis showed that high proportion of the PLCβ3-positive profiles were biotinylated isolectin B4-positive or transient receptor potential vanilloid subfamily 1-positive. PLCβ3 protein level in DRGs during CFA-induced inflammation was comparable to that at baseline. Intrathecal administration of PLCβ3 antisense oligodeoxynucleotide, which significantly suppressed PLCβ3 expression in DRGs, did not affect pain thresholds in normal conditions but inhibited CFA-induced thermal and mechanical hyperalgesia both at the early and late phases compared to that in mismatch oligodeoxynucleotide-treated mice. Intrathecal administration of PLCβ3 antisense oligodeoxynucleotide also inhibited surgical incision-induced thermal and mechanical hyperalgesia.

Conclusion: Our results uncover a unique role of PLCβ3 in the development and maintenance of inflammatory pain induced by CFA application and in those of surgical incision-induced pain, although PLCβ3 does not play a major role in thermal nociception or mechanical nociception in normal conditions.
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http://dx.doi.org/10.2147/JPR.S280565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737028PMC
December 2020

Joint Extraction of Retinal Vessels and Centerlines Based on Deep Semantics and Multi-Scaled Cross-Task Aggregation.

IEEE J Biomed Health Inform 2021 Jul 27;25(7):2722-2732. Epub 2021 Jul 27.

Retinal vessel segmentation and centerline extraction are crucial steps in building a computer-aided diagnosis system on retinal images. Previous works treat them as two isolated tasks, while ignoring their tight association. In this paper, we propose a deep semantics and multi-scaled cross-task aggregation network that takes advantage of the association to jointly improve their performances. Our network is featured by two sub-networks. The forepart is a deep semantics aggregation sub-network that aggregates strong semantic information to produce more powerful features for both tasks, and the tail is a multi-scaled cross-task aggregation sub-network that explores complementary information to refine the results. We evaluate the proposed method on three public databases, which are DRIVE, STARE and CHASE_DB1. Experimental results show that our method can not only simultaneously extract retinal vessels and their centerlines but also achieve the state-of-the-art performances on both tasks.
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http://dx.doi.org/10.1109/JBHI.2020.3044957DOI Listing
July 2021

ST6GAL1 Is a Novel Serum Biomarker for Lenvatinib-Susceptible FGF19-Driven Hepatocellular Carcinoma.

Clin Cancer Res 2021 Feb 7;27(4):1150-1161. Epub 2020 Dec 7.

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.

Purpose: Hepatocellular carcinoma (HCC) is characterized by high intertumor heterogeneity of genetic drivers. Two multitarget tyrosine kinase inhibitors (TKI), lenvatinib and sorafenib, are used as standard-of-care chemotherapeutics in patients with advanced HCC, but a stratification strategy has not been established because of a lack of efficacious biomarkers. Therefore, we sought biomarkers that indicate lenvatinib-susceptible HCC.

Experimental Design: We performed genetic screening of HCC driver genes involved in TKI susceptibility using a novel HCC mouse model in which tumor diversity of genetic drivers was recapitulated. A biomarker candidate was evaluated in human HCC cell lines. Secreted proteins from HCC cells were then screened using mass spectrometry. Serum and tumor levels of the biomarker candidates were analyzed for their association and prediction of overall survival in patients with HCC.

Results: We found that lenvatinib selectively eliminated FGF19-expressing tumors, whereas sorafenib eliminated MET- and NRAS-expressing tumors. FGF19 levels and lenvatinib susceptibility were correlated in HCC cell lines, and FGF19 inhibition eliminated lenvatinib susceptibility. Lenvatinib-resistant HCC cell lines, generated by long-term exposure to lenvatinib, showed FGF19 downregulation but were resensitized to lenvatinib by FGF19 reexpression. Thus, FGF19 is a tumor biomarker of lenvatinib-susceptible HCC. Proteome and secretome analyses identified ST6GAL1 as a tumor-derived secreted protein positively regulated by FGF19 in HCC cells. Serum ST6GAL1 levels were positively correlated with tumor FGF19 expression in patients with surgically resected HCC. Among patients with serum ST6GAL1-high HCC who underwent TKI therapy, lenvatinib therapy showed significantly better survival than sorafenib.

Conclusions: Serum ST6GAL may be a novel biomarker that identifies lenvatinib-susceptible FGF19-driven HCC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3382DOI Listing
February 2021

Determination of the cutoff point of the absolute value of MGMTmRNA for predicting the therapeutic resistance to temozolomide in glioblastoma.

J Neurosurg Sci 2020 Oct;64(5):434-439

Division of Neurosurgery, National Cancer Center Hospital, Tokyo, Japan.

Background: We previously reported that the absolute value of O6-methylguanine-DNA methyltransferase (MGMT) messenger RNA (mRNA) obtained using real-time reverse transcription polymerase chain reaction (RT-PCR) might be useful for predicting both the prognosis and the results of therapy for glioblastoma (GB) treated by temozolomide (TMZ).

Methods: MGMT mRNA was measured in 55 newly diagnosed cases of GB less than 75 and had a Karnofsky performance status (KPS) of at least 60 by real-time reverse transcription polymerase chain reaction (RT-PCR) using the TaqMan probe. A receiver operating characteristic analysis was performed to determine the cutoff points for progression free survival (PFS) and overall survival (OS).

Results: In 55 patients with GB, 1200 and 3600 for PFS, 1200, 2100 and 2900 copies/μgRNA for OS were the candidate cutoff points. Significantly longer PFS and OS were observed in patients who did not exceed 1200 copies/μg RNA.

Conclusions: One thousand and two hundred copies/μg RNA appeared to be the most reasonable cutoff point of MGMTmRNA in GB for deciding to use other anti-tumor drugs such as Bevacizumab together with TMZ.
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http://dx.doi.org/10.23736/S0390-5616.17.04209-6DOI Listing
October 2020
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