Publications by authors named "Yoshihisa Matsumoto"

129 Publications

The possibility of conducting a clinical trial on palliative care: A survey of whether a clinical study on cancer dyspnea is acceptable to cancer patients and their relatives.

J Pain Symptom Manage 2021 May 28. Epub 2021 May 28.

Department of Palliative Care, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan.

Context: Conducting randomized controlled trials (RCTs) on palliative care is difficult owing to barriers like fragility of the patients' health status and health care providers' concerns for patients. However, quality RCTs are required for care improvement.

Objectives: To investigate the willingness of cancer patients and their relatives to participate in a clinical study on cancer dyspnea and identify feasible clinical study designs for this condition.

Methods: A nationwide, cross-sectional, web-based survey was conducted with 206 cancer patients and 206 relatives of cancer patients. Their willingness to participate in clinical studies on cancer dyspnea and factors influencing this willingness were assessed in two scenarios: outpatients receiving anticancer treatment and terminally ill inpatients.

Results: About 23% patients and 23% relatives were willing to participate in clinical trials while 40% and 32%, respectively, were unwilling. Factors related to patient participation were quick and easy trials (outpatient 57%, terminally ill 53%) and oral medication with minimal potential side effects (outpatient 48%). Factors related to unwillingness to participate were placebo-controlled trials (outpatient 51%, terminally ill 50%), disagreements about participation between patients and families (outpatient 49%, terminally ill 49%), and continuous injections (outpatient 61%, terminally ill 47%). Compared to patients, relatives responded more reluctantly, especially for patients in terminal care. Conversely, patients were less reluctant in the terminal setting than the outpatient setting.

Conclusion: Some patients and relatives were reluctant to participate in clinical trials on cancer dyspnea. Thus, trials need to be minimally invasive, quick, and fully explained to and understood by patients and families.

Key Message: This article describes a survey that investigated the willingness of cancer patients and their relatives to participate in a clinical study on cancer dyspnea. Results indicate that we need to develop a study design that is minimally invasive, relatively quick, and provides sufficient explanation for patients and families.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.05.012DOI Listing
May 2021

A Japanese translation, cultural adaptation, and linguistic and content validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

Support Care Cancer 2021 May 28. Epub 2021 May 28.

Ottery & Associates, LLC, Vernon Hills, IL, USA.

Purpose: The Scored Patient-Generated Subjective Global Assessment (PG-SGA) is a globally recognized and used nutritional screening, assessment, monitoring, and triaging tool. The aim of this study was to translate and culturally adapt the original English PG-SGA for the Japanese speaking populations and to assess its linguistic validity (i.e., comprehensibility, difficulty) and content validity, as perceived by Japanese patients and healthcare professionals.

Methods: In accordance with methodology used in previous Dutch, Thai, German, and Norwegian PG-SGA studies, we followed the ten steps of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Translation and Cultural Adaptation for Patient-Reported Outcome Measures. The study enrolled 50 patients and 50 healthcare professionals (HCPs) to evaluate the comprehensibility and difficulty of the translated and culturally adapted PG-SGA. The HCPs also evaluated the content validity of the translation. We evaluated each item and quantified scale indices for content validity (item content validity index (I-CVI), scale content validity index (S-CVI)), comprehensibility (item comprehensibility index (I-CI), scale comprehensibility index (S-CI)), and difficulty (item difficulty index (I-DI), scale difficulty index (S-DI)).

Results: Patients evaluated the comprehensibility and difficulty of the patient component as excellent (S-CI = 0.97, S-DI = 0.96). The professionals rated the Japanese version of both components of the PG-SGA as very relevant (S-CVI = 0.94). The professionals evaluated the comprehensibility of the professional component as being acceptable (S-CI = 0.88) but difficult (S-DI = 0.69), based predominantly on items related to physical examination (I-DI = 0.33-0.67).

Conclusion: The PG-SGA was systematically translated and culturally adapted for the Japanese setting according to the ISPOR process. The Japanese version of the PG-SGA was perceived as comprehensive, easy to use, and relevant. Perceived difficulty in professional components, specifically in the context of metabolic demand and physical examination, will require appropriate training for professionals in order to optimize implementation.
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http://dx.doi.org/10.1007/s00520-021-06310-wDOI Listing
May 2021

Visualizing how to use parenteral opioids for terminal cancer dyspnea: A pilot, multicenter, prospective, observational study.

J Pain Symptom Manage 2021 May 13. Epub 2021 May 13.

Palliative and Supportive Care Division, Seirei Mikatahara General Hospital, Hamamatsu, Japan.

Context: How physicians use opioids for dyspnea in imminently dying cancer patients (terminal dyspnea) varies markedly, which could hamper quality care.

Objectives: To examine the adherence to an algorithm-based treatment for terminal dyspnea, and explore its outcomes over 24 hours.

Methods: This was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were: advanced cancer patients admitted to palliative care units, ECOG performance status=3-4, and a dyspnea intensity≥2 on the Integrated Palliative care Outcome Scale (IPOS). We developed an algorithm to visualize how palliative care physicians would use parenteral opioids. Participating physicians (palliative care specialists) initiated parenteral opioids, choosing whether to use the algorithm based on their preference. We measured the adherence rate to the algorithm over 24 hours (predefined goal=70%), and compared dyspnea IPOS scores and adverse events between patients with and without algorithm-based treatment.

Results: Of 164 patients (median survival=5 days), 71 (43%) received algorithm-based treatment, and 70 (99%; 95% confidence interval=92-100%) adhered to it over 24 hours. In a complete case analysis, mean dyspnea IPOS scores significantly decreased from 2.9 (standard error=0.1) to 1.5 (0.1) in the algorithm group (n=54; p<0.001), and 2.9 (0.1) to 1.6 (0.1) in the non-algorithm group (n=72; p<0.001). There was no significant between-group difference in changes in dyspnea IPOS scores (p=0.65). Adverse events were rare (n=5).

Conclusion: The algorithm-based treatment was feasible, and might be as effective and safe as the usual care by palliative care specialists. Its implementation may help physicians provide quality care for terminal dyspnea.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.05.001DOI Listing
May 2021

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Med Mol Morphol 2021 May 8. Epub 2021 May 8.

Department of Radiology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.
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http://dx.doi.org/10.1007/s00795-021-00290-wDOI Listing
May 2021

Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity.

J Radiat Res 2021 May;62(3):380-389

Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan.

Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4's DSB repair function in normal development.
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http://dx.doi.org/10.1093/jrr/rrab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127669PMC
May 2021

Patient-perceived symptomatic benefits of olanzapine treatment for nausea and vomiting in patients with advanced cancer who received palliative care through consultation teams: a multicenter prospective observational study.

Support Care Cancer 2021 Mar 20. Epub 2021 Mar 20.

Department of Palliative Medicine, Saitama Medical University, Irima, Saitama, Japan.

Purpose: To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer.

Methods: We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4).

Results: The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%).

Conclusion: Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.
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http://dx.doi.org/10.1007/s00520-021-06067-2DOI Listing
March 2021

ASO Author Reflections: Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma.

Ann Surg Oncol 2021 Mar 12. Epub 2021 Mar 12.

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

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http://dx.doi.org/10.1245/s10434-021-09810-5DOI Listing
March 2021

Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma.

Ann Surg Oncol 2021 Mar 12. Epub 2021 Mar 12.

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study.

Methods: Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis.

Results: Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis.

Conclusions: The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC.
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http://dx.doi.org/10.1245/s10434-021-09752-yDOI Listing
March 2021

Unanswered questions and future direction in the management of terminal breathlessness in patients with cancer.

ESMO Open 2020 30;5 Suppl 1:e000603. Epub 2020 Sep 30.

Division of Palliative and Supportive Care, Seirei Mikatahara General Hospital, Hamamatsu, Japan.

Breathlessness is among the most common and deteriorating symptoms in patients with advanced cancer, which may worsen towards the end of life. Breathlessness in patients with estimated life expectancy of weeks to days has unique clinical features: it tends to worsen rapidly over days to hours as death approaches often despite current symptom control measures. Breathlessness in patients during the last weeks to days of life can be called 'terminal breathlessness'. While evidence has accumulated for the management of breathlessness in patients with cancer who are not dying, such evidence may not be fully applied to terminal breathlessness. Only a few studies have investigated the best practice of terminal breathlessness in patients with cancer. In this paper, we summarise the current evidence for the management of terminal breathlessness, and propose future directions of clinical research.
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http://dx.doi.org/10.1136/esmoopen-2019-000603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046422PMC
September 2020

Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells.

J Radiat Res 2021 Mar;62(2):198-205

Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 Japan.

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as 'the dose-rate effect'. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70-/- mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.
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http://dx.doi.org/10.1093/jrr/rraa128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948855PMC
March 2021

Nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer: study protocol for a multicentre randomised controlled trial.

BMJ Open 2020 11 26;10(11):e037759. Epub 2020 Nov 26.

Department of Palliative Medicine, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

Introduction: It has been suggested that palliative care integrated into standard cancer treatment from the early phase of the disease can improve the quality of life of patients with cancer. In this paper, we present the protocol for a multicentre randomised controlled trial to examine the effectiveness of a nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer.

Methods And Analysis: A total of 206 patients will be randomised (1:1) to the intervention group or the control group (usual care). The intervention, triggered with a brief self-administered screening tool, comprises comprehensive need assessments, counselling and service coordination by advanced-level nurses. The primary outcome is the Trial Outcome Index of the Functional Assessment of Cancer Therapy (FACT) at 12 weeks. The secondary outcomes include participants' quality of life (FACT-Lung), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), illness perception (Prognosis and Treatment Perceptions Questionnaire), medical service use and survival. A mixed-method approach is expected to provide an insight about how this intervention works.

Ethics And Dissemination: This study has been approved by the Institutional Review Board of the National Cancer Center Japan (approval number: 2016-235). The findings will be disseminated through peer-reviewed publications and conference presentations and will be reflected on to the national healthcare policy.

Trial Registration Number: UMIN000025491.
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http://dx.doi.org/10.1136/bmjopen-2020-037759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692832PMC
November 2020

The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability.

Mutat Res 2021 Jan-Jun;822:111727. Epub 2020 Nov 2.

Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology, 2-12-1 Oookayama, Meguro-ku, Tokyo, 152-8550, Japan.

Polynucleotide kinase phosphatase (PNKP) has dual enzymatic activities as kinase and phosphatase for DNA ends, which are the prerequisite for the ligation, and thus is involved in base excision repair, single-strand break repair and non-homologous end joining for double-strand break (DSB) repair. In this study, we examined mechanisms for the recruitment of PNKP to DNA damage sites by laser micro-irradiation and live-cell imaging analysis using confocal microscope. We show that the forkhead-associated (FHA) domain of PNKP is essential for the recruitment of PNKP to DNA damage sites. Arg35 and Arg48 within the FHA domain are required for interactions with XRCC1 and XRCC4. PNKP R35A/R48A mutant failed to accumulate on the laser track and siRNA-mediated depletion of XRCC1 and/or XRCC4 reduced PNKP accumulation on the laser track, indicating that PNKP is recruited to DNA damage sites via the interactions between its FHA domain and XRCC1 or XRCC4. Furthermore, cells expressing PNKP R35A/R48A mutant exhibited increased sensitivity toward ionizing radiation in association with delayed SSB and DSB repair and genome instability, represented by micronuclei and chromosome bridges. Taken together, these findings revealed the importance of PNKP recruitment to DNA damage sites via its FHA domain for DNA repair and maintenance of genome stability.
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http://dx.doi.org/10.1016/j.mrfmmm.2020.111727DOI Listing
November 2020

Association Between Loneliness and the Frequency of Using Online Peer Support Groups Among Cancer Patients With Minor Children: A Cross-Sectional Web-Based Study.

J Pain Symptom Manage 2021 May 28;61(5):955-962. Epub 2020 Sep 28.

Department of Palliative Medicine, National Cancer Center Hospital East, Kashiwa, Japan.

Context: Cancer patients with minor children are increasing; however, they do not receive sufficient support.

Objective: This study aimed to investigate the association between loneliness and the frequency of using online peer support groups among cancer patients with minor children.

Methods: A cross-sectional web-based survey was conducted from April to May 2019. Cancer patients with minor children were recruited from an online peer support group called "Cancer Parents." Individuals diagnosed with cancer and whose youngest children were younger than 18 years were enrolled. Materials included: the UCLA Loneliness Scale version 3 (UCLA-LS), K6 scale, abbreviated Lubben Social Network Scale, and the sociodemographic/clinical characteristics questionnaire. Multivariate logistics regression analysis was performed to determine the factors associated with the high loneliness group (defined as those above the median score on the UCLA-LS).

Results: A total of 334 patients participated (79.9% female; mean age 43.1 years, standard deviation 5.8). The most common primary cancer type was breast (34.1%). The median score of the UCLA-LS was 45 (interquartile range 37-53). The multivariate logistics regression analysis revealed that the high loneliness group was significantly associated with the frequent use of online peer support group less than once a week (odds ratio [OR] = 0.47; 95% CI = 0.26-0.85; P = 0.012), with a smaller social network (OR = 0.78; 95% CI = 0.73-0.83; P < 0.001), and higher psychological distress (OR = 1.16; 95% CI = 1.09-1.23; P < 0.001).

Conclusions: Frequent use of online peer support groups was associated with less loneliness among cancer patients with minor children.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.09.035DOI Listing
May 2021

Linker region is required for efficient nuclear localization of polynucleotide kinase phosphatase.

PLoS One 2020 24;15(9):e0239404. Epub 2020 Sep 24.

Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan.

Polynucleotide kinase phosphatase (PNKP) is a DNA repair factor with dual enzymatic functions, i.e., phosphorylation of 5'-end and dephosphorylation of 3'-end, which are prerequisites for DNA ligation and, thus, is involved in multiple DNA repair pathways, i.e., base excision repair, single-strand break repair and double-strand break repair through non-homologous end joining. Mutations in PNKP gene causes inherited diseases, such as microcephaly and seizure (MCSZ) by neural developmental failure and ataxia with oculomotor apraxia 4 (AOA4) and Charcot-Marie-Tooth disease 2B2 (CMT2B2) by neurodegeneration. PNKP consists of the Forkhead-associated (FHA) domain, linker region, phosphatase domain and kinase domain. Although the functional importance of PNKP interaction with XRCC1 and XRCC4 through the FHA domain and that of phosphatase and kinase enzyme activities have been well established, little is known about the function of linker region. In this study, we identified a functional putative nuclear localization signal (NLS) of PNKP located in the linker region, and showed that lysine 138 (K138), arginine 139 (R139) and arginine 141 (R141) residues therein are critically important for nuclear localization. Furthermore, double mutant of K138A and R35A, the latter of which mutates arginine 35, central amino acid of FHA domain, showed additive effect on nuclear localization, indicating that the FHA domain as well as the NLS is important for PNKP nuclear localization. Thus, this study revealed two distinct mechanisms regulating nuclear localization and subnuclear distribution of PNKP. These findings would contribute to deeper understanding of a variety of DNA repair pathway, i.e., base excision repair, single-strand break repair and double-strand break repair.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239404PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514006PMC
November 2020

Safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer: A large-scale multicenter prospective observational study in real-world palliative care settings.

Gen Hosp Psychiatry 2020 Nov - Dec;67:35-41. Epub 2020 Sep 14.

Department of Palliative Medicine, Saitama Medical University, 38 Moroyama-hongo, Moroyama-co, Iruma, Saitama, Japan.

Objective: To clarify the safety and effectiveness of antipsychotic medication for delirium in patients with advanced cancer receiving palliative care.

Methods: This was a prospective observational study involving consecutive patients with advanced cancer and delirium receiving antipsychotics in inpatient hospices or psycho-oncology settings. Adjusted mean scores of the Delirium Rating Scale Revised-98 (DRS; range: 0-39) were calculated at baseline and Day 3 using generalized estimating equations. Adverse events over 7 days were evaluated.

Results: Data from 756 patients were analyzed (Mage = 72 ± 11 years, 62% male, 48% bedridden). The adjusted mean DRS score significantly decreased after antipsychotics administration (21.5 [95% confidence interval 19.5 to 23.4] to 20.8 [18.9 to 22.8], p = 0.03, effect size [ES] = 0.02). Significant improvement was associated with age of 75 or older (ES = 0.07), better performance status (0.32), longer estimated prognosis (0.25), psycho-oncological consultation settings (0.20), hyperactive (0.14) or mix-motor subtypes (0.24) of delirium, and quetiapine administration (0.19); significant deterioration was observed in patients with "days" prognosis (0.18). Extrapyramidal symptoms (9.8%) and somnolence (8.5%) were the most prevalent adverse events.

Conclusions: The use of antipsychotics as part of comprehensive delirium management was safe and may provide some symptomatic benefits for patients with terminal illness and delirium. Along with adequate non-pharmacological interventions, judicious use of antipsychotics is still recommended.
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http://dx.doi.org/10.1016/j.genhosppsych.2020.09.001DOI Listing
September 2020

Effects of enteral nutrition and parenteral nutrition on survival in patients with advanced cancer cachexia: Analysis of a multicenter prospective cohort study.

Clin Nutr 2021 Mar 31;40(3):1168-1175. Epub 2020 Jul 31.

Palliative and Supportive Care Division, Seirei Mikatahara General Hospital, 3453 Mikatahara-cho, Kita-ku, Hamamatsu City, Shizuoka, 433-8558, Japan. Electronic address:

Background & Aims: The benefits of artificial nutrition and hydration in patients with advanced cancer remain unknown. Therefore, we conducted a prospective study to evaluate effects of enteral nutrition (EN) and parenteral nutrition and hydration (PNH) on survival in palliative care units.

Methods: This study involved a secondary analysis of a multicenter cohort study. Data of primary nutritional administration routes during the first week after admission (oral intake, enteral tube feeding, parenteral nutrition, parenteral hydration, poor oral intake) were obtained. Data of averaged calorie sufficiency rate/total calorie intake [high (75% ≤ or 750 kcal/day ≤), moderate (50-75% or 500-750 kcal/day), low (25-50% or 250-500 kcal/day), very low (<25% or <250 kcal/day)] were also obtained. After investigating the implementation of artificial nutrition and hydration, participants were divided into three groups according to the nutritional administration route and calorie sufficiency rate/total calorie intake: EN, PNH, and control. We conducted time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses.

Results: Patients were divided into the EN group (n = 730), PNH group (n = 190), and control group (n = 533). Differences in survival rates among the three groups were significant (Log-rank P < 0.001). Median survival times were 43.0 (95% CI 40-46), 33.0 (95% CI 29-37), and 15.0 (95% CI 14-16) days, respectively (P < 0.001). In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the EN group and PNH groups (HR 0.43 [95% CI 0.37-0.49], P < 0.001; and HR 0.52 [95% CI 0.44-0.62], P < 0.001, respectively) than in the control group.

Conclusions: This study indicated the clinical benefits of EN and PNH for patients with advanced cancer. Nevertheless, managing symptoms to improve oral intake is essential before initiation of PNH, because EN was superior to PNH.
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http://dx.doi.org/10.1016/j.clnu.2020.07.027DOI Listing
March 2021

Differential expression of DNA-dependent protein kinase catalytic subunit in the brain of neonatal mice and young adult mice.

Proc Jpn Acad Ser B Phys Biol Sci 2020 ;96(5):171-179

Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology.

It is generally thought that younger people are more susceptible to cancer development after exposure to ionizing radiation in reference to epidemiological studies and animal experiments. However, little is known about the age-dependent alteration in DNA repair ability. In the present study, we examined the expression levels of proteins involved in the repair of DNA double-strand breaks through non-homologous end joining (NHEJ), i.e., DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray repair cross-complementing 4 (XRCC4) and XRCC4-like factor (XLF). We found that the expression of DNA-PKcs in brain tissues was higher in neonatal mice (1 week after birth) than in young adult mice (7 weeks after birth). In association with this, DNA double-strand breaks were repaired more rapidly in the brain tissues of neonatal mice than in those of young adult mice. The current results suggested a possible role for DNA-PKcs protecting developing brain tissues from DNA double-strand breaks.
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http://dx.doi.org/10.2183/pjab.96.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248211PMC
January 2021

The Shunt Point of the Sacral Dural Arteriovenous Fistula: A Case Report and Literature Review.

World Neurosurg 2020 11 14;143:518-526. Epub 2020 Feb 14.

Department of Cerebrovascular Medicine, St. Mary's Hospital, Fukuoka, Japan.

Background: The occurrence of sacral dural arteriovenous fistula (dAVF) is rare. The detailed vascular architecture of sacral dAVF, including 3-dimensional (3D) angiographic images with operative findings, has not been evaluated compared with that of the thoracic and lumbar levels. We report a case of sacral dAVF with 3D angiographic examination and operative findings, with a literature review.

Case Description: A 60-year-old man presented with progressive urinary incontinence and gait disturbance. A sacral dAVF was detected at the S1-2 level. The shunt point was at the medial side of the line between the intermediate sacral crest and the most medial point of the L5 pedicle circle at the anterior posterior view of the angiography; we defined this type as the medial type. After embolization, latent inflow arteries were visualized ipsilaterally and contralaterally. During surgery, because of dAVF recurrence, a vascular tangle was found on the dura. The surgical interruption of the draining vein improved the patient's symptoms. From the literature review, 92% of cases had medial-type shunt point. It is possible for sacral dAVF to have multiple inflow arteries originating ipsilaterally or bilaterally, and a venous pouch.

Conclusions: The shunt point of sacral dAVF tended to be located medially, not in the sacral foramen. Sacral dAVF has unique angioarchitecture. The differentiation of dAVF from epidural arteriovenous fistula may not be easy in some cases of sacral lesions. Therefore, further studies with a larger number of patients focused on the detailed vascular architecture are needed.
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http://dx.doi.org/10.1016/j.wneu.2020.02.037DOI Listing
November 2020

The association between health-related quality of life and achievement of personalized symptom goal.

Support Care Cancer 2020 Oct 22;28(10):4737-4743. Epub 2020 Jan 22.

Department of Palliative Medicine, National Cancer Center Hospital East, Kashiwa, Japan.

Purpose: The aim of study was to explore the potential association between patient's self-reported physical symptom management goals as personalized symptom goal (PSGs) and health-related quality of life (HRQOL) in cancer patients. The secondary outcome was to investigate the relationship between number of physical symptoms not achieving the PSGs and HRQOL in cancer patients.

Methods: This single-center prospective observational study comprised 140 consecutive outpatients. We evaluated the PSGs and HRQOL using the Functional Assessment of Cancer Therapy-General (FACT-G). Patients were administered a self-report questionnaire, including reports on their physical symptom intensity and PSGs using Edmonton Symptom Assessment System-revised (ESAS-r) scores. We investigated the correlation between PSGs achievement (ESAS-r score ≤ PSG score) and FACT-G total scores, and relationship between and number of physical symptoms not achieving the PSGs (ESAS-r score > PSG score) and FACT-G total scores.

Results: The patients who did not achieve PSGs of pain, tiredness, lack of appetite, and shortness of breath had a lower FACT-G total score (p < 0.05). Multivariate linear regression showed that higher number of physical symptoms not achieving the PSGs correlated with lower FACT-G scores (decreasing by 1.826 points for each such symptom, p < 0.01). Predictors of increased number of physical symptoms not achieving the PSGs were younger age and a higher symptom intensity of anxiety.

Conclusion: PSGs achievement was associated with HRQOL in cancer patients. Additionally, the number of unachieved PSGs were independent determinant of poor HRQOL, particularly in younger cancer patients and those with higher symptom intensity of anxiety.
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http://dx.doi.org/10.1007/s00520-020-05316-0DOI Listing
October 2020

Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial-JORTC-PAL08 (DIRECT) study.

Support Care Cancer 2020 Jun 25;28(6):2931-2939. Epub 2019 Nov 25.

Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, Osaka, Japan.

Purpose: Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP.

Methods: Patients (N = 70) with CNP unresponsive to or intolerant of opioid-pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables.

Results: Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046).

Conclusion: Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.
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http://dx.doi.org/10.1007/s00520-019-05138-9DOI Listing
June 2020

Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.

J Radiat Res 2019 Nov;60(6):719-728

 Laboratory for Advanced Nuclear Energy, Institute of Innovative Research, Tokyo Institute of Technology, 2-12-1, Oookayaka, Meguro-ku, 152-8550, Tokyo, Japan.

Pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a dual capability to self-renew and differentiate into all cell types necessary to develop an entire organism. Differentiation is associated with dynamic epigenetic alteration and transcriptional change, while self-renewal depends on maintaining the genome DNA accurately. Genome stability of PSCs is strictly regulated to maintain pluripotency. However, the DNA damage response (DDR) mechanism in PSCs is still unclear. There is accumulating evidence that genome stability and pluripotency are regulated by a transcriptional change in undifferentiated and differentiated states. iPSCs are ideal for analyzing transcriptional regulation during reprogramming and differentiation. This study aimed to elucidate the transcriptional alteration surrounding genome stability maintenance, including DNA repair, cell cycle checkpoints and apoptosis in fibroblasts, iPSCs and neural progenitor cells (NPCs) derived from iPSCs as differentiated cells. After ionizing radiation exposure, foci for the DNA double-stranded break marker γ-H2AX increased, peaking at 0.5 h in all cells (>90%), decreasing after 4 h in fibroblasts (32.3%) and NPCs (22.3%), but still remaining at 52.5% (NB1RGB C2 clone) and 54.7% (201B7 cells) in iPSCs. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were detected, indicating that iPSCs' apoptosis increases. In addition, RNA sequencing (RNA-Seq) analysis showed high expression of apoptosis genes (TP53, CASP3 and BID) in iPSCs. Results suggested that increased apoptosis activity maintains accurate, undifferentiated genome DNA in the cell population.
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http://dx.doi.org/10.1093/jrr/rrz057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357234PMC
November 2019

[Prognostic Value of Preoperative Serum C-Reactive Protein Level in Gastric Cancer].

Gan To Kagaku Ryoho 2019 Oct;46(10):1623-1625

Division of Digestive Surgery, Dept. of Surgery, Kyoto Prefectural University of Medicine.

Background: This study investigated the prognostic value of preoperative serum C-reactive protein(CRP)level in patients with gastric cancer(GC).

Methods: This retrospective study examined 446GC patients undergoing curative gastrectomy. The associations between preoperative CRP level and postoperative long-term outcomes were examined by univariate and multivariate analyses.

Results: The patients were divided into high(n=147)or low(n=299)CRP groups based on an optimal cut- off CRP value of 0.13mg/dL according to the ROC curve analysis. High CRP levels were significantly associated with other clinical factors such as older age(B65 years), high BMI(B25 kg/m2), poor performance status(PS), and advanced cT and cN+. In the survival analyses using only the clinical factors, high CRP levels were significantly associated with worse 5-year overall and cancer-specific survivals. The multivariate analysis for 5-year overall survival identified preoperative CRP to be an independent factor(HR: 1.95, 95%CI: 1.15-3.36, p=0.0129), as well as PS, tumor location, and cT.

Conclusion: Preoperative CRP level could be a useful prognostic indicator in patients with GC undergoing curative gastrectomy.
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October 2019

How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.

Support Care Cancer 2020 Jul 19;28(7):3051-3060. Epub 2019 Oct 19.

Department of Emergency & Palliative Medicine, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.

Purpose: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status.

Methods: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h.

Results: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h.

Conclusions: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.
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http://dx.doi.org/10.1007/s00520-019-05081-9DOI Listing
July 2020

A Multicenter Cohort Study to Explore Differentiating Factors between Tumor Fever and Infection among Advanced Cancer Patients.

J Palliat Med 2019 11 30;22(11):1331-1336. Epub 2019 Sep 30.

Department of Palliative Care, Hiroshima Prefectural Hospital, Hiroshima, Japan.

Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.
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http://dx.doi.org/10.1089/jpm.2018.0594DOI Listing
November 2019

Additive Duloxetine for Cancer-Related Neuropathic Pain Nonresponsive or Intolerant to Opioid-Pregabalin Therapy: A Randomized Controlled Trial (JORTC-PAL08).

J Pain Symptom Manage 2019 10 26;58(4):645-653. Epub 2019 Jun 26.

Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.

Context: Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.

Objectives: We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.

Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]-Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.

Results: Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002).

Conclusion: Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine.
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http://dx.doi.org/10.1016/j.jpainsymman.2019.06.020DOI Listing
October 2019

DNA Damage Response After Ionizing Radiation Exposure in Skin Keratinocytes Derived from Human-Induced Pluripotent Stem Cells.

Int J Radiat Oncol Biol Phys 2019 09 11;105(1):193-205. Epub 2019 May 11.

Laboratory for Future Interdisciplinary Research of Science and Technology, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan.

Purpose: Epidermal cells are positioned on the body surface and thus risk being exposed to genotoxic stress, including ionizing radiation (IR), ultraviolet rays, and chemical compounds. The biological effect of IR on the skin tissue is a significant problem for medical applications such as radiation therapy. Keratinocyte stem cells and progenitors are at risk for IR-dependent tumorigenesis during radiation therapy for cancer treatment. To elucidate the molecular mechanism of genome stability in epidermal cells, we derived skin keratinocytes from human-induced pluripotent stem cells (iPSCs) and analyzed their DNA damage response (DDR).

Methods And Materials: Skin keratinocytes were derived from iPSCs and designated as first- (P1), second- (P2), and third- (P3) passage cells to compare the differentiation states of DDR. After 2 Gy gamma-ray exposure, cells were immunostained with DNA double-strand break markers γ-H2AX/53BP1 and cell senescence markers p16/p21 for DDR analysis. DDR protein expression level, cell survival, and apoptosis were analyzed by western blotting, WST-8 assay and TUNEL assay, respectively. DDR of constructed 3D organoid modeling was also analyzed.

Results: P1, P2, and P3 keratinocytes were characterized with keratinocyte markers keratin 14 and p63 using immunofluorescence, and all cells were positive to both markers. Derived keratinocytes showed high expression of integrin α6 and CD71 (real-time (qRT)-PCR ratio: iPSCs: integrin α6: 1.12, CD71: 1.25, P1: integrin α6: 7.80, CD71: 0.43, P2: integrin α6: 5.53, CD71: 0.48), suggesting that P1 and P2 keratinocytes have potential as keratinocyte progenitors. Meanwhile, P3 keratinocytes showed low expression of integrin α6 and CD71 (qRT-PCR ratio: P3: integrin α6: 0.55, CD71: 0.10), suggesting differentiated keratinocytes. After IR exposure, the P1 and P2 keratinocytes showed an increase in DNA repair activity by a γ-H2AX/53BP1 focus assay (P1: γ-H2AX: 28.0%, 53BP1: 17.0%, P2: γ-H2AX: 37.7%, 53BP1: 28.3%) but not in P3 keratinocytes (P3: γ-H2AX: 74.7%, 53BP1: 63.7%) compared with iPSCs (γ-H2AX: 57.0%, 53BP1: 55.0%). Furthermore, in derived keratinocytes, expression of the cellular senescence markers p16 and p21 were increased compared with iPSCs (P16: non irradiated, iPSCs: 0%, P1: 12.5%, P2: 14.5%, P3: 29.7%, IR, iPSCs: 0%, P1: 19.5%, P2: 34.8%, P3: 64.5%). DDR protein expression, cellular sensitivity, and apoptosis activity decreased in derived keratinocytes compared with iPSCs.

Conclusions: We have demonstrated the derivation of keratinocytes from iPSCs and their characterization of differentiated states and DDR. Derived keratinocytes showed progenitors like character as a result of DDR. These results suggest that derived keratinocytes are useful tools for analyzing the effects of IR, such as DDR on the skin tissue from radiation therapy for cancer.
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http://dx.doi.org/10.1016/j.ijrobp.2019.05.006DOI Listing
September 2019

Usefulness of painDETECT and S-LANSS in identifying the neuropathic component of mixed pain among patients with tumor-related cancer pain.

Support Care Cancer 2020 Jan 30;28(1):279-285. Epub 2019 Apr 30.

Department of Palliative Care, Tokatsu Hospital, Nagareyama, Japan.

Purpose: Tumor-related cancer pain often comprises mixed pain with both nociceptive and neuropathic components. Whether tumor-related cancer pain includes a neuropathic component impacts the therapeutic strategy. The aim of this cross-sectional study was to investigate the usefulness of two screening tools for neuropathic pain, painDETECT and Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), in identifying the neuropathic component of mixed pain among patients with tumor-related cancer pain.

Method: This cross-sectional study recruited consecutive inpatients and outpatients at a single site. The diagnostic accuracy of painDETECT and S-LANSS was evaluated using receiver operating characteristic curve analysis and classification probability.

Results: Of the study group, 106 patients had tumor-related cancer pain. Analyses of the nociceptive and mixed pain groups (n = 104) showed that neither painDETECT nor S-LANSS had satisfactory areas under the curve (AUCs) for identifying the neuropathic component of mixed pain (0.59 for painDETECT and 0.56 for S-LANSS). By pain intensity, the AUC for painDETECT was significantly higher in the mild pain group than in the moderate or severe pain group (0.77 vs. 0.43, P = 0.002). All parameters of classification probability for both tools were higher in the mild pain group than in the moderate or severe pain group.

Conclusions: painDETECT and S-LANSS could not identify the neuropathic component of mixed pain among patients with tumor-related cancer pain, especially when pain was moderate or severe. Contrarily, these screening tools might be useful for identifying the neuropathic component of mixed pain for mild pain.
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http://dx.doi.org/10.1007/s00520-019-04819-9DOI Listing
January 2020

Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.

Strahlenther Onkol 2019 Jul 17;195(7):648-658. Epub 2019 Apr 17.

Department of Radiology, Sapporo Medical University School of Medicine, 060-8543, Chuo-ku, Sapporo, Hokkaido, Japan.

Background: We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP).

Patients And Methods: The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens.

Results: The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP.

Conclusion: IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.
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http://dx.doi.org/10.1007/s00066-019-01468-zDOI Listing
July 2019

[Inflammatory Pseudotumor in the Cecum-A Case Report and Review of Literature].

Gan To Kagaku Ryoho 2018 Dec;45(13):2072-2074

Division of Digestive Surgery, Dept. of Surgery, Kyoto Prefectural University of Medicine.

A 42-year-old woman with complaints of fever and abdominal pain, was diagnosed to have perforative appendicitis, for which emergency surgery was performed. Marked thickening and edema around the cecum, ileum, and the mesentery was observed. Ileocecal resection was performed, as malignant disease could not be excluded. Histopathological examination revealed abscess formation in the lining membrane of the intestine, inflammatory granulation and proliferation of the spindleshaped cells in the serosal membrane extensively, and an inflammatory pseudotumor(IPT)was diagnosed. It is generally difficult to clearly distinguish IPT from a malignant tumor before surgery. We thus report this case, along with a review of literature.
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December 2018